Targeted disruption of Gdi2 causes early embryonic lethality.

Introduction: GDI2 regulates the GDP/GTP exchange reaction of Rab proteins by inhibiting the dissociation of GDP and the subsequent binding of GTP, dysregulation of GDI2 has been reported in many different cancers. Recently, we found that GDI2 bound to the ITIM domain of Siglec-G under normal homeostasis, whereas Rab1a was recruited to the ITIM domain during bacterial infection. Therefore, GDI2 and Rab1a may regulate the immune response through interaction with the ITIM domain during bacterial infection.

Apolipoprotein A5, a unique modulator of fasting and postprandial triglycerides.

The discovery of apolipoprotein A5 (APOA5) in 2001 has raised a number of intriguing questions about its role in lipid transport and triglyceride (TG) homeostasis. Genome-wide association studies have consistently identified APOA5 as a regulator of plasma TG levels, which is further supported by studies in transgenic and knockout mouse models. The present review describes recent concepts pertaining to the roles of APOA5 in TG metabolism as related to the vascular compartment, liver, adipose tissue and the gut.

Single Gene Mutations in or Alter Extracellular Vesicle Production and Trafficking.

Patients with autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are born with normal or near-normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease-promoting extracellular vesicles (EVs) that induce genetically intact cells to participate in the renal disease process. We used centrifugation and size exclusion chromatography to isolate the EVs for study.

Treatment of sialorrhea with botulinum toxin injections in pediatric patients less than three years of age.

Objective: To determine the patient demographics and the efficacy and safety profile of botulinum toxin (BTX) injections for sialorrhea control in patients under the age of three.

Methods: This is a retrospective chart review study. Patients under three years of age who received BTX injections for sialorrhea management from 2010 to 2021 were assessed.

Analyzing Relationships Between Economic and Neighborhood-Related Social Determinants of Health and Intensive Care Unit Length of Stay for Critically Ill Children With Medical Complexity Presenting With Severe Sepsis.

Objectives: Of the Social Determinants of Health (SDoH), we evaluated socioeconomic and neighborhood-related factors which may affect children with medical complexity (CMC) admitted to a Pediatric Intensive Care Unit (PICU) in Shelby County, Tennessee with severe sepsis and their association with PICU length of stay (LOS). We hypothesized that census tract-level socioeconomic and neighborhood factors were associated with prolonged PICU LOS in CMC admitted with severe sepsis in the underserved community.

Methods: This single-center retrospective observational study included CMC living in Shelby County, Tennessee admitted to the ICU with severe sepsis over an 18-month period.

Progressive Reduction in Right Ventricular Contractile Function Attributable to Altered Actin Expression in an Aging Mouse Model of Arrhythmogenic Cardiomyopathy.

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder of desmosomal dysfunction, and PKP2 (plakophilin-2) has been reported to be the most common disease-causing gene when mutation-positive. In the early concealed phase, the ACM heart is at high risk of sudden cardiac death before cardiac remodeling occurs because of mistargeted ion channels and altered Ca handling. However, the results of pathogenic PKP2 variants on myocyte contraction in ACM pathogenesis remain unknown.

Impact of Therapeutics on Unified Immunity During Allergic Asthma and Respiratory Infections.

Asthma is a common chronic respiratory disease that affects millions of people worldwide. Patients with allergic asthma, the most prevalent asthma endotype, are widely considered to possess a defective immune response against some respiratory infectious agents, including viruses, bacteria and fungi. Furthermore, respiratory pathogens are associated with asthma development and exacerbations.

Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown.

Objectives: The prevalence of mental health issues has increased at an alarming rate during the COVID-19 pandemic. Furthermore, an exacerbated psychosocial burden in populations with chronic disease is observed. This cross-sectional study evaluated the psychosocial factors of pediatric type 1 diabetes (T1D) during the COVID-19 pandemic.

Pediatric traumatic brain injury: Resource utilization and outcomes at adult versus pediatric trauma centers.

Introduction: Traumatic brain injury is the leading cause of trauma-related death in children. We hypothesized that children with isolated traumatic brain injury would experience differential outcomes when treated at pediatric versus adult or combined trauma centers.

Methods: After institutional review board approval, the 2015 National Trauma Data Bank was queried for children up to age 16 years with isolated traumatic brain injury.

Targeted disruption of Rab1a causes early embryonic lethality.

Guanosine nucleotide diphosphate (GDP) dissociation inhibitor 2 (GDI2) regulates the GDP/guanosine triphosphate (GTP) exchange reaction of Rab proteins by inhibiting the dissociation of GDP and the subsequent binding of GTP. The present study aimed to determine the function of Rab1a , and thus generated mice with a trapped gene. It was demonstrated that is essential for embryonic development.

Effects of Medicare comprehensive medication review on racial/ethnic disparities in nonadherence to statin medications among patients with Alzheimer's Disease: an observational analysis.

Background: Alzheimer's Disease (AD) is the mostcommon cause of dementia, a neurological disorder characterized by memory loss and judgment impairment. Hyperlipidemia, a commonly co-occurring condition, should be treated to prevent associated complications. Medication adherence may be difficult for individuals with AD due to the complexity of AD management.

Prevalence of Upper Gastrointestinal Inflammation in Teens With Obesity Prior to Sleeve Gastrectomy.

Introduction: Upper gastrointestinal (UGI) pathologies are common in adolescents with obesity. This study aims to determine the prevalence of UGI inflammation on preoperative esophagogastroduodenoscopy (EGD) in adolescents undergoing sleeve gastrectomy (SG) and to assess weight loss outcomes.

Methods: This is a retrospective analysis of pathology reports from EGD biopsies performed prior to SG from September 2017 to August 2020.

mutation induces renal tubular cell nonautonomous disease.

TSC renal cystic disease is poorly understood and has no approved treatment. In a new principal cell-targeted murine model of cystic disease, the renal cystic epithelium is mostly composed of type A intercalated cells with an intact gene confirmed by sequencing, although these cells exhibit a -mutant disease phenotype. We used a newly derived targeted murine model in lineage tracing and extracellular vesicle (EV) characterization experiments and a cell culture model in EV characterization and cellular induction experiments to understand TSC cystogenesis.

and Expressions Are Regulated by and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2.

Studies showed that the gastrointestinal (GI) tract is one of the most important pathways for SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19). As SARS-CoV-2 cellular entry depends on the ACE2 receptor and TMPRSS2 priming of the spike protein, it is important to understand the molecular mechanisms through which these two proteins and their cognate transcripts interact and influence the pathogenesis of COVID-19. In this study, we quantified the expression, associations, genetic modulators, and molecular pathways for and mRNA expressions in GI tissues using a systems genetics approach and the expanded family of highly diverse BXD mouse strains.

Systems genetics analysis defines importance of TMEM43/ for cardiac- and metabolic-related pathways.

Broad cellular functions and diseases including muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC5) and cancer are associated with transmembrane protein43 (TMEM43/). The study aimed to investigate biological roles of through genetic regulation, gene pathways and gene networks, candidate interacting genes, and up- or downstream regulators. Cardiac transcriptomes from 40 strains of recombinant inbred BXD mice and two parental strains representing murine genetic reference population (GRP) were applied for genetic correlation, functional enrichment, and coexpression network analysis using systems genetics approach.

Combining whole exome sequencing with in silico analysis and clinical data to identify candidate variants in pediatric left ventricular noncompaction.

Background: Understanding the overall variant burden in pediatric patients with left ventricular noncompaction (LVNC) has clinical implications. Whole exome sequencing (WES) allows detection of coding variants in both candidate cardiomyopathy genes and those included on commercial panels. Other lines of evidence, including in silico analysis, are necessary to reduce the overwhelming number of variants to those most likely having a phenotypic impact.

SMAD2 and SMAD3 differentially regulate adiposity and the growth of subcutaneous white adipose tissue.

Adipose tissue is the primary site of energy storage, playing important roles in health. While adipose research largely focuses on obesity, fat also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety and total energy homeostasis. SMAD2/3 proteins are downstream mediators of activin signaling, which regulate critical preadipocyte and mature adipocyte functions.

Waitlist management in a pediatric weight management clinic: implementing an orientation session.

Background: This study evaluates implementation of an orientation session to address a waitlist of more than 2000 referrals to a pediatric weight management clinic in the Mid-South United States.

Methods: An hour-long group-based orientation to the pediatric weight management clinic was implemented to provide information about the structure and expectations of the clinic as well as education on healthy lifestyle recommendations. Families were contacted from the waitlist by telephone and invited to attend an orientation session prior to scheduling a clinic appointment.

Characteristics of phantom limb pain in U.S. civilians and service members.

Objectives: The population of Americans with limb loss is on the rise, with a different profile than in previous generations (e.g., greater incidence of amputation due to diabetes).

The Pediatric Trauma Society Annual Meeting: An Analysis of Scholarly Output From the First 5 Years.

Background: The Pediatric Trauma Society (PTS) is a multidisciplinary organization, with scientific presentations at its annual meeting addressing trauma care from prehospital through rehabilitation.

Objective: The purpose of this study was to identify and describe the scholarly areas of focus of presentations at the annual meeting over the society's first 5 years and evaluate research dissemination.

Methods: Data were collected on abstracts presented between 2014 and 2018, including titles, authors, and abstract classification.

Addressing Structural Racism Is Critical for Ameliorating the Childhood Obesity Epidemic in Black Youth.

Racism and childhood obesity are both pervasive factors adversely affecting the health and wellbeing of children and adolescents in the United States. The association between racism and obesity has been touched upon in the literature; yet most work has focused on a few dimensions of intersectionality of these two domains at one time. The renewed focus on structural racism as the primary contributor to distress of Black individuals in the United States has highlighted the urgency of identifying the contributions of racism to the childhood obesity epidemic.

Renal cystic disease in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is associated with or gene mutations resulting in hyperactivation of the mTORC1 pathway. This mTORC1 activation is associated with abnormal tissue development and proliferation such that in the kidney there are both solid tumors and cystic lesions. This review summarizes recent advances in tuberous sclerosis complex nephrology and focuses on the genetics and cell biology of tuberous sclerosis complex renal disease, highlighting a role of extracellular vesicles and the innate immune system in disease pathogenesis.