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We examined relationships between resilience resources (optimism, social support, and neighborhood social cohesion) and cardiovascular disease (CVD) incidence and assessed potential effect-measure modification by psychosocial risk factors (e.g., stress, depression) among adults without CVD in 3 cohort studies (2000-2018): the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study. We fitted adjusted Cox models accounting for within-neighborhood clustering while censoring at dropout or non-CVD death. We assessed for effect-measure modification by psychosocial risks. In secondary analyses, we estimated standardized risk ratios using inverse-probability-weighted Aalen-Johansen estimators to account for confounding, dropout, and competing risks (non-CVD deaths) and obtained 95% confidence intervals (CIs) using cluster bootstrapping. For high and medium (versus low) optimism (n = 6,243), adjusted hazard ratios (HRs) for incident CVD were 0.94 (95% CI: 0.78, 1.13) and 0.90 (95% CI: 0.75, 1.07), respectively. Corresponding HRs were 0.88 (95% CI: 0.74, 1.04) and 0.92 (95% CI: 0.79, 1.06) for social support (n = 7,729) and 1.10 (95% CI: 0.94, 1.29) and 0.99 (95% CI: 0.85, 1.16) for social cohesion (n = 7,557), respectively. Some psychosocial risks modified CVD HRs. Secondary analyses yielded similar findings. For optimism and social support, an inverse relationship was frequently most compatible with the data, but a positive relationship was also compatible. For neighborhood social cohesion, positive and null relationships were most compatible. Thus, specific resilience resources may be potential intervention targets, especially among certain subgroups.

PurposeSocial support may have benefits on cardiovascular health (CVH). CVH is evaluated using seven important metrics (Life's Simple 7; LS7) established by the American Heart Association (e.g., smoking, diet). However, evidence from longitudinal studies is limited and inconsistent. The objective of this study is to examine the longitudinal relationship between social support and CVH, and assess whether psychosocial risks (e.g., anger and stress) modify the relationship in a racially/ethnically diverse population.MethodsParticipants from three harmonized cohort studies - Jackson Heart Study, Mediators of Atherosclerosis in South Asians Living in America, and Multi-Ethnic Study of Atherosclerosis - were included. Repeated-measures modified Poisson regression models were used to examine the overall relationship between social support (in tertiles) and CVH (LS7 metric), and to assess for effect modification by psychosocial risk.ResultsAmong 7724 participants, those with high (versus low) social support had an adjusted prevalence ratio (aPR) and 95% confidence interval (CI) for ideal or intermediate (versus poor) CVH of 0.99 (0.96-1.03). For medium (versus low) social support, the aPR (95% CI) was 1.01 (0.98-1.05). There was evidence for modification by employment and anger. Those with medium (versus low) social support had an aPR (95% CI) of 1.04 (0.99-1.10) among unemployed or low anger participants. Corresponding results for employed or high anger participants were 0.99 (0.94-1.03) and 0.97 (0.91-1.03), respectively.ConclusionOverall, we observed no strong evidence for an association between social support and CVH. However, some psychosocial risks may be modifiers. Prospective studies are needed to assess the social support-CVH relationship by psychosocial risks in racially/ethnically diverse populations.

ObjectiveExamine prospective relationships between erectile dysfunction (ED) drugs EDand CD4 and CD8 T-cells, and immune markers among men who have sex with men (MSM).MethodsData from Multicenter AIDS Cohort Study, an observational prospective cohort study, with semi-annual follow-ups conducted in four U.S. centers from 1998 onwards was used. Marginal structural models using g-computation was fitted to estimate the mean differences for the effects of self-reported ED drug use on CD4 and CD8 T-cell outcomes and immune biomarkers.ResultsTotal of 1,391 men with HIV (MWH) and 307 men without HIV (MWOH) was included. Baseline mean CD4 cell count among MWH and MWOH was 499.9 cells/μL and 966.7 cells/μL, respectively. At baseline, 41.8% of MWH were virally suppressed. ED drug users reported a mean of 44.4 months of exposure to ED drugs. ED drug use was associated with increased CD4 cell outcomes among MWH but not MWOH. Mean differences in CD4 cell counts after 1 year of ED drug use was 57.6 cells/μL and increased to 117.7 after 10 years among MWH. CD8 counts were higher in ED drug users among MWH over 10 years than non-users; no consistent differences were found among MWOH. ED drug use appeared to reduce immune marker levels, such as IL-6 and increase markers, such as IL-10. We observed similar effects of ED drug use on biomarker levels among MWOH.ConclusionLong-term use of ED drugs do not adversely affect immune function among MWH or MWOH. Future studies on the relationships between different types of ED drugs and effects on T-cell subtypes are warranted.

BackgroundPsychosocial stressors increase the risks for cardiovascular disease across diverse populations. However, neighborhood level resilience resources may protect against poor cardiovascular health (CVH). This study used data from three CVH cohorts to examine longitudinally the associations of a resilience resource, perceived neighborhood social cohesion (hereafter referred to as neighborhood social cohesion), with the American Heart Association's Life's Simple 7 (LS7), and whether psychosocial stressors modify observed relationships.MethodsWe examined neighborhood social cohesion (measured in tertiles) and LS7 in the Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis, and Mediators of Atherosclerosis in South Asians Living in America study. We used repeated-measures, modified Poisson regression models to estimate the relationship between neighborhood social cohesion and LS7 (primary analysis, n = 6,086) and four biological metrics (body mass index, blood pressure, cholesterol, blood glucose; secondary analysis, n = 7,291). We assessed effect measure modification by each psychosocial stressor (e.g., low educational attainment, discrimination).ResultsIn primary analyses, adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) for ideal/intermediate versus poor CVH among high or medium (versus low) neighborhood social cohesion were 1.01 (0.97-1.05) and 1.02 (0.98-1.06), respectively. The psychosocial stressors, low education and discrimination, functioned as effect modifiers. Secondary analyses showed similar findings. Also, in the secondary analyses, there was evidence for effect modification by income.ConclusionWe did not find much support for an association between neighborhood social cohesion and LS7, but did find evidence of effect modification. Some of the effect modification results operated in unexpected directions. Future studies should examine neighborhood social cohesion more comprehensively and assess for effect modification by psychosocial stressors.

We investigated the longitudinal relationship between erectile dysfunction (ED) drug use with behavioral factors, including substance use and sexual activities in men who have sex with men from the Multicenter AIDS Cohort Study during 1998-2016 (n = 1636). We used a bivariate random-intercept model to evaluate ED drug use along with other behavioral factors to assess relationships between the two outcomes over time on a population level and also at the individual level. Average ED drug use among men who have sex with men (MSM) with HIV was positively correlated with average use of marijuana (r = .19), poppers (r = .27), and stimulants (r = .25). In this group, testosterone use (r = .32), multiple partners (r = .41), insertive anal intercourse with condom (r = .40), and insertive anal intercourse without condom (r = .43) all showed moderate correlations over time with average ED use (p

Simple Summary: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, but effective biomarkers has yet been developed. Here, we identified ATP1A1 as prognostic marker and therapeutic target via integrated analysis of DNA methylome and transcriptome of TNBC. These data will provide new insight into not only developing specific biomarker for TNBC but also understanding TNBC pathogenesis. Dysregulated DNA methylation in cancer is critical in the transcription machinery associated with cancer progression. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, but no treatment targeting TNBC biomarkers has yet been developed. To identify specific DNA methylation patterns in TNBC, methyl-binding domain protein 2 (MBD) sequencing data were compared in TNBC and the three other major breast cancer subtypes. Integrated analysis of DNA methylation and gene expression identified a gene set showing a correlation between DNA methylation and gene expression. ATPase Na+/K+-transporting subunit alpha 1 (ATP1A1) was found to be specifically hypomethylated in the coding sequence (CDS) region and to show increased expression in TNBC. The Cancer Genome Atlas (TCGA) database also showed that hypomethylation and high expression of ATP1A1 were strongly associated with poor survival in patients with TNBC. Furthermore, ATP1A1 knockdown significantly reduced the viability and tumor-sphere formation of TNBC cells. These results suggest that the hypomethylation and overexpression of ATP1A1 could be a prognostic marker in TNBC and that the manipulation of ATP1A1 expression could be a therapeutic target in this disease. [ABSTRACT FROM AUTHOR]

Introduction: Displaced populations face disproportionately high risk of communicable disease outbreaks given the strains of travel, health care circumstances in their country of origin, and limited access to health care in receiving countries. Study Objective: Understanding the role of demographic characteristics in outbreaks is important for timely and efficient control measures. Accordingly, this study assesses chickenpox outbreaks in three large refugee camps on mainland Greece from 2016 – 2017, using clinical line-list data from Médecins du Monde (MdM) clinics. Methods: Clinical line-list data from MdM clinics operating in Elliniko, Malakasa, and Raidestos camps in mainland Greece were used to characterize chickenpox outbreaks in these camps. Logistic regression was used to compare the odds of chickenpox by sex, camp, and yearly increase in age. Incidences were calculated for age categories and for sex for each camp outbreak. Results: Across camps, the median age was 19 years (IQR: 7.00 - 30.00 years) for all individuals and five years (IQR: 2.00 - 8.00 years) for cases. Males were 55.94% of the total population and 51.32% of all cases. There were four outbreaks of chickenpox across Elliniko (n = 1), Malakasa (n = 2), and Raidestos (n = 1) camps. The odds of chickenpox when controlling for age and sex was lower for Malakasa (OR = 0.46; 95% CI, 0.38 - 0.78) and Raidestos (OR = 0.36; 95% CI, 0.24 - 0.56) when compared Elliniko. Odds of chickenpox were comparable between Malakasa and Raidestos (OR = 1.49; 95% CI, 0.92 - 2.42). Across all camps, the highest incidence was among children zero-to-five years of age. The sex-specific incidence chickenpox was higher for males than females in Elliniko and Malakasa, while the incidence was higher among females in Raidestos. Conclusion: As expected, individuals five years of age and under made up the majority of chickenpox cases. However, 12% of cases were teenagers or older, highlighting the need to consider atypical age groups in vaccination strategies and control measures. To support both host and displaced populations, it is important to consider risk-reduction needs for both groups. Including host communities in vaccination campaigns and activities can help reduce the population burden of disease for both communities. [ABSTRACT FROM AUTHOR]

The purpose of this meta-analysis was to examine the effectiveness of aerobic exercise interventions on cardiopulmonary function and body composition in women with breast cancer. Of 24 relevant studies reviewed, 10 studies (N = 588) met the inclusion criteria. The findings indicated that aerobic exercise significantly improved cardiopulmonary function as assessed by absolute V[O.sub.2] peak (standardized mean difference [SMD] .916, p < .001), relative V[O.sub.2] peak (SMD .424, p < .05), and 12-minute walk test (SMD .502, p < .001). Similarly, aerobic exercise significantly improved body composition as assessed by percentage body fat (SMD -.890, p < .001), but body weight and lean body mass did not change significantly. Aerobic exercise during or after cancer adjuvant therapy seems to be an effective means of improving cardiopulmonary function and decreasing percentage body fat in women with breast cancer. Further studies are needed to examine the long-term benefits of aerobic exercise. Keywords: exercise; meta-analysis; breast cancer; cardiopulmonary function; body composition

Chong, Seon Ah, Soo Young Hong, Seok Jun Moon, Jee Won Park, Jeong-Hee Hong, Jeong Mi An, Syng-III Lee, Dong Min Shin, and Jeong Taeg Seo. Partial inhibition of SERCA is responsible for extracellular [Ca.sup.2.sup.+] dependence of [Al[F.sup.-.sub.4]-induced [[Ca.sup.2.sup.+].sub.i] oscillations in rat pancreatic acinar cells. Am J Physiol Cell Physiol 285: C1142-C1149, 2003. First published July 23, 2003; 10.1152/ajpcell.00566.2002. --[Al[F.sup.-.sub.4] is known to generate oscillations in intracellular [Ca.sup.2.sup.+] concentration [([Ca.sup.2.sup.+].sub.i)] by activating G proteins in many cell types. However, in rat pancreatic acinar cells, [Al[F.sup.-.sub.4]evoked [[Ca.sup.2.sup.+].sub.i] oscillations were reported to be dependent on extracellular [Ca.sup.2.sup.+], which contrasts with the [[Ca.sup.2.sup.+].sub.i] oscillations induced by cholecystokinin (CCK). Therefore, we investigated the mechanisms by which [Al[F.sup.-.sub.4] generates extracellular [Ca.sup.2.sup.+]-dependent [[Ca.sup.2.sup.+].sub.i] oscillations in rat pancreatic acinar cells. [Al[F.sup.-.sub.4]-induced [[Ca.sup.2.sup.+].sub.i] oscillations were stopped rapidly by the removal of extracellular [Ca.sup.2.sup.+] and were abolished on the addition of 20 mM caffeine and 2[micro]M thapsigargin, indicating that [Ca.sup.2.sup.+] influx plays a crucial role in maintenance of the oscillations and that an inositol 1,4,5-trisphos-phate-sensitive [Ca.sup.2.sup.+] store is also required. The amount of [Ca.sup.2.sup.+] in the intracellular [Ca.sup.2.sup.+] store was decreased as the [Al[F.sup.-.sub.4]-induced [[Ca.sup.2.sup.+].sub.i] oscillations continued. Measurement of [sup.45][Ca.sup.2.sup.+] influx into isolated microsomes revealed that [Al[F.sup.-.sub.4] directly inhibited sarco/endoplasmic reticulum [Ca.sup.2.sup.+]-ATPase (SERCA). The activity of plasma membrane [Ca.sup.2.sup.+]-ATPase during [Al[F.sup.-.sub.4] stimulation was not significantly different from that during CCK stimulation. After partial inhibition of SERCA with 1 nM thapsigargin, 20 pM CCK-evoked [[Ca.sup.2.sup.+].sub.i] oscillations were dependent on extracellular [Ca.sup.2.sup.+]. This study shows that [Al[F.sup.-.sub.4] induces [[Ca.sup.2.sup.+].sub.i] oscillations, probably by inositol 1,4,5-trisphosphate production via G protein activation but that these oscillations are strongly dependent on extracellular [Ca.sup.2.sup.+] as a result of the partial inhibition of SERCA. cholecystokinin; plasma membrane adenosine 5'-triphosphatase; G proteins; caffeine