Evaluating Process and Outcomes of Public Involvement in Applied Health and Social Care Research: A Rapid Systematic Review.

Objective: Public Involvement (PI) in applied health and social care research has grown exponentially in the UK. This review aims to synthesise published UK evidence that evaluates the process and/or outcome(s) of PI in applied health and social care research to identify key contextual factors, effective strategies, outcomes and public partner experiences underpinning meaningful PI in research.

Methods: Following a pre-registered protocol, we systematically searched four databases and two key journals for studies conducted within the UK between January 2006 and July 2024.

Ultrasensitive Protein Aggregate Quantification Assays for Neurodegenerative Diseases on the Simoa Platform.

Nanoscale aggregates play a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. However, quantifying these aggregates in complex biological samples, such as biofluids and postmortem brain tissue, has been challenging due to their low concentration and small size, necessitating the development of methods with high sensitivity and specificity. Here, we have developed ultrasensitive assays utilizing the Quanterix Simoa platform to detect α-synuclein, β-amyloid and tau aggregates, including those with common posttranslational modifications such as truncation of α-synuclein and AT8 phosphorylation of tau aggregates.

Effects of initial peritoneal dialysis prescription on clinical outcomes in Japanese peritoneal dialysis patients: a cohort study.

Effects of the initial peritoneal dialysis (PD) prescription on clinical outcomes are unknown in Japan. We conducted a cohort study using data from Peritoneal Dialysis Outcomes and Practice Patterns Study. The patients were divided into two groups by the volume of the initial PD prescription (≤ 4 L/day or > 4 L/day).

Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach.

Introduction: Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods.

Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping.

Background: Fuchs endothelial corneal dystrophy (FECD) is the most common repeat-mediated disease in humans. It exclusively affects corneal endothelial cells (CECs), with ≤81% of cases associated with an intronic TCF4 triplet repeat (CTG18.1).

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant.

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members.

Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease.

Fuchs endothelial corneal dystrophy (FECD) is an age-related cause of vision loss, and the most common repeat expansion-mediated disease in humans characterised to date. Up to 80% of European FECD cases have been attributed to expansion of a non-coding CTG repeat element (termed CTG18.1) located within the ubiquitously expressed transcription factor encoding gene, TCF4.

A Proximity Complementation Assay to Identify Small Molecules That Enhance the Traffic of ABCA4 Misfolding Variants.

ABCA4-related retinopathy is the most common inherited Mendelian eye disorder worldwide, caused by biallelic variants in the ATP-binding cassette transporter ABCA4. To date, over 2200 ABCA4 variants have been identified, including missense, nonsense, indels, splice site and deep intronic defects. Notably, more than 60% are missense variants that can lead to protein misfolding, mistrafficking and degradation.

Home versus in-centre haemodialysis for people with kidney failure.

Background: Home haemodialysis (HHD) may be associated with important clinical, social or economic benefits. However, few randomised controlled trials (RCTs) have evaluated HHD versus in-centre HD (ICHD). The relative benefits and harms of these two HD modalities are uncertain.

Association of day-case rates with post COVID-19 recovery of elective laparoscopic cholecystectomy activity across England.

Introduction: The aim of this study was to investigate the safety of day-case laparoscopic cholecystectomy, and the association between day-case rates and, post the COVID-19 pandemic, recovery of activity to prepandemic levels for integrated care boards (ICBs) in England.

Methods: This was a retrospective observational study of the Hospital Episodes Statistics (HES) data set. Elective laparoscopic cholecystectomies for the period 1 January 2019 to 31 December 2022 were identified.

Practicalities of Cell Sorting.

Cell sorting is a technique commonly used in academic and biotechnology laboratories in order to separate out cells or particles of interest from heterogeneous populations. Cell sorters use the same principles as flow cytometry analyzers, but instead of cell populations passing to the waste of the instrument, they can be collected for further studies including DNA sequencing as well as other genomic, in vitro and in vivo experiments. This chapter aims to give an overview of cell sorting, the different types of cell sorters, details on how a cell sorter works, as well as protocols that are useful when embarking on a journey with cell sorting.

"You're sort of building community in a bigger way": exploring the potential of creative, nature-based activities to facilitate community connections.

Background: This paper explores the opportunities that creative, nature-based activities offer for mobilising social connections via community-centred approaches to improve individual and collective wellbeing.

Methods: The study involved ethnographic methods and data was gathered from a nature for wellbeing project implemented in a rural village in North East England.

Results: The findings indicate creative, nature-based activities delivered within an environment marked by an ethic of care and kindness enabled the project to engage with participants at individual and collective levels simultaneously, which enhanced the project's ability to mobilise community skills and assets, and affect connectedness, equity and control within social groups facing significant disadvantages.

Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity.

Blindness poses a growing global challenge, with approximately 26% of cases attributed to degenerative retinal diseases. While gene therapy, optogenetic tools, photosensitive switches, and retinal prostheses offer hope for vision restoration, these high-cost therapies will benefit few patients. Understanding retinal diseases is therefore key to advance effective treatments, requiring in vitro models replicating pathology and allowing quantitative assessments for drug discovery.

Factors associated with conversion from day-case to in-patient elective inguinal hernia repair surgery across England: an observational study using administrative data.

Purpose: Elective primary inguinal hernia repair surgery is increasingly being conducted as a day-case procedure. However, some patients planned for day-case surgery have to stay in hospital for at least one night. The aim of this study was to identify the factors associated with conversion from day-case to in-patient management for elective inguinal hernia repair surgery.

Proof-of-concept for multiple AON delivery by a single U7snRNA vector to restore splicing defects in ABCA4.

The high allelic heterogeneity in Stargardt disease (STGD1) complicates the design of intervention strategies. A significant proportion of pathogenic intronic ABCA4 variants alters the pre-mRNA splicing process. Antisense oligonucleotides (AONs) are an attractive yet mutation-specific therapeutic strategy to restore these splicing defects.

Cerebral organoids with chromosome 21 trisomy secrete Alzheimer's disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy.

Understanding the role of small, soluble aggregates of beta-amyloid (Aβ) and tau in Alzheimer's disease (AD) is of great importance for the rational design of preventative therapies. Here we report a set of methods for the detection, quantification, and characterisation of soluble aggregates in conditioned media of cerebral organoids derived from human iPSCs with trisomy 21, thus containing an extra copy of the amyloid precursor protein (APP) gene. We detected soluble beta-amyloid (Aβ) and tau aggregates secreted by cerebral organoids from both control and the isogenic trisomy 21 (T21) genotype.

RP2-Associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History in a Large Cohort of Female Carriers.

Purpose: RP2-associated retinopathy typically causes severe early onset retinitis pigmentosa (RP) in affected males. However, there is a scarcity of reports describing the clinical phenotype of female carriers. We tested the hypothesis that RP2 variants manifest in female carriers with a range of functional and anatomic characteristics.

Day-case and in-patient elective inguinal hernia repair surgery across England: an observational study of variation and outcomes.

Purpose: Elective primary inguinal hernia repair surgery is increasingly being conducted as a day-case procedure. However, in England there is evidence of wide variation in day-case rates across hospitals. Reducing the extent of this variation has the potential to support more efficient use of resources (e.

Multicentre registry analysis of incremental peritoneal dialysis incidence and associations with patient outcomes.

Background: Incremental peritoneal dialysis (PD) is increasingly advocated to reduce treatment burden and costs, with potential to better preserve residual kidney function. Global prevalence of incremental PD use is unknown and use in Australia and New Zealand has not been reported.

Methods: Binational registry analysis including incident adult PD patients in Australia and New Zealand (2007-2017), examining incidence of and outcomes associated with incremental PD (first recorded PD exchange volume <42 L/week (incremental) vs.

Associations of neutral pH, low-GDP peritoneal dialysis solutions with patient survival, transfer to haemodialysis and peritonitis.

Background: Peritoneal dialysis (PD) solutions containing low levels of glucose degradation products (GDPs) are associated with attenuation of peritoneal membrane injury and vascular complications. However, clinical benefits associated with neutral-pH, low-GDP (N-pH/L-GDP) solutions remain unclear.

Methods: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the associations between N-pH/L-GDP solutions and all-cause mortality, cause-specific mortality, transfer to haemodialysis (HD) for ≥30 days and PD peritonitis in adult incident PD patients in Australia and New Zealand between 1 January 2005 and 31 December 2020 using adjusted Cox regression analyses.

Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models.

The photoreceptor outer segment is a highly specialized primary cilium that is essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.