Six at Sixty. 'Have you tested for 22q?'.

In 1997, the published our paper on the spectrum of clinical features associated with interstitial chromosome 22q11 deletions. This copy number variation is associated with an extraordinary range of clinical features, which led initially to its association with several diagnostic labels. Since 1997 work on clinical and basic science aspects of the syndrome and the genes reduced to hemizygosity have provided a wealth of information pertaining to both best practice care and underlying biology.

Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players.

 Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players.

Reducing the risk of visual disability for children with juvenile idiopathic arthritis uveitis through disease surveillance: past and future challenges.

Childhood blindness significantly impacts development, education, employment, and mental health, creating burden for families and society. Between 8% and 30% of children with Juvenile Idiopathic Arthritis (JIA) develop a potentially blinding chronic inflammatory eye disease, uveitis (JIAU). Alongside the use of disease-modifying agents and anti-TNF immunomodulators, JIAU surveillance has helped to reduce the risk of JIAU related blindness.

Comparing apples and oranges in youth depression treatments? A quantitative critique of the evidence base and guidelines.

Objectives: Should a young person receive psychotherapy or medication for their depression and on what evidence do we base this decision? In this paper, we test the factors across modalities that may influence comparability between medication and psychotherapy trials.

Methods: We included 92 randomised controlled trials (RCTs) of psychotherapy and medication for child and adolescent depression (mean age 4-18 years). Using meta-analyses, we compared (a) participant characteristics and (b) trial characteristics in medication and psychotherapy trials.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

Translation, adaptation and validation of an epilepsy screening instrument in two Ghanaian languages.

Introduction: The prevalence of epilepsy in sub-Saharan Africa varies considerably, and the exact estimate for Ghana remains unclear, particularly in peri-urban areas where data are scarce. More community-based studies are required to understand better the actual burden of epilepsy in these areas and the difficulties in accessing healthcare.

Objective: To adapt and validate a household survey epilepsy-screening instrument in Shai-Osudoku and Ningo-Prampram District of Greater Accra Region, Ghana.

Reduction of elevated Gli3 does not alter the progression of autosomal recessive polycystic kidney disease.

Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition.

Complex I deficiency remains the most frequent cause of Leigh syndrome spectrum.

This scientific commentary refers to 'Biallelic variants lead to a neurodevelopmental phenotype with gradual neurological impairment', by Kaiyrzhanov . (https://doi.org/10.

Tuberous sclerosis complex-associated kidney disease in children.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder which can have manifestations in the kidneys, along with other organ systems. Children with TSC may develop kidney lesions at any point during childhood, and typically these are angiomyolipomata (AML) and/or kidney cysts. Children may also have hypertension associated with TSC-associated kidney disease, and rarely reduced kidney function.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Utilities Associated with the Treatment of Growth Hormone Deficiency (GHD): A Time Trade-off (TTO) Study in the UK and Canada.

Purpose: Growth hormone deficiency (GHD) causes decreased growth rate in children, resulting in short stature in childhood and adulthood. Daily subcutaneous injections with growth hormone (GH) have been standard treatment. Newer weekly GH formulations now exist.

Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia.

Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender.

Refining computer-assisted SEEG planning with spatial priors - A novel comparison of implantation strategies across adult and paediatric centres.

Objectives: Computer-assisted planning (CAP) allows faster SEEG planning and improves grey matter sampling, orthogonal drilling angles to the skull, reduces risk scores and minimises intracerebral electrode length. Incorporating prior SEEG trajectories enhances CAP planning, refining output with centre-specific practices. This study significantly expands on the previous work, compares priors libraries between two centres, and describes differences between SEEG in adults and children in these centres.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Distribution and viability of ocular and non-ocular Chlamydia trachomatis in households in a trachoma-endemic community in Oromia, Ethiopia.

Background: We aimed to determine the household distribution and viability of Chlamydia trachomatis (Ct) from the eyes, face, and hands during the initial two visits of a year-long fortnightly cohort study in geographically defined adjacent households.

Methods/findings: We enrolled 298 individuals from 68 neighbouring households in Shashemene Woreda, Oromia, Ethiopia. All individuals above 2 years of age residing in these households were examined for signs of trachoma.

Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease.

It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry specific manner. Here we utilise genome-wide association studies and expression quantitative trait loci from African, East Asian and European ancestries to show that genes causing neurodegeneration are preferentially expressed in innate rather than adaptive immune cells, and that expression of these genes mediates the risk of neurodegenerative disease in monocytes in an ancestry-specific manner.

deletion rescues cerebellar hypotrophy in mutant zebrafish.

Defects in DNA single-strand break repair are associated with neurodevelopmental and neurodegenerative disorders. One such disorder is that resulting from mutations in , a scaffold protein that plays a central role in DNA single-strand base repair. XRCC1 is recruited at sites of single-strand breaks by PARP1, a protein that detects and is activated by such breaks and is negatively regulated by XRCC1 to prevent excessive PARP binding and activity.

Chronic Rhinosinusitis with Nasal Polyps and Biologics: A Call for Better Data Standardisation and Presentation in Clinical Studies.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often severe, debilitating and difficult to treat. Recent randomised control trials (RCTs) of biologics that target key inflammatory pathways have demonstrated clinical efficacy in treating CRSwNP. Such RCTs must facilitate meta-analysis.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in .

Recently, a novel African ancestry specific Parkinson's disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (). This variant (rs3115534-G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups, but is almost absent in European and Asian ancestry populations.

Growing up without violence (GWV): Study protocol for a cluster randomised trial and process evaluation of a school-based intervention preventing adolescent sexual exploitation in Brazil.

Background: Sexual exploitation of children and adolescents (SECA) is a mostly invisible phenomenon, having negative impacts on adolescents' health and well-being. There is increasing awarenessof preventative strategies to reduce sexual exploitation of children and adolescents, but limited evidence on their effectiveness and mechanisms. This project addresses this gap through the impact and process evaluation of 'Growing Up Without Violence' (GWV), the largest intervention in Brazil tackling SECA.

Reichert's membrane - A continuing enigma for developmental biologists.

Reichert's membrane (RM) is a basement membrane of gigantic proportions that surrounds the mammalian embryo following implantation. It is part of the parietal yolk sac, which originates from the wall of the preimplantation blastocyst. RM persists from implantation to birth in rodents and analogous structures occur in other mammals, including primates.

Social and economic patterning in UPF intake in toddlerhood and middle childhood: longitudinal data from the UK Gemini cohort.

Introduction: Children's consumption of ultra-processed food (UPF) may contribute to inequalities in obesity and wider health. Socioeconomic patterning in younger UK children's UPF intake is unknown.

Objective: To investigate socioeconomic patterning of UK toddlers' (21-months) and children's (7-years) UPF intake across several household and neighbourhood indicators.

Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study.

Background: Friedreich ataxia is a rare neurodegenerative disorder caused by frataxin deficiency. Both underweight and overweight occur in mitochondrial disorders, each with adverse health outcomes. We investigated the longitudinal evolution of anthropometric abnormalities in Friedreich ataxia and the hypothesis that both weight loss and weight gain are associated with faster disease progression.