The role of ATP-binding Cassette subfamily B member 6 in the inner ear.

ABCB6 has been implicated in dyschromatosis universalis hereditaria, a condition characterized by hyperpigmented and hypopigmented skin macules. Dyschromatosis universalis hereditaria can also present with hearing loss. Dyschromatosis universalis hereditaria-associated mutations in ABCB6 have been reported, but the role of this protein in the inner ear has not been studied.

Excess dietary sodium restores electrolyte and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.

The maintenance of fluid and electrolyte homeostasis by the kidney requires proper folding and trafficking of ion channels and transporters in kidney epithelia. Each of these processes requires a specific subset of a diverse class of proteins termed molecular chaperones. One such chaperone is GRP170, which is an Hsp70-like, endoplasmic reticulum (ER)-localized chaperone that plays roles in protein quality control and protein folding in the ER.

Limited Recommendations and Evidence for Timing and Frequency of Anti-Mullerian Hormone Screening in Female Pediatric Cancer Survivors: A Systematic Review from the Pediatric and Adolescent Committee of the Oncofertility Consortium.

Guidelines regarding the optimal use and timing of anti-Mullerian hormone (AMH) screening in childhood cancer survivors to evaluate for the risk of premature ovarian insufficiency or reduced fertility potential are lacking. We conducted a systematic review of the current evidence supporting AMH screening of female childhood cancer survivors with the overall objective to identify gaps in the literature needing further study, to allow for future data-driven recommendations. Search terms included "cancer, fertility, and anti-Mullerian hormone.

Surgery and the first 8000 days of life: a review.

The first 8000 days of life, from birth to adulthood, encompasses critical phases that shape a child's health and development. While global health efforts have focused on the first 1000 days, the next 7000 days (ages 2-21) are equally vital, especially concerning the unmet burden of surgical conditions in low- and middle-income countries (LMICs). Approximately 1.

SARS-CoV-2 Infection and COVID-19 in Children.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is common in children, and clinical manifestations can vary depending on age, underlying disease, and vaccination status. Most children will have asymptomatic or mild infection, but certain baseline characteristics can increase the risk of moderate to severe disease. The following article will provide an overview of the clinical manifestations of coronavirus disease 2019 in children, including the post-infectious phenomenon called multisystem inflammatory syndrome in children.

Economic Burden of Haemophilia from a Societal Perspective: A Scoping Review.

Introduction: Haemophilia is a rare genetic bleeding disorder that leads to musculoskeletal complications. The high cost of haemophilia treatment necessitates a thorough evaluation of its economic burden. However, due to the difficulty of estimating direct non-medical, indirect, and intangible costs, studies often underestimate the actual economic burden of haemophilia.

Histone H1 kills MRSA.

The antimicrobial activity of histones was discovered in the 1940s, but their mechanism of action is not fully known. Here we show that methicillin-resistant Staphylococcus aureus (MRSA) is susceptible to histone H1 (H1), even in the presence of divalent cations and serum. Through selective evolution and a genome-wide screen of a transposon library, as well as physiological and pharmacological experiments, we elucidated how H1 kills MRSA.

Comparison of GWAS results between de novo tinnitus and cancer treatment-related tinnitus suggests distinctive roles for genetic risk factors.

Tinnitus is a common sensorineural complication that can occur de novo or after cancer treatments involving cisplatin or radiotherapy. Considering the heterogeneous etiology and pathophysiology of tinnitus, the extent to which shared genetic risk factors contribute to de novo tinnitus and cancer treatment-induced tinnitus is not clear. Here we report a GWAS for de novo tinnitus using the UK Biobank cohort with nine loci showing significantly associated variants (p < 5 × 10).

Teleophthalmology Through Online Mentorship Over a 20-Year Period: Education and Capacity Building.

Purpose: Telemedicine is widely used for diabetic retinopathy, retinopathy of prematurity, and other ophthalmic diseases. However, there is limited research on the use of teleophthalmology in retinoblastoma. The goal of this study was to explore how Orbis Cybersight affected the capacity for treatment and management of children with retinoblastoma through online mentorship and to assess the efficacy of online mentoring through disease-specific knowledge change over time.

A glutamine metabolic switch supports erythropoiesis.

Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production.

Update on Pediatric Surveillance Recommendations for PTEN Hamartoma Tumor Syndrome, DICER1-Related Tumor Predisposition, and Tuberous Sclerosis Complex.

Phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex are rare conditions, which each increases risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection, and multidisciplinary care. In this article, we present updated surveillance recommendations and considerations for children and adolescents with phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex and provide suggestions for further research in each of these conditions.

Prevention and Treatment of Cancer-Related Infections, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy.

Utility of Caregiver Signaling Questions to Detect Neurocognitive Impairment in Children with Sickle Cell Disease.

The American Society of Hematology cerebrovascular guidelines for sickle cell disease (SCD) recommend surveillance using signaling questions to screen for neurocognitive difficulties, though the clinical utility of these signaling questions has yet to be established. This study aimed to determine the clinical utility of caregiver signaling questions for detecting significant neurocognitive impairment (defined as >1.5 standard deviation (SD) below the normative mean on 2 or more measures) and domain-specific impairment (defined as >1.

Optical characterization of molecular interaction strength in protein condensates.

Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular interactions are scarce. Here, we introduce two optical techniques-Brillouin microscopy and quantitative phase imaging (QPI)-to address this scarcity.

Accurate Measurement of Cell Number-Normalized Differential Gene Expression in Cells Treated With Retinoic Acid.

Genome-wide gene expression analysis is a commonly used method to quantitatively examine the transcriptional signature of any tissue or cell state. Standard bulk cell RNA sequencing (RNA-seq) quantifies RNAs in the cells of the tissue type of interest through massive parallel sequencing of cDNA synthesized from the cellular RNA. The subsequent analysis of global RNA expression and normalization of RNA expression levels between two or more samples generally assumes that cells from all samples produce equivalent amounts of RNA per cell.

Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies.

Development of the pediatric neuro-oncology services assessment aid: An assessment tool for pediatric neuro-oncology service delivery capacity.

Background: To enhance the quality of care available for children with central nervous system (CNS) tumors across the world, a systematic evaluation of capacity is needed to identify gaps and prioritize interventions. To that end, we created the pediatric neuro-oncology (PNO) resource assessment aid (PANORAMA) tool.

Methods: The development of PANORAMA encompassed 3 phases: operationalization, consensus building, and piloting.

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial.

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.

A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases.

Individualized genetic therapies-medicines that precisely target a genetic variant that may only be found in a small number of individuals, as few as only one-offer promise for addressing unmet needs in genetic disease, but present unique challenges for trial design. By nature these new individualized medicines require testing in individualized N-of-1 trials. Here, we provide a framework for maintaining scientific rigor in N-of-1 trials.