Altered Purinergic Signaling and CD8+ T Cell Dysregulation in STAT3 GOF Syndrome.

Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants in STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8+ T cells have been implicated as pathogenic drivers of autoimmunity.

The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

We describe humans with rare biallelic loss-of-function variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development.

Metabolic profile in first episode drug naïve patients with psychosis and its relation to cognitive functions and social cognition: a case control study.

1st episode drug naïve patients with psychosis might be at higher risk for cardiometabolic disturbances which could affect the different cognitive, and executive functions and domains of social cognition. This study aimed to study the metabolic parameters in 1st episode drug naïve patients with psychosis, to evaluate the relation of these cardiometabolic domains to the cognitive, executive functions, and social cognition. Socio-demographic characteristics of 150 first episode drug naïve patients with psychosis and 120 matched healthy control groups were collected.

Sleep in post-COVID-19 recovery period and its impact on different domains of quality of life.

Background: COVID-19 pandemic became a global health problem affecting the life of millions of people all over the world. The effects of this pandemic were not only on the physical and medical aspects but also on the psychological issues including anxiety disorders, depressive manifestations, sleep problems and others. Sleep disorders were very commonly reported during the novel Coronavirus-19 pandemic either in the acute phase of COVID-19 infection or after recovery.

COVID-19 Pandemic-Related Reductions in Pediatric Asthma Exacerbations Corresponded with an Overall Decrease in Respiratory Viral Infections.

Background: Respiratory viruses, air pollutants, and aeroallergens are all implicated in worsening pediatric asthma symptoms, but their relative contributions to asthma exacerbations are poorly understood. A significant decrease in asthma exacerbations has been observed during the coronavirus disease 2019 pandemic, providing a unique opportunity to study how major asthma triggers correlate with asthma activity.

Objective: To determine whether changes in respiratory viruses, air pollutants, and/or aeroallergens during the coronavirus disease 2019 pandemic were concomitant with decreased asthma exacerbations.

Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19.

Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood.

Post-COVID-19 fatigue and anhedonia: A cross-sectional study and their correlation to post-recovery period.

Background: Individuals infected by the novel coronavirus (SARS-CoV-2) have experienced different psychiatric manifestations during the period of infectivity and post-COVID-19 infection. Fatigue and anhedonia are among the frequently reported manifestations after recovery from this novel viral pandemic, leading to early evaluation of those patients and proper management of their complaints which have a drastic burden on different domains of life. Also, the period after recovery might have an effect on the severity of these two psychiatric presentations.

Pediatric Asthma Health Care Utilization, Viral Testing, and Air Pollution Changes During the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused dramatic changes in daily routines and health care utilization and delivery patterns in the United States. Understanding the influence of these changes and associated public health interventions on asthma care is important to determine effects on patient outcomes and identify measures that will ensure optimal future health care delivery.

Objective: We sought to identify changes in pediatric asthma-related health care utilization, respiratory viral testing, and air pollution during the COVID-19 pandemic.

Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes.

Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) did not differ by race, whereas a widely used monoclonal enzyme-linked immunosorbent assay (ELISA) quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals.

Mechanism of hyperinsulinism in short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency involves activation of glutamate dehydrogenase.

The mechanism of insulin dysregulation in children with hyperinsulinism associated with inactivating mutations of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) was examined in mice with a knock-out of the hadh gene (hadh(-/-)). The hadh(-/-) mice had reduced levels of plasma glucose and elevated plasma insulin levels, similar to children with SCHAD deficiency. hadh(-/-) mice were hypersensitive to oral amino acid with decrease of glucose level and elevation of insulin.

Extremes of clinical and enzymatic phenotypes in children with hyperinsulinism caused by glucokinase activating mutations.

Objective: Heterozygous activating mutations of glucokinase have been reported to cause hypoglycemia attributable to hyperinsulinism in a limited number of families. We report three children with de novo glucokinase hyperinsulinism mutations who displayed a spectrum of clinical phenotypes corresponding to marked differences in enzyme kinetics.

Research Design And Methods: Mutations were directly sequenced, and mutants were expressed as glutathionyl S-transferase-glucokinase fusion proteins.

Increased glucagon-like peptide-1 secretion and postprandial hypoglycemia in children after Nissen fundoplication.

Context: Postprandial hypoglycemia (PPH) is a frequent complication of Nissen fundoplication in children. The mechanism responsible for the PPH is poorly understood, but involves an exaggerated insulin response to a meal and subsequent hypoglycemia. We hypothesize that increased glucagon-like peptide-1 (GLP-1) secretion contributes to the exaggerated insulin surge and plays a role in the pathophysiology of this disorder.