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pubmed23n0343_17091

Social and emotional problems in children with neurofibromatosis type 1: evidence and proposed interventions.

To describe social and emotional problems in children and adolescents with neurofibromatosis type 1 (NF1) and propose interventions. Our hypothesis is that children with NF1 will have significantly more social and emotional problems, compared with their unaffected siblings and children in the general population. Forty-three children with NF1 and 22 unaffected siblings (ages 5 to 18 years) were assessed with a standardized test completed by parents and teachers (the Child Behavior Checklist). As with other aspects of NF1, there was variable expressivity. However, when rated by parents, children with NF1 had significantly more problems in comparison with test norms or unaffected siblings on 7 of 8 scales: Social Problems, Attention Problems, Anxiety/Depression, Withdrawal, Thought Problems, Somatic Complaints, and Aggressive Behavior. Children with NF1 also scored lower than unaffected siblings on measures assessing sports and other activities. Teachers reported fewer differences. We propose interventions in the form of information for parents; early screening and treatment for speech, motor, and cognitive problems; and an increased level of intervention to prevent and treat psychologic problems, including systematic screening with standardized tests.

Social and emotional problems in children with neurofibromatosis type 1: evidence and proposed interventions. To describe social and emotional problems in children and adolescents with neurofibromatosis type 1 (NF1) and propose interventions. Our hypothesis is that children with NF1 will have significantly more social and emotional problems, compared with their unaffected siblings and children in the general population. Forty-three children with NF1 and 22 unaffected siblings (ages 5 to 18 years) were assessed with a standardized test completed by parents and teachers (the Child Behavior Checklist). As with other aspects of NF1, there was variable expressivity. However, when rated by parents, children with NF1 had significantly more problems in comparison with test norms or unaffected siblings on 7 of 8 scales: Social Problems, Attention Problems, Anxiety/Depression, Withdrawal, Thought Problems, Somatic Complaints, and Aggressive Behavior. Children with NF1 also scored lower than unaffected siblings on measures assessing sports and other activities. Teachers reported fewer differences. We propose interventions in the form of information for parents; early screening and treatment for speech, motor, and cognitive problems; and an increased level of intervention to prevent and treat psychologic problems, including systematic screening with standardized tests.

pubmed23n1071_16641

Enhanced passive safety surveillance of the quadrivalent inactivated split-virion influenza vaccine (IIV4) in Finland during the 2019/20 influenza season.

The Enhanced Passive Safety Surveillance is a requirement of the European Medicines Agency (EMA) for seasonal influenza vaccines, aiming to rapidly detect any significant change in frequency or severity of expected reactogenicity or allergic events prior to widespread use of a vaccine in any particular year. The aim of this surveillance was to assess the quadrivalent inactivated split-virion influenza vaccine (IIV4) during routine immunization in Finland, as per the national immunization program for 2019/20. The primary objective was to investigate the suspected adverse drug reactions (ADR) occurring within 7 days following vaccination. Passive surveillance of individuals vaccinated with IIV4 was conducted within the first 4 to 6 weeks of the influenza season in Finland. Potential ADRs were reported via phone or posted adverse event forms. The vaccinee reporting rate and ADR reporting rate were calculated and compared with the known or expected safety data in order to identify any change which was clinically significant. Data were collected from 939 individuals, with 56 reports received for 163 suspected ADRs. Of these, 38 individuals reported 117 suspected ADRs within 7 days following vaccination, corresponding to an ADR reporting rate of 12.46% (95% CI: 10.41, 14.74%); vaccination-site pain, vaccination-site reaction, and pyrexia were the most frequently reported ADRs. The 18-to-65 years of age category had an ADR reporting rate of 12.56%, the over-65 years of age category had an ADR reporting rate of 16.22%, and no ADRs were reported for individuals aged 6 months to 18 years. No serious suspected ADRs were reported at any time post-vaccination, and the ADR rates were comparable to those reported for IIV4 in the 2018/19 seasonal assessment. The frequency of suspected ADRs was generally aligned with those reported in the Summary of Product Characteristics (SmPC), with the exception of asthenia, somnolence, and erythema, which were slightly higher. No reporting pattern by type, frequency, or severity was identified for the suspected ADRs. No clinically significant changes in what is known or expected for IIV4 was reported for the 2019/20 season, which supports the overall safety profile.

Enhanced passive safety surveillance of the quadrivalent inactivated split-virion influenza vaccine (IIV4) in Finland during the 2019/20 influenza season. The Enhanced Passive Safety Surveillance is a requirement of the European Medicines Agency (EMA) for seasonal influenza vaccines, aiming to rapidly detect any significant change in frequency or severity of expected reactogenicity or allergic events prior to widespread use of a vaccine in any particular year. The aim of this surveillance was to assess the quadrivalent inactivated split-virion influenza vaccine (IIV4) during routine immunization in Finland, as per the national immunization program for 2019/20. The primary objective was to investigate the suspected adverse drug reactions (ADR) occurring within 7 days following vaccination. Passive surveillance of individuals vaccinated with IIV4 was conducted within the first 4 to 6 weeks of the influenza season in Finland. Potential ADRs were reported via phone or posted adverse event forms. The vaccinee reporting rate and ADR reporting rate were calculated and compared with the known or expected safety data in order to identify any change which was clinically significant. Data were collected from 939 individuals, with 56 reports received for 163 suspected ADRs. Of these, 38 individuals reported 117 suspected ADRs within 7 days following vaccination, corresponding to an ADR reporting rate of 12.46% (95% CI: 10.41, 14.74%); vaccination-site pain, vaccination-site reaction, and pyrexia were the most frequently reported ADRs. The 18-to-65 years of age category had an ADR reporting rate of 12.56%, the over-65 years of age category had an ADR reporting rate of 16.22%, and no ADRs were reported for individuals aged 6 months to 18 years. No serious suspected ADRs were reported at any time post-vaccination, and the ADR rates were comparable to those reported for IIV4 in the 2018/19 seasonal assessment. The frequency of suspected ADRs was generally aligned with those reported in the Summary of Product Characteristics (SmPC), with the exception of asthenia, somnolence, and erythema, which were slightly higher. No reporting pattern by type, frequency, or severity was identified for the suspected ADRs. No clinically significant changes in what is known or expected for IIV4 was reported for the 2019/20 season, which supports the overall safety profile.

pubmed23n0604_5046

Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes.

The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Deltahsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Deltahsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Deltahsp70-II mutant was determined by flow cytometry. Furthermore, Deltahsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Deltahsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes re-expressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions.

Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes. The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Deltahsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Deltahsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Deltahsp70-II mutant was determined by flow cytometry. Furthermore, Deltahsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Deltahsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes re-expressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions.

pubmed23n0037_5636

Renal artery aneurysms.

The various types of renal artery aneurysms are described, the most common one being the congenital saccular aneurysm. Usually asymptomatic it may be associated with hypertension and generally undergoes atherosclerotic degeneration. An arteriovenous fistula may form and rupture into the renal pelvis or retroperitoneal space in some rare instances. Small, well calcified saccular aneurysms should be left alone and followed; larger, incompletely calcified or non-calcified aneurysms should be removed. Fusiform aneurysmal dilatation of the renal artery occurs distal to a focal fibromuscular dysplastic stenosis. This type is almost invariably found in hypertensive young people. Thrombosis of a branch may occur distal to the aneurysm. These aneurysms should be treated surgically, usually by excision of the stenotic area and its aneurysm, and anastomosis of branches back to the main renal artery. Dissecting aneurysms of the renal artery are the most damaging to the kidney. Complications are thrombosis of the branches, infarction of the kidney and a virulent form of hypertension. An operation should be done to correct the dissection and to remove part or all of the kidney when infarction is severe. Intrarenal arterial aneurysms are prone to hemorrhage and should be removed by local excision or partial nephrectomy.

Renal artery aneurysms. The various types of renal artery aneurysms are described, the most common one being the congenital saccular aneurysm. Usually asymptomatic it may be associated with hypertension and generally undergoes atherosclerotic degeneration. An arteriovenous fistula may form and rupture into the renal pelvis or retroperitoneal space in some rare instances. Small, well calcified saccular aneurysms should be left alone and followed; larger, incompletely calcified or non-calcified aneurysms should be removed. Fusiform aneurysmal dilatation of the renal artery occurs distal to a focal fibromuscular dysplastic stenosis. This type is almost invariably found in hypertensive young people. Thrombosis of a branch may occur distal to the aneurysm. These aneurysms should be treated surgically, usually by excision of the stenotic area and its aneurysm, and anastomosis of branches back to the main renal artery. Dissecting aneurysms of the renal artery are the most damaging to the kidney. Complications are thrombosis of the branches, infarction of the kidney and a virulent form of hypertension. An operation should be done to correct the dissection and to remove part or all of the kidney when infarction is severe. Intrarenal arterial aneurysms are prone to hemorrhage and should be removed by local excision or partial nephrectomy.

pubmed23n0368_7111

Regulation of tyrosine hydroxylase gene transcription by the cAMP-signaling pathway: involvement of multiple transcription factors.

The conversion of L-tyrosine to 3,4-dihydroxy-L-phenylalanine by tyrosine hydroxylase (TH) is the first and rate-limiting step in biosynthesis of catecholamine neurotransmitters. TH gene expression is regulated in a cell type-specific and cAMP-dependent manner. Evidence from this laboratory and others indicates that the cAMP response element (CRE), residing at -45 to -38 bp upstream of the transcription initiation site, is essential for both basal and cAMP-inducible transcription of the TH gene. To understand the control mechanisms of TH gene transcription in greater detail, we sought to identify and characterize the transcription factors involved in recognition and activation of the CRE of the TH gene. Remarkably, electrophoretic mobility shift assay and antibody supershift experiments indicated that all three major CRE-binding protein factors, i.e. CREB, ATF1, and CREM, may participate in forming specific DNA/protein complexes with the CRE of the TH gene. To address the transcriptional activation function of individual factors, we replaced the TH CRE with a GAL4-binding site and cotransfected this modified TH promoter-reporter gene with an effector plasmid that encodes GAL4-fused transcription factor. Our results indicate that CREB but not ATF1 can support basal promoter activity while both can robustly induce the promoter activity in response to co-expression of the catalytic subunit of cAMP-dependent protein kinase (PKA). We further show that the coactivator CBP up-regulates PKA-mediated activation of the TH promoter and, if tethered to the TH promoter by a GAL4-fusion, can robustly transactivate the TH promoter even in the absence of PKA. Collectively, our results suggest that multiple CRE-binding factors interact with the CRE and regulate, in conjunction with the coactivator CBP, the transcriptional activity of the TH gene.

Regulation of tyrosine hydroxylase gene transcription by the cAMP-signaling pathway: involvement of multiple transcription factors. The conversion of L-tyrosine to 3,4-dihydroxy-L-phenylalanine by tyrosine hydroxylase (TH) is the first and rate-limiting step in biosynthesis of catecholamine neurotransmitters. TH gene expression is regulated in a cell type-specific and cAMP-dependent manner. Evidence from this laboratory and others indicates that the cAMP response element (CRE), residing at -45 to -38 bp upstream of the transcription initiation site, is essential for both basal and cAMP-inducible transcription of the TH gene. To understand the control mechanisms of TH gene transcription in greater detail, we sought to identify and characterize the transcription factors involved in recognition and activation of the CRE of the TH gene. Remarkably, electrophoretic mobility shift assay and antibody supershift experiments indicated that all three major CRE-binding protein factors, i.e. CREB, ATF1, and CREM, may participate in forming specific DNA/protein complexes with the CRE of the TH gene. To address the transcriptional activation function of individual factors, we replaced the TH CRE with a GAL4-binding site and cotransfected this modified TH promoter-reporter gene with an effector plasmid that encodes GAL4-fused transcription factor. Our results indicate that CREB but not ATF1 can support basal promoter activity while both can robustly induce the promoter activity in response to co-expression of the catalytic subunit of cAMP-dependent protein kinase (PKA). We further show that the coactivator CBP up-regulates PKA-mediated activation of the TH promoter and, if tethered to the TH promoter by a GAL4-fusion, can robustly transactivate the TH promoter even in the absence of PKA. Collectively, our results suggest that multiple CRE-binding factors interact with the CRE and regulate, in conjunction with the coactivator CBP, the transcriptional activity of the TH gene.

pubmed23n0106_830

Magnetic resonance microscopy of chick embryos in ovo.

Magnetic resonance imaging (MRI) of the live 11-day chick embryo with special radiofrequency coils and 3-D imaging methods has produced contiguous 1.25-mm-thick slices with 200-microns pixel resolution, permitting definition of cardiac chambers, cerebral ventricles, spinal cord, liver, and lungs. It was the objective of this study to image younger chick embryos in ovo with higher spatial resolution through the application of implanted radiofrequency coils. Fertilized Arbor Acre eggs were windowed at 9, 6, and 4 days. Circular coils 18 mm in diameter tuned to 85.5 MHz were suspended around the developing embryo. The eggs were sealed with tape and maintained at 37 degrees C during the imaging procedure. MRI was performed in a 2.0-Tesla GE system utilizing a 3-D Fourier transform acquisition in sagittal and axial planes with a partial saturation sequence (TR = 400 ms, TE = 27 ms). Approximately 1 hour of imaging time was required to obtain 16 contiguous 600-microns-thick slices with 50-microns pixel resolution. Embryos remained viable through the imaging procedure. Embryos were photographed, fixed, and cleared for correlative anatomical study. Vitelline vessels, dorsal aorta, aortic arches, cardinal veins, and cardiac chambers were identified as areas of decreased signal intensity. Cerebral ventricles and the vitreous portion of the eye have signal intensities that are less than adjacent neural, scleral, and lens tissue. Further refinements in MR instrumentation and imaging sequences promise improvements in resolution and offer the potential for sequential observations of the intact embryo.

Magnetic resonance microscopy of chick embryos in ovo. Magnetic resonance imaging (MRI) of the live 11-day chick embryo with special radiofrequency coils and 3-D imaging methods has produced contiguous 1.25-mm-thick slices with 200-microns pixel resolution, permitting definition of cardiac chambers, cerebral ventricles, spinal cord, liver, and lungs. It was the objective of this study to image younger chick embryos in ovo with higher spatial resolution through the application of implanted radiofrequency coils. Fertilized Arbor Acre eggs were windowed at 9, 6, and 4 days. Circular coils 18 mm in diameter tuned to 85.5 MHz were suspended around the developing embryo. The eggs were sealed with tape and maintained at 37 degrees C during the imaging procedure. MRI was performed in a 2.0-Tesla GE system utilizing a 3-D Fourier transform acquisition in sagittal and axial planes with a partial saturation sequence (TR = 400 ms, TE = 27 ms). Approximately 1 hour of imaging time was required to obtain 16 contiguous 600-microns-thick slices with 50-microns pixel resolution. Embryos remained viable through the imaging procedure. Embryos were photographed, fixed, and cleared for correlative anatomical study. Vitelline vessels, dorsal aorta, aortic arches, cardinal veins, and cardiac chambers were identified as areas of decreased signal intensity. Cerebral ventricles and the vitreous portion of the eye have signal intensities that are less than adjacent neural, scleral, and lens tissue. Further refinements in MR instrumentation and imaging sequences promise improvements in resolution and offer the potential for sequential observations of the intact embryo.

pubmed23n0500_19985

IKr channel blockers: novel antiarrhythmic agents.

There have been extensive efforts to develop I(Kr) channel blockers as a new antiarrhythmic agent for atrial or ventricular fibrillation, since it was demonstrated that selective blockade of the rapidly activating delayed rectifier K+ channel (I(Kr)) in the heart is not deleterious for the total mortality in fatal ventricular arrhythmia patients. Among them, dofetilide and KCB-328 blocks the I(Kr) specifically. Therefore, it increases the action potential duration (APD) selectively. Ibutilide, trecetilide, nifekalant, dronedarone, BRL-32872, H345/52 and ersentilide block the I(Kr). However, they modify also other cardiac channels or receptors. The frequency dependence of the compounds in prolonging the APD varies from the strong reversed tendency of dofetilide to the relatively neutral profile of KCB-328 and BRL-32872. Every compound reported so far has a proarrhythmic potential of torsade de pointes induction under certain conditions, although depending on the structure, the intensity may be somewhat different. In the coming decade, efforts to improve the reverse frequency dependence profile of the I(Kr) blockers by optimizing the onset and recovery time constant of the HERG block (e.g. KCB-328, vesnarinone) or the balance between the block of I(Kr) and Ca++ channels in the heart (e.g. BRL-32872, H 345/52) to eliminate the proarrhythmic potential of the currently known I(Kr) blockers are warranted. Further trials are also needed to discover more favorable compounds with multiple receptors including I(Kr) (e.g. nifekalant, dronedarone) for treating ventricular arrhythmias.

IKr channel blockers: novel antiarrhythmic agents. There have been extensive efforts to develop I(Kr) channel blockers as a new antiarrhythmic agent for atrial or ventricular fibrillation, since it was demonstrated that selective blockade of the rapidly activating delayed rectifier K+ channel (I(Kr)) in the heart is not deleterious for the total mortality in fatal ventricular arrhythmia patients. Among them, dofetilide and KCB-328 blocks the I(Kr) specifically. Therefore, it increases the action potential duration (APD) selectively. Ibutilide, trecetilide, nifekalant, dronedarone, BRL-32872, H345/52 and ersentilide block the I(Kr). However, they modify also other cardiac channels or receptors. The frequency dependence of the compounds in prolonging the APD varies from the strong reversed tendency of dofetilide to the relatively neutral profile of KCB-328 and BRL-32872. Every compound reported so far has a proarrhythmic potential of torsade de pointes induction under certain conditions, although depending on the structure, the intensity may be somewhat different. In the coming decade, efforts to improve the reverse frequency dependence profile of the I(Kr) blockers by optimizing the onset and recovery time constant of the HERG block (e.g. KCB-328, vesnarinone) or the balance between the block of I(Kr) and Ca++ channels in the heart (e.g. BRL-32872, H 345/52) to eliminate the proarrhythmic potential of the currently known I(Kr) blockers are warranted. Further trials are also needed to discover more favorable compounds with multiple receptors including I(Kr) (e.g. nifekalant, dronedarone) for treating ventricular arrhythmias.

pubmed23n0799_477

Survivin mRNA Level in Blood Predict the Efficacy of Neoadjuvant Chemotherapy in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer.

In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by real-time quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P = 0.01 and P = 0.008, respectively) and pathologic response (both P = 0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P = 0.021 and P = 0.014, respectively for DFS; P = 0.009 and P = 0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.

Survivin mRNA Level in Blood Predict the Efficacy of Neoadjuvant Chemotherapy in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer. In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by real-time quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P = 0.01 and P = 0.008, respectively) and pathologic response (both P = 0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P = 0.021 and P = 0.014, respectively for DFS; P = 0.009 and P = 0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.

pubmed23n1024_11194

Staphylococci evade the innate immune response by disarming neutrophils and forming biofilms.

Staphylococcus aureus and Staphylococcus epidermidis can cause many types of infections, ranging from skin infections to implant-associated infections. The primary innate immune response against bacterial infections involves complement activation, recruitment of phagocytes (most importantly neutrophils), and subsequent killing of the pathogen. However, staphylococci are not innocent bystanders; they actively obstruct this immune attack. To do that, S. aureus secretes several immune-evasion proteins to resist attack by the innate immune system. Furthermore, S. aureus and S. epidermidis are known for their ability to form biofilms on implanted medical devices and host tissues, which provides another important immune-evasion mechanism. Understanding these different strategies to resist immune attack will help to develop novel therapies against staphylococcal infections.

Staphylococci evade the innate immune response by disarming neutrophils and forming biofilms. Staphylococcus aureus and Staphylococcus epidermidis can cause many types of infections, ranging from skin infections to implant-associated infections. The primary innate immune response against bacterial infections involves complement activation, recruitment of phagocytes (most importantly neutrophils), and subsequent killing of the pathogen. However, staphylococci are not innocent bystanders; they actively obstruct this immune attack. To do that, S. aureus secretes several immune-evasion proteins to resist attack by the innate immune system. Furthermore, S. aureus and S. epidermidis are known for their ability to form biofilms on implanted medical devices and host tissues, which provides another important immune-evasion mechanism. Understanding these different strategies to resist immune attack will help to develop novel therapies against staphylococcal infections.

pubmed23n0655_4670

Intracellular cholesterol homeostasis and amyloid precursor protein processing.

Many preclinical and clinical studies have implied a role for cholesterol in the pathogenesis of Alzheimer's disease (AD). In this review we will discuss the movement of intracellular cholesterol and how normal distribution, transport, and export of cholesterol are vital for regulation of the AD related protein, Abeta. We focus on cholesterol distribution in the plasma membrane, transport through the endosomal/lysosomal system, control of cholesterol intracellular signaling at the endoplasmic reticulum and Golgi, the HMG-CoA reductase pathway and finally export of cholesterol from the cell.

Intracellular cholesterol homeostasis and amyloid precursor protein processing. Many preclinical and clinical studies have implied a role for cholesterol in the pathogenesis of Alzheimer's disease (AD). In this review we will discuss the movement of intracellular cholesterol and how normal distribution, transport, and export of cholesterol are vital for regulation of the AD related protein, Abeta. We focus on cholesterol distribution in the plasma membrane, transport through the endosomal/lysosomal system, control of cholesterol intracellular signaling at the endoplasmic reticulum and Golgi, the HMG-CoA reductase pathway and finally export of cholesterol from the cell.

pubmed23n0912_7351

Kupffer cells in immune activation and tolerance toward HBV/HCV infection.

Kupffer cells (KCs) are macrophages that are found in the sinusoids of the liver. KCs are a crucial part of the innate immune system, acting as scavengers and phagocytes. KCs and sinusoidal endothelial cells together form the first immune barrier of the portal system. Studies show that KCs can not only maintain homeostasis in the immune response, but also facilitate the pathogenesis of type B and type C hepatitis (HBV/HCV) through their antigen-presenting function and secretion of soluble mediators. KCs can express toll-like receptors (TLRs), Fas ligand (FasL) and programmed cell death ligand 1 (PD-L1), and secrete large amounts of inflammatory factors leading to immune tolerance toward HBV/HCV. On the one hand, KCs contribute to the clearance of HBV/HCV due to their nature as innate immune cells. At the same time, KCs induce immune tolerance toward HBV/HCV, which leads to chronicity of the infection. The dual role of KCs in the immune response toward HBV/HCV means it is a gigantic challenge for scientists to illuminate the detailed mechanisms involved, but it also offers important potential therapeutic targets.

Kupffer cells in immune activation and tolerance toward HBV/HCV infection. Kupffer cells (KCs) are macrophages that are found in the sinusoids of the liver. KCs are a crucial part of the innate immune system, acting as scavengers and phagocytes. KCs and sinusoidal endothelial cells together form the first immune barrier of the portal system. Studies show that KCs can not only maintain homeostasis in the immune response, but also facilitate the pathogenesis of type B and type C hepatitis (HBV/HCV) through their antigen-presenting function and secretion of soluble mediators. KCs can express toll-like receptors (TLRs), Fas ligand (FasL) and programmed cell death ligand 1 (PD-L1), and secrete large amounts of inflammatory factors leading to immune tolerance toward HBV/HCV. On the one hand, KCs contribute to the clearance of HBV/HCV due to their nature as innate immune cells. At the same time, KCs induce immune tolerance toward HBV/HCV, which leads to chronicity of the infection. The dual role of KCs in the immune response toward HBV/HCV means it is a gigantic challenge for scientists to illuminate the detailed mechanisms involved, but it also offers important potential therapeutic targets.

pubmed23n1151_508

Identification and Characterization of Malolactic Bacteria Isolated from the Eastern Foothills of Helan Mountain in China.

Malolactic fermentation (MLF) converts malic acid into lactic acid by lactic acid bacteria (LAB). MLF may affect potential wine quality impact as global warming intensifies, and the alcohol in the wine increases, which threatens MLF. <iLactiplantibacillus plantarum</i is considered a new generation of MLF starter because of the ability of high ethanol tolerance and good enological characteristics. In this research, 132 LAB strains were isolated from the eastern foothills of Helan Mountain in Ningxia, China. Twenty-one higher ethanol tolerance isolates were obtained by 15% (<iv</i/<iv</i) ethanol preliminary screening. They were identified by 16S rRNA sequencing and differentiated by randomly amplified polymorphic DNA (RAPD). Stress factors include ethanol, pH, and SO<sub2</sub, and the combination of stresses was used to screen stress-tolerance strains. β-D-glucosidase activity, MLF performance, and biogenic amine content were tested to evaluate the enological characteristics. GC-MS detected the volatile components of the wine after MLF. The results showed that twenty strains were identified as <iL. plantarum</i, and one strain was <iLentilactobacillus hilgardii</i. Especially, the strains of A7, A18, A23, A50, and B28 showed strong resistance to high ethanol, low pH, and high SO<sub2</sub. A7, A50, and B28 showed better β-D-glucosidase activity and thus were inoculated into cabernet sauvignon wines whose ethanol content was 14.75% (<iv</i/<iv</i) to proceed MLF. A7 finished MLF in 36 d, while the control strains <iOenococcus oeni</i 31-DH and <iL. plantarum</i BV-S2 finished MLF in 24 d and 28 d, respectively. Nevertheless, A50 and B28 did not finish MLF in 36 d. The data showed that A7 brought a more volatile aroma than control. Notably, the esters and terpenes in the wine increased. These results demonstrated the potential applicability of <iL. plantarum</i A7 as a new MLF starter culture, especially for high-ethanol wines.

Identification and Characterization of Malolactic Bacteria Isolated from the Eastern Foothills of Helan Mountain in China. Malolactic fermentation (MLF) converts malic acid into lactic acid by lactic acid bacteria (LAB). MLF may affect potential wine quality impact as global warming intensifies, and the alcohol in the wine increases, which threatens MLF. <iLactiplantibacillus plantarum</i is considered a new generation of MLF starter because of the ability of high ethanol tolerance and good enological characteristics. In this research, 132 LAB strains were isolated from the eastern foothills of Helan Mountain in Ningxia, China. Twenty-one higher ethanol tolerance isolates were obtained by 15% (<iv</i/<iv</i) ethanol preliminary screening. They were identified by 16S rRNA sequencing and differentiated by randomly amplified polymorphic DNA (RAPD). Stress factors include ethanol, pH, and SO<sub2</sub, and the combination of stresses was used to screen stress-tolerance strains. β-D-glucosidase activity, MLF performance, and biogenic amine content were tested to evaluate the enological characteristics. GC-MS detected the volatile components of the wine after MLF. The results showed that twenty strains were identified as <iL. plantarum</i, and one strain was <iLentilactobacillus hilgardii</i. Especially, the strains of A7, A18, A23, A50, and B28 showed strong resistance to high ethanol, low pH, and high SO<sub2</sub. A7, A50, and B28 showed better β-D-glucosidase activity and thus were inoculated into cabernet sauvignon wines whose ethanol content was 14.75% (<iv</i/<iv</i) to proceed MLF. A7 finished MLF in 36 d, while the control strains <iOenococcus oeni</i 31-DH and <iL. plantarum</i BV-S2 finished MLF in 24 d and 28 d, respectively. Nevertheless, A50 and B28 did not finish MLF in 36 d. The data showed that A7 brought a more volatile aroma than control. Notably, the esters and terpenes in the wine increased. These results demonstrated the potential applicability of <iL. plantarum</i A7 as a new MLF starter culture, especially for high-ethanol wines.

pubmed23n0502_2585

Biological ageing: a fundamental, biological link between socio-economic status and health?

Socio-economic differences in health appear to be universal but the precise pathways that link socio-economic status and health remain unclear. Differential exposure to specific risk and protective factors are often cited as, at least, partial explanations of socio-economic differences in health. However, risk factors are culturally specific and risk factor-specific models of socio-economic differences in health may be inadequate: as soon as prevailing risk factors change, so too must associated explanations of socio-economic differences in health. An alternative, risk factor-independent, model of socio-economic differences in health proposes that fundamental pathways to health and disease exist and that risk and protective factors act by feeding into these pathways. We propose that biological ageing is one such fundamental pathway to health, disease and, thus, socio-economic differences in health. Biological ageing is the progressive decline in physiological ability to meet demands, that occurs over time. It is due to the accumulation of damage at the cellular level and the rate of biological ageing is determined by both environmental and genetic factors. There is increasing evidence that many known disease risk and protective factors influence the rate of cellular damage accumulation and hence biological ageing and that the pathogenesis of some important diseases is related to biological ageing. We discuss these issues and hypothesize that socio-economic differences in health are partly a result of poor people ageing faster than rich people due to the unhealthy environments to which they are exposed.

Biological ageing: a fundamental, biological link between socio-economic status and health? Socio-economic differences in health appear to be universal but the precise pathways that link socio-economic status and health remain unclear. Differential exposure to specific risk and protective factors are often cited as, at least, partial explanations of socio-economic differences in health. However, risk factors are culturally specific and risk factor-specific models of socio-economic differences in health may be inadequate: as soon as prevailing risk factors change, so too must associated explanations of socio-economic differences in health. An alternative, risk factor-independent, model of socio-economic differences in health proposes that fundamental pathways to health and disease exist and that risk and protective factors act by feeding into these pathways. We propose that biological ageing is one such fundamental pathway to health, disease and, thus, socio-economic differences in health. Biological ageing is the progressive decline in physiological ability to meet demands, that occurs over time. It is due to the accumulation of damage at the cellular level and the rate of biological ageing is determined by both environmental and genetic factors. There is increasing evidence that many known disease risk and protective factors influence the rate of cellular damage accumulation and hence biological ageing and that the pathogenesis of some important diseases is related to biological ageing. We discuss these issues and hypothesize that socio-economic differences in health are partly a result of poor people ageing faster than rich people due to the unhealthy environments to which they are exposed.

pubmed23n0904_23536

Premature coronary artery disease in India: coronary artery disease in the young (CADY) registry.

Coronary artery disease (CAD) occurs at younger age in India but only a limited number of studies have evaluated risk factors and management status. This is a multisite observational registry to assess risk factors and treatment patterns in young patients presenting with acute coronary syndrome (ACS) and stable ischemic heart disease (IHD). We recruited 997 young patients (men &lt;55, women &lt;65y) presenting with ACS or stable IHD successively at 22 centers across India. Details of baseline risk factors and management status were obtained. Descriptive statistics are reported. Mean age of participants was 49.1±8y, 72% were men and 68% had ACS. Family history of CAD was in 50%, diabetes 44%, hypertension 49%, history of dyslipidemia 11%, smoking/tobacco use 39%, and sedentary habits in 20%. 1.3% had "possible familial hypercholesterolemia". Metabolic risk factors (high BMI, diabetes and hypertension) were significantly greater in women (p&lt;0.01). Women were older at diagnosis of CAD and presented more often with non-ST elevation ACS. In the study cohort antiplatelet use was in 85%, beta-blockers 38%, statins 63% and ACE inhibitors/ARBs in 41% while in ACS patients it was 80.5%, 54.6%, 80.8% and 40.8%, respectively. 35.9% patients underwent percutaneous coronary intervention while coronary bypass surgery was performed in 10.4%. Conventional risk factors including family history continue to play a pivotal role in premature CAD in Indians. Women have more of metabolic risk factors, present at a later age and have non-ST elevation ACS more often. There is a need to focus on improving use of evidence-based drug therapies and interventions.

Premature coronary artery disease in India: coronary artery disease in the young (CADY) registry. Coronary artery disease (CAD) occurs at younger age in India but only a limited number of studies have evaluated risk factors and management status. This is a multisite observational registry to assess risk factors and treatment patterns in young patients presenting with acute coronary syndrome (ACS) and stable ischemic heart disease (IHD). We recruited 997 young patients (men &lt;55, women &lt;65y) presenting with ACS or stable IHD successively at 22 centers across India. Details of baseline risk factors and management status were obtained. Descriptive statistics are reported. Mean age of participants was 49.1±8y, 72% were men and 68% had ACS. Family history of CAD was in 50%, diabetes 44%, hypertension 49%, history of dyslipidemia 11%, smoking/tobacco use 39%, and sedentary habits in 20%. 1.3% had "possible familial hypercholesterolemia". Metabolic risk factors (high BMI, diabetes and hypertension) were significantly greater in women (p&lt;0.01). Women were older at diagnosis of CAD and presented more often with non-ST elevation ACS. In the study cohort antiplatelet use was in 85%, beta-blockers 38%, statins 63% and ACE inhibitors/ARBs in 41% while in ACS patients it was 80.5%, 54.6%, 80.8% and 40.8%, respectively. 35.9% patients underwent percutaneous coronary intervention while coronary bypass surgery was performed in 10.4%. Conventional risk factors including family history continue to play a pivotal role in premature CAD in Indians. Women have more of metabolic risk factors, present at a later age and have non-ST elevation ACS more often. There is a need to focus on improving use of evidence-based drug therapies and interventions.

pubmed23n0355_16698

Ultrastructural features of medullary chromaffin cell cultures.

The ultrastructural organization on the fourth day of culture of chromaffin cells isolated from the bovine adrenal medulla was characterized based on electron microscopic and morphological analysis. We established that medullary chromaffin cells could be divided into four morphologically different subtypes. Most cells (49.1% of those examined) had a dense cytoplasm and fine dense granules. Cells with dense cytoplasm and large granules represented a second type of chromaffin cell (21.1%). Cells of the third type had a light cytoplasm, granules with a light halo and a well-developed Golgi apparatus (26.3%). The fourth type of chromaffin cell was characterized by moderately dense cytoplasm with well-expressed varicose rough endoplasmic reticulum (about 3.5%). Among concomitant cell types, cortical adrenal cells from the zona fasciculata and zona glomerulosa, epithelial cells, fibroblasts, lymphocytes, brown lipoblasts and glial Schwann cells were present. Morphological analysis implies that cells with dense cytoplasm and fine granules and those with light cytoplasm and haloed granules (75.4% in total) are adrenaline-containing cells, whereas the cells with dense cytoplasm and large granules (26.3%) contain noradrenaline. Cells with moderately dense cytoplasm and varicose reticulum share common morphological properties with classical glandular cells and, by their properties, were closer to noradrenaline-containing cells. It is concluded that chromaffin cells, which are the main cell type among cultured cells from adult bovine adrenal medulla, are morphologically quite heterogeneous. Other cell types of different nature may also be present in the culture and can locally influence the properties of the investigated medullary chromaffin cells used in electrophysiological experiments.

Ultrastructural features of medullary chromaffin cell cultures. The ultrastructural organization on the fourth day of culture of chromaffin cells isolated from the bovine adrenal medulla was characterized based on electron microscopic and morphological analysis. We established that medullary chromaffin cells could be divided into four morphologically different subtypes. Most cells (49.1% of those examined) had a dense cytoplasm and fine dense granules. Cells with dense cytoplasm and large granules represented a second type of chromaffin cell (21.1%). Cells of the third type had a light cytoplasm, granules with a light halo and a well-developed Golgi apparatus (26.3%). The fourth type of chromaffin cell was characterized by moderately dense cytoplasm with well-expressed varicose rough endoplasmic reticulum (about 3.5%). Among concomitant cell types, cortical adrenal cells from the zona fasciculata and zona glomerulosa, epithelial cells, fibroblasts, lymphocytes, brown lipoblasts and glial Schwann cells were present. Morphological analysis implies that cells with dense cytoplasm and fine granules and those with light cytoplasm and haloed granules (75.4% in total) are adrenaline-containing cells, whereas the cells with dense cytoplasm and large granules (26.3%) contain noradrenaline. Cells with moderately dense cytoplasm and varicose reticulum share common morphological properties with classical glandular cells and, by their properties, were closer to noradrenaline-containing cells. It is concluded that chromaffin cells, which are the main cell type among cultured cells from adult bovine adrenal medulla, are morphologically quite heterogeneous. Other cell types of different nature may also be present in the culture and can locally influence the properties of the investigated medullary chromaffin cells used in electrophysiological experiments.

pubmed23n0107_10890

Evaluation of computer advisor in the interpretation of CT images of the head.

This paper describes the evaluation of a computer advisor system (BRAINS), which was constructed to aid in the interpretation of CT images of the head. It was developed at the National Hospital for Nervous Diseases, Queen Square, London. The system was transferred, without difficulty, to an 'external', that is previously unassociated, site (the Department of Diagnostic Radiology, University of Manchester) for an external evaluation. Response of external users to the system was mixed. Many were unfamiliar with the concept of formal description of images and the evaluation demonstrated the need for a person to person training programme. Users who accessed the HELP facilities most frequently were the most successful in obtaining accurate descriptions and hence satisfactory diagnostic advice. An objective appraisal of user's success in describing images to obtain the correct diagnosis as first choice indicated that, in general, the system performed well.

Evaluation of computer advisor in the interpretation of CT images of the head. This paper describes the evaluation of a computer advisor system (BRAINS), which was constructed to aid in the interpretation of CT images of the head. It was developed at the National Hospital for Nervous Diseases, Queen Square, London. The system was transferred, without difficulty, to an 'external', that is previously unassociated, site (the Department of Diagnostic Radiology, University of Manchester) for an external evaluation. Response of external users to the system was mixed. Many were unfamiliar with the concept of formal description of images and the evaluation demonstrated the need for a person to person training programme. Users who accessed the HELP facilities most frequently were the most successful in obtaining accurate descriptions and hence satisfactory diagnostic advice. An objective appraisal of user's success in describing images to obtain the correct diagnosis as first choice indicated that, in general, the system performed well.

pubmed23n0737_16179

Prevalence of the 23S rRNA A2058G point mutation and molecular subtypes in Treponema pallidum in the United States, 2007 to 2009.

The 23S rRNA A2058G point mutation in Treponema pallidum is associated with macrolide antibiotic treatment failure. Its prevalence and potential association with a molecular subtype within the United States are unknown. During 2007 to 2009, 11 clinics across the United States sent samples from genital ulcers to the Centers for Disease Control and Prevention. Molecular techniques were used to identify T. pallidum DNA sequences, the A2058G mutation, and subtype of T. pallidum. Accompanying epidemiologic information was abstracted from medical records. A total of 141 samples with T. pallidum were collected from individuals whose median age was 33 years (range, 13-68 years): 118 were male (69% reported as men having sex with men [MSM]). The A2058G mutation was carried in 75 samples (53%) with T. pallidum, with samples from MSM (versus women and other men) more likely carrying the A2058G mutation (65/82 samples versus 8/57 samples; prevalence ratio, 5.7; 95% confidence interval, 2.9-10.8). Of 98 strain-typed samples, 61 (62%) were the 14d9 subtype of T. pallidum, which was also associated with samples with T. pallidum from MSM (prevalence ratio, 3.5; 95% confidence interval, 1.9-6.5). However, among T. pallidum from MSM, the A2058G mutation was not associated with the 14d9 subtype. The A2058G mutation and 14d9 subtype of T. pallidum were present throughout the United States. Both were more commonly found in T. pallidum from MSM compared with women or other men but were not associated with each other. Treating syphilis with azithromycin should be done cautiously and only when treatment with penicillin or doxycycline is not feasible.

Prevalence of the 23S rRNA A2058G point mutation and molecular subtypes in Treponema pallidum in the United States, 2007 to 2009. The 23S rRNA A2058G point mutation in Treponema pallidum is associated with macrolide antibiotic treatment failure. Its prevalence and potential association with a molecular subtype within the United States are unknown. During 2007 to 2009, 11 clinics across the United States sent samples from genital ulcers to the Centers for Disease Control and Prevention. Molecular techniques were used to identify T. pallidum DNA sequences, the A2058G mutation, and subtype of T. pallidum. Accompanying epidemiologic information was abstracted from medical records. A total of 141 samples with T. pallidum were collected from individuals whose median age was 33 years (range, 13-68 years): 118 were male (69% reported as men having sex with men [MSM]). The A2058G mutation was carried in 75 samples (53%) with T. pallidum, with samples from MSM (versus women and other men) more likely carrying the A2058G mutation (65/82 samples versus 8/57 samples; prevalence ratio, 5.7; 95% confidence interval, 2.9-10.8). Of 98 strain-typed samples, 61 (62%) were the 14d9 subtype of T. pallidum, which was also associated with samples with T. pallidum from MSM (prevalence ratio, 3.5; 95% confidence interval, 1.9-6.5). However, among T. pallidum from MSM, the A2058G mutation was not associated with the 14d9 subtype. The A2058G mutation and 14d9 subtype of T. pallidum were present throughout the United States. Both were more commonly found in T. pallidum from MSM compared with women or other men but were not associated with each other. Treating syphilis with azithromycin should be done cautiously and only when treatment with penicillin or doxycycline is not feasible.

pubmed23n0303_7256

Effect of a fluoridated toothpaste on lesion development in plaque-filled dentine grooves: an intra-oral study.

Fluoride can inhibit caries at plaque-retention sites, but some studies indicate that fluoride is less effective in fissures than on smooth surfaces. To study the efficacy of fluoridated toothpastes at plaque-retention sites, an intra-oral model was used with bovine coronal dentine discs, in which grooves of two different widths were sawn. The discs were mounted in the partial prostheses of 31 participants divided into two groups. One group brushed with a non-fluoridated toothpaste and a second with a paste containing 1,000 ppm fluoride as NaF. After 3 months, the specimens were retrieved and from each a thin section was taken for microradiographic analysis. Lesions which developed in the grooves resembled natural lesions in terms of the presence of a surface layer and the mineral content profiles. Extensive lesions followed the direction of the dentinal tubules. The mineral loss was quantified half-way into and at the base of the grooves and ranged from 0 to 20,000 vol% x microns. Analysis of variance showed that the mineral loss was significantly influenced by the treatment and the width of the grooves (p &lt; 0.001). In the broad grooves the average mineral loss was 19% smaller in the fluoride group than in the non-fluoride group, in the narrow grooves this value was 7%. Taking the two treatment groups together, the average mineral loss was largest half-way into the broad grooves (4,921 vol% x microns) and smallest at the base of the narrow grooves (2,289 vol% x microns). The results with this new intra-oral model indicate that the dimensions of small grooves in dentine, and thus their accessibility, determine not only their susceptibility to caries but also the protective effect of a fluoridated toothpaste.

Effect of a fluoridated toothpaste on lesion development in plaque-filled dentine grooves: an intra-oral study. Fluoride can inhibit caries at plaque-retention sites, but some studies indicate that fluoride is less effective in fissures than on smooth surfaces. To study the efficacy of fluoridated toothpastes at plaque-retention sites, an intra-oral model was used with bovine coronal dentine discs, in which grooves of two different widths were sawn. The discs were mounted in the partial prostheses of 31 participants divided into two groups. One group brushed with a non-fluoridated toothpaste and a second with a paste containing 1,000 ppm fluoride as NaF. After 3 months, the specimens were retrieved and from each a thin section was taken for microradiographic analysis. Lesions which developed in the grooves resembled natural lesions in terms of the presence of a surface layer and the mineral content profiles. Extensive lesions followed the direction of the dentinal tubules. The mineral loss was quantified half-way into and at the base of the grooves and ranged from 0 to 20,000 vol% x microns. Analysis of variance showed that the mineral loss was significantly influenced by the treatment and the width of the grooves (p &lt; 0.001). In the broad grooves the average mineral loss was 19% smaller in the fluoride group than in the non-fluoride group, in the narrow grooves this value was 7%. Taking the two treatment groups together, the average mineral loss was largest half-way into the broad grooves (4,921 vol% x microns) and smallest at the base of the narrow grooves (2,289 vol% x microns). The results with this new intra-oral model indicate that the dimensions of small grooves in dentine, and thus their accessibility, determine not only their susceptibility to caries but also the protective effect of a fluoridated toothpaste.

pubmed23n0622_2081

Highly versatile fiber-based optical Fabry-Pérot gas sensor.

We develop a versatile, compact, and sensitive fiber-based optical Fabry-Pérot (FP) gas sensor. The sensor probe is composed of a silver layer and a vapor-sensitive polymer layer that are sequentially deposited on the cleaved fiber endface, thus forming an FP cavity. The interference spectrum resulting from the reflected light at the silver-polymer and polymer-air interfaces changes when the polymer is exposed to gas analytes. This structure enables using any polymer regardless of the polymer refractive index (RI), which significantly enhances the sensor versatility. In experiments, we use polyethylene glycol (PEG) 400 (RI=1.465-1.469) and Norland Optical Adhesive (NOA) 81 (RI=1.53-1.56) as the gas sensing polymer and show drastically different sensor response to hexanol, methanol, and acetone. The estimated sensitivity for methanol vapor is 3.5 pm/ppm and 0.1 pm/ppm for PEG 400 and NOA 81, respectively, with a detection limit on the order of 1-10 ppm. Gas sensing for the analytes delivered in both continuous flow mode and pulsed mode is demonstrated.

Highly versatile fiber-based optical Fabry-Pérot gas sensor. We develop a versatile, compact, and sensitive fiber-based optical Fabry-Pérot (FP) gas sensor. The sensor probe is composed of a silver layer and a vapor-sensitive polymer layer that are sequentially deposited on the cleaved fiber endface, thus forming an FP cavity. The interference spectrum resulting from the reflected light at the silver-polymer and polymer-air interfaces changes when the polymer is exposed to gas analytes. This structure enables using any polymer regardless of the polymer refractive index (RI), which significantly enhances the sensor versatility. In experiments, we use polyethylene glycol (PEG) 400 (RI=1.465-1.469) and Norland Optical Adhesive (NOA) 81 (RI=1.53-1.56) as the gas sensing polymer and show drastically different sensor response to hexanol, methanol, and acetone. The estimated sensitivity for methanol vapor is 3.5 pm/ppm and 0.1 pm/ppm for PEG 400 and NOA 81, respectively, with a detection limit on the order of 1-10 ppm. Gas sensing for the analytes delivered in both continuous flow mode and pulsed mode is demonstrated.

pubmed23n0599_23229

[EphrinB2 gene transfection promotes the differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells].

To study the effects of ephrinB2 gene transfection on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into vascular endothelial cells. Wistar rat BMSCs were isolated by density gradient centrifugation and purified on the basis of their adhesion ability. The BMSCs were transfected with a lenti-virus vector encoding a constitutively active form of human ephrinB2 gene, and the cell markers including CD105, CD73, CD44, von Willebrand factor (VWF) and vascular growth factor receptor 2 (KDR) were detected using flow cytometry. The potential of ephrinB2-BMSCs for differentiation into osteoblasts and adipoblasts in vitro were tested, and the differentiation of the cells into endothelial-like cells was induced by culture in the presence of 2% fetal bovine serum and 50 ng/ml vascular endothelial growth factor. EphrinB2-BMSCs were positive for the markers CD105, CD73 and CD44, and negative for the typical endothelial markers like VWF and KDR, and retained high potentials for differentiation into osteoblasts and adipoblasts in vitro after cultivation in respective media. After induced differentiation, ephrinB2-BMSCs expressed VWF and KDR and showed greater ability of differentiation into vascular endothelial cells and formation of capillary structures on matrix gel than the BMSCs without transfection. EphrinB2 gene transfection efficiently promotes the differentiation of BMSCs into vascular endothelial cells. These genetically engineered cells provide valuable sources for new therapies of coronary heart disease.

[EphrinB2 gene transfection promotes the differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells]. To study the effects of ephrinB2 gene transfection on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into vascular endothelial cells. Wistar rat BMSCs were isolated by density gradient centrifugation and purified on the basis of their adhesion ability. The BMSCs were transfected with a lenti-virus vector encoding a constitutively active form of human ephrinB2 gene, and the cell markers including CD105, CD73, CD44, von Willebrand factor (VWF) and vascular growth factor receptor 2 (KDR) were detected using flow cytometry. The potential of ephrinB2-BMSCs for differentiation into osteoblasts and adipoblasts in vitro were tested, and the differentiation of the cells into endothelial-like cells was induced by culture in the presence of 2% fetal bovine serum and 50 ng/ml vascular endothelial growth factor. EphrinB2-BMSCs were positive for the markers CD105, CD73 and CD44, and negative for the typical endothelial markers like VWF and KDR, and retained high potentials for differentiation into osteoblasts and adipoblasts in vitro after cultivation in respective media. After induced differentiation, ephrinB2-BMSCs expressed VWF and KDR and showed greater ability of differentiation into vascular endothelial cells and formation of capillary structures on matrix gel than the BMSCs without transfection. EphrinB2 gene transfection efficiently promotes the differentiation of BMSCs into vascular endothelial cells. These genetically engineered cells provide valuable sources for new therapies of coronary heart disease.

pubmed23n0710_21438

Increased risk of asthma and atopic dermatitis in perinatally HIV-infected children and adolescents.

The incidence of asthma and atopic dermatitis (AD) was evaluated in HIV-infected (n = 451) compared to HIV-exposed (n = 227) but uninfected (HEU) children and adolescents by abstraction from clinical charts. Asthma was more common in HIV-infected compared to HEU children by clinical diagnosis (25% vs. 20%, p = 0.101), by asthma medication use, (31% vs. 22%, p = 0.012), and by clinical diagnosis and/or medication use, (34% vs. 25%, p = 0.012). HIV-infected children had a greater risk of asthma compared to HEU children (HR = 1.37, 95% CI: 1.01 to 1.86). AD was more common in HIV-infected than HEU children (20% vs. 12%, p = 0.009)) and children with AD were more likely to have asthma in both cohorts (41% vs. 29%, p = 0.010). HIV-infected children and adolescents in this study had an increased incidence of asthma and AD, a finding critical for millions of HIV-infected children worldwide.

Increased risk of asthma and atopic dermatitis in perinatally HIV-infected children and adolescents. The incidence of asthma and atopic dermatitis (AD) was evaluated in HIV-infected (n = 451) compared to HIV-exposed (n = 227) but uninfected (HEU) children and adolescents by abstraction from clinical charts. Asthma was more common in HIV-infected compared to HEU children by clinical diagnosis (25% vs. 20%, p = 0.101), by asthma medication use, (31% vs. 22%, p = 0.012), and by clinical diagnosis and/or medication use, (34% vs. 25%, p = 0.012). HIV-infected children had a greater risk of asthma compared to HEU children (HR = 1.37, 95% CI: 1.01 to 1.86). AD was more common in HIV-infected than HEU children (20% vs. 12%, p = 0.009)) and children with AD were more likely to have asthma in both cohorts (41% vs. 29%, p = 0.010). HIV-infected children and adolescents in this study had an increased incidence of asthma and AD, a finding critical for millions of HIV-infected children worldwide.

pubmed23n1012_2382

Treatment of Diabetic Macular Edema with Multiple Dexamethasone Intravitreal Implants: Evidence from Real-Life Experience.

To gain information about multiple dexamethasone intravitreal implant (DEX-I) injections in diabetic macular edema (DME) eyes in real-life clinical settings. Patients with DME treated with multiple (≥5) DEX-I injections between January 1, 2014, and December 31, 2018, were retrospectively enrolled regardless of previous treatment with anti-VEGF agents. All patients were evaluated with best-corrected visual acuity (BCVA) in logMAR, ocular fundus, and spectral domain optical coherence tomography (SD-OCT) at baseline and at 3 months after the last DEX-I injection. Multiple DEX-I injections were administered when necessary in case of DME recurrence. Main efficacy measures were changes in BCVA and central retinal thickness (CRT) from baseline to 3 months after the last DEX-I injection; main secondary measures were an increase in intraocular pressure (IOP), the need for cataract surgery, endophthalmitis, and vitreous hemorrhage. Seventeen patients (18 eyes) with DME and mean age (± SD) of 54.3 ± 8.16 years were treated with DEX-I injections between 2014 and 2018. The majority of eyes (77.8%) had been treated with a mean of 6.3 ± 3.2 anti-VEGF agents before switching to DEX-I. During a mean follow-up period of 37.6 months and after a mean number of 5.9 DEX-I injections, visual acuity improved or stabilized in 77.8% of all eyes, accompanied by a significant reduction in CRT. An increase in IOP was recorded in 38.8% of all patients, while a surgical procedure was needed for cataract in 73.3% of all phakic patients. In this real-life experience in Italy, multiple DEX-I treatments showed good efficacy with no new safety concerns. The follow-up duration of &gt;3 years and a greater number of DEX-I intravitreal injections compared to other observations confirm the positive balance between risks and benefits of DEX-I in the long term.

Treatment of Diabetic Macular Edema with Multiple Dexamethasone Intravitreal Implants: Evidence from Real-Life Experience. To gain information about multiple dexamethasone intravitreal implant (DEX-I) injections in diabetic macular edema (DME) eyes in real-life clinical settings. Patients with DME treated with multiple (≥5) DEX-I injections between January 1, 2014, and December 31, 2018, were retrospectively enrolled regardless of previous treatment with anti-VEGF agents. All patients were evaluated with best-corrected visual acuity (BCVA) in logMAR, ocular fundus, and spectral domain optical coherence tomography (SD-OCT) at baseline and at 3 months after the last DEX-I injection. Multiple DEX-I injections were administered when necessary in case of DME recurrence. Main efficacy measures were changes in BCVA and central retinal thickness (CRT) from baseline to 3 months after the last DEX-I injection; main secondary measures were an increase in intraocular pressure (IOP), the need for cataract surgery, endophthalmitis, and vitreous hemorrhage. Seventeen patients (18 eyes) with DME and mean age (± SD) of 54.3 ± 8.16 years were treated with DEX-I injections between 2014 and 2018. The majority of eyes (77.8%) had been treated with a mean of 6.3 ± 3.2 anti-VEGF agents before switching to DEX-I. During a mean follow-up period of 37.6 months and after a mean number of 5.9 DEX-I injections, visual acuity improved or stabilized in 77.8% of all eyes, accompanied by a significant reduction in CRT. An increase in IOP was recorded in 38.8% of all patients, while a surgical procedure was needed for cataract in 73.3% of all phakic patients. In this real-life experience in Italy, multiple DEX-I treatments showed good efficacy with no new safety concerns. The follow-up duration of &gt;3 years and a greater number of DEX-I intravitreal injections compared to other observations confirm the positive balance between risks and benefits of DEX-I in the long term.

pubmed23n0985_26048

Strengthening Our Schools to Promote Resilience and Health Among LGBTQ Youth: Emerging Evidence and Research Priorities from <i>The State of LGBTQ Youth Health and Wellbeing</i> Symposium.

Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) adolescents face well-documented health disparities in suicide risk, substance use, and sexual health. These disparities are known to stem, in part, from stigma directed toward LGBTQ youth in the form of minority stressors such as violence, discrimination, and harassment. Given the proportion of time that LGBTQ students spend in school, schools provide a critical context within which protective factors may be developed and leveraged to improve the health and wellbeing of these populations. This article provides a summary of key findings from a discussion among researchers, practitioners, and community members who participated in "<iThe State of LGBTQ Youth Health and Wellbeing: Strengthening Schools and Families to Build Resilience,"</i a public symposium held in June 2017. We detail emerging science on and future priorities for school-based research with LGBTQ youth which were identified by attendees at this meeting, with a particular focus on intersectionality, supportive adults in schools, and in-school programs. We call for more school-based research on priority gaps such as how LGBTQ students' intersecting identities affect their in-school experiences, how to design professional development programs that cultivate supportive educators, and how to leverage gay-straight alliances/gender and sexuality alliances as sites of health programming for LGBTQ students.

Strengthening Our Schools to Promote Resilience and Health Among LGBTQ Youth: Emerging Evidence and Research Priorities from <i>The State of LGBTQ Youth Health and Wellbeing</i> Symposium. Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) adolescents face well-documented health disparities in suicide risk, substance use, and sexual health. These disparities are known to stem, in part, from stigma directed toward LGBTQ youth in the form of minority stressors such as violence, discrimination, and harassment. Given the proportion of time that LGBTQ students spend in school, schools provide a critical context within which protective factors may be developed and leveraged to improve the health and wellbeing of these populations. This article provides a summary of key findings from a discussion among researchers, practitioners, and community members who participated in "<iThe State of LGBTQ Youth Health and Wellbeing: Strengthening Schools and Families to Build Resilience,"</i a public symposium held in June 2017. We detail emerging science on and future priorities for school-based research with LGBTQ youth which were identified by attendees at this meeting, with a particular focus on intersectionality, supportive adults in schools, and in-school programs. We call for more school-based research on priority gaps such as how LGBTQ students' intersecting identities affect their in-school experiences, how to design professional development programs that cultivate supportive educators, and how to leverage gay-straight alliances/gender and sexuality alliances as sites of health programming for LGBTQ students.

pubmed23n0026_2114

Vasopressin analog DDAVP in the treatment of diabetes insipidus.

A synthetic vasopressin analog, 1-desamino-8D-arginine vasopressin (DDAVP also known as desmopressin), was found to be highly effective in the treatment of seven children and one adult with vasopressin-sensitive diabetes insipidus. The average duration of action of DDAVP was 10 to 11 hours, and with proper adjustment of dose, the subjects were able to control their symptoms satisfactorily with one or two inhalations daily. The youngest child in whom adequate control was achieved was 2 years of age. All subjects found the use of intranasal DDAVP superior to other forms of therapy, and none experienced any known side-effects after six months of treatment. All subjects in this study are currently using 2.5 mug to 10 mug of DDAVP once or twice daily.

Vasopressin analog DDAVP in the treatment of diabetes insipidus. A synthetic vasopressin analog, 1-desamino-8D-arginine vasopressin (DDAVP also known as desmopressin), was found to be highly effective in the treatment of seven children and one adult with vasopressin-sensitive diabetes insipidus. The average duration of action of DDAVP was 10 to 11 hours, and with proper adjustment of dose, the subjects were able to control their symptoms satisfactorily with one or two inhalations daily. The youngest child in whom adequate control was achieved was 2 years of age. All subjects found the use of intranasal DDAVP superior to other forms of therapy, and none experienced any known side-effects after six months of treatment. All subjects in this study are currently using 2.5 mug to 10 mug of DDAVP once or twice daily.

pubmed23n0850_20361

Does methyl jasmonate modify the oxidative stress response in Phaseolus coccineus treated with Cu?

The contribution of methyl jasmonate (MJ) as a signal molecule able to take part in the defense mechanism against copper (Cu)-imposed oxidative stress was studied in the leaves and roots of runner bean (Phaseolus coccineus) plants. Roots of plants cultivated hydroponically were preincubated in MJ (10µM) for 1h or 24h and subsequently exposed to Cu (50µM) for 5h (short-term experiment) or 5 days (long-term experiment). Enzymatic (activity of superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; guaiacol peroxidase, POX) and non-enzymatic (accumulation of malondialdehyde, MDA; homoglutathione, hGSH; proline; anthocyanins; low molecular weight organic acids, LMWOAs) responses were determined in the leaves and roots. The antioxidative defense mechanism was significantly activated after Cu supplementation. In most cases, activities of ROS (reactive oxygen species) scavenging enzymes like SOD, CAT, APX, POX, as well as MDA, hGSH and proline concentrations increased following Cu exposure. MJ showed a time-dependent effect on antioxidative enzymes activity. In the short-term experiment, MJ elevated CAT, APX and POX activities in the roots, and POX activity in the leaves of non-Cu-treated plants. In the long-term experiment, MJ not only decreased POX and partially CAT activity in the roots, but also increased the MDA level and partially CAT activity in the leaves of the control plants. In Cu-treated plants, MJ reduced APX, but elevated POX activity in the leaves after 5-h exposure. After 5-day-Cu treatment, MJ inhibited POX activity in the leaves and mainly reduced SOD and CAT activities in the roots. Moreover, in the long-term experiment, MJ reduced tartrate and pyruvate in the leaves of Cu-stressed plants, but mostly elevated tartrate and malate in the roots comparing with Cu alone treatment. MJ alone and under Cu excess did not alter accumulation of MDA, hGSH and proline comparing with Cu alone, but partially elevated anthocyanin concentration. The results indicated that MJ was both partially potent in modifying the antioxidative enzymes activity and metabolites accumulation in non-stress and Cu-stress conditions.

Does methyl jasmonate modify the oxidative stress response in Phaseolus coccineus treated with Cu? The contribution of methyl jasmonate (MJ) as a signal molecule able to take part in the defense mechanism against copper (Cu)-imposed oxidative stress was studied in the leaves and roots of runner bean (Phaseolus coccineus) plants. Roots of plants cultivated hydroponically were preincubated in MJ (10µM) for 1h or 24h and subsequently exposed to Cu (50µM) for 5h (short-term experiment) or 5 days (long-term experiment). Enzymatic (activity of superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; guaiacol peroxidase, POX) and non-enzymatic (accumulation of malondialdehyde, MDA; homoglutathione, hGSH; proline; anthocyanins; low molecular weight organic acids, LMWOAs) responses were determined in the leaves and roots. The antioxidative defense mechanism was significantly activated after Cu supplementation. In most cases, activities of ROS (reactive oxygen species) scavenging enzymes like SOD, CAT, APX, POX, as well as MDA, hGSH and proline concentrations increased following Cu exposure. MJ showed a time-dependent effect on antioxidative enzymes activity. In the short-term experiment, MJ elevated CAT, APX and POX activities in the roots, and POX activity in the leaves of non-Cu-treated plants. In the long-term experiment, MJ not only decreased POX and partially CAT activity in the roots, but also increased the MDA level and partially CAT activity in the leaves of the control plants. In Cu-treated plants, MJ reduced APX, but elevated POX activity in the leaves after 5-h exposure. After 5-day-Cu treatment, MJ inhibited POX activity in the leaves and mainly reduced SOD and CAT activities in the roots. Moreover, in the long-term experiment, MJ reduced tartrate and pyruvate in the leaves of Cu-stressed plants, but mostly elevated tartrate and malate in the roots comparing with Cu alone treatment. MJ alone and under Cu excess did not alter accumulation of MDA, hGSH and proline comparing with Cu alone, but partially elevated anthocyanin concentration. The results indicated that MJ was both partially potent in modifying the antioxidative enzymes activity and metabolites accumulation in non-stress and Cu-stress conditions.

pubmed23n0811_898

Dynamical modeling of the cell cycle and cell fate emergence in Caulobacter crescentus.

The division of Caulobacter crescentus, a model organism for studying cell cycle and differentiation in bacteria, generates two cell types: swarmer and stalked. To complete its cycle, C. crescentus must first differentiate from the swarmer to the stalked phenotype. An important regulator involved in this process is CtrA, which operates in a gene regulatory network and coordinates many of the interactions associated to the generation of cellular asymmetry. Gaining insight into how such a differentiation phenomenon arises and how network components interact to bring about cellular behavior and function demands mathematical models and simulations. In this work, we present a dynamical model based on a generalization of the Boolean abstraction of gene expression for a minimal network controlling the cell cycle and asymmetric cell division in C. crescentus. This network was constructed from data obtained from an exhaustive search in the literature. The results of the simulations based on our model show a cyclic attractor whose configurations can be made to correspond with the current knowledge of the activity of the regulators participating in the gene network during the cell cycle. Additionally, we found two point attractors that can be interpreted in terms of the network configurations directing the two cell types. The entire network is shown to be operating close to the critical regime, which means that it is robust enough to perturbations on dynamics of the network, but adaptable to environmental changes.

Dynamical modeling of the cell cycle and cell fate emergence in Caulobacter crescentus. The division of Caulobacter crescentus, a model organism for studying cell cycle and differentiation in bacteria, generates two cell types: swarmer and stalked. To complete its cycle, C. crescentus must first differentiate from the swarmer to the stalked phenotype. An important regulator involved in this process is CtrA, which operates in a gene regulatory network and coordinates many of the interactions associated to the generation of cellular asymmetry. Gaining insight into how such a differentiation phenomenon arises and how network components interact to bring about cellular behavior and function demands mathematical models and simulations. In this work, we present a dynamical model based on a generalization of the Boolean abstraction of gene expression for a minimal network controlling the cell cycle and asymmetric cell division in C. crescentus. This network was constructed from data obtained from an exhaustive search in the literature. The results of the simulations based on our model show a cyclic attractor whose configurations can be made to correspond with the current knowledge of the activity of the regulators participating in the gene network during the cell cycle. Additionally, we found two point attractors that can be interpreted in terms of the network configurations directing the two cell types. The entire network is shown to be operating close to the critical regime, which means that it is robust enough to perturbations on dynamics of the network, but adaptable to environmental changes.

pubmed23n0928_3367

Collagen degradation as a possibility to determine the post-mortem interval (PMI) of animal bones: a validation study referring to an original study of Boaks et al. (2014).

Estimation of the post-mortem interval (PMI) of unknown skeletal remains is a common forensic task. Boaks and colleagues demonstrated a new method for PMI estimation in showing a reduction of the collagen to non-collagen content (Co/NCo ratio) in porcine bones after a PMI of 12 months using the Sirius Red/Fast Green Collagen Staining Kit from Chondrex in 2014 (Boaks et al. Forensic Sci Int 240: 104-110, 2014). The aim of our study was to reproduce this method and to investigate if the method could be used for forensic issues. Sixteen fresh porcine bones were placed in prepared boxes where they were treated regularly with distilled water or with water from hay infusions. For determining the Co/NCo ratio, we used the Sirius Red/Fast Green Collagen Staining Kit from Chondrex, which stains collagenous (Co) proteins red and non-collagenous (NCo) proteins green Chondrex Inc. (2008). After a PMI of 1-3 months, an analysis of porcine bone thin sections was performed on the one hand with spectrophotometry, on the other hand with stereomicroscopy. Using spectrophotometry, we go low and partially negative Co/NCo ratios which were up to 100-fold lower than the results we expected to get. The data we got by stereomicroscopy and calculating the Co/NCo ratio from extracting the red and green content with the software MATLAB and so calculating the Co/NCo ratio showed a correlation between PMI and the Co/NCo ratio in the porcine bone samples. Regular addition of distilled water or water from a hay infusion did not produce any significant differences so that an increased presence of microorganisms had obviously no influence on collagen degradation.

Collagen degradation as a possibility to determine the post-mortem interval (PMI) of animal bones: a validation study referring to an original study of Boaks et al. (2014). Estimation of the post-mortem interval (PMI) of unknown skeletal remains is a common forensic task. Boaks and colleagues demonstrated a new method for PMI estimation in showing a reduction of the collagen to non-collagen content (Co/NCo ratio) in porcine bones after a PMI of 12 months using the Sirius Red/Fast Green Collagen Staining Kit from Chondrex in 2014 (Boaks et al. Forensic Sci Int 240: 104-110, 2014). The aim of our study was to reproduce this method and to investigate if the method could be used for forensic issues. Sixteen fresh porcine bones were placed in prepared boxes where they were treated regularly with distilled water or with water from hay infusions. For determining the Co/NCo ratio, we used the Sirius Red/Fast Green Collagen Staining Kit from Chondrex, which stains collagenous (Co) proteins red and non-collagenous (NCo) proteins green Chondrex Inc. (2008). After a PMI of 1-3 months, an analysis of porcine bone thin sections was performed on the one hand with spectrophotometry, on the other hand with stereomicroscopy. Using spectrophotometry, we go low and partially negative Co/NCo ratios which were up to 100-fold lower than the results we expected to get. The data we got by stereomicroscopy and calculating the Co/NCo ratio from extracting the red and green content with the software MATLAB and so calculating the Co/NCo ratio showed a correlation between PMI and the Co/NCo ratio in the porcine bone samples. Regular addition of distilled water or water from a hay infusion did not produce any significant differences so that an increased presence of microorganisms had obviously no influence on collagen degradation.

pubmed23n0735_20977

Minding Rachlin's eliminative materialism.

Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist ontology of science, but without eliminating the phenomenology of consciousness. This view implies that to be judged human, machines not only must exhibit complicated temporally structured patterns of behavior, but also must have first-person conscious experience. Although confirming machine sentience is likely to be problematic, extended contact with a machine that results in a person interacting with it as if it were conscious could reasonably lead to the conclusion that for all intents and purposes it is.

Minding Rachlin's eliminative materialism. Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist ontology of science, but without eliminating the phenomenology of consciousness. This view implies that to be judged human, machines not only must exhibit complicated temporally structured patterns of behavior, but also must have first-person conscious experience. Although confirming machine sentience is likely to be problematic, extended contact with a machine that results in a person interacting with it as if it were conscious could reasonably lead to the conclusion that for all intents and purposes it is.

pubmed23n0015_10544

Atrioventricular canal malformation interpreted as secondary to reduced compression upon the developing heart.

This study was undertaken to evaluate the nature and pathogenesis of malformations of the atrioventricular canal in relation to normal cardiogenesis. Serial histologic sections of normal human embryos and fetuses were made, from which three-dimensional images were reconstructed to show the relationship between the developing heart and its surrounding structures, and the course of development of the atrial septum and atrioventricular valves. Based on these reconstructions and on examination of the hearts of 59 patients with atrioventricular canal malformations, it is suggested that the spectrum of atrioventricular malformations may arise as a result of reduced compression of the developing atria by surrounding structures during embryonic Stages 13 through 18. Comparison of hearts with atrioventricular canal defects with normal embryos indicated that the malformations may be classified as primitive canals, complete canals, or partial canals, corresponding to failure of completion of normal development in Stages 14 through 18. In primitive canal the atrial septum was absent or had only a portion of septum primum. In complete canal both atrial septums were present, but the atrioventricular valve material was not subdivided and the four chambers were in communication. In partial canal, the atrioventricular valve was divided, but atrial and ventricular septal defects and valve clefts were present in varying degrees of severity. It is proposed that the spectrum of cardiac abnormalities which constitutes atrioventricular canal malformations may be understood as arising from varying degrees of lack of normal compression of the developing heart by surrounding structures. (Am J Pathol 95.579-598, 1979)

Atrioventricular canal malformation interpreted as secondary to reduced compression upon the developing heart. This study was undertaken to evaluate the nature and pathogenesis of malformations of the atrioventricular canal in relation to normal cardiogenesis. Serial histologic sections of normal human embryos and fetuses were made, from which three-dimensional images were reconstructed to show the relationship between the developing heart and its surrounding structures, and the course of development of the atrial septum and atrioventricular valves. Based on these reconstructions and on examination of the hearts of 59 patients with atrioventricular canal malformations, it is suggested that the spectrum of atrioventricular malformations may arise as a result of reduced compression of the developing atria by surrounding structures during embryonic Stages 13 through 18. Comparison of hearts with atrioventricular canal defects with normal embryos indicated that the malformations may be classified as primitive canals, complete canals, or partial canals, corresponding to failure of completion of normal development in Stages 14 through 18. In primitive canal the atrial septum was absent or had only a portion of septum primum. In complete canal both atrial septums were present, but the atrioventricular valve material was not subdivided and the four chambers were in communication. In partial canal, the atrioventricular valve was divided, but atrial and ventricular septal defects and valve clefts were present in varying degrees of severity. It is proposed that the spectrum of cardiac abnormalities which constitutes atrioventricular canal malformations may be understood as arising from varying degrees of lack of normal compression of the developing heart by surrounding structures. (Am J Pathol 95.579-598, 1979)

pubmed23n0328_7559

[Weight loss by changing eating behavior: the target goal in therapy of obesity].

Obesity develops as an interaction of genetic disposition and environmental factors (nutrition, physical activity). Mental disturbances are considered to be a consequence but not the cause of overweight. For long term weight maintenance three factors are important: normalization of fat intake, flexible control of food intake and an increase in physical activity.

[Weight loss by changing eating behavior: the target goal in therapy of obesity]. Obesity develops as an interaction of genetic disposition and environmental factors (nutrition, physical activity). Mental disturbances are considered to be a consequence but not the cause of overweight. For long term weight maintenance three factors are important: normalization of fat intake, flexible control of food intake and an increase in physical activity.

pubmed23n0419_20881

The aging of Israel's Arab population: needs, existing responses, and dilemmas in the development of services for a society in transition.

The Arab population of Israel is relatively young. However, a significant increase is expected in the number of elderly Arabs in the coming years. At the end of 2001 there were 38,500 Arab elderly, but their number is expected to reach 92,100 by 2020. This will represent a nearly 2.5-fold increase in absolute numbers. As the population ages, the number and percentage of people with chronic diseases and related disabilities will rise significantly. While the Arab elderly are much younger than the Jewish elderly, they are more disabled and therefore have greater medical and nursing needs. An extremely important measure of the need for formal services is an elderly person's functional ability, especially the ability to live independently. The percentage of Arab elderly who are disabled and need help with activities of daily living is twice as high as that of the Jewish elderly population. At present, 30% of the Arab elderly (39% of the women and 20% of the men), compared to 14% of Jewish elderly (17% of the women and 11% of the men), need help in at least one ADL (bathing, dressing, eating, mobility in the home, rising and sitting, getting in and out of bed). Concomitant with demographic changes are forces that affect the ability of informal support systems to provide care. For example, the rising number of Arab women in the labor force together with changes in elderly peoples' living arrangements have increased the need for formal services to share responsibility for the elderly with families. As services are developed, questions arise regarding the extent to which they have been adapted to the culture and norms of Arab society and meet that society's unique needs. This paper elaborates on some of these issues.

The aging of Israel's Arab population: needs, existing responses, and dilemmas in the development of services for a society in transition. The Arab population of Israel is relatively young. However, a significant increase is expected in the number of elderly Arabs in the coming years. At the end of 2001 there were 38,500 Arab elderly, but their number is expected to reach 92,100 by 2020. This will represent a nearly 2.5-fold increase in absolute numbers. As the population ages, the number and percentage of people with chronic diseases and related disabilities will rise significantly. While the Arab elderly are much younger than the Jewish elderly, they are more disabled and therefore have greater medical and nursing needs. An extremely important measure of the need for formal services is an elderly person's functional ability, especially the ability to live independently. The percentage of Arab elderly who are disabled and need help with activities of daily living is twice as high as that of the Jewish elderly population. At present, 30% of the Arab elderly (39% of the women and 20% of the men), compared to 14% of Jewish elderly (17% of the women and 11% of the men), need help in at least one ADL (bathing, dressing, eating, mobility in the home, rising and sitting, getting in and out of bed). Concomitant with demographic changes are forces that affect the ability of informal support systems to provide care. For example, the rising number of Arab women in the labor force together with changes in elderly peoples' living arrangements have increased the need for formal services to share responsibility for the elderly with families. As services are developed, questions arise regarding the extent to which they have been adapted to the culture and norms of Arab society and meet that society's unique needs. This paper elaborates on some of these issues.

pubmed23n0724_23915

IκB kinase α phosphorylation of TRAF4 downregulates innate immune signaling.

Despite their homology, IκB kinase α (IKKα) and IKKβ have divergent roles in NF-κB signaling. IKKβ strongly activates NF-κB while IKKα can downregulate NF-κB under certain circumstances. Given this, identifying independent substrates for these kinases could help delineate their divergent roles. Peptide substrate array technology followed by bioinformatic screening identified TRAF4 as a substrate for IKKα. Like IKKα, TRAF4 is atypical within its family because it is the only TRAF family member to negatively regulate innate immune signaling. IKKα's phosphorylation of serine-426 on TRAF4 was required for this negative regulation. Binding to the Crohn's disease susceptibility protein, NOD2, is required for TRAF4 phosphorylation and subsequent inhibition of NOD2 signaling. Structurally, serine-426 resides within an exaggerated β-bulge in TRAF4 that is not present in the other TRAF proteins, and phosphorylation of this site provides a structural basis for the atypical function of TRAF4 and its atypical role in NOD2 signaling.

IκB kinase α phosphorylation of TRAF4 downregulates innate immune signaling. Despite their homology, IκB kinase α (IKKα) and IKKβ have divergent roles in NF-κB signaling. IKKβ strongly activates NF-κB while IKKα can downregulate NF-κB under certain circumstances. Given this, identifying independent substrates for these kinases could help delineate their divergent roles. Peptide substrate array technology followed by bioinformatic screening identified TRAF4 as a substrate for IKKα. Like IKKα, TRAF4 is atypical within its family because it is the only TRAF family member to negatively regulate innate immune signaling. IKKα's phosphorylation of serine-426 on TRAF4 was required for this negative regulation. Binding to the Crohn's disease susceptibility protein, NOD2, is required for TRAF4 phosphorylation and subsequent inhibition of NOD2 signaling. Structurally, serine-426 resides within an exaggerated β-bulge in TRAF4 that is not present in the other TRAF proteins, and phosphorylation of this site provides a structural basis for the atypical function of TRAF4 and its atypical role in NOD2 signaling.

pubmed23n0661_6802

Treatment utilization by gender in patients with borderline personality disorder.

Minimal data exist on treatment utilization by gender in borderline personality disorder (BPD). This study used an online questionnaire to investigate initial and lifetime patterns of utilization of multiple treatment modalities by patients with BPD, and parental satisfaction with treatment. Respondents were parents of probands diagnosed with BPD who completed a 100-question anonymous Internet survey. Of the 495 surveys that were analyzed, 409 pertained to female subjects with BPD and 86 to male subjects with BPD. Results for probands with BPD across gender were notable for similar high lifetime levels of use of care, including hospitalization, day programs, and halfway houses, but not similar levels of use of drug/alcohol rehabilitation services, which was greater among the male subjects with BPD. The male subjects with BPD received significantly less lifetime psychotherapy and pharmacotherapy than the female subjects with BPD, although the duration of medication and psychotherapy treatment did not differ by gender. These results highlight the need for more research to better understand what might account for these gender differences in treatment and improve strategies to provide appropriate care for male patients with BPD.

Treatment utilization by gender in patients with borderline personality disorder. Minimal data exist on treatment utilization by gender in borderline personality disorder (BPD). This study used an online questionnaire to investigate initial and lifetime patterns of utilization of multiple treatment modalities by patients with BPD, and parental satisfaction with treatment. Respondents were parents of probands diagnosed with BPD who completed a 100-question anonymous Internet survey. Of the 495 surveys that were analyzed, 409 pertained to female subjects with BPD and 86 to male subjects with BPD. Results for probands with BPD across gender were notable for similar high lifetime levels of use of care, including hospitalization, day programs, and halfway houses, but not similar levels of use of drug/alcohol rehabilitation services, which was greater among the male subjects with BPD. The male subjects with BPD received significantly less lifetime psychotherapy and pharmacotherapy than the female subjects with BPD, although the duration of medication and psychotherapy treatment did not differ by gender. These results highlight the need for more research to better understand what might account for these gender differences in treatment and improve strategies to provide appropriate care for male patients with BPD.

pubmed23n0239_10829

Morphological comparison of isolates of Phakopsora pachyrhizi from different areas of the world.

Isolates of Phakopsora pachyrhizi from Australia, Indian, the Philippines, Taiwan, and Puerto Rico were compared with respect to morphology and development of "Wayne" soybean. The most extensive comparisons were made between the Puerto Rican and Taiwanese isolates; these were indistinguishable in their prepenetration, penetration, and early colonization phases. Examination of uredia of all isolates by light and scanning electron microscopy (SEM) revealed no differences in uredial morphology. All isolates were indistinguishable with respect to uredospore size, shape, and apparently the number and distribution of uredospore germ pores. The only difference observed was the appearance of germ pores; germ pores of the Puerto Rican isolate were easier to see by means of SEM than those of the four Eastern Hemisphere isolates, suggesting that the Puerto Rican isolate may have thinner germ pore plugs. This difference is not sufficient to consider the isolates as taxonomically distinct.

Morphological comparison of isolates of Phakopsora pachyrhizi from different areas of the world. Isolates of Phakopsora pachyrhizi from Australia, Indian, the Philippines, Taiwan, and Puerto Rico were compared with respect to morphology and development of "Wayne" soybean. The most extensive comparisons were made between the Puerto Rican and Taiwanese isolates; these were indistinguishable in their prepenetration, penetration, and early colonization phases. Examination of uredia of all isolates by light and scanning electron microscopy (SEM) revealed no differences in uredial morphology. All isolates were indistinguishable with respect to uredospore size, shape, and apparently the number and distribution of uredospore germ pores. The only difference observed was the appearance of germ pores; germ pores of the Puerto Rican isolate were easier to see by means of SEM than those of the four Eastern Hemisphere isolates, suggesting that the Puerto Rican isolate may have thinner germ pore plugs. This difference is not sufficient to consider the isolates as taxonomically distinct.

pubmed23n0344_13717

An unusual case of carbon monoxide poisoning.

Carbon monoxide, a gas originating from incomplete combustion of carbon-based fuels, is an important cause of human deaths. In this paper, we describe an unusual carbon monoxide poisoning in a dwelling without obvious sources of combustion gases, for which two adults had to be treated in a hyperbaric chamber. Carbon monoxide readings were taken in the house and in the neighboring homes. Methane gas and nitrogen oxide levels were also monitored in the house air. Soil samples were collected around the house and tested for hydrocarbon residues. The investigation revealed the presence of a pocket of carbon monoxide under the foundation of the house. The first readings revealed carbon monoxide levels of 500 ppm in the basement. The contamination lasted for a week. The investigation indicated that the probable source of contamination was the use of explosives at a nearby rain sewer construction site. The use of explosives in a residential area can constitute a major source of carbon monoxide for the neighboring populations. This must be investigated, and public health authorities, primary-care physicians, governmental authorities, and users and manufacturers of explosives must be made aware of this problem.

An unusual case of carbon monoxide poisoning. Carbon monoxide, a gas originating from incomplete combustion of carbon-based fuels, is an important cause of human deaths. In this paper, we describe an unusual carbon monoxide poisoning in a dwelling without obvious sources of combustion gases, for which two adults had to be treated in a hyperbaric chamber. Carbon monoxide readings were taken in the house and in the neighboring homes. Methane gas and nitrogen oxide levels were also monitored in the house air. Soil samples were collected around the house and tested for hydrocarbon residues. The investigation revealed the presence of a pocket of carbon monoxide under the foundation of the house. The first readings revealed carbon monoxide levels of 500 ppm in the basement. The contamination lasted for a week. The investigation indicated that the probable source of contamination was the use of explosives at a nearby rain sewer construction site. The use of explosives in a residential area can constitute a major source of carbon monoxide for the neighboring populations. This must be investigated, and public health authorities, primary-care physicians, governmental authorities, and users and manufacturers of explosives must be made aware of this problem.

pubmed23n0854_23262

Correcting Susceptibility-Induced Distortion in Diffusion-Weighted MRI using Constrained Nonrigid Registration.

Echo Planar Imaging (EPI) is the standard pulse sequence used in fast diffusion-weighted magnetic resonance imaging (MRI), but is sensitive to susceptibility-induced inhomogeneities in the main B<sub0</sub magnetic field. In diffusion MRI of the human head, this leads to geometric distortion of the brain in reconstructed diffusion images, and a lack of correspondence with undistorted high-resolution MRI scans that are used to define the subject anatomy. In this study, we have tested an approach to estimate and correct this distortion of using a non-linear registration framework based on mutual-information. We use the commonly acquired anatomical image as the registration-template and constrain the registration using spatial regularization and physics-based information about the characteristics of the distortion, but without requiring any additional data collection. Results are shown for simulated and experimental data.

Correcting Susceptibility-Induced Distortion in Diffusion-Weighted MRI using Constrained Nonrigid Registration. Echo Planar Imaging (EPI) is the standard pulse sequence used in fast diffusion-weighted magnetic resonance imaging (MRI), but is sensitive to susceptibility-induced inhomogeneities in the main B<sub0</sub magnetic field. In diffusion MRI of the human head, this leads to geometric distortion of the brain in reconstructed diffusion images, and a lack of correspondence with undistorted high-resolution MRI scans that are used to define the subject anatomy. In this study, we have tested an approach to estimate and correct this distortion of using a non-linear registration framework based on mutual-information. We use the commonly acquired anatomical image as the registration-template and constrain the registration using spatial regularization and physics-based information about the characteristics of the distortion, but without requiring any additional data collection. Results are shown for simulated and experimental data.

pubmed23n0572_21035

Type I collagen is overexpressed in medulloblastoma as a component of tumor microenvironment.

Medulloblastoma is the most common malignant brain tumor of children, and more specific and effective therapeutic management needs to be developed to improve upon existing survival rates and to avoid side-effects from current treatment. Gain of chromosome seven is the most frequent chromosome copy number aberration in medulloblastoma, suggesting that overexpression of genes on chromosome seven might be important for the pathogenesis of medulloblastoma. We used microarrays to identify chromosome seven genes overexpressed in medulloblastoma specimens, and validated using data from published gene expression datasets. The gene encoding the alpha 2 subunit of type I collagen, COL1A2, was overexpressed in all three datasets. Immunohistochemistry of tumor tissues revealed type I collagen in the leptomeninges, and in the extracellular matrix surrounding blood vessels and medulloblastoma cells. Expression of both type I collagen and the beta1 subunit of integrin, a subunit of a known type I collagen receptor, localized to the same area of medulloblastoma. Adherence of D283 medulloblastoma cells to type I collagen matrix in vitro depends on the beta1 subunit of integrin. Because medulloblastoma is characteristic of high vascularity, and because inhibition of type I collagen synthesis has been shown to suppress angiogenesis and tumor growth, our data suggest that type I collagen might be a potential therapeutic target for treating medulloblastoma.

Type I collagen is overexpressed in medulloblastoma as a component of tumor microenvironment. Medulloblastoma is the most common malignant brain tumor of children, and more specific and effective therapeutic management needs to be developed to improve upon existing survival rates and to avoid side-effects from current treatment. Gain of chromosome seven is the most frequent chromosome copy number aberration in medulloblastoma, suggesting that overexpression of genes on chromosome seven might be important for the pathogenesis of medulloblastoma. We used microarrays to identify chromosome seven genes overexpressed in medulloblastoma specimens, and validated using data from published gene expression datasets. The gene encoding the alpha 2 subunit of type I collagen, COL1A2, was overexpressed in all three datasets. Immunohistochemistry of tumor tissues revealed type I collagen in the leptomeninges, and in the extracellular matrix surrounding blood vessels and medulloblastoma cells. Expression of both type I collagen and the beta1 subunit of integrin, a subunit of a known type I collagen receptor, localized to the same area of medulloblastoma. Adherence of D283 medulloblastoma cells to type I collagen matrix in vitro depends on the beta1 subunit of integrin. Because medulloblastoma is characteristic of high vascularity, and because inhibition of type I collagen synthesis has been shown to suppress angiogenesis and tumor growth, our data suggest that type I collagen might be a potential therapeutic target for treating medulloblastoma.

pubmed23n0548_14909

The relationship between navicular drop and first metatarsophalangeal joint motion.

This study was conducted to determine whether navicular drop, as a representative measure of foot pronation, was associated with first metatarsal joint motion in 24 healthy subjects aged 21 to 40 years. The magnitude of first metatarsophalangeal joint motion was identified using a custom-built weightbearing goniometer designed to measure maximal hallux dorsiflexion in stance. The weightbearing measure of navicular drop was recorded using an adapted digital caliper. Statistical analysis demonstrated a significant negative correlation (P &lt; .05) between the two variables. Furthermore, simple regression analysis suggested that 33.2% of the variation in maximal hallux dorsiflexion could be explained by different navicular drop values.

The relationship between navicular drop and first metatarsophalangeal joint motion. This study was conducted to determine whether navicular drop, as a representative measure of foot pronation, was associated with first metatarsal joint motion in 24 healthy subjects aged 21 to 40 years. The magnitude of first metatarsophalangeal joint motion was identified using a custom-built weightbearing goniometer designed to measure maximal hallux dorsiflexion in stance. The weightbearing measure of navicular drop was recorded using an adapted digital caliper. Statistical analysis demonstrated a significant negative correlation (P &lt; .05) between the two variables. Furthermore, simple regression analysis suggested that 33.2% of the variation in maximal hallux dorsiflexion could be explained by different navicular drop values.

pubmed23n1122_9092

Transcription-replication coordination revealed in single live cells.

The coexistence of DNA replication and transcription during S-phase requires their tight coordination to prevent harmful conflicts. While extensive research revealed important mechanisms for minimizing these conflicts and their consequences, little is known regarding how the replication and transcription machinery are coordinated in real-time. Here, we developed a live-cell imaging approach for the real-time monitoring of replisome progression and transcription dynamics during a transcription-replication encounter. We found a wave of partial transcriptional repression ahead of the moving replication fork, which may contribute to efficient fork progression through the transcribed gene. Real-time detection of conflicts revealed their negative impact on both processes, leading to fork stalling or slowdown as well as lower transcription levels during gene replication, with different trade-offs observed in defined subpopulations of cells. Our real-time measurements of transcription-replication encounters demonstrate how these processes can proceed simultaneously while maintaining genomic stability, and how conflicts can arise when coordination is impaired.

Transcription-replication coordination revealed in single live cells. The coexistence of DNA replication and transcription during S-phase requires their tight coordination to prevent harmful conflicts. While extensive research revealed important mechanisms for minimizing these conflicts and their consequences, little is known regarding how the replication and transcription machinery are coordinated in real-time. Here, we developed a live-cell imaging approach for the real-time monitoring of replisome progression and transcription dynamics during a transcription-replication encounter. We found a wave of partial transcriptional repression ahead of the moving replication fork, which may contribute to efficient fork progression through the transcribed gene. Real-time detection of conflicts revealed their negative impact on both processes, leading to fork stalling or slowdown as well as lower transcription levels during gene replication, with different trade-offs observed in defined subpopulations of cells. Our real-time measurements of transcription-replication encounters demonstrate how these processes can proceed simultaneously while maintaining genomic stability, and how conflicts can arise when coordination is impaired.

pubmed23n0639_8716

Lifecourse socio-economic mobility and oral health in middle age.

Socio-economic variations in health exist for a wide range of health outcomes, including oral health and oral-health-related quality of life (OHRQoL). Less is known regarding how socio-economic trajectories may influence oral health and OHRQoL. This study examined whether social mobility is related to the number of teeth retained by age 50 years and OHRQoL measured at the same time, using data from the Newcastle Thousand Families Study, a birth cohort established in 1947. Women remaining in the non-manual class had the greatest tooth retention. While promotion of a healthier lifestyle and continued improvements in oral hygiene throughout life appear to be the public health interventions most likely to improve oral health into middle age, there may be sub-groups of the population on which different approaches in terms of public health interventions need to be focused.

Lifecourse socio-economic mobility and oral health in middle age. Socio-economic variations in health exist for a wide range of health outcomes, including oral health and oral-health-related quality of life (OHRQoL). Less is known regarding how socio-economic trajectories may influence oral health and OHRQoL. This study examined whether social mobility is related to the number of teeth retained by age 50 years and OHRQoL measured at the same time, using data from the Newcastle Thousand Families Study, a birth cohort established in 1947. Women remaining in the non-manual class had the greatest tooth retention. While promotion of a healthier lifestyle and continued improvements in oral hygiene throughout life appear to be the public health interventions most likely to improve oral health into middle age, there may be sub-groups of the population on which different approaches in terms of public health interventions need to be focused.

pubmed23n0617_10700

[Two new genera of land snails (Stylommatophora: Arionacea) from Chile].

We describe two new genera of land molluscs found under wet leaf litter in isolated fragments of a secondary native forest at the Hualpén Botanical Park (36 degrees 45'-36 degrees 49' S, 73 degrees 9'-73 degrees 13' W), University of Concepción, Chile. The new taxa are Pichikadi gen.n., of Punctidae, and Chellius gen.n., of Charopidae, with the following new species: Pichikadi hualpensis sp.n., and Chellius piramidalis sp.n. English diagnosis are presented for all taxa, together with an English identification key and English versions of figure captions and table headings. To facilitate subsequent studies and interpretations, we follow recent authors in using mainly shell characters, an approach that has favored the present taxonomic stability of the world's land micromollusca. The diagnosis and observations are complemented with a key for the species of these families inhabiting continental Chile.

[Two new genera of land snails (Stylommatophora: Arionacea) from Chile]. We describe two new genera of land molluscs found under wet leaf litter in isolated fragments of a secondary native forest at the Hualpén Botanical Park (36 degrees 45'-36 degrees 49' S, 73 degrees 9'-73 degrees 13' W), University of Concepción, Chile. The new taxa are Pichikadi gen.n., of Punctidae, and Chellius gen.n., of Charopidae, with the following new species: Pichikadi hualpensis sp.n., and Chellius piramidalis sp.n. English diagnosis are presented for all taxa, together with an English identification key and English versions of figure captions and table headings. To facilitate subsequent studies and interpretations, we follow recent authors in using mainly shell characters, an approach that has favored the present taxonomic stability of the world's land micromollusca. The diagnosis and observations are complemented with a key for the species of these families inhabiting continental Chile.

pubmed23n0053_3927

Restoration of venous outflow by simultaneous creation of an arteriovenous shunt and pedicle flap using a rat model of foot replantation.

Replantation of amputated rat feet utilizing an efferent arteriovenous shunt constructed between the distal posterior tibial artery and the proximal posterior tibial vein, in the absence of all other venous drainage, provides an alternative pathway to the normal venous drainage in a replanted rat foot. However, this substitute venous drainage was insufficient to prevent progressive ischemia and necrosis of some or all of a replanted rat foot. When a cutaneous pedicle flap supplemented the arteriovenous shunt, venous drainage was much improved, tissue hypoxia and edema began to subside on the third day, severe tissue necrosis was prevented, and seven of eight feet replanted by this technique survived. These observations may be useful in replantation in humans when veins in the amputated part are too small to be used or so damaged that they cannot be repaired or reconstructed by a vein graft, but arteries can still provide a means of returning blood from the amputated part. Constructing an alternative pathway to the normal venous drainage pattern may allow severely damaged parts to survive after replantation.

Restoration of venous outflow by simultaneous creation of an arteriovenous shunt and pedicle flap using a rat model of foot replantation. Replantation of amputated rat feet utilizing an efferent arteriovenous shunt constructed between the distal posterior tibial artery and the proximal posterior tibial vein, in the absence of all other venous drainage, provides an alternative pathway to the normal venous drainage in a replanted rat foot. However, this substitute venous drainage was insufficient to prevent progressive ischemia and necrosis of some or all of a replanted rat foot. When a cutaneous pedicle flap supplemented the arteriovenous shunt, venous drainage was much improved, tissue hypoxia and edema began to subside on the third day, severe tissue necrosis was prevented, and seven of eight feet replanted by this technique survived. These observations may be useful in replantation in humans when veins in the amputated part are too small to be used or so damaged that they cannot be repaired or reconstructed by a vein graft, but arteries can still provide a means of returning blood from the amputated part. Constructing an alternative pathway to the normal venous drainage pattern may allow severely damaged parts to survive after replantation.

pubmed23n0120_14446

Fluorometric assay of O-linked glycoproteins by reaction with 2-cyanoacetamide.

A simple assay for O-glycosylated glycoproteins involving the liberation of oligosaccharides by beta-elimination with dilute alkali and the subsequent derivatization of the reducing end with 2-cyanoacetamide is reported. The method can be used to quantitate microgram amounts of mucin within 30 min. The assay is 30 times less sensitive to protein or N-linked glycoproteins and 100 times less sensitive to DNA than to the corresponding weight of canine tracheal mucin. Of the substances tested, only cesium chloride and potassium thiocyanate caused substantial interference, but in neither case was this sufficiently serious to prevent the method being used for monitoring mucin purification schemes utilizing these reagents. The coefficients of variation for replicate analyses of canine tracheal mucin (14.0, 5.0, and 2.0 micrograms) were 3.6, 6.5, and 12.3%, respectively.

Fluorometric assay of O-linked glycoproteins by reaction with 2-cyanoacetamide. A simple assay for O-glycosylated glycoproteins involving the liberation of oligosaccharides by beta-elimination with dilute alkali and the subsequent derivatization of the reducing end with 2-cyanoacetamide is reported. The method can be used to quantitate microgram amounts of mucin within 30 min. The assay is 30 times less sensitive to protein or N-linked glycoproteins and 100 times less sensitive to DNA than to the corresponding weight of canine tracheal mucin. Of the substances tested, only cesium chloride and potassium thiocyanate caused substantial interference, but in neither case was this sufficiently serious to prevent the method being used for monitoring mucin purification schemes utilizing these reagents. The coefficients of variation for replicate analyses of canine tracheal mucin (14.0, 5.0, and 2.0 micrograms) were 3.6, 6.5, and 12.3%, respectively.

pubmed23n0713_23372

Extracting and integrating data from entire electronic health records for detecting colorectal cancer cases.

Identification of a cohort of patients with specific diseases is an important step for clinical research that is based on electronic health records (EHRs). Informatics approaches combining structured EHR data, such as billing records, with narrative text data have demonstrated utility for such tasks. This paper describes an algorithm combining machine learning and natural language processing to detect patients with colorectal cancer (CRC) from entire EHRs at Vanderbilt University Hospital. We developed a general case detection method that consists of two steps: 1) extraction of positive CRC concepts from all clinical notes (document-level concept identification); and 2) determination of CRC cases using aggregated information from both clinical narratives and structured billing data (patient-level case determination). For each step, we compared performance of rule-based and machine-learning-based approaches. Using a manually reviewed data set containing 300 possible CRC patients (150 for training and 150 for testing), we showed that our method achieved F-measures of 0.996 for document level concept identification, and 0.93 for patient level case detection.

Extracting and integrating data from entire electronic health records for detecting colorectal cancer cases. Identification of a cohort of patients with specific diseases is an important step for clinical research that is based on electronic health records (EHRs). Informatics approaches combining structured EHR data, such as billing records, with narrative text data have demonstrated utility for such tasks. This paper describes an algorithm combining machine learning and natural language processing to detect patients with colorectal cancer (CRC) from entire EHRs at Vanderbilt University Hospital. We developed a general case detection method that consists of two steps: 1) extraction of positive CRC concepts from all clinical notes (document-level concept identification); and 2) determination of CRC cases using aggregated information from both clinical narratives and structured billing data (patient-level case determination). For each step, we compared performance of rule-based and machine-learning-based approaches. Using a manually reviewed data set containing 300 possible CRC patients (150 for training and 150 for testing), we showed that our method achieved F-measures of 0.996 for document level concept identification, and 0.93 for patient level case detection.

pubmed23n0058_18750

Leiomyosarcoma of urinary bladder.

The authors report one case of a leiomyosarcoma of the urinary bladder in a seventy-two-year-old man. The treatment was transurethral resection. There has been no evidence of recurrence or metastasis in more than a two-year follow-up. The literature is reviewed and the size of the tumor on the prognosis is discussed.

Leiomyosarcoma of urinary bladder. The authors report one case of a leiomyosarcoma of the urinary bladder in a seventy-two-year-old man. The treatment was transurethral resection. There has been no evidence of recurrence or metastasis in more than a two-year follow-up. The literature is reviewed and the size of the tumor on the prognosis is discussed.

pubmed23n0261_5674

Atrial natriuretic peptide counteracts the vasoconstrictor effects of 5-hydroxytryptamine, U46619 and endothelin-1 in the human umbilical artery.

A role for atrial natriuretic peptide (ANP) in maintaining low vascular resistance within the fetoplacental circulation was investigated using isolated strips of human umbilical artery (HUA). Physiological levels of ANP significantly reduced the isometric contractile response of the HUA to U46619 (a stable thromboxane A2 mimetic), to 5-hydroxytryptamine and to endothelin-1, though no effect on agonist sensitivity could be demonstrated. These data suggest that ANP may modify vascular tone in vivo thereby counterbalancing several humoral factors which act to increase vascular resistance within the fetoplacental circulation.

Atrial natriuretic peptide counteracts the vasoconstrictor effects of 5-hydroxytryptamine, U46619 and endothelin-1 in the human umbilical artery. A role for atrial natriuretic peptide (ANP) in maintaining low vascular resistance within the fetoplacental circulation was investigated using isolated strips of human umbilical artery (HUA). Physiological levels of ANP significantly reduced the isometric contractile response of the HUA to U46619 (a stable thromboxane A2 mimetic), to 5-hydroxytryptamine and to endothelin-1, though no effect on agonist sensitivity could be demonstrated. These data suggest that ANP may modify vascular tone in vivo thereby counterbalancing several humoral factors which act to increase vascular resistance within the fetoplacental circulation.

pubmed23n0490_5861

[Epidemiology of blindness in Baden, Germany].

There is no exact knowledge concerning blinding diseases in Germany. Purpose of this study was to investigate the changes of diseases leading to new blindness in Baden (Southern Germany). We evaluated the ophthalmological diseases leading to blindness in Baden from the applications presented to the eye doctor for blind and low vision people in Baden, Germany from 1980 to 1999. 1511 applications for blindness (991 women and 520 men) aged 1-107 (mean age: 68 +/- 22 years) were evaluated. 62.5% of persons who had recently become blind, concerned patients aged 70 years or older, 4.6% under 10 years of age. Age-related macular degeneration (23.1%), glaucoma (22.0%), optic atrophy (19.1%), diabetic retinopathy (13.3%) and tapetoretinal degeneration (8.1%) were the main causes of blindness. There were only minimal changes over time. There were only marginal changes of the frequency of the eye diseases causing blindness for the time interval from 1980 to 1999. Age-related macular degeneration is the major cause especially in the higher age group. There are enormous deficits in the prevention of causes of visual impairment and blindness.

[Epidemiology of blindness in Baden, Germany]. There is no exact knowledge concerning blinding diseases in Germany. Purpose of this study was to investigate the changes of diseases leading to new blindness in Baden (Southern Germany). We evaluated the ophthalmological diseases leading to blindness in Baden from the applications presented to the eye doctor for blind and low vision people in Baden, Germany from 1980 to 1999. 1511 applications for blindness (991 women and 520 men) aged 1-107 (mean age: 68 +/- 22 years) were evaluated. 62.5% of persons who had recently become blind, concerned patients aged 70 years or older, 4.6% under 10 years of age. Age-related macular degeneration (23.1%), glaucoma (22.0%), optic atrophy (19.1%), diabetic retinopathy (13.3%) and tapetoretinal degeneration (8.1%) were the main causes of blindness. There were only minimal changes over time. There were only marginal changes of the frequency of the eye diseases causing blindness for the time interval from 1980 to 1999. Age-related macular degeneration is the major cause especially in the higher age group. There are enormous deficits in the prevention of causes of visual impairment and blindness.

pubmed23n1027_10615

Regulatory T cells isolated from endometriotic peritoneal fluid express a different number of Toll-like receptors.

To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.

Regulatory T cells isolated from endometriotic peritoneal fluid express a different number of Toll-like receptors. To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.

pubmed23n1029_23251

Cellular Refractive Index Comparison of Various Prostate Cancer and Noncancerous Cell Lines via Photonic-Crystal Biosensor.

The current clinical standard for mass screening of prostate cancer are prostate-specific antigen (PSA) biomarker assays. Unfortunately, the low specificity of PSA's bioassays to prostate cancer leads to high false-positive rates, as such there is an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we have successfully demonstrated, with the use of our Photonic-Crystal based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, detection of prostate cancer (PC-3) cells against benign prostate hyperplasia (BPH-1) cells. The PC-TIR biosensor achieved detection of individual prostate cancer cells utilizing cellular refractive index (RI) as the only contrast parameter. To further study this methodology <iin vitro,</i we report a comprehensive study of the cellular RI's of various prostate cancer and noncancerous cell lines (i.e. RWPE-1, BPH-1, PC-3, DU-145, and LNCaP) via reflectance spectroscopy and single-cell RI imaging utilizing the PC-TIR biosensor. Our study shows promising clinical potential in utilizing the PC-TIR biosensor system for the detection of prostate cancer against noncancerous prostate epithelial cells.

Cellular Refractive Index Comparison of Various Prostate Cancer and Noncancerous Cell Lines via Photonic-Crystal Biosensor. The current clinical standard for mass screening of prostate cancer are prostate-specific antigen (PSA) biomarker assays. Unfortunately, the low specificity of PSA's bioassays to prostate cancer leads to high false-positive rates, as such there is an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we have successfully demonstrated, with the use of our Photonic-Crystal based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, detection of prostate cancer (PC-3) cells against benign prostate hyperplasia (BPH-1) cells. The PC-TIR biosensor achieved detection of individual prostate cancer cells utilizing cellular refractive index (RI) as the only contrast parameter. To further study this methodology <iin vitro,</i we report a comprehensive study of the cellular RI's of various prostate cancer and noncancerous cell lines (i.e. RWPE-1, BPH-1, PC-3, DU-145, and LNCaP) via reflectance spectroscopy and single-cell RI imaging utilizing the PC-TIR biosensor. Our study shows promising clinical potential in utilizing the PC-TIR biosensor system for the detection of prostate cancer against noncancerous prostate epithelial cells.

pubmed23n0370_17362

Medical treatment for reflux oesophagitis does not consistently improve asthma control: a systematic review.

A systematic literature review was conducted to assess the effect of treating reflux oesophagitis on asthma outcomes. Randomised controlled trials of reflux oesophagitis treatment in adults or children that reported asthma health outcomes were included and assessed in accordance with the standard Cochrane systematic review process. Patients were typically adults with asthma and concurrent symptomatic gastro-oesophageal reflux who received interventions that included pharmacological therapy, conservative management, and surgery. The following outcome measures were assessed: lung function, peak expiratory flow, asthma symptoms, asthma medications, and nocturnal asthma. From 22 potentially relevant published and unpublished randomised controlled trials, 12 were included. Treatment duration ranged from 1 week to 6 months. Eight trials reported that treatment improved at least one asthma outcome, but these outcomes differed between trials. Overall, treatment of reflux oesophagitis did not consistently improve forced expiratory volume in one second (FEV(1)), peak expiratory flow rate, asthma symptoms, nocturnal asthma symptoms, or use of asthma medications in asthmatic subjects. Significant improvement in wheeze was reported in two studies. The published literature does not consistently support treatment of reflux oesophagitis as a means of controlling asthma. Further large randomised controlled trials in subjects with a demonstrated temporal relationship between gastro-oesophageal reflux and asthma are needed. These trials should be conducted over at least 6 months to allow adequate time to observe a treatment effect.

Medical treatment for reflux oesophagitis does not consistently improve asthma control: a systematic review. A systematic literature review was conducted to assess the effect of treating reflux oesophagitis on asthma outcomes. Randomised controlled trials of reflux oesophagitis treatment in adults or children that reported asthma health outcomes were included and assessed in accordance with the standard Cochrane systematic review process. Patients were typically adults with asthma and concurrent symptomatic gastro-oesophageal reflux who received interventions that included pharmacological therapy, conservative management, and surgery. The following outcome measures were assessed: lung function, peak expiratory flow, asthma symptoms, asthma medications, and nocturnal asthma. From 22 potentially relevant published and unpublished randomised controlled trials, 12 were included. Treatment duration ranged from 1 week to 6 months. Eight trials reported that treatment improved at least one asthma outcome, but these outcomes differed between trials. Overall, treatment of reflux oesophagitis did not consistently improve forced expiratory volume in one second (FEV(1)), peak expiratory flow rate, asthma symptoms, nocturnal asthma symptoms, or use of asthma medications in asthmatic subjects. Significant improvement in wheeze was reported in two studies. The published literature does not consistently support treatment of reflux oesophagitis as a means of controlling asthma. Further large randomised controlled trials in subjects with a demonstrated temporal relationship between gastro-oesophageal reflux and asthma are needed. These trials should be conducted over at least 6 months to allow adequate time to observe a treatment effect.

pubmed23n0638_21273

Colorimetric cyanide detection using an azobenzene acid in aqueous solutions.

An azo-based dye (I) was designed for the detection of cyanide by utilizing a new indirect method. In the presence of Cu(II), compound I could give rise to visible red-to-yellow color change. The resultant yellow solution could change to red immediately upon the addition of trace cyanide, with the detection limit of 0.15 ppm, but no changes were observed in the presence of other anions, including Cl(-), I(-), IO(3)(-), SO(4)(2-), NO(2)(-), Br(-), H(2)PO(4)(-), F(-), SCN(-), HSO(4)(-), ClO(4)(-) and CN(-), making compound I a selective and sensitive cyanide chemosensor.

Colorimetric cyanide detection using an azobenzene acid in aqueous solutions. An azo-based dye (I) was designed for the detection of cyanide by utilizing a new indirect method. In the presence of Cu(II), compound I could give rise to visible red-to-yellow color change. The resultant yellow solution could change to red immediately upon the addition of trace cyanide, with the detection limit of 0.15 ppm, but no changes were observed in the presence of other anions, including Cl(-), I(-), IO(3)(-), SO(4)(2-), NO(2)(-), Br(-), H(2)PO(4)(-), F(-), SCN(-), HSO(4)(-), ClO(4)(-) and CN(-), making compound I a selective and sensitive cyanide chemosensor.

pubmed23n1110_2303

Characterization of the molecular mechanism underlying the dwarfism of dsh mutant watermelon plants.

Developing dwarf watermelon is a major objective among breeders. The dsh dwarf watermelon germplasm developed in our laboratory is genetically stable. We previously produced preliminary evidence that Cla010726, which encodes a gibberellin 20-oxidase-like protein, is the primary gene controlling dwarfism in watermelon. However, the underlying genetic mechanism was unknown. In this study, we characterized the spontaneous recessive mutant dsh, which is a gibberellin (GA)-deficient mutant. Many of the phenotypic traits of dsh plants are similar to those of known GA-deficient mutants. The dsh plants were sensitive to exogenous bioactive GAs, which increased seedling height. Moreover, a quantitative analysis of endogenous GA<sub3</sub proved that the bioactive GA<sub3</sub content was substantially lower than normal in dsh. Additionally, the T<sub5</subClaGA20ox RNAi plants generally exhibited dwarfism, with short stems and internodes as well as small leaves and fruit. An examination of the transgenic plants carrying the ClaGA20ox1 promoter-GUS and mutant ClaGA20ox2 promoter-GUS constructs confirmed that two promoter sites are involved in the regulation of ClaGA20ox expression. Hence, mutations in the promoter of the GA20ox gene, which encodes a key enzyme involved in gibberellin biosynthesis, lead to the dwarfism of watermelon plants. The dsh mutant is a potentially useful germplasm resource for developing new watermelon varieties exhibiting dwarfism.

Characterization of the molecular mechanism underlying the dwarfism of dsh mutant watermelon plants. Developing dwarf watermelon is a major objective among breeders. The dsh dwarf watermelon germplasm developed in our laboratory is genetically stable. We previously produced preliminary evidence that Cla010726, which encodes a gibberellin 20-oxidase-like protein, is the primary gene controlling dwarfism in watermelon. However, the underlying genetic mechanism was unknown. In this study, we characterized the spontaneous recessive mutant dsh, which is a gibberellin (GA)-deficient mutant. Many of the phenotypic traits of dsh plants are similar to those of known GA-deficient mutants. The dsh plants were sensitive to exogenous bioactive GAs, which increased seedling height. Moreover, a quantitative analysis of endogenous GA<sub3</sub proved that the bioactive GA<sub3</sub content was substantially lower than normal in dsh. Additionally, the T<sub5</subClaGA20ox RNAi plants generally exhibited dwarfism, with short stems and internodes as well as small leaves and fruit. An examination of the transgenic plants carrying the ClaGA20ox1 promoter-GUS and mutant ClaGA20ox2 promoter-GUS constructs confirmed that two promoter sites are involved in the regulation of ClaGA20ox expression. Hence, mutations in the promoter of the GA20ox gene, which encodes a key enzyme involved in gibberellin biosynthesis, lead to the dwarfism of watermelon plants. The dsh mutant is a potentially useful germplasm resource for developing new watermelon varieties exhibiting dwarfism.

pubmed23n0594_14654

[Partial mole in 18 weeks of gestation].

Partial mole is a form of gestational trophoblastic disease which occasionally progresses to the second trimester of pregnancy and may be associated with serious medical complications. We present a case report of a partial mole diagnosed in 18 weeks of gestation associated with severe fetal polymalformation sequence.

[Partial mole in 18 weeks of gestation]. Partial mole is a form of gestational trophoblastic disease which occasionally progresses to the second trimester of pregnancy and may be associated with serious medical complications. We present a case report of a partial mole diagnosed in 18 weeks of gestation associated with severe fetal polymalformation sequence.

pubmed23n0415_2930

Overexpression and characterization of hydantoin racemase from Agrobacterium tumefaciens C58.

Hydantoin racemase enzyme together with a stereoselective hydantoinase and a stereospecific D-carbamoylase guarantee the total conversion from D,L-5-monosubstituted hydantoins with a low velocity of racemization to optically pure D-amino acids. In this work we have cloned and expressed the hydantoin racemase gene from two strains of Agrobacterium tumefaciens, C58 and LBA4404, in Escherichia coli BL21. The recombinant protein was purified in a one-step procedure by using immobilized cobalt affinity chromatography and showed an apparent molecular mass of 32,000 Da in SDS-gel electrophoresis. Size exclusion chromatography analysis determined a molecular mass of about 100,000 Da, suggesting that the native enzyme is a tetramer. The optimal conditions for hydantoin racemase activity were pH 7.5 and 55 degrees C with L-5-ethylhydantoin as substrate. Enzyme activity was slightly affected by the addition of Ni(2+) and Co(2+) and strongly inhibited by Cu(2+) and Hg(2+). No effect on enzyme activity was detected with Mn(2+), EDTA, or DTT. Kinetic studies showed the preference of the enzyme for hydantoins with short rather than long aliphatic side chains or hydantoins with aromatic rings.

Overexpression and characterization of hydantoin racemase from Agrobacterium tumefaciens C58. Hydantoin racemase enzyme together with a stereoselective hydantoinase and a stereospecific D-carbamoylase guarantee the total conversion from D,L-5-monosubstituted hydantoins with a low velocity of racemization to optically pure D-amino acids. In this work we have cloned and expressed the hydantoin racemase gene from two strains of Agrobacterium tumefaciens, C58 and LBA4404, in Escherichia coli BL21. The recombinant protein was purified in a one-step procedure by using immobilized cobalt affinity chromatography and showed an apparent molecular mass of 32,000 Da in SDS-gel electrophoresis. Size exclusion chromatography analysis determined a molecular mass of about 100,000 Da, suggesting that the native enzyme is a tetramer. The optimal conditions for hydantoin racemase activity were pH 7.5 and 55 degrees C with L-5-ethylhydantoin as substrate. Enzyme activity was slightly affected by the addition of Ni(2+) and Co(2+) and strongly inhibited by Cu(2+) and Hg(2+). No effect on enzyme activity was detected with Mn(2+), EDTA, or DTT. Kinetic studies showed the preference of the enzyme for hydantoins with short rather than long aliphatic side chains or hydantoins with aromatic rings.

pubmed23n0303_4433

Invasive fungal infections in liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent.

Invasive fungal infections and their risk factors were prospectively assessed in 130 consecutive liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent. Eleven percent (14) of the 130 patients had 17 episodes of invasive fungal infections. These included candidiasis (5%; 6 patients), cryptococcosis (5%; 6), aspergillosis (3%; 4), and chromomycosis (1%; 1). An elevated pretransplantation creatinine level, requirement of dialysis (pretransplantation or posttransplantation), duration of intensive care unit stay after transplantation surgery, and antibiotic use (other than for prophylaxis) within 4 weeks of transplantation were significant risk factors for fungal infections occurring within 100 days of transplantation. For fungal infections occurring after 100 days, persistence of renal dysfunction (serum creatinine level of &gt;2.5 mg/dL at 3 months), dialysis, and histopathologically documented recurrence of hepatitis C virus hepatitis were significant risk factors. Mortality was significantly higher among patients with fungal infections than among all other patients (57% vs. 15%; P = .0009). Our study identified specific risk factors for invasive fungal infections in liver transplant recipients receiving tacrolimus; strategies to prevent fungal infections or to initiate early antifungal therapy might be most effectively targeted at these patients.

Invasive fungal infections in liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent. Invasive fungal infections and their risk factors were prospectively assessed in 130 consecutive liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent. Eleven percent (14) of the 130 patients had 17 episodes of invasive fungal infections. These included candidiasis (5%; 6 patients), cryptococcosis (5%; 6), aspergillosis (3%; 4), and chromomycosis (1%; 1). An elevated pretransplantation creatinine level, requirement of dialysis (pretransplantation or posttransplantation), duration of intensive care unit stay after transplantation surgery, and antibiotic use (other than for prophylaxis) within 4 weeks of transplantation were significant risk factors for fungal infections occurring within 100 days of transplantation. For fungal infections occurring after 100 days, persistence of renal dysfunction (serum creatinine level of &gt;2.5 mg/dL at 3 months), dialysis, and histopathologically documented recurrence of hepatitis C virus hepatitis were significant risk factors. Mortality was significantly higher among patients with fungal infections than among all other patients (57% vs. 15%; P = .0009). Our study identified specific risk factors for invasive fungal infections in liver transplant recipients receiving tacrolimus; strategies to prevent fungal infections or to initiate early antifungal therapy might be most effectively targeted at these patients.

pubmed23n0817_4207

A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma.

Second-line treatment options in advanced hepatocellular carcinoma (HCC) are limited. Axitinib, a selective potent tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor VEGF) receptors 1, 2, and 3, merits exploration in HCC. This was a single-arm phase II trial of axitinib in advanced HCC. Eligible patients were Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib was started at 5 mg twice daily orally, titrated from 2 to 10 mg twice daily as tolerated. The primary end point was tumor control at 16 weeks by RECIST1.1; secondary end points were response rate, comparing response by RECIST1.1 to Choi and modified RECIST, exploring dynamic contrast-enhanced imaging models, safety, progression-free (PFS), and overall survival (OS). Thirty patients were treated. Of 26 patients evaluable for response, there were 3 partial responses (PR) per RECIST1.1; 13 PR by Choi, 6 PR and 1 complete response by modified RECIST. Tumor control rate at 16 weeks was 42.3%. Two-week perfusion changes were noted on functional imaging. Of 21 patients with evaluable α-fetoprotein response, 43% had &gt;50% decrease from baseline. Most common axitinib-related grade 3/4 adverse events (AEs) were hypertension, thrombocytopenia and diarrhea. Of 11 patients with any grade hypertension, 7 had disease control &gt;36 wks. Four patients discontinued treatment due to AEs. Median PFS was 3.6 months. Median OS was 7.1 months. With 42.3% tumor control at 16 weeks, primary endpoint was met. Axitinib has shown encouraging tolerable clinical activity in VEGF-pretreated HCC patients but further study should be in a selected population incorporating potential biomarkers of response.

A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma. Second-line treatment options in advanced hepatocellular carcinoma (HCC) are limited. Axitinib, a selective potent tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor VEGF) receptors 1, 2, and 3, merits exploration in HCC. This was a single-arm phase II trial of axitinib in advanced HCC. Eligible patients were Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib was started at 5 mg twice daily orally, titrated from 2 to 10 mg twice daily as tolerated. The primary end point was tumor control at 16 weeks by RECIST1.1; secondary end points were response rate, comparing response by RECIST1.1 to Choi and modified RECIST, exploring dynamic contrast-enhanced imaging models, safety, progression-free (PFS), and overall survival (OS). Thirty patients were treated. Of 26 patients evaluable for response, there were 3 partial responses (PR) per RECIST1.1; 13 PR by Choi, 6 PR and 1 complete response by modified RECIST. Tumor control rate at 16 weeks was 42.3%. Two-week perfusion changes were noted on functional imaging. Of 21 patients with evaluable α-fetoprotein response, 43% had &gt;50% decrease from baseline. Most common axitinib-related grade 3/4 adverse events (AEs) were hypertension, thrombocytopenia and diarrhea. Of 11 patients with any grade hypertension, 7 had disease control &gt;36 wks. Four patients discontinued treatment due to AEs. Median PFS was 3.6 months. Median OS was 7.1 months. With 42.3% tumor control at 16 weeks, primary endpoint was met. Axitinib has shown encouraging tolerable clinical activity in VEGF-pretreated HCC patients but further study should be in a selected population incorporating potential biomarkers of response.

pubmed23n0939_15193

Concurrent Alterations in EGFR-Mutant Lung Cancers Associated with Resistance to EGFR Kinase Inhibitors and Characterization of MTOR as a Mediator of Resistance.

<bPurpose:</b To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and to identify novel mechanisms of drug resistance, we molecularly profiled <iEGFR</i-mutant tumors prior to treatment and after progression on EGFR TKI using targeted next-generation sequencing.<bExperimental Design:</b Targeted next-generation sequencing was performed on 374 consecutive patients with metastatic <iEGFR</i-mutant lung cancer. Clinical data were collected and correlated with somatic mutation data. Erlotinib resistance due to acquired MTOR mutation was functionally evaluated by <iin vivo</i and <iin vitro</i studies.<bResults:</b In 200 <iEGFR</i-mutant pretreatment samples, the most frequent concurrent alterations were mutations in <iTP53, PIK3CA, CTNNB1</i, and <iRB1</i and focal amplifications in <iEGFR, TTF1, MDM2, CDK4</i, and <iFOXA1</i Shorter time to progression on EGFR TKI was associated with amplification of <iERBB2</i (HR = 2.4, <iP</i = 0.015) or <iMET</i (HR = 3.7, <iP</i = 0.019), or mutation in <iTP53</i (HR = 1.7, <iP</i = 0.006). In the 136 posttreatment samples, we identified known mechanisms of acquired resistance: EGFR T790M (51%), <iMET</i (7%), and <iERBB2</i amplifications (5%). In the 38 paired samples, novel acquired alterations representing putative resistance mechanisms included <iBRAF</i fusion, <iFGFR3</i fusion, <iYES1</i amplification, <iKEAP1</i loss, and an MTOR E2419K mutation. Functional studies confirmed the contribution of the latter to reduced sensitivity to EGFR TKI <iin vitro</i and <iin vivo</i<bConclusions:</b<iEGFR</i-mutant lung cancers harbor a spectrum of concurrent alterations that have prognostic and predictive significance. By utilizing paired samples, we identified several novel acquired alterations that may be relevant in mediating resistance, including an activating mutation in MTOR further validated functionally. <iClin Cancer Res; 24(13); 3108-18. ©2018 AACR</i.

Concurrent Alterations in EGFR-Mutant Lung Cancers Associated with Resistance to EGFR Kinase Inhibitors and Characterization of MTOR as a Mediator of Resistance. <bPurpose:</b To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and to identify novel mechanisms of drug resistance, we molecularly profiled <iEGFR</i-mutant tumors prior to treatment and after progression on EGFR TKI using targeted next-generation sequencing.<bExperimental Design:</b Targeted next-generation sequencing was performed on 374 consecutive patients with metastatic <iEGFR</i-mutant lung cancer. Clinical data were collected and correlated with somatic mutation data. Erlotinib resistance due to acquired MTOR mutation was functionally evaluated by <iin vivo</i and <iin vitro</i studies.<bResults:</b In 200 <iEGFR</i-mutant pretreatment samples, the most frequent concurrent alterations were mutations in <iTP53, PIK3CA, CTNNB1</i, and <iRB1</i and focal amplifications in <iEGFR, TTF1, MDM2, CDK4</i, and <iFOXA1</i Shorter time to progression on EGFR TKI was associated with amplification of <iERBB2</i (HR = 2.4, <iP</i = 0.015) or <iMET</i (HR = 3.7, <iP</i = 0.019), or mutation in <iTP53</i (HR = 1.7, <iP</i = 0.006). In the 136 posttreatment samples, we identified known mechanisms of acquired resistance: EGFR T790M (51%), <iMET</i (7%), and <iERBB2</i amplifications (5%). In the 38 paired samples, novel acquired alterations representing putative resistance mechanisms included <iBRAF</i fusion, <iFGFR3</i fusion, <iYES1</i amplification, <iKEAP1</i loss, and an MTOR E2419K mutation. Functional studies confirmed the contribution of the latter to reduced sensitivity to EGFR TKI <iin vitro</i and <iin vivo</i<bConclusions:</b<iEGFR</i-mutant lung cancers harbor a spectrum of concurrent alterations that have prognostic and predictive significance. By utilizing paired samples, we identified several novel acquired alterations that may be relevant in mediating resistance, including an activating mutation in MTOR further validated functionally. <iClin Cancer Res; 24(13); 3108-18. ©2018 AACR</i.

pubmed23n0720_22850

Drastic expression change of transposon-derived piRNA-like RNAs and microRNAs in early stages of chicken embryos implies a role in gastrulation.

Recent studies have shown that endogenous small RNAs regulate a variety of biological processes during vertebrate development; however, little is known about the role of small RNAs in regulating developmental signaling pathways during early embryogenesis. In this study, we applied Illumina sequencing to characterize an unexpected endogenous small RNA catalog and demonstrated a dramatic transition from transposon-derived piRNA-like small RNAs (pilRNAs) to microRNAs (miRNAs) in pre- and post-gastrula chicken embryos. The comprehensive expression profile of chicken miRNAs at the pre- and post-gastrula stages revealed that most known and new miRNAs were dynamically regulated during development. In addition to embryonic stem cell-related miRNAs, Gene Ontology (GO) analysis showed that miRNAs enriched in early stage chicken embryos targeted multiple signal transduction pathways associated with the reproductive process and embryogenesis, including Wnt and TGF-β, which specifies the neural fate of blastodermal cells. Intriguingly, a large cohort of pilRNAs primarily derived from the active and most abundant transposable elements (TEs) were enriched in chicken stage X blastoderms. Within stage X blastoderms, pilRNAs were specifically localized to the primordial germ cells (PGCs), indicating their post-zygotic origin. Together, these findings imply a role for small RNAs in gastrulation in early stage chicken embryos.

Drastic expression change of transposon-derived piRNA-like RNAs and microRNAs in early stages of chicken embryos implies a role in gastrulation. Recent studies have shown that endogenous small RNAs regulate a variety of biological processes during vertebrate development; however, little is known about the role of small RNAs in regulating developmental signaling pathways during early embryogenesis. In this study, we applied Illumina sequencing to characterize an unexpected endogenous small RNA catalog and demonstrated a dramatic transition from transposon-derived piRNA-like small RNAs (pilRNAs) to microRNAs (miRNAs) in pre- and post-gastrula chicken embryos. The comprehensive expression profile of chicken miRNAs at the pre- and post-gastrula stages revealed that most known and new miRNAs were dynamically regulated during development. In addition to embryonic stem cell-related miRNAs, Gene Ontology (GO) analysis showed that miRNAs enriched in early stage chicken embryos targeted multiple signal transduction pathways associated with the reproductive process and embryogenesis, including Wnt and TGF-β, which specifies the neural fate of blastodermal cells. Intriguingly, a large cohort of pilRNAs primarily derived from the active and most abundant transposable elements (TEs) were enriched in chicken stage X blastoderms. Within stage X blastoderms, pilRNAs were specifically localized to the primordial germ cells (PGCs), indicating their post-zygotic origin. Together, these findings imply a role for small RNAs in gastrulation in early stage chicken embryos.

pubmed23n0543_14461

The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study.

The clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women. The cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style. 178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38-3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05-3.49) and 2.01 (95% CI, 1.20-3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22-3.9) and 2.19 (95% CI, 1.12-4.29) respectively). our study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco.

The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study. The clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women. The cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style. 178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38-3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05-3.49) and 2.01 (95% CI, 1.20-3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22-3.9) and 2.19 (95% CI, 1.12-4.29) respectively). our study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco.

pubmed23n0964_9401

Source-Informed Segmentation: A Data-Driven Approach for the Temporal Segmentation of EEG.

Understanding the dynamics of brain function through non-invasive monitoring techniques requires the development of computational methods that can deal with the non-stationary properties of recorded activities. As a solution to this problem, a new data-driven segmentation method for recordings obtained through electroencephalography (EEG) is presented. The proposed method utilizes singular value decomposition (SVD) to identify the time intervals in the EEG recordings during which the spatial distribution of clusters of active cortical neurons remains quasi-stationary. Theoretical analysis shows that the spatial locality features of these clusters can be, asymptotically, captured by the most significant left singular subspace of the EEG data. A reference/sliding window approach is employed to dynamically extract this feature subspace, and the running projection error is monitored for significant changes using Kolmogorov-Smirnov test. Simulation results, for a wide range of possible scenarios regarding the spatial distribution of active cortical neurons, show that the algorithm is successful in accurately detecting the segmental structure of the simulated EEG data. The algorithm is also applied to experimental EEG recordings of a modified visual oddball task. Results identify a unique sequence of dynamic patterns in the event-related potential (ERP) response to each of the three involved stimuli. The proposed method, without using source localization methods or scalp topographical maps, is able to identify intervals of quasi-stationarity in the EEG recordings. The proposed segmentation technique can offer new insights on the dynamics of functional organization of the brain in action.

Source-Informed Segmentation: A Data-Driven Approach for the Temporal Segmentation of EEG. Understanding the dynamics of brain function through non-invasive monitoring techniques requires the development of computational methods that can deal with the non-stationary properties of recorded activities. As a solution to this problem, a new data-driven segmentation method for recordings obtained through electroencephalography (EEG) is presented. The proposed method utilizes singular value decomposition (SVD) to identify the time intervals in the EEG recordings during which the spatial distribution of clusters of active cortical neurons remains quasi-stationary. Theoretical analysis shows that the spatial locality features of these clusters can be, asymptotically, captured by the most significant left singular subspace of the EEG data. A reference/sliding window approach is employed to dynamically extract this feature subspace, and the running projection error is monitored for significant changes using Kolmogorov-Smirnov test. Simulation results, for a wide range of possible scenarios regarding the spatial distribution of active cortical neurons, show that the algorithm is successful in accurately detecting the segmental structure of the simulated EEG data. The algorithm is also applied to experimental EEG recordings of a modified visual oddball task. Results identify a unique sequence of dynamic patterns in the event-related potential (ERP) response to each of the three involved stimuli. The proposed method, without using source localization methods or scalp topographical maps, is able to identify intervals of quasi-stationarity in the EEG recordings. The proposed segmentation technique can offer new insights on the dynamics of functional organization of the brain in action.

pubmed23n1138_7947

Therapeutic Drug Monitoring of Amphotericin-B in Plasma and Peritoneal Fluid of Pediatric Patients after Liver Transplantation: A Case Series.

Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim of this study is to evaluate peritoneal levels of amphotericin-B following intravenous administration. Six liver recipients received liposomal amphotericin-B. Three of them were treated as prophylaxis; meanwhile, three patients received liposomal amphotericin-B to treat <iCandida albicans</i infection. Plasma and peritoneal amphotericin-B levels were measured by LC-MS/MS in two consecutive samplings. C<imin</i (pre-dose) and C<imax</i (2 h after the end of infusion) were evaluated as drug exposure parameters for both plasma and peritoneum. Our results showed that peritoneal amphotericin-B levels were significantly lower than plasma and that the correlation coefficient was 0.72 (<ip</i = 0.03) between plasma and peritoneal C<imin</i. Moreover, although peritoneal levels were within the therapeutic range, they never reached the PK/PD target (Cmax/MIC &amp;gt; 4.5). In conclusion, PK exposure parameters could be differently used to analyze amphotericin-B concentrations in plasma and peritoneum. However, liposomal amphotericin-B should be preferred in these patients as prophylactic rather than therapeutic treatment for fungal infections.

Therapeutic Drug Monitoring of Amphotericin-B in Plasma and Peritoneal Fluid of Pediatric Patients after Liver Transplantation: A Case Series. Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim of this study is to evaluate peritoneal levels of amphotericin-B following intravenous administration. Six liver recipients received liposomal amphotericin-B. Three of them were treated as prophylaxis; meanwhile, three patients received liposomal amphotericin-B to treat <iCandida albicans</i infection. Plasma and peritoneal amphotericin-B levels were measured by LC-MS/MS in two consecutive samplings. C<imin</i (pre-dose) and C<imax</i (2 h after the end of infusion) were evaluated as drug exposure parameters for both plasma and peritoneum. Our results showed that peritoneal amphotericin-B levels were significantly lower than plasma and that the correlation coefficient was 0.72 (<ip</i = 0.03) between plasma and peritoneal C<imin</i. Moreover, although peritoneal levels were within the therapeutic range, they never reached the PK/PD target (Cmax/MIC &amp;gt; 4.5). In conclusion, PK exposure parameters could be differently used to analyze amphotericin-B concentrations in plasma and peritoneum. However, liposomal amphotericin-B should be preferred in these patients as prophylactic rather than therapeutic treatment for fungal infections.

pubmed23n0005_12235

Vascular trauma secondary to diagnostic and therapeutic procedures: laparoscopy.

Diagnostic and therapeutic laparoscopy are safe procedures that only rarely cause significant morbidity. However, major abdominal arterial and venous injury may occur, requiring prompt recognition and laparotomy. Direct compression will control major hemorrhage until resuscitation is complete. Vascular repair utilizing principles of proximal and distal control, good exposure, appropriate anticoagulation, and lateral suture technic should result in restoration of normal blood flow without significant sequelae.

Vascular trauma secondary to diagnostic and therapeutic procedures: laparoscopy. Diagnostic and therapeutic laparoscopy are safe procedures that only rarely cause significant morbidity. However, major abdominal arterial and venous injury may occur, requiring prompt recognition and laparotomy. Direct compression will control major hemorrhage until resuscitation is complete. Vascular repair utilizing principles of proximal and distal control, good exposure, appropriate anticoagulation, and lateral suture technic should result in restoration of normal blood flow without significant sequelae.

pubmed23n0061_16363

Wernicke's encephalopathy--prevalence and clinical spectrum.

Although easily preventable, Wernicke's encephalopathy (WE) remains a regrettably frequent and largely undiagnosed disorder in alcoholics. Unselected autopsy materials from the United States and Australia give prevalence figures of 2%. In Oslo, Norway, the corresponding figures are somewhat lower, 0.6%-0.8%. Only a fraction of the cases discovered at autopsy have been diagnosed clinically (1%-20%). One third of the cases in postmortem materials have been acute with signs of ongoing thiamine deficiency. In contrast to classical concepts, stupor and coma have been predominating symptoms in such cases. Two thirds have had chronic disease with marked variations in severity of the lesions and corresponding variations in severity of the symptoms, from Korsakoff's psychosis or global dementia in severe cases to a slight memory reduction in mild ones. The wide spectrum of the clinical symptoms has not been fully appreciated and this may in part explain the low level of diagnostic accuracy of the disease.

Wernicke's encephalopathy--prevalence and clinical spectrum. Although easily preventable, Wernicke's encephalopathy (WE) remains a regrettably frequent and largely undiagnosed disorder in alcoholics. Unselected autopsy materials from the United States and Australia give prevalence figures of 2%. In Oslo, Norway, the corresponding figures are somewhat lower, 0.6%-0.8%. Only a fraction of the cases discovered at autopsy have been diagnosed clinically (1%-20%). One third of the cases in postmortem materials have been acute with signs of ongoing thiamine deficiency. In contrast to classical concepts, stupor and coma have been predominating symptoms in such cases. Two thirds have had chronic disease with marked variations in severity of the lesions and corresponding variations in severity of the symptoms, from Korsakoff's psychosis or global dementia in severe cases to a slight memory reduction in mild ones. The wide spectrum of the clinical symptoms has not been fully appreciated and this may in part explain the low level of diagnostic accuracy of the disease.

pubmed23n0634_16138

Role of nitroso radicals as drug targets in circulatory shock.

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO(-))] as mediators of shock and ischaemia/reperfusion injury. Reactive oxygen species can initiate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3 phosphate dehydrogenase, inhibition of membrane sodium/potassium adenosine 5'-triphosphate-ase activity, inactivation of membrane sodium channels and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock and ischaemia and reperfusion. Moreover, various studies have clearly shown that treatment with either OONO(-) decomposition catalysts, which selectively inhibit OONO(-), or with superoxide dismutase (SOD) mimetics, which selectively mimic the catalytic activity of the human SOD enzymes, have been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock and ischaemia/reperfusion injury.

Role of nitroso radicals as drug targets in circulatory shock. A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO(-))] as mediators of shock and ischaemia/reperfusion injury. Reactive oxygen species can initiate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3 phosphate dehydrogenase, inhibition of membrane sodium/potassium adenosine 5'-triphosphate-ase activity, inactivation of membrane sodium channels and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock and ischaemia and reperfusion. Moreover, various studies have clearly shown that treatment with either OONO(-) decomposition catalysts, which selectively inhibit OONO(-), or with superoxide dismutase (SOD) mimetics, which selectively mimic the catalytic activity of the human SOD enzymes, have been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock and ischaemia/reperfusion injury.

pubmed23n0807_21798

Affinity for music in Wolf-Hirschhorn syndrome: two case reports.

Wolf-Hirschhorn syndrome is a congenital malformation syndrome resulting from deletion of the short arm of chromosome 4. Individuals with Wolf-Hirschhorn syndrome may have a "Greek warrior helmet" appearance, growth retardation, developmental delay, muscular hypotonia, epilepsy, and difficulty with language including verbal communication. An affinity for music has not previously been reported in these patients. We describe two patients with Wolf-Hirschhorn syndrome who both have a strong affinity for music. One patient is a 20-year-old woman who likes to listen to music all day and can hum many tunes. The other patient is a 9-year-old girl who is calmed by music and received music therapy, with subsequent improvement in her communication skills (eye contact, joint attention, and vocalizations to request music). Individuals with Wolf-Hirschhorn syndrome may have a strong affinity for music and may benefit from music therapy. Additional studies are needed to investigate the interest in music in individuals with Wolf-Hirschhorn syndrome.

Affinity for music in Wolf-Hirschhorn syndrome: two case reports. Wolf-Hirschhorn syndrome is a congenital malformation syndrome resulting from deletion of the short arm of chromosome 4. Individuals with Wolf-Hirschhorn syndrome may have a "Greek warrior helmet" appearance, growth retardation, developmental delay, muscular hypotonia, epilepsy, and difficulty with language including verbal communication. An affinity for music has not previously been reported in these patients. We describe two patients with Wolf-Hirschhorn syndrome who both have a strong affinity for music. One patient is a 20-year-old woman who likes to listen to music all day and can hum many tunes. The other patient is a 9-year-old girl who is calmed by music and received music therapy, with subsequent improvement in her communication skills (eye contact, joint attention, and vocalizations to request music). Individuals with Wolf-Hirschhorn syndrome may have a strong affinity for music and may benefit from music therapy. Additional studies are needed to investigate the interest in music in individuals with Wolf-Hirschhorn syndrome.

pubmed23n1036_5018

Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies.

Diagnostic yield of genetic studies for Charcot-Marie-Tooth disease (CMT) is little known, with a lack of epidemiological data to build better diagnostic strategies outside the United States and Europe. We aimed to evaluate the performance of two molecular diagnostic strategies for patients with CMT, and to characterize epidemiological findings of these conditions in southern Brazil. We performed a single-center cross-sectional study, in which 94 patients (55 families) with CMT suspicion were evaluated. Overall, the diagnostic yield of the combined strategy of Multiplex-ligation-dependent-probe-amplification (MLPA) of PMP22/GJB1/MPZ and GJB1/MPZ/PMP22 Sanger sequencing was 63.6% (28/44) for index cases with demyelinating/intermediate CMT suspicion (21 CMT1A-PMP22, 5 CMTX1-GJB1 and 2 with probably CMT1B-MPZ diagnosis). Five of the 11 index cases (45.4%) with axonal CMT had at least a possible diagnosis with next generation sequencing (NGS) panel of 104 inherited neuropathies-related genes (one each with CMT1A-PMP22, CMT2A-MFN2, CMT2K-GDAP1, CMT2U-MARS, CMT2W-HARS1). Detailed clinical, neurophysiological and molecular data of families are provided. Sequential molecular diagnosis strategies with MLPA plus target Sanger sequencing for demyelinating/intermediate CMT had high diagnostic yield, and almost half of axonal CMT families had at least a possible diagnosis with the comprehensive NGS panel. Most frequent subtypes of CMT in our region are CMT1A-PMP22 and CMTX1-GJB1.

Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies. Diagnostic yield of genetic studies for Charcot-Marie-Tooth disease (CMT) is little known, with a lack of epidemiological data to build better diagnostic strategies outside the United States and Europe. We aimed to evaluate the performance of two molecular diagnostic strategies for patients with CMT, and to characterize epidemiological findings of these conditions in southern Brazil. We performed a single-center cross-sectional study, in which 94 patients (55 families) with CMT suspicion were evaluated. Overall, the diagnostic yield of the combined strategy of Multiplex-ligation-dependent-probe-amplification (MLPA) of PMP22/GJB1/MPZ and GJB1/MPZ/PMP22 Sanger sequencing was 63.6% (28/44) for index cases with demyelinating/intermediate CMT suspicion (21 CMT1A-PMP22, 5 CMTX1-GJB1 and 2 with probably CMT1B-MPZ diagnosis). Five of the 11 index cases (45.4%) with axonal CMT had at least a possible diagnosis with next generation sequencing (NGS) panel of 104 inherited neuropathies-related genes (one each with CMT1A-PMP22, CMT2A-MFN2, CMT2K-GDAP1, CMT2U-MARS, CMT2W-HARS1). Detailed clinical, neurophysiological and molecular data of families are provided. Sequential molecular diagnosis strategies with MLPA plus target Sanger sequencing for demyelinating/intermediate CMT had high diagnostic yield, and almost half of axonal CMT families had at least a possible diagnosis with the comprehensive NGS panel. Most frequent subtypes of CMT in our region are CMT1A-PMP22 and CMTX1-GJB1.

pubmed23n0951_6397

A thiadiazole-capped nanoribbon with 18 linearly fused rings.

Polycyclic aromatic hydrocarbons that extend over 2 nm in one dimension are seen as monodisperse graphene nanoribbons, which have attracted significant attention for a broad range of applications in organic electronics and photonics. Herein we report the synthesis of a stable bisthiadiazole-capped pyrene-containing nanoribbon with 18 linearly fused rings (NR-18-TD). Thanks to the presence of alternating tert-butyl and tri-iso-butylsilyl groups, NR-18-TD is highly soluble in organic solvents and therefore its structure and fundamental optoelectronic, redox and electrical properties could be unambiguously established. This work illustrates that NR-18-TD is a promising soluble NR-based n-type semiconductor for applications in organic electronics.

A thiadiazole-capped nanoribbon with 18 linearly fused rings. Polycyclic aromatic hydrocarbons that extend over 2 nm in one dimension are seen as monodisperse graphene nanoribbons, which have attracted significant attention for a broad range of applications in organic electronics and photonics. Herein we report the synthesis of a stable bisthiadiazole-capped pyrene-containing nanoribbon with 18 linearly fused rings (NR-18-TD). Thanks to the presence of alternating tert-butyl and tri-iso-butylsilyl groups, NR-18-TD is highly soluble in organic solvents and therefore its structure and fundamental optoelectronic, redox and electrical properties could be unambiguously established. This work illustrates that NR-18-TD is a promising soluble NR-based n-type semiconductor for applications in organic electronics.

pubmed23n1004_12021

pH-responsive lignin-based magnetic nanoparticles for recovery of cellulase.

Enzymatic hydrolysis of lignocellulose to produce bioethanol by cellulase is an important method to alleviate the energy crisis. In this paper, in order to overcome the shortcomings of low efficiency, high cost and easy deactivation of cellulase in the process of bio-refinery, pH-responsive lignin-based magnetic nanoparticles (Fe<sub3</subO<sub4</sub/LSQA) were synthesized to immobilize and recover cellulase. It was shown that a high immobilization ratio of 55.52% for cellulase was obtained. Meanwhile, the desorption ratio was 68.27% by adjusting the pH of the system. After five reusing cycles, the desorbed cellulase retained 31.79% of the relative activity due to the pH responsiveness of Fe<sub3</subO<sub4</sub/LSQA. These results not only provide a new idea for the recycling of cellulase, but also broaden the application of industrial lignin and increase the extra value.

pH-responsive lignin-based magnetic nanoparticles for recovery of cellulase. Enzymatic hydrolysis of lignocellulose to produce bioethanol by cellulase is an important method to alleviate the energy crisis. In this paper, in order to overcome the shortcomings of low efficiency, high cost and easy deactivation of cellulase in the process of bio-refinery, pH-responsive lignin-based magnetic nanoparticles (Fe<sub3</subO<sub4</sub/LSQA) were synthesized to immobilize and recover cellulase. It was shown that a high immobilization ratio of 55.52% for cellulase was obtained. Meanwhile, the desorption ratio was 68.27% by adjusting the pH of the system. After five reusing cycles, the desorbed cellulase retained 31.79% of the relative activity due to the pH responsiveness of Fe<sub3</subO<sub4</sub/LSQA. These results not only provide a new idea for the recycling of cellulase, but also broaden the application of industrial lignin and increase the extra value.

pubmed23n0591_1512

[Moderate alcohol consumption may be recommended for the prevention of heart attacks].

Numerous population studies have consistently demonstrated a lower risk ofheart attacks as a result of moderate alcohol consumption, especially in the presence of an increased cardiovascular risk. Nevertheless, this association is still considered to be controversial, probably as a result ofthe negative effects of excessive consumption. This does not mean that moderate alcohol consumption may not be recommended for the prevention of heart attacks in the relevant segments of the population.

[Moderate alcohol consumption may be recommended for the prevention of heart attacks]. Numerous population studies have consistently demonstrated a lower risk ofheart attacks as a result of moderate alcohol consumption, especially in the presence of an increased cardiovascular risk. Nevertheless, this association is still considered to be controversial, probably as a result ofthe negative effects of excessive consumption. This does not mean that moderate alcohol consumption may not be recommended for the prevention of heart attacks in the relevant segments of the population.

pubmed23n0036_900

Immune response to Trichinella spiralis in the rat. I. Development of cellular and humoral responses during chronic infection.

The immune response of rats to infection with Trichinella spiralis was studied serially for more than 1 year. Initial antigen-specific cellular reactivity, assessed by the lymphocyte transformation response, developed in the draining mesenteric nodes 3 days after infection. After 1 week reactive lymphocytes were detectable in the spleen and circulating blood, but the more 'remote' peripheral nodes did not harbor antigen-reactive cells until late in the second week. Thereafter, the patterns of antigen-responsiveness varied among the different lymphoid pools, but in all cases a decline in reactivity was seen after the first month. Serum hemagglutinating and homocytotropic antibodies, detectable by the tenth day, reached their peaks after 1 month of infection. Hemagglutinating titers persisted for more than 1 year but homocytotropic antibody was lost over this period. Comparisons are drawn between the evolution of the natural infection and the development of the host's immune response.

Immune response to Trichinella spiralis in the rat. I. Development of cellular and humoral responses during chronic infection. The immune response of rats to infection with Trichinella spiralis was studied serially for more than 1 year. Initial antigen-specific cellular reactivity, assessed by the lymphocyte transformation response, developed in the draining mesenteric nodes 3 days after infection. After 1 week reactive lymphocytes were detectable in the spleen and circulating blood, but the more 'remote' peripheral nodes did not harbor antigen-reactive cells until late in the second week. Thereafter, the patterns of antigen-responsiveness varied among the different lymphoid pools, but in all cases a decline in reactivity was seen after the first month. Serum hemagglutinating and homocytotropic antibodies, detectable by the tenth day, reached their peaks after 1 month of infection. Hemagglutinating titers persisted for more than 1 year but homocytotropic antibody was lost over this period. Comparisons are drawn between the evolution of the natural infection and the development of the host's immune response.

pubmed23n0880_1797

Glutathione-complexed [2Fe-2S] clusters function in Fe-S cluster storage and trafficking.

Glutathione-coordinated [2Fe-2S] complex is a non-protein-bound [2Fe-2S] cluster that is capable of reconstituting the human iron-sulfur cluster scaffold protein IscU. This complex demonstrates physiologically relevant solution chemistry and is a viable substrate for iron-sulfur cluster transport by Atm1p exporter protein. Herein, we report on some of the possible functional and physiological roles for this novel [2Fe-2S](GS4) complex in iron-sulfur cluster biosynthesis and quantitatively characterize its role in the broader network of Fe-S cluster transfer reactions. UV-vis and circular dichroism spectroscopy have been used in kinetic studies to determine second-order rate constants for [2Fe-2S] cluster transfer from [2Fe-2S](GS4) complex to acceptor proteins, such as human IscU, Schizosaccharomyces pombe Isa1, human and yeast glutaredoxins (human Grx2 and Saccharomyces cerevisiae Grx3), and human ferredoxins. Second-order rate constants for cluster extraction from these holo proteins were also determined by varying the concentration of glutathione, and a likely common mechanism for cluster uptake was determined by kinetic analysis. The results indicate that the [2Fe-2S](GS4) complex is stable under physiological conditions, and demonstrates reversible cluster exchange with a wide range of Fe-S cluster proteins, thereby supporting a possible physiological role for such centers.

Glutathione-complexed [2Fe-2S] clusters function in Fe-S cluster storage and trafficking. Glutathione-coordinated [2Fe-2S] complex is a non-protein-bound [2Fe-2S] cluster that is capable of reconstituting the human iron-sulfur cluster scaffold protein IscU. This complex demonstrates physiologically relevant solution chemistry and is a viable substrate for iron-sulfur cluster transport by Atm1p exporter protein. Herein, we report on some of the possible functional and physiological roles for this novel [2Fe-2S](GS4) complex in iron-sulfur cluster biosynthesis and quantitatively characterize its role in the broader network of Fe-S cluster transfer reactions. UV-vis and circular dichroism spectroscopy have been used in kinetic studies to determine second-order rate constants for [2Fe-2S] cluster transfer from [2Fe-2S](GS4) complex to acceptor proteins, such as human IscU, Schizosaccharomyces pombe Isa1, human and yeast glutaredoxins (human Grx2 and Saccharomyces cerevisiae Grx3), and human ferredoxins. Second-order rate constants for cluster extraction from these holo proteins were also determined by varying the concentration of glutathione, and a likely common mechanism for cluster uptake was determined by kinetic analysis. The results indicate that the [2Fe-2S](GS4) complex is stable under physiological conditions, and demonstrates reversible cluster exchange with a wide range of Fe-S cluster proteins, thereby supporting a possible physiological role for such centers.

pubmed23n0412_21854

Plasma C-reactive protein levels and their relationship to anthropometric and lipid characteristics among children.

C-reactive protein (CRP), a nonspecific marker of inflammatory status, is associated with cardiovascular disease (CVD) risk factors and the late occurrence of heart disease in adults. However, few studies assess the plasma CRP levels in healthy children. The purpose of this study is to evaluate the relationship between plasma CRP levels and anthropometric and lipid characteristics among children in Taiwan. After a multi-stage sampling of 85 junior high schools in Taipei, we randomly selected 835 children (410 boys and 425 girls) aged 12 to 16 years. Anthropometric and lipid profiles, including total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) were measured. We also calculated low-density lipoprotein cholesterol levels and the total cholesterol-to-HDL-C ratio as shown on the atherosclerotic index. In both genders, plasma CRP levels were significantly positively correlated with anthropometrics measures and inversely correlated with HDL-C levels. After adjusting for age, cigarette smoking, alcohol consumption, heart rate, and puberty development, children in the fourth quartile CRP subgroups were heavier and had significantly higher body mass index (BMI) and lower HDL-C levels than children with nondetected CRP. In multivariate regression models, CRP was significantly negatively associated with HDL-C levels even after adjusting for BMI in both genders. In this study, anthropometrics measures, especially BMI, were positively associated with plasma CRP levels. Furthermore, elevated CRP levels were associated with adverse lipids profiles. These data suggest that elevated plasma CRP levels might be associated with CVD risk factors that may be related to the late development of CVD in some Taiwanese children.

Plasma C-reactive protein levels and their relationship to anthropometric and lipid characteristics among children. C-reactive protein (CRP), a nonspecific marker of inflammatory status, is associated with cardiovascular disease (CVD) risk factors and the late occurrence of heart disease in adults. However, few studies assess the plasma CRP levels in healthy children. The purpose of this study is to evaluate the relationship between plasma CRP levels and anthropometric and lipid characteristics among children in Taiwan. After a multi-stage sampling of 85 junior high schools in Taipei, we randomly selected 835 children (410 boys and 425 girls) aged 12 to 16 years. Anthropometric and lipid profiles, including total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) were measured. We also calculated low-density lipoprotein cholesterol levels and the total cholesterol-to-HDL-C ratio as shown on the atherosclerotic index. In both genders, plasma CRP levels were significantly positively correlated with anthropometrics measures and inversely correlated with HDL-C levels. After adjusting for age, cigarette smoking, alcohol consumption, heart rate, and puberty development, children in the fourth quartile CRP subgroups were heavier and had significantly higher body mass index (BMI) and lower HDL-C levels than children with nondetected CRP. In multivariate regression models, CRP was significantly negatively associated with HDL-C levels even after adjusting for BMI in both genders. In this study, anthropometrics measures, especially BMI, were positively associated with plasma CRP levels. Furthermore, elevated CRP levels were associated with adverse lipids profiles. These data suggest that elevated plasma CRP levels might be associated with CVD risk factors that may be related to the late development of CVD in some Taiwanese children.

pubmed23n0018_6545

Scintigraphic detection of gastric calcification in dialysis patients.

The value of 99mTc HEDP bone scintigraphy as a means of detecting metastatic gastric calcification was studied in 45 chronic dialysis patients and in 55 former dialysis patients. For this group, all bone scans were obtained within 2 months after successful transplantation; radiotracer uptake by the stomach was not observed. In 15 of the first 35 chronic dialysis patients studied, gastric uptake was demonstrated without radioactive accumulation in the thyroid region. In all the dialysis patients, however, background activity had been normalized before scintigraphy by means of hemodialysis using recirculating dialysate. Without the latter, radioactive accumulation in the stomach was no longer noted. Thus, gastric uptake was presumably due to the formation of in vivo free pertechnetate, as a result of the dialysis method used, and in vitro experiments supported this hypothesis. These findings show that free pertechnetate can cause visualization of the stomach in the absence of thyroid imaging. The results of this study further indicate that bone scintigraphy is not a sensitive method for detecting metastatic gastric calcification in uremia.

Scintigraphic detection of gastric calcification in dialysis patients. The value of 99mTc HEDP bone scintigraphy as a means of detecting metastatic gastric calcification was studied in 45 chronic dialysis patients and in 55 former dialysis patients. For this group, all bone scans were obtained within 2 months after successful transplantation; radiotracer uptake by the stomach was not observed. In 15 of the first 35 chronic dialysis patients studied, gastric uptake was demonstrated without radioactive accumulation in the thyroid region. In all the dialysis patients, however, background activity had been normalized before scintigraphy by means of hemodialysis using recirculating dialysate. Without the latter, radioactive accumulation in the stomach was no longer noted. Thus, gastric uptake was presumably due to the formation of in vivo free pertechnetate, as a result of the dialysis method used, and in vitro experiments supported this hypothesis. These findings show that free pertechnetate can cause visualization of the stomach in the absence of thyroid imaging. The results of this study further indicate that bone scintigraphy is not a sensitive method for detecting metastatic gastric calcification in uremia.

pubmed23n0289_8841

Clinical application of flow cytometry to urological malignancies.

Flow cytometric DNA analysis provides rapid, quantitative objective information regarding the biological behavior of urological malignancies. Moreover, clinical applications of the many recent advances made the flow cytometry are expected to materialize soon. For instance, flow cytometric DNA ploidy analysis for human bladder cancers may provide a significant diagnostic and prognostic potential. Also, flow cytometric DNA analysis of irrigation specimens produces a higher sensitivity than conventional cytology for detecting bladder cancer. However, there are obvious pitfalls with this approach since diploid or near-diploid tumors cannot always be recognized by DNA analysis alone. One of the most significant advantages possible with flow cytometry is its capability of analyzing simultaneously multiple parameter on single cells. The integration of the DNA content with proliferative activity should yield important information significant to the biological behavior of individual tumors. Flow cytometric DNA/bromodeoxyuridine bivariate analysis can be used as an effective adjunct to histological examination for prognostication and decision-making in treatment of bladder cancer patients. Therefore, multiparameteric flow cytometric analysis can be used to isolate specific tumor cells from mixed cell populations, and should receive even increased attention as a valuable diagnostic technique and prognostic factor. In the present review, the efficacy of flow cytometric DNA ploidy analysis integrated with cell proliferation markers is discussed.

Clinical application of flow cytometry to urological malignancies. Flow cytometric DNA analysis provides rapid, quantitative objective information regarding the biological behavior of urological malignancies. Moreover, clinical applications of the many recent advances made the flow cytometry are expected to materialize soon. For instance, flow cytometric DNA ploidy analysis for human bladder cancers may provide a significant diagnostic and prognostic potential. Also, flow cytometric DNA analysis of irrigation specimens produces a higher sensitivity than conventional cytology for detecting bladder cancer. However, there are obvious pitfalls with this approach since diploid or near-diploid tumors cannot always be recognized by DNA analysis alone. One of the most significant advantages possible with flow cytometry is its capability of analyzing simultaneously multiple parameter on single cells. The integration of the DNA content with proliferative activity should yield important information significant to the biological behavior of individual tumors. Flow cytometric DNA/bromodeoxyuridine bivariate analysis can be used as an effective adjunct to histological examination for prognostication and decision-making in treatment of bladder cancer patients. Therefore, multiparameteric flow cytometric analysis can be used to isolate specific tumor cells from mixed cell populations, and should receive even increased attention as a valuable diagnostic technique and prognostic factor. In the present review, the efficacy of flow cytometric DNA ploidy analysis integrated with cell proliferation markers is discussed.

pubmed23n0005_7084

Passive enhancement of isolated pancreatic islet allografts.

Pancreatic islets from DA, Lewis, or DA X Lewis F1 rats were transplanted into the portal vein of Lewis or DA recipients made diabetic by prior treatment with Streptozotocin. The islets corrected the hyperglycaemia within 48 hr but were rejected within 5 days in all combinations. Passive enhancement of homozygous Lewis or DA islets with Lewis anti-DA or DA anti-Lewis antiserum in a single dose of 500 mul delayed rejection for several days, but where DA X Lewis F1 islets were used, rejection was delayed markedly with two of five animals in both the DA X Lewis F1 to DA and in DA microliters and 2.5 ml of enhancing serum were less effective than 500 mul in suppressing rejection. Thus, passive enhancement of allogeneic pancreatic islets was extremely effective in suppressing or delaying rejection of DA X Lewis F1 islets but was able to delay rejection of homozygous pancreatic islets by only a few days.

Passive enhancement of isolated pancreatic islet allografts. Pancreatic islets from DA, Lewis, or DA X Lewis F1 rats were transplanted into the portal vein of Lewis or DA recipients made diabetic by prior treatment with Streptozotocin. The islets corrected the hyperglycaemia within 48 hr but were rejected within 5 days in all combinations. Passive enhancement of homozygous Lewis or DA islets with Lewis anti-DA or DA anti-Lewis antiserum in a single dose of 500 mul delayed rejection for several days, but where DA X Lewis F1 islets were used, rejection was delayed markedly with two of five animals in both the DA X Lewis F1 to DA and in DA microliters and 2.5 ml of enhancing serum were less effective than 500 mul in suppressing rejection. Thus, passive enhancement of allogeneic pancreatic islets was extremely effective in suppressing or delaying rejection of DA X Lewis F1 islets but was able to delay rejection of homozygous pancreatic islets by only a few days.

pubmed23n0900_3241

Causes of larval drift of the fire salamander, Salamandra salamandra terrestris, and its effects on population dynamics.

The larval drift of the fire salamander was investigated over a period of three years in a mountain brook (Niederbergisches Land, F.R. Germany), as well in a laboratory water channel. The rate of larval drift fluctuated between 19% and 41% of the total population of larvae in a defined section of the brook during these three years. Most (83%) of the drifting larvae were hatchlings or very young stages. The drift was dependent on the strength of the current, the number of spawning females, the presence of suitable hiding places, sufficient space and adequate food. Hungry larvae drifted more often than satiated animals. The drift behaviour of hatchlings differed distinctly from that of older larvae. The significance of ecological factors on larval drift is discussed. It is evidently a more important factor in selection than has hitherto been recognized.

Causes of larval drift of the fire salamander, Salamandra salamandra terrestris, and its effects on population dynamics. The larval drift of the fire salamander was investigated over a period of three years in a mountain brook (Niederbergisches Land, F.R. Germany), as well in a laboratory water channel. The rate of larval drift fluctuated between 19% and 41% of the total population of larvae in a defined section of the brook during these three years. Most (83%) of the drifting larvae were hatchlings or very young stages. The drift was dependent on the strength of the current, the number of spawning females, the presence of suitable hiding places, sufficient space and adequate food. Hungry larvae drifted more often than satiated animals. The drift behaviour of hatchlings differed distinctly from that of older larvae. The significance of ecological factors on larval drift is discussed. It is evidently a more important factor in selection than has hitherto been recognized.

pubmed23n0639_21841

Comparison of nonsurgical root canal treatment and single-tooth implants.

The aim of this review was to compare the differences between nonsurgical root canal treatment and single-tooth implants. With the emerging field of implant dentistry gaining acceptance, the choice to retain a diseased tooth through the use of root canal therapy or extract it and replace the tooth with an implant-supported crown has become controversial. Many practitioners consider the single-tooth implant as a reasonable alternative to the preservation of a diseased tooth. An extensive search of the dental literature was accomplished to identify publications related to the differences in root canal therapy and dental implants. Several comparative studies were also considered. The treatment modalities were reviewed with respect to outcome measures and study design, success/failure, functional rehabilitation and psychological differences, complications related to treatment, cost differences, and factors influencing treatment planning considerations. With the reviewed information in hand, the practitioner should be better prepared to determine which treatment option is most appropriate for each individual patient.

Comparison of nonsurgical root canal treatment and single-tooth implants. The aim of this review was to compare the differences between nonsurgical root canal treatment and single-tooth implants. With the emerging field of implant dentistry gaining acceptance, the choice to retain a diseased tooth through the use of root canal therapy or extract it and replace the tooth with an implant-supported crown has become controversial. Many practitioners consider the single-tooth implant as a reasonable alternative to the preservation of a diseased tooth. An extensive search of the dental literature was accomplished to identify publications related to the differences in root canal therapy and dental implants. Several comparative studies were also considered. The treatment modalities were reviewed with respect to outcome measures and study design, success/failure, functional rehabilitation and psychological differences, complications related to treatment, cost differences, and factors influencing treatment planning considerations. With the reviewed information in hand, the practitioner should be better prepared to determine which treatment option is most appropriate for each individual patient.

pubmed23n0991_15832

Significance of CLASP2 expression in prognosis for muscle-invasive bladder cancer patients: A propensity score-based analysis.

Cytoplasmic linker-associated protein 2 (CLASP2) belongs to a family of microtubule plus-end tracking proteins that localize to the distal ends of microtubules and is involved in various microtubule-dependent processes. We previously showed that CLASP2 is involved in the epithelial-to-mesenchymal transition of bladder urothelial cancer. This research aimed to explore the significance of CLASP2 expression as a prognostic marker for muscle-invasive bladder urothelial cancer (MIBC) patients after radical cystectomy-pelvic lymph node dissection (RC-PLND). CLASP2 expression was analyzed in 76 benign bladder tissues and 160 MIBC tissues by tissue immunohistochemistry. Survival analysis and multiple regression analysis following propensity score matching were performed to investigate the correlation between high CLASP2 expression and MIBC patients' survival. CLASP2 expression was increased in MIBC patients, especially those with high-stage tumors or lymph node metastasis. In the follow-up of MIBC patients after propensity score matching, whether MIBC patients received adjuvant chemotherapy after RC-PLND, high CLASP2 expression was significantly associated with a poor prognosis. MIBC patients with low CLASP2 expression who received adjuvant chemotherapy tended to have an improved survival prognosis. CLASP2 expression is correlated with malignant progression of MIBC. High CLASP2 expression predicted a poor prognosis for MIBC patients after RC-PLND.

Significance of CLASP2 expression in prognosis for muscle-invasive bladder cancer patients: A propensity score-based analysis. Cytoplasmic linker-associated protein 2 (CLASP2) belongs to a family of microtubule plus-end tracking proteins that localize to the distal ends of microtubules and is involved in various microtubule-dependent processes. We previously showed that CLASP2 is involved in the epithelial-to-mesenchymal transition of bladder urothelial cancer. This research aimed to explore the significance of CLASP2 expression as a prognostic marker for muscle-invasive bladder urothelial cancer (MIBC) patients after radical cystectomy-pelvic lymph node dissection (RC-PLND). CLASP2 expression was analyzed in 76 benign bladder tissues and 160 MIBC tissues by tissue immunohistochemistry. Survival analysis and multiple regression analysis following propensity score matching were performed to investigate the correlation between high CLASP2 expression and MIBC patients' survival. CLASP2 expression was increased in MIBC patients, especially those with high-stage tumors or lymph node metastasis. In the follow-up of MIBC patients after propensity score matching, whether MIBC patients received adjuvant chemotherapy after RC-PLND, high CLASP2 expression was significantly associated with a poor prognosis. MIBC patients with low CLASP2 expression who received adjuvant chemotherapy tended to have an improved survival prognosis. CLASP2 expression is correlated with malignant progression of MIBC. High CLASP2 expression predicted a poor prognosis for MIBC patients after RC-PLND.

pubmed23n0875_9561

An autopsied case of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease presenting with hyperintensities on diffusion-weighted MRI before clinical onset.

A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram. Myoclonus was observed 8 weeks after clinical onset. The patient reached an akinetic mutism state and died 5 months after onset. Neuropathological examination showed widespread cerebral neocortical involvement of fine vacuole-type spongiform changes with large confluent vacuole-type spongiform changes. Spongiform degeneration with neuron loss and hypertrophic astrocytosis was also observed in the striatum and medial thalamus. The inferior olivary nucleus showed severe neuron loss with hypertrophic astrocytosis. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition with perivacuolar-type PrP deposition in the cerebral neocortex. Mild to moderate PrP deposition was also observed extensively in the basal ganglia, thalamus, cerebellum and brainstem, but it was not apparent in the inferior olivary nucleus. PrP gene analysis showed no mutations, and polymorphic codon 129 showed methionine homozygosity. Western blot analysis of protease-resistant PrP showed both type 1 scrapie type PrP (PrP<supSc</sup ) and type 2 PrP<supSc</sup . Based on the relationship between the neuroimaging and pathological findings, we speculated that cerebral cortical lesions with large confluent vacuoles and type 2 PrP<supSc</sup would show higher brightness and continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrP<supSc</sup . We believe the present patient had a combined form of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD), which suggests a broader spectrum of sCJD clinicopathological findings.

An autopsied case of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease presenting with hyperintensities on diffusion-weighted MRI before clinical onset. A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram. Myoclonus was observed 8 weeks after clinical onset. The patient reached an akinetic mutism state and died 5 months after onset. Neuropathological examination showed widespread cerebral neocortical involvement of fine vacuole-type spongiform changes with large confluent vacuole-type spongiform changes. Spongiform degeneration with neuron loss and hypertrophic astrocytosis was also observed in the striatum and medial thalamus. The inferior olivary nucleus showed severe neuron loss with hypertrophic astrocytosis. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition with perivacuolar-type PrP deposition in the cerebral neocortex. Mild to moderate PrP deposition was also observed extensively in the basal ganglia, thalamus, cerebellum and brainstem, but it was not apparent in the inferior olivary nucleus. PrP gene analysis showed no mutations, and polymorphic codon 129 showed methionine homozygosity. Western blot analysis of protease-resistant PrP showed both type 1 scrapie type PrP (PrP<supSc</sup ) and type 2 PrP<supSc</sup . Based on the relationship between the neuroimaging and pathological findings, we speculated that cerebral cortical lesions with large confluent vacuoles and type 2 PrP<supSc</sup would show higher brightness and continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrP<supSc</sup . We believe the present patient had a combined form of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD), which suggests a broader spectrum of sCJD clinicopathological findings.

pubmed23n0840_13547

Synthesis and Structure-Activity Relationships of Tambjamines and B-Ring Functionalized Prodiginines as Potent Antimalarials.

Synthesis and antimalarial activity of 94 novel bipyrrole tambjamines (TAs) and a library of B-ring functionalized tripyrrole prodiginines (PGs) against a panel of Plasmodium falciparum strains are described. The activity and structure-activity relationships demonstrate that the ring-C of PGs can be replaced by an alkylamine, providing for TAs with retained/enhanced potency. Furthermore, ring-B of PGs/TAs can be substituted with short alkyl substitutions at either 4-position (replacement of OMe) or 3- and 4-positions without impacting potency. Eight representative TAs and two PGs have been evaluated for antimalarial activity against multidrug-resistant P. yoelii in mice in the dose range of 5-100 mg/kg × 4 days by oral administration. The KAR425 TA offered greater efficacy than previously observed for any PG, providing 100% protection to malaria-infected mice until day 28 at doses of 25 and 50 mg/kg × 4 days, and was also curative in this model in a single oral dose (80 mg/kg). This study presents the first account of antimalarial activity in tambjamines.

Synthesis and Structure-Activity Relationships of Tambjamines and B-Ring Functionalized Prodiginines as Potent Antimalarials. Synthesis and antimalarial activity of 94 novel bipyrrole tambjamines (TAs) and a library of B-ring functionalized tripyrrole prodiginines (PGs) against a panel of Plasmodium falciparum strains are described. The activity and structure-activity relationships demonstrate that the ring-C of PGs can be replaced by an alkylamine, providing for TAs with retained/enhanced potency. Furthermore, ring-B of PGs/TAs can be substituted with short alkyl substitutions at either 4-position (replacement of OMe) or 3- and 4-positions without impacting potency. Eight representative TAs and two PGs have been evaluated for antimalarial activity against multidrug-resistant P. yoelii in mice in the dose range of 5-100 mg/kg × 4 days by oral administration. The KAR425 TA offered greater efficacy than previously observed for any PG, providing 100% protection to malaria-infected mice until day 28 at doses of 25 and 50 mg/kg × 4 days, and was also curative in this model in a single oral dose (80 mg/kg). This study presents the first account of antimalarial activity in tambjamines.

pubmed23n1082_4724

Exploring the Hereditary Nature of Migraine.

Migraine is a common neurological disorder which affects 15-20% of the population; it has a high socioeconomic impact through treatment and loss of productivity. Current forms of diagnosis are primarily clinical and can be difficult owing to comorbidity and symptom overlap with other neurological disorders. As such, there is a need for better diagnostic tools in the form of genetic testing. Migraine is a complex disorder, encompassing various subtypes, and has a large genetic component. Genetic studies conducted on rare monogenic subtypes, including familial hemiplegic migraine, have led to insights into its pathogenesis via identification of causal mutations in three genes (<iCACNA1A</i, <iATP1A2</i and <iSCN1A</i) that are involved in transport of ions at synapses and glutamatergic transmission. Study of familial migraine with aura pedigrees has also revealed other causal genes for monogenic forms of migraine. With respect to the more common polygenic form of migraine, large genome-wide association studies have increased our understanding of the genes, pathways and mechanisms involved in susceptibility, which are largely involved in neuronal and vascular functions. Given the preponderance of female migraineurs (3:1), there is evidence to suggest that hormonal or X-linked components can also contribute to migraine, and the role of genetic variants in mitochondrial DNA in migraine has been another avenue of exploration. Epigenetic studies of migraine have shown links between hormonal variation and alterations in DNA methylation and gene expression. While there is an abundance of preliminary studies identifying many potentially causative migraine genes and pathways, more comprehensive genomic and functional analysis to better understand mechanisms may aid in better diagnostic and treatment outcomes.

Exploring the Hereditary Nature of Migraine. Migraine is a common neurological disorder which affects 15-20% of the population; it has a high socioeconomic impact through treatment and loss of productivity. Current forms of diagnosis are primarily clinical and can be difficult owing to comorbidity and symptom overlap with other neurological disorders. As such, there is a need for better diagnostic tools in the form of genetic testing. Migraine is a complex disorder, encompassing various subtypes, and has a large genetic component. Genetic studies conducted on rare monogenic subtypes, including familial hemiplegic migraine, have led to insights into its pathogenesis via identification of causal mutations in three genes (<iCACNA1A</i, <iATP1A2</i and <iSCN1A</i) that are involved in transport of ions at synapses and glutamatergic transmission. Study of familial migraine with aura pedigrees has also revealed other causal genes for monogenic forms of migraine. With respect to the more common polygenic form of migraine, large genome-wide association studies have increased our understanding of the genes, pathways and mechanisms involved in susceptibility, which are largely involved in neuronal and vascular functions. Given the preponderance of female migraineurs (3:1), there is evidence to suggest that hormonal or X-linked components can also contribute to migraine, and the role of genetic variants in mitochondrial DNA in migraine has been another avenue of exploration. Epigenetic studies of migraine have shown links between hormonal variation and alterations in DNA methylation and gene expression. While there is an abundance of preliminary studies identifying many potentially causative migraine genes and pathways, more comprehensive genomic and functional analysis to better understand mechanisms may aid in better diagnostic and treatment outcomes.

pubmed23n0211_13257

Glutathione peroxidase blockage inhibits prostaglandin biosynthesis in rat platelets and aorta.

In the present study we demonstrated that the compound 3-amino-1,2,4-triazole (AMT) is a strong inhibitor of erythrocyte glutathione peroxidase (GSH-Px) activity. Moreover, AMT inhibits arachidonic-induced malondialdehyde formation in platelet-rich plasma and prostacyclin-like activity generation in aorta rings. These results give new lines of evidence on the connection between GSH-Px activity and prostaglandin synthesis in rat platelets and arterial vessel wall.

Glutathione peroxidase blockage inhibits prostaglandin biosynthesis in rat platelets and aorta. In the present study we demonstrated that the compound 3-amino-1,2,4-triazole (AMT) is a strong inhibitor of erythrocyte glutathione peroxidase (GSH-Px) activity. Moreover, AMT inhibits arachidonic-induced malondialdehyde formation in platelet-rich plasma and prostacyclin-like activity generation in aorta rings. These results give new lines of evidence on the connection between GSH-Px activity and prostaglandin synthesis in rat platelets and arterial vessel wall.

pubmed23n1162_1162

Recording Methods and the Capabilities of Modern Respiratory Rate Monitoring Devices (literature review).

Determination of respiratory rate is a necessary task in assessing the state of health in humans. This review provides a description of modern devices used for recording and monitoring respiratory rate. The advantages and disadvantages of the principles of operation of these devices are discussed.

Recording Methods and the Capabilities of Modern Respiratory Rate Monitoring Devices (literature review). Determination of respiratory rate is a necessary task in assessing the state of health in humans. This review provides a description of modern devices used for recording and monitoring respiratory rate. The advantages and disadvantages of the principles of operation of these devices are discussed.

pubmed23n0090_806

Immunization of sheep against modified peptides of gonadotropin releasing hormone conjugated to carriers.

The efficacy of antigens based on modified GnRH peptides in stimulating the production of antibodies against GnRH in sheep was tested. In the first study cysteine-containing GnRH peptides were conjugated to keyhold limpet haemocyanin (KLH) in 3 different orientations. The 3 conjugates were prepared in an emulsion of Freund's complete adjuvant (FCA) and were injected into 3 groups of 6 castrated male lambs. The 3 vaccines efficiently induced anti-GnRH titers in all the animals treated. The specificity of the GnRH antisera raised varied depending on the orientation of the GnRH molecule in the antigen and on the individual animal. In a second trial designed to evaluate carrier molecules, a cysteine-containing GnRH peptide was conjugated to either KLH, equine serum albumin, ovalbumin or tetanus toxoid. The conjugates were prepared with FCA and injected into intact male lambs. All 4 vaccines stimulated the production of antibodies against GnRH in all the animals treated. The conjugates prepared with equine serum albumin or ovalbumin were the most effective in raising high anti-GnRH titers. In 18 of 20 lambs treated, anti-GnRH titers resulted in a marked atrophy of the testes. We conclude that: 1) the different epitopes of the GnRH molecule are equally immunogenic in sheep; 2) the GnRH antibody response is affected by the carrier used; and, 3) anti-GnRH vaccines based on cysteine-substituted GnRH analogues show potential for use in immunocastration of livestock.

Immunization of sheep against modified peptides of gonadotropin releasing hormone conjugated to carriers. The efficacy of antigens based on modified GnRH peptides in stimulating the production of antibodies against GnRH in sheep was tested. In the first study cysteine-containing GnRH peptides were conjugated to keyhold limpet haemocyanin (KLH) in 3 different orientations. The 3 conjugates were prepared in an emulsion of Freund's complete adjuvant (FCA) and were injected into 3 groups of 6 castrated male lambs. The 3 vaccines efficiently induced anti-GnRH titers in all the animals treated. The specificity of the GnRH antisera raised varied depending on the orientation of the GnRH molecule in the antigen and on the individual animal. In a second trial designed to evaluate carrier molecules, a cysteine-containing GnRH peptide was conjugated to either KLH, equine serum albumin, ovalbumin or tetanus toxoid. The conjugates were prepared with FCA and injected into intact male lambs. All 4 vaccines stimulated the production of antibodies against GnRH in all the animals treated. The conjugates prepared with equine serum albumin or ovalbumin were the most effective in raising high anti-GnRH titers. In 18 of 20 lambs treated, anti-GnRH titers resulted in a marked atrophy of the testes. We conclude that: 1) the different epitopes of the GnRH molecule are equally immunogenic in sheep; 2) the GnRH antibody response is affected by the carrier used; and, 3) anti-GnRH vaccines based on cysteine-substituted GnRH analogues show potential for use in immunocastration of livestock.

pubmed23n0909_21709

Monte Carlo investigation of backscatter point spread function for X-ray imaging examinations.

X-ray imaging examinations, especially complex interventions, may result in relatively high doses to the patient's skin inducing skin injuries. A method was developed to determine the skin-dose distribution for non-uniform x-ray beams by convolving the backscatter point-spread-function (PSF) with the primary-dose distribution to generate the backscatter distribution that, when added to the primary dose, gives the total-dose distribution. This technique was incorporated in the dose-tracking system (DTS), which provides a real-time color-coded 3D-mapping of skin dose during fluoroscopic procedures. The aim of this work is to investigate the variation of the backscatter PSF with different parameters. A backscatter PSF of a 1-mm x-ray beam was generated by EGSnrc Monte-Carlo code for different x-ray beam energies, different soft-tissue thickness above bone, different bone thickness and different entrance-beam angles, as well as for different locations on the SK-150 anthropomorphic head phantom. The results show a reduction of the peak scatter to primary dose ratio of 48% when X-ray beam voltage is increased from 40 keV to 120 keV. The backscatter dose was reduced when bone was beneath the soft tissue layer and this reduction increased with thinner soft tissue and thicker bone layers. The backscatter factor increased about 21% as the angle of incidence of the beam with the entrance surface decreased from 90° (perpendicular) to 30°. The backscatter PSF differed for different locations on the SK-150 phantom by up to 15%. The results of this study can be used to improve the accuracy of dose calculation when using PSF convolution in the DTS.

Monte Carlo investigation of backscatter point spread function for X-ray imaging examinations. X-ray imaging examinations, especially complex interventions, may result in relatively high doses to the patient's skin inducing skin injuries. A method was developed to determine the skin-dose distribution for non-uniform x-ray beams by convolving the backscatter point-spread-function (PSF) with the primary-dose distribution to generate the backscatter distribution that, when added to the primary dose, gives the total-dose distribution. This technique was incorporated in the dose-tracking system (DTS), which provides a real-time color-coded 3D-mapping of skin dose during fluoroscopic procedures. The aim of this work is to investigate the variation of the backscatter PSF with different parameters. A backscatter PSF of a 1-mm x-ray beam was generated by EGSnrc Monte-Carlo code for different x-ray beam energies, different soft-tissue thickness above bone, different bone thickness and different entrance-beam angles, as well as for different locations on the SK-150 anthropomorphic head phantom. The results show a reduction of the peak scatter to primary dose ratio of 48% when X-ray beam voltage is increased from 40 keV to 120 keV. The backscatter dose was reduced when bone was beneath the soft tissue layer and this reduction increased with thinner soft tissue and thicker bone layers. The backscatter factor increased about 21% as the angle of incidence of the beam with the entrance surface decreased from 90° (perpendicular) to 30°. The backscatter PSF differed for different locations on the SK-150 phantom by up to 15%. The results of this study can be used to improve the accuracy of dose calculation when using PSF convolution in the DTS.

pubmed23n1138_17311

Gonioscopy-Assisted Transluminal Trabeculotomy: A Review.

<bAim:</b To review the recent evidence in the literature regarding the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in the management of pediatric and adult glaucoma.<bMethods:</b A literature search was performed in the electronic databases of PubMed, Google Scholar, Embase the Register of Controlled Trials, and Ovid Medline for studies evaluating the safety and outcomes of GATT in glaucoma.<bResults:</b GATT is a novel minimally invasive glaucoma surgery that allows the incision of the inner wall of Schlemm's canal increasing aqueous drainage through the physiologic outflow pathway with subsequent intraocular pressure reduction in different types if of glaucoma.<bConclusion:</b GATT demonstrated favorable results in a wide range of both primary and secondary open-angle and angle-closure glaucoma.

Gonioscopy-Assisted Transluminal Trabeculotomy: A Review. <bAim:</b To review the recent evidence in the literature regarding the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in the management of pediatric and adult glaucoma.<bMethods:</b A literature search was performed in the electronic databases of PubMed, Google Scholar, Embase the Register of Controlled Trials, and Ovid Medline for studies evaluating the safety and outcomes of GATT in glaucoma.<bResults:</b GATT is a novel minimally invasive glaucoma surgery that allows the incision of the inner wall of Schlemm's canal increasing aqueous drainage through the physiologic outflow pathway with subsequent intraocular pressure reduction in different types if of glaucoma.<bConclusion:</b GATT demonstrated favorable results in a wide range of both primary and secondary open-angle and angle-closure glaucoma.

pubmed23n0564_11824

Circadian rhythm of human salivary chromogranin A.

We investigated the circadian rhythm of chromogranin A (CgA) concentrations in saliva and blood samples from 40 male college students collected at 7 : 00, 8 : 00, 10 : 30, 12 : 30, 17 : 30, and 22 : 30. CgA concentrations were determined by ELISA. Salivary CgA levels peaked upon awakening, and then quickly decreased to the nadir after 1 hour and maintained a low level throughout the day. On the other hand, plasma CgA did not show any obvious circadian rhythm. These findings suggest that salivary and plasma CgA has different routes of secretion.

Circadian rhythm of human salivary chromogranin A. We investigated the circadian rhythm of chromogranin A (CgA) concentrations in saliva and blood samples from 40 male college students collected at 7 : 00, 8 : 00, 10 : 30, 12 : 30, 17 : 30, and 22 : 30. CgA concentrations were determined by ELISA. Salivary CgA levels peaked upon awakening, and then quickly decreased to the nadir after 1 hour and maintained a low level throughout the day. On the other hand, plasma CgA did not show any obvious circadian rhythm. These findings suggest that salivary and plasma CgA has different routes of secretion.

pubmed23n0566_4036

Peptidoglycan recognition protein (PGRP) from eri-silkworm, Samia cynthia ricini; protein purification and induction of the gene expression.

Peptidoglycan recognition protein (PGRP) was isolated from immunized hemolymph of the wild silkworm, Samia cynthia ricini, detecting the biding activity with (125)I-labeled peptidoglycan (PGN). The binding specificity of PGRP was tested by competitive inhibition of the binding to (125)I-labeled-PGN by a large excess amount of non-labeled-PGN or other glucans. The binding to labeled uncross-linked Lys-type PGN from Micrococcus luteus was strongly inhibited by non-labeled-PGN of the same structure and meso-diaminopimelic acid (DAP)-type cross-linked PGN from Bacillus cell wall, but only a little by cross-linked PGN from M. luteus cell wall. The PGRP cDNA encodes a 193 amino acid open reading frame. The deduced amino acid sequence had 62 to 91% identities to known lepidopteran PGRPs, but less than 40% to Drosophila PGRPs. The PGRP gene constitutively expressed at a low level in naive fat body, and strongly induced by an injection of DAP-type cross-linked and Lys-type uncross-linked PGNs, but only weakly by Lys-type cross-linked PGN from M. luteus. The silkworm possibly distinguish between PGNs based on the structure of cross-linking peptide, but has less if any preference for the diamino acid residue of the stem peptide.

Peptidoglycan recognition protein (PGRP) from eri-silkworm, Samia cynthia ricini; protein purification and induction of the gene expression. Peptidoglycan recognition protein (PGRP) was isolated from immunized hemolymph of the wild silkworm, Samia cynthia ricini, detecting the biding activity with (125)I-labeled peptidoglycan (PGN). The binding specificity of PGRP was tested by competitive inhibition of the binding to (125)I-labeled-PGN by a large excess amount of non-labeled-PGN or other glucans. The binding to labeled uncross-linked Lys-type PGN from Micrococcus luteus was strongly inhibited by non-labeled-PGN of the same structure and meso-diaminopimelic acid (DAP)-type cross-linked PGN from Bacillus cell wall, but only a little by cross-linked PGN from M. luteus cell wall. The PGRP cDNA encodes a 193 amino acid open reading frame. The deduced amino acid sequence had 62 to 91% identities to known lepidopteran PGRPs, but less than 40% to Drosophila PGRPs. The PGRP gene constitutively expressed at a low level in naive fat body, and strongly induced by an injection of DAP-type cross-linked and Lys-type uncross-linked PGNs, but only weakly by Lys-type cross-linked PGN from M. luteus. The silkworm possibly distinguish between PGNs based on the structure of cross-linking peptide, but has less if any preference for the diamino acid residue of the stem peptide.

pubmed23n0658_23964

Lupus mastitis: an uncommon complication of systemic or discoid lupus.

Lupus mastitis is an uncommon presentation of lupus erythematosus profundus or lupus panniculitis, a rare variant of lupus erythematosus characterized by inflammation of the subcutaneous fat. Lupus mastitis can present as single or multiple subcutaneous or deep breast masses, often clinically mimicking malignancy. Although lupus mastitis is rare, with less than 25 cases reported, the histologic features are distinct. Awareness of the entity and familiarity with the histologic features allow for accurate diagnosis and appropriate patient management. It most commonly affects women with a mean age at diagnosis of 40 years and an age range of 18 to 70 years. Typical histologic findings in lupus mastitis include a lymphocytic lobular panniculitis with plasma cells and hyaline fat necrosis. The lymphocytic infiltrate can be nodular, diffuse, periductal, and/or perilobular and germinal centers can frequently be identified. Lymphocytic vasculitis is also common. Immunohistochemistry shows a mixed T and B-cell population, with predominantly CD3+ CD4+ T cells intermixed with CD20-positive B cells and polyclonal plasma cells. Most commonly, lupus mastitis is seen in patients with a previous diagnosis of systemic or discoid lupus; however, it can also be the initial presentation of lupus in some patients. We report on 2 cases of lupus mastitis where the clinical impression was to rule out malignancy and review the literature to highlight the key clinicopathologic features.

Lupus mastitis: an uncommon complication of systemic or discoid lupus. Lupus mastitis is an uncommon presentation of lupus erythematosus profundus or lupus panniculitis, a rare variant of lupus erythematosus characterized by inflammation of the subcutaneous fat. Lupus mastitis can present as single or multiple subcutaneous or deep breast masses, often clinically mimicking malignancy. Although lupus mastitis is rare, with less than 25 cases reported, the histologic features are distinct. Awareness of the entity and familiarity with the histologic features allow for accurate diagnosis and appropriate patient management. It most commonly affects women with a mean age at diagnosis of 40 years and an age range of 18 to 70 years. Typical histologic findings in lupus mastitis include a lymphocytic lobular panniculitis with plasma cells and hyaline fat necrosis. The lymphocytic infiltrate can be nodular, diffuse, periductal, and/or perilobular and germinal centers can frequently be identified. Lymphocytic vasculitis is also common. Immunohistochemistry shows a mixed T and B-cell population, with predominantly CD3+ CD4+ T cells intermixed with CD20-positive B cells and polyclonal plasma cells. Most commonly, lupus mastitis is seen in patients with a previous diagnosis of systemic or discoid lupus; however, it can also be the initial presentation of lupus in some patients. We report on 2 cases of lupus mastitis where the clinical impression was to rule out malignancy and review the literature to highlight the key clinicopathologic features.

pubmed23n0809_10781

Surface engineered doping of hematite nanorod arrays for improved photoelectrochemical water splitting.

Given the narrow band gap enabling excellent optical absorption, increased charge carrier density and accelerated surface oxidation reaction kinetics become the key points for improved photoelectrochemical performances for water splitting over hematite (α-Fe2O3) photoanodes. In this study, a facile and inexpensive method was demonstrated to develop core/shell structured α-Fe2O3 nanorod arrays. A thin, Ag-doped overlayer of ~2-3 nm thickness was formed along α-Fe2O3 nanorods via ultrasonication treatment of solution-based β-FeOOH nanorods in Ag precursor solution followed by high temperature annealing. The obtained α-Fe2O3/AgxFe2-xO3 core/shell nanorod films demonstrated much higher photoelectrochemical performances as photoanodes than the pristine α-Fe2O3 nanorod film, especially in the visible light region; the incident photon-to-current efficiency (IPCE) at 400 nm was increased from 2.2% to 8.4% at 1.23 V vs. RHE (Reversible hydrogen electrode). Mott-Schottky analysis and X-ray absorption spectra revealed that the Ag-doped overlayer not only increased the carrier density in the near-surface region but also accelerated the surface oxidation reaction kinetics, synergistically contributing to the improved photoelectrochemical performances. These findings provide guidance for the design and optimization of nanostructured photoelectrodes for efficient solar water splitting.

Surface engineered doping of hematite nanorod arrays for improved photoelectrochemical water splitting. Given the narrow band gap enabling excellent optical absorption, increased charge carrier density and accelerated surface oxidation reaction kinetics become the key points for improved photoelectrochemical performances for water splitting over hematite (α-Fe2O3) photoanodes. In this study, a facile and inexpensive method was demonstrated to develop core/shell structured α-Fe2O3 nanorod arrays. A thin, Ag-doped overlayer of ~2-3 nm thickness was formed along α-Fe2O3 nanorods via ultrasonication treatment of solution-based β-FeOOH nanorods in Ag precursor solution followed by high temperature annealing. The obtained α-Fe2O3/AgxFe2-xO3 core/shell nanorod films demonstrated much higher photoelectrochemical performances as photoanodes than the pristine α-Fe2O3 nanorod film, especially in the visible light region; the incident photon-to-current efficiency (IPCE) at 400 nm was increased from 2.2% to 8.4% at 1.23 V vs. RHE (Reversible hydrogen electrode). Mott-Schottky analysis and X-ray absorption spectra revealed that the Ag-doped overlayer not only increased the carrier density in the near-surface region but also accelerated the surface oxidation reaction kinetics, synergistically contributing to the improved photoelectrochemical performances. These findings provide guidance for the design and optimization of nanostructured photoelectrodes for efficient solar water splitting.

pubmed23n0768_5054

Multifunctional finishing of wool fabrics by chitosan UV-grafting: an approach.

The aim of this study was the surface modification of wool fibers to confer a multifunctional finishing to the fabrics, improving the textile value and its applications without damage of comfort properties. The attention was focused on an economical and environmental friendly process to obtain an effective treatment with good durability to washing. Chitosan in acetic acid solution was applied by padding, and grafted by ultraviolet radiation, through radical reactions promoted by a photoinitiator. 2% chitosan grafted was enough to confer satisfactory antimicrobial activity (67% reduction of Escherichia coli) after an oxidative wool pre-treatment and 1h impregnation at 50 °C. Moreover treated wool fabrics showed a strong dyeability increase toward acid dye. However the evaluation of the treatment durability to laundering showed different behavior depending on the nature of the surfactants. Finally, anti-felting properties with respect to untreated fabrics were revealed, while no effect was shown toward anti-pilling properties.

Multifunctional finishing of wool fabrics by chitosan UV-grafting: an approach. The aim of this study was the surface modification of wool fibers to confer a multifunctional finishing to the fabrics, improving the textile value and its applications without damage of comfort properties. The attention was focused on an economical and environmental friendly process to obtain an effective treatment with good durability to washing. Chitosan in acetic acid solution was applied by padding, and grafted by ultraviolet radiation, through radical reactions promoted by a photoinitiator. 2% chitosan grafted was enough to confer satisfactory antimicrobial activity (67% reduction of Escherichia coli) after an oxidative wool pre-treatment and 1h impregnation at 50 °C. Moreover treated wool fabrics showed a strong dyeability increase toward acid dye. However the evaluation of the treatment durability to laundering showed different behavior depending on the nature of the surfactants. Finally, anti-felting properties with respect to untreated fabrics were revealed, while no effect was shown toward anti-pilling properties.

pubmed23n0902_16570

Changes in prevalence of precancerous oral submucous fibrosis from 1996 to 2013 in Taiwan: A nationwide population-based retrospective study.

Oral submucous fibrosis (OSF) has been regarded as a precancerous condition. Research examining the prevalence of OSF could be the first step in preventing or reducing malignant transformation. In this study, we probed a nationwide registered database to assess the prevalence, gender distribution, age, income, and urbanization status of OSF patients in Taiwan. A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Ministry of Health and Welfare, Taiwan. We identified dental visit patients diagnosed with OSF during the period between January 1, 1996 and December 31, 2013. In addition, demographic characteristics were analyzed by multivariate Poisson regression. The prevalence of OSF increased significantly from 8.3 (per 10<sup5</sup) in 1996 to 16.2 (per 10<sup5</sup) in 2013 (p &lt; 0.0001). Men had a significantly higher OSF prevalence than women (p &lt; 0.001). The mean age of patients with OSF increased from 1996 to 2013. Individuals living in rural areas had a higher risk of OSF compared with those living in urban areas [relative risk (RR), 1.10; 95% confidence interval (CI), 1.07-1.13]. The higher income group had a lower risk of OSF compared with the lower income group (RR, 0.76; 95% CI, 0.73-0.80). This large-scale government-centered survey demonstrates that the prevalence of OSF in Taiwan significantly increased from 1996 to 2013. The prevalence was higher among men than among women.

Changes in prevalence of precancerous oral submucous fibrosis from 1996 to 2013 in Taiwan: A nationwide population-based retrospective study. Oral submucous fibrosis (OSF) has been regarded as a precancerous condition. Research examining the prevalence of OSF could be the first step in preventing or reducing malignant transformation. In this study, we probed a nationwide registered database to assess the prevalence, gender distribution, age, income, and urbanization status of OSF patients in Taiwan. A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Ministry of Health and Welfare, Taiwan. We identified dental visit patients diagnosed with OSF during the period between January 1, 1996 and December 31, 2013. In addition, demographic characteristics were analyzed by multivariate Poisson regression. The prevalence of OSF increased significantly from 8.3 (per 10<sup5</sup) in 1996 to 16.2 (per 10<sup5</sup) in 2013 (p &lt; 0.0001). Men had a significantly higher OSF prevalence than women (p &lt; 0.001). The mean age of patients with OSF increased from 1996 to 2013. Individuals living in rural areas had a higher risk of OSF compared with those living in urban areas [relative risk (RR), 1.10; 95% confidence interval (CI), 1.07-1.13]. The higher income group had a lower risk of OSF compared with the lower income group (RR, 0.76; 95% CI, 0.73-0.80). This large-scale government-centered survey demonstrates that the prevalence of OSF in Taiwan significantly increased from 1996 to 2013. The prevalence was higher among men than among women.

pubmed23n0656_245

Bilateral non-arteritic anterior ischemic optic neuropathy (NA-AION): case report and review of the literature.

To present a 72-year-old woman affected by non-arteritic anterior ischemic optic neuropathy (NA-AION). To our knowledge, this clinical case, showing a bilateral form of NA-AION, is uncommon as only very few similar reports have been published in the scientific literature at this time. Visual acuity was reduced to 6/20 in both eyes, color vision was absent and computerized perimetry showed an absolute and general reduction of the retinal sensibility within 30 degrees around the fixation point. Pattern visual evoked potentials and pattern electroretinograms showed normal morphologies but delayed latencies and reduced amplitudes. An updated review of the literature has also been done.

Bilateral non-arteritic anterior ischemic optic neuropathy (NA-AION): case report and review of the literature. To present a 72-year-old woman affected by non-arteritic anterior ischemic optic neuropathy (NA-AION). To our knowledge, this clinical case, showing a bilateral form of NA-AION, is uncommon as only very few similar reports have been published in the scientific literature at this time. Visual acuity was reduced to 6/20 in both eyes, color vision was absent and computerized perimetry showed an absolute and general reduction of the retinal sensibility within 30 degrees around the fixation point. Pattern visual evoked potentials and pattern electroretinograms showed normal morphologies but delayed latencies and reduced amplitudes. An updated review of the literature has also been done.

pubmed23n0593_13931

Roles of complex gangliosides in the development of experimental autoimmune encephalomyelitis.

We induced experimental autoimmune encephalomyelitis (EAE) in GM2/GD2 synthase knockout mice (GM2/GD2-/-), which cannot synthesize complex gangliosides, such as GM1, GD1a, GD1b, GT1b, and GQ1b, to investigate the roles of complex gangliosides in the pathogenesis of this disease. We used myelin-oligodendrocyte glycoprotein (MOG) as an immunogen. In active immunization EAE, the severity of clinical score was not different but the disease onset was significantly delayed in GM2/GD2-/- compared with those in wild-type mice. When we transferred MOG-reactive T cells from GM2/GD2-/- or wild-type mice to wild-type mice, no significant differences were observed between the two groups. In contrast, when we transferred MOG-reactive T cells from wild-type mice to GM2/GD2-/- or to wild-type mice, the onset of EAE in GM2/GD2-/- mice was delayed. The recall response of MOG-specific T cells, the function of antigen presenting cells, or the expression of several adhesion molecules in the endothelium were not significantly different between GM2/GD2-/- and wild-type mice. On the other hand, quantitative analysis of cellular infiltration in the central nervous system (CNS) on day 9 of active immunization EAE showed that the CD4+ cell number in the CNS isolated from GM2/GD2-/- mice was significantly less than that from wild-type mice. It indicated that the delayed onset of EAE in GM2/GD2-/- mice was due to the delay of the migration of pathogenic T cells into the CNS. Thus, the complex gangliosides may be involved in the T cell-endothelial cell interaction in the pathogenetic process of EAE.

Roles of complex gangliosides in the development of experimental autoimmune encephalomyelitis. We induced experimental autoimmune encephalomyelitis (EAE) in GM2/GD2 synthase knockout mice (GM2/GD2-/-), which cannot synthesize complex gangliosides, such as GM1, GD1a, GD1b, GT1b, and GQ1b, to investigate the roles of complex gangliosides in the pathogenesis of this disease. We used myelin-oligodendrocyte glycoprotein (MOG) as an immunogen. In active immunization EAE, the severity of clinical score was not different but the disease onset was significantly delayed in GM2/GD2-/- compared with those in wild-type mice. When we transferred MOG-reactive T cells from GM2/GD2-/- or wild-type mice to wild-type mice, no significant differences were observed between the two groups. In contrast, when we transferred MOG-reactive T cells from wild-type mice to GM2/GD2-/- or to wild-type mice, the onset of EAE in GM2/GD2-/- mice was delayed. The recall response of MOG-specific T cells, the function of antigen presenting cells, or the expression of several adhesion molecules in the endothelium were not significantly different between GM2/GD2-/- and wild-type mice. On the other hand, quantitative analysis of cellular infiltration in the central nervous system (CNS) on day 9 of active immunization EAE showed that the CD4+ cell number in the CNS isolated from GM2/GD2-/- mice was significantly less than that from wild-type mice. It indicated that the delayed onset of EAE in GM2/GD2-/- mice was due to the delay of the migration of pathogenic T cells into the CNS. Thus, the complex gangliosides may be involved in the T cell-endothelial cell interaction in the pathogenetic process of EAE.

pubmed23n0687_4787

Comparison of surgical outcomes of lenke type 1 idiopathic scoliosis: vertebral coplanar alignment versus derotation technique.

Prospective clinical study. To compare the surgical outcomes of vertebral coplanar alignment (VCA) technique against the derotation maneuver with segmental pedicle screw instrumentation in patients with Lenke type 1 idiopathic scoliosis. Nowadays the majority of scoliosis correction begins with rod rotation and translation from the concave side, which bears potential neurovascular risks. The technique of VCA was introduced by Vallespir with the intention of correcting rotation and translation and restoring the normal sagittal profile of thoracic scoliosis simultaneously. The fusion levels were decided according to the Lenke criteria. In group A (24 cases), the VCA technique was used. The pedicle screws were inserted at each vertebral level on the convex side and at every other level on the concave side, an extended coplanar tube was secured in line with screw axis to each pedicle screw. Two rigid bars were inserted through the top of the slotted tube. The first rod was kept in this position, whereas the second bar was gently driven down through the slotted tube toward the bottom end. This causes the pedicle screws to align in the sagittal plane, and hence, correct both translation and rotation. The thoracic kyphosis was restored with spacers, which separate the coplanar tubes apart. The derotation maneuver was applied in group B (24 cases). Multiple clinical and radiographic parameters were evaluated and compared. The preoperative data were similar between the 2 groups in terms of age, sex, Risser sign, and curve magnitude. In group A, the coronal Cobb angle was corrected from an average of 58 to 16 degrees with a correction rate of 71.8%, and the thoracic kyphosis was restored from an average of 18 to 28 degrees. In group B, the coronal Cobb angle was reduced from 55 to 17 degrees with a correction rate of 68.4%, and the thoracic kyphosis was increased from an average of 15 to 18 degrees. Patients were followed for an average of 17 months (14 to 20 mo) with both groups showing no significant loss of correction. There were no vascular or neurological complications related to pedicle screw insertion or scoliosis correction. Two screws pullout occurred on the concave side in group B. There was 1 case of hemothorax related to a thoracoplasty procedure in group B. No pseudarthrosis occurred during follow-up in both the groups. In treating thoracic scoliosis, the VCA technique could achieve as good correction and clinical outcome as the derotation technique. The advantage lies in its superior renormalization effect of thoracic kyphosis compared with the derotation technique from the concave side.

Comparison of surgical outcomes of lenke type 1 idiopathic scoliosis: vertebral coplanar alignment versus derotation technique. Prospective clinical study. To compare the surgical outcomes of vertebral coplanar alignment (VCA) technique against the derotation maneuver with segmental pedicle screw instrumentation in patients with Lenke type 1 idiopathic scoliosis. Nowadays the majority of scoliosis correction begins with rod rotation and translation from the concave side, which bears potential neurovascular risks. The technique of VCA was introduced by Vallespir with the intention of correcting rotation and translation and restoring the normal sagittal profile of thoracic scoliosis simultaneously. The fusion levels were decided according to the Lenke criteria. In group A (24 cases), the VCA technique was used. The pedicle screws were inserted at each vertebral level on the convex side and at every other level on the concave side, an extended coplanar tube was secured in line with screw axis to each pedicle screw. Two rigid bars were inserted through the top of the slotted tube. The first rod was kept in this position, whereas the second bar was gently driven down through the slotted tube toward the bottom end. This causes the pedicle screws to align in the sagittal plane, and hence, correct both translation and rotation. The thoracic kyphosis was restored with spacers, which separate the coplanar tubes apart. The derotation maneuver was applied in group B (24 cases). Multiple clinical and radiographic parameters were evaluated and compared. The preoperative data were similar between the 2 groups in terms of age, sex, Risser sign, and curve magnitude. In group A, the coronal Cobb angle was corrected from an average of 58 to 16 degrees with a correction rate of 71.8%, and the thoracic kyphosis was restored from an average of 18 to 28 degrees. In group B, the coronal Cobb angle was reduced from 55 to 17 degrees with a correction rate of 68.4%, and the thoracic kyphosis was increased from an average of 15 to 18 degrees. Patients were followed for an average of 17 months (14 to 20 mo) with both groups showing no significant loss of correction. There were no vascular or neurological complications related to pedicle screw insertion or scoliosis correction. Two screws pullout occurred on the concave side in group B. There was 1 case of hemothorax related to a thoracoplasty procedure in group B. No pseudarthrosis occurred during follow-up in both the groups. In treating thoracic scoliosis, the VCA technique could achieve as good correction and clinical outcome as the derotation technique. The advantage lies in its superior renormalization effect of thoracic kyphosis compared with the derotation technique from the concave side.

pubmed23n0948_5205

Clinical effectiveness of carbapenems versus alternative antibiotics for treating ESBL-producing Enterobacteriaceae bacteraemia: a systematic review and meta-analysis.

The widespread administration of carbapenems to patients with ESBL-producing Enterobacteriaceae bacteraemia (ESBL-B) has accelerated the emergence of carbapenem-resistant Enterobacteriaceae. This study aimed to systematically review recently published data to evaluate the clinical effectiveness of carbapenems, compared with other antibiotics, in the treatment of ESBL-B. We searched the Ovid-Medline, Ovid-Embase, Cochrane Library and five Korean local databases until January 2016. We selected studies that reported overall mortality in patients with ESBL-B who had been treated with carbapenems and alternatives. Overall mortality was assessed as the primary outcome and sepsis-related mortality and adverse events were analysed as secondary outcomes. Thirty-five publications fulfilled the inclusion criteria. Regarding empirical therapy, there were no significant differences between the groups that received carbapenems and those that received non-carbapenems in relation to overall mortality. Regarding definitive therapy, overall mortality was lower for patients administered carbapenems compared with those administered non-carbapenems [risk ratio (RR) 0.78, 95% CI 0.61-0.98], non-β-lactam/β-lactamase inhibitor combinations (non-BL/BLI) (RR 0.71, 95% CI 0.56-0.90) and cephalosporins (RR 0.56, 95% CI 0.42-0.74). There were no differences between the carbapenems and the other antibiotics, namely BL/BLIs, quinolones and aminoglycosides. This meta-analysis showed that BL/BLIs may be promising alternative antibiotics for definitive therapy in patients with ESBL-B. However, the lack of robust data derived from randomized controlled trials limits the conclusions and inferences from the pooled data.

Clinical effectiveness of carbapenems versus alternative antibiotics for treating ESBL-producing Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. The widespread administration of carbapenems to patients with ESBL-producing Enterobacteriaceae bacteraemia (ESBL-B) has accelerated the emergence of carbapenem-resistant Enterobacteriaceae. This study aimed to systematically review recently published data to evaluate the clinical effectiveness of carbapenems, compared with other antibiotics, in the treatment of ESBL-B. We searched the Ovid-Medline, Ovid-Embase, Cochrane Library and five Korean local databases until January 2016. We selected studies that reported overall mortality in patients with ESBL-B who had been treated with carbapenems and alternatives. Overall mortality was assessed as the primary outcome and sepsis-related mortality and adverse events were analysed as secondary outcomes. Thirty-five publications fulfilled the inclusion criteria. Regarding empirical therapy, there were no significant differences between the groups that received carbapenems and those that received non-carbapenems in relation to overall mortality. Regarding definitive therapy, overall mortality was lower for patients administered carbapenems compared with those administered non-carbapenems [risk ratio (RR) 0.78, 95% CI 0.61-0.98], non-β-lactam/β-lactamase inhibitor combinations (non-BL/BLI) (RR 0.71, 95% CI 0.56-0.90) and cephalosporins (RR 0.56, 95% CI 0.42-0.74). There were no differences between the carbapenems and the other antibiotics, namely BL/BLIs, quinolones and aminoglycosides. This meta-analysis showed that BL/BLIs may be promising alternative antibiotics for definitive therapy in patients with ESBL-B. However, the lack of robust data derived from randomized controlled trials limits the conclusions and inferences from the pooled data.

pubmed23n0891_19253

The Blitz Anesthesia Technique in Non-English Speaking Patients Undergoing Glaucoma Surgery.

To describe a less invasive method of providing anesthesia in non-English speaking patients undergoing glaucoma surgery. Prospective observational study conducted in a tertiary Care Eye Institute, Wills Eye Institute, Philadelphia, PA, USA. The blitz anesthesia technique was applied to 15 non-English speaking patients (Vietnamese, Mandarin, Russian and Korean) during glaucoma surgery. With input from family members, a diagram was created for each patient. The diagram consisted of a translation and phonetic guide to pronunciation of common words or phrases in the patient's native language that might be used by the surgical team during the operation. The blitz anesthesia technique worked well to provide patient comfort during the procedures. All patients reported adequate pain control and described their experience as comfortable. Additionally, patients reported feeling reassured that they were able to understand basic information from the surgical team during their case. This technique decreased patient anxiety prior to and during the surgical procedure. Blitz anesthesia provided adequate pain control with no complications. Blitz anesthesia with a phonetic language diagram, a less invasive technique of providing anesthesia in non-English speaking patients undergoing glaucoma surgery. Almodin J, Ichhpujani P, Prasad A, Fudemberg SJ, Moster MR. The Blitz Anesthesia Technique in Non-English Speaking Patients Undergoing Glaucoma Surgery. J Current Glau Prac 2012;6(2):91-93.

The Blitz Anesthesia Technique in Non-English Speaking Patients Undergoing Glaucoma Surgery. To describe a less invasive method of providing anesthesia in non-English speaking patients undergoing glaucoma surgery. Prospective observational study conducted in a tertiary Care Eye Institute, Wills Eye Institute, Philadelphia, PA, USA. The blitz anesthesia technique was applied to 15 non-English speaking patients (Vietnamese, Mandarin, Russian and Korean) during glaucoma surgery. With input from family members, a diagram was created for each patient. The diagram consisted of a translation and phonetic guide to pronunciation of common words or phrases in the patient's native language that might be used by the surgical team during the operation. The blitz anesthesia technique worked well to provide patient comfort during the procedures. All patients reported adequate pain control and described their experience as comfortable. Additionally, patients reported feeling reassured that they were able to understand basic information from the surgical team during their case. This technique decreased patient anxiety prior to and during the surgical procedure. Blitz anesthesia provided adequate pain control with no complications. Blitz anesthesia with a phonetic language diagram, a less invasive technique of providing anesthesia in non-English speaking patients undergoing glaucoma surgery. Almodin J, Ichhpujani P, Prasad A, Fudemberg SJ, Moster MR. The Blitz Anesthesia Technique in Non-English Speaking Patients Undergoing Glaucoma Surgery. J Current Glau Prac 2012;6(2):91-93.

pubmed23n0240_14844

Survival of Staphylococcus aureus in intraperitoneal abscesses.

An examination of 10 strains of Staphylococcus aureus for survival within abscesses developing in the peritoneal cavity of mice revealed three distinct patterns of survival. Although non-haemolytic mutants were destroyed more rapidly than were their parent strains, this difference could not be attributed to any particular haemolysin. In abscesses generated with mixtures of non-haemolytic variants and their parent strains, the former were preferentially eliminated; this suggests that the non-haemolytic variants were inherently more sensitive to the conditions within these lesions. Subsequent studies confirmed that abscess homogenates were cidal for staphylococci and that this activity resided in the insoluble fraction of the homogenates. Staphylococci added to abscess homogenates were killed, but only after a lag. This lag could be shortened or eliminated by incubating homogenates before adding the test organism. After development of a suitable assay, it was found that the cidal activity in abscess homogenates could be increased 3-20-fold by pre-incubation. Staphylococcal strains differed in their relative sensitivities to the cidal material; those strains rapidly destroyed within abscesses were the most sensitive and strains capable of better survival were more resistant. The results support the concept that the cidal material is responsible for destruction of staphylococci within such lesions.

Survival of Staphylococcus aureus in intraperitoneal abscesses. An examination of 10 strains of Staphylococcus aureus for survival within abscesses developing in the peritoneal cavity of mice revealed three distinct patterns of survival. Although non-haemolytic mutants were destroyed more rapidly than were their parent strains, this difference could not be attributed to any particular haemolysin. In abscesses generated with mixtures of non-haemolytic variants and their parent strains, the former were preferentially eliminated; this suggests that the non-haemolytic variants were inherently more sensitive to the conditions within these lesions. Subsequent studies confirmed that abscess homogenates were cidal for staphylococci and that this activity resided in the insoluble fraction of the homogenates. Staphylococci added to abscess homogenates were killed, but only after a lag. This lag could be shortened or eliminated by incubating homogenates before adding the test organism. After development of a suitable assay, it was found that the cidal activity in abscess homogenates could be increased 3-20-fold by pre-incubation. Staphylococcal strains differed in their relative sensitivities to the cidal material; those strains rapidly destroyed within abscesses were the most sensitive and strains capable of better survival were more resistant. The results support the concept that the cidal material is responsible for destruction of staphylococci within such lesions.

pubmed23n0643_24635

Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram.

Many patients with localized node-negative renal cell carcinoma (RCC) are elderly with competing comorbidities. Their overall survival benefit after surgical treatment is unknown. We reviewed cases in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the impact of kidney cancer versus competing causes of death in patients with localized RCC and develop a comprehensive nomogram to quantitate survival differences. We identified individuals with localized, surgically treated clear-cell, papillary, or chromophobe RCC in SEER (1988 through 2003). We used Fine and Gray competing risks proportional hazards regressions to predict 5-year probabilities of three competing mortality outcomes: kidney cancer death, other cancer death, and noncancer death. We identified 30,801 cases of localized RCC (median age, 62 years; median tumor size, 4.5 cm). Five-year probabilities of kidney cancer death, other cancer death, and noncancer death were 4%, 7%, and 11%, respectively. Age was strongly predictive of mortality and most predictive of nonkidney cancer deaths (P &lt; .001). Increasing tumor size was related to death from RCC and inversely related to noncancer deaths (P &lt; .001). Racial differences in outcomes were most pronounced for nonkidney cancer deaths (P &lt; .001). Men were more likely to die than women from all causes (P &lt; .002). This nomogram integrates commonly available factors into a useful tool for comparing competing risks of death. Management of localized RCC must consider competing causes of mortality, particularly in elderly populations. Effective decision making requires treatment trade-off calculations. We present a tool to quantitate competing causes of mortality in patients with localized RCC.

Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram. Many patients with localized node-negative renal cell carcinoma (RCC) are elderly with competing comorbidities. Their overall survival benefit after surgical treatment is unknown. We reviewed cases in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the impact of kidney cancer versus competing causes of death in patients with localized RCC and develop a comprehensive nomogram to quantitate survival differences. We identified individuals with localized, surgically treated clear-cell, papillary, or chromophobe RCC in SEER (1988 through 2003). We used Fine and Gray competing risks proportional hazards regressions to predict 5-year probabilities of three competing mortality outcomes: kidney cancer death, other cancer death, and noncancer death. We identified 30,801 cases of localized RCC (median age, 62 years; median tumor size, 4.5 cm). Five-year probabilities of kidney cancer death, other cancer death, and noncancer death were 4%, 7%, and 11%, respectively. Age was strongly predictive of mortality and most predictive of nonkidney cancer deaths (P &lt; .001). Increasing tumor size was related to death from RCC and inversely related to noncancer deaths (P &lt; .001). Racial differences in outcomes were most pronounced for nonkidney cancer deaths (P &lt; .001). Men were more likely to die than women from all causes (P &lt; .002). This nomogram integrates commonly available factors into a useful tool for comparing competing risks of death. Management of localized RCC must consider competing causes of mortality, particularly in elderly populations. Effective decision making requires treatment trade-off calculations. We present a tool to quantitate competing causes of mortality in patients with localized RCC.

pubmed23n0233_11201

Liberation of the triosephosphate isomerase reaction intermediate and its trapping by isomerase, yeast aldolase, and methylglyoxal synthase.

When a mixture of triosephosphate isomerase (rabbit muscle) and dihydroxyacetone phosphate (DHAP) is quenched with acid, a compound is liberated, presumed to be the cis-enediol 3-phosphate, that decomposes to inorganic phosphate (Pi) and methylglyoxal [Iyengar, R., &amp; Rose, I.A. (1981) Biochemistry (preceding paper is this issue)]. The decomposition can be prevented by rapid neutralization if a catalytic amount of fresh isomerase is present. Varying the time between acidification and rescue gave a half-life of the liberate compound of approximately 12-17 ms. Varying the concentration of enzyme used for rescue gave a minimum second-order rate constant for trapping of 10(9)M(-1)s(-1). These results add further evidence favoring a stepwise mechanism for the aldose-ketose isomerase reactions in which a chemically defined enzyme-bound intermediate is found. The high rate of trapping over a wide pH range indicates that the enediol phosphate, not the enediolate phosphate, is the intermediate. One property of the enzyme is to stabilize the intermediate with respect to its fragmentation in solution by greater than 1000-fold. Yeast aldolase is also able to rescue all of the isomerase intermediate, though higher concentrations of enzyme are required. Although different enantiotopic protons of DHAP are abstracted by isomerase and aldolase, both enzymes use the same enediol phosphate intermediate. Methylglyoxal synthase at a 50-fold greater concentration was unable to compete with triosephosphate isomerase for cis-enediol phosphate. Either the synthetase has a low V/K for the cis isomer or it uses the trans-enediol phosphate form specifically. A new strategy for the chemical and enzymological characterization of enzyme reaction intermediates is proved here based on the liberation of the intermediate from the reaction equilibrium and its recovery by fresh enzyme or another enzyme species.

Liberation of the triosephosphate isomerase reaction intermediate and its trapping by isomerase, yeast aldolase, and methylglyoxal synthase. When a mixture of triosephosphate isomerase (rabbit muscle) and dihydroxyacetone phosphate (DHAP) is quenched with acid, a compound is liberated, presumed to be the cis-enediol 3-phosphate, that decomposes to inorganic phosphate (Pi) and methylglyoxal [Iyengar, R., &amp; Rose, I.A. (1981) Biochemistry (preceding paper is this issue)]. The decomposition can be prevented by rapid neutralization if a catalytic amount of fresh isomerase is present. Varying the time between acidification and rescue gave a half-life of the liberate compound of approximately 12-17 ms. Varying the concentration of enzyme used for rescue gave a minimum second-order rate constant for trapping of 10(9)M(-1)s(-1). These results add further evidence favoring a stepwise mechanism for the aldose-ketose isomerase reactions in which a chemically defined enzyme-bound intermediate is found. The high rate of trapping over a wide pH range indicates that the enediol phosphate, not the enediolate phosphate, is the intermediate. One property of the enzyme is to stabilize the intermediate with respect to its fragmentation in solution by greater than 1000-fold. Yeast aldolase is also able to rescue all of the isomerase intermediate, though higher concentrations of enzyme are required. Although different enantiotopic protons of DHAP are abstracted by isomerase and aldolase, both enzymes use the same enediol phosphate intermediate. Methylglyoxal synthase at a 50-fold greater concentration was unable to compete with triosephosphate isomerase for cis-enediol phosphate. Either the synthetase has a low V/K for the cis isomer or it uses the trans-enediol phosphate form specifically. A new strategy for the chemical and enzymological characterization of enzyme reaction intermediates is proved here based on the liberation of the intermediate from the reaction equilibrium and its recovery by fresh enzyme or another enzyme species.