Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years.

Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD.

Design, Setting, And Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital.

Depletion of Bone Marrow Hematopoietic Cells in Ebolavirus-Infected Rhesus Macaques: A Possible Cause of Hematologic Abnormalities in Ebolavirus Disease.

The pathophysiology of long-recognized hematologic abnormalities in Ebolavirus (EBOV) disease (EVD) is unknown. From limited human sampling (of peripheral blood), it has been postulated that emergency hematopoiesis plays a role in severe EVD, but the systematic characterization of the bone marrow (BM) has not occurred in human disease or in nonhuman primate models. In a lethal rhesus macaque model of EVD, 18 sternal BM samples exposed to the Kikwit strain of EBOV were compared to those from uninfected controls (n = 3).

Anesthesia and Sedation Exposure and Neurodevelopmental Outcomes in Infants Undergoing Congenital Cardiac Surgery: A Retrospective Cohort Study.

Background: Children undergoing complex cardiac surgery are exposed to substantial cumulative doses of sedative medications and volatile anesthetics and are more frequently anesthetized with ketamine, compared with healthy children. This study hypothesized that greater exposure to sedation and anesthesia in this population is associated with lower neurodevelopmental scores at 18 months of age.

Methods: A secondary analysis was conducted of infants with congenital heart disease who participated in a prospective observational study of environmental exposures and neurodevelopmental outcomes to assess the impact of cumulative volatile anesthetic agents and sedative medications.

Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes.

Liver damage and an exacerbated inflammatory response are hallmarks of Ebola virus (EBOV) infection. Little is known about the intrinsic response to infection in human hepatocytes and their contribution to inflammation. Here, we present an induced pluripotent stem cell (iPSC)-derived hepatocyte-like cell (HLC) platform to define the hepato-intrinsic response to EBOV infection.

Improving Blood Pressure Screening in Neonatal Follow-up Clinic: A Quality Improvement Initiative.

Introduction: The American Academy of Pediatrics recommends blood pressure screening at every health care encounter in children younger than 3 years if they have a history of prematurity or other neonatal complications requiring intensive care because these children have an increased risk for hypertension.

Methods: A multidisciplinary team conducted a quality improvement initiative to improve blood pressure screening at a single-center outpatient neonatal follow-up clinic. We developed a focused intervention program including a standardized blood pressure measurement protocol, staff training and education, and streamlined documentation.

Natural Occurring Polymorphisms in HIV-1 Integrase and RNase H Regulate Viral Release and Autoprocessing.

Recently, a genome-wide association study using plasma HIV RNA from antiretroviral therapy-naive patients reported that 14 naturally occurring nonsynonymous single-nucleotide polymorphisms (SNPs) in HIV derived from antiretrovirus drug-naive patients were associated with virus load (VL). Those SNPs were detected in reverse transcriptase, RNase H, integrase, envelope, and Nef. However, the impact of each mutation on viral fitness was not investigated.

FIB-SEM as a Volume Electron Microscopy Approach to Study Cellular Architectures in SARS-CoV-2 and Other Viral Infections: A Practical Primer for a Virologist.

The visualization of cellular ultrastructure over a wide range of volumes is becoming possible by increasingly powerful techniques grouped under the rubric "volume electron microscopy" or volume EM (vEM). Focused ion beam scanning electron microscopy (FIB-SEM) occupies a "Goldilocks zone" in vEM: iterative and automated cycles of milling and imaging allow the interrogation of microns-thick specimens in 3-D at resolutions of tens of nanometers or less. This bestows on FIB-SEM the unique ability to aid the accurate and precise study of architectures of virus-cell interactions.

Survival and Developmental Outcomes of Neonates Treated with Extracorporeal Membrane Oxygenation: A 10-Year Single-Center Experience.

Objective: To evaluate the associations between the primary indication for extracorporeal membrane oxygenation (ECMO) in neonates and neurodevelopmental outcomes at 12 and 24 months of age.

Study Design: This is a retrospective cohort study of neonates treated with ECMO between January 2006 and January 2016 in the Children's Hospital of Philadelphia newborn/infant intensive care unit. Primary indication for ECMO was classified as medical (eg, meconium aspiration syndrome) or surgical (eg, congenital diaphragmatic hernia).

Peripheral Neuronopathy Associated With Ebola Virus Infection in Rhesus Macaques: A Possible Cause of Neurological Signs and Symptoms in Human Ebola Patients.

Neurological signs and symptoms are the most common complications of Ebola virus disease. However, the mechanisms underlying the neurologic manifestations in Ebola patients are not known. In this study, peripheral ganglia were collected from 12 rhesus macaques that succumbed to Ebola virus (EBOV) disease from 5 to 8 days post exposure.

Filoviruses Infect Rhesus Macaque Synoviocytes in Vivo and Primary Human Synoviocytes in Vitro.

The most commonly reported symptom of post-Ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent Ebola virus infection is not well characterized in human patients or animal models. Through immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by Ebola virus/Kikwit, Ebola virus/Makona-C05, and Marburg virus/Angola in the rhesus macaque model. Furthermore, histologic analysis, immunohistochemistry, RNAscope in situ hybridization, and transmission electron microscopy showed that synoviocytes of the stifle, shoulder, and hip are a target for mouse-adapted Ebola virus/Yambuku-Mayinga infection during acute disease in rhesus macaques.

Autism spectrum disorder and neurodevelopmental delays in children with giant omphalocele.

Objective: To determine the prevalence and identify risk factors of autism spectrum disorders (ASDs) and neurodevelopmental delays in giant omphalocele (GO) survivors.

Materials And Methods: The study cohort consists of 47 GO survivors enrolled in our follow-up program between 07/2004 and 12/2015. All patients underwent assessments at 2 years of age or older.

Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis.

Simian hemorrhagic fever virus (SHFV) causes a fulminant and typically lethal viral hemorrhagic fever (VHF) in macaques (Cercopithecinae: spp.) but causes subclinical infections in patas monkeys (Cercopithecinae: ). This difference in disease course offers a unique opportunity to compare host responses to infection by a VHF-causing virus in biologically similar susceptible and refractory animals.

Persistence of Lassa Virus Associated With Severe Systemic Arteritis in Convalescing Guinea Pigs (Cavia porcellus).

Lassa fever (LF) survivors develop various clinical manifestations including polyserositis, myalgia, epididymitis, and hearing loss weeks to months after recovery from acute infection. We demonstrate a systemic lymphoplasmacytic and histiocytic arteritis and periarteritis in guinea pigs more than 2 months after recovery from acute Lassa virus (LASV) infection. LASV was detected in the arterial tunica media smooth muscle cells by immunohistochemistry, in situ hybridization, and transmission electron microscopy.

iMOVE: Intensive Mobility training with Variability and Error compared to conventional rehabilitation for young children with cerebral palsy: the protocol for a single blind randomized controlled trial.

Background: Cerebral palsy (CP) is the most common cause of physical disability in children. The best opportunity to maximize lifelong independence is early in motor development when there is the most potential for neuroplastic change, but how best to optimize motor ability during this narrow window remains unknown. We have systematically developed and pilot-tested a novel intervention that incorporates overlapping principles of neurorehabilitation and infant motor learning in a context that promotes upright mobility skill and postural control development.

Development of a novel real-time polymerase chain reaction assay for the quantitative detection of Nipah virus replicative viral RNA.

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that can result in severe pulmonary disease and fatal encephalitis in humans and is responsible for outbreaks in Bangladesh, Malaysia, Singapore, India and possibly the Philippines. NiV has a negative-sense RNA genome that contains six genes and serves as a template for production of viral mRNA transcripts. NiV mRNA transcripts are subsequently translated into viral proteins.

Autosomal dominant mannose-binding lectin deficiency is associated with worse neurodevelopmental outcomes after cardiac surgery in infants.

Objectives: The MBL2 gene is the major genetic determinant of mannose-binding lectin (MBL)-an acute phase reactant. Low MBL levels have been associated with adverse outcomes in preterm infants. The MBL2 missense variant causes autosomal dominant MBL deficiency.

Short-Term Neurodevelopmental Outcome in Children Born With High-Risk Congenital Lung Lesions.

Background: This study sought to evaluate neurodevelopmental outcome in survivors of high-risk congenital lung lesions (CLLs) who underwent prenatal intervention or postnatal surgery within the first month of life.

Methods: Forty-five high-risk CLL survivors underwent assessment using the Bayley Scales of Infant Development, 3rd Edition between July 2004 and December 2016. Scores were grouped as average, at-risk, and delayed based on SD intervals.

Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease.

Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy.

Why do children with severe bronchopulmonary dysplasia not attend neonatal follow-up care? Parental views of barriers.

Aim: To assess in children with severe bronchopulmonary dysplasia at a corrected age of 18-36 months: (i) Neonatal follow-up clinic attendance rates; (ii) Parent-identified reasons for difficulty attending neonatal follow-up.

Methods: Mixed methods study utilising semi-structured phone interviews with parents of infants eligible for follow-up with severe bronchopulmonary dysplasia (defined as gestational age <32 weeks and requiring ≥30% FiO and/or >2 L nasal cannula at 36 weeks post-menstrual age) at 18-36 months corrected age. Questions addressed barriers to neonatal follow-up attendance.

Rate and Risk Factors Associated with Autism Spectrum Disorder in Congenital Diaphragmatic Hernia.

To determine the rate and predictors of autism spectrum disorder (ASD) in congenital diaphragmatic hernia (CDH). Between 06/2004 and 09/2015 a total of 110 CDH survivors underwent neurodevelopmental (ND) testing and screening for ASD, followed by a full autism diagnostic evaluation if indicated at our institution. We found a 9 time higher rate of ASD in CDH children compared to the general population (P = 0.

Short-Term Neurodevelopmental Outcome in Congenital Diaphragmatic Hernia: The Impact of Extracorporeal Membrane Oxygenation and Timing of Repair.

Objectives: The purpose of this study was to assess the need and timing of extracorporeal membrane oxygenation in relation to congenital diaphragmatic hernia repair as modifiers of short-term neurodevelopmental outcomes.

Design: Retrospective study.

Setting: A specialized tertiary care center.