Impaired Endogenous Neurosteroid Signaling Contributes to Behavioral Deficits Associated With Chronic Stress.

Background: Chronic stress is a major risk factor for psychiatric illnesses, including depression. However, the pathophysiological mechanisms whereby stress leads to mood disorders remain unclear. Allopregnanolone acts as a positive allosteric modulator preferentially on δ subunit-containing GABA (gamma-aminobutyric acid A) receptors.

Common mouse models of tauopathy reflect early but not late human disease.

Background: Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer's Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level.

Methods: We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics.

Fetal anomaly diagnosis and termination of pregnancy.

The aim of this review was to discuss bioethics in prenatal diagnosis and health care after recent legislative and judicial changes affecting reproductive rights, such as the repeal of 'Roe v. Wade' in the United States. We recognize that abortion involves particular moralities that are not universal or shared by all cultures, groups, and individuals.

Neuromonitoring During ECMO Support in Children.

Extracorporeal membrane oxygenation is a potentially lifesaving intervention for children with severe cardiac or respiratory failure. It is used with increasing frequency and in increasingly more complex and severe diseases. Neurological injuries are important causes of morbidity and mortality in children treated with extracorporeal membrane oxygenation and include ischemic stroke, intracranial hemorrhage, hypoxic-ischemic injury, and seizures.

Factors Associated With Chronic Intestinal Inflammation Resembling Inflammatory Bowel Disease in Pediatric Intestinal Failure: A Matched Case-Control Study.

Background And Aims: There is a subset of intestinal failure patients with associated chronic intestinal inflammation resembling inflammatory bowel disease. This study aimed to evaluate factors associated with chronic intestinal inflammation in pediatric intestinal failure.

Methods: This was a single-center retrospective case-control study of children <18 years old with intestinal failure.

Ventricular Tachycardia in a Pediatric Patient with High-Risk Thrombotic Thrombocytopenia Purpura.

An 8-year-old previously healthy male was diagnosed with thrombotic thrombocytopenic purpura (TTP) and increased serum cardiac troponin I. Telemetry recorded non-sustained ventricular tachycardia, without ST-segment changes or other abnormalities on serial electrocardiogram. This case illustrates that cardiac monitoring by telemetry should be considered in high-risk TTP with elevated cardiac troponin.

Encoding of environmental illumination by primate melanopsin neurons.

Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare and challenging to target for electrophysiological recording. We developed a method of acute identification within the live, ex vivo retina.

Late Health Outcomes Among Survivors of Wilms Tumor Diagnosed Over Three Decades: A Report From the Childhood Cancer Survivor Study.

Purpose: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.

Methods: Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents.

Community consultation in the pediatric intensive care unit for an exception from informed consent Trial: A survey of patient caregivers.

Aim: To explore perspectives of families in the pediatric intensive care unit (PICU) about an emergency interventional trial on peri-arrest bolus epinephrine for acute hypotension using Exception From Informed Consent (EFIC).

Methods: We performed face-to-face interviews with families whose children were hospitalized in the PICU. A research team member provided an educational presentation about the planned trial and administered a survey with open- and closed-ended items.

Examining Early Career Pediatrician Characteristics, Sacrifices, and Satisfaction.

Objective: Explore relationships between pediatrician characteristics, sacrifices made for career, and career and life satisfaction.

Methods: Surveys of early career pediatricians (ECPs) who recently graduated residency (2016-18), as part of the AAP Pediatrician Life and Career Experience Study (PLACES) were administered in 2019. Logistic regression analyzed association of pediatrician characteristics with personal sacrifices (a lot vs some or no sacrifices) made for one's career and whether career was worth the sacrifices made to become a physician, and association of characteristics and sacrifices with overall career and life satisfaction.

Outcomes of Patients Treated for Hepatoblastoma with Low Alpha-Fetoprotein and/or Small Cell Undifferentiated Histology: A Report from the Children's Hepatic Tumors International Collaboration (CHIC).

Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels.

Gasdermin D pore-forming activity is redox-sensitive.

Reactive oxygen species (ROS) regulate the activities of inflammasomes, which are innate immune signaling organelles that induce pyroptosis. The mechanisms by which ROS control inflammasome activities are unclear and may be multifaceted. Herein, we report that the protein gasdermin D (GSDMD), which forms membrane pores upon cleavage by inflammasome-associated caspases, is a direct target of ROS.

Linking specific biological signatures to different childhood adversities: findings from the HERO project.

Background: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited.

Methods: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1β, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S.

Development and Validation of the Scale for Pain Self-Efficacy (SPaSE) in German and English Languages for Children and Adolescents.

No validated measure for pain self-efficacy in children and adolescents is currently available in the German language, and existing English versions have limitations. This study used a thorough development process to create the Scale for Pain Self-Efficacy (SPaSE) in both German and English languages. Scale development was based on self-efficacy theory, adapting items from existing self-efficacy measures, and review of patients' perspectives.

Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing.

CRISPR-Cas gene editing has revolutionized experimental molecular biology over the past decade and holds great promise for the treatment of human genetic diseases. Here we review the development of CRISPR-Cas9/Cas12/Cas13 nucleases, DNA base editors, prime editors, and RNA base editors, focusing on the assessment and improvement of their editing precision and safety, pushing the limit of editing specificity and efficiency. We summarize the capabilities and limitations of each CRISPR tool from DNA editing to RNA editing, and highlight the opportunities for future improvements and applications in basic research, as well as the therapeutic and clinical considerations for their use in patients.

Low nephron endowment increases susceptibility to renal stress and chronic kidney disease.

Preterm birth results in low nephron endowment and increased risk of acute kidney injury (AKI) and chronic kidney disease (CKD). To understand the pathogenesis of AKI and CKD in preterm humans, we generated potentially novel mouse models with a 30%-70% reduction in nephron number by inhibiting or deleting Ret tyrosine kinase in the developing ureteric bud. These mice developed glomerular and tubular hypertrophy, followed by the transition to CKD, recapitulating the renal pathological changes seen in humans born preterm.

A Unique Lens: Understanding What Nurses Are Best Positioned to Assess About Residents.

Background: Resident feedback is generally elicited from attending physicians, although nurses can also provide feedback on distinct domains. Physicians may be hesitant to accept feedback from nurses if they perceive that nurses are being asked about areas outside their expertise. Understanding specific resident behaviors that nurses are best suited to assess is critical to successful implementation of feedback from nurses to residents.