Epidemiology of Mpox Cases, and Tecovirimat and JYNNEOS Utilization, Alameda County, California, June-October 2022.

Context: The 2022 United States mpox outbreak disproportionately affected racial and ethnic minority gay, bisexual, and other men who have sex with men.

Program: We utilized surveillance data and vaccination registries to determine whether populations most impacted by mpox in Alameda County received JYNNEOS vaccines and tecovirimat (TPOXX) during June 1-October 31, 2022.

Implementation: Alameda County Public Health Department responded to the mpox epidemic through partnerships with local health care providers who serve communities disproportionately affected by mpox.

Reactivity of renal and mesenteric resistance vessels to angiotensin II is mediated by NOXA1/NOX1 and superoxide signaling.

Activation of NADPH oxidase (NOX) enzymes and the generation of reactive oxygen species and oxidative stress regulate vascular and renal function and contribute to the pathogenesis of hypertension. The present study examined the role of NOXA1/NOX1 function in vascular reactivity of renal and mesenteric resistance arteries/arterioles of wild-type and mice. A major finding was that renal blood flow is less sensitive to acute stimulation by angiotensin II (ANG II) in mice compared with wild-type mice, with a direct action on resistance arterioles independent of nitric oxide (NO) bioavailability.

Unique Cell Subpopulations and Disease Progression Markers in Canines with Atopic Dermatitis.

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with unclear molecular and cellular contributions behind the complex etiology. To unravel these differences between healthy control and AD skin we employed single-cell transcriptomics, utilizing the canine AD model for its resemblance to human clinical and molecular phenotypes. In this study, we show that there are overall increases in keratinocytes and T cells and decreases in fibroblast populations in AD dogs.

dCas9 fusion to computer-designed PRC2 inhibitor reveals functional TATA box in distal promoter region.

Bifurcation of cellular fates, a critical process in development, requires histone 3 lysine 27 methylation (H3K27me3) marks propagated by the polycomb repressive complex 2 (PRC2). However, precise chromatin loci of functional H3K27me3 marks are not yet known. Here, we identify critical PRC2 functional sites at high resolution.

Epidemiology of Coronavirus Disease 2019 at a County Jail-Alameda County, California, March 2020-March 2021.

Context: Coronavirus disease 2019 (COVID-19) incidence rates are 2- to 5-fold higher among persons incarcerated in the United States than in the general population.

Program Or Policy: We describe an outbreak investigation of COVID-19 at a jail (jail A) in Alameda County during March 2020-March 2021.

Implementation: To prevent COVID-19 cases among incarcerated persons and employees, staff at jail A and the county public health department worked to develop and recommend infection control measures implemented by jail A including, but not limited to, face covering use among incarcerated persons and staff; cohorting incarcerated persons at a higher risk of severe COVID-19 in dedicated housing units; quarantining all newly detained individuals for 14 days; and offering testing for all symptomatic incarcerated persons, newly incarcerated persons at day 2 and day 10, and all persons who resided in a housing unit where a COVID-19 case was detected.

Renal NOXA1/NOX1 Signaling Regulates Epithelial Sodium Channel and Sodium Retention in Angiotensin II-induced Hypertension.

NADPH oxidase (NOX)-derived reactive oxygen species (ROS) are implicated in the pathophysiology of hypertension in chronic kidney disease patients. Genetic deletion of NOX activator 1 () subunit of NOX1 decreases ROS under pathophysiological conditions. Here, we investigated the role of NOXA1-dependent NOX1 activity in the pathogenesis of angiotensin II (Ang II)-induced hypertension (AIH) and possible involvement of abnormal renal function.

Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens.

CRISPR screens have been used to connect genetic perturbations with changes in gene expression and phenotypes. Here we describe a CRISPR-based, single-cell combinatorial indexing assay for transposase-accessible chromatin (CRISPR-sciATAC) to link genetic perturbations to genome-wide chromatin accessibility in a large number of cells. In human myelogenous leukemia cells, we apply CRISPR-sciATAC to target 105 chromatin-related genes, generating chromatin accessibility data for ~30,000 single cells.

A hybrid effectiveness/implementation trial of an evidence-based intervention for HIV-serodiscordant African American couples.

Couples-based behavioral HIV prevention interventions have demonstrated efficacy, but few are routinely available in community-based settings in the United States. The Eban intervention, designed for heterosexual African American serodiscordant couples and proven efficacious in a cluster randomized trial, was implemented in community-based HIV service organizations in two cities disproportionately affected by the HIV epidemic. This article reports primarily on the effectiveness results related to condom use and results related to retention challenges within a Hybrid Type 2 implementation/effectiveness trial.

Barriers to Testing for Sexually Transmitted Infections among HIV-Serodiscordant Couples: The Influence of Discrimination.

Objectives: African Americans face challenges in accessing services for sexually transmitted infections (STIs). From 2012-2016, the EBAN II intervention was funded by the NIH to test the effectiveness of implementing a culturally congruent, evidence-based HIV/AIDS prevention program in Los Angeles and Oakland, California. This study examined the impact of personal characteristics and experiences of discrimination on the likelihood of being tested for STIs.

Combining surveillance systems to investigate local trends in tuberculosis-HIV co-infection.

Alameda County has some of the highest human immunodeficiency virus (HIV) and tuberculosis (TB) case rates of California counties. We identified TB-HIV co-infected patients in 2002-2015 by matching county TB and HIV registries, and assessed trends in TB-HIV case rates and estimated prevalence ratios for HIV co-infection. Of 2054 TB cases reported during 2002-2015, 91 (4%) were HIV co-infected.

Targeted demethylation at the CDKN1C/p57 locus induces human β cell replication.

The loss of insulin-secreting β cells is characteristic among type I and type II diabetes. Stimulating proliferation to expand sources of β cells for transplantation remains a challenge because adult β cells do not proliferate readily. The cell cycle inhibitor p57 has been shown to control cell division in human β cells.

A taxonomy of the scope and organization of local sexually transmitted disease services for policy and practice.

Local health departments (LHDs) and their organizational partners play a critical role in controlling sexually transmitted diseases (STDs) in the United States. We examine variation in the differentiation, integration, and concentration (DIC) of STD services and develop a taxonomy describing the scope and organization of local STD services. LHD STD programs (n = 115) in Alabama (AL) and California (CA) responded to surveys assessing STD services available in 2014.

GABA and Artesunate Do Not Induce Pancreatic α-to-β Cell Transdifferentiation In Vivo.

Recent reports identified activation of the GABA signaling pathway as a means to induce transdifferentiation of pancreatic α cells into β cells. These reports followed several previous studies that found that α cells were particularly well suited to conversion into β cells in mice, but only after nearly complete β cell loss or forced overexpression of key transcriptional regulators. The possibility of increasing β cell number via reprograming of α cells with a small molecule is enticing, as this could be a potential new pharmacologic therapy for diabetes.

Using a Social Network Strategy to Distribute HIV Self-Test Kits to African American and Latino MSM.

Background: Men who have sex with men (MSM) continue to be disproportionately impacted globally by the HIV epidemic. Studies suggest that HIV self-testing (HIVST) is highly acceptable among MSM. Social network strategies to increase testing are effective in reaching MSM, particularly MSM of color, who may not otherwise test.

Strategies to Increase HIV Testing Among MSM: A Synthesis of the Literature.

More than 30 years into the HIV epidemic, men who have sex with men (MSM) continue to be disproportionately impacted. It is estimated that worldwide nearly half of MSM infected with HIV are unaware of their status, making HIV testing along with early linkage to care crucial to HIV prevention efforts. However, there remain significant barriers to HIV testing among MSM, due largely to complex issues of layered stigma that deter MSM from accessing traditional, clinic-based testing.

TRAP-seq identifies cystine/glutamate antiporter as a driver of recovery from liver injury.

Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically.

Invasive Obstetric Procedures and Cesarean Sections in Women With Known Herpes Simplex Virus Status During Pregnancy.

Background: Neonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group.

The RSVP Project: Factors Related to Disengagement From Human Immunodeficiency Virus Care Among Persons in San Francisco.

Background: In the United States, an estimated two-thirds of persons with human immunodeficiency virus (HIV) infection do not achieve viral suppression, including those who have never engaged in HIV care and others who do not stay engaged in care. Persons with an unsuppressed HIV viral load might experience poor clinical outcomes and transmit HIV.

Objective: The goal of the Re-engaging Surveillance-identified Viremic Persons (RSVP) project in San Francisco, CA, was to use routine HIV surveillance databases to identify, contact, interview, and reengage in HIV care persons who appeared to be out of care because their last HIV viral load was unsuppressed.

Dietary salt regulates uroguanylin expression and signaling activity in the kidney, but not in the intestine.

The peptide uroguanylin (Ugn) is expressed at significant levels only in intestine and kidney, and is stored in both tissues primarily (perhaps exclusively) as intact prouroguanylin (proUgn). Intravascular infusion of either Ugn or proUgn evokes well-characterized natriuretic responses in rodents. Furthermore, Ugn knockout mice display hypertension and salt handling deficits, indicating that the Na(+) excretory mechanisms triggered when the peptides are infused into anesthetized animals are likely to operate under normal physiological conditions, and contribute to electrolyte homeostasis in conscious animals.

Modulation of the myogenic mechanism: concordant effects of NO synthesis inhibition and O2- dismutation on renal autoregulation in the time and frequency domains.

Renal blood flow autoregulation was investigated in anesthetized C57Bl6 mice using time- and frequency-domain analyses. Autoregulation was reestablished by 15 s in two stages after a 25-mmHg step increase in renal perfusion pressure (RPP). The renal vascular resistance (RVR) response did not include a contribution from the macula densa tubuloglomerular feedback mechanism.

Regular clinic attendance in two large San Francisco HIV primary care settings.

Although poor clinic attendance is associated with increased morbidity and mortality among HIV-infected individuals, less is known about predictors of retention and the acceptability of targeted interventions to increase regular clinic attendance. To better understand which patients are at risk for irregular clinic attendance and to explore interventions to aid in retention to care, we surveyed patients attending two outpatient HIV clinics affiliated with the University of California, San Francisco. A total of 606 participants were surveyed, and the analysis was restricted to the 523 male respondents.

Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor.

Objective: Vascular endothelial growth factor (VEGF) acts, in part, by triggering calcium ion (Ca(2+)) entry. Here, we sought understanding of a Synta66-resistant Ca(2+) entry pathway activated by VEGF.

Approach And Results: Measurement of intracellular Ca(2+) in human umbilical vein endothelial cells detected a Synta66-resistant component of VEGF-activated Ca(2+) entry that occurred within 2 minutes after VEGF exposure.

Superoxide enhances Ca2+ entry through L-type channels in the renal afferent arteriole.

Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization.