UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation.

The RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. The model posits that nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). However, the extent to which DNMT1 relies on ubiquitin signaling through UHRF1 in support of DNA methylation maintenance remains unclear.

Model based fitting of pattern reversal visually evoked potentials provides a reliable characterization of waveform components.

Objective: To introduce a novel approach to analyzing pattern reversal visual evoked potentials (prVEPs) using a difference-of-gammas model-based fitting method.

Methods: prVEP was recorded from uninjured youth ages 11-19 years during pre- or postseason sports evaluation. A difference-of-gammas model fit was used to extract the amplitude, peak time, and peak width of each of four gamma components.

Unlocking the Potential: A Systematic Review of Master Protocol in Pediatrics.

The use of master protocols allows for innovative approaches to clinical trial designs, potentially enabling new approaches to operations and analytics and creating value for patients and drug developers. Pediatric research has been conducted for many decades, but the use of novel designs such as master protocols in pediatric research is not well understood. This study aims to provide a systematic review on the utilization of master protocols in pediatric drug development.

Investigation of Cerebral Mitochondrial Injury in a Porcine Survivor Model of Carbon Monoxide Poisoning.

Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV).

Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection.

Background: Diabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.

Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes.

Immunological chaperones tapasin and TAP binding protein, related (TAPBPR) play key roles in antigenic peptide optimization and quality control of nascent class I major histocompatibility complex (MHC-I) molecules. The polymorphic nature of MHC-I proteins leads to a range of allelic dependencies on chaperones for assembly and cell-surface expression, limiting chaperone-mediated peptide exchange to a restricted set of human leukocyte antigen (HLA) allotypes. Here, we demonstrate and characterize xeno interactions between a chicken TAPBPR ortholog and a complementary repertoire of HLA allotypes, relative to its human counterpart.

Spring forces and calvarial thickness predict cephalic index changes following spring-mediated cranioplasty for sagittal craniosynostosis.

Background: Variables interacting to predict outcomes following spring-mediated cranioplasty (SMC) for non-syndromic craniosynostosis, including spring parameters and calvarial thickness, are poorly understood. This study assessed interactions between spring parameters and calvarial thickness to predict changes in cephalic index (CI) following SMC.

Methods: Patients undergoing SMC for non-syndromic sagittal craniosynostosis at our institution between 2014 and 2021 were included.

Endocrine Complications of Cystic Fibrosis.

Endocrine comorbidities have become increasingly important medical considerations as improving cystic fibrosis (CF) care increases life expectancy. Although the underlying pathophysiology of CF-related diabetes remains elusive, the use of novel technologies and therapeutics seeks to improve both CF-related outcomes and quality of life. Improvements in the overall health of those with CF have tempered concerns about pubertal delay and short stature; however, other comorbidities such as hypogonadism and bone disease are increasingly recognized.

One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.

EWS/FLI is the defining mutation of Ewing sarcoma. This oncogene drives malignant transformation and progression and occurs in a genetic background characterized by few other recurrent cooperating mutations. In addition, the tumor is absolutely dependent on the continued expression of EWS/FLI to maintain the malignant phenotype.

Barriers and facilitators to implementing telehealth services during the COVID-19 pandemic: A qualitative analysis of interviews with cystic fibrosis care team members.

Background: The COVID-19 pandemic forced cystic fibrosis (CF) care programs to rapidly shift from in-person care delivery to telehealth. Our objective was to provide a qualitative exploration of facilitators and barriers to: 1) implementing high-quality telehealth and 2) navigating reimbursement for telehealth services.

Methods: We used data from the 2020 State of Care CF Program Survey (n=286 U.

Neonatal encephalopathy: Etiologies other than hypoxic-ischemic encephalopathy.

Neonatal encephalopathy (NE) describes the clinical syndrome of a newborn with abnormal brain function that may result from a variety of etiologies. HIE should be distinguished from neonatal encephalopathy due to other causes using data gathered from the history, physical and neurological exam, and further investigations. Identifying the underlying cause of encephalopathy has important treatment implications.

An owner's manual for CD19 "CAR"-T cell therapy in managing pediatric and young adult B-cell acute lymphoblastic leukemia.

Despite excellent cure rates in newly diagnosed patients with B-cell acute lymphoblastic leukemia (B-ALL), therapies that improve outcomes for children with relapsed or refractory (r/r) B-ALL are needed. Chimeric antigen receptor (CAR)-T cell therapy has demonstrated durable responses and a manageable safety profile in children, adolescents, and young adults less than 26 years old with r/r B-ALL, including patients who have relapsed after allogeneic stem cell transplant. This comprehensive review summarizes current data, management practices, and future directions for the treatment of r/r B-ALL in pediatric and young adult patients with CAR-T cell therapy, including patient selection, patient preparation, and CAR-T cell infusion, as well as monitoring and management of short- and long-term safety events, long-term surveillance, and survivorship.

The spectrum of pediatric amplified musculoskeletal pain syndrome.

Background: Children presenting with musculoskeletal pain to pediatric rheumatology clinics are very heterogeneous and on a continuum from those with localized pain to total body pain. Many report intermittent, rather than constant, pain. We examined clinical and psychological characteristics of these children at presentation and specifically those who fulfilled the criteria for fibromyalgia.

Interventions for Children with Neurocognitive Impairments in Resource-Limited Settings: A Systematic Review.

Many children and adolescents around the world suffer from neurocognitive deficits due to chronic disorders, such as Human Immunodeficiency Virus (HIV) and malaria. Resource-limited settings exacerbate the risk of negative cognitive outcomes due to high prevalence of associated disorders, poverty, and limited access to interventions. Current literature does not provide consensus regarding the efficacy of interventions to support children with cognitive impairments in low-resource settings.

Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update.

The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins.

Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer.

While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes.