Local regulation of striatal dopamine release shifts from predominantly cholinergic in mice to GABAergic in macaques.

Dopamine critically regulates neuronal excitability and promotes synaptic plasticity in the striatum, thereby shaping network connectivity and influencing behavior. These functions establish dopamine as a key neuromodulator, whose release properties have been well-studied in rodents but remain understudied in nonhuman primates. This study aims to close this gap by investigating the properties of dopamine release in macaque striatum and comparing/contrasting them to better-characterized mouse striatum, using ex vivo brain slices from male and female animals.

Neighborhood opportunity and residential instability: associations with mental health in middle childhood.

Background: Neighborhood quality may contribute to child mental health, but families with young children often move, and residential instability has also been tied to adverse mental health. This study's primary goal was to disentangle the effects of neighborhood quality from those of residential instability on mental health in middle childhood.

Methods: 1,946 children from 1,652 families in the Upstate KIDS cohort from New York state, US, were followed prospectively from birth to age 10.

Examining the moderation of the relationship between socio-economic status and consumption intentions by food information labels.

Front-of-package-labelling needs to portray health and/or sustainability information effectively to all consumers in a way that is both effective and equitable. There is mixed evidence for the effectiveness of such labels based on socioeconomic status (SES). Framing health consequences in an intuitive manner could help to reduce disparities in label comprehension across SES.

A Retrospective Review of Oral N-Acetylcysteine for Habit-Driven Cutaneous Disorders.

Oral N-acetylcysteine (NAC) has shown efficacy for debilitating habit-driven and neuropsychiatric disorders in small, mostly adult studies. We retrospectively evaluated the therapeutic use and safety of oral NAC in 93 children from the Children's Hospital of Philadelphia. This study supports the use of oral NAC for habit-driven skin, hair, and nail abnormalities in pediatric patients.

Head and Neck Paraganglioma in Pacak-Zhuang Syndrome.

Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

Choroid plexus-targeted viral gene therapy for alpha-mannosidosis, a prototypical neurometabolic lysosomal storage disease.

The choroid plexuses (CP) are highly vascularized structures that project into the ventricles of the vertebrate brain. The polarized epithelia of the CP produce cerebrospinal fluid by transporting water and ions into the ventricles from the blood and normally secrete a large number of proteins. We assessed the feasibility of selective CP transduction with recombinant adeno-associated virus (rAAV) gene therapy vectors for treatment of lysosomal storage disease (LSD), a broad category of neurometabolic illness associated with significant burdens to affected patients and their families.

Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice.

Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain.

Pharmacokinetics and safety of bictegravir in pregnant and postpartum persons with HIV and their infants.

Background: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.

Setting: Nonrandomized, open-label, multi-center phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.

Methods: Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the 2nd and 3rd trimesters and postpartum was performed.

Neoadjuvant Intratumoral MBT(A) Immunotherapy Prevents Distant Metastases and Recurrence in Murine Models.

Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, offering novel avenues for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and antiCD40 antibody (MBTA therapy) followed by surgery in murine models of mouse tumor tissue (MTT) pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas.

Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only).

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

deletion rescues cerebellar hypotrophy in mutant zebrafish.

Defects in DNA single-strand break repair are associated with neurodevelopmental and neurodegenerative disorders. One such disorder is that resulting from mutations in , a scaffold protein that plays a central role in DNA single-strand base repair. XRCC1 is recruited at sites of single-strand breaks by PARP1, a protein that detects and is activated by such breaks and is negatively regulated by XRCC1 to prevent excessive PARP binding and activity.

The association of Neutrophil-to-Lymphocyte ratio with metabolic syndrome in U.S. Adults: Findings from the 1999-2018 National Health and Nutrition Examination survey.

Background: Identifying and treating metabolic syndrome (MetS) early is of great importance, as MetS portends numerous negative health outcomes. Identifying an inexpensive, readily available inflammatory biomarker that accurately predicts MetS could be of use to clinicians.

Methods: The aim of this study was to evaluate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and MetS in U.

Prenatal exposure to particulates and anthropometry through 9 years of age in a birth cohort.

Background: Previous research observed links between prenatal air pollution and risk of childhood obesity but the timing of the exposure is understudied.

Aim: We examined prenatal particulate matter (PM, PM) exposure and child anthropometry.

Materials & Methods: Children's body mass index z-scores (zBMI) at 0-3 (N = 4370) and 7-9 (n = 1191) years were derived from reported anthropometry at paediatric visits.

Improving generalizability of developmental research through increased use of homogeneous convenience samples: A Monte Carlo simulation.

Due to its heavy reliance on convenience samples (CSs), developmental science has a generalizability problem that clouds its broader applicability and frustrates replicability. The surest solution to this problem is to make better use, where feasible, of probability samples, which afford clear generalizability. Because CSs that are homogeneous on one or more sociodemographic factor may afford a clearer generalizability than heterogeneous CSs, the use of homogeneous CSs instead of heterogeneous CSs may also help mitigate this generalizability problem.

Maternal touch in object- and nonobject-oriented play interactions: A longitudinal study at 7 and 12 months.

Social touch is a crucial part of how mothers interact with their infants, with different touch types serving distinct purposes in these exchanges. However, there is still a limited understanding of how mothers' touch behavior adapts to specific interactive tasks, particularly throughout infancy. To address this gap, we observed mother-infant dyads at 7 and 12 months during three structured social play tasks: (a) play with objects, (b) play without objects, and (c) play with a difficult object.

Flux through membrane channel: linear transport single-molecule approaches.

One of the most subtle steps in the single-molecule approach to the flux through the membrane channel, which uses the one-dimensional Smoluchowski equation, is to describe the molecule's "behavior" at the contacts between the channel openings and the bulk. Earlier, to handle this issue, we introduced the so-called "radiation boundary conditions" that account for the interplay between the two types of trajectories of the molecules starting at the openings, specifically, the ones that eventually return to the channel and the ones that escape to infinity. The latter trajectories represent the true translocation events on the condition that initially the molecule entered the channel from the opposite side.

PDE11A is a phenotype modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: results of a 334 patients' series.

Purpose: Primary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing's syndrome due to bilateral nodules, is a heterogeneous disease at the clinical, hormonal and morphological levels. ARMC5 inactivating pathogenic variants are causative of PBMAH and rare variants of PDE11A have been associated with PBMAH.

Methods: Leukocyte DNA of 354 PBMAH index cases was sequenced for ARMC5 and PDE11A genes by Next generation sequencing (NGS).

Prenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer.

Background: Cell-free DNA (cfDNA) sequence analysis to screen for fetal aneuploidy can incidentally detect maternal cancer. Additional data are needed to identify DNA-sequencing patterns and other biomarkers that can identify pregnant persons who are most likely to have cancer and to determine the best approach for follow-up.

Methods: In this ongoing study we performed cancer screening in pregnant or postpartum persons who did not perceive signs or symptoms of cancer but received unusual clinical cfDNA-sequencing results or results that were nonreportable (i.

A Study of Short-Chain Fatty Acids During the Canalicular and Early Saccular Phases of Fetal Lung Development and Childhood Asthma.

Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype.

The PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.

ASAP1 is a multidomain Arf GTPase-activating protein (ArfGAP) that catalyzes GTP hydrolysis on the small GTPase Arf1 and is implicated in cancer progression. The PH domain of ASAP1 enhances its activity greater than 7 orders of magnitude but the underlying mechanisms remain poorly understood. Here, we combined Nuclear Magnetic Resonance (NMR), Molecular Dynamic (MD) simulations and mathematical modeling of functional data to build a comprehensive structural-mechanistic model of the complex of Arf1 and the ASAP1 PH domain on a membrane surface.