Physical activity and mental health: a systematic review and best-evidence synthesis of mediation and moderation studies.

Background: While evidence consistently demonstrates that physical activity is beneficial to mental health, it remains relatively unknown how physical activity benefits mental health, and which factors influence the effect of physical activity on mental health. This understanding could vastly increase our capacity to design, recommend, and prescribe physical activity in more optimal ways. The purpose of this study was to systematically review and synthesise evidence of all mediators and moderators of the relationship between physical activity and mental health.

Optimisation of a novel series of ENaC inhibitors, leading to the selection of the long-acting inhaled clinical candidate ETD001, a potential new treatment for cystic fibrosis.

Cystic Fibrosis (CF) results from the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel of key importance in the airway epithelia. CFTR helps control optimal hydration of the airways, a crucial requirement for healthy lungs. CFTR modulators have recently been approved as an effective treatment option for many genetic variants of CF.

Vision-related quality of life after unilateral occipital stroke.

Background/objectives: Stroke damage to the primary visual cortex induces large, homonymous visual field defects that impair daily living. Here, we asked if vision-related quality of life (VR-QoL) is impacted by time since stroke.

Subjects/methods: We conducted a retrospective meta-analysis of 95 occipital stroke patients (female/male = 26/69, 27-78 years old, 0.

ETD001: A novel inhaled ENaC blocker with an extended duration of action in vivo.

Background: Inhibiting ENaC in the airways of people with cystic fibrosis (pwCF) is hypothesized to enhance mucociliary clearance (MCC) and provide clinical benefit. Historically, inhaled ENaC blockers have failed to show benefit in pwCF challenging this hypothesis. It is however unknown whether the clinical doses were sufficient to provide the required long duration of action in the lungs and questions whether a novel candidate could offer advantages where others have failed?

Methods: Dose-responses with the failed ENaC blockers (VX-371, BI 1265162, AZD5634, QBW276) together with ETD001 (a novel long acting inhaled ENaC blocker) were established in a sheep model of MCC and were used to predict clinically relevant doses that would provide a long-lasting enhancement of MCC in pwCF.

Hospital corridors as lived spaces: The reconfiguration of social boundaries during the early stages of the Covid pandemic.

This article explores the meanings and uses of a hospital corridor through 98 diary entries produced by the staff of an English specialist hospital during the early stages of the COVID-19 pandemic. Drawing on Lefebvre's (1991, The production of space. Blackwell) threefold theorisation of space, corridors are seen as conceived, perceived and lived spaces, produced through and enabling the reconfiguration and reinterpretation of social interactions.

Nanostructure Explains the Behavior of Slippery Covalently Attached Liquid Surfaces.

Slippery covalently-attached liquid surfaces (SCALS) with low contact angle hysteresis (CAH, <5°) and nanoscale thickness display impressive anti-adhesive properties, similar to lubricant-infused surfaces. Their efficacy is generally attributed to the liquid-like mobility of the constituent tethered chains. However, the precise physico-chemical properties that facilitate this mobility are unknown, hindering rational design.

The impact of surgical repair on left ventricular outflow tract in atrioventricular septal defect with common atrioventricular valve orifice.

Objective: Although a narrow left ventricular outflow tract in atrioventricular septal defect is related to its intrinsic morphology, the contribution from the repair technique remains to be quantified.

Methods: A total of 108 patients with an atrioventricular septal defect with a common atrioventricular valve orifice were divided into 2 groups: 2-patch (N = 67) and modified 1-patch (N = 41) repair. The left ventricular outflow tract morphometric was analyzed by quantifying the degree of disproportion between subaortic and aortic annular dimensions (disproportionate morphometrics ratio was defined as ≤ 0.

Niclosamide does not modulate airway epithelial function through blocking of the calcium activated chloride channel, TMEM16A.

Niclosamide and benzbromarone have been described as inhibitors of the calcium activated chloride channel, TMEM16A, and on this basis have been considered and tested as clinical candidates for the treatment of airway diseases. However, both compounds have previously demonstrated activity on a range of additional biological targets and it is unclear from the literature to what extent any activity on TMEM16A may contribute to efficacy in these models of airway disease. The aim of the present study was therefore to examine the pharmacology and selectivity of these clinical candidates together with a structurally unrelated TMEM16A blocker, Ani9, in a range of functional assays to better appreciate the putative role of TMEM16A in the regulation of both epithelial ion transport and the development of an airway epithelial mucus secretory phenoptype.

Sensemaking in the early stages of the COVID-19 pandemic: A narrative exploration of polarised morality in an NHS Trust.

This article presents an analysis of personal diaries kept by health-care staff within a specialist NHS Trust in England during the initial 3 months of the COVID-19 pandemic. It adopts a moral sensemaking perspective to explore how NHS employees mobilised and reframed ideas of right and wrong in order to make sense of unprecedented uncertainty and displacement. By focussing on how the macro and micro politics of the pandemic were played out in the organisation, the study finds that polarised moral judgements were invoked in order to justify and rationalise a broad array of associated emergent emotions, intuitions, behaviours and practices.

"Now You See Me, Now You Don't": How Digital Consumers Manage Their Online Visibility in Game-Like Conditions.

Organizations continue to create digital interfaces and infrastructure that are designed to heighten consumers' online visibility and encourage them to part with their data. The way these digital systems operate and the rules they are governed by are often opaque, leaving consumers to deploy their own strategies for managing their online information sharing with organizations. In this study, we draw upon Erving Goffman's metaphor of expression games and three forms of concealment or cover moves to explore how consumers, who have been well socialized as digital natives, engage in dynamic and game-like interactions with organizations in an attempt to manage their level of online visibility and information sharing in relation, , to the 'convenience' and 'benefits' that are afforded to them.

The role of abnormal subaortic morphometry as a substrate for left ventricular outflow tract obstruction following atrioventricular septal defect repair.

Objectives: Although left ventricular outflow tract (LVOT) obstruction is a recognized risk after atrioventricular (AV) septal defect (AVSD) repair, quantitative assessments to define the substrate of the obstruction are lacking.

Methods: Morphometric analyses were based on measurements from early 2-dimensional echocardiographic scans (within 3 months postoperatively) for 117 patients (82 CAVVO = common AV valve; 35 SAVVO = separate AV valve orifices), which were compared to 50 age/weight matched controls (atrial septal defect/ventricular septal defect). Late echocardiographic analyses were performed in 57 patients with AVSD (follow-up range, 1.

Hybrid halide perovskite neutron detectors.

Interest in fast and easy detection of high-energy radiation (x-, γ-rays and neutrons) is closely related to numerous practical applications ranging from biomedicine and industry to homeland security issues. In this regard, crystals of hybrid halide perovskite have proven to be excellent detectors of x- and γ-rays, offering exceptionally high sensitivities in parallel to the ease of design and handling. Here, we demonstrate that by assembling a methylammonium lead tri-bromide perovskite single crystal (CHNHPbBr SC) with a Gadolinium (Gd) foil, one can very efficiently detect a flux of thermal neutrons.

Online paediatric chronic pain management: assessing the needs of UK adolescents and parents, using a cross-sectional survey.

Background: Adolescent chronic pain is prevalent, and interdisciplinary treatment is recommended. Although it is well known that technology is a key part of adolescents' daily lives, there have not been any online, interdisciplinary interventions developed for adolescents with chronic pain in a UK healthcare context. Little is known about how adolescents currently use online resources to manage chronic pain, or what guidance they seek.

Potentiating TMEM16A does not stimulate airway mucus secretion or bronchial and pulmonary arterial smooth muscle contraction.

The calcium-activated chloride channel (CaCC) TMEM16A enables chloride secretion across several transporting epithelia, including in the airways. Additional roles for TMEM16A have been proposed, which include regulating mucus production and secretion and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, could affect any of these proposed biological roles in the airways.

TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis.

Enhancing non-CFTR (cystic fibrosis transmembrane conductance regulator)-mediated anion secretion is an attractive therapeutic approach for the treatment of cystic fibrosis (CF) and other mucoobstructive diseases. To determine the effects of TMEM16A potentiation on epithelial fluid secretion and mucociliary clearance. The effects of a novel low-molecular-weight TMEM16A potentiator (ETX001) were evaluated in human cell and animal models of airway epithelial function and mucus transport.

Superior Vena Cava Inflow Following Repair for Anomalous Right Pulmonary Venous Drainage in Children.

Risk of superior vena cava (SVC) obstruction following repair of anomalous right upper pulmonary veins in children is unclear. The incidence and outcome of subclinical obstruction remained unknown. Retrospective single institutional study (07/1993-02/2017) in a pediatric population (N = 42, median age 3.

Effectiveness of interdisciplinary interventions in paediatric chronic pain management: a systematic review and subset meta-analysis.

Background: Paediatric chronic pain is a significant problem that can have devastating impacts on quality of life. Multimodal interdisciplinary interventions are the mainstay of paediatric treatment. The aim of this article is to provide a comprehensive review of the effectiveness of interdisciplinary interventions in the management of paediatric chronic pain.

Protocol for a cluster randomised controlled trial evaluating a parenting with home visitation programme to prevent physical and emotional abuse of children in Indonesia: the Families First Programme.

Introduction: Every year, up to 1 billion children are victims of violence worldwide. Most child abuse takes place in the context of punishment. The Families First Programme, an adaptation of the Positive Discipline in Everyday Parenting Programme to the West Java context, is a parenting support programme anchored on children's rights that gives parents guidance on child development, parenting and positive discipline practices.

More than support to court: Rape victims and specialist sexual violence services.

This article explores the involvement of specialist sexual violence services, including Independent Sexual Violence Advisers (ISVAs), in supporting victims/survivors of rape and sexual abuse to engage with the criminal justice system (CJS) in England and Wales. The underpinning research, conducted in one area of England, included referral data from the police and key specialist sexual violence services, interviews with 15 victims/survivors of sexual violence in contact with the police and specialist services, and interviews with 14 practitioners from sexual violence and related services. We examine the complex needs of victims/survivors of sexual violence (who have experienced historical child sexual abuse, acquaintance rape or rape in the context of intimate partner abuse), how their needs differ and vary over time, and the ways in which these diverse and changing needs are met by specialist sexual violence services.

Choose to change maternity weight management pilot.

Obesity during pregnancy is associated with increased risk of adverse health outcomes during pregnancy. There is limited research available regarding effective interventions during pregnancy for obese women and this is combined with local inadequate service provision to support obese mothers in Greater Manchester (GM). Choose to Change (CTC) aims to develop, deliver and evaluate a community based weight management programme to limit excessive gestational weight gain.

Family structure and sexual and reproductive health outcomes among adolescents in rural Sierra Leone.

Orphanhood is common in sub-Saharan Africa, and is a critical issue shaping global assistance for children. Care arrangements for children are often fluid, and many 'orphaned' children have a surviving biological parent. This study examines the protective effects of family-level factors on early sex and pregnancy in rural Sierra Leone.

Variomics screen identifies the re-entrant loop of the calcium-activated chloride channel ANO1 that facilitates channel activation.

The calcium-activated chloride channel ANO1 regulates multiple physiological processes. However, little is known about the mechanism of channel gating and regulation of ANO1 activity. Using a high-throughput, random mutagenesis-based variomics screen, we generated and functionally characterized ∼6000 ANO1 mutants and identified novel mutations that affected channel activity, intracellular trafficking, or localization of ANO1.

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling.

The calcium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the most frequently amplified chromosomal regions in human cancer, but its functional role in tumorigenesis has remained unclear. The 11q13 region is amplified in ∼15% of breast cancers. Whether ANO1 is amplified in breast tumors, the extent to which gene amplification contributes to ANO1 overexpression, and whether overexpression of ANO1 is important for tumor maintenance have remained unknown.