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Obesity and associated comorbidities are a major health burden, and novel therapeutics to help treat obesity are urgently needed. There is increasing evidence that targeting the amylin receptors (AMYRs), heterodimers of the calcitonin G protein-coupled receptor (CTR) and receptor activity-modifying proteins, improves weight control and has the potential to act additively with other treatments such as glucagon-like peptide-1 receptor agonists. Recent data indicate that AMYR agonists, which can also independently activate the CTR, may have improved efficacy for treating obesity, even though selective activation of CTRs is not efficacious. AM833 (cagrilintide) is a novel lipidated amylin analog that is undergoing clinical trials as a nonselective AMYR and CTR agonist. selleck inhibitor In the current study, we have investigated the pharmacology of AM833 across 25 endpoints and compared this peptide with AMYR selective and nonselective lipidated analogs (AM1213 and AM1784), and the clinically used peptide agonists pramlintide (AMYR selective) and salmon CT (nonselective). We also profiled human CT and rat amylin as prototypical selective agonists of CTR and AMYRs, respectively. Our results demonstrate that AM833 has a unique pharmacological profile across diverse measures of receptor binding, activation, and regulation. SIGNIFICANCE STATEMENT AM833 is a novel nonselective agonist of calcitonin family receptors that has demonstrated efficacy for the treatment of obesity in phase 2 clinical trials. This study demonstrates that AM833 has a unique pharmacological profile across diverse measures of receptor binding, activation, and regulation when compared with other selective and nonselective calcitonin receptor and amylin receptor agonists. The present data provide mechanistic insight into the actions of AM833.Adolescents are an increasing proportion of low and middle-income country populations. Their coming of age is foundational for health behaviour, as well as social and productive citizenship. We mapped intervention areas for adolescent sexual and reproductive health, including HIV, mental health and violence prevention to sectors responsible for them using a framework that highlights settings, roles and alignment. Out of 11 intervention areas, health is the lead actor for one, and a possible lead actor for two other interventions depending on the implementation context. All other interventions take place outside of the health sector, with the health sector playing a range of bilateral, trilateral supporting roles or in several cases a minimal role. Alignment across the sectors varies from indivisible, enabling or reinforcing to the other extreme of constraining and counterproductive. Governance approaches are critical for brokering these varied relationships and interactions in multisectoral action for adolescent health, to understand the context of such change and to spark, sustain and steer it.

In low- and middle-income countries, children experience multiple risks for delayed development. We evaluated a multicomponent, group-based early child development intervention including behavioural recommendations on responsive stimulation, nutrition, water, sanitation, hygiene, mental health and lead exposure prevention.

We conducted a 9-month, parallel, multiarm, cluster-randomised controlled trial in 31 rural villages in Kishoreganj District, Bangladesh. Villages were randomly allocated to group sessions ('group'); alternating groups and home visits ('combined'); or a passive control arm. Sessions were delivered fortnightly by trained community members. The primary outcome was child stimulation (Family Care Indicators); the secondary outcome was child development (Ages and Stages Questionnaire Inventory, ASQi). Other outcomes included dietary diversity, latrine status, use of a child potty, handwashing infrastructure, caregiver mental health and knowledge of lead. Analyses were intention to treat. Dat, multicomponent interventions can be effective at improving child development outcomes in rural Bangladesh, and that they have the potential to be delivered at scale.

The trial is registered in ISRCTN (ISRCTN16001234).

The trial is registered in ISRCTN (ISRCTN16001234).

COVID-19 has changed the epidemiology of trauma. However, Taiwan is a country with a low COVID-19 threat, and people's daily lives have remained mostly unchanged during this period. The purpose of this study is to investigate whether the trend of trauma incidence and the service of trauma care is affected by the relatively minor COVID-19 pandemic in Taiwan.

A single-institute, retrograde cohort study.

An observational study based on the trauma registry of Chang Gung Memorial Hospital (CGMH).

Trauma patients presented to the emergency department of CGMH in the period of 1 January to 30 June 2020 (week 1 to week 26) were designated as the COVID-19 group, with 1980 patients in total. Patients of the same period in 2015-2019 were designated as the pre-COVID-19 group, with 10 334 patients overall.

The primary outcome is the incidence of trauma admission. Differences in trauma mechanism, severity, location and outcome were also compared in both groups.

A decrease in trauma incidence during March and April 2020 was noticed. Significant change (p<0.001) in trauma mechanisms was discovered, with decreased burn (5.8% vs 3.6%) and assault (4.8% vs 1.2%), and increased transport accidents (43.2% vs 47.2%) and suicide (0.2% vs 1.0%) in the COVID-19 cohort. A shift in injury locations was also found with a 5% decrement of workplace injuries (19.8% vs 14.8%, p<0.001).

The limited COVID-19 outbreak in Taiwan has led to a decreased incidence of trauma patients, and the reduction is mostly attributed to the decline in workplace injuries.

The limited COVID-19 outbreak in Taiwan has led to a decreased incidence of trauma patients, and the reduction is mostly attributed to the decline in workplace injuries.

Since its emergence in late 2019, SARS-CoV-2 has caused a global pandemic that has significantly challenged healthcare systems. Healthcare workers have previously been shown to have experienced higher rates of infection than the general population. We aimed to assess the extent of infection in staff working in our healthcare setting.

A retrospective analysis of antibody results, compared with staff demographic data, and exposure to patients with COVID-19 infection.

A large teaching hospital in the North West of England.

4474 staff in diverse clinical and non-patient facing roles who volunteered for SARS-CoV-2 antibody testing by the Roche Elecsys assay between 29 May and 4 July 2020.

Seroprevalence was 17.4%. Higher rates were seen in Asian/Asian British (OR 1.61, 95% CI 1.27 to 2.04) and Black/Black British (OR 2.08, 95% CI 1.25 to 3.45) staff. Staff working in any clinical location were more likely to be seropositive (OR 2.68, 95% 2.27 to 3.15). Staff were at an increased risk of seropositivity ass. This has implications for potential unrecorded transmission in both staff and patients.

Staff working in clinical areas where patients with COVID-19 were nursed were more likely to have detectable antibodies. The relationship between seropositivity in healthcare workers and the increase in 'per 100 COVID-19 bed-days' of the area in which they worked, although statistically significant, was weak, suggesting other contributing factors to the risk profile. Of staff with detectable antibodies and therefore evidence of prior infection, a quarter self-reported that they had experienced no compatible symptoms. This has implications for potential unrecorded transmission in both staff and patients.

People with progressive multiple sclerosis (PwPMS) report that they recognise the benefits of activity on their physical and psychological health but need support to achieve their physical activity goals. We aimed to systematically develop a theoretically informed intervention that would enable PwPMS to more readily engage in regular physical activity.

We used an intervention mapping approach to inform intervention development.

We conducted semistructured interviews with PwPMS and their families/carers and physiotherapists recruited from secondary care settings.

Fourteen PwPMS with an Expanded Disability Status Scale score of between 6 and 8 and 7 of their families/carers and 13 physiotherapists and 1 physiotherapy technician participated.

Interview data suggested that the development of supportive coaching relationships with physiotherapists could promote the ability of PwPMS to achieve a desirable and achievable physical activity plan. These interview data informed the prototype 'Lifestyle Exercisn achieved through the embedding of self-management principles in the design and delivery of the LEAP-MS intervention.

We have followed an inclusive, systematic and transparent process to develop the LEAP-MS intervention that enables detailed description of components, context and guiding principles to inform ongoing evaluation. Importantly, PwPMS expressed the need for autonomy in developing physical activity plans. This has been achieved through the embedding of self-management principles in the design and delivery of the LEAP-MS intervention.

To determine the extent and nature of changes in utilisation of healthcare services during COVID-19 pandemic.

Systematic review.

Eligible studies compared utilisation of services during COVID-19 pandemic to at least one comparable period in prior years. Services included visits, admissions, diagnostics and therapeutics. Studies were excluded if from single centres or studied only patients with COVID-19.

PubMed, Embase, Cochrane COVID-19 Study Register and preprints were searched, without language restrictions, until 10 August, using detailed searches with key concepts including COVID-19, health services and impact.

Risk of bias was assessed by adapting the Risk of Bias in Non-randomised Studies of Interventions tool, and a Cochrane Effective Practice and Organization of Care tool. Results were analysed using descriptive statistics, graphical figures and narrative synthesis.

Primary outcome was change in service utilisation between prepandemic and pandemic periods. Secondary outcome was the change s of reductions may help health systems reduce unnecessary care in the postpandemic recovery.

CRD42020203729.

CRD42020203729.

Workers at sea have high mortality, injuries and illnesses and work in a hazardous environment compared to ashore workers. The present study was designed to measure the incidence of occupational injuries and diseases among seafarers and quantify the contribution of differences in rank and job onboard on seafarers' diseases and injuries rates.

Descriptive epidemiological study.

This study's data were based on contacts (n=423) for medical requests from Compagnie Maritime d'Affrètement/Compagnie Générale Maritime (CMA-CGM) container ships to the Italian Telemedical Maritime Assistance Service in Rome from 2016 to 2019, supplemented by data on the estimated total at-risk seafarer population on container ships (n=13 475) over the study period.

Distribution of injuries by anatomic location and types of diseases across seafarers' ranks and worksites. We determined the incidence rate and incidence rate ratio (IRR) with a 95% CI.

The total disease rate was 25 per 1000 seafarer-years, and the overall injury rate was 6.