Discovery and Characterization of Novel Antagonists of the Proinflammatory Orphan Receptor GPR84.

GPR84 is a poorly characterized, nominally orphan, proinflammatory G protein-coupled receptor that can be activated by medium chain length fatty acids. It is attracting considerable interest as a potential therapeutic target for antagonist ligands in both inflammatory bowel diseases and idiopathic pulmonary fibrosis. Successful screening of more than 300 000 compounds from a small molecule library followed by detailed analysis of some 50 drug-like hits identified 3-((5,6-bis(4-methoxyphenyl)-1,2,4-triazin-3-yl)methyl)-1-indole as a high affinity and highly selective competitive antagonist of human GPR84.

The utility of maraviroc, an antiretroviral agent used to treat HIV, as treatment for opioid abuse? Data from MRI and behavioural testing in rats.

Background: Maraviroc is an antiretroviral agent and C-C chemokine coreceptor 5 (CCR5) antagonist that is currently used to treat human immunodeficiency virus. CCR5/μ-opioid receptor heterodimerization suggests that maraviroc could be a treatment for oxycodone abuse. We treated rats with maraviroc to explore its effect on oxycodone-seeking and its interference with the analgesic effects of oxycodone.

Identification of a Novel Allosteric Site at the M Muscarinic Acetylcholine Receptor.

The M muscarinic acetylcholine receptor (mAChR) has emerged as an exciting therapeutic target for the treatment of addiction and behavioral disorders. This has been in part due to promising preclinical studies with the M mAChR selective negative allosteric modulator (NAM), ML375. The binding site of ML375 remains unknown, however, making it difficult to develop improved M mAChR selective modulators.

Combining Realist approaches and Normalization Process Theory to understand implementation: a systematic review.

Background: Realist approaches and Normalization Process Theory (NPT) have both gained significant traction in implementation research over the past 10 years. The aim of this study was therefore to explore how the approaches are combined to understand problems of implementation, to determine the degree of complementarity of the two approaches and to provide practical approaches for using them together.

Methods: Systematic review of research studies combining Realist and NPT approaches.

The Effectiveness of Smoking Cessation, Alcohol Reduction, Diet and Physical Activity Interventions in Improving Maternal and Infant Health Outcomes: A Systematic Review of Meta-Analyses.

Diet, physical activity, smoking and alcohol behaviour-change interventions delivered in pregnancy aim to prevent adverse pregnancy outcomes. This review reports a synthesis of evidence from meta-analyses on the effectiveness of interventions at reducing risk of adverse health outcomes. Sixty-five systematic reviews (63 diet and physical activity; 2 smoking) reporting 602 meta-analyses, published since 2011, were identified; no data were identified for alcohol interventions.

Clinicians' perceived barriers and enablers to the dietary management of adults with type 2 diabetes in primary care: A systematic review.

Background: Dietary management of type 2 diabetes is considered as a key remission and management strategy. This review explored clinicians' perceived barriers and enablers to the dietary management of adults with type 2 diabetes in primary care.

Methods: MEDLINE, EMBASE, CINAHL, PsycINFO and ASSIA were searched from 1980 to 16 June 2020.

Socioeconomic inequalities and adverse pregnancy outcomes in the UK and Republic of Ireland: a systematic review and meta-analysis.

Objective: There has been an unprecedented rise in infant mortality associated with deprivation in recent years in the United Kingdom (UK) and Republic of Ireland. A healthy pregnancy can have significant impacts on the life chances of children. The objective of this review was to understand the association between individual-level and household-level measures of socioeconomic status and adverse pregnancy outcomes.

Artemisinin-resistant K13 mutations rewire Plasmodium falciparum's intra-erythrocytic metabolic program to enhance survival.

The emergence and spread of artemisinin resistance, driven by mutations in Plasmodium falciparum K13, has compromised antimalarial efficacy and threatens the global malaria elimination campaign. By applying systems-based quantitative transcriptomics, proteomics, and metabolomics to a panel of isogenic K13 mutant or wild-type P. falciparum lines, we provide evidence that K13 mutations alter multiple aspects of the parasite's intra-erythrocytic developmental program.

Challenges, opportunities and solutions for local physical activity stakeholders: an implementation case study from a cross-sectoral physical activity network in Northeast England.

Background: Increasingly, national policy initiatives and programmes have been developed to increase physical activity (PA). However, challenges in implementing and translating these policies into effective local-level programmes have persisted, and change in population PA levels has been small. This may be due to insufficient attention given to the implementation context, and the limited interactions between local policy-makers, practitioners and researchers.

Attracting, recruiting and retaining nurses and care workers working in care homes: the need for a nuanced understanding informed by evidence and theory.

The care home sector relies on nurses and care workers to deliver care to residents living with frailty and complex needs. However, attracting, recruiting and retaining staff is one of the biggest challenges facing this sector. There is evidence available that describes factors that influence staff decisions to join and/or remain in the care home workforce, for example, individual rewards (such as feeling valued at work or training opportunities), relationships with colleagues and residents, supportive management or working arrangements (including flexible hours).

The effectiveness of smoking cessation, alcohol reduction, diet and physical activity interventions in changing behaviours during pregnancy: A systematic review of systematic reviews.

Background: Pregnancy is a teachable moment for behaviour change. Multiple guidelines target pregnant women for behavioural intervention. This systematic review of systematic reviews reports the effectiveness of interventions delivered during pregnancy on changing women's behaviour across multiple behavioural domains.

'Everything takes too long and nobody is listening': Developing theory to understand the impact of advice on stress and the ability to cope.

Shrinking state spending in the UK has been accompanied by a profound restructuring of the welfare system, leading to financial insecurity for many people, culminating in extreme stress and serious deterioration of physical and mental health. Theory surrounding the impact of welfare advice on stress is lacking; this paper undertakes an in depth exploration of the experiences of stress among welfare advice seekers, considering these in light of existing substantive theories of stress and coping to generate new insight. A thematic analysis explored the experiences of stress in welfare advice seekers.

The European Research Network on Signal Transduction (ERNEST): Toward a Multidimensional Holistic Understanding of G Protein-Coupled Receptor Signaling.

G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family of transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles in human physiology and health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with the goal of harnessing the substantial growth in knowledge of GPCR structure and dynamics to push forward the development of molecular modulators of GPCR function.

Community-based prehabilitation before elective major surgery: the PREP-WELL quality improvement project.

Optimising health and well-being before elective major surgery via prehabilitation initiatives is important for good postoperative outcomes. In a busy tertiary centre in North East England, the lack of a formal prehabilitation service meant that opportunities were being missed to optimise patients for surgery. This quality improvement project aimed to implement and evaluate a community-based prehabilitation service for people awaiting elective major surgery: PREP-WELL.

Inequities and inequalities in outdoor walking groups: a scoping review.

Background: Outdoor walking groups are widely-used programmes aimed at improving physical activity and health outcomes. Despite being promoted as accessible and inclusive, emerging work highlights participation biases based on gender, age and socioeconomic status, for example. To explicate the impact of outdoor walking groups on physical activity inequities, we conducted a scoping review of published outdoor walking group literatures.

Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs.

Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-coupled receptor (GPCR) have failed, largely due to cholinergic adverse responses. Employing novel chemogenetic and phosphorylation-deficient, G protein-biased, mouse models, paired with a toolbox of probe molecules, we establish previously unappreciated pharmacologically targetable M1 mAChR neurological processes, including anxiety-like behaviors and hyper-locomotion.

Parents' and carers' awareness and perceptions of UK supermarket policies on less healthy food at checkouts: A qualitative study.

Background: In the retail environment strategic placement of food influences purchasing. Foods placed at checkouts have tended to be less healthy. In response to consumer concern some UK supermarkets voluntarily committed to removing less healthy food from their checkouts.