A qualitative assessment of barriers to healthcare and HIV prevention services among men who have sex with men in non-metropolitan areas of the south.

HIV cases are increasing in the rural Southern United States, especially among men who have sex with men (MSM). To facilitate healthcare access and encourage HIV prevention for non-metropolitan MSM, it is essential to examine their barriers to care. This qualitative study conducted semi-structured interviews with 20 MSM living in non-metropolitan areas of the South. Analysis revealed that MSM experience multiple barriers accessing healthcare in non-metropolitan areas such as finding knowledgeable and affirming providers with desired characteristics and beliefs and communicating with providers about sexual health and HIV prevention. To aid in identification, many respondents expressed a desire for providers to publicly signal that they provide care for sexual and gender minority patients and are an inclusive clinical space. Overall, results suggest that MSM face unique healthcare-related challenges, beyond those typically experienced by the broader population in non-metropolitan areas, because of tailored identity-based needs. To better support MSM in non-metropolitan areas, especially in the South where increased experiences of stigma are found, providers should seek further training regarding sexual health communication and HIV prevention, indicate on websites and in offices that they support sexual and gender minority patients, and provide telehealth services to MSM living in more geographically isolated areas.

Evolving Primary Care Utilization of Transgender and Gender-Nonconforming People at a Community Sexual Health Clinic.

Purpose: Prior research has found that transgender people are less likely to have access to health care and health insurance than their cisgender peers and are more likely to delay seeking care due to systemic discrimination and stigma. To this end, this study seeks to measure transgender and gender-nonconforming (TGNC) clients' primary care utilization and compare them to their cisgender peers. Methods: Demographic data and self-reported primary care utilization from 14,372 clients attending a community health center in Los Angeles, CA, from 2018 to 2020 were examined. Descriptive statistics and multivariable regression analyses were used to examine correlates of gender identity on primary care utilization metrics-Hepatitis A, Hepatitis B, and Human Papillomavirus (HPV) vaccinations and recent primary care visits. Results: Of TGNC clients, 38.0% reported being vaccinated for Hepatitis A compared to 49.2% of cisgender clients (p<0.01) and 42.6% reported being vaccinated for Hepatitis B compared to 51.6% of cisgender clients (p<0.01). TGNC clients had higher odds of engaging with the HPV vaccination series than their cisgender peers (adjusted odds ratio [aOR]=1.28, 95% confidence interval [CI] 1.03-1.59). TGNC clients had higher odds of seeing their primary care provider within the preceding 2 years (aOR=1.72, 95% CI 1.01-2.93) compared to non-TGNC clients. Conclusions: This study's results found that TGNC clients were more likely to access certain primary care services more often than their cisgender counterparts. Our results support the efficacy of such interventions, such as a health care setting designed to support the health of gender minority people, and see similar, if not greater, primary care engagement in transgender persons compared to their cisgender peers.

High proportions of rectal and pharyngeal chlamydia and gonorrhoea cases among cisgender men are missed using current CDC screening recommendations.

OBJECTIVES: Pharyngeal and rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are often undiagnosed due to their asymptomatic nature. This study aims to determine (1) the prevalence of CT/NG infections by anatomical site among cisgender men; (2) the proportion of missed CT/NG rectal/pharyngeal infections if urogenital testing alone was performed or screening depended on self-reported behaviour alone; and (3) the predictive probability of self-reported behaviours for rectal CT/NG. METHODS: This cross-sectional study used electronic health records collected at a sexual health clinic in Los Angeles from 18 November 2018 until 28 February 2020. The included patients were ≥18 years of age cisgender men who received CT/NG testing at least once during the study period. We calculated the proportion of missed pharyngeal/rectal CT/NG infections if only urogenital testing had been done and if testing was based only on self-reported anal sex. Separately, we ran logistic regressions for predictive probability of self-reported anal sex on CT/NG rectal infections. RESULTS: Overall, there were 13 476 unique patients with 26 579 visits. The prevalence of any extragenital CT/NG infection was 37.28%. Over 80% rectal/pharyngeal CT cases and over 65% rectal/pharyngeal NG cases would be missed if urogenital testing alone was performed. Likewise, over 35% rectal CT/NG cases would be missed had testing relied on self-reported sexual behaviours alone. CONCLUSIONS: The proportion of missed rectal and pharyngeal CT/NG infections is high. Our data from a sexual health clinic lend support to three-site opt-out testing for cisgender men attending a sexual health/Lesbian, Gay, Bisexual, Transgender, Queer/Questioning (LGBTQ+) specialty clinic regardless of their sexual orientation or reported sexual behaviours.

Evidence supporting the standardisation of extragenital gonorrhoea and chlamydia screenings for women.

OBJECTIVE: Current guidelines for women do not include extragenital screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) and do not mention anal sex behaviour. The objective of this cross-sectional study was to determine the number of potentially missed CT and NG cases by relying on urogenital screening and self-reported anal sex behaviour among women. METHODS: Demographic and clinical data of 4658 women attending a community health centre in Los Angeles, California, USA from 2015 to 2018 were examined. CT and NG were detected using nucleic acid amplification test (APTIMA Combo 2, Hologic Gen-Probe, San Diego, California). Demographic and behavioural factors were also examined to assess potentially missed NG/CT cases. Multivariable regression analyses were used to determine whether reported anal sex behaviour predicts NG/CT rectal infection. RESULTS: A total of 193 NG cases and 552 CT cases were identified; however, 53.9% of NG cases and 25.5% of CT cases were identified exclusively through extragenital screening. Of all positive cases of rectal CT, 87.0% did not report anal sex without a condom and 91.3% did not report any anal sex with their last sexual partner. Of all positive cases of rectal NG, 78.9% did not report anal sex without a condom and 76.3% did not report any anal sex with their last sexual partner. Anal sex with last partner was not predictive of NG/CT rectal infection. CONCLUSIONS: Relying solely on urogenital screening and reported behaviour misses NG/CT cases. Extragenital NG/CT screening should be conducted in all women regardless of reported anal sex behaviour.

Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).

Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H2O2-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H2O2-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2) activation.

Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD). Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200µM H2O2 for 6h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI) double staining and Hoechst 33342 fluorescent staining. Reduced (GSH) and oxidized glutathione (GSSG) were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100nM) of RTA 408 markedly attenuated H2O2-induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQO1, Grx1, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes.

Glutaredoxin 1 (Grx1) Protects Human Retinal Pigment Epithelial Cells From Oxidative Damage by Preventing AKT Glutathionylation.

PURPOSE: Glutaredoxin 1 (Grx1) belongs to the oxidoreductase family and is a component of the endogenous antioxidant defense system. However, its physiological function remains largely unknown. In this study, we investigated whether and how Grx1 overexpression protects the retinal pigment epithelial (RPE) cells against H2O2-induced apoptosis. METHODS: Human retinal pigment epithelial (ARPE-19) cells were transfected with either a Grx1-containing plasmid or an empty vector. Primary human RPE cells were transfected with Grx1 small interfering RNA (siRNA) or scrambled siRNA. Cell viability was measured with the WST8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI) double staining. The level of protein glutathionylation (PSSG) was measured by immunoblotting using anti-PSSG antibody. Protein kinase B (AKT) activation was examined by Western blot. Protein kinase B glutathionylation was detected by immunoprecipitation followed by immunoblotting with anti-PSSG antibody. RESULTS: Glutaredoxin 1 overexpression protected ARPE-19 cells from H2O2-induced cell viability loss. Conversely, Grx1 gene knockdown sensitized primary human RPE cells to H2O2. Assessment of apoptosis indicated that cells transfected with the Grx1-containing plasmid were more resistant to H2O2 with fewer cells undergoing apoptosis as compared to empty vector-transfected cells. Hydrogen peroxide-induced PSSG accumulation was also attenuated by Grx1 enrichment. Furthermore, Grx1 overexpression prevented H2O2-induced AKT glutathionylation, resulting in a sustained phospho-AKT elevation in RPE cells. CONCLUSIONS: Glutaredoxin 1 can protect RPE cells against oxidative stress-induced apoptosis. The mechanism of this protection is associated with its ability to stimulate the phosphorylation of AKT by preventing AKT glutathionylation. Considering Grx1's protective abilities in RPE cells, Grx1 could be a potential pharmacological target for retinal degenerative diseases.