Academic Achievement of Children With Neurofibromatosis Type 1.

Background And Objectives: Learning difficulties are frequently reported in children with neurofibromatosis type 1 (NF1), yet little is known about the extent and predictors of their academic functions across ages. We aimed to examine the developmental patterns of academic achievement in these children from childhood to adolescence and how these patterns differ across demographic and NF1-related disease factors.

Methods: This cross-sectional study integrated data of 1512 children with NF1 (mean age, 11.

Higher order interaction analysis quantifies coordination in the epigenome revealing novel biological relationships in Kabuki syndrome.

Complex direct and indirect relationships between multiple variables, termed higher order interactions (HOIs), are characteristics of all natural systems. Traditional differential and network analyses fail to account for the omic datasets richness and miss HOIs. We investigated peripheral blood DNA methylation data from Kabuki syndrome type 1 (KS1) and control individuals, identified 2,002 differentially methylated points (DMPs), and inferred 17 differentially methylated regions, which represent only 189 DMPs.

Spring-Wire Technique as a Cost-Effective Alternative for Volar Rim Fragment Fixation in Distal Radius Fractures.

Introduction Volar rim fragment fixation is difficult to manage, as it is distal to the watershed line, rendering normal volar plates unable to securely capture it. This fragment must be precisely addressed as volar carpal subluxation is unavoidable when fixation is not efficient. The spring-wire technique maintains a stable fixation of this key fragment, which has been previously described in a small series.

Overall mortality for community-dwelling adults over 50 years at risk of malnutrition.

Background: It is well reported that malnutrition in acute care is associated with poorer health outcomes including increased mortality. However, the consequences of malnutrition on survival in community settings is uncertain. Malnutrition in people 65 years or over is often cited.

Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.

Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS).

Diurnal 11-ketotestosterone and 17-hydroxyprogesterone saliva profiles in paediatric classical congenital adrenal hyperplasia.

Objectives: The most suitable biochemical markers for therapy adjustment in patients with congenital adrenal hyperplasia are controversial. 11-Oxygenated androgens are a promising new approach. The objective of this study was to investigate the diurnal rhythm of 11-ketotestosterone in children and adolescents in saliva and to correlate it with salivary 17-hydroxyprogesterone.

Impact of maintaining serum potassium concentration ≥ 3.6mEq/L versus ≥ 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial.

Background: Atrial Fibrillation After Cardiac Surgery (AFACS) occurs in about one in three patients following Coronary Artery Bypass Grafting (CABG). It is associated with increased short- and long-term morbidity, mortality and costs. To reduce AFACS incidence, efforts are often made to maintain serum potassium in the high-normal range (≥ 4.

Effectiveness of septoplasty compared to medical management in adults with obstruction associated with a deviated nasal septum: the NAIROS RCT.

Background: The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking.

Objective: The objective was to determine the clinical effectiveness and cost-effectiveness of septoplasty, with or without turbinate reduction, compared with medical management, in the management of nasal obstruction associated with a deviated nasal septum.

The effects of a sleeve knee brace during stair negotiation in patients with symptomatic patellofemoral osteoarthritis.

Background: The patellofemoral joint is an important source of pain in knee osteoarthritis. Most biomechanical research in knee osteoarthritis has focused on the tibiofemoral joint during level walking. It is unknown what happens during stair negotiation in patients with patellofemoral joint osteoarthritis, a task commonly increasing pain.

Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.

Objectives: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ.

Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction: multicentre, open label, randomised controlled trial.

Objective: To assess the clinical effectiveness of septoplasty.

Design: Multicentre, randomised controlled trial.

Setting: 17 otolaryngology clinics in the UK's National Health Service.

Predicting congenital renal tract malformation genes using machine learning.

Congenital renal tract malformations (RTMs) are the major cause of severe kidney failure in children. Studies to date have identified defined genetic causes for only a minority of human RTMs. While some RTMs may be caused by poorly defined environmental perturbations affecting organogenesis, it is likely that numerous causative genetic variants have yet to be identified.

Success and Pitfalls of Genetic Testing in Undiagnosed Diseases: Whole Exome Sequencing and Beyond.

Novel approaches to uncover the molecular etiology of neurodevelopmental disorders (NDD) are highly needed. Even using a powerful tool such as whole exome sequencing (WES), the diagnostic process may still prove long and arduous due to the high clinical and genetic heterogeneity of these conditions. The main strategies to improve the diagnostic rate are based on family segregation, re-evaluation of the clinical features by reverse-phenotyping, re-analysis of unsolved NGS-based cases and epigenetic functional studies.

Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans.

ERI1 is a 3'-to-5' exoribonuclease involved in RNA metabolic pathways including 5.8S rRNA processing and turnover of histone mRNAs. Its biological and medical significance remain unclear.

AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model.

Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored at the membrane of the endoplasmic reticulum (ER), in two previously genetically unexplained HSP-affected siblings. Subsequently, international collaboration recognized additional HSP-affected individuals with similar bi-allelic truncating AMFR variants, resulting in a cohort of 20 individuals from 8 unrelated, consanguineous families.

Predictors and risk factors for admission to critical care in cervicofacial infections: a Maxillofacial Trainee Research Collaborative (MTReC) study.

Cervicofacial infections carry significant morbidity. Patients present on a broad spectrum of severity, with some requiring outpatient management and others admission to higher level care. Recognition of risk factors is helpful in decision making regarding the need for admission to higher level care.

What is the overlap between malnutrition, frailty and sarcopenia in the older population? Study protocol for cross-sectional study using UK Biobank.

Background: In an increasingly older adult population, understanding the inter-relationship between three age related conditions malnutrition, frailty and sarcopenia is important in order to improve their recognition, treatment and prevention. This study aims to determine the overlap between malnutrition, frailty and sarcopenia by measuring estimates of prevalence for each individual condition. In addition, we will compare two models of frailty which are the accumulation of deficits and phenotype models.

Rapid evidence synthesis to enable innovation and adoption in health and social care.

Background: The rapid identification and adoption of effective innovations in healthcare is a known challenge. The strongest evidence base for innovations can be provided by evidence synthesis, but this is frequently a lengthy process and even rapid versions of this can be time-consuming and complex. In the UK, the Accelerated Access Review and Academic Health Science Network (AHSN) have provided the impetus to develop a consistently rapid process to support the identification and adoption of high-value innovations in the English NHS.

Carer's perceptions of paediatric epilepsy services with and without epilepsy specialist nurses: A thematic analysis.

Purpose: To obtain in-depth perspectives from carers concerning their relationships with paediatric epilepsy services with and without an Epilepsy Specialist Nurse (ESN).

Methods: Semi-structured interviews with 58 carers, 37 from service areas with an ESN, and 21 from areas without an ESN in the North-West of England, were conducted and analysed using Thematic Analysis adopting a realist epistemological position.

Results: Four themes relating to different aspects of carers' needs were identified.

11-Oxygenated androgens are not secreted by the human ovary: in-vivo data from four different cases of hyperandrogenism.

Objective: Differentiation of an adrenal from an ovarian source of hyperandrogenemia can be challenging. Recent studies have highlighted the importance of 11-oxygenated C19 steroids to the androgen pool in humans. The aim of this study was to confirm the origin of 11-oxygenated androgens in females and to explore their potential use in the diagnostics of hyperandrogenic disorders.

Evaluating a tool to improve engagement and recruitment of under-served groups in trials.

Background: Despite substantial awareness that certain groups (e.g. ethnic minorities) are under-represented and under-served in trials, limited progress has been made in addressing this.

Treatment of acute distal biceps tendon ruptures - A survey of the British Elbow and Shoulder Society surgical membership.

Background: Acute distal biceps tendon ruptures result in weakness and deformity. While in other jurisdictions the rate of surgical repair has outpaced rises in incidence, UK practice for distal biceps tendon ruptures is unknown. The aim of this survey was to characterise current UK clinical practice.

11-Oxygenated C19 steroids are the predominant androgens responsible for hyperandrogenemia in Cushing's disease.

Background: Symptoms of hyperandrogenism are common in patients with Cushing's disease (CD), yet they are not sufficiently explained by androgen concentrations. In this study, we analyzed the contribution of 11-oxygenated C19 steroids (11oxC19) to hyperandrogenemia in female patients with CD.

Methods: We assessed saliva day profiles in females with CD pre (n = 23) and post (n = 13) successful transsphenoidal surgery, 26 female controls, 5 females with CD treated with metyrapone and 5 treated with osilodrostat for cortisol, cortisone, androstenedione (A4), 11-hydroxyandrostenedione (11OHA4), testosterone (TS), 11-ketotestosterone (11KT), as well as metabolites of classic and 11-oxygenated androgens in 24-h urine.