Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells.

Background: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors.

Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency.

A rare neurodevelopmental disorder has been linked to a well-conserved splice site variant in the TRAPPC4 gene (c.454 + 3A > G), which causes mis-splicing of TRAPPC4 transcripts and reduced levels of TRAPPC4 protein. Patients present with severe progressive neurological symptoms including seizures, microcephaly, intellectual disability and facial dysmorphism.

TRAPPopathies: Severe Multisystem Disorders Caused by Variants in Genes of the Transport Protein Particle (TRAPP) Complexes.

The TRAPP (TRAnsport Protein Particle) protein complex is a multi-subunit complex involved in vesicular transport between intracellular compartments. The TRAPP complex plays an important role in endoplasmic reticulum-to-Golgi and Golgi-to-plasma membrane transport, as well as autophagy. TRAPP complexes comprise a core complex, TRAPPI, and the association of peripheral protein subunits to make two complexes, known as TRAPPII and TRAPPIII, which act as Guanine Nucleotide Exchange Factors (GEFs) of Rab11 and Rab1, respectively.

"Humanly Possible": Geographies, Metrics and Methods to Address Immunization Inequalities.

The year 2024 marks the 50th anniversary of the World Health Organization (WHO) Expanded Program on Immunization (EPI) [...

Inequality in Childhood Immunization Coverage: A Scoping Review of Data Sources, Analyses, and Reporting Methods.

Immunization through vaccines among children has contributed to improved childhood survival and health outcomes globally. However, vaccine coverage among children is unevenly distributed across settings and populations. The measurement of inequalities is essential for understanding gaps in vaccine coverage affecting certain sub-populations and monitoring progress towards achieving equity.

Novel CDKL5 targets identified in human iPSC-derived neurons.

CDKL5 Deficiency Disorder (CDD) is a debilitating epileptic encephalopathy disorder affecting young children with no effective treatments. CDD is caused by pathogenic variants in Cyclin-Dependent Kinase-Like 5 (CDKL5), a protein kinase that regulates key phosphorylation events in neurons. For therapeutic intervention, it is essential to understand molecular pathways and phosphorylation targets of CDKL5.

Defining Biomarkers in Stem Cell-Derived Tissue Constructs for Drug and Disease Screening.

The development of stem cell-derived tissue constructs (SCTCs) for clinical applications, including regenerative medicine, drug and disease screening offers significant hope for detecting and treating intractable disorders. SCTCs display a variety of biomarkers that can be used to understand biological mechanisms, assess drug interactions, and predict disease. Although SCTCs can be derived from patients and share the same genetic make-up, they are nevertheless distinct from human patients in many significant ways, which can undermine the clinical significance of measurements in SCTCs.

Inequality in Immunization: Holding on to Equity as We 'Catch Up'.

Immunization, hailed as one of the most successful public health interventions in the world, has contributed to major advancements in health as well as social and economic development [...

Inequalities in Immunization against Maternal and Neonatal Tetanus: A Cross-Sectional Analysis of Protection at Birth Coverage Using Household Health Survey Data from 76 Countries.

Substantial progress in maternal and neonatal tetanus elimination has been made in the past 40 years, with dramatic reductions in neonatal tetanus incidence and mortality. However, twelve countries have still not achieved maternal and neonatal tetanus elimination, and many countries that have achieved elimination do not meet key sustainability thresholds to ensure long-lasting elimination. As maternal and neonatal tetanus is a vaccine-preventable disease (with coverage of the infant conferred by maternal immunization during and prior to pregnancy), maternal tetanus immunization coverage is a key metric for monitoring progress towards, equity in, and sustainability of tetanus elimination.

Within-Country Inequality in COVID-19 Vaccination Coverage: A Scoping Review of Academic Literature.

Since December 2020, COVID-19 vaccines have become increasingly available to populations around the globe. A growing body of research has characterised inequalities in COVID-19 vaccination coverage. This scoping review aims to locate, select and assess research articles that report on within-country inequalities in COVID-19 vaccination coverage, and to provide a preliminary overview of inequality trends for selected dimensions of inequality.

Strengthening and expanding health inequality monitoring for the advancement of health equity: a review of WHO resources and contributions.

As part of its commitment to advance health equity, the World Health Organization (WHO) has a developed area of work to promote and strengthen health inequality monitoring. This includes an emphasis on the collection, analysis and use of disaggregated health data, which are central to evidence-informed decision making. The aim of this paper is to review WHO's work on health inequality monitoring, namely the 2022-27 Inequality monitoring and analysis strategy and corresponding activities, resources and tools.

Severe NAD(P)HX Dehydratase (NAXD) Neurometabolic Syndrome May Present in Adulthood after Mild Head Trauma.

We have previously reported that pathogenic variants in a key metabolite repair enzyme NAXD cause a lethal neurodegenerative condition triggered by episodes of fever in young children. However, the clinical and genetic spectrum of NAXD deficiency is broadening as our understanding of the disease expands and as more cases are identified. Here, we report the oldest known individual succumbing to NAXD-related neurometabolic crisis, at 32 years of age.

Expanding the Allelic Heterogeneity of -Associated Autosomal Recessive Cerebellar Ataxia.

Background And Objectives: The term autosomal recessive cerebellar ataxia (ARCA) encompasses a diverse group of heterogeneous degenerative disorders of the cerebellum. Spinocerebellar ataxia autosomal recessive 10 (SCAR10) is a distinct classification of cerebellar ataxia caused by variants in the gene. Little is known about the molecular role of ANO10 or its role in disease.

Global state of education-related inequality in COVID-19 vaccine coverage, structural barriers, vaccine hesitancy, and vaccine refusal: findings from the Global COVID-19 Trends and Impact Survey.

Background: COVID-19 vaccine coverage and experiences of structural and attitudinal barriers to vaccination vary across populations. Education-related inequality in COVID-19 vaccine coverage and barriers within and between countries can provide insight into the hypothesised role of education as a correlate of vaccine access and acceptability. We aimed to characterise patterns of within-country education-related inequality in COVID-19 vaccine indicators across 90 countries.

Persistent Unilateral Force Production Deficits Following Hand Injury in Experienced Climbers: A Reliability and Retrospective Injury Study.

Introduction: In climbing, research is needed to guide clinical and training advice regarding strength differences between hands. The objectives of this study were to establish test-retest reliability of a field-based apparatus measuring sport-specific unilateral isometric hand strength and to investigate whether these measures detect between-hand differences in climbers with and without a history of unilateral hand injury.

Methods: A reliability and case-control injury study was carried out.

Education-related inequalities in beliefs and behaviors pertaining to COVID-19 non-pharmaceutical interventions.

Background: The coronavirus pandemic has exposed existing social inequalities in relation to disease preventive behaviors, risk of exposure, testing and healthcare access, and consequences as a result of illness and containment measures across different population groups. However, due to a lack of data, to date there has been limited evidence of the extent of such within-country inequalities globally.

Methods: We examined education-related inequalities in four COVID-19 prevention and testing indicators within 90 countries, using data from the University of Maryland Social Data Science Center Global COVID-19 Trends and Impact Survey, in partnership with Facebook, over the period 1 June 2021 to 31 December 2021.

Shell Disease Syndrome Is Associated with Reduced and Shifted Epibacterial Diversity on the Carapace of the Crustacean Cancer pagurus.

Cancer pagurus is highly susceptible to shell disease syndrome. However, little is known about concomitant changes in the epibacterial community. We compared the bacterial communities of black spot affected and nonaffected areas of the carapace by amplicon sequencing of 16S rRNA genes and 16S rRNA.