The Ocular Surface and the Anterior Segment of the Eye in the Pseudoexfoliation Syndrome: A Comprehensive Review.

Pseudoexfoliation syndrome (PXS) is an age-related fibrillopathy where fibrillar exfoliation material accumulates and deposits in ocular and extra-ocular tissue. Within the eye, this substance accumulates on the ocular surface and in the anterior segment of the eye, impacting ocular structures such as the conjunctiva, Tenon's capsule, sclera, cornea, iris, ciliary body, trabecular meshwork, and lens. This review aims to collate the current literature on how each anatomical part of the eye is affected by PXS, with a strong focus on molecular changes.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches.

Co-selection for antibiotic resistance by environmental contaminants.

The environment is increasingly recognised as a hotspot for the selection and dissemination of antibiotic resistant bacteria and antibiotic resistance genes. These can be selected for by antibiotics and non-antibiotic agents (such as metals and biocides), with the evidence to support this well established by observational and experimental studies. However, there is emerging evidence to suggest that plant protection products (such as herbicides), and non-antibiotic drugs (such as chemotherapeutic agents), can also co-select for antibiotic resistance.

Transient cortical beta-frequency oscillations associated with contextual novelty in high density mouse EEG.

Beta-frequency oscillations (20-30 Hz) are prominent in both human and rodent electroencephalogram (EEG) recordings. Discrete epochs of beta (or Beta2) oscillations are prevalent in the hippocampus and other brain areas during exploration of novel environments. However, little is known about the spatial distribution and temporal relationships of beta oscillations across the cortex in response to novel contexts.

Practitioner, patient and public views on the acceptability of mobile stroke units in England and Wales: A mixed methods study.

Background: Evidence for Mobile Stroke Units (MSUs) demonstrates that onset to treatment times for intravenous thrombolysis can be reduced and access to mechanical thrombectomy might be improved. Despite growing use of MSUs internationally, to date there have been no studies in NHS England and NHS Wales exploring the acceptability of MSUs to clinicians, patient and public representatives and other key stakeholders, which are important when considering potential feasibility and implementation.

Methods: This study used a mixed methods design with a cross-sectional survey and qualitative workshops and interviews between October 2023 to May 2024.

Evaluating the Cost-Effectiveness of Antenatal Screening for Major Structural Anomalies During the First Trimester of Pregnancy: A Decision Model.

Objective: To assess the cost-effectiveness of modifying current antenatal screening by adding first trimester structural anomaly screening to standard of care second trimester anomaly screening.

Design: Health economic decision model.

Setting: National Health Service (NHS) in England and Wales.

A face-to-face survey on the practice of ophthalmic clinicians in the management of dry eye disease in patients undergoing cataract surgery.

Introduction: Dry eye disease (DED) can impact the accuracy of biometry measurements prior to cataract surgery (CS), influence visual performance post-CS, and can be exacerbated by CS. We performed a survey to evaluate the DED practice of clinicians directly caring for CS patients.

Design: Prospective face-to-face survey.

Antenatal pelvic floor muscle exercise intervention led by midwives in England to reduce postnatal urinary incontinence: APPEAL feasibility and pilot randomised controlled cluster trial.

Objectives: To assess the feasibility of an intervention of midwifery support for antenatal pelvic floor muscle exercises (PFME) to prevent postnatal urinary incontinence (UI).

Design: Feasibility and pilot cluster randomised controlled trial. Clusters were community midwifery teams.

Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.

Oxidised Apolipoprotein Peptidome Characterises Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.

Association of classroom-level stressors with psychological distress in teachers.

Background: Poor mental health is highly prevalent among schoolteachers. Different occupational, contextual and personal factors have been identified as sources of their psychological distress.

Aims: To explore the association of classroom-level variables with teachers' mental health over the course of an academic year.

Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.

Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals.

Jargon and Readability in Plain Language Summaries of Health Research: Cross-Sectional Observational Study.

Background: The idea of making science more accessible to nonscientists has prompted health researchers to involve patients and the public more actively in their research. This sometimes involves writing a plain language summary (PLS), a short summary intended to make research findings accessible to nonspecialists. However, whether PLSs satisfy the basic requirements of accessible language is unclear.

A UK population-based case-control study of blood tests before cancer diagnosis in patients with non-specific abdominal symptoms.

Background: Abnormal results in commonly used primary care blood tests could be early markers of cancer in patients presenting with non-specific abdominal symptoms.

Methods: Using linked data from the UK Clinical Practice Research Datalink (CPRD) and national cancer registry we compared blood test use and abnormal results from the 24-months pre-diagnosis in 10,575 cancer patients (any site), and 52,875 matched-controls aged ≥30 presenting, with abdominal pain or bloating to primary care.

Results: Cancer patients had two-fold increased odds of having a blood test (odds ratio(OR):1.

A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.

Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei profiles from 391 disease-case and control brains, we report 13,939 genes whose expression correlated with genetic variation, of which 16.7-40.

Cognitive reserve and its impact on cognitive and functional abilities, physical activity and quality of life following a diagnosis of dementia: longitudinal findings from the Improving the experience of Dementia and Enhancing Active Life (IDEAL) study.

Background: The concept of cognitive reserve may explain inter-individual differences in susceptibility to neuropathological changes. Studies suggest that experiences over a lifetime impact on cognitive reserve, and it is hypothesised that following a dementia diagnosis, greater reserve levels are linked to accelerated disease progression.

Objective: To investigate the longitudinal impact of cognitive reserve on cognitive and functional abilities, physical activity and quality of life in people with dementia.

Multimorbidity clusters and their associations with health-related quality of life in two UK cohorts.

Background: Identifying clusters of multiple long-term conditions (MLTCs), also known as multimorbidity, and their associated burden may facilitate the development of effective and cost-effective targeted healthcare strategies. This study aimed to identify clusters of MLTCs and their associations with long-term health-related quality of life (HRQoL) in two UK population-based cohorts.

Methods: Age-stratified clusters of MLTCs were identified at baseline in UK Biobank (n = 502,363, 54.

COLOFIT: Development and Internal-External Validation of Models Using Age, Sex, Faecal Immunochemical and Blood Tests to Optimise Diagnosis of Colorectal Cancer in Symptomatic Patients.

Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death.

Aim: To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations.

Methods: We included all adults (≥ 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT.

Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study.

Aims: To assess outcomes of oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c), where specific treatment guidance is limited.

Materials And Methods: Using hospital-linked UK primary care records (Clinical Practice Research Datalink; 2004-2020), we identified 7084 people with a pancreatic condition (acute pancreatitis, chronic pancreatitis, pancreatic cancer and haemochromatosis) preceding diabetes diagnosis (type 3c cohort), initiating oral glucose-lowering therapy (metformin, sulphonylureas, SGLT2-inhibitors, DPP4-inhibitors or thiazolidinediones), and without concurrent insulin treatment. We stratified by pancreatic exocrine insufficiency [PEI] (n = 5917 without PEI, 1167 with PEI) and matched to 97 227 type 2 diabetes (T2D) controls.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

High patient acceptance of immediately sequential bilateral cataract surgery (ISBCS) as part of a one-stop see-and-treat pathway within an innovative NHS cataract unit.

Background: Constituting ~0.5% of all NHS cataract operations, national provision of immediately sequential bilateral cataract surgery (ISBCS) is limited. Combining offering ISBCS within a novel one-stop see-and-treat (S&T) cataract pathway would offer patients the opportunity for two cataract operations in a single hospital visit.

Congenital hyperinsulinism in the Ukraine: a 10-year national study.

Introduction: Congenital Hyperinsulinism (CHI) has not been previously studied in Ukraine. We therefore aimed to elucidate the genetics, clinical phenotype, histological subtype, treatment and long-term outcomes of Ukrainian patients with CHI.

Methods: Forty-one patients with CHI were recruited to the Ukrainian national registry between the years 2014-2023.