Incident Proteinuria differs by HIV Serostatus among Men with Pre-diabetes: The Multicenter AIDS Cohort Study.

BACKGROUND: Pre-diabetes is associated with proteinuria, a risk factor for chronic kidney disease. While people living with HIV (PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among pre-diabetic persons. METHODS: Urine protein-to-creatinine ratio (PCR) was measured at semi-annual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of anti-diabetic medications were included. Pre-diabetes was defined as fasting glucose (FG) of 100-125 mg/dL confirmed within a year by a repeat FG or hemoglobin A1c 5.7-6.4%. Incident proteinuria was defined as PCR > 200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-diabetes differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria. RESULTS: Between 2006 and 2019, among 1276 men with pre-diabetes, 128/613 PWH (21%) and 50/663 PWOH (8%) developed proteinuria over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-diabetes was 3.3 times [95% CI: 2.3-4.8 times] greater than in PWOH (p < 0.01). Among PWH, current CD4 count <500 cells/mm3 (p < 0.01) and current use of protease inhibitors (p = 0.03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk. CONCLUSION: Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population.

CD4 T cell-activating neoantigens enhance personalized cancer vaccine efficacy.

Personalized cancer vaccines aim to activate and expand cytotoxic antitumor CD8+ T cells to recognize and kill tumor cells. However, the role of CD4+ T cell activation in the clinical benefit of these vaccines is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for the pancreatic cancer cell line Panc02, which activates tumor-specific CD8+ T cells but required combinatorial checkpoint modulators to achieve therapeutic efficacy. To determine the effects of neoantigen-specific CD4+ T cell activation, we generated a vaccine (PancVAX2) targeting both major histocompatibility complex class I- (MHCI-) and MHCII-specific neoantigens. Tumor-bearing mice vaccinated with PancVAX2 had significantly improved control of tumor growth and long-term survival benefit without concurrent administration of checkpoint inhibitors. PancVAX2 significantly enhanced priming and recruitment of neoantigen-specific CD8+ T cells into the tumor with lower PD-1 expression after reactivation compared with the CD8+ vaccine alone. Vaccine-induced neoantigen-specific Th1 CD4+ T cells in the tumor were associated with decreased Tregs. Consistent with this, PancVAX2 was associated with more proimmune myeloid-derived suppressor cells and M1-like macrophages in the tumor, demonstrating a less immunosuppressive tumor microenvironment. This study demonstrates the biological importance of prioritizing and including CD4+ T cell-specific neoantigens for personalized cancer vaccine modalities.

The Relationship Between Posttraumatic Stress Disorder and Alcohol Misuse and Smoking Among Aging Men Who Have Sex With Men: No Evidence of Exercise or Volunteering Impact.

OBJECTIVES: To determine if the association between posttraumatic stress disorder (PTSD) and substance use (alcohol misuse or smoking tobacco) is mediated/moderated by exercise or volunteering among aging (≥40 years) men who have sex with men (MSM), and if this mediation/moderation differs by HIV serostatus. METHODS: Multicenter AIDS Cohort Study data were used. Three datasets with PTSD measured during different time periods (10/1/2017-3/31/2018, 898 men; 4/1/2018-9/30/2018, 890 men; 10/1/2018-3/31/2019, 895 men) were analyzed. Longitudinal mediation analyses estimated the mediation effect of exercise and volunteering on the outcomes. RESULTS: Nine percent of MSM had evidence of PTSD. There was no statistically significant mediation effect of exercise or volunteering regardless of substance use outcome. The odds of smoking at a future visit among MSM with PTSD were approximately double those of MSM without PTSD. Results did not differ by HIV serostatus. DISCUSSION: There is a particular need for effective smoking cessation interventions for aging MSM with PTSD.

Virtual Reality Game Selection for Traumatic Brain Injury Rehabilitation: A Therapist's Wish List for Game Developers.

This project explored the selection process of commercially available virtual reality (VR) games for traumatic brain injury rehabilitation. Occupational therapy practitioners (OTPs) developed a classification framework that they used to evaluate VR games. The classification framework focused on movements required to effectively play the game, cognitive demand, position for game play, ease in menu navigation, and perceived therapeutic applications. OTPs used the ratings to aid in game selection and identified relevant game examples that allowed customizable settings and basic navigation with a game focus on functional activities. The OTPs and the research team identified the need for further work on accessibility and adaptability of game features (e.g., difficulty and limb usage) allowing for more individualization to optimize outcomes of VR-enhanced rehabilitation. The classification framework was useful in evaluating the potential therapeutic benefit of commercially available VR games. However, trial of the game by clinicians prior to use was still warranted.

Cumulative exposure to viremia: Methods for the implementation of standardized variables in longitudinal HIV studies.

Measures of viremic exposure over time, including HIV viral copy-years or durable viremic suppression, may be more relevant measures of viral load exposure for comorbid outcomes and mortality than single time point viral load measures. However, there are many subjective decisions that go into creating a cumulative variable such as HIV viral copy-years, including the appropriate anchoring point to begin accumulating exposure, the handling of viral load levels below an assay's lower limit of detection (LLD), the handling of gaps in the viral load trajectory, and when to apply the log10 transformation (before or after the accumulation calculation). Different decisions produce different values for HIV viral copy-years, and such differences could impact inferences in subsequent analyses of relationships with outcomes. In this paper, we develop several HIV viral copy-years variables that are standardized across:•Anchoring point•Handling of viral loads measured below the LLD and missing viral load measures•Application of the log10 transformation. These standardized variables may be consistently used in analyses of longitudinal cohort data. We also define a supplementary dichotomous HIV viral load exposure variable that may be used in tandem, or alternatively to, the HIV viral copy-years variables.

Comparison of anal pre-cancer screening strategies among men who have sex with men.

PURPOSE: Comparison of anal pre-cancer screening strategies in men who have sex with men (MSM). METHODS: MSM in the Multicenter AIDS Cohort Study underwent repeated anal cytology (aCyt), oncogenic human papillomavirus (oncHPV) testing. A subset received High-Resolution Anoscopy (HRA). We evaluated three screening strategies for their ability to predict anal histological High-Grade Squamous Intraepithelial lesion (HSIL): single aCyt, sequential aCyt, and oncHPV co-testing. Multivariable logistic regression models evaluated risk of HSIL among participants undergoing HRA within 5 years of screening. Sensitivity and specificity were estimated among participants with HRA, and results corrected for verification bias using weighted generalized estimating equations. RESULTS: There were 1426 MSM with aCyt screening (48% people with HIV [PWH]) and 428 that underwent HRA. Median age was 57 years, 14% of PWH had CD4< 350 cells/mm3. HSIL probability was higher in MSM with one (39%, p < 0.01) or two abnormal aCyt results (46%, p < 0.01), versus those with normal aCyt (23-24%). Among men with abnormal aCyt, men with oncHPV+ had significantly higher risk than those who were oncHPV- (47% vs. 16%, p < 0.01). Specificity was modest with single aCyt+ (50%) but increased with sequential aCyt+ (79%) or oncHPV+ (67%). Sensitivity was high with single oncHPV+ (88%), moderate with single aCyt+ (66%) and oncHPV+ co-testing (61%), and low with sequential aCyt+ (39%). After correcting for potential verification bias, specificity increased and sensitivity decreased, but inferences were similar. CONCLUSION: None of the screening strategies evaluated had both sufficient specificity and sensitivity to warrant routine widespread use.

Trans women have worse cardiovascular biomarker profiles than cisgender men independent of hormone use and HIV serostatus.

BACKGROUND: Feminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW). METHODS: TW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations. RESULTS: TW (HIV+ n  = 75, HIV- n  = 47) and CM (HIV+ n  = 40, HIV- n  = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P  < 0.05). In multivariable analysis, TW had higher EN-RAGE, IL-6, IL-8, P selectin, PAI-1, oxLDL and sTNFRI/II concentrations, and lower vWF, independent of HIV serostatus and current FHT use. Both being a TW and a PWH were associated with lower ET-1. CONCLUSIONS: Compared to matched cisgender men, trans women have altered profiles of biomarkers associated with systemic inflammation and CVD. Further work is needed to decipher the contributions of FHT to CVD risk in TW with HIV.

Preliminary experiences in acute occupational therapy for in-patients with coronavirus-19 (COVID-19): leveraging assistive technology in three case studies of male veterans.

PURPOSE: Coronavirus 2019 (COVID-19) was first identified in December 2019 with millions of cases reported globally in the succeeding months. Initial hospitalisation strives to minimise multisystem organ failure and of those that survive, individuals can present with profound rehabilitation needs. The purpose of this case series is to describe occupational therapy (OT) and special technology considerations for three male Veteran patients hospitalised with suspected or confirmed COVID-19. METHODS: This is a descriptive case series using a retrospective electronic health record review at a Veterans Administration hospital. The case series includes three male Veterans with confirmed or suspected COVID-19 (ages 69-78) who were referred to OT. The cases were selected to demonstrate the novel use of technology and strategies to reduce the risk of transmission. In two of three of our cases, we describe acute rehabilitation with a focus on activity tolerance, participation in occupations, and discharge planning. In all cases, we measured vital signs and activity tolerance as primary outcomes. RESULTS AND CONCLUSIONS: The findings suggest that outcome measures focussing on activity tolerance to maintain stable vital signs during the recovery phase is central to the progression of activities. We observed in our cases that the Person-Environment-Occupation-Performance (PEOP) model can guide practice and complement the medical model in management of these patients. We utilised technology to engage family members in the rehabilitation care and minimise exposure risks.IMPLICATIONS FOR REHABILITATIONAcute occupational therapy for rehabilitation early in the recovery of Cornavirus-2019 can be guided by the Person-Occupation-Environment-Performance model as seen in this case series of three Veteran patients.Assistive technology can serve dual roles in supporting the rehabilitation of individuals with Cornavirus-2019 and lowering the risk of virus transmission to staff.

Risk for incident diabetes is greater in prediabetic men with HIV than without HIV.

BACKGROUND: Diabetes mellitus is a major comorbidity in people with HIV (PWH). Hyperglycemia below diabetic range defines prediabetes (prediabetes mellitus). We compared the progression from prediabetes mellitus to diabetes mellitus in PWH and people without HIV (PWOH). METHODS: Fasting glucose was measured semiannually in the MACS since 1999. Men with prediabetes mellitus (fasting glucose between 100 and 125 mg/dl, confirmed within a year by fasting glucose in the prediabetes mellitus range or HbA1c between 5.7 and 6.4%) were included. The first visit with prediabetes mellitus was the baseline visit. Incident diabetes mellitus was defined as fasting glucose at least 126 mg/dl, confirmed at a subsequent visit, or self-reported diabetes mellitus, or use of anti-diabetes mellitus medication. We used binomial transition models to compare the progression from prediabetes mellitus to diabetes mellitus by HIV serostatus, adjusted for age, number of previous prediabetes mellitus to diabetes mellitus transitions, ethnicity, BMI, family history of diabetes mellitus, and hepatitis C virus (HCV) infection. RESULTS: Between 1999 and 2019, 1584 men (793 PWH; 791 PWOH) with prediabetes mellitus were included. At baseline, PWH were younger (48 vs. 51 years, P < 0.01), had lower BMI (26 vs. 27), were more frequently nonwhite (47 vs. 30%), and HCV-infected as per last measure (8 vs. 4%) than PWOH (all P < 0.01). Over a median 12-year follow-up, 23% of participants developed diabetes mellitus. In adjusted analyses, the risk for incident diabetes mellitus was 40% (95% CI: 0--80%) higher among PWH than PWOH (P = 0.04). CONCLUSION: Among men with prediabetes mellitus, PWH had an increased risk of incident diabetes mellitus adjusted for competing risk factors, warranting the evaluation of diabetes mellitus prevention strategies.

Social inequalities contribute to racial/ethnic disparities in depressive symptomology among men who have sex with men.

PURPOSE: Racial/ethnic minorities experience disproportionate rates of depressive symptoms in the United States. The magnitude that underlying factors-such as social inequalities-contribute to these symptoms is unknown. We sought to identify exposures that explain racial/ethnic differences in clinically significant depressive symptomology among men who have sex with men (MSM). METHODS: Data from the Multicenter AIDS Cohort Study (MACS), a prospective cohort study, were used to examine clinically significant symptoms of depression (Center for Epidemiologic Studies Depression Scale score ≥ 20) among non-Latinx White, non-Latinx Black, and Latinx MSM. We included 44,823 person-visits by 1729 MSM seen in the study sites of Baltimore/Washington, DC; Chicago; Pittsburgh/Columbus; and Los Angeles from 2000 to 2017. Regression models estimated the percentage of depressive symptom risk explained by social, treatment, and health-related variables related to race/ethnicity. Machine-learning methods were used to predict the impact of mitigating differences in determinants of depressive symptoms by race/ethnicity. RESULTS: At the most recent non-missing MACS visit, 16% of non-Latinx White MSM reported clinically significant depressive symptoms, compared to 22% of non-Latinx Black and 25% of Latinx men. We found that income and social-environmental stress were the largest contributors to racial/ethnic disparities in risk for depressive symptoms. Similarly, setting the prevalence of these two exposures to be equal across racial/ethnic groups was estimated to be most effective at reducing levels of clinically significant depressive symptoms. CONCLUSION: Results suggested that reducing socioeconomic inequalities and stressful experiences may be effective public health targets to decrease racial/ethnic disparities in depressive symptoms among MSM.

Risk of smoking-related cancers among women and men living with and without HIV.

OBJECTIVES: We investigated whether the effect of smoking on the incidence of smoking-related cancers differs by HIV-infection status, if sex modifies the impact of risk factors for smoking-related cancers, and the sex-specific attributable risk of smoking on cancer incidence. DESIGN: Data from two large prospective studies in the United States were analyzed: 6789 men in the Multicenter AIDS Cohort Study from 1984 through 2018 and 4423 women in the Women's Interagency HIV Study from 1994 through 2018. METHODS: Incidence rates, relative risks, and adjusted population attributable fractions (PAFs) were calculated for smoking-related cancers. RESULTS: During study follow-up, there were 214 incident smoking-related cancers in the men and 192 in the women. The age-adjusted incidence ratess for smoking-related cancers were higher in the women (392/100 000) than for the men (198/100 000; P < 0.01) and higher for people living with HIV (PLWH, 348/100 000) than for those without HIV (162/100 000; P < 0.01). Unadjusted incidence rates in PLWH were higher than in those without HIV when stratifying by cumulative pack-years of smoking (all P values <0.01). In adjusted interaction models, the effects of cumulative pack-years of smoking were significantly stronger in women. The adjusted PAFs for smoking-related cancers were nonsignificantly higher in the women than in the men (39 vs. 28%; P = 0.35). CONCLUSION: HIV looks to be an independent risk factor for smoking-related cancers and women appear to have a greater risk than men. These results highlight the need for interventions to help PLWH, especially women, quit smoking and sustain cessation to reduce their risk of smoking-related cancers.

Understanding Geospatial Factors Associated With Cervical Cancer Screening Uptake in Amazonian Peruvian Women.

PURPOSE: Cervical cancer (CC) is the most common and second-most deadly cancer among Peruvian women. Access to services is strongly associated with CC screening uptake. This study investigated geospatial features contributing to utilization of screening. We used geolocated data and screening information from a Knowledge, Attitudes, and Practice (KAP) survey implemented in Iquitos, Peru in 2017. MATERIALS AND METHODS: The KAP collected cross-sectional CC screening history from 619 female interviewees age 18-65 years within 5 communities of varying urbanization levels. We used spatial statistics to determine if screened households tended to cluster together or cluster around facilities offering screening in greater numbers than expected, given the underlying population density. RESULTS: On the basis of K-functions, screened households displayed greater clustering among each other as compared with clustering among unscreened households. Neighborhood-level factors, such as outreach, communication, or socioeconomic condition, may be functioning to generate pockets of screened households. Cross K-functions showed that screened households are generally located closer to health facilities than unscreened households. The significance of facility access is apparent and demonstrates that travel and time barriers to seeking health services must be addressed. CONCLUSION: This study highlights the importance of considering geospatial features when determining factors associated with CC screening uptake. Given the observed clustering of screened households, neighborhood-level dynamics should be further studied to understand how they may be influencing screening rates. In addition, results demonstrate that accessibility issues must be carefully considered when designing an effective cancer screening program that includes screening, follow-up, and treatment.

Achieving Tiered Model Quality in 3D Structure from Motion Models Using a Multi-Scale View-Planning Algorithm for Automated Targeted Inspection.

This study presents a novel multi-scale view-planning algorithm for automated targeted inspection using unmanned aircraft systems (UAS). In industrial inspection, it is important to collect the most relevant data to keep processing demands, both human and computational, to a minimum. This study investigates the viability of automated targeted multi-scale image acquisition for Structure from Motion (SfM)-based infrastructure modeling. A traditional view-planning approach for SfM is extended to a multi-scale approach, planning for targeted regions of high, medium, and low priority. The unmanned aerial vehicle (UAV) can traverse the entire aerial space and facilitates collection of an optimized set of views, both close to and far away from areas of interest. The test case for field validation is the Tibble Fork Dam in Utah. Using the targeted multi-scale flight planning, a UAV automatically flies a tiered inspection using less than 25% of the number of photos needed to model the entire dam at high-priority level. This results in approximately 75% reduced flight time and model processing load, while still maintaining high model accuracy where needed. Models display stepped improvement in visual clarity and SfM reconstruction integrity by priority level, with the higher priority regions more accurately modeling smaller and finer features. A resolution map of the final tiered model is included. While this study focuses on multi-scale view planning for optical sensors, the methods potentially extend to other remote sensors, such as aerial LiDAR.

Energy conserving thermoregulatory patterns and lower disease severity in a bat resistant to the impacts of white-nose syndrome.

The devastating bat fungal disease, white-nose syndrome (WNS), does not appear to affect all species equally. To experimentally determine susceptibility differences between species, we exposed hibernating naïve little brown myotis (Myotis lucifugus) and big brown bats (Eptesicus fuscus) to the fungus that causes WNS, Pseudogymnoascus destructans (Pd). After hibernating under identical conditions, Pd lesions were significantly more prevalent and more severe in little brown myotis. This species difference in pathology correlates with susceptibility to WNS in the wild and suggests that survival is related to different host physiological responses. We observed another fungal infection, associated with neutrophilic inflammation, that was equally present in all bats. This suggests that both species are capable of generating a response to cold tolerant fungi and that Pd may have evolved mechanisms for evading host responses that are effective in at least some bat species. These host-pathogen interactions are likely mediated not just by host physiological responses, but also by host behavior. Pd-exposed big brown bats, the less affected species, spent more time in torpor than did control animals, while little brown myotis did not exhibit this change. This differential thermoregulatory response to Pd infection by big brown bat hosts may allow for a more effective (or less pathological) immune response to tissue invasion.