Chromosome 4 Duplication Associated with Strabismus Leads to Gene Expression Changes in iPSC-Derived Cortical Neurons.

Background/objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but the mechanisms by which they contribute to strabismus are unknown. This work aims to investigate the mechanisms of the smallest of the three, a 23 kb duplication on chromosome 4 (hg38|4:25,554,985-25,578,843).

Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.

A notion of the continuous production of amyloid-β (Aβ) via the proteolysis of Aβ-protein-precursor (AβPP) in Alzheimer's disease (AD)-affected neurons constitutes both a cornerstone and an article of faith in the Alzheimer's research field. The present Perspective challenges this assumption. It analyses the relevant empirical data and reaches an unexpected conclusion, namely that in AD-afflicted neurons, the production of AβPP-derived Aβ is either discontinued or severely suppressed, a concept that, if proven, would fundamentally change our understanding of the disease.

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.

Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis of proteins relevant for the manifestation of neuromuscular diseases in the following aspects: (i) evaluation of the effect of genetic variants on the corresponding protein, (ii) prediction of the underlying genetic defect based on the proteomic signature of muscle biopsies, (iii) analysis of pathophysiologies underlying different entities of muscular diseases, key for the definition of new intervention concepts, and (iv) patient stratification according to biochemical fingerprints as well as (v) monitoring the success of therapeutic interventions. This review presents-also through exemplary case studies-the various advantages of mass proteomics in the investigation of genetic muscle diseases, discusses technical limitations, and provides an outlook on possible future application concepts. Hence, proteomics is an excellent large-scale analytical tool for the diagnostic workup of (hereditary) muscle diseases and warrants systematic profiling of underlying pathophysiological processes.

Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases.

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack of clinically validated early-stage biomarkers and the limited availability of effective anti-fibrotic therapies. Current research is focused on uncovering the pathogenetic mechanisms that drive liver fibrosis.

Cyclin G1 Regulates the Alveolarization in Models of Bronchopulmonary Dysplasia by Inhibiting AT2 Cell Proliferation.

Disrupted neonatal lung alveologenesis often leads to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. The inhibition of type 2 alveolar (AT2) cell proliferation plays an important role in the arrest of alveologenesis. However, the mechanism of AT2 cell proliferation retardation in BPD is still not fully elucidated.

Unraveling the Molecular Mechanisms of Mosquito Salivary Proteins: New Frontiers in Disease Transmission and Control.

Mosquito-borne diseases are a group of illnesses caused by pathogens transmitted by mosquitoes, and they are globally prevalent, particularly in tropical and subtropical regions. Pathogen transmission occurs during mosquito blood feeding, a process in which mosquito saliva plays a crucial role. Mosquito saliva contains a variety of biologically active proteins that facilitate blood feeding by preventing blood clotting, promoting vasodilation, and modulating the host's immune and inflammatory responses.

NADH Reductive Stress and Its Correlation with Disease Severity in Leigh Syndrome: A Pilot Study Using Patient Fibroblasts and a Mouse Model.

Nicotinamide adenine dinucleotide (NAD) is a critical cofactor in mitochondrial energy production. The NADH/NAD ratio, reflecting the balance between NADH (reduced) and NADoxidized, is a key marker for the severity of mitochondrial diseases. We recently developed a streamlined LC-MS/MS method for the precise measurement of NADH and NAD.

Management and Outcome of Invasive Clindamycin-Resistant MRSA Community-Associated Infections in Children.

Background: Clindamycin resistance among community-associated methicillin-resistant (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children's hospital.

A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates.

Effective gentamicin dosing is crucial to the survival of neonates with suspected sepsis but requires a careful balance between attaining both effective peak and safe trough concentrations. We aimed to systematically compare existing gentamicin dosing guidelines for neonates in Australia to determine the extent to which they reach therapeutic targets. Simulations of a single gentamicin dose to a virtual representative neonatal population according to each Australian guideline were performed using population pharmacokinetic modelling.

Neuroendocrine Transformation as a Mechanism of Resistance to Targeted Lung Cancer Therapies: Emerging Mechanisms and Their Therapeutic Implications.

Lung cancer is the leading cause of cancer-related deaths worldwide, highlighting a major clinical challenge. Lung cancer is broadly classified into two histologically distinct subtypes, termed small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Identification of various oncogenic drivers of NSCLC has facilitated the development of targeted therapies that have dramatically improved patient outcomes.

Patient Acceptability of the First Integrative Pediatric Oncology Unit in Spain-The Pediatric Cancer Center Barcelona Experience: A Retrospective Study.

Pediatric cancer patients and their families are increasingly combining conventional treatment with complementary therapies. These therapies are not covered by most public healthcare systems, and Spain is not an exception. To address this need, the Pediatric Cancer Center Barcelona, at the Hospital Sant Joan de Déu (Spain), established the first integrative pediatric oncology unit in 2019.

PROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia.

Background: Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that utilize the ubiquitin-proteasome system to selectively degrade target proteins. This innovative technology has shown remarkable efficacy and specificity in degrading oncogenic proteins and has progressed through various stages of preclinical and clinical development for hematologic malignancies, including adult acute myeloid leukemia (AML). However, the application of PROTACs in pediatric AML remains largely unexplored.

A Survey of Parents' Perspective of Receiving a Developmental Diagnosis for Their Child.

Receiving a diagnosis, such as cerebral palsy (CP), can have lasting impacts on caregivers and families. Previous literature has described that caregivers wish to receive a diagnosis together, without delay, in a private, direct, honest, and sympathetic way. This study aimed to understand the experience of caregivers of children with cerebral palsy (CP) or similar conditions when receiving a diagnosis for their child.

The Development of the Radial Bow in Children: Normative Values.

Background: Radial bowing is necessary for forearm rotation. Fractures or deformities of the forearm that affect the radial bow may disrupt normal forearm rotation.

Objective: The purpose of this study was to evaluate the development and establish normative values for the pediatric and adolescent radial bow.

Thematic Review of Endocrine Disruptors and Their Role in Shaping Pubertal Timing.

This review examines the inconsistent effects of endocrine-disrupting chemicals (EDCs) and pollutants on pubertal timing, emphasizing the methodological challenges contributing to variability in findings. Data from nine key studies reveal that chemicals such as BPA, phthalates, and PFAS impact pubertal onset differently based on exposure timing, dosage, and sex. For instance, BPA is linked to earlier puberty in girls but delayed onset in boys, while other EDCs show mixed effects across populations.

Thrombocytopenia in Critically Ill Children: A Review for Practicing Clinicians.

Thrombocytopenia frequently occurs in patients before, during, and after admission to Pediatric Intensive Care Units (PICUs). In critically ill children, it is often due to multifactorial causes and can be a sign of significant organ dysfunction. This review summarizes the potential causes/mechanisms of thrombocytopenia in acutely ill children, their identification, and treatments, with special attention paid to septic patients.

Mapping the Gaps: A Scoping Review of Virtual Care Solutions for Caregivers of Children with Chronic Illnesses.

: Caregivers of children with chronic illnesses, including chronic pain, experience high levels of distress, which impacts their own mental and physical health as well as child outcomes. Virtual care solutions offer opportunities to provide accessible support, yet most overlook caregivers' needs. We conducted a scoping review to create an interactive Evidence and Gap Map (EGM) of virtual care solutions across a stepped care continuum (i.

Dual Biologic or Small Molecule Therapy in Pediatric Inflammatory Bowel Disease: A Single Center Experience.

Purpose: Currently, there is no clinical data reported on the therapy of dual biological agents in pediatric-onset inflammatory bowel disease (PIBD) patients in China. The purpose of this study was to evaluate the efficacy and safety of dual biologic therapy or biologics combined with small molecule drugs in refractory PIBD patients in China.

Methods: Clinical, laboratory, endoscopic, and ultrasound data of PIBD patients from the Department of Gastroenterology of Beijing Children's Hospital between January 2021 and October 2024 were retrospectively analyzed.

The Evaluation of Serum KIM-1 in a Pediatric Cohort of Renal Transplantation-A Pilot Study.

Introduction: Renal transplantation ensures particular advantages for patients with end-stage kidney disease. However, in some cases, early complications may result in allograft dysfunction, which can ultimately lead to the loss of the graft. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes.

Severe Lipoatrophy in a Growth Hormone Deficient Toddler Girl Treated with a Non-Pegylated Long-Acting Growth Hormone.

Background: Recombinant growth hormone (rhGH) has been used since 1985 to treat growth hormone (GH)-induced short stature, typically associated with transient adverse events. However, lipoatrophy, characterized by irreversible damage to subcutaneous fat, was first reported in 1999 and linked to antibody formation. In 2021, localized lipoatrophy was observed in 14.

Body Composition in Preterm Infants: Current Insights and Emerging Perspectives.

In recent years, significant advancements in respiratory and nutritional care have markedly improved the survival rates of preterm infants and enhanced long-term health outcomes. Despite these improvements, emerging research highlights the lasting impacts of early growth patterns on an individual's health trajectory. Adults born prematurely face a higher incidence of health issues related to their early birth.

Empowerment in Adolescent Patients with a Disability/Chronic Condition: A Scoping Review.

Background/objectives: Empowerment has been associated with several positive outcomes in healthcare; however, there is limited insight on empowerment levels within the adolescent population of those with a chronic condition/disability. The aim of this scoping review was to identify gaps in the existing literature on empowerment levels within this population.

Methods: Five databases (MEDLINE [Ovid], EMBASE [Ovid], PsycINFO [Ebsco], CINHAL [Ebsco] and Web of Science [UBC]) and grey literature were searched.

A Pilot Study on the Freelisting Method Among Adolescents with Chronic Musculoskeletal Pain: Feasibility, Acceptability and Study Findings.

: To assess the feasibility and acceptability of freelisting for adolescents with chronic musculoskeletal pain (CMP) and use freelisting to identify how adolescents with CMP cope with pain. : This was a mixed-methods cross-sectional single-center study of patients 12-18 years old, diagnosed with CMP. Twenty-seven subjects participated in an interview which included the freelisting exercise, probing questions, Connor-Davidson Resilience Scale 10-item, and semi-structured interview.

Antimicrobial Stewardship in the Pediatric Emergency Department: An Observational Pre-Post Study.

: To face antimicrobial resistance, antimicrobial stewardship programs (ASPs) have been implemented in the pediatric age, but the area of urgency remains understudied. We aimed to assess the impact of an educational program on optimizing antibiotic appropriateness in a pediatric ED. : We conducted a pre-post observational study with an audit, intervention, and feedback given to prescribers.

Impact of Soft Drink Intake on Bone Development and Risk of Fractures in a Danish Cohort of Schoolchildren.

Background And Aims: Soft drink consumption is suspected to negatively impact bone health in children, but longitudinal evidence is limited. This study assessed the association between soft drink intake and bone health outcomes in Danish schoolchildren aged 7.7-12 years, within a physical activity intervention framework.