Discovery and SAR of JTE-151: A Novel RORγ Inhibitor for Clinical Development.

A number of RORγ inhibitors have been reported over the past decade. There were also several examples advancing to human clinical trials, however, none of them has reached the market yet, suggesting that there could be common obstacles for their future development. As was expected from the general homology of nuclear receptor ligands, insufficient selectivity as well as poor physicochemical properties were identified as potential risks for a RORγ program.

Structure-Guided Design of a Domain-Selective Bromodomain and Extra Terminal N-Terminal Bromodomain Chemical Probe.

Small-molecule-mediated disruption of the protein-protein interactions between acetylated histone tails and the tandem bromodomains of the bromodomain and extra-terminal (BET) family of proteins is an important mechanism of action for the potential modulation of immuno-inflammatory and oncology disease. High-quality chemical probes have proven invaluable in elucidating profound BET bromodomain biology, with seminal publications of both pan- and domain-selective BET family bromodomain inhibitors enabling academic and industrial research. To enrich the toolbox of structurally differentiated N-terminal bromodomain (BD1) BET family chemical probes, this work describes an analysis of the GSK BRD4 bromodomain data set through a lipophilic efficiency lens, which enabled identification of a BD1 domain-biased benzimidazole series.

Unintentional ingestion of putative delta-8 tetrahydrocannabinol by two youth requiring critical care: a case report.

Background: Delta-8 tetrahydrocannabinol (THC) is a psychoactive cannabinoid from the cannabis plant that can be synthetically converted from cannabidiol (CBD). Most states permit the full or restricted sale of hemp and hemp-derived CBD products, and therefore, delta-8 THC products are on the rise. Delta-8 THC consumption can cause intoxication.

In Vitro Testing of Trichomonas vaginalis Drug Susceptibility: Evaluation of Minimal Lethal Concentrations for Metronidazole and Tinidazole That Correspond With Treatment Failure.

Background: The only drugs approved by the US Food and Drug Administration for oral treatment of trichomoniasis belong to the 5-nitroimidazole group. Most individuals infected with Trichomonas vaginalis can be cured with a standard treatment of metronidazole or tinidazole, but it is estimated that more than 159,000 people fail treatment each year. Although a minimal lethal concentration (MLC) corresponding to treatment failure has been reported for metronidazole, the MLC for tinidazole associated with treatment failure has not been determined.

Pilot Testing a Brief Partner-Inclusive Hybrid Intervention for Perinatal Mood and Anxiety Disorders.

The necessity of hybrid and more accessible options for perinatal mood and anxiety disorders (PMADs) has taken on increased urgency in the wake of the COVID-19 pandemic and its lasting impacts. In the New Family Wellness Project (NFWP), participants engage in a hybrid in-person and teletherapy six-session intervention for new parents early in their postpartum period. This small, phase 1 clinical research examined early outcomes of the NFWP's cognitive behavioral intervention on adverse mental health outcomes (i.

Health Equity Morbidity and Mortality Conferences in Obstetrics and Gynecology.

Maternal mortality and morbidity continue to occur at unacceptably high levels in the United States, with communities of color experiencing significantly higher rates than their White counterparts, even after adjustment for confounding factors such as socioeconomic status. Many obstetrics and gynecology departments across the country have begun to incorporate routine discussion and analysis of health equity into peer review and educational processes, including grand rounds and morbidity and mortality conferences. Despite the desire and drive, there is little published guidance on best practices for incorporation of an equity component into these conferences.

Horizons and Group Motivational Enhancement Therapy: HIV Prevention for Alcohol-Using Young Black Women, a Randomized Experiment.

Introduction: Black women are at disproportionately greater risk for HIV and sexually transmitted infections than women of other ethnic/racial backgrounds. Alcohol use may further elevate the risk of HIV/sexually transmitted infection acquisition and transmission.

Study Design: A random-assignment parallel-group comparative treatment efficacy trial was conducted with random assignment to 1 of 3 conditions.

Exploring Changes in Racial/Ethnic Disparities of HIV Diagnosis Rates Under the "Ending the HIV Epidemic: A Plan for America" Initiative.

Objectives: Racial/ethnic disparities in HIV diagnosis rates remain despite the availability of effective treatment and prevention tools in the United States. In 2019, President Trump announced the "Ending the HIV Epidemic: A Plan for America" (EHE) initiative to reduce new HIV infections in the United States at least 75% by 2025 and at least 90% by 2030. The objective of this study was to show the potential effect of the EHE initiative on racial/ethnic disparities in HIV diagnosis rates at the national level.

Pathophysiology for the Pediatric Critical Care Fellow: Three Representative Simulation Cases.

Introduction: During the course of fellowship training, pediatric critical care fellows are expected to develop a broad and in-depth understanding of the pathophysiology of multiple disease processes. The simulation-based pediatric critical care pathophysiology curriculum we present uses scenarios created by pediatric critical care fellows to teach complex pathophysiology.

Methods: Each of the three representative cases presented covered a specific pathophysiologic process and required participants to acutely manage (1) an 18-year-old patient with altered mental status in the setting of hepatic encephalopathy; (2) an 8-year-old patient with sepsis, coagulopathy, and acute kidney injury; or (3) a 12-year-old patient with status epilepticus.

Achieving Independence in Toileting: Self-Catheterization Efficacy and the Role of the School Nurse.

The school nurse is the most consistent healthcare provider for students who require scheduled intermittent self-catheterization; however, there is little literature regarding the role of the school nurse for educating and promoting self-catheterization independence for pediatric populations in the school setting. School nurses are dependent on research to identify best practices when implementing teaching strategies with young students who are ready to start catheterizing independently. The intent of this article is to contribute relevant information that is both useful and evidence based, so the school nurse is equipped with information to support the assessment, planning, and implementation of independent self-catheterization of school-age children.

Social and Structural Factors Associated with Sustained Viral Suppression Among Heterosexual Black Men with Diagnosed HIV in the United States, 2015-2017.

This paper describes sociodemographic, sexual risk behavior, and clinical care factors associated with sustained viral suppression (SVS) among heterosexual Black men with diagnosed HIV in the US. Sample was 968 men, 2015-2017 cycles of Medical Monitoring Project. We used prevalence ratios and a multivariable logistic regression model to identify independent predictors of SVS.

US Regional Changes in Racial/Ethnic Disparities in HIV Diagnoses Among Women in the United States, 2012 and 2017.

Racial/ethnic and geographic disparities in HIV diagnosis rates exist among women in the United States. Black/African American women are disproportionately affected; rates are highest in the South and Northeast. Monitoring progress towards eliminating disparities in HIV diagnosis rates among women is a national HIV prevention goal.

Successfully Recruiting Black and Hispanic/Latino Adolescents for Sexually Transmitted Infection and HIV Prevention Research.

Disparities in rates of sexually transmitted infections (STIs) and HIV between Black/African American and Hispanic/Latino adolescents and their white counterparts are well documented. Researchers may encounter notable challenges recruiting Black/African American and Hispanic/Latino adolescents for sexual risk reduction studies. In this article, we present information to assist with planning, implementing, and evaluating recruitment and retention strategies.

Factors Affecting Pre-Exposure Prophylaxis Implementation for Women in the United States: A Systematic Review.

Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective pill that HIV-negative individuals can take once daily to prevent HIV infection. Although PrEP is a private, user-controlled method that empowers women to protect themselves without relying on a partner's behavior, women's PrEP use has been extremely low. We systematically reviewed the literature to identify and summarize factors that may be affecting PrEP implementation for women in the United States.

Disparities in Incidence of Human Immunodeficiency Virus Infection Among Black and White Women - United States, 2010-2016.

Incident human immunodeficiency virus (HIV) infections among adolescent females and women declined during 2010-2016, with the largest decrease (21%) occurring among black women (1). However, in 2016, although black women accounted for 13% of the U.S.

Psychological and social determinants of health, antiretroviral therapy (ART) adherence, and viral suppression among HIV-positive black women in care.

Black women are disproportionately affected by HIV, accounting for 61% of women diagnosed in 2016. Black women with HIV are less likely to be adherent to antiretroviral therapy (ART) and virally suppressed compared to women of other racial/ethnic groups. We analyzed 2013-2014 data from 1703 black women patients in the Centers for Disease Control and Prevention's Medical Monitoring Project to examine whether select psychological and social determinants of health (SDH) factors were associated with ART adherence and viral suppression.

Parents' Strategies to Support Mealtime Participation of Their Children With Autism Spectrum Disorder.

Objective: We identified and described the strategies parents use to support the mealtime participation of their child with autism spectrum disorder (ASD).

Method: Twelve families with children with ASD (ages 2-7 yr) participated in videotaped mealtime observations. Qualitative content analysis was used to identify strategies families used to facilitate participation.

Trends in Geographic Rates of HIV Diagnoses Among Black Females in the United States, 2010-2015.

Background: HIV diagnoses among females in the United States declined 22% from 2010 to 2015, including a 27% decline in diagnoses among black females. Despite this progress, disparities persist. Black females accounted for 60% of new HIV diagnoses among females in 2015.

Effectively Addressing Human Immunodeficiency Virus Disparities Affecting US Black Women.

Black women have disproportionately higher rates of human immunodeficiency virus (HIV) infection, and low percentages being linked to care and becoming virally suppressed, compared with women of other races/ethnicities. To date, few evidence-based HIV prevention and care interventions tailored for black women exist. We highlight three essential factors to consider in designing culturally and gender-appropriate studies to address HIV-related disparities affecting black women: (1) social determinants of HIV risk, (2) determinants of equity, and (3) perceptions of black women's sexuality.

Acceptability of oral rapid HIV testing at dental clinics in communities with high HIV prevalence in South Florida.

Background: Expanding HIV screening for populations at risk necessitates testing in nontraditional settings. We assessed HIV testing in dental clinics in South Florida, an urban area with the highest rates of HIV diagnoses in the United States in 2015.

Aims: We explored patients' acceptance of oral HIV rapid tests administered by dental providers and identified reasons for accepting or declining HIV testing.

Developing FAITHH: Methods to Develop a Faith-Based HIV Stigma-Reduction Intervention in the Rural South.

Human immunodeficiency virus (HIV) disproportionately affects Blacks/African Americans, particularly those residing in the southern United States. HIV-related stigma adversely affects strategies to successfully engage people in HIV education, prevention, and care. Interventions targeting stigma reduction are vital as additional tools to move toward improved outcomes with HIV prevention and care, consistent with national goals.

Testing our FAITHH: HIV stigma and knowledge after a faith-based HIV stigma reduction intervention in the Rural South.

Eliminating racial/ethnic HIV disparities requires HIV-related stigma reduction. African-American churches have a history of addressing community concerns, including health issues, but may also contribute to stigma. We developed and pilot tested a faith-based, anti-stigma intervention with 12 African-American churches in rural Alabama.

Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients.

Objectives: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault.

Design: Retrospective, two-center, cohort study from 2003 to 2016.

Setting: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals.