Cluster randomised controlled trial of double-dose azithromycin mass drug administration, facial cleanliness and fly control measures for trachoma control in Oromia, Ethiopia: the stronger SAFE trial protocol.

Introduction: Trachoma is caused by the bacterium (). The WHO recommends the SAFE strategy for trachoma elimination: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Multiple rounds of SAFE implementation have proven insufficient to eliminate trachoma in Ethiopia, where over 50% of the global trachoma burden remains.

Safety and effectiveness of ataluren in patients with Duchenne muscular dystrophy: single-center experience from Saudi Arabia.

Objective: Duchenne muscular dystrophy (DMD) is a rare X-linked neurodegenerative disorder caused by mutations in the gene. This study examined the efficacy and safety of ataluren, the first oral treatment for DMD with nonsense mutations (nmDMD), in patients in the Middle East.

Methods: This retrospective longitudinal study assessed the outcomes of seven boys with nmDMD who received treatment with ataluren and follow-up at a single center since 2016.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Reverse-engineering the Venus figurines: An eco-life-course hypothesis for the aetiology of obesity in the Palaeolithic.

Evolutionary perspectives on obesity have been dominated by genetic frameworks, but plastic responses are also central to its aetiology. While often considered a relatively modern phenomenon, obesity was recorded during the Palaeolithic through small statuettes of the female form (Venus figurines). Even if the phenotype was rare, these statuettes indicate that some women achieved large body sizes during the last glacial maximum, a period of nutritional stress.

Investigating the pathogenicity of the recessive p.A251T variant in monogenic diabetes using iPSC-derived beta-like cells.

Monogenic diabetes, formerly called Maturity-Onset Diabetes of the Young (MODY), involves single-gene mutations, typically with dominant inheritance, and has been associated with variants in 14 genes. Among these, mutations are the most common, and their diagnosis allows the use of alternative therapies, including sulfonylureas. In an earlier study, we described a variant displaying recessive transmission, p.

Rare dysfunctional SCN2A variants are associated with malformation of cortical development.

Objective: SCN2A encodes the voltage-gated sodium (Na+) channel α subunit Na1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders.

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Editorial Perspective: How can we develop effective and timely interventions for young people with chronic loneliness?

Loneliness is an adaptive experience evolved to create motivation to engage in social relationships. However, for some young people, loneliness can become chronic which can have serious negative health consequences. Despite this, there is a relative lack of evidence for interventions.

Associations of body composition at birth and accretion from 0 to 5 years with kidney function and volume at the 10-year follow-up: the Ethiopian Infant Anthropometry and Body Composition birth cohort.

Background: Fat mass (FM) and fat-free mass (FFM) in early life are associated with later obesity and cardiometabolic disease.

Objectives: This study aimed to assess the associations of FM and FFM at birth and conditional FM and FFM accretion from 0 to 5 y with kidney outcomes at the 10-y follow-up.

Methods: The Ethiopian Infant Anthropometry and Body Composition birth cohort included term infants born in Jimma town, with a birth weight ≥1500 g, and having no congenital malformations.

Ages and Stages Questionnaires in the assessment of young children after cardiac surgery.

Aims: This study explored the prospective use of the Ages and Stages Questionnaires-3 in follow-up after cardiac surgery.

Materials And Method: For children undergoing cardiac surgery at 5 United Kingdom centres, the Ages and Stages Questionnaires-3 were administered 6 months and 2 years later, with an outcome based on pre-defined cut-points: Red = 1 or more domain scores >2 standard deviations below the normative mean, Amber = 1 or more domain scores 1-2 standard deviations below the normal range based on the manual, Green = scores within the normal range based on the manual.

Results: From a cohort of 554 children <60 months old at surgery, 306 participated in the postoperative assessment: 117 (38.

Antimicrobial resistance-attributable mortality: a patient-level analysis.

Background: The impact of antimicrobial resistance (AMR) on death at the patient level is challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK teaching hospital.

Methods: This retrospective study investigated all deceased patients in 2022.

Cohort trends in intrinsic capacity in England and China.

To understand how the health of older adults today compares to that of previous generations, we estimated intrinsic capacity and subdomains of cognitive, locomotor, sensory, psychological and vitality capacities in participants of the English Longitudinal Study of Ageing and the China Health and Retirement Longitudinal Study. Applying multilevel growth curve models, we found that more recent cohorts entered older ages with higher levels of capacity, while subsequent age-related declines were somewhat compressed compared to earlier cohorts. Trends were most evident for the cognitive, locomotor and vitality capacities.

Associations of early childhood exposure to severe acute malnutrition and recovery with cardiometabolic risk markers in later childhood: 5-year prospective matched cohort study in Ethiopia.

Background: Impaired fetal and accelerated postnatal growth are associated with cardiometabolic disease. Few studies investigated how recovery from severe acute malnutrition (SAM) is associated with childhood cardiometabolic risk.

Objectives: We evaluated cardiometabolic risk in children with SAM treated through community-based management, relative to controls, 5-y postrecovery.

A comparative study of experimental and simulated ultrasound beam propagation through cranial bones.

Transcranial ultrasound is used in a variety of treatments, including neuromodulation, opening the blood-brain barrier, and high intensity focused ultrasound therapies. To ensure safety and efficacy of these treatments, numerical simulations of the ultrasound field within the brain are used for treatment planning and evaluation. This study investigates the accuracy of numerical modelling of the propagation of focused ultrasound through cranial bones.

Refining management strategies for Lennox-Gastaut syndrome: Updated algorithms and practical approaches.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy (DEE) characterized by multiple types of drug-resistant seizures (which must include tonic seizures) with classical onset before 8 years (although some cases with later onset have also been described), abnormal electroencephalographic features, and cognitive and behavioral impairments. Management and treatment of LGS are challenging, due to associated comorbidities and the treatment resistance of seizures. A panel of five epileptologists reconvened to provide updated guidance and treatment algorithms for LGS, incorporating recent advancements in antiseizure medications (ASMs) and understanding of DEEs.

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

Assessing Contrast Sensitivity Function in CRB1-Retinopathies: Exploring Child-Friendly Measures of Visual Function.

Purpose: Mutations affecting the CRB1 gene can result in a range of retinal phenotypes, including early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa, cone-rod dystrophy (CORD), and macular dystrophy (MD). As research into treatment strategies advances towards clinical translation, there is a need to establish reliable outcome metrics. This study explores the contrast sensitivity function (CSF) across different spatial frequencies in individuals with CRB1-retinopathies using the child-friendly PopCSF test, an iPad-based "gamified" assessment.

Association between birth length, linear growth velocities, and primary school achievement at age 10 years: evidence from the Ethiopian iABC birth cohort.

Background: Childhood is a period marked by dynamic growth. Evidence of the association between childhood linear growth and school achievement comes mostly from cross-sectional data. We assessed associations between birth length, childhood linear growth velocities, and stunting with school achievement.

The use of nanocarriers in treating Batten disease: A systematic review.

The neuronal ceroid lipofuscinoses, commonly known as Batten disease, are a group of lysosomal storage disorders affecting children. There is extensive central nervous system and retinal degeneration, resulting in seizures, vision loss and a progressive cognitive and motor decline. Enzyme replacement and gene therapies are being developed, and mRNA and oligonucleotide therapies are more recently being considered.

Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.

Heritability of children's Secure Base Script Knowledge in middle childhood: a twin study with the Attachment Script Assessment.

Background: Are individual differences in attachment security inborn or shaped by the social environment? In infancy and early childhood, the evidence points to a substantial role of the environment, but a large twin study in early adolescence showed considerable heritability. Here we examined the twin heritability of attachment in middle childhood. We hypothesized that in middle childhood some heritability would emerge.

Efficient assay for evaluating drug efficacy and synergy against emerging SARS-CoV-2 strains.

Novel and repurposed antiviral drugs are available for the treatment of coronavirus disease 2019 (COVID-19). However, antiviral combinations may be more potent and lead to faster viral clearance, but the methods for screening antiviral combinations against respiratory viruses are not well established and labor-intensive. Here, we describe a time-efficient (72-96 h) and simple drug-sensitivity assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using standard 96-well plates.