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  • Little is known about how effort is represented for different kinds of tasks. Recently, we suggested that it would help to establish empirical benchmarks for this problem. Accordingly, Feghhi and Rosenbaum (Journal of Experimental Psychology Human Perception and Performance, 45983-994, 2019) estimated how many additional digits to be memorized corresponded to navigating through a narrow gap versus a wide gap. The estimates were based on a study in which participants chose between walking paths with associated memory demands. We found that participants were equally willing to choose to walk through a narrow gap as to walk through a wide gap when the narrow-gap walk required memorization of 0.55 fewer digits on average than the wide-gap walk. In the present experiment, we sought to replicate and extend this previous finding in two ways (1) by presenting the memory digits in auditory rather than visual form to test the hypothesis that participants used phonological recoding of the visually presented digits; and (2) by providing a new metric of the relative difficulty of navigation errors compared to recall errors. We provided 36 university students with two action/memorization options per trial and asked them to choose the easier option. Each option had varying degrees of physical demand (walking through a wide or narrow gap) and mental demand (memorizing 6, 7, or 8 digits). We expected performance to be comparable to what we observed earlier with visually presented digits to be memorized, and this prediction was confirmed. We also used a new metric to show that navigation errors were implicitly judged to be 17% more costly than recall errors. The fact that this percentage was not 0 indicates that reducing percent error was not the only basis for reducing effort.Genome-wide association studies (GWAS) have identified hundreds of primarily non-coding disease-susceptibility variants that further need functional interpretation to prioritize and discriminate the disease-relevant variants. We present a comprehensive genome-wide non-coding variant prioritization scheme followed by validation using Pyrosequencing and TaqMan assays in asthma. We implemented a composite Functional Annotation Score (cFAS) to investigate over 32,000 variants consisting of 1525 GWAS-lead asthma-susceptibility variants and their LD proxies (r2 ≥ 0.80). Functional annotation pipeline in cFAS revealed 274 variants with significant score at 1% false discovery rate. This study implicates a novel locus 4p16 (SLC26A1) with eQTL variant (rs11936407) and known loci in 17q12-21 and 5q22 which encode ORM1-like protein 3 (ORMDL3, rs406527, and rs12936231) and thymic stromal lymphopoietin (TSLP, rs3806932 and rs10073816) epithelial gene, respectively. Follow-up validation analysis through pyrosequencing of CpG sites in and nearby rs4065275 and rs11936407 showed genotype-dependent hypomethylation on asthma cases compared with healthy controls. Prioritized variants are enriched for asthma-specific histone modification associated with active chromatin (H3K4me1 and H3K27ac) in T cells, B cells, lung, and immune-related interferon gamma signaling pathways. Our findings, together with those from prior studies, suggest that SNPs can affect asthma by regulating enhancer activity, and our comprehensive bioinformatics and functional analysis could lead to biological insights into asthma pathogenesis.Graphic abstract.Whether effects of psychotherapies for depression are sustained after treatment is an important clinical issue. In older depressed children and adolescents such treatments have been shown to be sustained for several months. Rates of remission ranged from 62-69% at 3 months-1 year in one large scale study. To date there has been no data to inform whether the effects of earlier interventions for depression in the preschool period are sustained. To address this, we used data from a randomized controlled trial of a novel early intervention for depression called "Parent Child Interaction Therapy Emotion Development" (PCIT-ED) that has shown efficacy for depression, parenting stress and parenting practices. Participants and their caregivers were re-assessed 18 weeks after treatment completion. All study procedures were approved by the Washington University School of Medicine Internal Review Board prior to data collection. Study findings demonstrated a high rate of sustained gains in remission from depression, decreased parenting stress and parental depression 18 weeks after completion of a trial of PCIT-ED in a population of young children. Parental response to the child expression of emotion, a key treatment target drifted **** towards baseline after 3 months. Relapse rates were 17% and predictors of relapse were the presence of an externalizing disorder, a higher number of co-morbid disorders and poorer guilt reparation and emotion regulation measured at treatment completion. https://www.selleckchem.com/products/cdk2-inhibitor-73.html This extends the body of literature demonstrating parent-child interaction therapy (PCIT) to have sustained effects on targeted disruptive symptom profiles to early childhood depression. This relatively low relapse rate after 18 weeks is comparable or better than many empirically proven treatments for depression in older children.Mother-to-child transmission of hepatitis B virus (HBV) is the main route of transmission in Asia, and characterization of HBV quasispecies is needed to further understand virus evolution and adaptation. To understand changes in HBV during mother-to-child transmission, we enrolled nine pairs of mothers and children in the study, including a set of twins. Three groups were infected with HBV genotype C, and six groups were infected with HBV genotype B. The full-length HBV genome was amplified by PCR from serum samples before antiviral treatment, the whole viral genomes from each pair were sequenced, and the complexity and diversity of the quasispecies were analyzed. The entropy of transmitted HBV in children was found to be lower than their mothers, suggesting that there was a bottleneck effect during HBV transmission from the mother to the child. Selective evolution was shown by calculating πN and πS in the whole genomes, and the highest values were obtained for the X gene, which plays a role in viral replication and immune escape.
    Little is known about how effort is represented for different kinds of tasks. Recently, we suggested that it would help to establish empirical benchmarks for this problem. Accordingly, Feghhi and Rosenbaum (Journal of Experimental Psychology Human Perception and Performance, 45983-994, 2019) estimated how many additional digits to be memorized corresponded to navigating through a narrow gap versus a wide gap. The estimates were based on a study in which participants chose between walking paths with associated memory demands. We found that participants were equally willing to choose to walk through a narrow gap as to walk through a wide gap when the narrow-gap walk required memorization of 0.55 fewer digits on average than the wide-gap walk. In the present experiment, we sought to replicate and extend this previous finding in two ways (1) by presenting the memory digits in auditory rather than visual form to test the hypothesis that participants used phonological recoding of the visually presented digits; and (2) by providing a new metric of the relative difficulty of navigation errors compared to recall errors. We provided 36 university students with two action/memorization options per trial and asked them to choose the easier option. Each option had varying degrees of physical demand (walking through a wide or narrow gap) and mental demand (memorizing 6, 7, or 8 digits). We expected performance to be comparable to what we observed earlier with visually presented digits to be memorized, and this prediction was confirmed. We also used a new metric to show that navigation errors were implicitly judged to be 17% more costly than recall errors. The fact that this percentage was not 0 indicates that reducing percent error was not the only basis for reducing effort.Genome-wide association studies (GWAS) have identified hundreds of primarily non-coding disease-susceptibility variants that further need functional interpretation to prioritize and discriminate the disease-relevant variants. We present a comprehensive genome-wide non-coding variant prioritization scheme followed by validation using Pyrosequencing and TaqMan assays in asthma. We implemented a composite Functional Annotation Score (cFAS) to investigate over 32,000 variants consisting of 1525 GWAS-lead asthma-susceptibility variants and their LD proxies (r2 ≥ 0.80). Functional annotation pipeline in cFAS revealed 274 variants with significant score at 1% false discovery rate. This study implicates a novel locus 4p16 (SLC26A1) with eQTL variant (rs11936407) and known loci in 17q12-21 and 5q22 which encode ORM1-like protein 3 (ORMDL3, rs406527, and rs12936231) and thymic stromal lymphopoietin (TSLP, rs3806932 and rs10073816) epithelial gene, respectively. Follow-up validation analysis through pyrosequencing of CpG sites in and nearby rs4065275 and rs11936407 showed genotype-dependent hypomethylation on asthma cases compared with healthy controls. Prioritized variants are enriched for asthma-specific histone modification associated with active chromatin (H3K4me1 and H3K27ac) in T cells, B cells, lung, and immune-related interferon gamma signaling pathways. Our findings, together with those from prior studies, suggest that SNPs can affect asthma by regulating enhancer activity, and our comprehensive bioinformatics and functional analysis could lead to biological insights into asthma pathogenesis.Graphic abstract.Whether effects of psychotherapies for depression are sustained after treatment is an important clinical issue. In older depressed children and adolescents such treatments have been shown to be sustained for several months. Rates of remission ranged from 62-69% at 3 months-1 year in one large scale study. To date there has been no data to inform whether the effects of earlier interventions for depression in the preschool period are sustained. To address this, we used data from a randomized controlled trial of a novel early intervention for depression called "Parent Child Interaction Therapy Emotion Development" (PCIT-ED) that has shown efficacy for depression, parenting stress and parenting practices. Participants and their caregivers were re-assessed 18 weeks after treatment completion. All study procedures were approved by the Washington University School of Medicine Internal Review Board prior to data collection. Study findings demonstrated a high rate of sustained gains in remission from depression, decreased parenting stress and parental depression 18 weeks after completion of a trial of PCIT-ED in a population of young children. Parental response to the child expression of emotion, a key treatment target drifted back towards baseline after 3 months. Relapse rates were 17% and predictors of relapse were the presence of an externalizing disorder, a higher number of co-morbid disorders and poorer guilt reparation and emotion regulation measured at treatment completion. https://www.selleckchem.com/products/cdk2-inhibitor-73.html This extends the body of literature demonstrating parent-child interaction therapy (PCIT) to have sustained effects on targeted disruptive symptom profiles to early childhood depression. This relatively low relapse rate after 18 weeks is comparable or better than many empirically proven treatments for depression in older children.Mother-to-child transmission of hepatitis B virus (HBV) is the main route of transmission in Asia, and characterization of HBV quasispecies is needed to further understand virus evolution and adaptation. To understand changes in HBV during mother-to-child transmission, we enrolled nine pairs of mothers and children in the study, including a set of twins. Three groups were infected with HBV genotype C, and six groups were infected with HBV genotype B. The full-length HBV genome was amplified by PCR from serum samples before antiviral treatment, the whole viral genomes from each pair were sequenced, and the complexity and diversity of the quasispecies were analyzed. The entropy of transmitted HBV in children was found to be lower than their mothers, suggesting that there was a bottleneck effect during HBV transmission from the mother to the child. Selective evolution was shown by calculating πN and πS in the whole genomes, and the highest values were obtained for the X gene, which plays a role in viral replication and immune escape.
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  • Introduction Minimally invasive spine surgery has become more prevalent in recent years, but the delivery of interbody devices with small footprints may insufficiently restore the disc space, which may lead to instability and non-union. Vertically expandable interbody implants have partially addressed this limitation, but lateral fusion support remains a concern. The purpose of this study was to evaluate two-year safety and effectiveness outcomes with a multidimensional, expandable interbody fusion device (Luna 3D Interbody Fusion System, Benvenue Medical, Inc., Santa Clara, CA) that is delivered through a minimally invasive approach (6-8 mm) that expands in situ to approximate an anterior lumbar interbody fusion footprint of 25 mm diameter. Material and methods This was a retrospective, single-center study that evaluated the clinical utility of a multi-expandable interbody cage in patients undergoing posterior or transforaminal lumbar interbody fusion. Key patient-reported outcomes included **** pain severit mean ODI score decreased by 61%, **** pain severity decreased by 67%, and leg pain severity decreased by 80% (all p less then 0.001). Comparing radiographic measures from baseline to two years, anterior disc height increased from 7.6 mm to 15.5 mm, posterior disc height increased from 2.9 mm to 10.1 mm, average disc height increased from 5.6 mm to 13.3 mm, foraminal height increased from 12.2 mm to 20.2 mm, and segmental lordosis increased from 6.2 degrees to 14.0 degrees (all changes p less then 0.001). One case of non-union was observed and the corresponding two-year fusion rate was 98%. Conclusions The utilization of a minimally invasive, multidimensional, expandable interbody implant was safe and effective over two years of clinical follow-up. The implant allows the surgeon to re-establish sagittal balance and to provide a larger surface area for fusion as compared to traditional minimally invasive interbody devices. Copyright © 2020, Kucharzyk et al.Enteritis associated with systemic lupus erythematosus (SLE) is a rare and unusual manifestation of the gastrointestinal (GI) consequences of SLE itself. Complications of the enteritis component include mesenteric vasculitis, intestinal pseudo-obstruction, and protein-losing enteropathy. Lupus enteritis is very responsive to treatment with pulse steroids in almost 70% of the patients, but it is critical to diagnose it early to prevent devastating organ damage. The case describes a 21-year-old Caucasian female with a past medical history of uncomplicated laparoscopic appendectomy (one month prior to the time of presentation), major depressive disorder, asthma, iron deficiency anemia, pelvic inflammatory disease secondary to sexually transmitted Chlamydia trachomatis infection, and SLE (diagnosed two weeks prior to presentation). She had been transferred from an outside facility with complaints of severe right upper quadrant (RUQ) abdominal pain for one day. The patient had run out of her prescription for sterochloroquine. She was discharged with instructions for outpatient follow-up with gastroenterology and rheumatology. Copyright © 2020, Ronen et al.Although most cases of acute pancreatitis are attributed to alcohol and gallstones, acute pancreatitis can be a presenting feature or complication of a viral etiology (influenza). We report a rare case of acute pancreatitis secondary to H1N1 influenza A virus in the setting of chronic lymphocytic leukemia. The typical flu-like respiratory illness usually observed with influenza was absent preceding the episode of pancreatitis owing to the different antigenic properties of influenza A (compared to influenza B) and an underlying immunocompromised state. Copyright © 2020, Avalos et al.Skeletal transcutaneous osseointegration was performed on a 54-year-old female transfemoral amputee. None of the available osseointegration implants achieved press-fit stability, so an implant was cemented in position. Although initially stable, by six months the patient reported painful loading and radiographs revealed cement mantle lucency. The osseointegration implant was removed, antibiotics were delivered via implanted spacer and intravenously, and revision osseointegration three months later achieved appropriate immediate press-fit stability. Cemented transcutaneous osseointegration implants loosen within one year. Osseointegration is only successful when bone grows directly onto the implant. Copyright © 2020, Hoellwarth et al.Background Education is undergoing a transformation. The traditional passive lectures are failing to capture and inspire the new generation of learners who value more active and collaborative learning techniques. Objective We sought to create a novel educational technique to integrate into our curriculum that would be more personalized, employ more active learning and collaboration, and allow for an effective assessment of resident strengths and weaknesses. Discussion We created a monthly assembly line education academic half-day that evolved to replace one of the typical in-classroom didactics each month. Faculty run small-group simulation rooms, procedure workshops, competitive ultrasound, and wellness stations through which residents and medical students rotate. Conclusion This novel education technique resulted in a more personalized approach that increased resident interest, sparked the creation of a very popular MedEd-Simulation elective, and allowed the faculty to gain a better sense of resident strengths and deficiencies. https://www.selleckchem.com/products/cc-115.html Copyright © 2020, Rosario et al.Central nervous system (CNS) histoplasmosis occurs in 5-20% of all cases and is most commonly seen in immunosuppressed patients who have acquired immunodeficiency syndrome (AIDS) or have received organ transplant. The prevalence of histoplasmosis in patients greater than 65 years old between the years of 1999-2008 in the state of Texas was about 2-3 cases per 100,000 patients year. Since 1990 with the discovery of Triazoles, itraconazole (ICZ) has become the standard initial and suppressive therapy in patients with mild-moderate histoplasmosis without CNS involvement. However, poor penetration of ICZ into the brain, in vitro fluconazole resistance and lack of controlled-trials pose challenge in the treatment of cerebral histoplasmosis. Copyright © 2020, Peddi et al.
    Introduction Minimally invasive spine surgery has become more prevalent in recent years, but the delivery of interbody devices with small footprints may insufficiently restore the disc space, which may lead to instability and non-union. Vertically expandable interbody implants have partially addressed this limitation, but lateral fusion support remains a concern. The purpose of this study was to evaluate two-year safety and effectiveness outcomes with a multidimensional, expandable interbody fusion device (Luna 3D Interbody Fusion System, Benvenue Medical, Inc., Santa Clara, CA) that is delivered through a minimally invasive approach (6-8 mm) that expands in situ to approximate an anterior lumbar interbody fusion footprint of 25 mm diameter. Material and methods This was a retrospective, single-center study that evaluated the clinical utility of a multi-expandable interbody cage in patients undergoing posterior or transforaminal lumbar interbody fusion. Key patient-reported outcomes included back pain severit mean ODI score decreased by 61%, back pain severity decreased by 67%, and leg pain severity decreased by 80% (all p less then 0.001). Comparing radiographic measures from baseline to two years, anterior disc height increased from 7.6 mm to 15.5 mm, posterior disc height increased from 2.9 mm to 10.1 mm, average disc height increased from 5.6 mm to 13.3 mm, foraminal height increased from 12.2 mm to 20.2 mm, and segmental lordosis increased from 6.2 degrees to 14.0 degrees (all changes p less then 0.001). One case of non-union was observed and the corresponding two-year fusion rate was 98%. Conclusions The utilization of a minimally invasive, multidimensional, expandable interbody implant was safe and effective over two years of clinical follow-up. The implant allows the surgeon to re-establish sagittal balance and to provide a larger surface area for fusion as compared to traditional minimally invasive interbody devices. Copyright © 2020, Kucharzyk et al.Enteritis associated with systemic lupus erythematosus (SLE) is a rare and unusual manifestation of the gastrointestinal (GI) consequences of SLE itself. Complications of the enteritis component include mesenteric vasculitis, intestinal pseudo-obstruction, and protein-losing enteropathy. Lupus enteritis is very responsive to treatment with pulse steroids in almost 70% of the patients, but it is critical to diagnose it early to prevent devastating organ damage. The case describes a 21-year-old Caucasian female with a past medical history of uncomplicated laparoscopic appendectomy (one month prior to the time of presentation), major depressive disorder, asthma, iron deficiency anemia, pelvic inflammatory disease secondary to sexually transmitted Chlamydia trachomatis infection, and SLE (diagnosed two weeks prior to presentation). She had been transferred from an outside facility with complaints of severe right upper quadrant (RUQ) abdominal pain for one day. The patient had run out of her prescription for sterochloroquine. She was discharged with instructions for outpatient follow-up with gastroenterology and rheumatology. Copyright © 2020, Ronen et al.Although most cases of acute pancreatitis are attributed to alcohol and gallstones, acute pancreatitis can be a presenting feature or complication of a viral etiology (influenza). We report a rare case of acute pancreatitis secondary to H1N1 influenza A virus in the setting of chronic lymphocytic leukemia. The typical flu-like respiratory illness usually observed with influenza was absent preceding the episode of pancreatitis owing to the different antigenic properties of influenza A (compared to influenza B) and an underlying immunocompromised state. Copyright © 2020, Avalos et al.Skeletal transcutaneous osseointegration was performed on a 54-year-old female transfemoral amputee. None of the available osseointegration implants achieved press-fit stability, so an implant was cemented in position. Although initially stable, by six months the patient reported painful loading and radiographs revealed cement mantle lucency. The osseointegration implant was removed, antibiotics were delivered via implanted spacer and intravenously, and revision osseointegration three months later achieved appropriate immediate press-fit stability. Cemented transcutaneous osseointegration implants loosen within one year. Osseointegration is only successful when bone grows directly onto the implant. Copyright © 2020, Hoellwarth et al.Background Education is undergoing a transformation. The traditional passive lectures are failing to capture and inspire the new generation of learners who value more active and collaborative learning techniques. Objective We sought to create a novel educational technique to integrate into our curriculum that would be more personalized, employ more active learning and collaboration, and allow for an effective assessment of resident strengths and weaknesses. Discussion We created a monthly assembly line education academic half-day that evolved to replace one of the typical in-classroom didactics each month. Faculty run small-group simulation rooms, procedure workshops, competitive ultrasound, and wellness stations through which residents and medical students rotate. Conclusion This novel education technique resulted in a more personalized approach that increased resident interest, sparked the creation of a very popular MedEd-Simulation elective, and allowed the faculty to gain a better sense of resident strengths and deficiencies. https://www.selleckchem.com/products/cc-115.html Copyright © 2020, Rosario et al.Central nervous system (CNS) histoplasmosis occurs in 5-20% of all cases and is most commonly seen in immunosuppressed patients who have acquired immunodeficiency syndrome (AIDS) or have received organ transplant. The prevalence of histoplasmosis in patients greater than 65 years old between the years of 1999-2008 in the state of Texas was about 2-3 cases per 100,000 patients year. Since 1990 with the discovery of Triazoles, itraconazole (ICZ) has become the standard initial and suppressive therapy in patients with mild-moderate histoplasmosis without CNS involvement. However, poor penetration of ICZ into the brain, in vitro fluconazole resistance and lack of controlled-trials pose challenge in the treatment of cerebral histoplasmosis. Copyright © 2020, Peddi et al.
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  • BACKGROUND AND PURPOSE Cognitive impairment occurs frequently in multiple sclerosis (MS). However, the prevalence and clinical characteristics of cognitive MS phenotype are not well established. The aim of the study was to characterize the clinical course and neurocognitive impairment of patients with MS meeting an Expanded Disability Status Scale (EDSS)-defined cognitive phenotype. METHODS A total of 2302 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study were studied. Predominant cognitive MS phenotype was defined as EDSS Cerebral Functional System (FS) subscore ≥3 and remaining EDSS FS subscores ≤2 on at least one clinical visit. Demographic/clinical characteristics, phenotype stability and neurocognitive domain impairment of these subjects were assessed. RESULTS A total of 60 of 2302 (2.6%) patients (age 52.8 ± 10.8 years, 68% female, 82% relapsing MS) met criteria for phenotype designation. A total of 29 of 60 (48%) were designatgnitive status. © 2020 European Academy of Neurology.Asthma affects 300 million people across all age-groups and ethnicities and is the most common chronic condition affecting children. In the UK, the health care costs associated with asthma are estimated at £1.1 billion, however this amount typically excludes some societal costs (e.g. absence from work to care for children). The total number of days missed from school in England in the 2017/18 academic year was 59.1 million of which 54.7% were due to illness although the reasons for those illness-related absences are unknown. This article is protected by copyright. All rights reserved.Integration of various photodetectors with different light-sensitive materials and detection capacity is an inevitable way to achieve entire color/spectrum detection. However, the uneven capacity of each photodetector would drag the overall performance behind, especially the response speed. A response time down to nanosecond level has not previously been reported for a filter-free color/spectrum-sensitive photodetector, as far as is known. Here, a self-powered filterless color-sensitive photodetection array based on an in situ formed gradient perovskite absorber film with continuously tunable bandgap is demonstrated. Ultrahigh-speed response at nanosecond level is achieved in all the ingredient photodetectors. The junction capacitance being influenced by carrier concentration in the absorber is identified to be responsible for the detection speed. https://www.selleckchem.com/products/LY2228820.html Without any optic or mechanical supporting system, the designed color detector exhibits an external quantum efficiency (EQE) up to 94% and a high spectral resolution of around 80 nm for the whole visible spectrum. This work offers a guidance to achieve fast response of perovskite-based photodetectors from the point of view of carrier-donor control and demonstrates a new avenue to establish color-sensitive photodetectors/spectrometers. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Ferroelectric field-effect transistors (FeFETs) are one of the most interesting ferroelectric devices; however, they, usually suffer from low interface quality. The recently discovered 2D layered ferroelectric materials, combining with the advantages of van der Waals heterostructures (vdWHs), may be promising to fabricate high-quality FeFETs with atomically thin thickness. Here, dual-gated 2D ferroelectric vdWHs are constructed using MoS2 , hexagonal boron nitride (h-BN), and CuInP2 S6 (CIPS), which act as a high-performance nonvolatile memory and programmable rectifier. It is first noted that the insertion of h-BN and dual-gated coupling device configuration can significantly stabilize and effectively polarize ferroelectric CIPS. Through this design, the device shows a record-high performance with a large memory window, large on/off ratio (107 ), ultralow programming state current (10-13 A), and long-time endurance (104 s) as nonvolatile memory. As for programmable rectifier, a wide range of gate-tunable rectification behavior is observed. Moreover, the device exhibits a large rectification ratio (3 × 105 ) with stable retention under the programming state. This demonstrates the promising potential of ferroelectric vdWHs for new multifunctional ferroelectric devices. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Organic color-centers (OCCs) have emerged as promising single-photon emitters for solid-state quantum technologies, chemically specific sensing, and near-infrared bioimaging. However, these quantum light sources are currently synthesized in bulk solution, lacking the spatial control required for on-chip integration. The ability to pattern OCCs on solid substrates with high spatial precision and molecularly defined structure is essential to interface electronics and advance their quantum applications. Herein, a lithographic generation of OCCs on solid-state semiconducting single-walled carbon nanotube films at spatially defined locations is presented. By using light-driven diazoether chemistry, it is possible to directly pattern p-nitroaryl OCCs, which demonstrate chemically specific spectral signatures at programmed positions as confirmed by Raman mapping and hyperspectral photoluminescence imaging. This light-driven technique enables the fabrication of OCC arrays on solid films that fluoresce in the shortwave infrared and presents an important step toward the direct writing of quantum emitters and other functionalities at the molecular level. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Invasive alien species are a significant threat to both economic and ecological systems. Identifying the processes that give rise to invasive populations is essential for implementing effective control strategies. We conducted an ancestry analysis of invasive feral ***** (Sus scrofa, Linnaeus, 1758), a highly destructive ungulate that is widely distributed throughout the contiguous United States, to describe introduction pathways, sources of newly emergent populations and processes contributing to an ongoing invasion. Comparisons of high-density single nucleotide polymorphism genotypes for 6,566 invasive feral ***** to a comprehensive reference set of S. scrofa revealed that the vast majority of feral ***** were of mixed ancestry, with dominant genetic associations to Western heritage breeds of domestic pig and European populations of wild boar. Further, the rapid expansion of invasive feral ***** over the past 30 years was attributable to secondary introductions from established populations of admixed ancestry as opposed to direct introductions of domestic breeds or wild boar.
    BACKGROUND AND PURPOSE Cognitive impairment occurs frequently in multiple sclerosis (MS). However, the prevalence and clinical characteristics of cognitive MS phenotype are not well established. The aim of the study was to characterize the clinical course and neurocognitive impairment of patients with MS meeting an Expanded Disability Status Scale (EDSS)-defined cognitive phenotype. METHODS A total of 2302 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study were studied. Predominant cognitive MS phenotype was defined as EDSS Cerebral Functional System (FS) subscore ≥3 and remaining EDSS FS subscores ≤2 on at least one clinical visit. Demographic/clinical characteristics, phenotype stability and neurocognitive domain impairment of these subjects were assessed. RESULTS A total of 60 of 2302 (2.6%) patients (age 52.8 ± 10.8 years, 68% female, 82% relapsing MS) met criteria for phenotype designation. A total of 29 of 60 (48%) were designatgnitive status. © 2020 European Academy of Neurology.Asthma affects 300 million people across all age-groups and ethnicities and is the most common chronic condition affecting children. In the UK, the health care costs associated with asthma are estimated at £1.1 billion, however this amount typically excludes some societal costs (e.g. absence from work to care for children). The total number of days missed from school in England in the 2017/18 academic year was 59.1 million of which 54.7% were due to illness although the reasons for those illness-related absences are unknown. This article is protected by copyright. All rights reserved.Integration of various photodetectors with different light-sensitive materials and detection capacity is an inevitable way to achieve entire color/spectrum detection. However, the uneven capacity of each photodetector would drag the overall performance behind, especially the response speed. A response time down to nanosecond level has not previously been reported for a filter-free color/spectrum-sensitive photodetector, as far as is known. Here, a self-powered filterless color-sensitive photodetection array based on an in situ formed gradient perovskite absorber film with continuously tunable bandgap is demonstrated. Ultrahigh-speed response at nanosecond level is achieved in all the ingredient photodetectors. The junction capacitance being influenced by carrier concentration in the absorber is identified to be responsible for the detection speed. https://www.selleckchem.com/products/LY2228820.html Without any optic or mechanical supporting system, the designed color detector exhibits an external quantum efficiency (EQE) up to 94% and a high spectral resolution of around 80 nm for the whole visible spectrum. This work offers a guidance to achieve fast response of perovskite-based photodetectors from the point of view of carrier-donor control and demonstrates a new avenue to establish color-sensitive photodetectors/spectrometers. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Ferroelectric field-effect transistors (FeFETs) are one of the most interesting ferroelectric devices; however, they, usually suffer from low interface quality. The recently discovered 2D layered ferroelectric materials, combining with the advantages of van der Waals heterostructures (vdWHs), may be promising to fabricate high-quality FeFETs with atomically thin thickness. Here, dual-gated 2D ferroelectric vdWHs are constructed using MoS2 , hexagonal boron nitride (h-BN), and CuInP2 S6 (CIPS), which act as a high-performance nonvolatile memory and programmable rectifier. It is first noted that the insertion of h-BN and dual-gated coupling device configuration can significantly stabilize and effectively polarize ferroelectric CIPS. Through this design, the device shows a record-high performance with a large memory window, large on/off ratio (107 ), ultralow programming state current (10-13 A), and long-time endurance (104 s) as nonvolatile memory. As for programmable rectifier, a wide range of gate-tunable rectification behavior is observed. Moreover, the device exhibits a large rectification ratio (3 × 105 ) with stable retention under the programming state. This demonstrates the promising potential of ferroelectric vdWHs for new multifunctional ferroelectric devices. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Organic color-centers (OCCs) have emerged as promising single-photon emitters for solid-state quantum technologies, chemically specific sensing, and near-infrared bioimaging. However, these quantum light sources are currently synthesized in bulk solution, lacking the spatial control required for on-chip integration. The ability to pattern OCCs on solid substrates with high spatial precision and molecularly defined structure is essential to interface electronics and advance their quantum applications. Herein, a lithographic generation of OCCs on solid-state semiconducting single-walled carbon nanotube films at spatially defined locations is presented. By using light-driven diazoether chemistry, it is possible to directly pattern p-nitroaryl OCCs, which demonstrate chemically specific spectral signatures at programmed positions as confirmed by Raman mapping and hyperspectral photoluminescence imaging. This light-driven technique enables the fabrication of OCC arrays on solid films that fluoresce in the shortwave infrared and presents an important step toward the direct writing of quantum emitters and other functionalities at the molecular level. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Invasive alien species are a significant threat to both economic and ecological systems. Identifying the processes that give rise to invasive populations is essential for implementing effective control strategies. We conducted an ancestry analysis of invasive feral swine (Sus scrofa, Linnaeus, 1758), a highly destructive ungulate that is widely distributed throughout the contiguous United States, to describe introduction pathways, sources of newly emergent populations and processes contributing to an ongoing invasion. Comparisons of high-density single nucleotide polymorphism genotypes for 6,566 invasive feral swine to a comprehensive reference set of S. scrofa revealed that the vast majority of feral swine were of mixed ancestry, with dominant genetic associations to Western heritage breeds of domestic pig and European populations of wild boar. Further, the rapid expansion of invasive feral swine over the past 30 years was attributable to secondary introductions from established populations of admixed ancestry as opposed to direct introductions of domestic breeds or wild boar.
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  • Bovine leukemia virus (BLV) causes a lymphoproliferative disease in cattle and is transmitted horizontally and vertically via infected lymphocytes. Although transplacental infection is considered the predominant route of vertical transmission of BLV, the molecular mechanisms of this process remain to be elucidated. Notably, how BLV passes through the blood-placental barrier remains unclear, given that BLV is transmitted primarily by cell-to-cell contact. One hypothesis is that B cell migration to the placenta may be induced by certain endometrium-expressed chemokines. To test this hypothesis, we performed an in vitro cell migration assay using bovine B cell lines and endometrial epithelial cells. Cell migration assays showed that two bovine B cell lines, BL2M3 and BL3.1 cells, were attracted to the supernatant of bovine endometrial epithelial cells (BEnEpCs). Quantitative real-time RT-PCR showed that expression levels of mRNAs encoding the chemokines CCL2 and CXCL10 were higher in BEnEpCs than in MDBK cells. https://www.selleckchem.com/products/wp1066.html Additionally, an inhibition assay using immune serum against CCL2 and CXCL10 showed suppression of migration of bovine B cell lines. A syncytium assay showed that cells expressing BLV envelope (Env) protein fused with BEnEpCs. Here we found that bovine B cells are attracted by chemokines produced in the endometrium and that cells expressing BLV Env protein fused with endometrium epithelial cells. These results explain part of the molecular mechanism of transplacental transmission during BLV infection, although further analysis will be required. Advances in these areas are expected to contribute to controlling the spread of BLV. The accurate identification of Taylorella equigenitalis strains is essential to improve worldwide prevention and control strategies for contagious equine metritis (CEM). This study compared 367 worldwide equine strains using multilocus sequence typing according to the geographical origin, isolation year and equine breed. The strains were divided into 49 sequence types (STs), including 10 described for the first time. Three major and three minor clonal complexes (CCs), and 11 singletons, were identified. The genetic heterogeneity was low (0.13 STs/strain) despite the wide diversity of geographical origins (n = 16), isolation years (1977-2018) and equine breeds (n = 18). It was highest outside Europe and in the 1977-1997 period; current major STs and CCs already existed before 1998. Previous data associated the major CC1 with the first CEM outbreaks in 1977-1978 in the United Kingdom, Australia and the United States, and revealed its circulation in France. Our study confirms its circulation in France over a longer period of time (1992-2018) and its distribution in Spain and Germany but not throughout Europe. In addition to CC1, relationships between non-European and European countries were observed only through ST4, ST17 and ST30. Within Europe, several STs emerged with cross-border circulation, in particular ST16 and ST46 from the major complexes CC2 and CC8. These results constitute a baseline for monitoring the spread of CEM outbreaks. A retrospective analysis of a higher number of strains isolated worldwide between 1977 and the early 2000s would be helpful to obtain an exhaustive picture of the original CEM situation. Gut is often subject to infection by different pathogens like Y. enterocolitica. To date, biotypes (BTs) 1A have been considered as non-pathogenic, because they do not express plasmid of virulence pYV; however, BTs 1A strains present other chromosomic virulence genes and recent studies suggest an implication of this microorganism in reactive arthritis. Although many studies highlighted the molecular basis of pathogenesis of Ye infection, scanty data are available about several environmental BTs 1A strains, often isolated in cases of foodborne disease but not included in pathogenicity studies. The aim of our work was to verify the ability of different Ye 1A strains to adhere and penetrate IPEC-J2 cells and to modulate intestinal innate immunity. Our results showed that all strains under study were able to adhere and penetrate enterocytes, causing inflammatory responses. Indeed, adhesion and invasion of enterocytes is an essential step in Ye pathogenesis (Fàbrega and Vila, 2012). Moreover, our data suggest the possible involvement of strains Ye2/O9 in reactive arthritis, due to their ability (i) to penetrate enterocytes as pathogenic Ye1/O8 strains do, and (ii) to increase IL-6, IL-8, IL-12 and IL-18 release. Lastly, our results confirm that IPEC-J2 cells are a very good model to evaluate host-pathogen interaction, and indicate IL-8, TNF-α, TLRs1 and 4 as possible markers of the ability of Ye strains to penetrate enterocytes. Moreover, we showed that Ye strains differently affect the host's innate immune responses. V.Antimicrobials have been commonly used to control bacterial diseases in farm animals. The efficacy of these drugs deterred the development of other control measures, such as vaccines, which are currently getting more attention due to the increased concern about antimicrobial resistance. Glässer's disease is caused by Glaesserella (Haemophilus) parasuis and affects pork production around the world. Balance between colonization and immunity seems to be essential in disease control. Reduction in antimicrobial use in veterinary medicine requires the implementation of preventive measures, based on alternative tools such as vaccination and other strategies to guarantee a beneficial microbial colonization of the animals. The present review summarizes and discusses the current knowledge on diagnosis and control of Glässer's disease, including prospects on alternatives to antimicrobials. Non-S. aureus staphylococci (NAS) are the most frequently isolated pathogens from bovine milk and can cause intramammary infections (IMI). They can also be found in teat canals, on bovine skin and in cows' environment, which may lead to unnoticed contamination of milk samples. The aim of this study was to investigate the role of NAS species as mastitis-causing pathogens or contaminants, and to identify possible differences between NAS species. A longitudinal study was conducted with consecutive milk sampling in five German dairy herds. Species identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Infections were distinguished from contaminations using two different definitions based on the repeated detection of an NAS species. Of 15 NAS species found, eight and ten, respectively, were associated with an IMI. Staphylococcus simulans and S. chromogenes were associated with IMI in more than 90 % of the findings. S. warneri, S. xylosus, S. microti, S. haemolyticus, and S.
    Bovine leukemia virus (BLV) causes a lymphoproliferative disease in cattle and is transmitted horizontally and vertically via infected lymphocytes. Although transplacental infection is considered the predominant route of vertical transmission of BLV, the molecular mechanisms of this process remain to be elucidated. Notably, how BLV passes through the blood-placental barrier remains unclear, given that BLV is transmitted primarily by cell-to-cell contact. One hypothesis is that B cell migration to the placenta may be induced by certain endometrium-expressed chemokines. To test this hypothesis, we performed an in vitro cell migration assay using bovine B cell lines and endometrial epithelial cells. Cell migration assays showed that two bovine B cell lines, BL2M3 and BL3.1 cells, were attracted to the supernatant of bovine endometrial epithelial cells (BEnEpCs). Quantitative real-time RT-PCR showed that expression levels of mRNAs encoding the chemokines CCL2 and CXCL10 were higher in BEnEpCs than in MDBK cells. https://www.selleckchem.com/products/wp1066.html Additionally, an inhibition assay using immune serum against CCL2 and CXCL10 showed suppression of migration of bovine B cell lines. A syncytium assay showed that cells expressing BLV envelope (Env) protein fused with BEnEpCs. Here we found that bovine B cells are attracted by chemokines produced in the endometrium and that cells expressing BLV Env protein fused with endometrium epithelial cells. These results explain part of the molecular mechanism of transplacental transmission during BLV infection, although further analysis will be required. Advances in these areas are expected to contribute to controlling the spread of BLV. The accurate identification of Taylorella equigenitalis strains is essential to improve worldwide prevention and control strategies for contagious equine metritis (CEM). This study compared 367 worldwide equine strains using multilocus sequence typing according to the geographical origin, isolation year and equine breed. The strains were divided into 49 sequence types (STs), including 10 described for the first time. Three major and three minor clonal complexes (CCs), and 11 singletons, were identified. The genetic heterogeneity was low (0.13 STs/strain) despite the wide diversity of geographical origins (n = 16), isolation years (1977-2018) and equine breeds (n = 18). It was highest outside Europe and in the 1977-1997 period; current major STs and CCs already existed before 1998. Previous data associated the major CC1 with the first CEM outbreaks in 1977-1978 in the United Kingdom, Australia and the United States, and revealed its circulation in France. Our study confirms its circulation in France over a longer period of time (1992-2018) and its distribution in Spain and Germany but not throughout Europe. In addition to CC1, relationships between non-European and European countries were observed only through ST4, ST17 and ST30. Within Europe, several STs emerged with cross-border circulation, in particular ST16 and ST46 from the major complexes CC2 and CC8. These results constitute a baseline for monitoring the spread of CEM outbreaks. A retrospective analysis of a higher number of strains isolated worldwide between 1977 and the early 2000s would be helpful to obtain an exhaustive picture of the original CEM situation. Gut is often subject to infection by different pathogens like Y. enterocolitica. To date, biotypes (BTs) 1A have been considered as non-pathogenic, because they do not express plasmid of virulence pYV; however, BTs 1A strains present other chromosomic virulence genes and recent studies suggest an implication of this microorganism in reactive arthritis. Although many studies highlighted the molecular basis of pathogenesis of Ye infection, scanty data are available about several environmental BTs 1A strains, often isolated in cases of foodborne disease but not included in pathogenicity studies. The aim of our work was to verify the ability of different Ye 1A strains to adhere and penetrate IPEC-J2 cells and to modulate intestinal innate immunity. Our results showed that all strains under study were able to adhere and penetrate enterocytes, causing inflammatory responses. Indeed, adhesion and invasion of enterocytes is an essential step in Ye pathogenesis (Fàbrega and Vila, 2012). Moreover, our data suggest the possible involvement of strains Ye2/O9 in reactive arthritis, due to their ability (i) to penetrate enterocytes as pathogenic Ye1/O8 strains do, and (ii) to increase IL-6, IL-8, IL-12 and IL-18 release. Lastly, our results confirm that IPEC-J2 cells are a very good model to evaluate host-pathogen interaction, and indicate IL-8, TNF-α, TLRs1 and 4 as possible markers of the ability of Ye strains to penetrate enterocytes. Moreover, we showed that Ye strains differently affect the host's innate immune responses. V.Antimicrobials have been commonly used to control bacterial diseases in farm animals. The efficacy of these drugs deterred the development of other control measures, such as vaccines, which are currently getting more attention due to the increased concern about antimicrobial resistance. Glässer's disease is caused by Glaesserella (Haemophilus) parasuis and affects pork production around the world. Balance between colonization and immunity seems to be essential in disease control. Reduction in antimicrobial use in veterinary medicine requires the implementation of preventive measures, based on alternative tools such as vaccination and other strategies to guarantee a beneficial microbial colonization of the animals. The present review summarizes and discusses the current knowledge on diagnosis and control of Glässer's disease, including prospects on alternatives to antimicrobials. Non-S. aureus staphylococci (NAS) are the most frequently isolated pathogens from bovine milk and can cause intramammary infections (IMI). They can also be found in teat canals, on bovine skin and in cows' environment, which may lead to unnoticed contamination of milk samples. The aim of this study was to investigate the role of NAS species as mastitis-causing pathogens or contaminants, and to identify possible differences between NAS species. A longitudinal study was conducted with consecutive milk sampling in five German dairy herds. Species identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Infections were distinguished from contaminations using two different definitions based on the repeated detection of an NAS species. Of 15 NAS species found, eight and ten, respectively, were associated with an IMI. Staphylococcus simulans and S. chromogenes were associated with IMI in more than 90 % of the findings. S. warneri, S. xylosus, S. microti, S. haemolyticus, and S.
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  • BACKGROUND Pregnant women who suffer from depressive disorders are likely to be treated with antidepressant (AD) medications. Recent meta-analyses underlined the possible relation between AD use and several neonatal outcomes, although the underlying mechanisms remains unclear. METHODS To summarise and evaluate the associations between AD use in pregnancy and neonatal outcomes, we conducted an umbrella review of meta-analyses of observational studies published up to December 2019 in PubMed and Embase. Summary risk estimates for the associations between use of AD as a whole, or specific AD classes and drugs, and the risk of neonatal outcomes were reported. RESULTS Our review included 22 meta-analyses investigating 69 associations. However, none were supported by convincing evidence. Highly suggestive evidence regarded the associations between (i) any time AD exposure and the risk of preterm birth (relative risk, 1.68; 95% confidence interval 1.52, 1.86), (ii) any time exposure to selective serotonin reuptake inhibitors (SSRIs) and the risk of preterm birth (1.43; 1.22, 1.37) and (iii) respiratory distress (1.33; 1.14, 1.55), and (iv) SSRI exposure during the first trimester of pregnancy and the risk of cardiovascular malformations (1.25; 1.13, 1.39). Suggestive evidence was obtained for any time AD exposure on 1-min low Apgar score (absolute average difference, -0.34; -0.53, -0.14). CONCLUSIONS Overall, the effects of AD exposure during pregnancy on neonatal outcomes have been extensively studied, but few of the associations are graded as high quality evidence. More prospective studies and large collaborations with comprehensive standardised reporting of analyses are needed. Cannabis legalization and commercialization has resulted in novel alternative cannabis products on the market, including edible and vaporized cannabis, which may appeal to youth with psychiatric problems. Psychiatric comorbidity in adolescent use and poly-use (i.e., use of >2 products) of combustible, edible, and vaporized cannabis products has largely gone uninvestigated. This 2015 cross-sectional survey of Los Angeles, California area adolescents (Mage = 16.1, N = 3177) characterized associations of various psychiatric problems with use and poly-use of combustible, edible, and vaporized cannabis. Exposure variables included past 30-day non-cannabis substance use (alcohol, e-cigarettes, combustible cigarettes, and nonmedical prescription opioid and stimulant use; yes/no), and psychiatric problems including past-week depressive symptom frequency, past 6-month ADHD symptom and conduct problem frequency, anhedonia, and five dimensions of impulsivity (sensation seeking, perseverance, lack of premeditation, positive urgency, and negative urgency). Outcome variables included past 30-day use (yes/no) of combustible, edible, and vaporized cannabis, independently, and number of cannabis products used (single, dual-use, poly-use). Results showed that all forms of non-cannabis substance use (ORs range 13.7-36.1) and all psychiatric symptoms and traits (ORs in SD units range 1.1-2.1) were positively associated with combustible, edible, and vaporized cannabis product use. The magnitude of comorbidity did not significantly differ by cannabis product type used in most cases. Psychiatric comorbidity was typically stronger in poly-product than single-product cannabis use and greater for externalizing-type than internalizing-type psychiatric problems. Practitioners, policy makers, and scientists should be aware that pervasive psychiatric comorbidity may be observed across the spectrum of cannabis product use among adolescents, particularly poly-product users. Body-focused repetitive behaviors (BFRBs) and non-suicidal self-injury (NSSI) are recognized as distinct categories in the DSM-5. However, definitions and assessment of NSSI sometimes encompasses behaviors similar to BFRBs, and little data exist about their clinical differences. The current study examined clinical characteristics and symptom features associated with NSSI vs. BFRBs. The current sample included 1523 individuals who endorsed moderate to severe NSSI (n = 165) or BFRBs hair pulling group (n = 102), skin picking group (n = 216), nail picking group (n = 253), nail biting group (n = 487), and cheek biting group (n = 300). Responders were asked to complete questionnaires on clinical features relevant for BFRBs and NSSI. https://www.selleckchem.com/products/sch-527123.html NSSI and BFRBs had significant differences on several clinical features. Individuals in the NSSI group were more likely than individuals with BFRBs to report engaging in the behavior for social-affective reasons (i.e., to get out of doing something, or receive attention from others). Individuals in the NSSI group were also more likely to engage in the behavior to regulate tension and feelings of emptiness, and to experience relief during the act. In contrast, individuals in the BFRB groups were more likely to engage in the behavior automatically without reflective awareness, to reduce boredom, or to fix appearance. The NSSI group obtained significantly higher scores on questionnaires assessing stress, anxiety, depression, and harm avoidance. Overall, the results showed several notable differences between NSSI and BFRBs that are consistent with clinical literature and definitions of these problems in the DSM-5. Duloxetine has been increasingly administered, but the associated cardiovascular adverse event risk is not clearly understood. Therefore, we identified the association between duloxetine and cardiovascular adverse events through an analysis of heart rate and blood pressure change. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and psycINFO in June 2019. The title, abstract, and full text were checked in order to obtain articles. A meta-analysis was conducted with random effect model and quality of articles was evaluated using Cochrane Risk of Bias 2.0. The manuscript has been written according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) harm checklist. A total of 4009 studies were screened by the title and abstract. After reviewing 186 full texts, 17 studies were finally selected for the meta-analysis. Nine of the 17 studied duloxetine given for mood disorders and 8 for pain control. The duration of 14 studies was under 13 weeks.
    BACKGROUND Pregnant women who suffer from depressive disorders are likely to be treated with antidepressant (AD) medications. Recent meta-analyses underlined the possible relation between AD use and several neonatal outcomes, although the underlying mechanisms remains unclear. METHODS To summarise and evaluate the associations between AD use in pregnancy and neonatal outcomes, we conducted an umbrella review of meta-analyses of observational studies published up to December 2019 in PubMed and Embase. Summary risk estimates for the associations between use of AD as a whole, or specific AD classes and drugs, and the risk of neonatal outcomes were reported. RESULTS Our review included 22 meta-analyses investigating 69 associations. However, none were supported by convincing evidence. Highly suggestive evidence regarded the associations between (i) any time AD exposure and the risk of preterm birth (relative risk, 1.68; 95% confidence interval 1.52, 1.86), (ii) any time exposure to selective serotonin reuptake inhibitors (SSRIs) and the risk of preterm birth (1.43; 1.22, 1.37) and (iii) respiratory distress (1.33; 1.14, 1.55), and (iv) SSRI exposure during the first trimester of pregnancy and the risk of cardiovascular malformations (1.25; 1.13, 1.39). Suggestive evidence was obtained for any time AD exposure on 1-min low Apgar score (absolute average difference, -0.34; -0.53, -0.14). CONCLUSIONS Overall, the effects of AD exposure during pregnancy on neonatal outcomes have been extensively studied, but few of the associations are graded as high quality evidence. More prospective studies and large collaborations with comprehensive standardised reporting of analyses are needed. Cannabis legalization and commercialization has resulted in novel alternative cannabis products on the market, including edible and vaporized cannabis, which may appeal to youth with psychiatric problems. Psychiatric comorbidity in adolescent use and poly-use (i.e., use of >2 products) of combustible, edible, and vaporized cannabis products has largely gone uninvestigated. This 2015 cross-sectional survey of Los Angeles, California area adolescents (Mage = 16.1, N = 3177) characterized associations of various psychiatric problems with use and poly-use of combustible, edible, and vaporized cannabis. Exposure variables included past 30-day non-cannabis substance use (alcohol, e-cigarettes, combustible cigarettes, and nonmedical prescription opioid and stimulant use; yes/no), and psychiatric problems including past-week depressive symptom frequency, past 6-month ADHD symptom and conduct problem frequency, anhedonia, and five dimensions of impulsivity (sensation seeking, perseverance, lack of premeditation, positive urgency, and negative urgency). Outcome variables included past 30-day use (yes/no) of combustible, edible, and vaporized cannabis, independently, and number of cannabis products used (single, dual-use, poly-use). Results showed that all forms of non-cannabis substance use (ORs range 13.7-36.1) and all psychiatric symptoms and traits (ORs in SD units range 1.1-2.1) were positively associated with combustible, edible, and vaporized cannabis product use. The magnitude of comorbidity did not significantly differ by cannabis product type used in most cases. Psychiatric comorbidity was typically stronger in poly-product than single-product cannabis use and greater for externalizing-type than internalizing-type psychiatric problems. Practitioners, policy makers, and scientists should be aware that pervasive psychiatric comorbidity may be observed across the spectrum of cannabis product use among adolescents, particularly poly-product users. Body-focused repetitive behaviors (BFRBs) and non-suicidal self-injury (NSSI) are recognized as distinct categories in the DSM-5. However, definitions and assessment of NSSI sometimes encompasses behaviors similar to BFRBs, and little data exist about their clinical differences. The current study examined clinical characteristics and symptom features associated with NSSI vs. BFRBs. The current sample included 1523 individuals who endorsed moderate to severe NSSI (n = 165) or BFRBs hair pulling group (n = 102), skin picking group (n = 216), nail picking group (n = 253), nail biting group (n = 487), and cheek biting group (n = 300). Responders were asked to complete questionnaires on clinical features relevant for BFRBs and NSSI. https://www.selleckchem.com/products/sch-527123.html NSSI and BFRBs had significant differences on several clinical features. Individuals in the NSSI group were more likely than individuals with BFRBs to report engaging in the behavior for social-affective reasons (i.e., to get out of doing something, or receive attention from others). Individuals in the NSSI group were also more likely to engage in the behavior to regulate tension and feelings of emptiness, and to experience relief during the act. In contrast, individuals in the BFRB groups were more likely to engage in the behavior automatically without reflective awareness, to reduce boredom, or to fix appearance. The NSSI group obtained significantly higher scores on questionnaires assessing stress, anxiety, depression, and harm avoidance. Overall, the results showed several notable differences between NSSI and BFRBs that are consistent with clinical literature and definitions of these problems in the DSM-5. Duloxetine has been increasingly administered, but the associated cardiovascular adverse event risk is not clearly understood. Therefore, we identified the association between duloxetine and cardiovascular adverse events through an analysis of heart rate and blood pressure change. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and psycINFO in June 2019. The title, abstract, and full text were checked in order to obtain articles. A meta-analysis was conducted with random effect model and quality of articles was evaluated using Cochrane Risk of Bias 2.0. The manuscript has been written according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) harm checklist. A total of 4009 studies were screened by the title and abstract. After reviewing 186 full texts, 17 studies were finally selected for the meta-analysis. Nine of the 17 studied duloxetine given for mood disorders and 8 for pain control. The duration of 14 studies was under 13 weeks.
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  • BACKGROUND The aim of this study was to assess the association of high-sensitivity cardiac troponin (hs-cTnT) and other cardiac, kidney, hyperglycemia, and inflammatory biomarkers with peripheral neuropathy (PN) in a community-based population. METHODS We conducted a cross-sectional analysis of 3056 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent standardized monofilament PN testing and had measures of cardiac function (hs-cTnT, N-terminal pro-B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β-2 microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [Hb A1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and inflammation (C-reactive protein) assessed at visit 6 (2016-2017; age 71-94 years). We used logistic regression to assess the associations of these biomarkers (modeled in diabetes-specific tertiles) with PN in older adult Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email journals.permissions@oup.com.AIMS Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased cardiovascular disease (CVD) risk. We previously reported that pro-inflammatory activation of circulating monocytes is a potential mechanism by which Lp(a) mediates CVD. Since potent Lp(a)-lowering therapies are emerging, it is of interest whether patients with elevated Lp(a) experience beneficial anti-inflammatory effects following large reductions in Lp(a). METHODS AND RESULTS Using transcriptome analysis, we show that circulating monocytes of healthy individuals with elevated Lp(a), as well as CVD patients with increased Lp(a) levels, both have a pro-inflammatory gene expression profile. The effect of Lp(a)-lowering on gene expression and function of monocytes was addressed in two local sub-studies, including 14 CVD patients with elevated Lp(a) who received apolipoprotein(a) [apo(a)] antisense (AKCEA-APO(a)-LRx) (NCT03070782), as well as 18 patients with elevated Lp(a) who received proprotein convertase subtilisin/kexin type 9 antibody (PCSK9ab) treatment (NCT02729025). AKCEA-APO(a)-LRx lowered Lp(a) by 47% and reduced the pro-inflammatory gene expression in monocytes of CVD patients with elevated Lp(a), which coincided with a functional reduction in transendothelial migration capacity of monocytes ex vivo (-17%, P  less then  0.001). In contrast, PCSK9ab treatment lowered Lp(a) by 16% and did not alter transcriptome nor functional properties of monocytes, despite an additional reduction of 65% in low-density lipoprotein cholesterol (LDL-C). CONCLUSION Potent Lp(a)-lowering following AKCEA-APO(a)-LRx, but not modest Lp(a)-lowering combined with LDL-C reduction following PCSK9ab treatment, reduced the pro-inflammatory state of circulating monocytes in patients with elevated Lp(a). These ex vivo data support a beneficial effect of large Lp(a) reductions in patients with elevated Lp(a). © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.Intravenous third-line anaesthetic agents are typically titrated in refractory status epilepticus to achieve either seizure suppression or burst suppression on continuous EEG. However, the optimum treatment paradigm is unknown and little data exist to guide the withdrawal of anaesthetics in refractory status epilepticus. Premature withdrawal of anaesthetics risks the recurrence of seizures, whereas the prolonged use of anaesthetics increases the risk of treatment-associated adverse effects. https://www.selleckchem.com/products/cpi-0610.html This study sought to measure the accuracy of features of EEG activity during anaesthetic weaning in refractory status epilepticus as predictors of successful weaning from intravenous anaesthetics. We prespecified a successful anaesthetic wean as the discontinuation of intravenous anaesthesia without developing recurrent status epilepticus, and a wean failure as either recurrent status epilepticus or the resumption of anaesthesia for the purpose of treating an EEG pattern concerning for incipient status epilepticus. We evalh an area under the curve of 83.3%. Distinct signatures in the spatial networks of functional connectivity emerge during successful anaesthetic liberation in status epilepticus; these findings are absent in patients with anaesthetic wean failure. Identifying features that emerge during successful anaesthetic weaning may allow faster and more successful anaesthetic liberation after refractory status epilepticus. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email journals.permissions@oup.com.Transapical mitral valve repair with NeoChord implantation is effective and safe to replace ruptured chordae due to degenerative disease. Redo transapical neochordae implantation has never been reported in the literature. We present a case report of a 53-year-old man who underwent a reoperative neochord implantation for recurrent severe mitral regurgitation, resulting from degenerative disease progression with a new native chordal rupture. We report the midterm durability of reoperative Neochord repair. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.BACKGROUND Recent advances in the study and clinical applications of circulating tumor DNA (ctDNA) are limited by practical considerations of sample collection. Whole-genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations and fragmentation patterns. We hypothesized that low-depth/shallow WGS (sWGS) data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may remove contaminating genomic DNA from small blood volumes. Dried blood spots have practical advantages for sample collection, may facilitate serial sampling, and could support novel study designs in humans and animal models. METHODS We developed a protocol for the isolation and analysis of cell-free DNA from dried blood spots using filter paper cards and bead-based size selection. DNA extracted and size-selected from dried spots was analyzed using sWGS and polymerase chain reaction (PCR). RESULTS Analyzing a 50 μL dried blood spot from frozen whole blood of a patient with melanoma, we identified ctDNA based on the presence of tumor-specific somatic copy-number alterations, and found a fragment-size profile similar to that observed in plasma DNA.
    BACKGROUND The aim of this study was to assess the association of high-sensitivity cardiac troponin (hs-cTnT) and other cardiac, kidney, hyperglycemia, and inflammatory biomarkers with peripheral neuropathy (PN) in a community-based population. METHODS We conducted a cross-sectional analysis of 3056 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent standardized monofilament PN testing and had measures of cardiac function (hs-cTnT, N-terminal pro-B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β-2 microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [Hb A1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and inflammation (C-reactive protein) assessed at visit 6 (2016-2017; age 71-94 years). We used logistic regression to assess the associations of these biomarkers (modeled in diabetes-specific tertiles) with PN in older adult Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email journals.permissions@oup.com.AIMS Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased cardiovascular disease (CVD) risk. We previously reported that pro-inflammatory activation of circulating monocytes is a potential mechanism by which Lp(a) mediates CVD. Since potent Lp(a)-lowering therapies are emerging, it is of interest whether patients with elevated Lp(a) experience beneficial anti-inflammatory effects following large reductions in Lp(a). METHODS AND RESULTS Using transcriptome analysis, we show that circulating monocytes of healthy individuals with elevated Lp(a), as well as CVD patients with increased Lp(a) levels, both have a pro-inflammatory gene expression profile. The effect of Lp(a)-lowering on gene expression and function of monocytes was addressed in two local sub-studies, including 14 CVD patients with elevated Lp(a) who received apolipoprotein(a) [apo(a)] antisense (AKCEA-APO(a)-LRx) (NCT03070782), as well as 18 patients with elevated Lp(a) who received proprotein convertase subtilisin/kexin type 9 antibody (PCSK9ab) treatment (NCT02729025). AKCEA-APO(a)-LRx lowered Lp(a) by 47% and reduced the pro-inflammatory gene expression in monocytes of CVD patients with elevated Lp(a), which coincided with a functional reduction in transendothelial migration capacity of monocytes ex vivo (-17%, P  less then  0.001). In contrast, PCSK9ab treatment lowered Lp(a) by 16% and did not alter transcriptome nor functional properties of monocytes, despite an additional reduction of 65% in low-density lipoprotein cholesterol (LDL-C). CONCLUSION Potent Lp(a)-lowering following AKCEA-APO(a)-LRx, but not modest Lp(a)-lowering combined with LDL-C reduction following PCSK9ab treatment, reduced the pro-inflammatory state of circulating monocytes in patients with elevated Lp(a). These ex vivo data support a beneficial effect of large Lp(a) reductions in patients with elevated Lp(a). © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.Intravenous third-line anaesthetic agents are typically titrated in refractory status epilepticus to achieve either seizure suppression or burst suppression on continuous EEG. However, the optimum treatment paradigm is unknown and little data exist to guide the withdrawal of anaesthetics in refractory status epilepticus. Premature withdrawal of anaesthetics risks the recurrence of seizures, whereas the prolonged use of anaesthetics increases the risk of treatment-associated adverse effects. https://www.selleckchem.com/products/cpi-0610.html This study sought to measure the accuracy of features of EEG activity during anaesthetic weaning in refractory status epilepticus as predictors of successful weaning from intravenous anaesthetics. We prespecified a successful anaesthetic wean as the discontinuation of intravenous anaesthesia without developing recurrent status epilepticus, and a wean failure as either recurrent status epilepticus or the resumption of anaesthesia for the purpose of treating an EEG pattern concerning for incipient status epilepticus. We evalh an area under the curve of 83.3%. Distinct signatures in the spatial networks of functional connectivity emerge during successful anaesthetic liberation in status epilepticus; these findings are absent in patients with anaesthetic wean failure. Identifying features that emerge during successful anaesthetic weaning may allow faster and more successful anaesthetic liberation after refractory status epilepticus. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email journals.permissions@oup.com.Transapical mitral valve repair with NeoChord implantation is effective and safe to replace ruptured chordae due to degenerative disease. Redo transapical neochordae implantation has never been reported in the literature. We present a case report of a 53-year-old man who underwent a reoperative neochord implantation for recurrent severe mitral regurgitation, resulting from degenerative disease progression with a new native chordal rupture. We report the midterm durability of reoperative Neochord repair. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.BACKGROUND Recent advances in the study and clinical applications of circulating tumor DNA (ctDNA) are limited by practical considerations of sample collection. Whole-genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations and fragmentation patterns. We hypothesized that low-depth/shallow WGS (sWGS) data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may remove contaminating genomic DNA from small blood volumes. Dried blood spots have practical advantages for sample collection, may facilitate serial sampling, and could support novel study designs in humans and animal models. METHODS We developed a protocol for the isolation and analysis of cell-free DNA from dried blood spots using filter paper cards and bead-based size selection. DNA extracted and size-selected from dried spots was analyzed using sWGS and polymerase chain reaction (PCR). RESULTS Analyzing a 50 μL dried blood spot from frozen whole blood of a patient with melanoma, we identified ctDNA based on the presence of tumor-specific somatic copy-number alterations, and found a fragment-size profile similar to that observed in plasma DNA.
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  • Administration of CQCQD significantly inhibited JAK-2 activation and down-regulated phosphorylation of downstream substrate STAT-3 the same as AG490, resulting in inhibition of inflammatory mediators and amelioration of pancreatitis. CONCLUSION The results suggested that CQCQD exerted anti-inflammatory effects on AP via reducing expression and phosphorylation of JAK and STAT.OBJECTIVE To determine the efficacy of Scutellaria barbata flavonoids and polysaccharides on Ishikawa endometrial carcinoma cells co-cultured with U937 macrophages. METHODS The presence of CD163 and CD206 was determined by flow cytometry. Thiazolyl Blue Tetrazolium Bromide assays were used to assess the proliferation effect of tumor-associated macrophages (TAMs) on Ishikawa cells. The secretion of interleukin (IL)-10 in the co-culture conditioned media was examined using an enzyme-linked immunosorbent assay. The protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor (NF)-κB p65 were detected by Western blot. The mRNA expression levels of TLR4 and MyD88 were analyzed by real-time polymerase chain reaction (PCR). The expression levels of IL-12, IL-1β and tumor necrosis factor-α (TNF-α) were evaluated with real-time PCR. RESULTS Compared with the U937 control group, the expression levels of CD163 and CD206 in the TAM group were higher (P less then 0.05). TAMs co-cultured with Ishikawa cells for 24 or 48 h showed higher proliferation rates (P less then 0.05). The expression levels of IL-12 decreased than compared with those in the U937 untreated group (P less then 0.05) and those of the Scutellaria barbata flavonoids group (P less then 0.05). https://www.selleckchem.com/products/odm-201.html The expression levels of CD206, CD163, IL-10, IL-1β and TNF-α, NF-κB p65 and TLR4/MyD88 in the TAMs control group were greater than those in the U937 untreated group (P less then 0.05) and those of the Scutellaria barbata flavonoids group (P less then 0.05). CONCLUSION Scutellaria barbata flavonoids may inhibit TAM activation by blocking the TLR4/MyD88/NF-κB signaling pathway.OBJECTIVE To investigate the effect of mulberry leaf flavonoids (MLF) on apoptosis of pancreatic cells induced by high glucose. METHODS Long exposure to high glucose induces apoptosis of pancreatic β cells, which can lead to diabetes. In this study, we used the rat insulinoma cell line, INS-1. High glucose (33.3 mM) was used to establish a glucotoxicity model. The MTT assay was used to evaluate the MLF effect on cell viability. INS-1 cells were treated with various concentrations of MLF (125, 250 and 500 mg/L) for 24 h, and then stimulated with 5.5 or 33.3 mM glucose for 48 h. Then, the cell supernatants were collected for enzyme-linked immunosorbent assay to determine the level of superoxide dismutase (***), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6). Western blotting was used to determine the expression of Bcl-2, Bax, caspase-3 and Caspase-9. Cell apoptosis was measured by Annexin V-FITC/propidium iodide double staining and flow cytometry. RESULTS MLF (125-500 mg/L) improved cell viability. Furthermore, MLF (250 and 500 mg/L) inhibited apoptosis induced by high glucose. The anti-apoptosis effect of MLF was associated with increased ***, CAT and GSH-Px expression, as well as reduced MDA levels in high-glucose-treated INS-1 cells. Moreover, MLF upregulated Bcl-2 expression, downregulated Bax expression, and reduced the expression of caspase-3 and Caspase-9. Finally, MLF decreased the secretion of inflammatory cytokines and insulin in high-glucose-induced INS-1 cells. CONCLUSION MLF is a potential therapeutic agent for preventing diabetes and related disorders.Behcet's disease is a condition with a complicated and unclear etiology that comprises multi-systemic, chronic, inflammatory vasculitis. Behcet's disease can affect every tissue and organ in the body, and is characterized by recurrent oral and genital ulcers, ocular inflammation, skin lesions, and other manifestations. The incidence of Behcet's disease has a distinct regional specificity, and is most prevalent along the Silk Road, a route that stretched between the Mediterranean, Middle East and Far East. This article reviews the recent literature to evaluate the prevalence, clinical manifestations, pathogenesis and mechanism, and current treatments of Behcet's disease. Furthermore, the etiology of Behcet's disease will be evaluated from the aspect of Traditional Chinese Medicine (TCM) syndrome differentiation. As Behcet's disease is complex and intractable, its treatment warrants further research. Traditionally, Behcet's disease is treated with Western Medicine (WM) via medications that act locally and systemically; this WM treatment protocol usually has a good effect, but relapse can occur after reducing the dosage. Thus, it may be ideal to treat Behcet's disease via a combination of WM and TCM. Recent studies have indicated that such a combination of Chinese and Western treatments has a better effect than either treatment alone. The aim of the present review is to describe the clinical features of Behcet's disease, and to outline its possible pathogenesis in terms of both TCM and WM. Based on these findings, the present review proposes a Behcet's disease treatment protocol composed of a combination of Chinese and WM that can effectively improve the occurrence of relapse caused by the reduction of the dosage of Western medication.Diabetes mellitus is a chronic endocrine/metabolism disease characterized by hyperglycemia arising from defects in insulin action, insulin secretion, or both. Diabetes mellitus is often complicated by visceral lesions, which can lead to serious complications and death. A variety of new agents are in development for the treatment of the disease. Astragalus polysaccharides are monomer components extracted from the Traditional Chinese Medicine, Huangqi (Radix Astragali Mongolici), which have been studied widely for treating diabetes mellitus with promising effects in recent years. This paper reviews recent advances in experimental studies on the effects of Astragalus polysaccharides in treating diabetes mellitus. The effects of Astragalus polysaccharides on the etiology and complication of diabetes mellitus including insulin resistance and secretion, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic foot, and infection complicated by diabetes mellitus are discussed.
    Administration of CQCQD significantly inhibited JAK-2 activation and down-regulated phosphorylation of downstream substrate STAT-3 the same as AG490, resulting in inhibition of inflammatory mediators and amelioration of pancreatitis. CONCLUSION The results suggested that CQCQD exerted anti-inflammatory effects on AP via reducing expression and phosphorylation of JAK and STAT.OBJECTIVE To determine the efficacy of Scutellaria barbata flavonoids and polysaccharides on Ishikawa endometrial carcinoma cells co-cultured with U937 macrophages. METHODS The presence of CD163 and CD206 was determined by flow cytometry. Thiazolyl Blue Tetrazolium Bromide assays were used to assess the proliferation effect of tumor-associated macrophages (TAMs) on Ishikawa cells. The secretion of interleukin (IL)-10 in the co-culture conditioned media was examined using an enzyme-linked immunosorbent assay. The protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor (NF)-κB p65 were detected by Western blot. The mRNA expression levels of TLR4 and MyD88 were analyzed by real-time polymerase chain reaction (PCR). The expression levels of IL-12, IL-1β and tumor necrosis factor-α (TNF-α) were evaluated with real-time PCR. RESULTS Compared with the U937 control group, the expression levels of CD163 and CD206 in the TAM group were higher (P less then 0.05). TAMs co-cultured with Ishikawa cells for 24 or 48 h showed higher proliferation rates (P less then 0.05). The expression levels of IL-12 decreased than compared with those in the U937 untreated group (P less then 0.05) and those of the Scutellaria barbata flavonoids group (P less then 0.05). https://www.selleckchem.com/products/odm-201.html The expression levels of CD206, CD163, IL-10, IL-1β and TNF-α, NF-κB p65 and TLR4/MyD88 in the TAMs control group were greater than those in the U937 untreated group (P less then 0.05) and those of the Scutellaria barbata flavonoids group (P less then 0.05). CONCLUSION Scutellaria barbata flavonoids may inhibit TAM activation by blocking the TLR4/MyD88/NF-κB signaling pathway.OBJECTIVE To investigate the effect of mulberry leaf flavonoids (MLF) on apoptosis of pancreatic cells induced by high glucose. METHODS Long exposure to high glucose induces apoptosis of pancreatic β cells, which can lead to diabetes. In this study, we used the rat insulinoma cell line, INS-1. High glucose (33.3 mM) was used to establish a glucotoxicity model. The MTT assay was used to evaluate the MLF effect on cell viability. INS-1 cells were treated with various concentrations of MLF (125, 250 and 500 mg/L) for 24 h, and then stimulated with 5.5 or 33.3 mM glucose for 48 h. Then, the cell supernatants were collected for enzyme-linked immunosorbent assay to determine the level of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6). Western blotting was used to determine the expression of Bcl-2, Bax, caspase-3 and Caspase-9. Cell apoptosis was measured by Annexin V-FITC/propidium iodide double staining and flow cytometry. RESULTS MLF (125-500 mg/L) improved cell viability. Furthermore, MLF (250 and 500 mg/L) inhibited apoptosis induced by high glucose. The anti-apoptosis effect of MLF was associated with increased SOD, CAT and GSH-Px expression, as well as reduced MDA levels in high-glucose-treated INS-1 cells. Moreover, MLF upregulated Bcl-2 expression, downregulated Bax expression, and reduced the expression of caspase-3 and Caspase-9. Finally, MLF decreased the secretion of inflammatory cytokines and insulin in high-glucose-induced INS-1 cells. CONCLUSION MLF is a potential therapeutic agent for preventing diabetes and related disorders.Behcet's disease is a condition with a complicated and unclear etiology that comprises multi-systemic, chronic, inflammatory vasculitis. Behcet's disease can affect every tissue and organ in the body, and is characterized by recurrent oral and genital ulcers, ocular inflammation, skin lesions, and other manifestations. The incidence of Behcet's disease has a distinct regional specificity, and is most prevalent along the Silk Road, a route that stretched between the Mediterranean, Middle East and Far East. This article reviews the recent literature to evaluate the prevalence, clinical manifestations, pathogenesis and mechanism, and current treatments of Behcet's disease. Furthermore, the etiology of Behcet's disease will be evaluated from the aspect of Traditional Chinese Medicine (TCM) syndrome differentiation. As Behcet's disease is complex and intractable, its treatment warrants further research. Traditionally, Behcet's disease is treated with Western Medicine (WM) via medications that act locally and systemically; this WM treatment protocol usually has a good effect, but relapse can occur after reducing the dosage. Thus, it may be ideal to treat Behcet's disease via a combination of WM and TCM. Recent studies have indicated that such a combination of Chinese and Western treatments has a better effect than either treatment alone. The aim of the present review is to describe the clinical features of Behcet's disease, and to outline its possible pathogenesis in terms of both TCM and WM. Based on these findings, the present review proposes a Behcet's disease treatment protocol composed of a combination of Chinese and WM that can effectively improve the occurrence of relapse caused by the reduction of the dosage of Western medication.Diabetes mellitus is a chronic endocrine/metabolism disease characterized by hyperglycemia arising from defects in insulin action, insulin secretion, or both. Diabetes mellitus is often complicated by visceral lesions, which can lead to serious complications and death. A variety of new agents are in development for the treatment of the disease. Astragalus polysaccharides are monomer components extracted from the Traditional Chinese Medicine, Huangqi (Radix Astragali Mongolici), which have been studied widely for treating diabetes mellitus with promising effects in recent years. This paper reviews recent advances in experimental studies on the effects of Astragalus polysaccharides in treating diabetes mellitus. The effects of Astragalus polysaccharides on the etiology and complication of diabetes mellitus including insulin resistance and secretion, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic foot, and infection complicated by diabetes mellitus are discussed.
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