Non-clinical and first-in-human characterization of ECC5004/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist.

Aims: GLP-1 receptor agonists (GLP-1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity. We performed non-clinical and first-in-human (FIH) evaluation of ECC5004/AZD5004, an oral small-molecule GLP-1 RA.

Materials And Methods: ECC5004 was profiled in cell lines overexpressing human GLP-1R, in glucose-stimulated insulin secretion (GSIS) assays in a human β-cell line and non-human primates (NHPs).

Analysing the behaviour change techniques in an effective food literacy program to inform future program design.

Aim: Food literacy programs aim to improve food related skills and knowledge and are selected Governments as a strategy to address dietary intakes at a community level. The purpose of this research is to identify behaviour change techniques in a food literacy program, which were assessed by the achievement of participant goals related to food literacy and dietary behaviour changes.

Methods: Consensus methods were applied to map behaviour change techniques to an adult food literacy program.

Laryngeal Vibrotactile Stimulation Is Feasible, Acceptable To People With Unexplained Chronic Cough.

Objectives: Unexplained chronic cough (UCC) is common and has significant impacts on quality of life. Ongoing cough can sensitize the larynx, increasing the urge to cough and perpetuating the cycle of chronic cough. Vibrotactile stimulation (VTS) of the larynx is a noninvasive stimulation technique that can modulate laryngeal somatosensory and motor activity.

Determining the Effectiveness of an Adult Food Literacy Program Using a Matched Control Group.

Objective: To determine the effect of Food Sensations for Adults on food literacy behaviors and selected dietary behaviors.

Methods: A quasi-experimental design using preprogram and postprogram questionnaires over 4 weeks with a control group (n = 75) matched for sex, age group, and socioeconomic disadvantage to program participants (n = 867). General linear mixed models assessed change in food literacy behavior frequency in 3 self-reported domains (plan and manage, selection, and preparation) and fruit and vegetable servings.

Anti-doping sciences, abjection and women's sport as a protected category.

In this article we explore the relationships amongst anti-doping sciences, 'abjection,' and the protection of 'women's' sport. We introduce three novel concepts: 'abjection bias,' 'abjection potential,' and 'intersectional abjection,' as tools with the potential to provide greater nuance to understanding the context for these contentious issues in contemporary sport. The debate concerning participation in women's sport-especially elite sport-of people who do not fit within traditional definition of 'women' is increasingly fraught with acrimony with anti-doping sciences often recruited as arbitrator.

Development of the Menu Assessment Scoring Tool (MAST) to Assess the Nutritional Quality of Food Service Menus.

Preventing the rise in obesity is a global public health priority. Neighbourhood environments can help or undermine people's efforts to manage their weight, depending on availability of nutritious and nutrient-poor 'discretionary' foods. The proportion of household food budgets spent on eating outside the home is increasing.

Sp3 is essential for normal lung morphogenesis and cell cycle progression during mouse embryonic development.

Members of the Sp family of transcription factors regulate gene expression via binding GC boxes within promoter regions. Unlike Sp1, which stimulates transcription, the closely related Sp3 can either repress or activate gene expression and is required for perinatal survival in mice. Here, we use RNA-seq and cellular phenotyping to show how Sp3 regulates murine fetal cell differentiation and proliferation.

High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone.

Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients.

IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance.

The cytokine interleukin-6 (IL-6) is involved in a diverse set of physiological processes. Traditionally, IL-6 has been thought of in terms of its inflammatory actions during the acute phase response and in chronic conditions such as rheumatoid arthritis and obesity. However, IL-6 is also an important signaling molecule during exercise, being acutely released from working muscle fibers with increased exercise duration, intensity, and muscle glycogen depletion.

Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria.

Background: Gram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population.

Methods: We perform an epidemiological and sequencing based analysis of Gram-negative bloodstream infections (327 isolates (296 successfully sequenced) from 287 patients) in children <18 years old between 2008 and 2018 in Oxfordshire, UK.

Versatile DIY Route for Incorporation of a Wide Range of Electrode Materials into Rotating Ring Disk Electrodes.

Rotating ring disk electrodes (RRDEs) are a powerful and versatile tool for mechanistically investigating electrochemical reactions at electrode surfaces, particularly in the area of electroanalysis and catalysis. Despite their importance, only limited electrode materials (typically glassy carbon, platinum, and gold) and combinations thereof are available commercially. In this work, we present a method employing three-dimensional (3D) printing in conjunction with machined brass components to produce housing, which can accommodate any electrode material in, .

A Novel Hypomorphic Mouse Model Implicates Apurinic/Apyrimidinic Endonuclease 1 in Oxidative DNA Damage Repair in Gastric Epithelial Cells.

Though best known for its role in oxidative DNA damage repair, apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that regulates multiple host responses during oxidative stress, including the reductive activation of transcription factors. As knockout of the APE1-encoding gene, , is embryonically lethal, we sought to create a viable model with generalized inhibition of APE1 expression. A hypomorphic (HM) mouse with decreased APE1 expression throughout the body was generated using a construct containing a neomycin resistance () cassette knocked into the site.

Patient Satisfaction with Virtual vs In-Person Voice Therapy.

Objective: To determine whether there is a difference in patient satisfaction between in-person and virtual voice therapy.

Methods: Patient satisfaction answers to the National Research Corporation (NRC) Health patient survey were retrieved for two separate 11 month periods. The first was for an in-person cohort, from April 2019 to February 2020.

The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages.

Immaturity of alveolar macrophages (AMs) around birth contributes to the susceptibility of newborns to lung disease. However, the molecular features differentiating neonatal and mature, adult AMs are poorly understood. In this study, we identify the unique transcriptomes and enhancer landscapes of neonatal and adult AMs in mice.

The Validation and Improvement of a Food Literacy Behavior Checklist for Food Literacy Programs.

Food literacy is a multidimensional construct required to achieve diet quality. The Food Sensations for Adults (FSA) program aims to improve the food literacy of low to middle-income adults living in Western Australia and is funded by the Western Australian Department of Health. The original published behavior checklist used to measure change in food literacy has been revised based on experience of the facilitators and the iterative development of the program.

Transmission of community- and hospital-acquired SARS-CoV-2 in hospital settings in the UK: A cohort study.

Background: Nosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. Identifying the risk factors and drivers for these nosocomial transmissions is critical for infection prevention and control interventions. The main aim of our study was to quantify the relative importance of different transmission pathways of SARS-CoV-2 in the hospital setting.

Multiple Copies of in Paraburkholderia unamae Regulate Flagellar Gene Expression, Motility, and Biofilm Formation.

FlhDC is a heterohexameric complex that acts as a master regulator of flagellar biosynthesis genes in numerous bacteria. Previous studies have identified a single operon encoding this complex. However, we found that two loci are present throughout , and two additional copies are also present in Paraburkholderia unamae.

Effectiveness of Foodbank Western Australia's for Adults Food Literacy Program in Regional Australia.

Background: for Adults, funded by the Western Australian Department of Health, is a four-week nutrition education program focused on food literacy, with demonstrated success amongst Western Australians. In the last two years, 25% of programs have been in regional and remote areas and therefore the aim of this research is to explore the impact of the program in regional areas.

Methods: Participants answered validated pre- and post-questionnaires to assess change in food literacy behaviours (2016-2018).

Lack of pharmacokinetic interaction between the HIV-1 maturation inhibitor GSK3640254 and combination oral contraceptives in healthy women.

Aims: GSK3640254 is a next-generation maturation inhibitor likely to be coadministered with combined oral contraceptives in HIV-positive women.

Methods: This phase I, open-label, 1-way study assessed pharmacokinetic and pharmacodynamic interactions of GSK3640254 200 mg and ethinyl oestradiol 0.03 mg/levonorgestrel 0.

An analysis of the incidence, causes and preventative approaches to gram-negative bloodstream infections of hepatopancreatobiliary origin.

Background: Gram-negative bloodstream infection (GNBSI) is a threat to public health in terms of mortality and antibiotic resistance. The hepatopancreatobiliary (HPB) cohort accounts for 15%-20% of GNBSI, yet few strategies have been explored to reduce HPB GNBSI.

Aim: To identify clinical factors contributing to HPB GNBSI and strategies for its prevention.