Heavy alcohol consumption but not smoking predicts mortality in patients with acute coronary syndrome.

The relationship of heavy alcohol consumption (HAC) and smoking to mortality in those with CHD, and mechanisms through which these effects are elicited are not clear. In order to improve our understanding, we examined the relationship of Alcohol T-Scores (ATS), an epigenetic biomarker of chronic HAC, and cg05575921 methylation, a biomarker of smoking intensity, with all-cause mortality and degree of coronary artery obstruction in a cohort of 217 subjects admitted for CHD-related acute coronary syndrome (ACS). We found that 65% of the subjects had ATS values indicative of chronic HAC.

An Outline of a Simple, Interpretable Epigenetic Composite Score for Mortality Prediction for Accelerated Underwriting.

Background.—: In principle, it is generally accepted that DNA methylation measures can be used to predict mortality. However, as of yet, no epigenetic metric has been successfully incorporated into underwriting procedures.

Fluoxetine and Sertraline Inhibit Height Growth and Growth Hormone Signaling During Puberty.

Purpose: The aim of this study was to examine the effect of fluoxetine and sertraline on height growth and insulin-like growth factor-1 (IGF-1) during puberty.

Methods: In this 6-month cohort study, electronic medical records were used to identify 8- to 15-year-old participants, within 1 month of starting fluoxetine (n = 39) or sertraline (n = 27), and sexual maturation stages 2 to 4 were confirmed. Conditions that interfere with height growth led to exclusion.

Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study.

Objective: Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult.

Methods: Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis.

Regulatory elements in (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits.

Purpose: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.

Methods: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.

Results: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.

WONOEP appraisal: Genetic insights into early onset epilepsies.

Early onset epilepsies occur in newborns and infants, and to date, genetic aberrations and variants have been identified in approximately one quarter of all patients. With technological sequencing advances and ongoing research, the genetic diagnostic yield for specific seizure disorders and epilepsies is expected to increase. Genetic variants associated with epilepsy include chromosomal abnormalities and rearrangements of various sizes as well as single gene variants.

Target trial emulation of preconception serum vitamin D status on fertility outcomes: a couples-based approach.

Objective: To evaluate associations between preconception 25-hydroxyvitamin D (25(OH)D) levels and biomarkers in female and male partners on live birth (LB), pregnancy loss, and semen quality.

Design: Secondary analysis using the folic acid and zinc supplementation trial of couples seeking infertility treatment at four US centers (2013-2017). A target trial emulation framework was applied to estimate associations.

Time to Functional Loss as an Endpoint in Huntington's Disease Trials: Enrichment and Sample Size.

Background: Clinical trial scenarios can be modeled using data from observational studies, providing critical information for design of real-world trials. The Huntington's Disease Integrated Staging System (HD-ISS) characterizes disease progression over an individual's lifespan and allows for flexibility in the design of trials with the goal of delaying progression. Enrichment methods can be applied to the HD-ISS to identify subgroups requiring smaller estimated sample sizes.

miR-193b-3p/ PGC-1α pathway regulates an insulin dependent anti-inflammatory response in Parkinson's disease.

It has been shown that many miRNAs, including miR-193b-3p, are differentially expressed in Parkinson's disease (PD). Dysregulation of miR-193b-3p/PGC-1α axis may alter homeostasis in cells and can induce an inflammatory response commonly accompanied by metabolic disturbances. The aim of the present study is to investigate if dysregulation of the miR-193-3p/PGC-1α axis may contribute to the pathological changes observed in the PD brain.

The Association of Female and Male Preconception Dyslipidemia With Live Birth in Couples Seeking Fertility Treatment.

Context: Dyslipidemia is common, and resultant endothelial dysfunction may impact reproductive outcomes. No prospective study has examined the effect of preconception lipid parameters in both female and male partners or their interaction on live birth.

Objective: To determine whether live birth is associated with preconception lipids in both partners by planned fertility treatment.

Climate change and disorders of the nervous system.

Anthropogenic climate change is affecting people's health, including those with neurological and psychiatric diseases. Currently, making inferences about the effect of climate change on neurological and psychiatric diseases is challenging because of an overall sparsity of data, differing study methods, paucity of detail regarding disease subtypes, little consideration of the effect of individual and population genetics, and widely differing geographical locations with the potential for regional influences. However, evidence suggests that the incidence, prevalence, and severity of many nervous system conditions (eg, stroke, neurological infections, and some mental health disorders) can be affected by climate change.

Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex.

GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network activity and associated neurological symptoms, assumingly in a cell type-specific manner. This GABAergic centric study focuses on identifying specific interneuron subpopulations within TSC, emphasizing the unique characteristics of medial ganglionic eminence (MGE)- and caudal ganglionic eminence (CGE)-derived interneurons.

Etiology of diarrheal hospitalizations following rotavirus vaccine implementation and association of enteric pathogens with malnutrition among under-five children in India.

Malnourished children are at higher risk of mortality and morbidity following diarrheal illness and certain enteropathogens have been associated with malnutrition in children. Very few studies have comprehensively looked at the etiology of diarrhea in malnourished children and most have used conventional diagnostic methods with suboptimal sensitivity. We used a highly sensitive molecular approach against a broad range of pathogens causing diarrhea and examined their association with malnutrition.

Identification of gene regulatory networks affected across drug-resistant epilepsies.

Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies).

Astroglial calcium signaling and homeostasis in tuberous sclerosis complex.

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by the development of benign tumors in various organs, including the brain, and is often accompanied by epilepsy, neurodevelopmental comorbidities including intellectual disability and autism. A key hallmark of TSC is the hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway, which induces alterations in cortical development and metabolic processes in astrocytes, among other cellular functions. These changes could modulate seizure susceptibility, contributing to the progression of epilepsy and its associated comorbidities.

Advancement of Autogenous Vaccines in the Poultry Industry.

Autogenous vaccines, also known as "custom" vaccines, have become an essential instrument in the production veterinarian's toolbox for the control of emerging and evolving diseases. Autogenous vaccines require a reduced burden of U.S.

Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

Background: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making.

Methods: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons.

Differential microRNA editing may drive target pathway switching in human temporal lobe epilepsy.

MicroRNAs have emerged as important regulators of the gene expression landscape in temporal lobe epilepsy. The mechanisms that control microRNA levels and influence target choice remain, however, poorly understood. RNA editing is a post-transcriptional mechanism mediated by the adenosine acting on RNA (ADAR) family of proteins that introduces base modification that diversifies the gene expression landscape.

MAIP: An Open-Source Tool to Enrich High-Throughput Screening Output and Identify Novel, Druglike Molecules with Antimalarial Activity.

Efforts to tackle malaria must continue for a disease that threatens half of the global population. Parasite resistance to current therapies requires new chemotypes that are able to demonstrate effectiveness and safety. Previously, we developed a machine-learning-based approach to predict compound antimalarial activity, which was trained on the compound collections of several organizations.

Loss of maturity and homeostatic functions in Tuberous Sclerosis Complex-derived astrocytes.

Introduction: Constitutive activation of the mTOR pathway, as observed in Tuberous Sclerosis Complex (TSC), leads to glial dysfunction and subsequent epileptogenesis. Although astrocytes are considered important mediators for synaptic clearance and phagocytosis, little is known on how astrocytes contribute to the epileptogenic network.

Methods: We employed singlenuclei RNA sequencing and a hybrid fetal calf serum (FCS)/FCS-free cell culture model to explore the capacity of TSC-derived astrocytes to maintain glutamate homeostasis and clear debris in their environment.