Crystallographic approach to fragment-based hit discovery against Schistosoma mansoni purine nucleoside phosphorylase.

Several Schistosoma species cause Schistosomiasis, an endemic disease in 78 countries that is ranked second amongst the parasitic diseases in terms of its socioeconomic impact and human health importance. The drug recommended for treatment by the WHO is praziquantel (PZQ), but there are concerns associated with PZQ, such as the lack of information about its exact mechanism of action, its high price, its effectiveness - which is limited to the parasite's adult form - and reports of resistance. The parasites lack the de novo purine pathway, rendering them dependent on the purine salvage pathway or host purine bases for nucleotide synthesis.

Necrobiosis Lipoidica following Breast Reduction.

Necrobiosis lipoidica (NL) is a rare granulomatous skin disorder of unknown physiopathology that is frequently associated with diabetes mellitus. The typical skin lesions of NL present as chronic, bilateral, well-defined red to yellow-brown plaques with telangectasias, a violaceous border and a waxy atrophic center. The lower legs are the most often involved areas, but NL may exceptionally develop on scar tissue following surgery.

Observation of New Resonances Decaying to J/ψK^{+} and J/ψϕ.

The first observation of exotic states with a new quark content cc[over ¯]us[over ¯] decaying to the J/ψK^{+} final state is reported with high significance from an amplitude analysis of the B^{+}→J/ψϕK^{+} decay. The analysis is carried out using proton-proton collision data corresponding to a total integrated luminosity of 9  fb^{-1} collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The most significant state, Z_{cs}(4000)^{+}, has a mass of 4003±6_{-14}^{+4}  MeV, a width of 131±15±26  MeV, and spin parity J^{P}=1^{+}, where the quoted uncertainties are statistical and systematic, respectively.

Testing the Efficacy of a 1-Day Police Decision-Making and Autonomic Modulation Intervention: A Quasi-Random Pragmatic Controlled Trial.

Contemporary discourse has identified several urgent priorities concerning police training and education, including: (a) empirically testing and validating the effectiveness of current programming in reducing lethal force decision-making errors; (b) integrating evidence-based content and pedagogical approaches into police curriculum; and (c) understanding the breadth and length of programming necessary to ensure learning and transfer of skills to operational field settings. Widespread calls to identify effective and actionable training programs have been met with numerous research studies, systematic reviews, and policy recommendations that reveal the need to train officers' internal physiological awareness, which is foundational in shaping cognitive decision-making, emotion regulation, and behavior under stressful conditions. Several investigations have shown improvements to both lethal force errors and physiological recovery following a multi-day autonomic modulation (AM) intervention.

State of the art approach to managing angina and ischemia: tailoring treatment to the evidence.

Stable angina represents a chronic and often debilitating condition that affects daily activities and quality of life in patients with chronic coronary syndromes (CCS). Current European Society of Cardiology guidelines recommend a four-step approach for the medical treatment of patients taking into consideration hemodynamic variables (heart rate and blood pressure) and the presence or absence of left ventricular dysfunction. However, CCS patients often have several comorbidities and risk factors.

Clotting factor concentrates for preventing bleeding and bleeding-related complications in previously treated individuals with haemophilia A or B.

Background: The hallmark of severe hemophilia (A or B) is recurrent bleeding into joints and soft tissues with progressive joint damage, despite on-demand treatment. Prophylaxis has long been used, but not universally adopted, because of medical, psychosocial, and cost controversies.

Objectives: To determine the effectiveness of clotting factor concentrate prophylaxis in managing previously-treated individuals with hemophilia A or B.

Identifying and Managing Malnutrition, Frailty and Sarcopenia in the Community: A Narrative Review.

Malnutrition, frailty and sarcopenia are becoming increasingly prevalent among community-dwelling older adults; yet are often unidentified and untreated in community settings. There is an urgent need for community-based healthcare professionals (HCPs) from all disciplines, including medicine, nursing and allied health, to be aware of, and to be able to recognise and appropriately manage these conditions. This paper provides a comprehensive overview of malnutrition, frailty and sarcopenia in the community, including their definitions, prevalence, impacts and causes/risk factors; and guidance on how these conditions may be identified and managed by HCPs in the community.

Sequential gains and losses during gambling feedback: Differential effects in time-frequency delta and theta measures.

One critical aspect of reward-feedback is the impact of local outcome history-how past experiences with choices and outcomes influences current behavior and neural activity. Yet, prior event-related potential work in this area has been contentious. This study contributes to this field by using time-frequency measures to better isolate constituent processes.

Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17-21, 2021. The conference, now held annually, highlighted cutting-edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person.

Posttraumatic Stress Disorder Symptoms and Coping Motives are Independently Associated with Cannabis Craving Elicited by Trauma Cues.

Cannabis use is common among individuals with posttraumatic stress disorder (PTSD), although its use can ultimately worsen PTSD outcomes. Cannabis-use coping motives may help explain the PTSD-cannabis relationship. Frequent pairing of trauma cues with substance use to cope with negative affect can lead to conditioned substance craving.

Medical management of anginal symptoms in women with stable angina pectoris: A systematic review of randomised controlled trials.

Background: Medical therapies are used to improve stable anginal symptoms and quality of life in clinical practice however the evidence for the use of antianginal medication in women is largely unknown. We conducted a systematic review to investigate the extent of the evidence-base for the medical management of anginal symptoms in women with stable angina.

Methods: MEDLINE, EMBASE, Cochrane and ClinicalTrials.

Enhancing the evidential value of textile fibres Part 2: Application of a database-driven fibre comparison strategy to a cold-case investigation.

This paper describes the involvement of our laboratory in a Western Australian 'cold-case' investigation that spanned 24 years. The investigation was widely considered to be the largest in Australian history. During the investigative phase, our laboratory was tasked with the collection of trace evidence of all types in connection with a sexual assault and two homicides that were suspected to be related.

Ebola vaccine-induced protection in nonhuman primates correlates with antibody specificity and Fc-mediated effects.

Although substantial progress has been made with Ebola virus (EBOV) vaccine measures, the immune correlates of vaccine-mediated protection remain uncertain. Here, five mucosal vaccine vectors based on human and avian paramyxoviruses provided nonhuman primates with varying degrees of protection, despite expressing the same EBOV glycoprotein (GP) immunogen. Each vaccine produced antibody responses that differed in Fc-mediated functions and isotype composition, as well as in magnitude and coverage toward GP and its conformational and linear epitopes.

Initiation of Moderately Frequent Cannabis use in Adolescence and Young Adulthood is Associated with Declines in Verbal Learning and Memory: A Longitudinal Comparison of Pre- versus Post-Initiation Cognitive Performance.

Objective: Cannabis use is associated with relative cognitive weaknesses as observed by cross-sectional as well as longitudinal research. Longitudinal studies, controlling for relevant confounds, are necessary to differentiate premorbid from post-initiation contributions to these effects.

Methods: We followed a sample of adolescents and young adults across ten years.

A Digital Toolkit (M-Healer) to Improve Care and Reduce Human Rights Abuses Against People With Mental Illness in West Africa: User-Centered Design, Development, and Usability Study.

Background: The resources of West African mental health care systems are severely constrained, which contributes to significant unmet mental health needs. Consequently, people with psychiatric conditions often receive care from traditional and faith healers. Healers may use practices that constitute human rights violations, such as flogging, caging, forced fasting, and chaining.

An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma.

Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery.

Cardiometabolic health in premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is an increasing public health problem with a prevalence now approaching 4%. POI results in adverse effects on the skeleton and central nervous system as well as disturbances of metabolic and cardiological factors that predispose to a major increased risk of cardiovascular disease (CVD). This article reviews the effects of the premature loss of ovarian function on lipids and lipoproteins, glucose and insulin metabolism, body composition, hemostasis and blood pressure, together with effects on the development of metabolic syndrome and diabetes mellitus.

Bispecific repurposed medicines targeting the viral and immunological arms of COVID-19.

Effective agents to treat coronavirus infection are urgently required, not only to treat COVID-19, but to prepare for future outbreaks. Repurposed anti-virals such as remdesivir and human anti-inflammatories such as barcitinib have received emergency approval but their overall benefits remain unclear. Vaccines are the most promising prospect for COVID-19, but will need to be redeveloped for any future coronavirus outbreak.

Intervening for HIV prevention and mental health: a review of global literature.

Introduction: Numerous effective HIV prevention options exist, including behaviour change interventions, condom promotion and biomedical interventions, like voluntary medical male circumcision and pre-exposure prophylaxis. However, populations at risk of HIV also face overlapping vulnerabilities to common mental disorders and severe mental illness. Mental health status can affect engagement in HIV risk behaviours and HIV prevention programmes.

Re-amputation and survival following toe amputation: outcome data from a tertiary referral centre.

Purpose: Toe amputation is a commonly performed procedure for irreversible foot sepsis. However, outcome and predictors of outcome are poorly understood. Our aim was to determine survival and rate of progression to further amputation following index toe amputation.

Utility of viscoelastography with TEG 6s to direct management of haemostasis during obstetric haemorrhage: a prospective observational study.

Background: The TEG 6s is an automated cartridge-based device with limited description of use in obstetric haemorrhage. The aim of this analysis was to describe the utility of TEG 6s in identifying abnormal laboratory results of coagulation and platelet count, and inform an interventional treatment algorithm for postpartum haemorrhage.

Methods: A prospective observational cohort study of 521 women with moderate to severe obstetric haemorrhage (>1000 mL blood loss), including 372 women with at least one TEG 6s test.