Optimizing experimental designs for model selection of ion channel drug-binding mechanisms.

The rapid delayed rectifier current carried by the human Ether-à-go-go-Related Gene (hERG) channel is susceptible to drug-induced reduction, which can lead to an increased risk of cardiac arrhythmia. Establishing the mechanism by which a specific drug compound binds to hERG can help reduce uncertainty when quantifying pro-arrhythmic risk. In this study, we introduce a methodology for optimizing experimental voltage protocols to produce data that enable different proposed models for the drug-binding mechanism to be distinguished.

The Sole Essential Low Molecular Weight Tropomyosin Isoform of Caenorhabditis elegans Is Essential for Pharyngeal Muscle Function.

Tropomyosin is an actin-binding protein that plays roles ranging from regulating muscle contraction to controlling cytokinesis and cell migration. The simple nematode Caenorhabditis elegans provides a useful model for studying the core functions of tropomyosin in an animal, having a relatively simple anatomy and a single tropomyosin gene, lev-11, that produces seven isoforms. Three higher molecular weight isoforms regulate the contraction of body wall and other muscles, but comparatively less is known of the functions of four lower molecular weight isoforms (LEV-11C, E, T, U).

Humus gnosis: soil fertility, research and funding in the life of Sir Albert Howard.

Sir Albert Howard helped popularize the idea of translating 'Eastern' practice into 'Western' science in the field of agriculture. His approach to composting has been foundational to organic farming and counterposed with the field of agricultural chemistry. This depiction of feuding ideologies - organic versus chemical - is based largely on Howard's opposition to the fragmentation of scientific knowledge and its products, especially artificial fertilizer.

Illness risk representations underlying women's breast cancer risk appraisals: A theory-informed qualitative analysis.

Objectives: This study assessed the utility of Cameron's Illness Risk Representation (IRR) framework in understanding how women interpret their breast cancer risk after receiving a clinically derived estimate.

Design: Secondary qualitative analysis of two studies within the BC-Predict trial, using semi-structured telephone interviews with women aged 47-74 who received breast cancer risk estimates via population screening.

Methods: Forty-eight women were informed of their 10-year breast cancer risk (low (<1.

Lengthy Shifts and Decision Fatigue in Out-of-Hours Primary Care: A Qualitative Study.

Rationale: Demands on healthcare workers are high: services are stretched, shifts are long and healthcare professionals (HCPs) regularly work lengthy periods without a break. Spending time continuously 'on task' changes decision-making in predictable ways, as described by the 'decision fatigue' phenomenon where decision-makers progressively shift towards making less cognitively effortful decisions as the time worked without a break increases. This phenomenon has been observed repeatedly in large quantitative observational studies, however, individual healthcare workers' experiences have not been explored.

Electrotaxis disrupts patterns of cell-cell interactions of human corneal epithelial cells in vitro.

Electrotaxis, the process by which eukaryotic cells establish a polarity and move directionally along an electric field, is a well-studied mechanism to steer the migration of cells in vitro and in vivo. While the influence of an electric field on single cells in culture is well-documented, the influence of the electric field on cell-cell interactions has not been well studied. In this work, we quantify the length, duration and number of cell-cell interactions during electrotaxis of human corneal epithelial cells and compare the properties of these interactions with those arising in the absence of an electric field.

Access and pricing of medicines for patients with rare diseases in the European Union: an industry perspective. A 2025 update.

Introduction: In a previous publication, we provided an overview of the current situation of patient access to orphan drugs in the European Union (EU), of the evolving rare disease policy landscape and recommendations for areas of improvement throughout the lifecycle of orphan drugs. This article aims to provide an update on evolving new policies impacting access to orphan drugs in the European Union from a health technology developers perspective.

Areas Covered: We provide an update of the emerging competitiveness gap in the pharmaceutical sector between the EU and the United States.

Optimal Weight Loss of Pink Pigeon (Nesoenas mayeri) Eggs During Incubation.

Incubation of pink pigeon (Nesoenas mayeri) eggs under foster doves is an important element of the captive breeding program for this threatened species, and determining optimal species-specific incubation conditions could help to maximize hatchability. We analyzed 7 years of records (n = 104 eggs) from a captive collection to investigate whether the existing guideline for optimal total weight loss of 15% is appropriate for the pink pigeon. Successfully hatched eggs lost on average 14% of their initial mass during incubation, while a weight loss of 15.

From cytoplasm to lumen-mapping the free pools of protein subunits of three photosynthetic complexes using quantitative mass spectrometry.

The phycobilisome (PBS) captures light energy and transfers it to photosystem I (PSI) and photosystem II (PSII). Which and how many copies of protein subunits in PBSs, PSI, and PSII remain unbound in thylakoids are unknown. Here, quantitative mass spectrometry (QMS) was used to quantify substantial pools of free extrinsic subunits of PSII and PSI.

The Effect of Leisure-Time Exercise on Mental Health Among Adults: A Bibliometric Analysis of Randomized Controlled Trials.

Adequate levels of leisure-time exercise (LTE) are associated with mental health benefits. Despite increased research in recent years through randomized controlled trials (RCTs), a systematic literature review summarizing these findings is lacking. Here, we examined publication trends, impact, and research gaps regarding LTE's effects on mental health in the form of a bibliometric analysis.

Footwear Choice and Locomotor Health Throughout the Life Course: A Critical Review.

In this paper, we review and discuss epidemiological and experimental evidence on the effects of daily footwear on gait and life-long health. We consider different types of footwear, including "minimal shoes", and their design features, comparing them to barefoot walking, with a focus on overall gait and the function of the heel pad. Narrative review.

The Clinical Nurse Specialist as the Manager of the Family Medicine Clinic: A Hybrid Solution Between Four Major Commonwealth Realms.

There exist several interconnected issues that hinder the development of family medicine in Commonwealth realms such as the United Kingdom, Canada, New Zealand, and Australia. These issues affect both the medical and nursing professions. Family physicians, in most countries including the United Kingdom, are not considered "specialists" and are called "general practitioners" instead.

The Creation of a Systematic Framework to Assess Dog Laws and Their Relationship to Societal Changes in the United Kingdom.

Dogs and humans have shared a complex relationship throughout history, with law serving as an important tool to manage dogs' integration into human societies. As dogs increasingly become regarded as family members in Western countries, and as similar trends emerge globally, it is vital to understand how legislation balances the interests of stakeholders. Existing studies often focus on localised disputes and fragmented legal areas, limiting understanding of how dog-related laws interact and potentially conflict.

Impact of Phage Therapy on Pseudomonas syringae pv. syringae and Plant Microbiome Dynamics Through Coevolution and Field Experiments.

Bacteriophages (phages) are viruses that infect and lyse bacteria and have the potential for controlling bacterial diseases. Isolation of phages targeting the cherry pathogen Pseudomonas syringae pv. syringae (Pss) led to five distinct phage genotypes.

An environmental scan of current mentorship: fostering the next generations in cardiothoracic surgery in the UK.

Objectives: Mentorship is critical to the professional development of junior colleagues in cardiothoracic surgery. Despite its presumed importance and frequent discussion, its impact within cardiothoracic surgery training remains uncharacterised within the UK. We aimed to evaluate mentorship experience and identify gaps in the system of mentorship education.

Bradykinin's carbamylation as a mechanistic link to impaired wound healing in patients with kidney dysfunction.

Background: Uremic impairment of wound healing is a well-established phenomenon, however the etiology of this condition continues to be a medical enigma. Carbamylation, posttranslational modification (PTM) occurring with high frequency in uremic milieu, is known to have impact on structural and functional properties of proteins and peptides. Herein we show that carbamylation of the members of kinin-kallikrein system, that play an essential role in wound healing process, results in its aberrant functionality and impedes the complex process of tissue regeneration in uremic patients.

Modifiable risk factors of vaccine hesitancy: insights from a mixed methods multiple population study combining machine learning and thematic analysis during the COVID-19 pandemic.

Background: Vaccine hesitancy, the delay in acceptance or reluctance to vaccinate, ranks among the top threats to global health. Identifying modifiable factors contributing to vaccine hesitancy is crucial for developing targeted interventions to increase vaccination uptake.

Methods: This mixed-methods multiple population study utilized gradient boosting machines and thematic analysis to identify modifiable predictors of vaccine hesitancy during the COVID-19 pandemic.

Hall Crown Technique Use Among USA Pediatric Dentists.

To examine the provider acceptance and clinical usage of the Hall technique (HT) among active pediatric dental members of the American Academy of Pediatric Dentistry ([AAPD] pediatric dentist member). A 19-item web-based survey was distributed to all AAPD pediatric dentist members using Qualtrics. This survey-based questionnaire was available from January 2024 to March 2024, included questions regarding demographics, and explored various clinical scenarios and the likelihood of a clinician to utilize the HT.

Personalized predictions to identify individuals most likely to achieve 10% weight loss with a lifestyle intervention.

Objective: The objective of this study is to generate an algorithm for making predictions about individual treatment responses to a lifestyle intervention for weight loss to maximize treatment effectiveness and public health impact.

Methods: Using data from Action for Health in Diabetes (Look AHEAD), a national, multisite clinical trial that ran from 2001 to 2012, and machine-learning techniques, we generated predicted individual treatment effects for each participant. We tested for heterogeneity in treatment response and computed the degree to which treatment effects could be improved by targeting individuals most likely to benefit.

Adaptive locomotion of active solids.

Active systems composed of energy-generating microscopic constituents are a promising platform to create autonomous functional materials that can, for example, locomote through complex and unpredictable environments. Yet coaxing these energy sources into useful mechanical work has proved challenging. Here we engineer active solids based on centimetre-scale building blocks that perform adaptive locomotion.

High temporal variability not trend dominates Mediterranean precipitation.

State-of-the-art climate models project a substantial decline in precipitation for the Mediterranean region in the future. Supporting this notion, several studies based on observed precipitation data spanning recent decades have suggested a decrease in Mediterranean precipitation, with some attributing a large fraction of this change to anthropogenic influences. Conversely, certain researchers have underlined that Mediterranean precipitation exhibits considerable spatiotemporal variability driven by atmospheric circulation patterns maintaining stationarity over the long term.

Injury patterns and patient outcomes of abdominal trauma in the elderly population: a 5-year experience of a Major Trauma Centre.

Introduction: The management of abdominal trauma in older patients is challenging due to preexisting comorbidities, impaired physiology, frailty and atypical clinical presentations. Few studies focus on the characteristics of abdominal trauma in older populations.

Methods: A retrospective service evaluation was conducted during the period January 2017 - December 2022 at University Hospital Southampton, the designated Major Trauma Centre (MTC) of Wessex Trauma Network in the United Kingdom.

Impact of treatment for adolescent and young adults with essential thrombocythemia and polycythemia vera.

Essential thrombocythemia (ET) and polycythemia vera (PV) are rare in adolescent and young adult (AYA). These conditions, similar to those in older patients, are linked with thrombotic complications and the potential progression to secondary myelofibrosis (sMF). This retrospective study of ET and PV patients diagnosed before age 25 evaluated complication rates and impact of cytoreductive drugs on outcomes.

Understanding hospital activity and outcomes for people with multimorbidity using electronic health records.

As the prevalence of multimorbidity grows, provision of effective healthcare is more challenging. Both multimorbidity and complexity in healthcare delivery may be associated with worse outcomes. We studied consecutive, unique emergency non-surgical hospitalisations for patients over 50 years old to three hospitals in Scotland, UK between 2016 and 2024 using linked primary care and hospital records to define multimorbidity (2 + long-term conditions), and timestamped hospital electronic health record (EHR) contacts with nursing and rehabilitation providers to describe intensity of inpatient care.

An osteobiography of a celebrity chimpanzee reflects the changing roles of modern zoos.

The role of zoos has shifted markedly from their origins in the nineteenth century to the present day. Long-lived and charismatic individual animals have been central to zoological collections, as priorities have changed from a primary focus on entertainment to a greater emphasis on education, conservation, research and welfare. Here, we construct the osteobiography of a celebrity chimpanzee to highlight the changing practices of modern zoos over a near half-century timescale.