Antineoplastic activity of GP-2250 in-vitro and in mouse xenograft models.

This study examined the antineoplastic effects of GP-2250 (misetionamide), an oxathiazine derivative with broad activity, in multiple cancer cell lines and mouse xenograft models. Antineoplastic activity of GP-2250 was tested in >300 cancer cell lines using the OncoPanel cytotoxicity assay. GP-2250 activity was further tested in mouse xenograft models, in which GP-2250 or vehicle (10 ml/kg) was administered daily for 28 days by intraperitoneal injection in the lower right abdomen of CrTac:NCR-Foxn1nu mice with tumor volumes of 100 to 200 mm 3 .

Extracorporeal Membrane Oxygenation Without Invasive Ventilation for Respiratory Failure in Adults: A Systematic Review.

Objectives: Extracorporeal membrane oxygenation (ECMO) is an advanced treatment for acute severe respiratory failure. Patients on ECMO are frequently maintained sedated and immobilized until weaning from ECMO, first, and then from mechanical ventilation. Avoidance of sedation and invasive ventilation during ECMO may have potential advantages.

Positivity and coping as key to well-being and psychological adjustment during the pandemic of COVID-19: A follow-up study in Portugal.

This follow-up study aimed to analyze the protective role of positivity and coping strategies on the well-being and psychological distress levels reported during Portugal's first and third waves of COVID-19. The total sample consisted of 135 participants (82.0% women) with ages ranging from 20 to 72 years (M = 39.

Coronary angiography findings in resuscitated and refractory out-of-hospital cardiac arrest: A systematic review and meta-analysis.

Introduction: Coronary angiography (CAG) frequently reveals coronary artery disease (CAD) after out-of-hospital cardiac arrest (OHCA), but its use is not standardized and often reported in different subpopulations. This systematic review and meta-analysis accurately describes angiographic features in resuscitated and refractory OHCA.

Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to October 31, 2022.

Antiandrogen agents in COVID-19: a meta-analysis of randomized trials.

Introduction: Antiandrogen therapy can reduce the expression of transmembrane protease 2, which is essential for severe acute respiratory syndrome coronavirus-2 to enter the host cells. Prior trials suggested the efficacy of antiandrogen agents in patients with COVID-19. We investigated whether antiandrogen agents reduce mortality compared to placebo or usual care.

Is Urology a gender-biased career choice? A survey-based study of the Italian medical students' perception of specialties.

Background: Despite the well-established worldwide phenomenon of "the feminisation of medicine," in Italy, Urology remains a male-dominated field.

Objective: The aims of our work are to assess data on medical students' choice of surgical specialty in Italy to investigate if a gender-biased trend exists and to find the key points that influence the decision-making process when choosing a specialty, with a focus on Urology.

Design: Data about access to residency programs in 2017-2020 were analysed through descriptive statistics.

Designing optimized drug candidates with Generative Adversarial Network.

Drug design is an important area of study for pharmaceutical businesses. However, low efficacy, off-target delivery, time consumption, and high cost are challenges and can create barriers that impact this process. Deep Learning models are emerging as a promising solution to perform de novo drug design, i.

An international study on psychological coping during COVID-19: Towards a meaning-centered coping style.

Background/objective: This study examined the role of different psychological coping mechanisms in mental and physical health during the initial phases of the COVID-19 crisis with an emphasis on meaning-centered coping.

Method: A total of 11,227 people from 30 countries across all continents participated in the study and completed measures of psychological distress (depression, stress, and anxiety), loneliness, well-being, and physical health, together with measures of problem-focused and emotion-focused coping, and a measure called the Meaning-centered Coping Scale (MCCS) that was developed in the present study. Validation analyses of the MCCS were performed in all countries, and data were assessed by multilevel modeling (MLM).

Dealing With the Pandemic of COVID-19 in Portugal: On the Important Role of Positivity, Experiential Avoidance, and Coping Strategies.

The global COVID-19 pandemic crisis has caused an unprecedented impact on most areas of people's lives. Thus, framed within the scope of Existential Positive Psychology (PP2.0), this study aimed at assessing the psychological distress of adults living in Portugal during the first national lockdown, how they are coping with stress, as well to contribute to a deeper understanding about the role that positivity, experiential avoidance, and coping strategies have in psychological distress and well-being.

Appraisal and coping predict health and well-being during the COVID-19 pandemic: An international approach.

COVID-19 has had a devastating impact on people worldwide. We conducted an international survey (n = 3646) examining the degree to which people's appraisals and coping activities around the pandemic predicted their health and well-being. We obtained subsamples from 12 countries-Bangladesh, Bulgaria, China, Colombia, India, Israel, the Netherlands, Norway, Peru, Portugal, Turkey and the United States.

Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy.

Background: In childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.

Methods: Twenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study.

Are there gender differences in left ventricular remodeling after myocardial infarction in rats?

Objective: An unclear issue is whether gender may influence at cardiac remodeling after myocardial infarction (MI). We evaluated left ventricle remodeling in female and male rats post-MI.

Methods: Rats were submitted to anterior descending coronary occlusion.

Gender-based differences in cardiac remodeling and ILK expression after myocardial infarction.

Background: Gender can influence post-infarction cardiac remodeling.

Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI).

Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area).

Reactivity of atropaldehyde, a felbamate metabolite in human liver tissue in vitro.

Antiepileptic therapy with a broad spectrum drug felbamate (FBM) has been limited due to reports of hepatotoxicity and aplastic anemia associated with its use. It was proposed that a bioactivation of FBM leading to formation of alpha,beta-unsaturated aldehyde, atropaldehyde (ATPAL) could be responsible for toxicities associated with the parent drug. Other members of this class of compounds, acrolein and 4-hydroxynonenal (HNE), are known for their reactivity and toxicity.

Anticonvulsant and antiepileptogenic effects of fluorofelbamate in experimental status epilepticus.

Purpose: To examine the seizure-protective properties of fluorofelbamate, a felbamate analog, on acute and chronic seizures in an experimental model of self-sustaining status epilepticus (SSSE).

Methods: SSSE was induced by stimulation of the perforant path for 30 min (PPS) through chronically implanted electrodes in free-running adult male Wistar rats. Fluorofelbamate was injected intravenously (i.

Interaction between human serum albumin and the felbamate metabolites 4-Hydroxy-5-phenyl-[1,3]oxazinan-2-one and 2-phenylpropenal.

Felbamate is an anti-epileptic drug associated with hepatotoxicity and aplastic anemia. These toxicities are believed to be mediated by the formation of the reactive species 2-phenylpropenal. 4-Hydroxy-5-phenyl-[1,3]oxazinan-2-one is a metabolic precursor for 2-phenylpropenal.

Linkage disequilibrium of HLA-A11 and A1 with one of the polymorphisms of the gamma-aminobutyric acid receptor type B.

The gamma-aminobutyric acid receptor type B 1 (GABA(B) R1) is located approximately at 200 kb telomeric to HLA-A on chromosome 6. It has 11 single-nucleotide polymorphisms (SNPs). We studied the most common of its SNPs (T1974C) in a panel of 118 normal Caucasians from New England and 161 epileptic patients of Caucasian ancestry residing in USA.

Felbamate-induced apoptosis of hematopoietic cells is mediated by redox-sensitive and redox-independent pathways.

Felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an approved antiepileptic drug shown to be effective in a variety of seizure disorders refractory to other treatments. However, its use has been restricted because of association with occurrence of rare cases of aplastic anemia and hepatic failure. Since it was shown that FBM metabolism requires glutathione (GSH), we used two experimental protocols to determine if the effects of specific metabolites were sensitive to redox pathways.

The chemistry, toxicology, and identification in rat and human urine of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one: a reactive metabolite in felbamate bioactivation.

4-Hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one has been proposed to be a reactive metabolite of the anti-epileptic drug felbamate [Thompson et al. (1996) Chem. Res.

Role of glutathione S-transferases A1-1, M1-1, and P1-1 in the detoxification of 2-phenylpropenal, a reactive felbamate metabolite.

Felbamate has proven to be an effective therapy for treating refractory epilepsy. However, felbamate therapy has been limited due to the associated reports of hepatotoxicity and aplastic anemia. Previous research from our laboratory has proposed 2-phenylpropenal as the reactive metabolite in felbamate bioactivation and identified its mercapturates in the urine of rats and patients undergoing felbamate therapy.

A self-complementary, self-assembling microsphere system: application for intravenous delivery of the antiepileptic and neuroprotectant compound felbamate.

Felbamate (FBM) is a novel antiepileptic drug (AED) and neuroprotectant (NP) compound that interacts with strychnine-insensitive (SI) glycine receptors in brain (IC(50) = 374 microM). FBM concentrations required to interact with SI glycine receptors are consistent with brain levels following oral and intraperitoneal administration of AED and NP doses. Because of the solubility limits of FBM, an intravenous (iv) form has not been developed.

A mechanistic approach to understanding species differences in felbamate bioactivation: relevance to drug-induced idiosyncratic reactions.

In an attempt to understand the species-selective toxicity of felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM), which is thought to result from bioactivation to 2-phenylpropenal, FBM metabolism was evaluated in rats and humans. The formation of 2-phenylpropenal was monitored by the amount of its mercapturates excreted in urine. The data show a relative 5-fold increase in mercapturate excretion in patient urine as a result of differences in metabolism through P450-, esterase-, and aldehyde dehydrogenase-mediated pathways.