Hancockcote5595

Positive, prosocial interactions are essential for survival, development, and well-being. These intricate and complex behaviors are mediated by an amalgamation of neural circuit mechanisms working in concert. Impairments in prosocial behaviors, which occur in a large number of neuropsychiatric disorders, result from disruption of the coordinated activity of these neural circuits. In this review, we focus our discussion on recent findings that utilize modern approaches in rodents to map, monitor, and manipulate neural circuits implicated in a variety of prosocial behaviors. We highlight how modulation by oxytocin, serotonin, and dopamine of excitatory and inhibitory synaptic transmission in specific brain regions is critical for regulation of adaptive prosocial interactions. We then describe how recent findings have helped elucidate pathophysiological mechanisms underlying the social deficits that accompany neuropsychiatric disorders. We conclude by discussing approaches for the development of more efficacious and targeted therapeutic interventions to ameliorate aberrant prosocial behaviors.Models of addiction are based on neurobiological, behavioral, and pharmacological studies in animals, but translational support from human studies is limited. Studies are lacking in examining acute responses to alcohol in drinkers with alcohol use disorder (AUD), particularly in terms of relevant intoxicating doses and measurement of stimulating and rewarding effects throughout the breath alcohol concentration (BrAC) time curve. Participants were N = 60 AUD drinkers enrolled in the Chicago Social Drinking Project and examined in three random-order and blinded sessions for subjective and physiological responses to a beverage containing 0.0 g/kg, 0.8 g/kg, and 1.2 g/kg alcohol. check details BrAC in the alcohol sessions at 60 min was 0.09 g/dL and 0.13 g/dL, respectively. Both doses of alcohol produced significant biphasic effects on subjective measures of stimulation, euphoria, reward (liking and wanting), sedation, and neuroendocrine and cardiovascular factors. Increased pleasurable effects of alcohol were pronounced during the rising limb-to-peak BrAC and sedating effects emerged during the declining limb. Alcohol dose-dependently increased feel drug ratings and rewarding effects at peak BrAC or early declining limb, and physiological responses at the rising limb. Thus, rather than the notion of an overall tolerance, results show an alcohol response phenotype characterized by sensitivity to alcohol's stimulating, rewarding and physiological effects. The results of this study may aid in the conceptualization of alcohol addiction as a disorder characterized by the persistence of enhanced hedonic alcohol responses rather than chronic tolerance and reward deficiency.The ingestion of alcohol yields acute biphasic subjective effects stimulation before sedation. Despite their predictive relevance to the development of alcohol use disorders (AUD), the neurobiological markers accounting for the biphasic effects of alcohol remain poorly understood in humans. Informed by converging lines of evidence, this study tested the hypothesis that alcohol ingestion acutely increases gamma-aminobutyric acid (GABA)-mediated inhibition, which would positively and negatively predict the feeling of stimulation and sedation, respectively. To do so, healthy participants (n = 20) ingested a single dose of 94% ABV alcohol (males 1.0 ml/kg; females 0.85 ml/kg) in a randomized placebo-controlled cross-over design. The alcohol's biphasic effects were assessed with the Brief-Biphasic Alcohol Effects Scale, and non-invasive neurobiological markers were measured with transcranial magnetic stimulation, before and every 30 min (up to 120 min) after the complete ingestion of the beverage. Results showed that acute alcohol ingestion selectively increased the duration of the cortical silent period (CSP) as compared to placebo, suggesting that alcohol increases non-specific GABAergic inhibition. Importantly, CSP duration positively and negatively predicted increases in the feeling of stimulation and sedation, respectively, suggesting that stimulation emerges as GABAergic inhibition increases and that sedation emerges as GABAergic inhibition returns to baseline values. Overall, these results suggest that modulations of GABAergic inhibition are central to the acute biphasic subjective effects of alcohol, providing a potential preventive target to curb the progression of at-risk individuals to AUD.Chronic stress is a risk factor for Major Depressive Disorder (MDD), and in rodents, it recapitulates human behavioral, cellular and molecular changes. In MDD and after chronic stress, neuronal dysfunctions and deficits in GABAergic signaling are observed and responsible for symptom severity. GABA signals predominantly through GABAA receptors (GABAA-R) composed of various subunit types that relate to downstream outcomes. Activity at α2-GABAA-Rs contributes to anxiolytic properties, α5-GABAA-Rs to cognitive functions, and α1-GABAA-Rs to sedation. Therefore, a therapy aiming at increasing α2- and α5-GABAA-Rs activity, but devoid of α1-GABAA-R activity, has potential to address several symptomologies of depression while avoiding side-effects. This study investigated the activity profiles and behavioral efficacy of two enantiomers of each other (GL-II-73 and GL-I-54), separately and as a racemic mixture (GL-RM), and potential disease-modifying effects on neuronal morphology. Results confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the α2-, α3-, α5-GABAA-Rs and α5-containing GABAA-Rs, respectively, and separately reduces immobility in the forced swim test and improves stress-induced spatial working memory deficits. Using unpredictable chronic mild stress (UCMS), we show that acute and chronic administration of GL-RM provide pro-cognitive effects, with mild efficacy on mood symptoms, although at lower doses avoiding sedation. Morphology studies showed reversal of spine density loss caused by UCMS after chronic GL-RM treatment at apical and basal dendrites of the PFC and CA1. Together, these results support using a racemic mixture with combined α2-, α3-, α5-GABAA-R profile to reverse chronic stress-induced mood symptoms, cognitive deficits, and with anti-stress neurotrophic effects.Selenium (Se) is an essential trace element for humans and other animals. The human body mainly acquires Se from plant foods, especially cereal grains. Rice is the staple food for more than half of the world's population. Increasing the Se concentration of rice grains can increase the average human dietary Se intake. This review summarizes recent advances in the molecular mechanisms of Se uptake, transport, subcellular distribution, retranslocation, volatilization, and Se-containing protein degradation in plants, especially rice. The strategies for improving Se concentration in rice grains by increasing Se accumulation, reducing Se volatilization, and optimizing Se form were proposed, which provide new insight into Se biofortification in rice by improving the utilization efficiency of Se.Computational drug repurposing methods adapt Artificial intelligence (AI) algorithms for the discovery of new applications of approved or investigational drugs. Among the heterogeneous datasets, electronic health records (EHRs) datasets provide rich longitudinal and pathophysiological data that facilitate the generation and validation of drug repurposing. Here, we present an appraisal of recently published research on computational drug repurposing utilizing the EHR. Thirty-three research articles, retrieved from Embase, Medline, Scopus, and Web of Science between January 2000 and January 2022, were included in the final review. Four themes, (1) publication venue, (2) data types and sources, (3) method for data processing and prediction, and (4) targeted disease, validation, and released tools were presented. The review summarized the contribution of EHR used in drug repurposing as well as revealed that the utilization is hindered by the validation, accessibility, and understanding of EHRs. These findings can support researchers in the utilization of medical data resources and the development of computational methods for drug repurposing.

This study aimed to explore whether sex is influences tinnitus severity and whether the risk factors for tinnitus severity are the same in tinnitus patients of different sexes.

This was a retrospective study of data from 1427 patients complaining of tinnitus in a local hospital otolaryngology clinic from November 2019 to January 2022. All patients were interviewed and assessed by otoscopy, pure-tone audiometry, tinnitus handicap inventory (THI), visual analogue scale (VAS), and tinnitus refinement test.

THI values were higher in females than in males (P = 0.00). Types of tinnitus sounds (OR 0.667, P = 0.000) and degree of hearing loss (OR 1.318, P = 0.000) were risk factors for tinnitus severity in males. Types of tinnitus sounds (OR 0.789, P = 0.005), sensation level (OR 1.023, P = 0.037), tinnitus types (OR 1.163, P = 0.041), tinnitus location (OR 1.198, P = 0.026), and the degree of hearing loss (OR 1.303, P = 0.000) were risk factors for tinnitus severity in females. Sex was an influencing factor for tinnitus severity. There were different risk factors for the tinnitus severity in different sexes.

The risk factors for tinnitus severity differed according to sex in tinnitus patients, and the risk factors for tinnitus severity were greater in women than in men. These findings add to the literature on sex differences in tinnitus and suggest that medical and psychological screening of affected individuals and customized tinnitus treatment for each individual with tinnitus are needed.

ChiCTR2200057958, 2022/3/24 (retrospectively registered trials).

ChiCTR2200057958, 2022/3/24 (retrospectively registered trials).Ants are among the most successful organisms on Earth. It has been suggested that forming symbioses with nutrient-supplementing microbes may have contributed to their success, by allowing ants to invade otherwise inaccessible niches. However, it is unclear whether ants have evolved symbioses repeatedly to overcome the same nutrient limitations. Here, we address this question by comparing the independently evolved symbioses in Camponotus, Plagiolepis, Formica and Cardiocondyla ants. Our analysis reveals the only metabolic function consistently retained in all of the symbiont genomes is the capacity to synthesise tyrosine. We also show that in certain multi-queen lineages that have co-diversified with their symbiont for millions of years, only a fraction of queens carry the symbiont, suggesting ants differ in their colony-level reliance on symbiont-derived resources. Our results imply that symbioses can arise to solve common problems, but hosts may differ in their dependence on symbionts, highlighting the evolutionary forces influencing the persistence of long-term endosymbiotic mutualisms.The European project ORCHESTRA intends to create a new pan-European cohort to rapidly advance the knowledge of the effects and treatment of COVID-19. Establishing processes that facilitate the merging of heterogeneous clusters of retrospective data was an essential challenge. In addition, data from new ORCHESTRA prospective studies have to be compatible with earlier collected information to be efficiently combined. In this article, we describe how we utilized and contributed to existing standard terminologies to create consistent semantic representation of over 2500 COVID-19-related variables taken from three ORCHESTRA studies. The goal is to enable the semantic interoperability of data within the existing project studies and to create a common basis of standardized elements available for the design of new COVID-19 studies. We also identified 743 variables that were commonly used in two of the three prospective ORCHESTRA studies and can therefore be directly combined for analysis purposes. Additionally, we actively contributed to global interoperability by submitting new concept requests to the terminology Standards Development Organizations.