A Web-Based Tool to Assess Social Inclusion and Support Care Planning in Mental Health Supported Accommodation: Development and Preliminary Test Study.

Background: Individuals with severe mental illness living in supported accommodation are often socially excluded. Social inclusion is an important aspect of recovery-based practice and quality of life. The Social Inclusion Questionnaire User Experience (SInQUE) is a measure of social inclusion that has been validated for use with people with mental health problems.

The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence.

Background: Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.

Objectives: The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.

Methods: NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam.

Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices.

The cardiotoxicity risk of hydroxychloroquine (HCQ) and azithromycin (AZM) has been the subject of intensive research triggered by safety concerns in COVID-19 patients. HCQ and AZM have been associated with QT interval prolongation and drug-induced arrhythmias, however other cardiotoxicity mechanisms remain largely unexplored. Our group has pioneered the living heart slice preparation, an platform that maintains native cardiac tissue architecture and physiological electrical and contractile properties.

Spelling Errors in Brief Computer-Mediated Texts Implicitly Lead to Linearly Additive Penalties in Trustworthiness.

Background: Spelling errors in documents lead to reduced trustworthiness, but the mechanism for weighing the psychological assessment (i.e., integrative versus dichotomous) has not been elucidated.

It was not easy to identify the study design from the title and abstract of articles indexed as diagnostic (test) accuracy studies in EMBASE in 2012 and 2019.

Objective: To quantify use of shorthand description of research design in the titles and abstracts of diagnostic test accuracy studies, comparing 2012 and 2019.

Study Design And Setting: Joint examination, using pre-specified criteria, by two investigators of 320 randomly sampled articles indexed as "diagnostic (test) accuracy studies" in EMBASE in 2012 and 2019.

Results: The percentage of abstracts with shorthand descriptions of study design was 11% in 2012 and 15% in 2019, a difference of 4% (95% CI -3, 12).

Symptom scores in the diagnosis of pediatric cow's milk protein allergy: A systematic review.

Background: Cow's milk protein allergy (CMPA) is an immune-mediated allergic response to proteins in milk that is common in infants. Broad CMPA symptoms make diagnosis a challenge, particularly in primary care. Symptom scores may improve a clinician's awareness of symptoms, indicating a need for further testing.

Correction: Spelling Errors and Shouting Capitalization Lead to Additive Penalties to Trustworthiness of Online Health Information: Randomized Experiment With Laypersons.

[This corrects the article DOI: 10.2196/15171.].

Spelling Errors and Shouting Capitalization Lead to Additive Penalties to Trustworthiness of Online Health Information: Randomized Experiment With Laypersons.

Background: The written format and literacy competence of screen-based texts can interfere with the perceived trustworthiness of health information in online forums, independent of the semantic content. Unlike in professional content, the format in unmoderated forums can regularly hint at incivility, perceived as deliberate rudeness or casual disregard toward the reader, for example, through spelling errors and unnecessary emphatic capitalization of whole words (online shouting).

Objective: This study aimed to quantify the comparative effects of spelling errors and inappropriate capitalization on ratings of trustworthiness independently of lay insight and to determine whether these changes act synergistically or additively on the ratings.

Global shortage of neonatal and paediatric antibiotic trials: rapid review.

Objectives: There have been few clinical trials (CTs) on antibiotics that inform neonatal and paediatric drug labelling. The rate of unlicensed and off-label prescribing in paediatrics remains high. It is unclear whether the current neonatal and paediatric antibiotic research pipeline is adequate to inform optimal drug dosing.

Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor.

Biased agonism describes the ability of distinct G protein-coupled receptor (GPCR) ligands to stabilise distinct receptor conformations leading to the activation of different cell signalling pathways that can deliver different physiologic outcomes. This phenomenon is having a major impact on modern drug discovery as it offers the potential to design ligands that selectively activate or inhibit the signalling pathways linked to therapeutic effects with minimal activation or blockade of signalling pathways that are linked to the development of adverse on-target effects. However, the explosion in studies of biased agonism at multiple GPCR families in recombinant cell lines has revealed a high degree of variability on descriptions of biased ligands at the same GPCR and raised the question of whether biased agonism is a fixed attribute of a ligand in all cell types.

Plasma membrane localization of the μ-opioid receptor controls spatiotemporal signaling.

Differential regulation of the μ-opioid receptor (MOR), a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor, contributes to the clinically limiting effects of opioid analgesics, such as morphine. We used biophysical approaches to quantify spatiotemporal MOR signaling in response to different ligands. In human embryonic kidney (HEK) 293 cells overexpressing MOR, morphine caused a Gβγ-dependent increase in plasma membrane-localized protein kinase C (PKC) activity, which resulted in a restricted distribution of MOR within the plasma membrane and induced sustained cytosolic extracellular signal-regulated kinase (ERK) signaling.

Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.

Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates.

Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity.

This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology.