Search

Expanding on previous work, we present an HIV Prevention Cycle of Care model to facilitate understanding of the complexity of issues involved in pre-exposure prophylaxis implementation for gay, bisexual, and other men who have sex with men (MSM) in the USA, including individual, client-provider, and overarching issues such as health equity, stigma, and prevention nomenclature. The HIV prevention cycle of care applies to MSM who test negative for HIV. The Prevention Cycle of Care model includes seven steps: prevention knowledge, prevention self-awareness and preferences, prevention motivation, health-care access and cost, provider issues, adherence and persistence, and periodic reassessment and adjustment. HIV prevention is complex in an era of emerging multiple modalities, and more research is needed to successfully implement pre-exposure prophylaxis options over time and across diverse communities of MSM who are sexually active.

BackgroundVaccine access, coupled with the belief that vaccines are important, beneficial, and safe, plays a pivotal role in achieving high levels of vaccination to reduce the spread and severity of COVID-19 in the United States (U.S.) and globally. Many factors can influence vaccine intentions and uptake.MethodsWe conducted a scoping review of factors (e.g., access-related factors, racism) known to influence vaccine intentions and uptake, using publications from various databases and websites published December 1, 2020-April 30, 2021. Descriptive statistics were used to present results.ResultsOverall, 1094 publications were identified through the database search, of which 133 were included in this review. Among the publications included, over 60% included mistrust in vaccines and vaccine-safety concerns, 43% included racism/discrimination, 35% included lack of vaccine access (35%), and 8% had no contextual factors when reporting on vaccine intentions and disparities in vaccine uptake.ConclusionsFindings revealed during a critical period when there was a well-defined goal for adult COVID-19 vaccination in the U.S., some publications included several contextual factors while others provided limited or no contextual factors when reporting on disparities in vaccine intentions and uptake. Failing to contextualize inequities and other factors that influence vaccine intentions and uptake might be perceived as placing responsibility for vaccination status on the individual, consequently, leaving social and structural inequities that impact vaccination rates and vaccine confidence, among people of color, intact.

OBJECTIVES HIV prevalence is an estimated 14% among transgender women (TW) and 3% among transgender men (TM). HIV care is vital for viral suppression but is hindered by transphobia and HIV stigma. We assessed HIV care outcomes among transgender persons (TG) with HIV in the United States. DESIGN Systematic review and meta-analysis of peer-reviewed journal articles. METHODS We searched multiple electronic databases and CDC's HIV Prevention Research Synthesis database for 2006-September 2018. Eligible reports were US-based studies that included TG and reported HIV care outcomes. Random-effects models were used to calculate HIV care outcome rates. The protocol is registered with PROSPERO (CRD42018079564). RESULTS Few studies reported outcomes for TM; therefore, only TW meta-analysis results are reported. Twenty-one studies were identified having low-to-medium risk-of-bias scores. Among TW with HIV, 82% had ever received HIV care; 72% were receiving care, and 83% of those were retained in HIV care. Sixty-two percent were currently virally suppressed. Among those receiving HIV care or antiretroviral therapy (ART), 67% were virally suppressed at last test. Sixty-five percent were linked to HIV care ≤3 months after diagnosis. Seventy-one percent had ever been prescribed ART. Approximately 66% were taking ART, and 66% were ART-adherent. Only 56% were currently adherent the previous year. CONCLUSIONS HIV care outcomes for TW were not ideal, and research gaps exists for TM. High heterogeneity was observed; therefore, caution should be taken interpreting the findings. Integrating transgender-specific health needs are needed to improve outcomes of transgender persons across the HIV care continuum.

An important subgroup of gay, bisexual, and other men who have sex with men (MSM) with behavioral indications refuse daily oral PrEP when recommended by a provider. Emerging HIV prophylaxis products (e.g., injectable, event-driven) offer more options to MSM who refuse daily PrEP. Herein we assess reasons for refusal and likelihood to use various products among MSM who refused PrEP.MSM who reported anal sex without condoms or PrEP and refused daily oral PrEP in the past 6 months were recruited through clinics, community venues, and online in Atlanta, Chicago, and Raleigh-Durham. Men were asked their main reason for recently refusing daily PrEP and likelihood of using various PrEP options in the future. Bivariate and multivariable regression models were used to estimate associations.MSM (n=93; 70% Black, 48% age 18-29) reported their main reason for refusing daily PrEP were potential side effects (35%), a daily pill regimen (22%), and not having enough information (18%). Reported likelihood of using PrEP products was 58% for penile gel, 54% for event-driven oral, 52% for injectable, and 50% for daily PrEP. MSM who reported daily regimen as the main reason for refusing PrEP had greater odds of likelihood to use an injectable (AOR=5.21, 95%CI=1.32-20.52). Younger men (18-29 vs 30+ years) had greater odds of likelihood to use condoms (AOR=3.40, 95%CI=1.15-10.04) and daily PrEP (AOR=2.76, 95%CI=1.06-7.16); there were no product preference differences by race.Most men who refused daily PrEP indicated likelihood of using some form of PrEP in the future.

Background Transgender women (TGW) in the U.S. experience high rates of stigma, depression, and elevated rates of suicide. This study examined correlates of suicidal ideation and estimated the conditional indirect effects of perceived stigma and psychosocial mediators on suicidal ideation. Methods Using a cross-sectional study design, TGW (N = 92) were recruited through snowball sampling in Atlanta, Georgia. Structured interviews were conducted. Suicidal ideation was assessed by combining two variables that measured suicidal thoughts. Logistic regression models were performed to identify the potential risk and protective factors for suicidal ideation. We examined hypothesized psychosocial factors, including anxiety, depression, psychosocial impact of gender minority status, and substance use behaviors as potential mediators for the relationship between perceived stigma and suicidal ideation. All models were controlled for age, race, education, and homelessness. Results Suicidal ideation was reported by 33% (N = 30) of the study participants. In multivariable analysis, suicidal ideation was associated with sexual abuse (AOR = 3.17, 95% CI = 1.10–9.30), anxiety (AOR = 1.74, 95% CI = 1.10–2.73), family verbal abuse (AOR = 2.99, 95% CI = 1.10–8.40), stranger verbal abuse (AOR = 3.21, 95% CI = 1.02–10.08), and psychosocial impact of gender minority status (AOR = 3.42, 95% CI = 1.81–6.46). Partner support was found to be the protective factor for suicidal ideation (AOR = 0.34, 95% CI = 0.13–0.90). In the mediation analysis, the psychosocial impact of gender minority status mediated the relationship between perceived stigma and suicidal ideation. The estimated conditional indirect effect was 0.46, (95% CI = 0.12–1.11). Conclusion Interventions that aim to reduce suicidal behaviors among TGW should address stigma, psychosocial impact of gender minority status, and different forms of violence and abuse.

Objective: Transgender women with diagnosed HIV experience social and structural factors that could negatively affect their overall health and HIV-related health outcomes. We describe estimates from the Centers for Disease Control and Prevention Medical Monitoring Project (MMP) of sociodemographic characteristics, HIV stigma, discrimination, and mental health outcomes among transgender women with diagnosed HIV. Methods: We analyzed pooled data of all transgender women with diagnosed HIV (N = 217) from the 2015 through 2018 MMP cycles. We reported unweighted frequencies, weighted percentages, and 95% CIs for all characteristics. We post-stratified data to known population totals by age, race and ethnicity, and sex at birth from the National HIV Surveillance System. Results: Approximately 46% of transgender women with diagnosed HIV identified as Black or African American, 67% lived at or below the federal poverty level, 18% had experienced homelessness in the past year, 26% experienced mild to severe symptoms of depression, 30% experienced mild to severe anxiety symptoms, 32% reported physical violence by an intimate partner, and 30% reported forced sex during their lifetime. Despite 80% being very satisfied with their current HIV care, 94% experienced current HIV stigma and 20% experienced health care–related discrimination since being diagnosed with HIV. Among transgender women with diagnosed HIV who experienced discrimination, 46% and 51% experienced health care discrimination attributed to their gender and sexual orientation or sexual practices, respectively. Conclusions: Our findings underscore a need to address unmet ancillary services, such as housing, intimate partner violence, and mental health needs, and the need for strategies to reduce experiences with HIV stigma and discrimination in care for transgender women with diagnosed HIV in the United States.

HIV pre-exposure prophylaxis (PrEP) is a preventive medication that could reduce new infections among men who have sex with men (MSM). There are limited data on differing reasons for PrEP nonuse by condomless anal sex (CAS). We examined demographic and behavioral variables associated with PrEP use and reasons for PrEP nonuse by CAS. Data are from the M-cubed Study, collected in a 2018 baseline assessment of MSM (n = 798) in Atlanta, Detroit, and New York City. Participants reported current PrEP use (31%), previous use (8%), and never use (61%). MSM reporting CAS [adjusted odds ratio (aOR) = 2.60, confidence interval (95% CI) = 1.73–3.91], age 18–29 (aOR = 2.11, 95% CI = 1.26–3.52), 30–39 (aOR = 2.12, 95% CI = 1.25–3.59), with a college degree (aOR = 1.96, 95% CI = 1.20–3.21), or postgraduate education (aOR = 2.58, 95% CI = 1.51–4.40) had greater odds of current (vs. never) use; uninsured (aOR = 0.30, 95% CI = 0.16–0.57) men had lower odds of current (vs. never) use. For never use, more MSM who reported CAS (vs. did not) endorsed the following reasons (p's

Background Daily oral pre‐exposure prophylaxis (PrEP) is available and recommended for men who have sex with men (MSM) at risk for HIV infection. Other HIV prevention products are being developed, including long‐acting injectable (LAI) and event‐based oral and topical formulations. Understanding preferences for potential products by MSM can help direct further development of prevention messaging. Methods We present baseline data from HIV‐negative participants enrolled in the US Mobile Messaging for Men (M‐cubed) Study. Participants were asked their likelihood of and rank order preference for using daily oral PrEP and various potential prevention products (one‐ to ‐three‐month injections, 2‐1‐1 sexual event oral dosing, anal or penile gel, or anal suppository), and their sociodemographic characteristics. Bivariate and multivariable logistics regression assessed demographic associations with likelihood of use and rank order preference. Results Overall, most MSM reported a likelihood of using LAI (74%), sexual event‐based pills (67%) and penile gel (64%). Men who reported recent unprotected (condomless and PrEPless) anal sex most preferred a penile gel formulation (74%), followed closely by LAI and event‐based pills (73% each). Current PrEP users (vs. non‐users) had greater odds of reporting likelihood to use LAI (AOR = 3.29, 95% CI = 2.12 to 5.11), whereas men reporting recent unprotected anal sex had a greater odds of likelihood to use a penile gel (AOR = 1.79, 95% CI = 1.27 to 2.52) and an anal suppository (AOR = 1.48, 95% CI = 1.08 to 2.02). Hispanic/Latino (vs. White) MSM (AOR = 2.29, 95% CI = 1.40 to 3.73) and, marginally, Black MSM (AOR = 1.54, 95% CI = 1.00 to 2.38) had greater odds of reporting likelihood to use penile gel. Similar patterns were found for rank ordering preference of products, including condoms. Conclusions Most MSM were interested in using various potential future HIV prevention products, especially LAI. However, two typologies of potential users emerged: men who prefer sexual event‐based methods (condoms, event‐based pill, sexual gels and suppositories) and men who prefer non‐sexual event‐based methods (daily pill, LAI). Men who reported recent unprotected anal sex preferred a penile gel product most, followed closely by sexual event‐based pills and LAI. Racial/ethnic differences were noted as well. These findings on product preferences can help in formulation development and messaging.

Substance use is strongly associated with suicide completions. However, little is known about the patterns of substances used in suicide deaths. The purpose of this analysis is to determine latent classes of toxicology-reported substances among individuals who completed suicide. The sample consists of suicide victims in the National Violent Death Reporting System (NVDRS) during years 2003–2017 (n = 202,838). Toxicology reports were used to construct latent class analyses of substance use among suicide victims. Correlates for latent class membership included sex, race/ethnicity, previous experiences of child abuse, homelessness, and intimate partner violence (IPV) victimization. The majority of suicide victims were male (77.7%), straight/heterosexual (99.5%) and white (88.3%). The final unconditional model yielded a four-class model, including a “No substance/single substance use” class, an “Alcohol and other substance” class, a “Marijuana and other substance” class, and an “Opiate use” class. Compared to the reference class of “No substance/single substance,” females were more likely than males to be classified in the “Alcohol and other substance” class, the “Multi-substance use” class, and the “Opiate use” class. Homelessness was associated with classification in the “Marijuana and other substance” class and the “Opiate use” class compared to the “No substance/single substance” class. IPV was associated with both polysubstance use classes (“Alcohol plus other substance” and “Marijuana plus other substance”) along with the “Opiate use” class compared to the “No substance/single substance” class. These classes highlight profiles of suicide descendants and emphasize the importance of polysubstance use prevention among females, homeless individuals, and those who experience IPV.

Sexual minority (lesbian, gay, and bisexual [LGB]) populations experience disparities in cigarette use, but sparse evidence exists about novel and other alternative tobacco product use. In this study, we compared rates of novel and other alternative tobacco product use, risk perceptions, and worldview between LGB and heterosexual (HET) adults. An online survey administered in 2014-2015, using a weighted probability sample of 11,525 U.S. adults, assessed awareness of tobacco products; ever and current use of e-cigarettes, cigars, little cigars and cigarillos, and hookahs; perceptions of e-cigarettes; and worldview (individualism vs. communitarianism). Bivariate and adjusted multivariable analyses were performed to determine differences between LGB and HET groups. In the adjusted analyses, LGB adults were 1.5 times more likely to have ever used e-cigarettes (95% CI 1.2-1.9) and 1.9 times more likely to have ever used hookahs (95% CI 1.5-2.4) as compared to HET adults. A lower percentage of LGB adults, as compared to HET adults (16.7% vs. 19.2%), believed that exposure to vapors from e-cigarettes was "harmful" and reported that they "did not know" of any harm (35.1% vs. 39.8%). LGB were 20% less likely than were HET adults to endorse an individualistic worldview. These results suggest that a disparity exists, whereby LGB adults are more likely to have used e-cigarettes and hookahs. In addition, although vapor from e-cigarettes contains nicotine and other chemicals, LGB adults are less likely to perceive exposure to secondhand vapor as harmful. Tailored awareness campaigns and interventions are needed to convey the risks and curb use of these products.

This study assessed the prevalence of self-reported HIV infection among a community sample of transgender women and identified associated contextual, experiential, and behavioral factors. Ninety-two transgender women completed a self-administered interview. Recruitment occurred through an LGBT service organization, a transgender support group, transgender advocates, and informal communications. Eighty-two percent were African American/Black. Of 83 who knew their status, 60% reported being HIV infected. High rates of childhood sexual abuse (52%), rape (53%), intimate partner violence (56%), and incarceration (57%) were reported. Many did not have health insurance (53%), were not employed full-time nor in school (63%) and had been recently homeless (49%). HIV-infected transgender women as compared to HIV-uninfected transgender women were more likely to be African American/Black ( P = 0.04), and older than 34 years ( P = 0.01), unemployed/not in school ( P

Chromosomal aberrations (CAs) in blood lymphocytes have been shown to be associated with overall cancer risk and aging. However, their relationship to bladder cancer risk remains to be elucidated. In a case-control study of bladder cancer in Egypt, we examined the relationship between the increased frequency of CAs in blood lymphocytes and bladder cancer risk. High frequency of CAs was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 3.90, 95% confidence interval (CI) = 2.65–5.73]. The associations were somewhat stronger in squamous cell carcinomas (SCC, OR = 4.90) than in urothelial carcinomas (UC, OR = 3.62). We also identified chromosome specific CAs for chromosomes 3, 4, 5, 8, 9, 10, 11, 12, 17, 19 that were significantly associated with an increased risk of bladder cancer. We observed particularly strong associations between aberrations of chromosomes 12, 13, 17 and risk of SCC (OR = 7.06, 6.91 and 6.23, respectively). Conclusion: increased frequency of chromosomal aberrations in blood lymphocytes was significantly associated with bladder cancer risk. Overall and chromosome specific aberrations in blood lymphocytes may be a unique set of biomarkers for risk assessments of SCC and UC.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Mammalian apurinic/apyrimidinic endonuclease (APE1) initiates the repair of abasic sites (AP-sites), which are highly toxic, mutagenic, and implicated in carcinogenesis. Also, reducing the activity of APE1 protein in cancer cells and tumors sensitizes mammalian tumor cells to a variety of laboratory and clinical chemotherapeutic agents. In general, mouse models are used in studies of basic mechanisms of carcinogenesis, as well as pre-clinical studies before transitioning into humans. Human APE1 (hAPE1) has previously been cloned, expressed, and extensively characterized. However, the knowledge regarding the characterization of mouse APE1 (mAPE1) is very limited. Here we have expressed and purified full-length hAPE1 and mAPE1 in and from E. coli to near homogeneity. mAPE1 showed comparable fast reaction kinetics to its human counterpart. Steady-state enzyme kinetics showed an apparent K(m) of 91 nM and k(cat) of 4.2 s(-1) of mAPE1 for the THF cleavage reaction. For hAPE1 apparent K(m) and k(cat) were 82 nM and 3.2 s(-1), respectively, under similar reaction conditions. However, k(cat)/K(m) were in similar range for both APE1s. The optimum pH was in the range of 7.5-8 for both APE1s and had an optimal activity at 50-100 mM KCl, and they showed Mg(2+) dependence and abrogation of activity at high salt. Circular dichroism spectroscopy revealed that increasing the Mg(2+) concentration altered the ratio of "turns" to "β-strands" for both proteins, and this change may be associated with the conformational changes required to achieve an active state. Overall, compared to hAPE1, mAPE1 has higher K(m) and k(cat) values. However, overall results from this study suggest that human and mouse APE1s have mostly similar biochemical and biophysical properties. Thus, the conclusions of mouse studies to elucidate APE1 biology and its role in carcinogenesis may be extrapolated to apply to human biology. This includes the development and validation of effective APE1 inhibitors as chemosensitizers in clinical studies.

In this report the associations between telomere length variation (TLV), mean telomere length in blood lymphocytes and lung cancer risk were examined.The study design is case-control. Cases (N=191) were patients newly diagnosed with histologically confirmed non-small cell lung cancer. Controls (N=207) were healthy individuals recruited from the same counties as cases and matched to cases on age and gender. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and lung cancer risk.Telomere length variation across all chromosomal ends was significantly associated with lung cancer risk; adjusted odds ratios 4.67 [95% confidence interval (CI): 1.46-14.9] and 0.46 (95% CI: 0.25-0.84) for younger (age≤60) and older (age60) individuals, respectively. TLV and mean telomere length jointly affected lung cancer risk: when comparing individuals with short telomere length and high TLV to those with long telomere length and low TLV, adjusted odd ratios were 8.21 (95% CI: 1.71-39.5) and 0.33 (95% CI: 0.15-0.72) for younger and older individuals, respectively.TLV in blood lymphocytes is significantly associated with lung cancer risk and the associations were modulated by age. TLV in combination with mean telomere length might be useful in identifying high risk population for lung cancer computerized tomography screening.

Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.

Telomere lengths are tightly regulated within a narrow range in normal human cells. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in elongating short telomeres. However, much about the molecular mechanisms of regulating excessively long telomeres is unknown. In this report, we demonstrated that the telomerase enzymatic component, hTERT, plays a dual role in the regulation of telomere length. It shortens excessively long telomeres and elongates short telomeres simultaneously in one cell, maintaining the optimal telomere length at each chromosomal end for efficient protection. This novel hTERT-mediated telomere-shortening mechanism not only exists in cancer cells, but also in primary human cells. The hTERT-mediated telomere shortening requires hTERT’s enzymatic activity, but the telomerase RNA component, hTR, is not involved in that process. We found that expression of hTERT increases telomeric circular DNA formation, suggesting that telomere homologous recombination is involved in the telomere-shortening process. We further demonstrated that shelterin protein TPP1 interacts with hTERT and recruits hTERT onto the telomeres, suggesting that TPP1 might be involved in regulation of telomere shortening. This study reveals a novel function of hTERT in telomere length regulation and adds a new element to the current molecular model of telomere length maintenance.

Protein purification is still very empirical, and a unified method for purifying proteins without an affinity tag is not available yet. In the postgenomic era, functional genomics, however, strongly demands such a method. In this paper we have formulated a unique method that can be applied for purifying any recombinant basic protein from Escherichia coli. Here, we have found that if the pH of the buffer is merely one pH unit below the isoelectric point (pI) of the recombinant proteins, most of the latter bind to the column. This result supports the Henderson-Hasselbalch principle. Considering that E. coli proteins are mostly acidic, and based on the pI determined theoretically, apparently all recombinant basic proteins (at least pI-1 > or = 6.94) may be purified from E. coli in a single step using a cation-exchanger resin, SP-Sepharose, and a selected buffer pH, depending on the pI of the recombinant protein. Approximately, two-fifths of human proteome, including many if not all nucleic acid-interacting proteins, have a pI of 7.94 or higher; virtually all these 12,000 proteins may be purified using this method in a single step.

Background: Cancer cells are characterized by frequent chromosome aberrations (CA), which reflect defects of the underlying mechanisms that maintain genomic stability. Chromosome aberrations in peripheral blood lymphocytes has been shown to be associated with overall cancer risk in previous small studies. However, the relationship between types of chromosome aberrations in blood lymphocytes and lung cancer risk has not been well defined. In a case-control study of non-small cell lung cancer, we evaluated if CA in autosomes and sex chromosomes were predictive of lung cancer risk. Method: Chromosome aberrations were determined by G-banding analysis of metaphase chromosomes from short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between CAs and lung cancer risk. Results: Autosome instability (defined as CA in any of the 22 pairs of autosomes in > 5% of the cells) was significantly associated with lung cancer risk among individuals who were 67 years of age) and in African American males. We observed no significant association between loss of chromosome X and lung cancer risk in both males and females. Conclusion: Autosome instability and loss of chromosome Y in blood lymphocytes were significantly associated with lung cancer risk. Analysis of chromosome aberrations in blood lymphocytes may be a promising tool for the identification of sub-population who are at high risk of developing lung cancer. Citation Format: Bing Sun, Ying Wang, Krishna Kota, Yaru Shi, Kepher H. Makambi, Christopher A. Loffredo, Peter G. Shields, Curtis C. Harris, Yun-Ling Zheng. Autosome instability and loss of chromosome Y in blood lymphocytes predict lung cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4157. doi:10.1158/1538-7445.AM2014-4157