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This study aimed to understand the long-term outcomes of patients with heart failure with recovered ejection fraction, identify predictors of adverse events, and develop a risk stratification model. From an academic healthcare system, we retrospectively identified 133 patients (median age 66, 38% female, 30% ischemic etiology) who had an improvement in left ventricular ejection fraction (LVEF) from40% to ≥53%. Significant predictors of all-cause mortality, hospitalization, and future reduction in LVEF were identified through Cox regression analysis. Kaplan-Meier survival was 70% at 5 years. Freedom from hospitalization was 58% at 1 year, and the risk of future LVEF reduction to40% was 28% at 3 years. Diuretic dose and B-type natriuretic peptide (BNP) at the time of LVEF recovery were the strongest predictors of mortality and hospitalization in multivariate-adjusted analysis (BNP hazard ratio 1.13 per 100 pg/ml increase [p0.01]; furosemide-equivalent dose hazard ratio 1.19 per 40 mg increase [p = 0.02]). An all-cause mortality Cox proportional hazard risk model incorporating New York Heart Association functional class, BNP and diuretic dose at the time of recovery showed excellent risk discrimination (c-statistic 0.79) and calibration. In conclusion, patients with heart failure with recovered ejection fraction have heterogenous clinical outcomes and are not "cured." A risk model using New York Heart Association functional class, BNP, and diuretic dose can accurately stratify mortality risk.

The Young Men and Media study developed and pilot tested a community-informed, online HIV prevention program for adolescent sexual minority males (ASMM) in the United States. The developed intervention uses nine interactive modules to increase sexual health knowledge, promote critical examination of pornography, and decrease sexual risk among ASMM. Participants (N = 154, age 14–17 years) were recruited online in Spring 2020 and randomized to the intervention (n = 77) or other existing HIV websites (n = 77). Of the 65 intervention participants who logged in to the website, most completed all nine modules and found the content useful (average module score 4.3 out of 5 stars). The intervention also showed improved HIV/STI knowledge, increased pornography knowledge, and reduced beliefs that pornography is an accurate depiction of male-male sex. Results indicate that the Young Men and Media intervention is feasible, acceptable, and may positively impact sexual health outcomes.

Objective Lesbian, gay, and bisexual (LGB) individuals who report greater minority stress (e.g., discrimination) are at an elevated risk for multiple health problems. However, few studies have examined physiological mechanisms that might link minority stress to health. This study tested how cardiovascular and cortisol responses to a laboratory-induced social stressor differed when that stressor contained an additional minority stress component. Method LGB adults (n = 141; 51% male, 49% female) participated in a social stress task in which they were interviewed by a prerecorded confederate. Participants were randomized to receive information that their interviewer held either antigay or progay social/political beliefs. Cardiovascular reactivity and salivary cortisol were assessed at baseline, during the task, and during recovery. Results All participants experienced significant task-related increases in heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP). However, participants in the antigay condition had greater increases in HR and SBP during the task and smaller decreases in SBP during recovery. Salivary cortisol increased significantly only in the antigay condition. High frequency heart rate variability (hfHRV) was constant throughout the stress task for participants in the progay condition but decreased significantly during the task for participants in the antigay condition. Conclusions Minority stress has the potential to affect LGB individuals' health through cardiovascular and endocrine mechanisms. Moreover, its physiological signature may differ from other social stress in ways that have implications for health and emotion regulation more broadly. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The use of mobile health (mHealth) technologies addressing HIV disparities among gay, bisexual, and other men who have sex with men (GBMSM) has increased. A systematic review of mHealth interventions for HIV prevention and treatment among GBMSM was conducted to summarize the current evidence and provide recommendations for future research. PRISMA guidelines were followed (PROSPERO ID: 148452). Studies identified via PubMed, PsychInfo, or Embase were included that (i) were in English, (ii) were published in a peer-reviewed journal prior to July 1, 2019, (iii) presented primary results, (iv) included only GBMSM, and (v) reported the results of an mHealth intervention (e.g., text message, phone/mobile application [app]) to improve HIV prevention or treatment outcomes. Of 1,636 identified abstracts, 16 published studies met inclusion criteria. Eleven studies were conducted in the United States. One study was a fully powered randomized controlled trial (RCT), seven were single-arm pilots with pre–post assessments, four were pilot RCTs, and four tested public health campaigns with post-assessments. Seven developed study-specific apps, five used text messaging, and four used existing social networking apps. Most (81%) targeted prevention outcomes. Nine cited a specific behavioral theory. All studies found that a mHealth approach was feasible and acceptable. All interventions provided evidence of preliminary efficacy or promising trends on primary outcomes. Although mHealth interventions for HIV prevention and treatment appear feasible and acceptable, most published studies are small pilot trials. Additional research assessing the efficacy and mechanisms of mHealth interventions is needed.

OBJECTIVE This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors. RESEARCH DESIGN AND METHODS We prospectively enrolled 758 children, 6–18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2–6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. RESULTS Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = −0.12, P < 0.001), item-color recall (β = −0.08, P = 0.010), and forward digit span (β = −0.06, P = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = −0.08, P = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (β = −0.10 and β = −0.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (β = −0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for. CONCLUSIONS A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.

Background: Liquid biopsies offer significant potential for informing on cancer progression and therapeutic resistance via minimally invasive serial monitoring of genetic alterations. Although the cancer epigenome is a central driving force in most neoplasia, the accuracy of monitoring the tumor methylome using liquid biopsies remains relatively unknown. Objectives: to investigate how well two types of liquid biopsy (urine and blood) capture the prostate cancer methylome, and may thus serve as a non-invasive surrogate for studying the tumor epigenome. Methods: A cohort of four metastatic treatment naïve prostate cancer (PCa) patients was selected. Matched biopsy cores (tumor and histologically matched-normal), post-DRE, pre-biopsy urine, and peripheral blood plasma were available for each subject. DNA methylation was profiled utilizing the Infinium® MethylationEPIC BeadChip (Illumina) and analysed using the RnBeads software. Significantly (FDR adjusted P < 0.05) differentially methylated probes (DMPs) between tumor and MN were identified and examined in the liquids (done at a grouped and individual subject level). Results: DNA methylation analysis of urine and blood in men with metastatic PCa showed highly correlated patterns between the different liquid types (ρ = 0.93, P < 0.0001), with large contributions from non-tumor sources. DNA methylation profiles of liquids were more similar between subjects, than intra-individual liquid-tumor correlations. Overall, both urine and plasma are viable surrogates for tumor tissue biopsies, capturing up to 39.40% and 64.14% of tumor-specific methylation alterations, respectively. Conclusion: We conclude that both urine and blood plasma are easily accessible and sensitive biofluids for the study of PCa epigenomic alterations.

Introduction Knowledge about sexual health is a key determinant of sexual behavior among adolescent sexual minority males (ASMM). No measures exist to assess anal sex knowledge, even though anal sex is the primary route by which ASMM acquire sexually transmitted infections (STIs), including a disproportionate burden of human immunodeficiency virus (HIV). Aim We developed a new measure as a first step toward assessing the prevalence and correlates of anal sex knowledge and potential effects of interventions to improve knowledge. Methods Two coders independently outlined domains of knowledge within 2 sex education videos designed to address anal sex knowledge among ASMM. An initial set of 56 items, some duplicative, encompassed all domains. A larger team, including a psychometrician, then iteratively revised and reduced the set of items, and assessed construct validity via cognitive testing among ASMM (N = 4, aged 16–17 years old, 75% identifying as racial/ethnic minorities). For the final set of 10 items, factor structure and convergent and divergent validity were assessed using baseline responses to an online survey within a randomized controlled pilot trial among 154 ASMM. Open-ended questions assessed their comprehension and the acceptability of items. Outcomes We examined correlates that we anticipated would be theoretically related (ie, the HIV Knowledge Questionnaire [HIV-KQ-18] and the STD-Knowledge Questionnaire [STD-KQ]) and theoretically distinct (ie, the Patient Health Questionnaire [PHQ-2], Generalized Anxiety Disorder scale [GAD-2], and employment status). Results The one-factor model explained 42% of the items’ common variance and demonstrated acceptable internal reliability (Cronbach’s alpha = 0.72). The measure withstood tests of convergent and divergent validity when compared to current measures (HIV knowledge, r = 0.35 and STI knowledge, r = 0.24, both P < .05; internalizing mental health symptoms, r = -0.07 and employment status, r = 0.13, both P > .05). Few respondents found words unfamiliar or uncomfortable. Clinical Implications A method for assessing anal sex knowledge may offer opportunities to intervene to lessen harmful sequelae of a lack of knowledge. Strength & Limitations We developed a brief, psychometrically valid measure of anal sex knowledge. The measure may neither generalize to all anal health knowledge nor to more sexually experienced, older SMM. Conclusion The resulting 10-item, single-factor measure, the Inventory of Anal Sex Knowledge (iASK), is psychometrically sound and addresses the lack of anal sex knowledge measures among ASMM. The iASK can function to assess the prevalence and sequelae of anal sex knowledge among ASMM as well as the impact of interventions targeting anal sex knowledge.

Purpose: Psychosocial syndemic indicators (e.g., internalizing symptoms, alcohol/substance use, and violence exposure) have been associated with increased risk for HIV among older adolescent sexual minority males and adult sexual minority men. No studies have examined these concerns among early adolescents (

Adolescent sexual minority males (ASMM; < 18 years old) do not typically receive sexual education that addresses male-male relationships from traditional sources (i.e., school, parents). Therefore, many rely on sexually explicit online media (SEOM; i.e., pornography) to find sexual health information. The current study describes SEOM use by ASMM in the United States (U.S.) and examines the association between exposure to condomless anal sex (CAS) in SEOM and engagement in CAS. In 2017, ASMM (N= 206; M age=16, range: 14–17; 51% racial/ethnic minorities) from across the U.S. completed an online sexual health survey, including questions about SEOM use and sexual behaviors. Most (86%) reported that they had viewed SEOM. Engagement with SEOM was frequent (86% reported viewing ≥ one time per week) and lengthy (70% reported viewing for ≥ 15 minutes per session). Youth perceived that SEOM influenced how they, and other ASMM, think and behave sexually. Further, exposure to risky sexual behavior in SEOM appears to be associated with youths’ dyadic sexual behavior. To support the healthy sexual development of ASMM, it is important to acknowledge the near-universal use of SEOM by ASMM, to identify ways to maximize its potential value, and to minimize potential harms.

Individuals seeking bariatric surgery evidence risk for binge and disordered eating behaviors, which can lead to poorer post-surgical weight loss outcomes. Use of avoidant coping strategies to manage stress, along with symptoms of depression, are associated with disordered eating in the general population. However, the role of coping has not been examined among candidates for bariatric surgery, and coping and depression have rarely been considered in combination. Given the emerging standard that psychologists are involved in evaluations and treatment before and after surgery, consideration of these variables is clinically relevant. Participants were 399 patients undergoing pre-surgical bariatric psychological assessment. Hierarchical linear regression analyses tested whether gender, age, and BMI; approach and avoidance coping; and depression and anxiety were associated with disordered eating (binge eating, restraint, eating concerns, shape concerns, weight concerns) in a cross-sectional study design. In initial steps of the model controlling demographic variables, approach coping predicted less and avoidance coping predicted more disordered eating across most outcomes examined. In models including depression and anxiety, avoidance (but not approach) coping remained a relevant predictor. The effects of depression were also quite robust, such that participants who were more depressed reported more disordered eating. More anxious participants reported more restrained eating. Avoidance coping and depressive symptoms emerged as key variables in understanding recent disordered eating among patients considering bariatric surgery. Pre-surgical psychological evaluations and treatment approaches could be enhanced with consideration of patient coping strategies, particularly avoidant coping responses to stress, independent of psychological distress.

Social scientists have long utilized observations of human behavior in research designs. For researchers studying couples, observation of romantic partners has led to important discoveries about how such behavior is associated with physical, mental, and family health. Historically, these methods have been used in in-person laboratory paradigms that place notable limitations on reach and inclusion. This has, in turn, restricted the generalizability of such research to couples who may not attend an in-person laboratory assessment. Transferring the observational laboratory into an online format has the potential to expand the capabilities of these methods to include more diverse couples. This article presents two empirical studies that used online methods to conduct observational behavioral research with sexual and gender minority couples, populations that could be difficult to reach using traditional methods in many places. We demonstrate that we were able to reach, recruit, and enroll diverse couples that more closely resemble the population of same-sex couples in the United States than likely would have been reached in-person. Further, we show that the quality of the observational data collected via the internet allowed for over 94% of collected data to be coded, with acceptable interrater reliabilities and convergent validity. These studies provide a proof-of-concept of online observational methods, accompanied by a tutorial for using such methods. We discuss possible extensions of these online methods, their limitations, and the potential to help further the field of close relationships by reaching more diverse relationships and increasing the generalizability of our research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Owing to multiple and multilevel ecological factors, sexual and gender minority (SGM) populations exhibit persistent mental health disparities. SGM populations are also at increased risk for never being reached by evidence-based mental health care in real-world settings, which is essential for reducing these disparities. To be maximally effective in reducing these disparities, we must strive to bring our research findings into routine clinical care quickly. Implementation science can help SGM health researchers achieve this goal. This perspective outlines how researchers can use implementation science theories and methods to reduce SGM mental health disparities more efficiently and more durably.

Improved prostate cancer detection methods would avoid over-diagnosis of clinically indolent disease informing appropriate treatment decisions. The aims of this study were to investigate the role of a panel of Inflammation biomarkers to inform the need for a biopsy to diagnose prostate cancer. Peripheral blood serum obtained from 436 men undergoing transrectal ultrasound guided biopsy were assessed for a panel of 18 inflammatory serum biomarkers in addition to Total and Free Prostate Specific Antigen (PSA). This panel was integrated into a previously developed Irish clinical risk calculator (IPRC) for the detection of prostate cancer and high-grade prostate cancer (Gleason Score ≥ 7). Using logistic regression and multinomial regression methods, two models (Logst-RC and Multi-RC) were developed considering linear and nonlinear effects of the panel in conjunction with clinical and demographic parameters for determination of the two endpoints. Both models significantly improved the predictive ability of the clinical model for detection of prostate cancer (from 0.656 to 0.731 for Logst-RC and 0.713 for Multi-RC) and high-grade prostate cancer (from 0.716 to 0.785 for Logst-RC and 0.767 for Multi-RC) and demonstrated higher clinical net benefit. This improved discriminatory power and clinical utility may allow for individualised risk stratification improving clinical decision making.

Background Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our aim was to investigate the dynamics of personal DNA methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration. Results Forty-eight plasma samples from 9 mPCa patients were collected, longitudinally, over 13–21 months. After circulating cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify differentially methylated genes (DMGs) in cfDNA, which were subsequently validated in two independent mPCa (cfDNA and FFPE tissue) cohorts. Individual cfDNA global methylation patterns were temporally stable throughout the disease course. However, a proportion of CpG sites presented a dynamic temporal pattern that was consistent with clinical events, including different therapies, and were prominently associated with genes linked to immune response pathways. Additionally, study of the tumour fraction of cfDNA identified > 2000 DMGs with dynamic methylation patterns. Conclusions Longitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with disease progression and therapy administration, thus highlighting the potential of using liquid biopsies to study PCa evolution at a methylomic level.

Functional support—the availability of material aid, emotional support, or companionship—promotes general well-being. For men who have sex with men (MSM) living with HIV, having a person who supports you associates with viral suppression. This study examines the association between supportive partnerships and HIV viral suppression among middle-aged and aging MSM living with HIV. A total of 423 middle-aged and aging MSM (mean age, 58.2 years) from the Multicenter AIDS Cohort Study provided self-reported data about their partnerships. Separate Poisson regression models assessed how partnership type, support, strain, and duration from April 2017 were associated with repeated viral load measurements up to April 2019. Of the follow-up visits (N = 1289), 90.0% of participants were virally suppressed. Most participants reported being non-Hispanic White (61.0%) and college-educated (83.4%). Participants were asked about their primary partnerships (i.e., “someone they are committed to above anyone else”) and secondary partnerships (i.e., those who can also be intimate or supportive but not necessarily romantic or sexual). The participants reported: no partnerships (45.2%), only primary partnerships (31.0%), only secondary partnerships (11.1%), or both primary and secondary partnerships (12.8%). Primary and secondary partnerships had mean (SD) durations of 15.9 (11.3) and 25.2 (16.5) years, respectively. Participants reporting both primary and secondary partnerships (compared with no partnership) showed significantly higher odds of being virally suppressed (adjusted prevalence ratio [aPR], 1.04; 95% CI, 1.00–1.08; p = 0.043). Albeit not statistically significant, primary-only (aPR, 1.01; 95% CI, 0.97–1.06; p = 0.547) or secondary-only (aPR, 1.03; 95% CI, 0.98–1.08; p = 0.224) partnership types were positively associated with viral suppression. Partner support and strain were not associated with viral suppression in any partnership group. Being older and non-Hispanic Black were positively and negatively associated with viral suppression, respectively. Encouraging partnerships should be considered one of clinicians’ many tools to help middle-aged and aging MSM achieve long-term viral suppression.

Background: Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine-derived cell-free messenger RNA (cf-RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in biopsy naive patients. Methods: Post-digital rectal examination urine samples previously analyzed separately for both cellular methylation and cf-RNA expression within the Movember GAP1 urine biomarker cohort were selected for a fully integrated analysis (n = 207). A robust feature selection framework, based on bootstrap resampling and permutation, was utilized to find the optimal combination of clinical and urinary markers in a random forest model, deemed ExoMeth. Out-of-bag predictions from ExoMeth were used for diagnostic evaluation in men with a clinical suspicion of prostate cancer (PSA ≥ 4 ng/mL, adverse digital rectal examination, age, or lower urinary tract symptoms). Results: As ExoMeth risk score (range, 0-1) increased, the likelihood of high-grade disease being detected on biopsy was significantly greater (odds ratio = 2.04 per 0.1 ExoMeth increase, 95% confidence interval [CI]: 1.78-2.35). On an initial TRUS biopsy, ExoMeth accurately predicted the presence of Gleason score ≥3 + 4, area under the receiver-operator characteristic curve (AUC) = 0.89 (95% CI: 0.84-0.93) and was additionally capable of detecting any cancer on biopsy, AUC = 0.91 (95% CI: 0.87-0.95). Application of ExoMeth provided a net benefit over current standards of care and has the potential to reduce unnecessary biopsies by 66% when a risk threshold of 0.25 is accepted. Conclusion: Integration of urinary biomarkers across multiple assay methods has greater diagnostic ability than either method in isolation, providing superior predictive ability of biopsy outcomes. ExoMeth represents a more holistic view of urinary biomarkers and has the potential to result in substantial changes to how patients suspected of harboring prostate cancer are diagnosed.

Background Adolescent sexual minority males (ASMM) are disproportionately at risk of HIV. Purpose This study documents the sexual debut behaviors of ASMM, tests whether sexual debut and sexual behavior differed by race/ethnicity, and explores the association between early anal sex debut and engaging in condomless anal sex. Methods Sexually active ASMM (N = 118; ages 14-17) in the United States completed an online sexual health survey. We used Fisher exact tests to explore differences by race/ethnicity in sexual debut characteristics and hypothesized relationships between sexual debut and risk behavior. Results The average age of sexual debut with a male partner was 14 years (SD = 2.4). Approximately one-third (31%) reported anal sex at their sexual debut, with non-Latino black/African American ASMM more likely to report anal sex at debut (63%) compared with non-Latino white (28%), Latino (21%), or mixed race/other identified youth (19%; χ = 12.1, P = 0.01). All participants (100%) who reported an anal sex debut before the age of 14 years reported engaging in condomless anal sex in their lifetime, compared to 60% of those who reported an anal sex debut when they were 14 years old or older (χ = 5.6, P = 0.03). Participants wanted information about how to safely and comfortably have anal sex (59%) and skills around partner communication (>50%) before debut. Conclusion Sexually active ASMM begin engaging in sexual behavior with other males early and with incomplete knowledge and skills regarding sexual health and safety.

Aim: The NK-1 receptor antagonist HTX-019 (CINVANTI® [aprepitant injectable emulsion]) was approved for preventing chemotherapy-induced nausea and vomiting based on bioequivalence studies in healthy volunteers. The objective of this study was to evaluate HTX-019 safety in cancer patients. Patients & methods: This retrospective analysis evaluated the safety of HTX-019 130 mg 30-min intravenous infusion, as part of a three-drug antiemetic regimen. Results: No treatment-emergent adverse events (TEAEs) were deemed related to HTX-019. During treatment cycles, three of 100 patients developed five reversible TEAEs: dyspnea, hot flash, pain, nausea and visual disturbance. Between cycles, six patients had TEAEs of dizziness (three patients), infusion-site events (two patients) and headache (two patients). Conclusion: HTX-019 is safe in cancer patients receiving chemotherapy.

Classifying indolent prostate cancer represents a significant clinical challenge. We investigated whether integrating data from different omic platforms could identify a biomarker panel with improved performance compared to individual platforms alone. DNA methylation, transcripts, protein and glycosylation biomarkers were assessed in a single cohort of patients treated by radical prostatectomy. Novel multiblock statistical data integration approaches were used to deal with missing data and modelled via stepwise multinomial logistic regression, or LASSO. After applying leave-one-out cross-validation to each model, the probabilistic predictions of disease type for each individual panel were aggregated to improve prediction accuracy using all available information for a given patient. Through assessment of three performance parameters of area under the curve (AUC) values, calibration and decision curve analysis, the study identified an integrated biomarker panel which predicts disease type with a high level of accuracy, with Multi AUC value of 0.91 (0.89, 0.94) and Ordinal C-Index (ORC) value of 0.94 (0.91, 0.96), which was significantly improved compared to the values for the clinical panel alone of 0.67 (0.62, 0.72) Multi AUC and 0.72 (0.67, 0.78) ORC. Biomarker integration across different omic platforms significantly improves prediction accuracy. We provide a novel multiplatform approach for the analysis, determination and performance assessment of novel panels which can be applied to other diseases. With further refinement and validation, this panel could form a tool to help inform appropriate treatment strategies impacting on patient outcome in early stage prostate cancer.

Background Executive functioning (EF) describes a set of neurocognitive processes critical to enacting complex health behaviors. However, theoretical frameworks for understanding sexual risk behavior have generally neglected neurocognitive constructs, and beyond a few studies of individuals selected for high substance use, the literature contains virtually no research on this topic with other adults at risk for HIV infection, such as men who have sex with men (MSM). Purpose This study tested whether EF was associated with condomless anal intercourse (CAI) among MSM. Methods Seventy MSM completed cognitive tests assessing EF at two time points-baseline, and approximately 30 min later after engaging in a stressful interpersonal task. Men also reported their sexual behaviors over the past 3 months, including the frequency of CAI. Results Baseline EF was unrelated to CAI. However, CAI was associated with the degree to which performance improved from baseline to post-stressor administration. Compared with norms for practice effects, men who reported CAI improved less than expected from baseline to post-stressor EF performance, whereas men who reported no CAI exhibited a more normative practice effect. Conclusions MSM with histories of greater sexual risk improved less than anticipated from baseline to post-stressor on tests of EF, suggesting that they might be more cognitively depleted by the stressful interpersonal task they engaged in between administrations. It is possible that certain individuals struggle to maintain executive control in stressful interpersonal situations, a finding that could contribute to the difficulty some individuals face executing precautionary behaviors during a sexual encounter.

The mental health burden among people living with HIV/AIDS (PLWHA) is high and often involves multiple comorbid psychological and substance use-related psychosocial problems. These co-occurring problems, or syndemics, additively impair engagement in HIV disease management. Existing psychotherapies for mental health and HIV health have generally focused on a single psychosocial problem and little research exists to guide future psychotherapies that address multiple mental health issues.To address this gap in understanding, we conducted qualitative interviews with multiply comorbid PLWHA (N = 30) who completed cognitive-behavioural therapy (CBT) for depression and medication adherence.Themes emerged regarding participants' perspectives on how overlapping substance use and mood disorders interacted to reduce the benefit of CBT. Substance use was a dominant theme compared to other syndemics, highlighting the need for integrated mental health and substance use interventions. Interviews also suggested modifications of which psychosocial concerns participants felt should be prioritized in treatment delivery. Finally, participants described content they would want in a psychotherapy intervention, including intimacy and sexual health.Future psychotherapeutic interventions for syndemic problems and HIV self-care will need to comprehensively address complex concerns, including issues salient to the overall well-being of PLWHA. This may improve client engagement and, ultimately, mental, and physical health outcomes. Clinical or methodological significance of this article: Although mental health comorbidity is common and often complex among clients living with HIV, little research exists to guide psychotherapy for such intricate mental health concerns. The current study used content analysis of in-depth qualitative interviews with clients living with HIV and multiple mental health comorbidities who had recently completed cognitive-behavioural therapy. Recommendations based on these findings suggest strategies for clinicians working with similar clients to consider and offers suggestions for future treatment development research.

The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA.

BACKGROUND Understanding how youth perceive eating healthy foods can inform programs and policies that aim to improve healthy eating. We assessed the reasons for and the most common locations of eating healthy foods among Georgia's (GA) high school (HS) students. METHODS Using the 2013 GA HS Youth Risk Behavior Survey, we examined motivations for and locations of eating healthy foods by sociodemographic characteristics and daily fruit and vegetable intake. Weighted chi-square tests were used to examine differences in responses for each perception. RESULTS Nineteen percent of GA HS students consumed fruit ≥3 times/day and 11% consumed vegetables ≥3 times/day. The most frequently chosen response to motivations for eating healthy foods was the desire to be healthy (42%), followed by enjoying their taste (18%). The most likely location to eat healthy foods was at home (80%), followed by at school (13%). CONCLUSIONS GA HS students are most motivated to eat healthy foods by the desire to be healthy and their enjoyment of the taste of healthy foods. Incorporating messages that align with students' motivations to eat healthy foods could be considered when developing promotional programs/policies targeting healthy eating.

Low-SES couples have limited resources to manage the chronic and acute stressors with which they are disproportionately faced. Although these couples are at greater risk for negative individual and relationship outcomes, evaluations of the impact of couple relationship education (CRE) in low-SES couples have been plagued by methodological problems, most notably challenges associated with recruitment and retention. We review the literature on challenges couples face associated with low-SES, as well as on recruitment, retention, and CRE in low-SES, ethnic minority populations. We illustrate some of these challenges in a case study of CRE for low-SES couples transitioning to parenthood. In this pilot study, 21 couples were recruited from a community health clinic and randomized to either an experimental treatment condition (EXP; N = 11) or a treatment-as-usual control condition (TAU; N = 10). This study sought to mitigate documented challenges with recruitment and retention: We leveraged community partnerships, attempted to build and maintain strong relationships with study participants, provided incentives for assessments as well as intervention meetings, and attempted to reduce potential barriers to enrollment and retention. Nonetheless, we had low rates of recruitment and retention. We integrate these findings and experiences with our review of previous work in this area. We make recommendations for future CRE research and practice that have potential implications for public policy in this area.

This study describes the primary and secondary partnerships of aging gay men participating in the Understanding Patterns of Healthy Aging Among Men Who Have Sex with Men substudy of the Multicenter AIDS Cohort Study and examines differences in the prevalence of these relationship structures by HIV status while adjusting for age, education, and race/ethnicity. Relationships were compared within the following structural categories: “only a primary partnership”, “only a secondary partnership”, “both a primary and secondary relationship”, or “neither a primary nor secondary relationship”. There were 1,054 participants (51.9% HIV negative/48.1% HIV positive) included in the study. Participants had a median age of 62.0 years (interquartile range: 56.0–67.0) and most reported being non-Hispanic white (74.6%) and college educated (88.0%). Of the 1,004 participants with available partnership status data, 384 (38.2%) reported no primary or secondary partnerships, 108 (10.8%) reported secondary-only partnership, 385 (38.3%) reported primary-only partnership, and 127 (12.6%) reported both primary and secondary partnerships. Of participants who reported primary partnerships only, the prevalence rates (PRs) were lower among those 62 years and older, HIV positive, black non-Hispanic and Hispanics. Of participants who reported only having a secondary partnership, the PRs were higher among those 62 years and older and HIV positive. Of participants who did not report having either a primary or secondary partnership, the PRs were higher among those 62 years and older, HIV positive, and black non-Hispanic compared with their respective referent groups. There was no significant difference in PRs of having both primary and secondary partnerships by age category, HIV status, race/ethnicity, and education. This study aimed to fill a knowledge gap in the literature regarding both primary and secondary supportive partnerships among aging HIV-positive and HIV-negative gay men.

Relationship power is an important dyadic construct in close relationships that is associated with relationship health and partner's individual health. Understanding what predicts power in heterosexual couples has proven difficult, and even less is known about gay couples. Resource models of power posit that demographic characteristics associated with social status (e.g., age, income) confer power within the relationship, which in turn shapes relationship outcomes. We tested this model in a sample of gay male couples (N = 566 couples) and extended it by examining race and HIV status. Multilevel modeling was used to test associations between demographic bases of power and decision-making power. We also examined relative associations among demographic bases and decision-making power with relationship satisfaction given the literature on power imbalances and overall relationship functioning. Results showed that individual income was positively associated with decision-making power, as was participant's HIV status, with HIV-positive men reporting greater power. Age differences within the relationship interacted with relationship length to predict decision-making power, but not satisfaction. HIV-concordant positive couples were less satisfied than concordant negative couples. Higher power partners were less satisfied than lower power partners. Demographic factors contributing to decision-making power among same-sex male couples appear to share some similarities with heterosexual couples (e.g., income is associated with power) and have unique features (e.g., HIV status influences power). However, these same demographics did not reliably predict relationship satisfaction in the manner that existing power theories suggest. Findings indicate important considerations for theories of power among same-sex male couples. (PsycINFO Database Record

OBJECTIVES : To provide descriptive information on behavioral health (BH) productivity and billing practices within a pediatric primary care setting. METHODS : This retrospective investigation reviewed 30 months of electronic medical records and financial data. RESULTS : The percent of BH provider time spent in direct patient care (productivity) was 35.28% overall, with a slightly higher quarterly average (M = 36.42%; SD = 6.46%). In the 646.75 hr BH providers spent in the primary care setting, $52,050.00 was charged for BH services delivered ($80.48 hourly average). CONCLUSIONS : BH productivity and billing within pediatric primary care were suboptimal and likely multifactorially derived. To promote integrated primary care sustainability, the authors recommend three future aims: improve BH productivity, demonstrate the value-added contributions of BH services within primary care, and advocate for BH-supporting health care reform.© The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. Language: en

Objective Gay, bisexual, and other men who have sex with men (GBMSM) remain at high risk of HIV infection via condomless anal sex. Sexually explicit media (SEM) likely influences GBMSM's sexual behavior and has been associated with condomless anal sex. SEM messages may be especially potent during formative developmental periods. Method We examined the association between age of first SEM exposure and condomless anal sex in a sample of adult GBMSM (N = 1,114) recruited using the Internet. Results Every 1-year delay in age of first SEM exposure resulted in a 3% decrease in the odds of engaging in condomless anal sex as an adult (odds ratio = .97, 95% CI [.95, .99], p = .01). This association remained significant in 3 separate multivariable models that controlled for age of sexual debut, age of anal sex debut, and current age, respectively. This association was moderated by ethnicity such that the effect was stronger among Latino men. Conclusions GBMSM who were exposed to SEM earlier in their lives report more sexual risk behavior as adults. SEM exposure in GBMSM is an important sexual development milestone deserving further research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Endotoxin exacerbates asthma. We designed the Louisa Environmental Intervention Project (LEIP) and assessed its effectiveness in reducing household endotoxin and improving asthma symptoms in rural Iowa children. Asthmatic school children (N = 104 from 89 homes) of Louisa and Keokuk counties in Iowa (aged 5-14 years) were recruited and block-randomized to receive extensive (education + professional cleaning) or educational interventions. Environmental sampling collection and respiratory survey administration were done at baseline and during three follow-up visits. Mixed-model analyses were used to assess the effect of the intervention on endotoxin levels and asthma symptoms in the main analysis and of endotoxin reduction on asthma symptoms in exploratory analysis. In the extensive intervention group, dust endotoxin load was significantly reduced in post-intervention visits. The extensive compared with the educational intervention was associated with significantly decreased dust endotoxin load in farm homes and less frequent nighttime asthma symptoms. In exploratory analysis, dust endotoxin load reduction from baseline was associated with lower total asthma symptoms score (Odds ratio: 0.52, 95% confidence interval: 0.29-0.92). In conclusion, the LEIP intervention reduced household dust endotoxin and improved asthma symptoms. However, endotoxin reductions were not sustained post-intervention by residents.

BACKGROUND: Cigarette smokers show greater delay discounting (devaluation of delayed consequences) than non-smokers, suggesting that rapid devaluation of the future contributes to tobacco use through a mechanism in which tobacco-related health consequences are too delayed to discourage smoking. However, little work has quantified delay discounting in relation to electronic cigarette (EC) use, a tobacco product that many users believe to pose fewer negative health consequences than cigarettes. METHODS: We assessed discounting of delayed monetary rewards in a web-based sample of 976 participants, stratified by both EC use (current and never) and cigarette use (current, former, and never). RESULTS: Controlling for demographic variance, current EC users generally showed greater discounting than never EC users (p = .019). Current cigarette smokers also showed greater discounting than former and never smokers (p < .001). However, the between-group difference for EC use was much smaller (η(p)(2) = .006) than for cigarette use (η(p)(2) = .026). Moreover, differences in discounting in relation to EC use were not statistically apparent in most pairwise comparisons. Most notably, the difference between former smokers who achieved smoking cessation by transitioning to ECs (i.e., exclusive EC users) and those who have never used ECs or cigarettes was nonsignificant and small (η(p)(2) = .010). CONCLUSIONS: The smaller effect size for the association between delay discounting and current EC use, relative to current cigarette use, suggests that public perception of ECs as a safer alternative to cigarettes attenuates the role of delay discounting in decisions to use ECs.

BACKGROUND:Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. METHODS:We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of

Recently, behavioral prevention interventions for HIV have been criticized as being ineffective, costly, or inefficient. In this commentary, using HIV-positive men who have sex with men (MSM) as an illustrative high-risk population, we argue that the opposite is true – that behavioral interventions for HIV prevention, if implemented with the populations who need them, are affordable and critical for future prevention efforts. We base this argument on recent evidence showing that 1) adherence to antiretroviral treatment (ART) for prevention purposes is necessary to suppress HIV replication and reduce transmissibility, 2) individuals living with HIV have multiple psychosocial concerns that impact self-care and moderate the potential effectiveness of health behavior interventions, and 3) intensive interventions targeting both concerns together (psychosocial and HIV care) can show clinically significant improvement. We follow by comparing the cost of these types of interventions to the cost of standard clinical treatment for HIV with ART, and demonstrate a cost-savings of potential intensive behavioral interventions for, in this case, HIV-positive MSM who have uncontrolled virus. Keeping this evidence in mind, we conclude that individual intervention must remain a mainstay of HIV prevention for certain critical populations.

Behavioral interventions to reduce sexual risk behavior depend on strong health behavior theory. By identifying the psychosocial variables that lead causally to sexual risk, theories provide interventionists with a guide for how to change behavior. However, empirical research is critical to determining whether a particular theory adequately explains sexual risk behavior. A large body of cross-sectional evidence, which has been reviewed elsewhere, supports the notion that certain theory-based constructs (e.g., self-efficacy) are correlates of sexual behavior. However, given the limitations of inferring causality from correlational research, it is essential that we review the evidence from more methodologically rigorous studies (i.e., longitudinal and experimental designs). This systematic review identified 44 longitudinal studies in which investigators attempted to predict sexual risk from psychosocial variables over time. We also found 134 experimental studies (i.e., randomized controlled trials of HIV interventions), but of these only 9 (6.7 %) report the results of mediation analyses that might provide evidence for the validity of health behavior theories in predicting sexual behavior. Results show little convergent support across both types of studies for most traditional, theoretical predictors of sexual behavior. This suggests that the field must expand the body of empirical work that utilizes the most rigorous study designs to test our theoretical assumptions. The inconsistent results of existing research would indicate that current theoretical models of sexual risk behavior are inadequate, and may require expansion or adaptation.

The dynamics of the give and take between therapist and client(s) is frequently of interest to therapy process researchers. Characterizing the ways that therapists respond to clients and clients respond to therapists can be challenging in therapeutic encounters involving a single therapist and a single client. The complexity of this challenge increases as the number of people involved in a therapeutic encounter increases not only because there are more people responding to one another but also because the patterns of responding can become more complex. This manuscript demonstrates how dyadic cross-lagged panel models can be extended to psychotherapeutic encounters involving 3 people and used to test processes that exist between dyadic subsets of the larger group as well as the group as one cohesive unit. Three hundred seventy-nine talk turns of fundamental frequency from a couple therapy session were modeled using 3 dyadic cross-lagged panel models, and each individual's respiratory sinus arrhythmia (RSA) was treated as a moderator. Although the regression coefficients for each dyadic subset (e.g., therapist-husband) were nonsignificant, an eigenvalue/eigenvector decomposition of the regression coefficients from the 3 dyadic cross-lagged panel models suggests that interdependence exists at the level of the whole group (i.e., therapist-husband-wife) rather than between pairs of individuals within the group (e.g., husband-wife). Further, an interaction involving husband's RSA suggested that interdependence involving the husband ceased when the husband displayed greater regulatory effort. This combination of statistical methods allows for clearly distinguishing between dyadic therapeutic processes and group-level therapeutic processes. (PsycINFO Database Record

Background Epidemiological studies have linked exposures to ambient fine particulate matter (PM2.5) and traffic with autonomic nervous system imbalance (ANS) and cardiac pathophysiology, especially in individuals with preexisting disease. It is unclear whether metabolic syndrome (MetS) increases susceptibility to the effects of PM2.5. We hypothesized that exposure to traffic-derived primary and secondary organic aerosols (P + SOA) at ambient levels would cause autonomic and cardiovascular dysfunction in rats exhibiting features of MetS. Male Sprague Dawley (SD) rats were fed a high-fructose diet (HFrD) to induce MetS, and exposed to P + SOA (20.4 ± 0.9 μg/m3) for 12 days with time-matched comparison to filtered-air (FA) exposed MetS rats; normal diet (ND) SD rats were separately exposed to FA or P + SOA (56.3 ± 1.2 μg/m3). Results In MetS rats, P + SOA exposure decreased HRV, QTc, PR, and expiratory time overall (mean effect across the entirety of exposure), increased breathing rate overall, decreased baroreflex sensitivity (BRS) on three exposure days, and increased spontaneous atrioventricular (AV) block Mobitz Type II arrhythmia on exposure day 4 relative to FA-exposed animals receiving the same diet. Among ND rats, P + SOA decreased HRV only on day 1 and did not significantly alter BRS despite overall hypertensive responses relative to FA. Correlations between HRV, ECG, BRS, and breathing parameters suggested a role for autonomic imbalance in the pathophysiologic effects of P + SOA among MetS rats. Autonomic cardiovascular responses to P + SOA at ambient PM2.5 levels were pronounced among MetS rats and indicated blunted vagal influence over cardiovascular physiology. Conclusions Results support epidemiologic findings that MetS increases susceptibility to the adverse cardiac effects of ambient-level PM2.5, potentially through ANS imbalance. Electronic supplementary material The online version of this article (doi:10.1186/s12989-017-0196-2) contains supplementary material, which is available to authorized users.

The aim of this study is to evaluate the accuracy of capillary hemoglobin (Hb) measurements in detecting anemia among low-income toddlers (aged 12–35 months) and pregnant women. In analyses of data among toddlers from Kansas City (n = 402) and St. Louis, Missouri (n = 236), and pregnant women at

Researchers commonly use repeated-measures actor-partner interdependence models (RM-APIM) to understand how romantic partners change in relation to one another over time. However, traditional interpretations of the results of these models do not fully or correctly capture the dyadic temporal patterns estimated in RM-APIM. Interpretation of results from these models largely focuses on the meaning of single-parameter estimates in isolation from all the others. However, considering individual coefficients separately impedes the understanding of how these associations combine to produce an interdependent pattern that emerges over time. Additionally, positive within-person, or actor, effects are commonly misinterpreted as indicating growth from one time point to the next when they actually represent decline. We suggest that change-as-outcome RM-APIMs and vector field diagrams (VFDs) can be used to improve the understanding and presentation of dyadic patterns of association described by standard RM-APIMs. The current article briefly reviews the conceptual foundations of RM-APIMs, demonstrates how change-as-outcome RM-APIMs and VFDs can aid interpretation of standard RM-APIMs, and provides a tutorial in making VFDs using multilevel modeling. (PsycINFO Database Record

Background: Surgery is considered to be the first line treatment for solid tumours. Recently, retrospective studies reported that general anaesthesia was associated with worse long-term cancer-free survival when compared with regional anaesthesia. This has important clinical implications; however, the mechanisms underlying those observations remain unclear. We aim to investigate the effect of anaesthetics isoflurane and propofol on prostate cancer malignancy. Methods: Prostate cancer (PC3) cell line was exposed to commonly used anaesthetic isoflurane and propofol. Malignant potential was assessed through evaluation of expression level of hypoxia-inducible factor-1α (HIF-1α) and its downstream effectors, cell proliferation and migration as well as development of chemoresistance. Results: We demonstrated that isoflurane, at a clinically relevant concentration induced upregulation of HIF-1α and its downstream effectors in PC3 cell line. Consequently, cancer cell characteristics associated with malignancy were enhanced, with an increase of proliferation and migration, as well as development of chemoresistance. Inhibition of HIF-1α neosynthesis through upper pathway blocking by a PI-3K-Akt inhibitor or HIF-1α siRNA abolished isoflurane-induced effects. In contrast, the intravenous anaesthetic propofol inhibited HIF-1α activation induced by hypoxia or CoCl2. Propofol also prevented isoflurane-induced HIF-1α activation, and partially reduced cancer cell malignant activities. Conclusions: Our findings suggest that modulation of HIF-1α activity by anaesthetics may affect cancer recurrence following surgery. If our data were to be extrapolated to the clinical setting, isoflurane but not propofol should be avoided for use in cancer surgery. Further work involving in vivo models and clinical trials is urgently needed to determine the optimal anaesthetic regimen for cancer patients.

As the leading culprit in cancer incidence for American men, prostate cancer continues to pose significant diagnostic, prognostic, and therapeutic tribulations for clinicians. The vast spectrum of disease behavior warrants better molecular classification to facilitate the development of more robust biomarkers that can identify the more aggressive and clinically significant tumor subtypes that require treatment. The untranslated portion of the human transcriptome, namely noncoding RNAs (ncRNA), is emerging as a key player in cancer initiation and progression and boasts many attractive features for both biomarker and therapeutic research. Genetic linkage studies show that many ncRNAs are located in cancer-associated genomic regions that are frequently deleted or amplified in prostate cancer, whereas aberrant ncRNA expression patterns have well-established links with prostate tumor cell proliferation and survival. The dysregulation of pathways controlled by ncRNAs results in a cascade of multicellular events leading to carcinogenesis and tumor progression. The characterization of RNA species, their functions, and their clinical applicability is a major area of biologic and clinical importance. This review summarizes the growing body of evidence, supporting a pivotal role for ncRNAs in the pathogenesis of prostate cancer. We highlight the most promising ncRNA biomarkers for detection and risk stratification and present the state-of-play for RNA-based personalized medicine in treating the “untreatable” prostate tumors. Clin Cancer Res; 20(1); 35–43. ©2013 AACR.

STUDY OBJECTIVE To determine if self-reported sleep duration was associated with weight-control behaviors among US high school students. DESIGN National Youth Risk Behavior Survey. SETTING United States, 2007. PARTICIPANTS US high school students (N = 12,087). MEASUREMENTS Students were asked if they had engaged in several weight-control behaviors during the 30 days before the survey to lose or maintain weight. Self-reported sleep duration categories included very short (≤ 5 h), short (6 or 7 h), referent moderate (8 or 9 h), and long (≥ 10 h). Sex-specific logistic regression analyses with race/ethnicity, grade, and body mass index category as covariates were conducted using SUDAAN to account for complex study design. RESULTS Approximately half the students reported short sleep duration (51.8% of males and 54.3% of females), whereas very short sleep durations were reported by another 14.8% of males and 16.9% of females. Among males, very short sleepers were significantly (P < 0.05) more likely than moderate sleepers to report dieting (36.3% versus 26.1%), fasting (14.2% versus 4.3%), and purging (4.3% versus 1.1%) to lose or maintain weight during the 30 days before the survey. Among females, the respective very short, short, and moderate sleepers varied (P < 0.05) in dieting (59.9%, 55.0%, and 47.5% respectively), fasting (28.3%, 15.2%, and 10.3%, respectively), and taking diet pills (13.3%, 6.8%, and 4.3%, respectively). Prevalence of purging was significantly higher only for very short sleepers (12.3%, 6.0%, and 3.9%, respectively). CONCLUSION Self-reported short sleep duration was associated with dieting and three unhealthy weight-control behaviors in this population. If our findings are confirmed, intervention studies should be conducted to examine the effect of educational interventions.

Context Pulmonary large cell carcinoma (LCC) includes tumors not readily diagnosed as adenocarcinoma (ADC) or squamous cell carcinoma on morphologic grounds, without regard to immunophenotype, according to the World Health Organization (WHO). This ambiguous designation may cause confusion over selection of mutation testing and directed therapies. Several groups have proposed the use of immunohistochemistry (IHC) to recategorize LCC as ADC or squamous cell carcinoma; however, it remains unclear if strictly defined LCCs are a clinicopathologically distinct lung tumor subset. Objective —To compare the pathologic, molecular, and clinical features of 2 morphologically similar tumors: solid-subtype ADC and LCC. Design Tumors were included on the basis of solid growth pattern; tumors with squamous or neuroendocrine differentiation were excluded. Solid ADC (n = 42) and LCC (n = 57) were diagnosed by using WHO criteria (5 intracellular mucin droplets in ≥2 high-power fields for solid ADC) and tested for KRAS, EGFR, and ALK alterations. Results —Both solid ADC and LCC groups were dominated by tumors with “undifferentiated”-type morphology and both had a high frequency of thyroid transcription factor 1 expression. KRAS was mutated in 38% of solid ADCs versus 43% of LCCs (P = .62). One ALK-rearranged and 1 EGFR-mutated tumor were detected in the solid ADC and LCC groups, respectively. There were no significant differences in clinical features or outcomes; the prevalence of smoking in both groups was greater than 95%. Conclusions Other than a paucity of intracellular mucin, LCC lacking squamous or neuroendocrine differentiation is indistinguishable from solid-subtype ADC. We propose the reclassification of these tumors as mucin-poor solid adenocarcinomas.

Urological malignancies (cancers of the prostate, bladder, kidney and testes) account for 15% of all human cancers and more than 500,000 deaths worldwide each year. This group of malignancies is spread across multiple generations, affecting the young (testicular) through middle and old-age (kidney, prostate and bladder). Like most human cancers, urological cancers are characterized by widespread epigenetic insult, causing changes in DNA hypermethylation and histone modifications leading to silencing of tumor suppressor genes and genomic instability. The inherent stability yet dynamic plasticity of the epigenome lends itself well to therapeutic manipulation. Epigenetic changes are amongst the earliest lesions to occur during carcinogenesis and are essentially reversible (unlike mutations). For this reason, much attention has been placed over the past two decades on deriving pharmacological compounds that can specifically target and reverse such epi-mutations, either halting cancer on its developmental trajectory or reverting fully formed cancers to a more clinically manageable state. This review discusses DNA methyltransferase and histone deacetylase inhibitors that have been extensively studied in preclinical models and clinical trials for advanced and metastatic urological cancers.

// Eamon P. Mulvaney 1 , Christine Shilling 3 , Sarah B. Eivers 1 , Antoinette S. Perry 1 , Anders Bjartell 4 , Elaine W. Kay 3 , R. William Watson 2 , B. Therese Kinsella 1 1 UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland 2 UCD School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland 3 Department of Pathology, Beaumont Hospital and Royal College of Surgeons, Dublin, Ireland 4 Department of Translational Medicine, Division of Urological Cancers, Skane University Hospital Malmo, Lund University, Sweden Correspondence to: B. Therese Kinsella, email: therese.kinsella@ucd.ie Keywords: thromboxane, receptor, prostate, cancer, prostanoid Received: June 09, 2016 Accepted: September 19, 2016 Published: September 26, 2016 ABSTRACT The prostanoid thromboxane (TX)A 2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA 2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown. This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

An emerging HIV epidemic can be seen among men who have sex with men (MSM) in Vietnam, with prevalence as high as 18%. Transactional sex represents a risk factor for HIV transmission/acquisition among MSM globally, particularly in urban contexts, but remains largely underinvestigated in Ho Chi Minh City (HCMC), Vietnam. In 2010, 23 MSM who reported exchanging sex for money in the last month completed a brief survey and semistructured qualitative interview at The Life Centre, a non-governmental organization in HCMC, to assess sociodemographics, individual- and structural-level HIV risk factors and explore acceptable future prevention interventions. Participants' mean age was 24 years. Equal proportions of respondents self-identified as heterosexual/straight, homosexual/gay, and bisexual. Participants had a mean of 158 male clients in the past year, with a median of 60 male clients in the past year (interquartile range [IQR]=70) and reported inconsistent condom use and inaccurate perceptions of HIV risk. Nearly half of the sample reported engaging in unprotected anal sex with a male partner in the past 12 months and one-third with a male client. Major themes that emerged for HIV prevention interventions with male sex workers were those that: (1) focused on individual factors (drug and alcohol use, barriers to condom use, knowledge of asymptomatic STIs, enhancement of behavioral risk-reduction skills, and addressing concomitant mental health issues); (2) incorporated interpersonal and relational contexts (led by peer educators, built interpersonal skills, attended to partner type and intimacy dynamics); and (3) considered the exogenous environments in which individual choices/relationships operate (stigma of being MSM in Vietnam, availability of alternative economic opportunities, and varied sexual venues). HIV prevention efforts are needed that address the specific needs of MSM who engage in transactional sex in HCMC. Universally, MSM endorsed HIV prevention interventions, suggesting a need and desire for efforts in this context.

Objective The efficacy of docetaxel has recently been shown to be increased under hypoxic conditions through the down-regulation of hypoxia-inducible-factor 1α (HIF1A). Overexpression of the hypoxia-responsive gene class III β-tubulin (TUBB3) has been associated with docetaxel resistance in a number of cancer models. We propose that administration of docetaxel to prostate patients has the potential to reduce the hypoxic response through HIF1A down-regulation and that TUBB3 down-regulation participates in sensitivity to docetaxel. Methods The cytotoxic effect of docetaxel was determined in both 22Rv1 and DU145 prostate cancer cell lines and correlated with HIF1A expression levels under aerobic and hypoxic conditions. Hypoxia-induced chemoresistance was investigated in a pair of isogenic docetaxel-resistant PC3 cell lines. Basal and hypoxia-induced TUBB3 gene expression levels were determined and correlated with methylation status at the HIF1A binding site. Results Prostate cancer cells were sensitive to docetaxel under both aerobic and hypoxic conditions. Hypoxic cytotoxicity of docetaxel was consistent with a reduction in detected HIF1A levels. Sensitivity correlated with reduced basal and hypoxia-induced HIF1A and TUBB3 expression levels. The TUBB3 HIF1A binding site was hypermethylated in prostate cell lines and tumor specimens, which may exclude transcription factor binding and induction of TUBB3 expression. However, acquired docetaxel resistance was not associated with TUBB3 overexpression. Conclusion These data suggest that the hypoxic nature of a tumor may have relevance as regard to their response to docetaxel. Further investigation into the nature of this relationship may allow identification of novel targets to improve tumor control in prostate cancer patients.

IGFBP7 belongs to a family of insulin-like growth factor-1 regulatory binding proteins. IGFBP7 hypermethylation is associated with its down-regulation in various carcinomas. In prostate cancer IGFBP7 down-regulation has been widely reported but to our knowledge the mechanisms behind this event are unknown. We performed a denaturing high performance liquid chromatography screening and validation strategy to profile the methylation status of IGFBP7 in prostate cancer.We combined denaturing high performance liquid chromatography and bisulfite sequencing to examine IGFBP7 methylation in a panel of prostate cancer cell lines. Quantitative methylation specific polymerase chain reaction was used to determine methylation levels in prostate tissue specimens of primary prostate cancer, histologically benign prostate adjacent to tumor, high grade prostatic intraepithelial neoplasia and benign prostatic hyperplasia. IGFBP7 gene expression was measured by quantitative methylation specific polymerase chain reaction in cell lines and tissue specimens.IGFBP7 was methylated in the 4 prostate cancer cell lines DU145, LNCaP, PC-3 and 22RV1. Quantitative methylation specific polymerase chain reaction analysis revealed that promoter methylation was associated with decreased IGFBP7 expression. Quantitative methylation specific polymerase chain reaction showed that IGFBP7 methylation was more frequently detected in prostate cancer (60% (31/52)) and high grade prostatic intraepithelial neoplasia (40% (6/15)) samples compared to histologically benign prostate adjacent to tumor (10%) and benign prostatic hyperplasia (0%) samples.To our knowledge this is the first report of aberrant IGFBP7 promoter hypermethylation and concurrent IGFBP7 gene silencing in prostate cancer cell lines. Results demonstrate that CpG methylation of IGFBP7 may represent a novel biomarker of prostate cancer and pre-invasive neoplasms. Thus, future examination of IGFBP7 methylation and expression in a larger patient cohort, including bodily fluids, is justified to further evaluate its role in a diagnostic and prognostic setting.

Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.

Our study assesses the relationships between self-reported adverse childhood experiences (ACEs) (including sexual, physical, or verbal abuse, along with household dysfunction including parental separation or divorce, domestic violence, mental illness, substance abuse, or incarcerated household member) and unemployment status in five US states in 2009.We examined these relationships using the 2009 Behavioral Risk Factor surveillance system survey data from 17,469 respondents (aged 18-64 years) who resided in five states, completed the ACE Questionnaire, and provided socio-demographic and social support information. We also assessed the mediation of these relationships by respondents' educational attainment, marital status, and social support.About two-third of respondents reported having had at least one ACEs, while 15.1% of men and 19.3% of women reported having had ≥4 ACEs. Among both men and women, the unemployment rate in 2009 was significantly higher among those who reported having had any ACE than among those who reported no ACEs (p0.05). Educational attainment, marital status, and social support mediated the relationship between ACEs and unemployment, particularly among women.ACEs appear to be associated with increased risk for unemployment among men and women. Further studies may be needed to better understand how education, marital status, and social support mediate the association between multiple ACEs and unemployment.

To investigate whether level of positive mental health complements mental illness in predicting students at risk for suicidal behavior and impaired academic performance.A sample of 5,689 college students participated in the 2007 Healthy Minds Study and completed an Internet survey that included the Mental Health Continuum-Short Form and the Patient Health Questionnaire screening scales for depression and anxiety disorders, questions about suicide ideation, plans, and attempts, and academic impairment.Just under half (49.3%) of students were flourishing and did not screen positive for a mental disorder. Among students who did, and those who did not, screen for a mental disorder, suicidal behavior and impaired academic performance were lowest in those with flourishing, higher among those with moderate, and highest in those with languishing mental health.Positive mental health complements mental disorder screening in mental health surveillance and prediction of suicidal behavior and impairment of academic performance.

Sleep disturbances are associated with an increased risk for many chronic diseases and unhealthy behaviors. A history of adverse childhood experiences (ACEs) is also associated with similar adult health outcomes. We studied the relationship between multiple ACEs and the likelihood of experiencing self-reported sleep disturbances in adulthood.We used data from the adverse childhood experiences (ACE) study, a retrospective cohort study of 17,337 adult health maintenance organization members in California who completed a survey about eight ACEs, which included childhood abuse and growing up with various forms of household dysfunction. The self-reported sleep disturbances measured included ever having trouble falling or staying asleep and feeling tired after a good night's sleep. We used an integer count of the number of ACEs (the ACE score) to assess the cumulative impact of these experiences on the likelihood of self-reported sleep disturbances.Thirty-three percent of the cohort reported trouble falling or staying asleep, while 24% reported feeling tired after sleeping. All eight ACE categories were associated with an increased likelihood of self-reported sleep disturbances (p0.05). Compared to persons with an ACE score of 0, those with an ACE score ≥ 5 were 2.1 (95% CI: 1.8-2.4) times more likely to report trouble falling or staying asleep and 2.0 (95% CI: 1.7-2.3) times more likely to report feeling tired even after a good night's sleep. The trend for increasing odds for both types of self-reported sleep disturbance with increasing ACE scores was statistically significant (p0.0001).Adverse childhood experiences were associated with self-reported sleep disturbances in adulthood, and the ACE score had a graded relationship to these sleep disturbances. A history of ACEs should be obtained for patients with self-reported sleep disturbances to coordinate services that ameliorate the long-term effects of these events.