Effectiveness of Nirsevimab Immunoprophylaxis Against Respiratory Syncytial Virus-related Outcomes in Hospital Care Settings: A Seasonal Cohort Study of Infants in Catalonia (Spain).

Background: In Catalonia, infants <6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyze nirsevimab's effectiveness in hospital-related outcomes of the seasonal cohort (born during the RSV epidemic from October to January 2024) and compared them with the catch-up cohort (born from April to September 2023).

Methods: Retrospective cohort study of all infants born between October 1, 2023, and January 21, 2024, according to their immunization with nirsevimab (immunized and nonimmunized).

COVID-19 Symptoms Only Minutely Influenced by Genes Among Children in a Nationwide Twin Cohort.

Background: The World Health Organization classified coronavirus disease (COVID-19) as a pandemic by March 11, 2020. Children had a milder disease than adults, and many were asymptomatic. The pandemic could be seen as a natural experiment with several changes, including time spent at home.

The Relationship Between the Positive Drain Tip Cultures and the Incidence of Surgical Site Infection After Pediatric Cardiovascular Surgery.

Background: Surgical site infection (SSI) is a significant complication following pediatric cardiovascular surgery. Although drain tip cultures (DTC) are sometimes used postoperatively to predict SSIs, their diagnostic value in pediatric cardiovascular surgery remains unclear. This study aimed to assess the diagnostic utility of DTC for predicting SSIs in pediatric cardiovascular surgery patients.

Titanium clips and ligamentum flavum-epidural fat patch graft for midline lumbar durotomy closure in pediatric neurosurgery.

Objective: CSF leaks are a significant source of patient morbidity following intradural spine surgeries. Watertight dural closure is crucial during these procedures to minimize the risk of a CSF leak. This study reports postoperative outcomes and changes in patient management after switching to penetrating titanium clips for dural closure in a large cohort of pediatric patients receiving a tethered cord release (TCR) or a selective dorsal rhizotomy (SDR).

The utility of routine intraoperative CSF during ventricular shunt insertion: a 10-year retrospective cohort study.

Objective: Ventricular shunt insertion is a common procedure in pediatric neurosurgical practice. In many areas of medicine there is a push toward rationalization of healthcare resources and a reduction in low-value tests or procedures. The intraoperative sampling of CSF at the time of shunt insertion is one traditional aspect of care that has not been rigorously evaluated.

Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.

Background And Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum.

KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.

IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.

Hepatic and Pancreatic Cellular Response to Early Life Nutritional Mismatch.

To determine the basis for perinatal nutritional mismatch causing metabolic dysfunction associated steatotic liver disease (MASLD) and diabetes mellitus, we examined adult phenotype, hepatic transcriptome, and pancreatic β-islet function. In prenatal caloric restricted rat with intrauterine growth restriction (IUGR) and postnatal exposure to high fat with fructose (HFhf) or high carbohydrate (RC), we investigated male and female IUGR-Hfhf and IUGR-RC, versus HFhf and CON offspring. Males more than females displayed adiposity, glucose intolerance, insulin resistance, hyperlipidemia, hepatomegaly with hepatic steatosis.

Caregiver food allergy self-efficacy explains the relationship between perceived food allergy severity and burden.

Objective: Caregiver perceived food allergy severity is associated with food allergy burden, while caregiver food allergy self-efficacy has been linked to improved quality of life for caregivers. This study examined the mediating effect of caregiver food allergy self-efficacy on the relationship between perceived food allergy severity and caregiver food allergy burden.

Methods: Caregivers of children diagnosed with IgE-mediated food allergy were recruited from pediatric allergy clinics to complete demographic and medical questionnaires, the Food Allergy Independent Measure-Parent Form, the Food Allergy Self-Efficacy Scale for Parents, and the Food Allergy Quality of Life-Parental Burden.

Brain Transcriptome Changes Associated With an Acute Increase of Protein O-GlcNAcylation and Implications for Neurodegenerative Disease.

Enhancing protein O-GlcNAcylation by pharmacological inhibition of the enzyme O-GlcNAcase (OGA) has been considered as a strategy to decrease tau and amyloid-beta phosphorylation, aggregation, and pathology in Alzheimer's disease (AD). There is still more to be learned about the impact of enhancing global protein O-GlcNAcylation, which is important for understanding the potential of using OGA inhibition to treat neurodegenerative diseases. In this study, we investigated the acute effect of pharmacologically increasing O-GlcNAc levels, using the OGA inhibitor Thiamet G (TG), in normal mouse brains.

Outcomes of Triceps Surae Lengthening Surgery in Children With Charcot-Marie-Tooth Disease: A Multisite Investigation.

Background: Orthopaedic surgical intervention in children with Charcot-Marie-Tooth (CMT) often includes triceps surae lengthening (TSL) and foot procedures to address instability and pain due to equinus and cavovarus deformities. These surgeries may unmask underlying weakness in this progressive disease causing increased calcaneal pitch and excessive dorsiflexion in terminal stance leading to crouch. The purpose of this study was to evaluate changes in ankle function during gait following TSL surgery in children with CMT.

Neurodevelopmental and Mental Health Outcomes in a National Clinical Sample of Youth With Sex Chromosome Trisomies Compared With Matched Controls.

Objective: To compare the prevalence of neurodevelopmental and mental health diagnoses in a national sample of youth with sex chromosome trisomies (SCTs) with matched controls.

Methods: Patients in PEDSnet and a diagnosis code mapping to 47,XXY/Klinefelter syndrome (n = 1171), 47,XYY/Double Y syndrome (n = 243), or 47,XXX/Trisomy X syndrome (n = 262) were matched with controls using propensity scores. Generalized estimating equations computed odds ratios (OR) with 95% confidence intervals (CI) for the prevalence of diagnoses within the neurodevelopmental and mental health composites, psychotropic medication prescriptions, and encounters with behavioral health and therapy providers.

Glutathione, Vitamin C, and Cysteine Use in Autistic Children With Disruptive Behavior: A Double-Blind, Placebo-Controlled Crossover Pilot Study.

Objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication differences and restricted interests. One proposed biologic mechanism underlying ASD is oxidative stress, leading to the clinical use of glutathione based on anecdotal reports of improved behavior in autistic children. In this pilot study, we tested this observation using a randomized clinical trial format to collect preliminary data on glutathione safety and efficacy.

Control of striatal circuit development by the chromatin regulator .

The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.

Monitoring Treatment Fidelity in a Pragmatic Pediatric Rehabilitation Trial Comparing Two Physical Therapy Schedules: Analysis and Unexpected Findings.

Objective: This study aimed to describe the monitoring of treatment fidelity in a pragmatic pediatric rehabilitation trial using the National Institutes of Health Behavior Change Consortium framework, and to identify child and therapist factors that influence treatment fidelity.

Methods: Therapists (n = 28) were trained in the key ingredients (1-on-1, functional, goal-directed, motor learning intervention) and study protocol for a comparative effectiveness trial titled: A Comparison: High Intensity periodic vs. Every week therapy in children with cerebral palsy (ACHIEVE) for children ages 2 to 8 years with cerebral palsy.

Inpatient Audiologic Services Facilitate Early Hearing Detection.

Purpose: Infants needing neonatal intensive care unit (NICU) intervention have protracted timelines for diagnosis after not passing their newborn hearing screening despite being at higher risk for congenital hearing loss. The primary aim of this study was to evaluate the outcomes of early hearing detection for infants with a history of NICU admission. The secondary aim was to determine if diagnostic audiology services within the NICU setting accelerated diagnosis and intervention.

Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation.

Quantification of transcription activities in mammalian preimplantation embryos is challenging due to a huge amount of maternally stored transcripts and paucity of research materials. Here, we investigate genome-wide transcription activities of mouse and human preimplantation embryos by quantifying elongating RNA polymerase II. Two transcriptional waves are identified in early mouse embryos, with summits at the 2-cell and 8-cell stages.

Lack of context modulation in human single neuron responses in the medial temporal lobe.

In subjects implanted with intracranial electrodes, we use two different stories involving the same person (or place) to evaluate whether and to what extent context modulates human single-neuron responses. Nearly all neurons (97% during encoding and 100% during recall) initially responding to a person/place do not modulate their response with context. Likewise, nearly none (<1%) of the initially non-responsive neurons show conjunctive coding, responding to particular persons/places in a particular context during the tasks.

Accuracy and Performance Characteristics of Administrative Codes for the Diagnosis of Autoinflammatory Syndromes: A Discovery and Validation Study.

Objective: The aim of this study was to evaluate and validate the accuracy and performance characteristics of administrative codes in diagnosing autoinflammatory syndromes (AISs).

Methods: We identified potential AIS patients from the electronic medical records at the University of Iowa Hospital and Clinics and the Stead Family Children's Hospital using a screening filter based on the 10th edition of the International Classification of Diseases (ICD-10) codes and interleukin-1 antagonists. Diagnostic criteria for adult-onset Still disease, systemic juvenile idiopathic arthritis, Behçet disease (BD), familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), and SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome and chronic nonbacterial osteomyelitis (SAPHO-CNO) were reviewed for each patient.

Tear neuropeptides are associated with clinical symptoms and signs of dry eye patients.

Purpose: To evaluate levels of 3 tear-soluble neuropeptides in dry eye patients and to identify the correlations with clinical signs and symptoms.

Methods: A total of 16 dry eye patients and 12 healthy volunteers were enrolled. Dry eye disease (DED) diagnosis was based on the 2017 Report of the Tear Film & Ocular Surface Society International Dry Eye Workshop (TFOS DEWS II).

Effectiveness of behavioural and psychological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.

Objective: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of behavioural and psychological interventions for managing paediatric obesity.

Methods: Eligible studies, published between 1985 and 2022, included 0 to 18 year olds with outcomes reported ≥3 months post-baseline, including patient-reported outcome measures (PROMs), cardiometabolic and anthropometric outcomes, and adverse events (AEs). We pooled data using a random effects model and assessed certainty of evidence (CoE) related to minimally important difference estimates for outcomes using GRADE.

Maralixibat Reduces Serum Bile Acids and Improves Cholestatic Pruritus in Adolescents With Alagille Syndrome.

Background: Alagille syndrome (ALGS) is a multisystem cholestatic disorder. Maralixibat is approved for the treatment of cholestatic pruritus in ALGS with limited data in adults.

Methods: Participants were included if they received ≥ 2 doses of maralixibat at age ≥ 16 years in one of the three previously published maralixibat ALGS clinical trials.

Effects of HMG CoA reductase (HMGCR) deficiency on skeletal muscle development.

Pathogenic variants in HMGCR were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern.