Virtual library docking for cannabinoid-1 receptor agonists with reduced side effects.

Virtual library docking can reveal unexpected chemotypes that complement the structures of biological targets. Seeking agonists for the cannabinoid-1 receptor (CB1R), we dock 74 million tangible molecules and prioritize 46 high ranking ones for de novo synthesis and testing. Nine are active by radioligand competition, a 20% hit-rate.

Comparative analysis prediction of prostate and testicular cancer mortality using machine learning: accuracy study.

Background: The mortality rates of prostate and testicular cancer are higher mortality in the northeast region.

Objective: We aimed to compare the efficacy of machine learning libraries in predicting testicular and prostate cancer mortality.

Design And Setting: A comparative analysis of the pyMannKendall and Prophet machine-learning algorithms was conducted to develop predictive models using data from DATASUS (TabNet) to Caicó (Brazil) and Rio Grande do Norte (Brazil).

Docking 14 million virtual isoquinuclidines against the mu and kappa opioid receptors reveals dual antagonists-inverse agonists with reduced withdrawal effects.

Large library docking of tangible molecules has revealed potent ligands across many targets. While make-on-demand libraries now exceed 75 billion enumerated molecules, their synthetic routes are dominated by a few reaction types, reducing diversity and inevitably leaving many interesting bioactive-like chemotypes unexplored. Here, we investigate the large-scale enumeration and targeted docking of isoquinuclidines.

Impact of musical rhythm on blood, physiological and welfare parameters in stabled horses.

The aim of this study was to evaluate the effects of two styles of classical music, based on different tempos (BPM), on the physiological and blood parameters of horses during social isolation and restriction of movements. First experiment was carried out using nine horses of no defined breed, distributed in Control, Slow-tempo music and Moderate-tempo music .For social isolation and restriction of movement, the animals were housed daily in individual stalls for two hours and exposed to the stimuli for 60 min, and eye temperature, heart rate, and respiratory rate were assessed.

Eighteen-year trends in the rates of intra-operative cardiac arrest and associated mortality at a public university hospital in Brazil.

Background: Intra-operative cardiac arrest is a rare but life-threatening event. Over the past two decades, various initiatives have improved the care of patients undergoing surgery at our quaternary teaching hospital in Brazil. We aimed to evaluate the epidemiology of intra-operative cardiac arrest and associated 30-day mortality over an 18-year period.

Immunoinformatics-Based Design of Multi-epitope DNA and mRNA Vaccines Against Zika Virus.

In this study, we used an immunoinformatics approach to predict antigenic epitopes of Zika virus (ZIKV) proteins to assist in designing a vaccine antigen against ZIKV. We performed the prediction of CD8+ T-lymphocyte and antigenic B-cell epitopes of ZIKV proteins. The binding interactions of T-cell epitopes with major histocompatibility complex class I (MHC-I) proteins were assessed.

An update on the mechanisms and risk factors for anesthesia-related cardiac arrest in children: a narrative review.

The relation between surgery and anesthesia safety in children and a country's Human Development Index (HDI) value has been described previously. The aim of this narrative review was to provide an update on the mechanisms and risk factors of Anesthesia-Related Cardiac Arrest (ARCA) in pediatric surgical patients in countries with different HDI values and over time (pre-2001 vs. 2001‒2024).

Regulatory T cell-derived enkephalin gates nociception.

T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression.

The presence of a deep lateral femoral notch sign in ACL-injured patients is associated with a 2.7° steeper posterior tibial slope and a 19% higher frequency of lateral meniscal injuries.

Purpose: The purpose of this study was to study the relationship between the presence of a deep lateral femoral notch sign (DLFNS) in anterior cruciate ligament (ACL)-injured patients and a higher posterior lateral tibial slope (LPTS), a reduced meniscal bone angle (MBA), a higher LPTS/MBA ratio and a higher incidence of concomitant injuries in primary ACL tears.

Methods: A retrospective case-control study was performed in patients submitted to primary ACL reconstruction with an available preoperative magnetic resonance imaging (MRI) scan. Patients with ACL tears and a femoral impactation with a depth ≥2 mm were assorted to the DLFNS group and patients with ACL tear and without a DLFNS to the control group.

Comparison between inhalational anesthetics in terms of DNA damage and immunological markers.

This study compared genetic damage and immunological markers between surgical patients who underwent inhalational anesthesia with isoflurane or sevoflurane. Blood samples were collected from surgical patients (n = 18 in the isoflurane group and n = 17 in the sevoflurane group) at baseline (before the anesthesia procedure) and the day after anesthesia. DNA damage was detected using an alkaline comet assay; proinflammatory interleukin (IL)-6 was detected by flow cytometry, and white blood cells were detected via an automatic hematology analyzer.

Large library docking for cannabinoid-1 receptor agonists with reduced side effects.

Large library docking can reveal unexpected chemotypes that complement the structures of biological targets. Seeking new agonists for the cannabinoid-1 receptor (CB1R), we docked 74 million tangible molecules, prioritizing 46 high ranking ones for de novo synthesis and testing. Nine were active by radioligand competition, a 20% hit-rate.

Global neonatal perioperative mortality: A systematic review and meta-analysis.

Study Objective: There are large differences in health care among countries. A higher perioperative mortality rate (POMR) in neonates than in older children and adults has been recognized worldwide. The aim of this study was to provide a systematic review of published 24-h and 30-day POMRs in neonates from 2011 to 2022 in countries with different Human Development Index (HDI) levels.

Music and Tactile Stimuli during Daily Milking Affect the Welfare and Productivity of Dairy Cows.

The objective of this study was to evaluate the effects of tactile stimuli and music during daily milking on the productive, physiological, well-being, and health parameters of dairy cows. The experiment, which lasted 39 days, was conducted on a commercial farm with forty crossbred cows (age: 36 to 42 months; weight: 350 to 400 kg) distributed in a completely randomized design (2 × 2) via the following treatments: (Con)-cows not exposed to stimuli, (Tac)-cows exposed to tactile stimuli before milking, (Mus)-cows exposed to music during milking, (Tac+Mus)-cows exposed to both stimuli. In this study, classical music with a slow (75 to 107 BPM) and moderate tempo (90 to 100 BPM) was played, and tactile stimuli was provided manually using a flexible stick in the posterior region and udders of the cows.

Docking for EP4R antagonists active against inflammatory pain.

The lipid prostaglandin E (PGE) mediates inflammatory pain by activating G protein-coupled receptors, including the prostaglandin E2 receptor 4 (EP4R). Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce nociception by inhibiting prostaglandin synthesis, however, the disruption of upstream prostanoid biosynthesis can lead to pleiotropic effects including gastrointestinal bleeding and cardiac complications. In contrast, by acting downstream, EP4R antagonists may act specifically as anti-inflammatory agents and, to date, no selective EP4R antagonists have been approved for human use.

Comparative analysis of the biocompatibility of endothelial cells on surfaces treated by thermal plasma and cold atmospheric plasma.

In recent years, cold atmospheric plasma (CAP) is used for surface disinfection. However, little is known about its ability to improve biocompatibility of metallic surfaces when compared to thermal plasma methods. In this context, the study aimed to evaluate the response of human endothelial cells (Ea.

Global anaesthesia-related cardiac arrest rates in children: a systematic review and meta-analysis.

Background: Neonates and infants have a higher perioperative risk of cardiac arrest and mortality than adults. The Human Development Index (HDI) ranges from 0 to 1, representing the lowest and highest levels of development, respectively. The relation between anaesthesia safety and country HDI has been described previously.

Multiple stations in an integrated design of cardiovascular system morphology for medical undergraduate.

The morphology knowledge is essential for clinical, diagnostic and surgical practice in medicine. However, it is a great challenge teaching this science in an integrated curriculum, since it has the need of active methods associated with technology, in a total impaired workload. Therefore, this work described an educational design of multiple practice stations in order to teach morphology of the cardiovascular system in the undergraduate medical education.

Pain and Itch Processing in Aged Mice.

Most reports agree that aging negatively impacts pain processing and that the prevalence of chronic pain increases significantly with age. To improve current therapies, it is critical that aged animals be included in preclinical studies. Here we compared sensitivities to pain and itch-provoking stimuli in naïve and injured young and aged mice.

Fast, Multiple-Use Optical Biosensor for Point-of-Care Glucose Detection with Mobile Devices Based on Bienzyme Cascade Supported on Polyamide 6 Microparticles.

Non-invasive glucose determination provides major advantages in health monitoring and protection. It enables widespread point-of-care testing, which is affordable, sensitive, specific, rapid and equipment-free. This work reports on the development and analytical performance of a colorimetric biosensor in detecting glucose in human urine.

Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.

The serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has unusual anti-depressant and substance-withdrawal effects, and stabilizes the inward-open conformation.

Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect.

The general consensus is that increases in neuronal activity in the anterior cingulate cortex (ACC) contribute to pain's negative affect. Here, using imaging of neuronal calcium dynamics in mice, we report that nitrous oxide, a general anesthetic that reduces pain affect, paradoxically, increases ACC spontaneous activity. As expected, a noxious stimulus also increased ACC activity.

The Road to Becoming a World Champion in Futsal.

Purpose: The aim of the current study was to report the training program and monitoring outcomes of the Portuguese national futsal team during the preparation and competition phases of the FIFA Futsal World Cup Lithuania 2021™. For that, the variations in training load and wellness were measured, as well as their relationship.

Methods: The study followed a retrospective cohort design.

Modulation of gene expression and inflammation but not DNA damage after sevoflurane anesthesia.

This study assessed, for the first time, the expression of the genes hOGG1, TP53, and IL-6 in leukocytes by real-time quantitative polymerase chain reaction in surgical patients before (baseline), during (2 h of anesthesia) and 1 day after sevoflurane anesthesia. Additionally, DNA damage was detected by the comet assay, serum interleukin (IL)-6 was detected by flow cytometry, and differential leukocyte counting was also performed. TP53 and hOGG1 expression was downregulated on the day after anesthesia compared to before anesthesia.