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.

is overexpressed in keloid keratinocytes and its inhibition alters profibrotic gene expression.

Background: Keloids are disfiguring, fibrotic scar-like lesions that are challenging to treat and commonly recur after therapy. A deeper understanding of the mechanisms driving keloid formation is necessary for the development of more effective therapies. Reduced vitamin D receptor (VDR) expression has been observed in keloids, implicating vitamin D signaling in keloid pathology.

Stroke Prevention in Hispanic Children with Sickle Cell Anemia: the SACRED trial.

Sickle cell anemia (SCA) is recognized globally, but little is known about affected Hispanic populations. In partnership with Dominican Republic, a Hispanic Caribbean Island with a large SCA population, a TCD screening program provided hydroxyurea to children with conditional velocities. Building local capacity, ten Dominican medical graduates were certified in TCD examinations and trained in hydroxyurea management.

Phase 1 Study of Quercetin, a Natural Antioxidant in Children and Young Adults with Fanconi Anemia (FA).

Fanconi anemia (FA) is a rare inherited disorder characterized by progressive bone marrow failure (BMF) and a predisposition to malignancy. Systemic reactive-oxygen species (ROS) and increased sensitivity of FA hematopoietic progenitors to ROS play a key role in the pathogenesis of BMF. Treatment with antioxidants improve hematopoietic function in Fancc-/- mice.

Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

Background: The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine.

Methods: The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6 months to 16 years with estimated glomerular filtration rate (eGFR) 30-89 ml/min/1.

The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis.

The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation.

Prothrombin prevents fatal T cell-dependent anemia during chronic virus infection of mice.

Thrombin promotes the proliferation and function of CD8+ T cells. To test if thrombin prevents exhaustion and sustains antiviral T cell activity during chronic viral infection, we depleted the thrombin-precursor prothrombin to 10% of normal levels in mice prior to infection with the clone 13 strain of lymphocytic choriomeningitis virus. Unexpectedly, prothrombin insufficiency resulted in 100% mortality after infection that was prevented by depletion of CD8+ T cells, suggesting that reduced availability of prothrombin enhances virus-induced immunopathology.

Mortality Patterns in Pediatric Pulmonary Vein Stenosis: Insights Into Right Ventricular Systolic Pressure Associations.

Background: Pulmonary vein stenosis in children is associated with a poor prognosis. However, the cause and risk factors for mortality remain uncertain.

Methods: This retrospective, single-center study identified children with primary and secondary pulmonary vein stenosis through a cardiac catheterization database.

Eighth Annual Society of Thoracic Surgeons Pedimacs Report.

Background: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs).

Methods: From September 19, 2012, to December 31, 2023, there were 1648 devices in 1349 patients (<19 years) from 39 North American Hospitals with 100 patients enrolled in 2023.

Results: Cardiomyopathy was the most common underlying etiology (59%), followed by congenital heart disease (26%) and myocarditis (8%).

Potentialities and critical issues of liquid biopsy in clinical practice: An umbrella review.

Background: Liquid biopsy (LB) is a laboratory test performed on a fluid sample aiming at analyzing molecular data derived from circulating cells and related entities, or from nucleic acids. This umbrella review aims to map and evaluate the evidence supporting the use of LB in medicine across different medical specialities and conditions.

Methods: We searched three repositories from database inception up to October 1, 2023 and we included meta-analyses of observational studies reporting data on the use of LB, compared to gold standard, and its accuracy (area under the curve, AUC).

Consensus outcomes between health professionals and parents for oral corticosteroids in treating preschool wheeze: a multi-national survey and nominal group technique study.

Objective: To obtain priority consensus for outcome measures of oral corticosteroid treatment of preschool wheeze that represent stakeholder groups.

Design: (1) A systematic review to identify a set of outcome measures; (2) an international survey for healthcare professionals (HCPs) and a nominal group meeting with parents; (3) a final consensus nominal group meeting with key HCPs (trial investigators and paediatric emergency medicine clinicians) and the same parent group.

Main Outcome Measures: Consensus priority of treatment outcome measures, outcome minimal clinically important differences (MCIDs) and level of concerns about adverse effects.

Heart Transplantation Outcomes for Fontan Patients When Using Contemporary Strategies: Heart-Liver Transplantation and Ventricular Assist Device Therapy.

Background: With an increasing number of Fontan patients surviving into adulthood, the burden of end-stage heart failure is increasing. Prior studies have reported suboptimal heart transplantation (HTx) outcomes. Therefore, the authors describe their institutional experience of HTx in patients with Fontan circulation failure, including heart-liver transplantation (HLTx) and pretransplant systemic ventricular assist device (SVAD) therapies.

Oxidative Stress Early After Hematopoietic Stem Cell Transplant.

HSCT conditioning regimens cause massive lysis of hematopoietic cells with release of toxic intracellular molecules into the circulation. To describe the response to oxidative stress early after hemopoietic stem cell transplantation (HSCT) and assess the association of early oxidative stress with later transplant outcomes. Key components of in the body's physiological response to oxidative stress were studied in a cohort of 122 consecutive pediatric allogeneic HSCT recipients.

A Controversial Clinical Case of a Child With Hypoplastic Left Heart Syndrome.

We present the case of a child born with hypoplastic left heart syndrome. After developing multiple complications following the first surgical stage (Norwood procedure), her parents decide not to proceed with the second stage (Glenn operation). Cardiac surgeons, pediatric intensivists, a psychologist, and a bioethicist analyze whether further surgical intervention is ethically obligatory.

Screening for Structural Heart Defects: A Single-Center Retrospective Cost Analysis for Fetal Echocardiography in Adults with Congenital Heart Disease.

Fetal echocardiography (FE) is recommended for parents with congenital heart disease (pCHD) due to a 3-6% recurrence risk of congenital heart disease (CHD). This study aimed to evaluate the cost of FE for detecting neonatal CHD in pCHD. FE data were collected between 12/2015 and 12/2022.

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.

Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.

The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.

Background: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.

Trochleoplasty Utilization in the Management of Patellofemoral Instability: Results From an International Survey of Surgeons.

Background: Considerable variability exists in the described clinical and radiographic indications for use, surgical techniques, postoperative management, and risk profile after trochleoplasty for the management of patellofemoral instability (PFI). In areas of clinical uncertainty, a cohesive summary of expert opinion and identification of areas of variation in current practice can be useful in guiding current practice and future research efforts.

Purpose: To assess the current indications for use, surgical techniques, postoperative rehabilitation practices, and observed complication profile for trochleoplasty in the management of PFI among surgeons who perform this procedure.

Community Implementation and Evaluation of the Chicago Parent Program.

The purpose of this study was to describe and evaluate the implementation of the Chicago Parent Program (CPP) in a community setting. Included are details of the co-designed implementation by academic and community partners, and parenting and child behavior outcomes. Two hundred eighty caregivers of children aged 2-5 years participated in the CPP in seven community sites.

Communicating neurological prognosis in the prenatal period: a narrative review and practice guidelines.

Clinicians may face an array of challenges in conducting fetal neurological consultations including prognostic uncertainty, a lack of training in fetal counseling, and limited opportunity to build rapport with families. In this setting, it is critical to employ high-quality, family-centered care to allow expectant parents to make informed decisions. Despite the challenges and gravity of these consultations, there remains limited data outlining best conduct and communication practices.

A thermally polarized, dissolved-phase Xe phantom for quality-control and multisite comparisons of gas-exchange imaging.

Harmonizing and validating Xe gas exchange imaging across multiple sites is hampered by a lack of a quantitative standard that 1) displays the unique spectral properties of Xe observed from human subjects in vivo and 2) has short enough T times to enable practical imaging. This work describes and demonstrates the development of two dissolved-phase, thermally polarized phantoms that mimic the in-vivo, red blood cell and membrane resonances of Xe dissolved in human lungs. Following optimization, combinations of two common organic solvents, acetone and dimethyl sulfoxide, resulted in two in-vivo-like dissolved-phase Xe phantoms yielding chemical shifts of 212.