Immunogenicity and Reactogenicity of High-dose or Standard-dose Influenza Vaccine in a Second Consecutive Influenza Season.

Background: Pediatric hematopoietic cell transplant (HCT) recipients are at high-risk for morbidity from influenza virus infection. We demonstrated in a primary phase II randomized controlled trial that two post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart were more immunogenic than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen.

You Don't Always Get What You Want!

Background: Mutations in several genes of Caenorhabditis elegans confer altered sensitivities to volatile anesthetics. A mutation in one gene, gas-1(fc21), causes animals to be immobilized at lower concentrations of all volatile anesthetics than in the wild type, and it does not depend on mutations in other genes to control anesthetic sensitivity. gas-1 confers different sensitivities to stereoisomers of isoflurane, and thus may be a direct target for volatile anesthetics.

Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy.

Objective: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF).

Design: IMPAACT2015 was a U.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

Background: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking.

Objectives: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP.

Methods: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy.

HSPA8 Chaperone Complex Drives Chaperone-Mediated Autophagy Regulation in Acute Promyelocytic Leukemia Cell Differentiation.

Introduction: Acute myeloid leukemia (AML) is a cancer of the hematopoietic system characterized by hyperproliferation of undifferentiated cells of the myeloid lineage. While most of AML therapies are focused toward tumor debulking, all-trans retinoic acid (ATRA) induces neutrophil differentiation in the AML subtype acute promyelocytic leukemia (APL). Macroautophagy has been extensively investigated in the context of various cancers and is often dysregulated in AML where it can have context-dependent pro- or anti-leukemogenic effects.

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019).

Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program.

Background: Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results.

Objectives: We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex.

Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014.

Background: IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks.

Methods: Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF.

The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

Background: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown.

Methods: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart.

Development of webcam-collected and artificial-intelligence-derived social and cognitive performance measures for neurodevelopmental genetic syndromes.

This study focused on the development and initial psychometric evaluation of a set of online, webcam-collected, and artificial intelligence-derived patient performance measures for neurodevelopmental genetic syndromes (NDGS). Initial testing and qualitative input was used to develop four stimulus paradigms capturing social and cognitive processes, including social attention, receptive vocabulary, processing speed, and single-word reading. The paradigms were administered to a sample of 375 participants, including 163 with NDGS, 56 with idiopathic neurodevelopmental disability (NDD), and 156 neurotypical controls.

Navigating Health Equity Through Mobility Justice: Youth of Color Organizing for Transportation Equity in Our Backyards.

There is growing awareness that the built environment and transportation affect many aspects of individual and community well-being and health. Built environment and transportation planning and decision-making, however, rarely integrate robust engagement and input from youth, particularly racially/ethnically and economically diverse youth, despite the likelihood that such planning and decisions will affect their futures. Strategies are needed that prepare, engage, and ultimately empower youth in changing systems, processes, and programs that promote equitable mobility access and opportunity for youth now and in these futures.

Associations of home and neighborhood environments with children's physical activity in the U.S.-based Neighborhood Impact on Kids (NIK) longitudinal cohort study.

Introduction: Physical activity is important for children's health and well-being. Supportiveness for physical activity of home and neighborhood environments may affect children's PA, but most studies are cross-sectional. We examined environmental predictors of change in children's physical activity over two years.

Characterizing changes in behaviors associated with chemical exposures during the COVID-19 pandemic.

The COVID-19 pandemic-and its associated restrictions-have changed many behaviors that can influence environmental exposures including chemicals found in commercial products, packaging and those resulting from pollution. The pandemic also constitutes a stressful life event, leading to symptoms of acute traumatic stress. Data indicate that the combination of environmental exposure and psychological stress jointly contribute to adverse child health outcomes.

Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Week 24 Results From IMPAACT 2014.

Background: We studied the pharmacokinetics (PK) and safety of 100-mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination (100/300/300 mg DOR FDC) treatment in adolescents with HIV-1.

Methods: Adolescents ages 12 to younger than 18 years were enrolled in 2 sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100-mg single-dose doravirine in adolescents ≥35 kg.

Clinically Complex LRBA Deficiency Due to a Founder Allele in the Georgian Jewish Population.

Pathogenic variants in LRBA, encoding the LPS Responsive Beige-Like Anchor (LRBA) protein, are responsible for recessive, early-onset hypogammaglobulinemia, severe multi-organ autoimmunity, and lymphoproliferation, with increased risk for malignancy. LRBA deficiency has a wide clinical spectrum with variable age of onset and disease severity. Three apparently unrelated patients with LRBA deficiency, of Georgian Jewish descent, were homozygous for LRBA c.

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts.

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.

Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.

Design, Setting, And Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US.

Diagnosis and clinical management of Wiskott-Aldrich syndrome: current and emerging techniques.

Introduction: Wiskott-Aldrich syndrome (WAS) serves as the prototype of how variants in a gene, which encodes a protein central to actin cytoskeletal homeostasis can manifest clinically in a variety of ways including infection, atopy, autoimmunity, inflammation, bleeding, neutropenia, non-malignant lymphoproliferation, and malignancy. Despite the discovery of the gene almost 30 years ago, our understanding of the pathophysiological mechanisms underlying WAS continues to unfold.

Areas Covered: This review will provide an overview of the approach to the diagnosis of WAS as well as the management of its associated complications.

Combining Urinary Biomarker Data From Studies With Different Measures of Urinary Dilution.

Background: Guidance is lacking for how to combine urinary biomarker data across studies that use different measures of urinary dilution, that is, creatinine or specific gravity.

Methods: Among 741 pregnant participants from four sites of The Infant Development and Environment Study (TIDES) cohort, we assessed the relation of maternal urinary di-2-ethylhexyl phthalate (DEHP) concentrations with preterm birth. We compared scenarios in which all sites measured either urinary creatinine or specific gravity, or where measure of dilution differed by site.