LGBTQI+ inclusion in sport and exercise psychology teaching

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Kinetoplastids:related protozoan pathogens, different diseases

Kinetoplastids are a group of flagellated protozoans that include the species Trypanosoma and Leishmania, which are human pathogens with devastating health and economic effects. The sequencing of the genomes of some of these species has highlighted their genetic relatedness and underlined differences in the diseases that they cause. As we discuss in this Review, steady progress using a combination of molecular, genetic, immunologic, and clinical approaches has substantially increased understanding of these pathogens and important aspects of the diseases that they cause. Consequently, the paths for developing additional measures to control these “neglected diseases” are becoming increasingly clear, and we believe that the opportunities for developing the drugs, diagnostics, vaccines, and other tools necessary to expand the armamentarium to combat these diseases have never been better

High hypoxia status in pancreatic cancer is associated with multiple hallmarks of an immunosuppressive tumor microenvironment

Introduction: Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is a particularly lethal disease that is often diagnosed late and is refractory to most forms of treatment. Tumour hypoxia is a key hallmark of PDAC and is purported to contribute to multiple facets of disease progression such as treatment resistance, increased invasiveness, metabolic reprogramming, and immunosuppression.Methods: We used the Buffa gene signature as a hypoxia score to profile transcriptomics datasets from PDAC cases. We performed cell-type deconvolution and gene expression profiling approaches to compare the immunological phenotypes of cases with low and high hypoxia scores. We further supported our findings by qPCR analyses in PDAC cell lines cultured in hypoxic conditions.Results: First, we demonstrated that this hypoxia score is associated with increased tumour grade and reduced survival suggesting that this score is correlated to disease progression. Subsequently, we compared the immune phenotypes of cases with high versus low hypoxia score expression (HypoxiaHI vs. HypoxiaLOW) to show that high hypoxia is associated with reduced levels of T cells, NK cells and dendritic cells (DC), including the crucial cDC1 subset. Concomitantly, immune-related gene expression profiling revealed that compared to HypoxiaLOW tumours, mRNA levels for multiple immunosuppressive molecules were notably elevated in HypoxiaHI cases. Using a Random Forest machine learning approach for variable selection, we identified LGALS3 (Galectin-3) as the top gene associated with high hypoxia status and confirmed its expression in hypoxic PDAC cell lines.Discussion: In summary, we demonstrated novel associations between hypoxia and multiple immunosuppressive mediators in PDAC, highlighting avenues for improving PDAC immunotherapy by targeting these immune molecules in combination with hypoxia-targeted drugs.<br/

Computational Design of a PDZ Domain Peptide Inhibitor that Rescues CFTR Activity

The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial chloride channel mutated in patients with cystic fibrosis (CF). The most prevalent CFTR mutation, ΔF508, blocks folding in the endoplasmic reticulum. Recent work has shown that some ΔF508-CFTR channel activity can be recovered by pharmaceutical modulators (“potentiators” and “correctors”), but ΔF508-CFTR can still be rapidly degraded via a lysosomal pathway involving the CFTR-associated ligand (CAL), which binds CFTR via a PDZ interaction domain. We present a study that goes from theory, to new structure-based computational design algorithms, to computational predictions, to biochemical testing and ultimately to epithelial-cell validation of novel, effective CAL PDZ inhibitors (called “stabilizers”) that rescue ΔF508-CFTR activity. To design the “stabilizers”, we extended our structural ensemble-based computational protein redesign algorithm to encompass protein-protein and protein-peptide interactions. The computational predictions achieved high accuracy: all of the top-predicted peptide inhibitors bound well to CAL. Furthermore, when compared to state-of-the-art CAL inhibitors, our design methodology achieved higher affinity and increased binding efficiency. The designed inhibitor with the highest affinity for CAL (kCAL01) binds six-fold more tightly than the previous best hexamer (iCAL35), and 170-fold more tightly than the CFTR C-terminus. We show that kCAL01 has physiological activity and can rescue chloride efflux in CF patient-derived airway epithelial cells. Since stabilizers address a different cellular CF defect from potentiators and correctors, our inhibitors provide an additional therapeutic pathway that can be used in conjunction with current methods

Call-to-action: the need for a mental health research agenda for sports match officials

Little research has examined the mental health symptoms and disorders of sports match officials, in any sport, anywhere in the world. This lack of research has created a deficit of mental health knowledge for sports match officials and prevented the design, testing, and dissemination of evidence-based mental health interventions. The purposes of this paper are to briefly outline the limited research that does exist on the mental health symptoms and disorders of sports match officials and to establish a research agenda that begins to build an evidence-base for future multidisciplinary research and practice. Only through collaborative efforts, that aim to help both individuals and organizations, can poor mental health in this population be addressed

Narrative review of mental illness in cricket with recommendations for mental health support

Introduction: Epidemiology reporting within the cricketing medical literature has emerged over the past 2 years, with a focus on physical injuries. Despite mental health in elite sport gaining increasing recognition, few studies have addressed mental health symptoms and disorders within cricket. Recently, cricketers have been prominent in the mainstream media describing their lived experiences of mental illness. As a result, some have withdrawn from competition and suggested there is an unmet need for mental health services within the sport. Objectives: (i) To appraise the existing evidence on mental health symptoms and disorders amongst cricketers. (ii) To provide guidance on shaping mental health research and services within cricket. Design: A narrative review of the literature from inception of available databases until 26 July 2019, with analysis and recommendations. Results: Five studies were included in this narrative review. Studies covered a range of mental health symptoms and disorders, including distress, anxiety, depression, sleep disturbance, suicide, adverse alcohol use, illicit drug use, eating disorders and bipolar disorder. Results indicated that cricketers are at high risk for distress, anxiety, depression and adverse alcohol use. When compared with the general population, cricketers are more likely to experience anxiety and depressive symptoms. Rates of suicide were proposed to be high for test cricketers. Overall, studies to date have been of low quality, demonstrating non-rigorous research methods. Some studies have relied on non-validated questionnaires to collect self-reported data on mental health symptoms and disorders, while others have presented biographical data obtained through searches of the media. Conclusions: The results of this narrative review highlight the lack of evidence underpinning mental health services for athletes within cricket. We suggest the following recommendations for future research and practice: (i) normalising mental health symptoms and disorders; (ii) working with and helping vulnerable demographic segments within the target population; (iii) designing and implementing early recognition systems of mental health symptoms and disorders; (iv) addressing the mental health needs of cricketers on a population basis

Equity in communication: a policy template for promoting organizational health literacy

The policy template presented in this post provides the reader with ideas on how they could promote organizational health literacy within their own and other organizations. The reader may jump straight to the policy template, should they wish. Use the hyperlinked Table of Contents (next page) or the bookmarks tool within the PDF reader being used to view this post. This post contains an overview about the policy template, followed by the steps used to develop the policy template. A brief discussion is presented at the end

Narrative review of mental illness in cricket with recommendations for mental health support

IntroductionEpidemiology reporting within the cricketing medical literature has emerged over the past 2 years, with a focus on physical injuries. Despite mental health in elite sport gaining increasing recognition, few studies have addressed mental health symptoms and disorders within cricket. Recently, cricketers have been prominent in the mainstream media describing their lived experiences of mental illness. As a result, some have withdrawn from competition and suggested there is an unmet need for mental health services within the sport.Objectives(i) To appraise the existing evidence on mental health symptoms and disorders amongst cricketers. (ii) To provide guidance on shaping mental health research and services within cricket.DesignA narrative review of the literature from inception of available databases until 26 July 2019, with analysis and recommendations.ResultsFive studies were included in this narrative review. Studies covered a range of mental health symptoms and disorders, including distress, anxiety, depression, sleep disturbance, suicide, adverse alcohol use, illicit drug use, eating disorders and bipolar disorder. Results indicated that cricketers are at high risk for distress, anxiety, depression and adverse alcohol use. When compared with the general population, cricketers are more likely to experience anxiety and depressive symptoms. Rates of suicide were proposed to be high for test cricketers. Overall, studies to date have been of low quality, demonstrating non-rigorous research methods. Some studies have relied on non-validated questionnaires to collect self-reported data on mental health symptoms and disorders, while others have presented biographical data obtained through searches of the media.ConclusionsThe results of this narrative review highlight the lack of evidence underpinning mental health services for athletes within cricket. We suggest the following recommendations for future research and practice: (i) normalising mental health symptoms and disorders; (ii) working with and helping vulnerable demographic segments within the target population; (iii) designing and implementing early recognition systems of mental health symptoms and disorders; (iv) addressing the mental health needs of cricketers on a population basis.</jats:sec