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Background: The onset of the COVID-19 pandemic in the United States in March 2020 caused a dramatic change in the way many people lived. Few aspects of daily life were left undisrupted by the pandemic's onset as well as the accompanying policies to control the spread of the disease. Previous research has found that the pandemic may have significantly impacted the mental health of lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals-potentially more so than other individuals. However, the pandemic did not affect all areas of the United States at the same time, and there may be regional variation in the impact of the onset of the pandemic on depressive symptoms among LGBTQ individuals., Objective: To assess regional variation of the impact of the pandemic, we conducted a time series analysis stratified by US geographic region to examine symptoms of depression and anxiety among a sample of primarily cisgender gay and bisexual men before and after the onset of the COVID-19 pandemic in the United States., Methods: In total, 5007 participants completed assessments as part of the Together 5000 study, an ongoing prospective cohort study. Depressive and anxiety symptoms were measured using the Patient Health Questionnaire-4. Patient Health Questionnaire-4 scores were graphed as a function of days from March 15, 2020. Locally estimated scatterplot smoothing trend lines were applied. A sieve-bootstrap Mann-Kendall test for monotonic trend was conducted to assess the presence and direction of trends in the scatterplots. We then compared the observed trends to those observed for 1 year prior (2018-2019) to the pandemic onset using data collected from the same sample., Results: Significant positive trends were detected for the Northeast (P=.03) and Midwest (P=.01) regions of the United States in the 2020 assessment, indicating that symptoms of anxiety and depression were increasing in the sample in these regions immediately prior to and during the onset of the pandemic. In contrast, these trends were not present in data from the 2018 to 2019 assessment window., Conclusions: Symptoms of anxiety and depression increased among the study population in the Northeast and Midwest during the beginning months of the COVID-19 pandemic, but similar increase was not observed in the South and West regions. These trends were also not found for any region in the 2018 to 2019 assessment window. This may indicate region-specific trends in anxiety and depression, potentially driven by the burden of the pandemic and policies that varied from region to region. Future studies should consider geographic variation in COVID-19 spread and policies as well as explore potential mechanisms by which this could influence the mental health of LGBTQ individuals., (©Chloe Mirzayi, Drew Westmoreland, Matthew Stief, Christian Grov. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 26.01.2024.)

Background: In the summer of 2022, the United States faced a nationwide outbreak of mpox, with cases concentrated in sexual and gender minorities who have sex with men. Understanding rates of mpox vaccine uptake and concomitant behavioral change is essential to guide the implementation of targeted public health responses to the potential reemergence of mpox., Methods: Between August 2022 and November 2022, 8551 individuals recruited via geosocial networking apps completed a brief survey that assessed mpox vaccine uptake, intentions to get a mpox vaccine, and behavioral change., Results: In August, 17.4% of participants reported having received at least 1 dose of the mpox vaccine. By November, this prevalence estimate was 35.0%. Black participants were significantly less likely to be vaccinated, and vaccine hesitancy increased among Black participants over time. Among those who had not yet received a vaccination, the intention to get vaccinated decreased over time. We observed trends that coincided with the evolving outbreak, such as decreased worry about mpox and less engagement in risk reduction behaviors over time., Conclusions: Despite a 2-fold increase in mpox vaccine uptake between August 2022 and November 2022 in sexual and gender minorities who have sex with men, disparities in vaccine uptake were observed among Black participants. Findings will guide the implementation of public health responses to the potential reemergence of mpox and other viral infectious diseases (eg, meningitis) with a specific focus on optimizing vaccine uptake in Black communities., Competing Interests: Potential conflicts of interest . A. W. C. reports the following grant or contract: UG3-AI169652 (NIH). C. G. reports the following grants or contracts: R01 AI150502 Rendina/Talan (NIH), UH3 AI 133675 Grov (NIH), UG3-DA058304 Spinelli/Ghandi/Carrico (NIH) and participation on the following data and safety monitoring board or advisory board: UG3AI169658—Schnall/ Garofalo/Duncan (NIH). C. M. reports the following grants or contracts to their institution: 3UH3AI133675-04S1 Nash/Grov MPI (NIH). D. N. reports consulting fees from Gilead and AbbVie. D. A. W. reports NIAAA K01AA029047 (NIH) and NIH Loan Repayment Program L60AA030435 (NIH); grant or department funds received/used for attending meetings and/or travel; and a leadership or fiduciary role on the Student Award Review Subcommittee for the Society for the Scientific Study of Sexuality. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicle-treated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (μCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

One-quarter of gay, bisexual, and other men who have sex with men (GBMSM) with diagnosed HIV are not engaged in HIV care. Between 2018 and 2019, 50 GBMSM completed qualitative interviews 3 months after receiving an HIV-positive result. Interviews explored barriers to and facilitators of engagement and retention in HIV testing and care. Thematic analysis revealed five major themes: (1) reason for HIV testing (e.g., self-testing), (2) linkage to care (e.g., appointment/logistic issues and social support as encouragement), (3) barriers to engagement in care (e.g., financial burden, competing priorities, and fear/stigma), (4) facilitators of engagement (e.g., financial assistance, patient-provider relationships, auxiliary support services, and health agency), and (5) PrEP as a missed prevention opportunity. Addressing individual-, social-, and policy-level barriers could improve GBMSM's engagement in HIV care. Further, capitalizing on GBMSM's health agency through partnerships with local agencies and fostering better patient-provider relationships could optimize HIV care continuity.

Since the emergence of the COVID-19 pandemic, there has been an increasing body of research focused on the effects that measures like stay-at-home orders and social distancing are having on other aspects of health, including mental health and sexual health. Currently, there are limited extant data on the effects of the pandemic on sexual and gender minorities. Between April 15, 2020, and May 15, 2020, we invited participants in an ongoing U.S. national cohort study (Together 5000) to complete a cross-sectional online survey about the pandemic, and its effects on mental and sexual health and well-being (n = 3991). Nearly all (97.7%) were living in an area where they were told they should only leave their homes for essentials. Most (70.1%) reported reducing their number of sex partners as a result of the pandemic. Among the 789 participants prescribed HIV pre-exposure prophylaxis (PrEP), 29.9% said they stopped taking their PrEP entirely, and 14.2% started selectively skipping doses. For those who had been taking PrEP, discontinuing PrEP was associated with having no new sex partners (β = 0.90, 95% CI 0.40-1.40). Among the 152 HIV-positive participants, 30.9% said they were unable to maintain an HIV-related medical appointment because of the pandemic and 13.8% said they had been unable to retrieve HIV medications. Additionally, 35.3% of participants were experiencing moderate to severe anxiety because of the pandemic and 36.7% reported symptoms of depression. In a multivariable logistic regression, reporting a new sex partner in the prior 30 days was significantly associated with being aged 30 or older (vs. not, AOR = 1.21), being Black (AOR = 1.79) or Latinx (AOR = 1.40, vs. white), and being unsure if they had been in close contact with someone diagnosed with COVID-19 (AOR = 1.32, vs. no contact). It was unassociated with COVID-19-induced anxiety, depression, or knowing someone hospitalized with COVID-19. The pandemic has caused disruptions in sexual behavior (partner reduction) as well as difficulties navigating PrEP and HIV care continua. Findings will guide more comprehensive public health responses to optimize HIV prevention and treatment in the era of COVID-19., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Improving HIV testing rates and increasing early detection among men who have sex with men (MSM) are critical strategies for enhancing overall health and decreasing HIV transmission. Remote testing and phone delivery of HIV test results may reduce barriers such as geographic isolation or HIV-related stigma. In 2018-19, 50 MSM completed qualitative interviews about their experience receiving a positive HIV test result via phone through their participation in a research study that included remote HIV testing. Interview topics included the acceptability of, and concerns about, phone delivery of HIV results, as well as suggestions for improvement. Interviews were transcribed, coded, and analysed using an inductive thematic approach. Overall, participants reported high acceptability of phone delivery of HIV-positive results. Participants praised the support and information provided by study staff. Benefits identified included increased convenience compared to in-person medical visits, allowing participants to emotionally process their test results privately, as well as receiving the results from supportive and responsive staff members. A few participants indicated drawbacks to phone-based HIV test result delivery, such as logistical concerns about receiving a phone call during the day (e.g., while at work), reduced confidentiality, and the lack of in-person emotional support. Overall, participants described phone delivery of positive HIV-results as acceptable. At-home testing with phone delivery has the potential to increase HIV testing access, especially to geographically isolated or medically underserved patients.

Background: Larger patient caseloads and increased workplace responsibility for nurse practitioners (NPs) may exacerbate factors leading to compassion fatigue (CF)., Purpose: The purpose of this study is to analyze the rate of burnout in practicing NPs by looking at contributing factors that play a role in CF and compassion satisfaction (CS)., Methods: A NP social media platform was used to distribute a survey to a convenience sample of 208 NPs. Data included the Professional Quality of Life Scale V (ProQOL V) tool, demographic data, and protective factor questions. The data were dissected for CF and protective factors of CS., Results: The relationship of mindfulness practices and levels of CS was statistically significant. The relationship between support from family, coworkers, and administration and levels of CS was also found statistically significant. A large association was found between the correlation of burnout and support from coworkers., Implications for Practice: Findings showed an average to high level of CS with a low-to-average burnout rate among the NPs surveyed. There was a direct impact between the amount of support participants received from individual support systems and their level of CS. These findings could be beneficial for new NP graduates in establishing a sense of community while reducing the risk for burnout., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2020 American Association of Nurse Practitioners.)

Internet-based recruitment can be effective in reaching large numbers of geographically diverse individuals. Geosocial sexual networking apps on smartphones have emerged as the modal way in which men who have sex with men (MSM) meet sex partners, and as venues for sexual health research. We report on the performance of three types of ads-text-only, text with male figure (no face), and text with male figure (with face)-used on a geosocial sexual networking app to advertise free at-home HIV testing and to enroll in an online study. We ran five 2-week-long ads on a popular MSM geosocial app between fall 2017 and spring 2018 (~2.19 million impressions). Ads were evaluated in terms of the click-through rate (CTR = advertisement clicks/advertisement impressions), conversion rates (CR = number of enrolled participants/ad-generated clicks), cost per enrolled participant, and demographic composition of survey respondents. We enrolled n = 4,023 individuals, n = 2,430 of whom completed HIV testing-$6.21 spent on advertising per participant enrolled and $10.29 spent for everyone who completed HIV testing. Cost per enrolled participant was associated with the content of the ad used-ads featuring male figures (with or without a face shown) were more cost efficient than ads featuring text alone. These ads also outperformed text-only ads across a range of metrics, including responsiveness among younger MSM as well as MSM of color. Advertising materials that combine text with images may have greater appeal among priority populations.

Background: Gay, bisexual, and other men who have sex with men continue to bear a large burden of the HIV epidemic in the United States and are among the only populations with increasing incidence in recent years., Objective: The Together 5000 (T5K) Study aimed to enroll a US-based, racially diverse sample of HIV-negative men, transmen, and transwomen who are not on pre-exposure prophylaxis (PrEP) into an observational cohort to inform the design, implementation, scale-up, and evaluation of HIV prevention programs., Methods: We used internet-based strategies to enroll a large, racially diverse national sample of HIV-negative men, transmen, and transwomen aged 16 to 49 years at high risk of HIV acquisition via sexual networking apps. Study participants are contacted every 6 months (in between annual surveys) for a brief survey on HIV testing, HIV diagnosis, and PrEP use (ie, attempts to access, PrEP initiation, and PrEP discontinuation). Participants complete annual self-administered at-home HIV testing and Web-based surveys. Using baseline serologic data and self-reported HIV testing history, we reconstructed a cohort of persons who were HIV negative at 12 months before baseline to estimate HIV incidence leading up to cohort enrollment., Results: The study sample included 8777 participants from all 50 US states, Puerto Rico, and Guam; 50.91% (4468/8777) were persons of color and 25.30% (2221/8777) were young individuals aged 16 to 24 years. Per eligibility criteria, all T5K participants reported having sex with >2 male partners in the 90 days before enrollment, self-reported not having been diagnosed with HIV, and were not actively taking PrEP. In addition, 79.39% (6968/8777) reported >2 insertive condomless anal sex (CAS) acts, 61.02% (5356/8777) reported >1 receptive CAS acts in the past 90 days. Furthermore, most (7525/8777, 85.74%) reported never having taken PrEP. In total, 70.25% (6166/8777) were sent a self-administered at-home HIV test kit and 82.29% (5074/6166) of those sent a kit returned a sample for testing. The HIV incidence rate during the 12-month period leading up to enrollment was estimated to be 2.41 (95% CI 2.02-2.90) per 100 person-years., Conclusions: A large, national, and racially diverse fully Web-based cohort of HIV-negative men, transmen, and transwomen at high risk for HIV seroconversion has successfully been recruited into longitudinal follow-up. This cohort is at high risk for HIV acquisition and can provide important insights related to the real-world uptake, impact, and equity of HIV prevention interventions in the United States. Participants can be invited to participate in trials aimed at testing strategies to improve the uptake of and engagement in these interventions., International Registered Report Identifier (irrid): RR1-10.2196/13715., (©Denis Nash, Matthew Stief, Caitlin MacCrate, Chloe Mirzayi, Viraj V Patel, Donald Hoover, David W Pantalone, Sarit Golub, Gregorio Millett, Alexa B D’Angelo, Drew Anne Westmoreland, Christian Grov. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 17.09.2019.)

Purpose: The aim of the article was to examine factors associated with completing enrollment milestones in the Together 5000 cohort of at-risk men (n = 8661), transmen (n = 53), and transwomen (n = 63) who have sex with men., Methods: Between 2017 and 2018, participants completed an online enrollment survey and were offered opportunities to complete an incentivized secondary online survey as well as self-administered at-home HIV testing (OraSure). We explored factors associated with completing each study component., Results: In total, 8777 individuals completed our enrollment survey, 6166 (70.3%) completed the secondary survey, and 5010 returned the at-home HIV test kit that was mailed to them (81.3% of those mailed a kit). In our multivariable models, those who were White, with more years of education, were more likely to complete study components, although the magnitude of these associations was small. For example, 50.9% of those enrolled, 47.9% of those completing the secondary survey, and 46.8% of those completing HIV testing were persons of color-a statistically significant, but meaningfully insignificant decline., Conclusions: These findings highlight the need for researchers to identify barriers that may prevent persons of color and younger individuals from participating in research studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cultural categories related to sexuality and gender vary considerably cross-culturally. While Western cultures categorize people primarily in terms of sexual attractions (i.e., gay, straight, bisexual), many cultures distinguish between groups based on additional issues such as gender role presentation and position preference in anal sex (i.e., insertive/receptive). The current study gathered data on three categories of natal males in Mumbai, India-hijra, kothi, and panthi (N = 93). Hijra are androphilic (sexually attracted to adult men), typically sexually receptive, transgender, sometimes castrated, and live in fictive kinship networks that are hierarchically organized. Kothi are also androphilic, typically sexual receptive and relatively feminine but less so than hijra; unlike hijra, kothi are never castrated. Hijra and kothi were understood by some participants to be mutually compatible, and so three groups were identified-those endorsing hijra only (n = 11), kothi only (n = 22), and both hijra and kothi (n = 22). Panthi (n = 38) are the masculine insertive partners of hijra and kothi. Measures employed were self-report and viewing time measures of sexual attraction, sexual behavior and position preference, self-described masculinity/femininity, recalled childhood gender atypicality, gendered occupational preferences, and gender presentation milestones (i.e., wearing female clothes, castration). All hijra and kothi groups were found to be exclusively androphilic in viewing time and self-reported sexual attractions, and to be gender-atypical on all measures. Panthi were found to be relatively male-typical and to have a bisexual pattern of viewing time and self-reported sexual attractions. Kothi were found to be less extreme in their female typicality and to report less female gender presentation milestones than hijra or hijra/kothi. Most hijra and hijra/kothi and all kothi said that they were not castrated. Contrary to the manner in which they are socially defined, a third of panthi report having been receptive in anal sex, and a third of all hijra and kothi groups report having been insertive at some time.

Single chain- urokinase (scu-PA) is the proenzyme of the plasminogen activator urokinase (tcu-PA). In human blood scu-PA is of great stability. Activated phagocytes generate large amounts of single chain- urokinase and of reactive oxidants (chloramines and HOCl). Since these cells participate in physiologic fibrinolysis, we were interested in the interaction between plasmatic scu-PA and chloramines. The oxidants dose dependently induce the activation of plasmatic scu-PA. Optimal activation of scu-PA occurs at about 3-5 mmol/l of chloramine-T. The findings suggest a control mechanism of scu-PA stability/activity by oxidatively modifiable plasma proteins, such as alpha-2-antiplasmin. The oxidation mechanism seems to be mediated by singlet molecular oxygen, an excited oxygen species. Basing on this scu-PA/oxidant synergism a sensitive and fast functional assay of scu-PA in human plasma is presented. Plasmatic inhibitors normally interfering with functional scu-PA measurements are inactivated by addition of chloramine-T, imitating the physiological oxidants generated by activated phagocytes. The scu-PA concentration in plasma of n = 36 healthy individuals has been determined to be 5.8 +/- 1.6 ng/ml. The lower detection limit of plasma scu-PA by the procedure described is about 1.5 ng/ml of plasma. By means of this technique scu-PA concentration during thrombolytic therapy can be measured within minutes in undiluted (direct) plasma samples, allowing adjustments of the scu-PA dosage. The present study gives further credence for a role of singlet molecular oxygen, possibly a new type of locally acting hormones (autacoid), in the regulation of the fibrinolytic pathway.

The activity of O6-methylguanine-DNA methyltransferase was determined in fibroblast cultures from 45 patients with lung cancer, 39 patients with cutaneous malignant melanoma, and 29 healthy controls. This enzyme is a critical parameter for the capacity to repair O6-methylguanine (O6-mGua) adducts in DNA, and a decreased activity might therefore be responsible for an enhanced susceptibility to cancer. The assay was performed with 8 x 10(6) fibroblasts which were homogenized and incubated with a known amount of O6-mGua containing DNA. The remaining substrate was determined fluorimetrically after high performance liquid chromatographic separation. O6-mGua repair was significantly reduced in lung cancer patients [6.64 +/- 4.32 (SD) pmol O6-methylguanine repaired/8 x 10(6) cells] as compared to healthy controls [10.35 +/- 5.42, P less than 0.0022] or patients with cutaneous malignant melanoma [10.83 +/- 6.66]. The lowest mean values were detected in a subgroup of 16 lung cancer patients with a tumor manifestation below 46 years of age (5.06 +/- 3.89). Fibroblasts from 4 patients with lung cancer had no detectable repair. We conclude that a reduced capacity to remove O6-mGua adducts may represent a further mechanism of individually enhanced lung cancer risk.