Covalent-fragment screening identifies selective inhibitors of multiple Staphylococcus aureus serine hydrolases important for growth and biofilm formation.

is a leading cause of bacteria-associated mortality worldwide. This is largely because infection sites are often difficult to localize and the bacteria forms biofilms which are not effectively cleared using classical antibiotics. Therefore, there is a need for new tools to both image and treat infections.

Single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenic Staphylococcus aureus communities.

Isogenic bacterial cell populations are phenotypically heterogenous and may include subpopulations of antibiotic tolerant or heteroresistant cells. The reversibility of these phenotypes and lack of biomarkers to differentiate functionally different, but morphologically identical cells is a challenge for research and clinical detection. To overcome this, we present ´Cellular Phenotypic Profiling and backTracing (CPPT)´, a fluorescence-activated cell sorting platform that uses fluorescent probes to visualize and quantify cellular traits and connects this phenotypic profile with a cell´s experimentally determined fate in single cell-derived growth and antibiotic susceptibility analysis.

Development of an inducer-free, virulence gene promoter-controlled, and fluorescent reporter-labeled CRISPR interference system in .

The dCas9-based Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) interference (CRISPRi) gene regulation technique requires two components: a catalytically inactive Cas9 protein (dCas9) and a single-guide RNA that targets the gene of interest. This system is commonly activated by expressing dCas9 through an inducible gene promoter, but these inducers may affect cellular physiology, and accessibility and permeability of the inducer are limited in relevant model systems. Here, we have developed an alternative approach for CRISPRi activation in the clinical isolate USA300 LAC, where dCas9 was expressed through endogenous virulence gene promoters (vgp); coagulase, autolysin, or fibronectin-binding protein A.

Activity-based protein profiling of serine hydrolases and penicillin-binding proteins in .

is a gut commensal bacterium which is gaining increasing relevance as an opportunistic, nosocomial pathogen. Its high level of intrinsic and acquired antimicrobial resistance is causing a lack of treatment options, particularly for infections with vancomycin-resistant strains, and prioritizes the identification and functional validation of novel druggable targets. Here, we use activity-based protein profiling (ABPP), a chemoproteomics approach using functionalized covalent inhibitors, to detect active serine hydrolases across 11 and strains.

Barriers and facilitators to implementing evidence-based integrated HIV and behavioral health care: perspectives from seven federal ending the HIV epidemic jurisdictions.

The federal Ending the HIV Epidemic (EHE) initiative was created to reduce new US HIV infections, largely through pre-exposure prophylaxis and HIV treatments that reduce HIV transmissibility to zero. Behavioral health disorders (mental health and substance use) remain significant barriers to achieving EHE goals. Addressing behavioral health (BH) disorders within HIV primary care settings has been promoted as a critical EHE strategy.

Deciphering host dynamics using dual activity-based protein profiling of ATP-interacting proteins.

Unlabelled: The utilization of ATP within cells plays a fundamental role in cellular processes that are essential for the regulation of host-pathogen dynamics and the subsequent immune response. This study focuses on ATP-binding proteins to dissect the complex interplay between and human cells, particularly macrophages (THP-1) and keratinocytes (HaCaT), during an intracellular infection. A snapshot of the various protein activity and function is provided using a desthiobiotin-ATP probe, which targets ATP-interacting proteins.

Interventions for Integrating Behavioral Health into HIV Settings for US Adults: A Narrative Review of Systematic Reviews and Meta-analyses, 2010-2020.

Mental health and substance use disorders can negatively affect physical health, illness management, care access, and quality of life. These behavioral health conditions are prevalent and undertreated among people with HIV and may worsen outcomes along the entire HIV Care Continuum. This narrative review of tested interventions for integrating care for HIV and behavioral health disorders summarizes and contextualizes findings from systematic reviews and meta-analyses conducted in the past decade.

Comprehensive virulence profiling and evolutionary analysis of specificity determinants in two-component systems.

In the genome, a set of highly conserved two-component systems (TCSs) composed of histidine kinases (HKs) and their cognate response regulators (RRs) sense and respond to environmental stimuli, which drive the adaptation of the bacteria. This study investigates the complex interplay between TCSs in USA300, a predominant methicillin-resistant strain, revealing shared and unique virulence regulatory pathways and genetic variations mediating signal specificity within TCSs. Using TCS-related mutants from the Nebraska Transposon Mutant Library, we analyzed the effects of inactivated TCS HKs and RRs on the production of various virulence factors, infection abilities, and adhesion assays.

Long-Term Efficacy of Successful Excisional Goniotomy with the Kahook Dual Blade.

Purpose: To report clinical outcomes of successful excisional goniotomy with the Kahook Dual Blade (KDB), through 60 months.

Patients And Methods: This was a noncomparative, single-surgeon, retrospective review of eyes receiving successful KDB goniotomy with or without concomitant phacoemulsification between October 2015 and January 2016 with five years of uninterrupted follow-up. Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), and complications were recorded.

Evaluation of online educational curriculum on HPV vaccination practices among adult primary care providers.

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. While HPV is a vaccine-preventable illness, vaccine utilization rates in the United States remain low, particularly among adults.

Methods: The objective of this study was to assess the impact of an online, asynchronous educational module on HPV vaccination for adult primary care providers.

Biochemical and Cellular Characterization of the Function of Fluorophosphonate-Binding Hydrolase H (FphH) in Support a Role in Bacterial Stress Response.

The development of new treatment options for bacterial infections requires access to new targets for antibiotics and antivirulence strategies. Chemoproteomic approaches are powerful tools for profiling and identifying novel druggable target candidates, but their functions often remain uncharacterized. Previously, we used activity-based protein profiling in the opportunistic pathogen to identify active serine hydrolases termed fluorophosphonate-binding hydrolases (Fph).

Activity-Based Protein Profiling in Methicillin-Resistant Staphylococcus aureus Reveals the Broad Reactivity of a Carmofur-Derived Probe.

Activity-based protein profiling is a powerful chemoproteomic technique to detect active enzymes and identify targets and off-targets of drugs. Here, we report the use of carmofur- and activity-based probes to identify biologically relevant enzymes in the bacterial pathogen Staphylococcus aureus. Carmofur is an anti-neoplastic prodrug of 5-fluorouracil and also has antimicrobial and anti-biofilm activity.

Transgender Women's Experiences Using SMARTtest, a Smartphone Application to Facilitate Self- and Partner-HIV/Syphilis Testing Using the INSTI Multiplex.

We present experiences of transgender women (TW) who have sex with men with SMARTtest, a smartphone app to accompany the INSTI Multiplex, a one-minute, dual blood-based HIV/syphilis rapid test. TW participants (N = 11) received 10 INSTI Multiplex tests to take home for self- and/or partner-testing and installed the SMARTtest app on their phones. The SMARTtest app aimed to support INSTI Multiplex users in correctly performing the test, interpreting the results, and connecting with care following a positive HIV or syphilis screening.

Durable Viral Suppression Among Young Adults Living with HIV Receiving Ryan White Services in New York City.

Identifying factors associated with durable viral suppression (DVS) can inform interventions to support young adults living with HIV (YALWH) in sustaining optimal health. We examined associations between client characteristics and DVS among YALWH aged 18-29 who completed an intake assessment and received ≥ 1 Ryan White Part A service in New York City from 1/2017 to 12/2019. Individuals were classified as achieving DVS at least once if they had ≥ 2 suppressed viral load test results ≥ 90 days apart with: (a) no intervening unsuppressed viral load test results in a 12-month period; and (b) no unsuppressed viral load test results after achieving DVS in that 12-month period.

A quality-improvement approach to urgent-care antibiotic stewardship for respiratory tract infections during the COVID-19 pandemic: Lessons learned.

Objective: We investigated a decrease in antibiotic prescribing for respiratory illnesses in 2 academic urgent-care clinics during the coronavirus disease 2019 (COVID-19) pandemic using semistructured clinician interviews.

Methods: We conducted a quality-improvement project from November 2020 to May 2021. We investigated provider antibiotic decision making using a mixed-methods explanatory design including interviews.

Dedicated teams to optimize quality and safety of surgery: A systematic review.

Background: A dedicated operating team is defined as a surgical team consisting of the same group of people working together over time, optimally attuned in both technical and/or communicative aspects. This can be achieved through technical and/or communicative training in a team setting. A dedicated surgical team may contribute to the optimization of healthcare quality and patient safety within the perioperative period.

Negotiating Use of a Blood-Based, Dual HIV and Syphilis Test with Potential Sexual Partners Among a Sample of Cisgender Men and Transgender Women Who Have Sex with Men in New York City.

Cisgender men who have sex with men (cMSM) and transgender women (TGW) are disproportionally burdened by HIV. Among these populations, HIV partner-testing is a highly acceptable harm reduction tool. Particularly, cMSM and TGW report a stronger preference for blood-based tests that include assays for multiple STIs.

Crosstalk between Selenium and Sulfur Is Associated with Changes in Primary Metabolism in Lettuce Plants Grown under Se and S Enrichment.

This study investigated the beneficial effects of selenium (Se) and sulfur (S) enrichment on the primary metabolism in butterhead lettuce. The plants were treated with three levels of Se via foliar application in the presence of two S levels in the nutrient solution under greenhouse conditions. The lettuce plants that were exposed to the lower selenate level (1.

Sustained Reduction in Urgent Care Antibiotic Prescribing During the Coronavirus Disease 2019 Pandemic: An Academic Medical Center's Experience.

We compared antibiotic prescribing before and during the -coronavirus disease 2019 (COVID-19) pandemic at 2 academic urgent care clinics and found a sustained decrease in prescribing driven by respiratory encounters and despite transitioning to telemedicine. Antibiotics were rarely prescribed during encounters for COVID-19 or COVID-19 symptoms. COVID-19 revealed opportunities for outpatient stewardship programs.

Brachial and Axillary Artery Vascular Access for Endovascular Interventions.

Background: Endovascular access is usually achieved through the common femoral artery due to its large size and accessibility. Access through the upper extremity can however be necessary due to anatomic reasons, obesity, or peripheral arterial disease. The 2 main methods of access are surgical cutdown and percutaneous puncture.

Experiences of Transgender Women Who Used a Dual HIV/Syphilis Rapid Self-test to Screen Themselves and Potential Sexual Partners (the SMARTtest Study).

HIV/syphilis self- and partner-testing may be especially appropriate for transgender women, since they shoulder a disproportionate burden of HIV, other STIs (e.g., syphilis), and report high levels of medical mistrust.