Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial.

Background: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate COVID-19.

Methods: This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure.

Synthetic Naphthoquinone Inhibits Herpes Simplex Virus Type-1 Replication Targeting Na, K ATPase.

Since 1970 acyclovir (ACV) has been the reference drug in treating herpes simplex virus (HSV) infections. However, resistant herpes simplex virus type 1 (HSV-1) strains have emerged, narrowing the treatment efficacy. The antiviral activity of classical Na, K ATPase enzyme (NKA) inhibitors linked the viral replication to the NKA's activity.

Barriers That Interfere with Access to Tuberculosis Diagnosis and Treatment across Countries Globally: A Systematic Review.

This study evaluated the barriers that interfere with access to diagnosis and treatment of tuberculosis (TB) from the perspective of the patient and health professionals globally. Using the PICo acronym, the question we asked was "What are the barriers that interfere with access to tuberculosis diagnosis and treatment (I) from the perspective of patients and/or health professionals (P) across countries globally (Co)?". We searched the following databases: EMBASE, Scopus, MEDLINE, Latin American and Caribbean Literature in Health Sciences (LILACS), and Web of Science.

In Silico Drug Repurposing Uncovered the Antiviral Potential of the Antiparasitic Drug Oxibendazole Against the Chikungunya Virus.

Chikungunya virus (CHIKV) has been reported in over 120 countries and is the causative agent of Chikungunya fever. The debilitating nature of this disease, which can persist months to years after acute infection, drastically impacts the quality of life of patients. Yet, specific antivirals are lacking for the treatment of this disease, which makes the search for new drugs necessary.

Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-Naphthoquinone Hybrids.

Background: Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science.

Randomized, Multicenter Study to Assess the Effects of Different Doses of Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension.

Background: Sildenafil, approved for pulmonary arterial hypertension (PAH), has a recommended adult dose of 20 mg TID, with a previously approved 5-mg TID dose by the US Food and Drug Administration. Safety concerns arose because of common off-label use of higher doses, particularly after pediatric data linked higher doses to increased mortality. To assess this, the Food and Drug Administration mandated a study evaluating the effects of various sildenafil doses on mortality in adults with PAH.

Spider's Silk as a Potential Source of Antibiotics: An Integrative Review.

Spiders produce webs, which are still a largely unexplored source of antibacterial compounds, although the reports of its application in the medical field. Therefore, this study aims to present an integrative review of the antibacterial activity of spider webs. The research was conducted using Google Scholar, Scielo, Web of Science, PubMed, ScienceDirect, Medline EBSCO, LILACS, and Embase.

N, N'-disubstituted Ureas as Novel Antiplatelet Agents: Synthesis, Pharmacological Evaluation and In Silico Studies.

Introduction: Thrombotic disorders are among the leading causes of morbidity and mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic limitations and adverse effects such as hemorrhagic conditions, highlighting the importance of developing more effective antiplatelet agents. ethod: In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet profiles through in vitro, ex vivo, and in silico studies.

Social protection as a right of people affected by tuberculosis: a scoping review and conceptual framework.

Background: Tuberculosis is an infectious disease strongly influenced by social determinants closely associated with cycles of poverty and social exclusion. Within this context, providing social protection for people affected by the disease constitutes a powerful instrument for reducing inequalities and enhancing inclusion and social justice. This study aimed to identify and synthesize strategies and measures aimed at ensuring social protection as a right of people affected by tuberculosis.

Anticancer Activity and Molecular Targets of Substances in Oral Squamous Cell Carcinoma Models.

Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, with high morbidity and mortality rates. The development of new drugs to treat OSCC is paramount. plant species have shown many biological activities.

Chemoselective Synthesis of Mannich Adducts from 1,4-Naphthoquinones and Profile as Autophagic Inducers in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, accounting for approximately 90% of all oral cancers, and is the eighth most common cancer in men. Cisplatin and carboplatin are the main chemotherapy drugs used in the clinic. However, in addition to their serious side effects, such as damage to the nervous system and kidneys, there is also drug resistance.

Integral health care for transgender adolescents: subsidies for nursing practice.

Objective: to analyze the integral health care for transgender adolescents from the perspective of their guardians.

Method: qualitative research based on the Social Network framework proposed by Lia Sanicola, developed with 22 guardians of transgender adolescents in Brazil through semi-structured individual online interviews. The empirical material was analyzed using the content analysis technique, thematic modality.

Technology for nursing consultation with transsexual women in the light of Leininger's transcultural theory.

Objective: to describe the construction and validation of a nursing consultation technology for transgender women.

Methods: a methodological study developed in three stages with construction based on the Leininger's Cross-Cultural Theory, content validation performed by experts in transgender sexual health and evaluation by nurses of care for transgender women. Items with a minimum agreement of 80% were considered validated, according to the Content Validity Index and binomial test.

26-Week Open-Label Extension Study Evaluating the Safety and Tolerability of Flexible Doses of Oral Ziprasidone in Children and Adolescents with Bipolar I Disorder (Most Recent Episode Manic).

To describe the longer-term effectiveness, safety, and tolerability of open-label ziprasidone in children and adolescents with bipolar I disorder (BD-I). A subset of 23 participants aged 10-17 years, who were previously treated in a multi-site, 4-week randomized controlled trial received open-label ziprasidone (20-80 mg twice a day) for up to 26 weeks. The most common adverse events (AEs) were fatigue (30%), somnolence (17%), and nausea (13%).

Pro-Apoptotic Antitumoral Effect of Novel Acridine-Core Naphthoquinone Compounds against Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a global public health problem with high incidence and mortality. The chemotherapeutic agents used in the clinic, alone or in combination, usually lead to important side effects. Thus, the discovery and development of new antineoplastic drugs are essential to improve disease prognosis and reduce toxicity.

Dynamics of Primary Social Networks to Support Mothers, Fathers, or Guardians of Transgender Children and Adolescents: A Systematic Review.

Mothers, fathers, or guardians of children and adolescents who do not identify with the gender they were assigned at birth face barriers in their social network to recognize their children's gender identity. This study aimed to analyze the scientific evidence on the dynamics of primary social networks to support mothers, fathers, or guardians of transgender children and adolescents. This is a systematic review of qualitative studies guided by the PRISMA guidelines.

Efficacy, Safety, and Tolerability of Flexibly Dosed Ziprasidone in Children and Adolescents with Mania in Bipolar I Disorder: A Randomized Placebo-Controlled Replication Study.

To evaluate the acute efficacy, safety, and tolerability of flexibly dosed ziprasidone in children and adolescents with Bipolar I Disorder (BD-I). Participants, 10-17 years of age, meeting The criteria, were randomized 1:1 in a 4-week double-blind (DB) study, to receive ziprasidone (20-80 mg/twice a day) or placebo. Some were then enrolled in a 26-week open-label extension (OLE) study.

Gender violence perpetrated against trans women.

Objectives: to identify scientific evidence on gender violence perpetrated against trans women.

Methods: integrative review, carried out in June 2020, without time frame, in the Scopus, MEDLINE, Embase, CINAHL, WoS, PsycInfo and LILACS databases. The controlled descriptors of DeCS, MeSH and their entry terms were used: "Transgender People", "Transgender", "Gender Identity", "Transsexuality", "Gender Violence", "Aggression", "Sexual Offenses", "Rape", "Violence", "Domestic Violence".

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

Background: Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M) inhibitor with potent pan-human-coronavirus activity in vitro.

Methods: We conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated.

Prognostic relevance of magnesium alterations in patients with a myocardial infarction and left ventricular dysfunction: insights from the EPHESUS trial.

Aims: Magnesium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). The relation between serum magnesium and clinical outcomes is insufficiently elucidated in this population.

Methods And Results: The EPHESUS trial randomized 6632 patients to either eplerenone or placebo.

Effects of tauroursodeoxycholic acid on glucose homeostasis: Potential binding of this bile acid with the insulin receptor.

Aims: The bile acid (BA), tauroursodeoxycholic acid (TUDCA) regulates glucose homeostasis; however, it is not clear whether its effects on insulin signaling are due to its direct interaction with the insulin receptor (IR) or through activation of the G-coupled BA receptor, TGR5. We, herein, investigated whether the actions of TUDCA on glucose homeostasis occur via IR or TGR5 activation.

Main Methods: Glucose homeostasis was evaluated in high-fat diet (HFD)-obese or control (CTL) mice, after 30 days or one intraperitoneal (ip) injection of 300 mg/kg TUDCA, respectively.