Developing a behaviour change intervention using information about greenhouse gas emissions to reduce liquid antibiotic prescribing.

Introduction: The determinants of antimicrobial prescribing often involve social influence, which can be harnessed through behaviour change techniques (BCTs). While previous studies have used BCTs to address antimicrobial resistance, there is a lack of evidence regarding their application to address climate change-related issues in antibiotic prescribing. This study aimed to develop a behaviour change intervention (BCI) using information about greenhouse gas emissions to reduce liquid antibiotic prescribing.

Targeted exonic sequencing identifies novel variants in a cerebral small vessel disease cohort.

Background And Aims: Cerebral small vessel diseases (CSVDs) are a set of conditions that affect the small blood vessels in the brain and can cause severe neurological pathologies such as stroke and vascular dementia. The most common monogenic CSVD is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which is caused by mutations in NOTCH3. However, only 15-20% of CADASIL cases referred for genetic testing have pathogenic mutations in NOTCH3.

Sirtuin Proteins and Memory: A Promising Target in Alzheimer's Disease Therapy?

Sirtuins (SIRTs), nicotine adenine dinucleotide (+)-dependent histone deacetylases, have emerged as critical regulators in many signalling pathways involved in a wide range of biological processes. Currently, seven mammalian SIRTs have been characterized and are found across a number of cellular compartments. There has been considerable interest in the role of SIRTs in the brain due to their role in a plethora of metabolic- and age-related diseases, including their involvement in learning and memory function in physiological and pathophysiological conditions.

Obesity at the age of 4-5 related to asthma diagnosis in later childhood: A longitudinal study using linked routinely collected data from Wales.

Introduction: Obesity and asthma are two of the most common childhood conditions and their prevalence have increased over the last decades. Several cross-sectional studies provide strong evidence for a positive association between these two conditions. However, few longitudinal studies have examined the temporal relationship between them.

Residential mobility amongst children and young people in Wales: A longitudinal study using linked administrative records.

Background: Child poverty remains a major global concern and a child's experience of deprivation is heavily shaped by where they live and the stability of their local neighbourhood. This study examines frequencies and patterns of residential mobility in children and young people (CYP) at a population level using novel geospatial techniques to assess how often their physical environment changes and to identify geographical variations in social mobility.

Methods: We used routinely collected administrative records held in the Secure Anonymised Information Linkage (SAIL) Databank for CYP aged under 18 years living in Wales between 2012 and 2022.

Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis.

Among the intrathecal inflammatory niches where compartmentalized inflammation persists and plays a pivotal role in progressive multiple sclerosis (MS), choroid plexus (CP) has recently received renewed attention. To better characterize the neuropathological/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post-mortem pathologically confirmed MS and 10 healthy donors, using immunochemistry/immunofluorescence and in-situ sequencing. Significant inflammation was detected in the CP of 21 out of the 40 MS cases (52%).

PathVar: A Customisable NGS Variant Calling Algorithm Implicates Novel Candidate Genes and Pathways in Hemiplegic Migraine.

The exponential growth of next-generation sequencing (NGS) data requires innovative bioinformatics approaches to unravel the genetic underpinnings of diseases. Hemiplegic migraine (HM), a debilitating neurological disorder with a genetic basis, is one such condition that warrants further investigation. Notably, the genetic heterogeneity of HM is underscored by the fact that approximately two-thirds of patients lack pathogenic variants in the known causal ion channel genes.

Understanding variations in the built environment over time to inform longitudinal studies of young children's physical activity behaviour - The BEACHES project.

We know relatively little about the role the neighbourhood built environment plays in promoting young children's physical activity, particularly its longitudinal effect either through repeated exposure to the same environment or through change in exposure by moving from one neighbourhood to another. This study characterised the neighbourhood environment of young children in the PLAYCE cohort study over three timepoints from 2015 to 2023. There were statistically significant differences in built environment attributes between timepoints and across socio-economic status, however they did not represent practically significant differences.

Clinical and neuroradiological spectrum of biallelic variants in NOTCH3.

Background: NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), patients with biallelic variants in NOTCH3 are extremely rare and not well characterised.

Identification of Polymorphisms in EAAT1 Glutamate Transporter Gene Associated with Reduced Migraine Risk.

Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: , , and .

Digital Pathology Identifies Associations between Tissue Inflammatory Biomarkers and Multiple Sclerosis Outcomes.

Background: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping.

Aims: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS.

A bioadhesive pacing lead for atraumatic cardiac monitoring and stimulation in rodent and porcine models.

Current clinically used electronic implants, including cardiac pacing leads for epicardial monitoring and stimulation of the heart, rely on surgical suturing or direct insertion of electrodes to the heart tissue. These approaches can cause tissue trauma during the implantation and retrieval of the pacing leads, with the potential for bleeding, tissue damage, and device failure. Here, we report a bioadhesive pacing lead that can directly interface with cardiac tissue through physical and covalent interactions to support minimally invasive adhesive implantation and gentle on-demand removal of the device with a detachment solution.

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression.

Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL.

Outcome-based Risk Assessment of Non-HLA Antibodies in Heart Transplantation: A Systematic Review.

Background: Current monitoring after heart transplantation (HT) employs repeated invasive endomyocardial biopsies (EMB). Although positive EMB confirms rejection, EMB fails to predict impending, subclinical, or EMB-negative rejection events. While non-human leukocyte antigen (non-HLA) antibodies have emerged as important risk factors for antibody-mediated rejection after HT, their use in clinical risk stratification has been limited.

Adhesive anti-fibrotic interfaces on diverse organs.

Implanted biomaterials and devices face compromised functionality and efficacy in the long term owing to foreign body reactions and subsequent formation of fibrous capsules at the implant-tissue interfaces. Here we demonstrate that an adhesive implant-tissue interface can mitigate fibrous capsule formation in diverse animal models, including rats, mice, humanized mice and pigs, by reducing the level of infiltration of inflammatory cells into the adhesive implant-tissue interface compared to the non-adhesive implant-tissue interface. Histological analysis shows that the adhesive implant-tissue interface does not form observable fibrous capsules on diverse organs, including the abdominal wall, colon, stomach, lung and heart, over 12 weeks in vivo.

Children and young people's body mass index measures derived from routine data sources: A national data linkage study in Wales.

Background: Routine monitoring of Body Mass Index (BMI) in general practice, and via national surveillance programmes, is essential for the identification, prevention, and management of unhealthy childhood weight. We examined and compared the presence and representativeness of children and young people's (CYPs) BMI recorded in two routinely collected administrative datasets: general practice electronic health records (GP-BMI) and the Child Measurement Programme for Wales (CMP-BMI), which measures height and weight in 4-5-year-old school children. We also assessed the feasibility of combining GP-BMI and CMP-BMI data for longitudinal analyses.

Developing oral health services for people experiencing severe and multiple disadvantage: a case study from Southwest England.

People experiencing severe and multiple disadvantage (SMD) have disproportionately high levels of dental disease and tooth loss but have limited access to dental care. This paper presents an evidence-based case study of co-designing, implementing, evaluating and refining a community dental clinic for people experiencing SMD in the Southwest of England. It shares challenges, lessons, and solutions.

Unravelling the Genetic Landscape of Hemiplegic Migraine: Exploring Innovative Strategies and Emerging Approaches.

Migraine is a severe, debilitating neurovascular disorder. Hemiplegic migraine (HM) is a rare and debilitating neurological condition with a strong genetic basis. Sequencing technologies have improved the diagnosis and our understanding of the molecular pathophysiology of HM.

CpG methylation changes in human mesenchymal and neural stem cells in response to in vitro niche modifications.

Stem cell therapies hold promise in addressing the burden of neurodegenerative diseases with human embryonic neural stem cells (hNSC-H9s) and bone marrow-derived human mesenchymal stem cells (hMSCs) as viable candidates. The induction of hMSC neurospheres (hMSC-IN) generate a more lineage-restricted common neural progenitor-like cell population, potentially tunable by heparan sulfate proteoglycans (HSPGs). We examined CpG (5 mC) site methylation patterns using Illumina Infinium 850 K EPIC arrays in hNSC-H9, hMSCs and hMSC-IN cultures with HSPG agonist heparin at early and late phases of growth.

Is obesity more likely among children sharing a household with an older child with obesity? Cross-sectional study of linked National Child Measurement Programme data and electronic health records.

Background/objectives: We identified household members from electronic health records linked to National Child Measurement Programme (NCMP) data to estimate the likelihood of obesity among children living with an older child with obesity.

Methods: We included 126 829 NCMP participants in four London boroughs and assigned households from encrypted Unique Property Reference Numbers for 115 466 (91.0%).

Improving the strategy to identify historical military remains: a literature review and Y-STR meta-analysis.

Unlabelled: The identification of historical military remains by Unrecovered War Casualties-Army (UWC-A) currently relies on Y-chromosome Short Tandem Repeat (Y-STR) testing when maternal relatives are not available, or when a mitochondrial DNA match does not provide sufficient certainty of identification. However, common Y-STR profiles (using Yfiler™) between sets of remains or families often prevent identification. To resolve these cases, an investigation of additional Y-DNA markers is needed for their potential inclusion into the DNA identification strategy.

Epigenetic Regulation in Schizophrenia: Focus on Methylation and Histone Modifications in Human Studies.

Despite extensive research over the last few decades, the etiology of schizophrenia (SZ) remains unclear. SZ is a pathological disorder that is highly debilitating and deeply affects the lifestyle and minds of those affected. Several factors (one or in combination) have been reported as contributors to SZ pathogenesis, including neurodevelopmental, environmental, genetic and epigenetic factors.