Purinergic P2Y and P2Y receptors control enteric nervous system activity through neuro-glia-macrophage crosstalk.

Purines are important mediators of intercellular communication in the enteric nervous system (ENS) that participate in physiological gut functions and disease. Purinergic transmission is prominent in mechanisms of crosstalk between enteric neurons and glia where enteric glia exhibit high responsiveness to adenosine diphosphate (ADP) through P2Y receptors and neurons to adenosine triphosphate (ATP) through P2X receptors. Despite functional data suggesting that enteric glia are the primary site of P2Y expression in the ENS, gene sequencing suggests that P2Y expression is more enriched in neurons than glia.

Third-party perceptions of mistreatment: A meta-analysis and integrative model of reactions to perpetrators and victims.

Third parties have increasingly become the focus of research on mistreatment in organizations. Much of that work is grounded in deonance theory, which argues that third parties should react to the perpetrators of mistreatment with anger. Deonance theory is less explicit as to how third parties should react to the victims of mistreatment, though empirical work has pointed to empathy as one potential reaction.

Early life adversity promotes gastrointestinal dysfunction through a sex-dependent phenotypic switch in enteric glia.

Irritable bowel syndrome and related disorders of gut-brain interaction (DGBI) are common and exhibit a complex, poorly understood etiology that manifests as abnormal gut motility and pain. Risk factors such as biological sex, stressors during critical periods, and inflammation are thought to influence DGBI vulnerability by reprogramming gut-brain circuits, but the specific cells affected are unclear. Here, we used a model of early life stress to understand cellular mechanisms in the gut that produce DGBIs.

A phase 2b, Randomized, double blinded comparison of the safety and efficacy of the monoclonal antibody mixture SYN023 and human rabies immune globulin in patients exposed to rabies.

Background: SYN023 is an anti-rabies monoclonal antibody mixture administered as part of post-exposure prophylaxis regimens. The rabies virus neutralizing antibody (RVNA) concentration generally accepted as an adequate immune response to vaccination is ≥ 0.5 IU/mL.

Geriatric Bariatric Surgery: Outcomes at a Single Institution.

Obesity, especially in those over the age of 65, is associated with multiple comorbidities and decreased quality of life. Bariatric surgery is an effective method of weight loss and management of comorbidities and is increasingly utilized in younger and middle-aged populations. A retrospective review was performed of patients ≥65 years old who underwent bariatric surgery between 2018 and 2021 at a single institution to evaluate the safety and efficacy of bariatric surgery in older populations.

Rethinking Data Collection Methods During the Pandemic: Development and Implementation of CATI for the All of Us Research Program.

The All of Us Research Program is a longitudinal cohort study aiming to build a diverse database to advance precision medicine. The COVID-19 pandemic hindered the ability of participants to receive in-person assistance at enrollment sites to complete digital surveys. Therefore, the program implemented Computer-Assisted Telephone Interviewing (CATI) to facilitate survey completion remotely to combat the disrupted data collection procedures.

Sexually Dimorphic Effects of Histamine Degradation by Enteric Glial Histamine -Methyltransferase (HNMT) on Visceral Hypersensitivity.

Histamine is a neuromodulator that affects gut motility and visceral sensitivity through intrinsic and extrinsic neural pathways, yet the mechanisms regulating histamine availability in these pathways remain poorly understood. Here, we show that enteric glia contribute to histamine clearance in the enteric nervous system (ENS) through their expression of the enzyme histamine -methyltransferase (HNMT). Glial HNMT expression was initially assessed using immunolabeling and gene expression, and functionally tested using CRISPR-Cas9 to create a Cre-dependent conditional ablation model targeting glia.

Functional Intraregional and Interregional Heterogeneity between Myenteric Glial Cells of the Colon and Duodenum in Mice.

Enteric glia are a unique population of peripheral neuroglia that regulate homeostasis in the enteric nervous system (ENS) and intestinal functions. Despite existing in functionally diverse regions of the gastrointestinal tract, enteric glia have been approached scientifically as a homogeneous group of cells. This assumption is at odds with the functional specializations of gastrointestinal organs and recent data suggesting glial heterogeneity in the brain and ENS.

The Impact of COVID-19 on the All of Us Research Program.

The All of Us Research Program, a health and genetics epidemiologic data collection program, has been substantially affected by the coronavirus disease 2019 (COVID-19) pandemic. Although the program is highly digital in nature, certain aspects of the data collection require in-person interaction between staff and participants. Before the pandemic, the program was enrolling approximately 12,500 participants per month at more than 400 clinical sites.

Impedance Planimetry and the Changing Paradigm of Esophageal Dysphagia.

Objectives: Patients presenting with dysphagia can encounter a pathway to therapy and relief that is expensive and frustrating. High resolution impedance planimetry (HRIP) is a new mechanism for enhancing and possibly hastening that process. A balloon with integrated pressure sensors is utilized to measure luminal geometry and pressure by volume-controlled distention.

The relationship among home language use, parental beliefs, and Spanish-speaking children's vocabulary.

This study investigated the relationship among home language use, parents' beliefs about dual language development, and Spanish-speaking children's vocabulary knowledge. Parents ( = 162) completed a questionnaire about their home language use and beliefs about dual language development, and elementary-age children ( = 190)-Kindergarten ( = 5.71, = .

LPAR1 regulates enteric nervous system function through glial signaling and contributes to chronic intestinal pseudo-obstruction.

Gastrointestinal motility disorders involve alterations to the structure and/or function of the enteric nervous system (ENS) but the causal mechanisms remain unresolved in most cases. Homeostasis and disease in the ENS are processes that are regulated by enteric glia. Signaling mediated through type I lysophosphatidic acid receptors (LPAR1) has recently emerged as an important mechanism that contributes to disease, in part, through effects on peripheral glial survival and function.

Rabies virus neutralizing activity, pharmacokinetics, and safety of the monoclonal antibody mixture SYN023 in combination with rabies vaccination: Results of a phase 2, randomized, blinded, controlled trial.

Background: SYN023-002 is a randomized, blinded, controlled study comparing rabies virus neutralizing activity (RVNA) and safety of SYN023, a monoclonal anti-rabies antibody mixture, to human-serum derived anti-rabies immunoglobulin (RIG) when administered with commercially available vaccines to healthy adult volunteers.

Methods: Participants were randomized among 4 treatment groups (SYN023 + Imovax, SYN023 + RabAvert, HyperRab + Imovax, HyperRab + RabAvert). On Day 0, subjects received 1 dose of RIG (0.

Breastfeeding Disparities and Their Mediators in an Urban Birth Cohort of Black and White Mothers.

Black mothers in the United States have shorter breastfeeding (BF) durations and less exclusive breastfeeding (EBF) than others. The factors underlying these disparities require investigation. Using longitudinal data from a CDC-sponsored birth cohort in Cincinnati, Ohio, we analyzed the factors mediating racial disparity in BF outcomes.

Safety, Pharmacokinetics, and Neutralizing Activity of SYN023, a Mixture of Two Novel Antirabies Monoclonal Antibodies Intended for Use in Postrabies Exposure Prophylaxis.

SYN023 is a mixture of 2 humanized monoclonal antirabies antibodies (CTB011, CTB012). Two first-in-human studies evaluated ascending intramuscular (IM) injected doses (Study SYN023-001; N = 15) and IM vs subcutaneous (SC) administration (Study SYN023-003; N = 35) in healthy adults. In both studies, end points were safety, pharmacokinetics (PK), pharmacodynamics/rabies virus neutralizing activity (RVNA), and immunogenicity (anti-SYN023 antibodies).

Early Elementary Grade Dual Language Learners from Spanish-speaking Homes Struggling with English Reading Comprehension: The Dormant Role of Language Skills.

This study investigated contributors of English reading comprehension outcomes among predominantly U.S.-born first and third grade ( = 73) dual language learners (DLLs) from Spanish-speaking, low-income homes who attend English-only instructional schools in the Southern region of the U.

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation.

Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses.

Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats.

Microglia are dynamic cells that have roles in neuronal plasticity as well as in recovery responses following neuronal injury. Although many hypothesize that hyperactivation of microglia contributes to alcohol-induced neuropathology, in other neurodegenerative conditions disruption of normal microglial processes also contributes to neuronal loss, particularly as microglia become dystrophic or dysfunctional. Based on the observation of a striking, abnormal morphology in microglia during binge-like ethanol exposure, the present study investigated the impact of excessive ethanol exposure on microglia number and dystrophic morphology in a model of alcohol dependence that includes neurodegeneration in both adult and adolescent rats.

Recent developments in the PySCF program package.

PySCF is a Python-based general-purpose electronic structure platform that supports first-principles simulations of molecules and solids as well as accelerates the development of new methodology and complex computational workflows. This paper explains the design and philosophy behind PySCF that enables it to meet these twin objectives. With several case studies, we show how users can easily implement their own methods using PySCF as a development environment.

Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop.

Activin A functions in BMP signaling in two ways: it either engages ACVR1B to activate Smad2/3 signaling or binds ACVR1 to form a non-signaling complex (NSC). Although the former property has been studied extensively, the roles of the NSC remain unexplored. The genetic disorder fibrodysplasia ossificans progressiva (FOP) provides a unique window into ACVR1/Activin A signaling because in that disease Activin can either signal through FOP-mutant ACVR1 or form NSCs with wild-type ACVR1.

Spanish-speaking English learners' English language and literacy skills: The predictive role of conceptually-scored vocabulary.

Vocabulary represents a key barrier to language and literacy development for many English learners. This study examined the relationship between Spanish-speaking English learners' conceptually-scored Spanish-English vocabulary, academic English proficiency, and English reading comprehension. Second- and fourth-grade English learners ( = 62) completed standardized conceptually-scored vocabulary measures in the fall and state-administered standardized measures of academic English proficiency and English reading comprehension in the spring.