Synthesis of 2-arylpyridines by the Suzuki–Miyaura cross-coupling of PyFluor with hetero (aryl) boronic acids and esters

The Suzuki–Miyaura cross-coupling of pyridine-2-sulfonyl fluoride (PyFluor) with hetero(aryl) boronic acids and pinacol boronic esters is reported. The reactions can be performed using Pd(dppf)Cl2 as the catalyst, at temperatures between 65 and 100 °C and in the presence of water and oxygen. This transformation generates 2-arylpyridines in modest to good yields (5%–89%)

Survey-Based Examination of Demographics, Potential Causes and Treatments of Aberrant Behavior Syndrome(Berserk Male Syndrome) in Camelids

The objective of this study was to examine potential signs, causal factors and treatment interventions for camelids displaying Aberrant Behavior Syndrome (ABS), also known as Berserk Male Syndrome. A survey was developed for camelid owners and veterinarians with camelid experience using Survey Monkey software. Respondents were asked to describe the behaviors associated with the most recent case of ABS they were involved with, information about the animal displaying ABS, and evaluation of the efficacy of treatment interventions used. The majority of respondents identified a general demographic of an intact male camelid raised by its biological mother with daily or weekly handing by humans. Aggressive behavior emerged at one to three years of age, and was directed more frequently at humans than at other animals. Treatment interventions included behavioral modification, castration, moving and/or isolating the animal. All treatments had a higher rate of failure than success. The results of this survey indicate a need for research to identify causal factors and treatments for this behavioral disorder

Effectiveness of interventions to improve health behaviours of health professionals : A systematic review

Objective To evaluate the effectiveness of interventions designed to improve the health behaviours of health professionals. Design Systematic review. Data sources Database searches: Medline, Cochrane library, Embase and CINAHL. Review methods This systematic review used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to compare randomised controlled trials of health professionals, published between 2010 and 2021, which aimed to improve at least one health behaviour such as physical activity, diet, smoking status, mental health and stress. Two independent reviewers screened articles, extracted data and assessed quality of studies and reporting. The quality of articles was assessed using the Effective Public Health Practice Project quality assessment tool and the completeness of intervention reporting was assessed. Outcome measures The outcome assessed was change in behaviour between intervention and control groups from baseline to follow-up. Results Nine studies met the eligibility criteria, totalling 1107 participants. Health behaviours targeted were mental health and stress, physical activity, and smoking cessation, physical activity and nutrition. Six interventions observed significant improvements in the health behaviour in the intervention compared with control groups. Seven of the studies selected in person workshops as the mode of intervention delivery. The quality of the included studies was high with 80% (7/9) graded as moderate or strong. Conclusions Although high heterogeneity was found between interventions and outcomes, promising progress has occurred across a variety of health behaviours. Improving reporting and use of theories and models may improve effectiveness and evaluation of interventions. Further investigation is needed to recommend effective strategies. PROSPERO registration number CRD42021238684

Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration

H2O2 is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H2O2 is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H2O2 also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H2O2 acts through an Src kinase to activate a negative regulator of PI3K signaling, SHIP-1 via phosphorylation, providing a molecular mechanism for H2O2-induced chemotaxis deficiency. We hypothesize that although H2O2 serves as an early recruitment trigger for innate immune cells, it appears to operate as an inhibitor of T lymphocyte immune adaptive responses that are not required until later in the repair process

Neuronal pentraxins mediate synaptic refinement in the developing visual system

Peer reviewedPublisher PD

The role of G protein gene GNB3 C825T Polymorphism in HIV-1 acquisition, progression and immune activation

<p>Abstract</p> <p>Background</p> <p>The <it>GNB3 C825T </it>polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The <it>GNB3 </it>825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. <it>GNB3 </it>825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. <it>Ex vivo </it>immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.</p> <p>Results</p> <p><it>GNB3 </it>genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, <it>GNB3 </it>genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25⁺FOXP3⁺) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups.</p> <p>Conclusions</p> <p>In contrast to previous reports, we were unable to provide evidence to suggest that the <it>GNB3 C825T </it>polymorphism affects HIV-1 acquisition or disease progression within African populations. <it>Ex vivo </it>immune activation and plasma chemokine levels were similarly unaffected by <it>GNB3 </it>genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of <it>GNB3 </it>polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.</p

Collagen Fiber Regulation in Human Pediatric Aortic Valve Development and Disease

Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), a post-translational modification critical to stabilizing the collagen triple helix. Quantitative data analysis reported significant regulation of collagen HYP sites across patient categories. Non-collagen type ECM proteins identified (26 of the 44 total proteins) have direct interactions in collagen synthesis, regulation, or modification. Network analysis identified BAMBI (BMP and Activin Membrane Bound Inhibitor) as a potential upstream regulator of the collagen interactome. This is the first study to detail the collagen types and HYP modifications associated with human AV development and pCAVS. We anticipate that this study will inform new therapeutic avenues that inhibit valvular degradation in pCAVS and engineered options for valve replacement

Impact of home food production on nutritional blindness, stunting, wasting, underweight and mortality in children: a systematic review and meta-analysis of controlled trials

Vitamin A deficiency is highly prevalent and remains the major cause of nutritional blindness in children in low-and middle-income countries, despite supplementation programmes. Xeropthalmia (severe drying and thickening of the conjunctiva) is caused by vitamin A deficiency and leads to irreversible blindness. Vitamin A supplementation programmes effectively reduce vitamin A deficiency but many rural children are not reached. Home food production may help prevent rural children’s vitamin A deficiency. We aimed to systematically review trials assessing effects of home food production (also called homestead food production and agricultural interventions) on xeropthalmia, night blindness, stunting, wasting, underweight and mortality (primary outcomes).. We searched Medline, Embase, Scopus, Cochrane CENTRAL and trials registers to February 2019. Inclusion of studies, data extraction and risk of bias were assessed independently in duplicate. Random-effects meta-analysis, sensitivity analyses, subgrouping and GRADE were used. We included 16 trials randomizing 2498 children, none reported xerophthalmia, night-blindness or mortality. Home food production may slightly reduce stunting (mean difference (MD) 0.13 (z-score), 95% CI 0.01 to 0.24), wasting (MD 0.05 (z-score), 95% CI -0.04 to 0.14) and underweight (MD 0.07 (z-score), 95% CI -0.01 to 0.15) in young children (all GRADE low-consistency evidence), and increase dietary diversity (standardized mean difference (SMD) 0.24, 95% CI 0.15 to 0.34). Home food production may usefully complement vitamin A supplementation for rural children. Large, long-duration trials with good randomization, allocation concealment and correct adjustment for clustering are needed to assess effectiveness of home food production on nutritional blindness in young children. Prospero registration: CRD42019126455 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019126455