Serum biomarkers related to frailty predict negative outcomes in older adults with hip fracture.

PURPOSE: Hip fracture is a public health problem worldwide. Traditional prognostic models do not include blood biomarkers, such as those obtained by proteomics. This study aimed to investigate the relationships between serum inflammatory biomarkers and frailty in older adults with hip fracture as well as adverse outcomes at one and three months after discharge. METHODS: A total of 45 patients aged 75 or older who were admitted for hip fracture were recruited. At admission, a Comprehensive Geriatric Assessment (CGA) was conducted, which included a frailty assessment using the Clinical Frailty Scale (CFS). Blood samples were collected before surgery. Participants were followed up at one and three months after discharge. The levels of 45 cytokines were analyzed using a high-throughput proteomic approach. Binary logistic regression was used to determine independent associations with outcomes, such as functional recovery, polypharmacy, hospital readmission, and mortality. RESULTS: The results showed that IL-7 (OR 0.66 95% CI 0.46-0.94, p = 0.022) and CXCL-12 (OR 0.97 95% CI 0.95-0.99, p = 0.011) were associated with better functional recovery at three months after discharge, while CXCL-8 (OR 1.07 95% CI 1.01-1.14, p = 0.019) was associated with an increased risk of readmission. CONCLUSIONS: These findings suggest that immunology biomarkers may represent useful predictors of clinical outcomes in hip fracture patients.

Experienced barriers to adherence to pre-exposure prophylaxis for HIV prevention among MSM: a systematic review and meta-ethnography of qualitative studies.

Men who have sex with men (MSM) in the United States are at disproportionate risk for HIV. Once-daily pre-exposure prophylaxis (PrEP) for HIV prevention is a highly effective method of preventing HIV infection; however, optimal adherence is necessary to maintain effectiveness. Many studies have profiled perceived barriers to adherence among at-risk MSM; however, nearly a decade after FDA approval, there has been little work examining experienced barriers to adherence among MSM who have previously used the medication. To assess the current state of this literature and its implications for behavioral interventions, we conducted a meta-ethnography (i.e., A systematic review and synthesis of qualitative studies) of experiences with PrEP use among cis-gender MSM in the United States. We found that structural-level interventions, such as telehealth and pharmacist-prescribed approaches to PrEP distribution, may circumvent barriers to uptake and adherence for some MSM, but may not be enough for already underserved communities, such as MSM of color. Furthermore, interpersonal-level factors, such as enacted PrEP stigma by providers and peers, highlight the necessary consideration of social identity in the branding of PrEP for HIV prevention. Tailored interventions should consider experienced barriers to PrEP adherence across socioecological levels to be most effective.

Circulating Cytokines and Lower Body Muscle Performance in Older Adults at Hospital Admission.

BACKGROUND: Aging-related traits, including gradual loss of skeletal muscle mass and chronic inflammation, are linked to altered body composition and impaired physical functionality, which are important contributing factors to the disabling process. We sought to explore the potential relationship between lower-body muscle strength decline and inflammatory mediators in older adults. METHODS: We performed a cross-sectional analysis in 38 older adults admitted to an acute care of the elderly unit (57.9% women, mean age=87.9±4.9 years; mean body mass index [BMI]=26.5±4.7 kg/m2). Clinical and functional outcomes including weight, height, BMI, dependence, physical and cognitive performance, and muscle strength measured by one-repetition maximum (1RM) for leg-extension, leg-press, chest-press and handgrip strength, were assessed. Blood serum content of 59 cytokines, chemokines and growth factors was assessed by protein arrays. Multivariate linear regression analyses were used to examine the relationship between cytokine concentrations and muscle strength parameters. RESULTS: After controlling for confounding factors (age, sex, BMI, cumulative illness rating score and physical performance score), 1RM leg-press had a significant negative relationship with GRO (CXCL2) (ß= -18.13, p=0.049), MIG (CXCL9) (ß= -13.94, p=0.004), IGF-1 (ß= -19.63, p=0.003), CK-BETA 8 (CCL23) (ß= -28.31, p=0.018) and GCP-2 (CXCL6) (ß= -25.78, p=0.004). Likewise, 1RM leg-extension had a significant negative relationship with IGFBP-1 (ß= -11.49, p=0.023). CONCLUSIONS: Thus, several serum cytokines/chemokines and growth factors are negatively associated with lower muscle strength in older patients. Further investigation is required to elucidate the mechanism of elevated inflammatory mediators leading to lower muscle strength.

"I Do Try To Use Condoms, But ": Knowledge and Interest in PrEP Among Male Sex Workers in Mexico City.

In Mexico City, male sex workers (MSWs) are up to 126 times more likely to be living with HIV than the general public. We conducted interviews with 23 MSWs in Mexico City to examine their subjective understandings about their sexual risk behaviors and explore opportunities about HIV pre-exposure prophylaxis (PrEP) as a prevention approach in this group. Despite knowledge about sexual HIV risks, most participants reported condomless anal sex with clients. There was very little prior knowledge about PrEP, but very high interest in using a daily pill for prevention. Several participants expected an increase in condomless anal sex if taking PrEP, because of monetary incentives from clients or a perceived increase in pleasure. Additionally, seasonal sex workers expressed interest in using PrEP only during months when they were performing sex work. PrEP implementation efforts through Mexico's healthcare system should recognize the varying needs and sexual risk behaviors of MSWs.

Gender affirmative HIV care framework: Decisions on feminizing hormone therapy (FHT) and antiretroviral therapy (ART) among transgender women.

BACKGROUND: Integration of feminizing hormone therapy (FHT) and antiretroviral therapy (ART) is critical in providing gender-affirming HIV care for transgender (trans) women living with HIV. However, interpersonal communications with HIV providers who are not competent with FHT may complicate this integration. METHODS: We conducted semi-structured interviews with trans women (n = 9) who self-reported as HIV-positive and their HIV providers (n = 15) from community-based venues (e.g., clinics) in Manila, Philippines. RESULTS: We identified five key themes from our qualitative data: (1) provider's concerns; (2) patient's goals; (3) affirmative vs. non-affirmative provider rhetoric; (4) alignment vs. misalignment of provider rhetoric to patient goals; and (5) FHT and ART-related decisions. Based on these themes, we describe a gender-affirmative HIV care framework to understand FHT-ART decisions among trans women living with HIV. Based on our data, this framework shows that provider-patient communications regarding ART and FHT consists primarily of provider concerns and patient goals regarding FHT. These communications can take on a gender-affirmative or non-affirmative style of rhetoric that either aligns or misaligns with patient goals and may lead to differences in FHT and ART-related decisions among trans women living with HIV. CONCLUSION: There exist mixed regimens and beliefs about taking FHT and ART among this sample of trans women. While trans participants' main source of health information is their HIV provider, providers are likely to communicate non-affirmative rhetoric that negatively impacts trans women's decision to take FHT and ART. Research is needed to elucidate co-prescriptions of gender-affirmative services with HIV care among this group in the Philippines.

Cardiac Safety of Rupatadine in a Single-Ascending-Dose and Multiple-Ascending-Dose Study in Healthy Japanese Subjects, Using Intensive Electrocardiogram Assessments-Comparison With the Previous White Caucasian Thorough QT Study.

A thorough QT/QTc study in healthy white Caucasian subjects demonstrated that rupatadine has no proarrhythmic potential and raised no cardiac safety concerns. The present phase 1 study aimed to confirm the cardiac safety of rupatadine in healthy Japanese subjects. In this randomized, double-blind, placebo-controlled study, 27 healthy Japanese subjects were administered single and multiple escalating rupatadine doses of 10, 20, and 40 mg or placebo. Triplicate electrocardiogram (ECG) recordings were performed on days -1, 1, and 5 at several points, and time-matched pharmacokinetic samples were also collected. Concentration-effect analysis based on the change in the QT interval corrected using Fridericia's formula (QTcF) from average baseline was performed. Data from the formal TQT study in white Caucasian subjects was used for a comparison analysis. The ECG data for rupatadine at doses up to 40 mg did not show an effect on the QTc interval of regulatory concern. The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a significant shortening of QTcF on days 1 and 5 four hours after a standardized meal. The data from this study exhibited no statistically significant differences in the QTc effect between Japanese and white Caucasian subjects.

A Systematic Review of Behavioral Interventions to Reduce Condomless Sex and Increase HIV Testing for Latino MSM.

Latino men who have sex with men (MSM) in the United States are disproportionately affected by HIV, and there have been calls to improve availability of culturally sensitive HIV prevention programs for this population. This article provides a systematic review of intervention programs to reduce condomless sex and/or increase HIV testing among Latino MSM. We searched four electronic databases using a systematic review protocol, screened 1777 unique records, and identified ten interventions analyzing data from 2871 Latino MSM. Four studies reported reductions in condomless anal intercourse, and one reported reductions in number of sexual partners. All studies incorporated surface structure cultural features such as bilingual study recruitment, but the incorporation of deep structure cultural features, such as machismo and sexual silence, was lacking. There is a need for rigorously designed interventions that incorporate deep structure cultural features in order to reduce HIV among Latino MSM.

Sexual and Behavioral Health Disparities Among Sexual Minority Hispanics/Latinos: Findings From the National Health and Nutrition Examination Survey, 2001-2014.

INTRODUCTION: Hispanics/Latinos (henceforth, Latinos) are the largest minority group in the U.S. With growing health disparities among this group, the highest burden remains among sexual and gender minority Latinos. Differences regarding sexual orientation have not been fully explored within this group using national representative samples. This study analyzed sexual and behavioral health disparities associated with sexual minority status among Latinos in the U.S. METHODS: The study included data from 5,598 Latino adults who participated in the 2001-2014 waves of the National Health and Nutrition Examination Survey. Data analysis was conducted in 2016. Bivariate and multivariable logistic regression analyses examined the prevalence of HIV, sexually transmitted infections, mental health problems, cigarette smoking, and alcohol/illicit drug use among sexual minorities and heterosexual Latino adults. Sexual minorities were defined as "gay, lesbian, and bisexual" (GLB) and "other" non-heterosexual groups. RESULTS: GLB Latinos reported higher prevalence of mental health problems and cigarette smoking compared with heterosexuals. After adjusting for covariates, GLB Latinos had greater odds of testing positive for HIV, lifetime diagnosis of sexually transmitted infections, poor mental health outcomes, cigarette smoking (including lifetime and current smoking status), and illicit drug use than heterosexuals. CONCLUSIONS: The disproportionate impact of health disparities among Latinos varies significantly by sexual orientation, with GLB individuals facing elevated prevalence. In particular, elevated odds for HIV/sexually transmitted infections, mental health problems, smoking, and illicit substance use were found. Further research, including longitudinal studies to understand the trajectories of risks, is needed to identify intervention opportunities in this population.

Leg loss in Lutzomyia longipalpis (Diptera: Psychodidae) due to pyrethroid exposure: Toxic effect or defense by autotomy?

BACKGROUND & OBJECTIVES: Phlebotomine sandflies lose their legs after exposure to pyrethroids. In some insects leg loss helps to defend them from intoxication and predation, a phenomenon known as autotomy. A field observation has shown that sandflies that have lost some legs are still able to blood-feed. The aims of the study were to determine whether leg loss in sandflies, after exposure to deltamethrin, is due to autotomy and to establish the effect of the leg loss on blood-feeding. METHODS: Two experiments were carried out with Lutzomyia longipalpis: (i) Females were individually exposed to a sublethal time of deltamethrin and mortality and the number of leg loss were recorded; and (ii) Groups of females with complete legs or with 1-3 legs lost due to pyrethroid exposure were offered a blood meal and percentages of blood-fed and fully-fed females were recorded. RESULTS: Most females lost a median of 1 leg within 1-48 h post-exposure to deltamethrin. Mortality (after 24 h) was significantly higher for exposed females with lost legs (31.1%), compared to exposed females with complete legs (7.3%), and there were no differences in mortality between females with complete legs and the control (unexposed females). There were no differences between the three treatments in the percentages of blood-fed and fully-fed females. INTERPRETATION & CONCLUSION: Leg loss in sandflies is a toxic effect of pyrethroids and there was no evidence of autotomy. The loss of up to three legs after exposure to pyrethroids does not affect blood-feeding behaviour in laboratory and probably also in wild conditions.

Online Hookup Sites for Meeting Sexual Partners Among Men Who Have Sex with Men in Rhode Island, 2013: A Call for Public Health Action.

Frequent use of websites and mobile telephone applications (apps) by men who have sex with men (MSM) to meet sexual partners, commonly referred to as "hookup" sites, make them ideal platforms for HIV prevention messaging. This Rhode Island case study demonstrated widespread use of hookup sites among MSM recently diagnosed with HIV. We present the advertising prices and corporate social responsibility (CSR) programs of the top five sites used by newly diagnosed HIV-positive MSM to meet sexual partners: Grindr, Adam4Adam, Manhunt, Scruff, and Craigslist. Craigslist offered universal free advertising. Scruff offered free online advertising to selected nonprofit organizations. Grindr and Manhunt offered reduced, but widely varying, pricing for nonprofit advertisers. More than half (60%, 26/43) of newly diagnosed MSM reported meeting sexual partners online in the 12 months prior to their diagnosis. Opportunities for public health agencies to promote HIV-related health messaging on these sites were limited. Partnering with hookup sites to reach high-risk MSM for HIV prevention and treatment messaging is an important public health opportunity for reducing disease transmission risks in Rhode Island and across the United States.

Marijuana Use and Psychiatric Disorders in Perinatally HIV-Exposed Youth: Does HIV Matter?

OBJECTIVE:  To examine longitudinal reciprocal relationships between marijuana use and psychiatric disorders, and identify the role of HIV in a sample (N = 340) of youth perinatally infected with HIV (PHIV+) and youth perinatally exposed but uninfected with HIV (PHIV-) (60.6% PHIV+; 9-16 years at baseline; 51% female). METHODS: Cross-lagged structural equation modeling was used to examine longitudinal associations between changes in marijuana use and changes in any behavioral, mood, and anxiety disorders at three time points across adolescence. RESULTS: Marijuana use predicted behavioral and mood disorders in youth, regardless of HIV status. Behavioral and mood disorders predicted marijuana use for PHIV- youth; behavioral disorders predicted marijuana use for PHIV+ youth. Anxiety disorders and marijuana use were not associated for either group. CONCLUSIONS: For PHIV+ and PHIV- youth, interventions that target early marijuana use may reduce later psychiatric disorders. Similarly, treatment for early behavioral disorders may prevent subsequent marijuana use.

Intimate Partner Violence Risk among Undergraduate Women from an Urban Commuter College: the Role of Navigating Off- and On-Campus Social Environments.

The current attention that is being paid to college sexual assault in policy circles and popular media overlooks a critical issue: the possible role played by the urban social environment in intimate partner violence (IPV) risk for the large number of urban commuter college students throughout the USA and beyond. This article helps to illuminate this dynamic using qualitative research collected at an urban commuter campus in New York City. Specifically, we conducted focus groups and in-depth interviews with 18 female undergraduate students, exploring the nature and consequences of IPV in students' lives, perceived prevalence of IPV, and resources for addressing IPV. Our results indicate that college attendance may both elevate and protect against IPV risk for students moving between urban off- and on-campus social environments. Based on this, we present a preliminary model of IPV risk for undergraduate women attending urban commuter colleges. In particular, we find that enrolling in college can sometimes elevate risk of IPV when a partner seeks to limit and control their student partner's experience of college and/or is threatened by what may be achieved by the partner through attending college. These findings suggest a role for urban commuter colleges in helping to mitigate IPV risk through policy formulation and comprehensive ongoing screening and prevention activities.

HIV treatment adherence measurement and reporting concordance in youth with perinatally acquired HIV infection and their caregivers.

We examined youth-caregiver adherence report concordance and association of different adherence self-report items with HIV RNA viral load (VL) in perinatally HIV-infected adolescents assessed in 2003-2008. Youth (n=194; 9-19 years) and their caregivers completed a multi-step 2-day recall, one item on last time medications were missed, and one item on responsibility for managing youths' medications. Across early (9-12 years), middle (13-15 years), and late (16+years) adolescence, both youth and caregivers reported having primary responsibility for youths' medication regimens and demonstrated poor to moderate youth-caregiver concordance on adherence items. Responses to the last-time-missed item had greater association with VL than did the 2-day recall, particularly for longer times (e.g., past month). By age group, significant associations with VL were found for caregiver reports in early adolescence, caregiver and youth reports in middle adolescence, and youth reports in late adolescence, suggesting that caregivers offer better reports of youth adherence during early adolescence, but by later adolescence, youth are better informants. Although design limitations preclude definitive conclusions about the reliability and validity of specific adherence items, this study suggests important issues related to age group, caregiver vs. youth informants of adherence, and recall periods for child adherence assessment that warrant further research.

Sexual Health Knowledge in a Sample of Perinatally HIV-infected and Perinatally-exposed Uninfected Youth.

This study describes sexual health knowledge in perinatally HIV-infected (PHIV+) and perinatally-exposed uninfected (PHIV-) ethnic-minority youth, ages 9-16 years, residing in NYC (n=316). Data on youth sexual health knowledge (e.g., pregnancy, STDs, birth control) and caregiver-adolescent communication about sexual health were examined. Participants in both groups answered only 35% of the sexual health knowledge questions correctly (mean=6.6/19). Higher scores were found among youth who reported more communication about sex with caregivers (vs. those who did not report talking about sex with caregivers; 8.54 vs. 5.84, p<.001) and among PHIV+ youth who were aware of their status (vs. PHIV+ youth who were not; 7.27 vs. 4.70, p<.001). Age was positively correlated with sexual health knowledge (beta=.489, p<.001). Both PHIV+ and PHIV- youth had poor sexual health knowledge, suggesting a need for sexual health education for both groups. Data suggest that interventions focused on caregiver-child risk communication may be important for prevention.

Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.

OBJECTIVES: The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. METHODS: We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. RESULTS: A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. CONCLUSIONS: A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.

Substance use and the development of sexual risk behaviors in youth perinatally exposed to HIV.

OBJECTIVE: To examine the longitudinal association between sexual behavior and substance use in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed-but-uninfected (PHIV-) youth. METHODS: Growth curve modeling was used with data from N = 340 PHIV-exposed youth (60.6% PHIV+; 9-22 years) to estimate the onset of penetrative and unprotected sex across time, adding alcohol and marijuana use trajectories as time-varying covariates and examining HIV-status differences. RESULTS: The odds of penetrative or unprotected sex more than doubled across time. Alcohol and marijuana use significantly increased the odds of engaging in sex and unprotected sex, with no HIV-status differences. The association between unprotected sex and alcohol use was less salient for PHIV+ than PHIV- youth. CONCLUSIONS: Similar to youth from other populations, PHIV+ and PHIV- youth are increasingly engaging in sex and substance use as they age. Targeted interventions to prevent sexual risk behavior and further HIV transmission should address the influence of substance use.

A GFP promoter fusion library for the study of Salmonella biofilm formation and the mode of action of biofilm inhibitors.

Salmonella, an important foodborne pathogen, forms biofilms in many different environments. The composition of these biofilms differs depending on the growth conditions, and their development is highly coordinated in time. To develop efficient treatments, it is therefore essential that biofilm formation and its inhibition be understood in different environments and in a time-dependent manner. Many currently used techniques, such as transcriptomics or proteomics, are still expensive and thus limited in their application. Therefore, a GFP-promoter fusion library with 79 important Salmonella biofilm genes was developed (covering among other things matrix production, fimbriae and flagella synthesis, and c-di-GMP regulation). This library is a fast, inexpensive, and easy-to-use tool, and can therefore be conducted in different experimental setups in a time-dependent manner. In this paper, four possible applications are highlighted to illustrate and validate the use of this reporter fusion library.

GHEP-ISFG collaborative exercise on mixture profiles of autosomal STRs (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03): results and evaluation.

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment. The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025:2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories.

Asking only "Did you use a condom?" underestimates the prevalence of unprotected sex among perinatally HIV infected and perinatally exposed but uninfected youth.

Among young adults who use condoms, incomplete condom use (putting a condom on after beginning or taking a condom off before finishing sex) and condom failure (condom breaking or slipping off during sex) are common. Therefore, sexual behavior surveys that ask only if a condom was used are likely to underestimate the actual prevalence of unprotected sex. This study examined data from 135 sexually active perinatally HIV-infected (PHIV+) youth and perinatally exposed but uninfected (PHIV-) youth, ages 13 to 24. Participants were asked whether they used a condom on their first and their most recent occasion of vaginal sex. Youth who reported using a condom were asked a follow-up question about whether there was any time during that occasion when sex was not protected by a condom. This follow-up question identified additional participants--almost double the proportions who initially said they did not use a condom--who had unprotected sex. Incomplete condom use was similar among PHIV+ and PHIV-youth, boys and girls, Latinos and African Americans, and younger and older youth. These findings illustrate the importance of asking specifically about whether any unprotected behavior occurred from start to finish of sex to achieve more valid estimates of sexual risk behavior.