A microRNA expression and regulatory element activity atlas of the mouse immune system.

To better define the control of immune system regulation, we generated an atlas of microRNA (miRNA) expression from 63 mouse immune cell populations and connected these signatures with assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation followed by sequencing (ChIP-seq) and nascent RNA profiles to establish a map of miRNA promoter and enhancer usage in immune cells. miRNA complexity was relatively low, with >90% of the miRNA compartment of each population comprising <75 miRNAs; however, each cell type had a unique miRNA signature. Integration of miRNA expression with chromatin accessibility revealed putative regulatory elements for differentially expressed miRNAs, including miR-21a, miR-146a and miR-223. The integrated maps suggest that many miRNAs utilize multiple promoters to reach high abundance and identified dominant and divergent miRNA regulatory elements between lineages and during development that may be used by clustered miRNAs, such as miR-99a/let-7c/miR-125b, to achieve distinct expression. These studies, with web-accessible data, help delineate the cis-regulatory elements controlling miRNA signatures of the immune system.

Linking Cardiac Psychology and Cardiovascular Medicine via Self-Determination Theory and Shared Decision-Making.

Despite considerable progress in recent years, research in cardiac psychology is not widely translated into routine practice by clinical cardiologists or clinical health psychologists. Self-determination theory (SDT), which addresses how basic psychological needs of autonomy, competence, and relatedness contribute to the internalization of motivation, may help bridge this research-practice gap through its application to shared decision-making (SDM). This narrative review discusses the following: (a) brief background information on SDT and SDM, (b) the application of SDT to health behavior change and cardiology interventions, and (c) how SDT and SDM may be merged using a dissemination and implementation (D&I) framework. We address barriers to implementing SDM in cardiology, how SDM and SDT address the need for respect of patient autonomy, and how SDT can enhance D&I of SDM interventions through its focus on autonomy, competence, and relatedness and its consideration of other constructs that facilitate the internalization of motivation.

Meaning Salience and Meaning in Life Prospectively Predict Lower Distress During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic is a widespread source of stress with adverse mental health impacts. Meaning in life, both as a trait and as momentary awareness of what is personally meaningful (meaning salience), is associated with positive health outcomes and may buffer against the deleterious effects of stress. PURPOSE: This project examines prospective associations between baseline meaning salience (daily, post-laboratory stressor) and meaning in life with perceived stress during COVID-19. METHODS: A community sample of healthy adults (n = 147) completed a laboratory stress protocol in 2018-2019, where perceived stress, meaning in life, and meaning salience (daily, post-stressor) were assessed. During April and July 2020 (n = 95, and 97, respectively), participants were re-contacted and reported perceived stress. General linear mixed-effects models accounting for repeated measures of stress during COVID-19 were conducted. RESULTS: Partial correlations holding constant baseline perceived stress showed that COVID-19 perceived stress was correlated with daily meaning salience (r = -.28), post-stressor meaning salience (r = -.20), and meaning in life (r = -.22). In mixed-effects models, daily and post-stressor meaning salience and higher meaning in life, respectively, predicted lower perceived stress during COVID-19, controlling for age, gender, and baseline perceived stress. CONCLUSIONS: Individuals more capable of accessing meaning when exposed to laboratory stress reported lower perceived stress during a global health crisis. Despite study limitations concerning generalizability, results support meaning in life and meaning salience as important aspects of psychological functioning that may promote well-being by affecting stress appraisals and available resources for coping.

The COVID-19 pandemic is a widespread source of stress. Having a sense of meaning in life, or that you have goals in life and a sense that the things you do are worthwhile and significant, is an important part of psychological well-being and might help reduce stress. We collected data on 147 healthy adults in 2018­2019 regarding their stress levels, sense of meaning in life, and how often they were aware of their life's meaning on daily basis and after a stress task in the laboratory. We re-contacted these adults in both April and July 2020 to ask about their stress, and 95 adults responded. Adults who had higher meaning in life in 2018­2019 experienced less stress during the early months of the COVID-19 pandemic. Adults who were more aware of their life's meaning each day and immediately after a stress task in the laboratory also experienced less stress during the COVID-19 pandemic. Results from this study provide evidence that having a strong sense of meaning in life overall and being aware of your life's meaning each day and during times of stress, may promote psychological well-being and reduce stress during times when stress is widespread and abundant.

Mindfulness is inversely associated with psychological symptoms in long-term cardiac arrest survivors.

Identifying correlates of psychological symptoms in cardiac arrest (CA) survivors is a major research priority. In this longitudinal survey study, we evaluated associations between mindfulness, baseline psychological symptoms, and 1-year psychological symptoms in long-term CA survivors. We collected demographic and CA characteristics at baseline. At both timepoints, we assessed posttraumatic stress symptoms (PTS) through the PTSD Checklist-5 (PCL-5) and depression and anxiety symptoms through the Patient Health Questionnaire-4 (PHQ-4). At follow-up, we assessed mindfulness through the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R). We used adjusted linear regression to predict 1-year PCL-5 and PHQ-4 scores, with particular consideration of the CAMS-R as a cross-sectional correlate of outcome. We included 129 CA survivors (mean age: 52 years, 52% male, 98% white). At 1-year follow-up, in adjusted models, CAMS-R (ß: -0.35, p < 0.001) and baseline PCL-5 scores (ß: 0.56, p < 0.001) were associated with 1-year PCL-5 scores. CAMS-R (ß: -0.34, p < 0.001) and baseline PHQ-4 scores were associated with 1-year PHQ-4 scores (ß: 0.37, p < 0.001). In conclusion, mindfulness was inversely associated with psychological symptoms in long-term CA survivors. Future studies should examine the longitudinal relationship of mindfulness and psychological symptoms after CA.

Dimensions of depressive symptomatology in mothers derived from factor analyses.

PURPOSE: Subtypes of depression have been under studied in women during the peripartum period and the year after childbirth and delivery. Due to heterogeneity of depression, researchers have attempted to identify phenotypes of maternal and postpartum depression based on key symptoms that may represent underlying genes and biological etiology (Leuchter et al. Dialog Clinic Neurosci 16(4):525, 2014). METHODS: The current study collected self-report data from 587 women and utilized exploratory and confirmatory factor analyses (CFA) to identify subtypes of depression symptoms across two measures. RESULTS: Findings of the study showed that: (1) using the Beck Depression Inventory (BDI-II) and the Postpartum Depression Screening Scale (PDSS), a five-factor solution best fit the data in our sample of mothers with infants aged 4-14 months. The factors included: anxiety/thought disorder; cognitive depression; suicide; somatic/neurovegetative; and sleep [χ2 (454, N = 587) = 1102.61, p < 0.001, comparative fit index (CFI) = 0.93, Tucker Lewis index (TLI) = 0.92, root mean square error of approximation (RMSEA) = 0.05]; and (2) the following factors significantly positively predicted interview-based diagnosis of depression: cognitive symptoms of depression and sleep [χ2 (482, N = 587) = 1170.40, p < 0.001, TLI = 0.91, CFI = 0.93, RMSEA = 0.05]. CONCLUSIONS: Future research could assess the clinical benefits of screening for maternal mood disorders.

The relationship between sleep and opioids in chronic pain patients.

BACKGROUND: Sleep problems are common among chronic pain patients who take opioids. There are documented effects of opioids on sleep architecture; however, the long-term effects of opioids on sleep remain unknown. This study examined whether opioid-naïve participants have better sleep quality than current and previous chronic users of opioids. We also explored whether sleep differed between methadone and buprenorphine users, and whether amount of time since abstaining from opioids was associated with sleep quality. METHOD: Participants were 120 people with chronic pain (84.2% Caucasian, Mage = 42.0 years, SD = 11.44). They were in one of four groups of 30 participants each: (1) current users of methadone for opioid use disorder (OUD); (2) current users of buprenorphine for OUD; (3) a history of medication-assisted therapy for OUD but currently opioid-abstinent for at least 6 months; (4) those who have less than one month of cumulative lifetime opioids (opioid-naïve group). Only participants in group 1 and group 2 were taking opioids during the time of the study. Participants completed the Pittsburgh Sleep Quality Index and the SF-36. RESULTS: A MANCOVA revealed that all three groups with current or previous opioid use (i.e., groups 1-3) differed significantly from the opioid-naïve group (group 4) on sleep quality, sleep duration, sleep disturbances, and daytime dysfunction after controlling for sleep medications (all p < .05). For group 1 (methadone users), 2 (buprenorphine users), and 3 (prolonged abstinence), there were no statistically significant differences between each group. There was also a significant relationship between opioid-abstinent weeks and sleep disturbances in the opioid-abstinent group (r = - 0.604, p < .001). DISCUSSION: The results of this study suggest that opioids interfere with sleep quality, even after months of abstention. Further research into the long-term effects of opioids is warranted and may contribute further to the importance of addressing sleep problems in this population.

The Impact of Psychological Functioning on Cardiovascular Disease.

PURPOSE OF REVIEW: We report on recent findings pertaining to the relationship of both negative and positive indicators of psychological functioning with cardiovascular disease (CVD) and briefly describe possible mechanistic pathways to account for these relationships. RECENT FINDINGS: A body of observational literature suggests that (1) depression is predictive of CVD and is a consequence of CVD; (2) anxiety is related to CVD but the precise nature of this relationship remains unclear; and (3) negative affectivity and Type D personality are constructs that combine aspects of negative psychological functioning that have shown relationships with CVD and are worthy of future investigation. Positive psychological constructs of meaning/purpose and optimism predict better cardiovascular outcomes and other positive psychological constructs have received promising, but limited, attention in the literature. Key remaining questions concern the magnitude and directionality of possible causal relationships as well as the mechanisms accounting for them.

Hyperarousal Symptoms in Survivors of Cardiac Arrest Are Associated With 13 Month Risk of Major Adverse Cardiovascular Events and All-Cause Mortality.

BACKGROUND: Key dimensions of cardiac arrest-induced posttraumatic stress disorder (PTSD) symptoms include reexperiencing, avoidance, numbing, and hyperarousal. It remains unknown which dimensions are most predictive of outcome. PURPOSE: To determine which dimensions of cardiac arrest-induced PTSD are predictive of clinical outcome within 13 months posthospital discharge. METHODS: PTSD symptoms were assessed in survivors of cardiac arrest who were able to complete psychological screening measures at hospital discharge via the PTSD Checklist-Specific scale, which queries for 17 symptoms using five levels of severity. Responses on items for each symptom dimension of the four-factor numbing model (reexperiencing, avoidance, numbing, and hyperarousal) were converted to Z-scores and treated as continuous predictors. The combined primary endpoint was all-cause mortality (ACM) or major adverse cardiovascular events (MACE; hospitalization for myocardial infarction, unstable angina, heart failure, emergency coronary revascularization, or urgent defibrillator/pacemaker placements) within 13 months postdischarge. Four bivariate Cox proportional hazards survival models evaluated associations between individual symptom dimensions and ACM/MACE. A multivariable model then evaluated whether significant bivariate predictors remained independent predictors of the primary outcome after adjusting for age, sex, comorbidities, premorbid psychiatric diagnoses, and initial cardiac rhythm. RESULTS: A total of 114 patients (59.6% men, 52.6% white, mean age: 54.6 ± 13 years) were included. In bivariate analyses, only hyperarousal was significantly associated with ACM/MACE. In a fully adjusted model, 1 standard deviation increase in hyperarousal symptoms corresponded to a two-times increased risk of experiencing ACM/MACE. CONCLUSIONS: Greater level of hyperarousal symptoms was associated with a higher risk of ACM/MACE within 13 months postcardiac arrest. This initial evidence should be further investigated in a larger sample.

Systematic assessment of commercially available low-input miRNA library preparation kits.

High-throughput sequencing is increasingly favoured to assay the presence and abundance of microRNAs (miRNAs) in biological samples, even from low RNA amounts, and a number of commercial vendors now offer kits that allow miRNA sequencing from sub-nanogram (ng) inputs. Although biases introduced during library preparation have been documented, the relative performance of current reagent kits has not been investigated in detail. Here, six commercial kits capable of handling <100ng total RNA input were used for library preparation, performed by kit manufactures, on synthetic miRNAs of known quantities and human total RNA samples. We compared the performance of miRNA detection sensitivity, reliability, titration response and the ability to detect differentially expressed miRNAs. In addition, we assessed the use of unique molecular identifiers (UMI) sequence tags in one kit. We observed differences in detection sensitivity and ability to identify differentially expressed miRNAs between the kits, but none were able to detect the full repertoire of synthetic miRNAs. The reliability within the replicates of all kits was good, while larger differences were observed between the kits, although none could accurately quantify the relative levels of the majority of miRNAs. UMI tags, at least within the input ranges tested, offered little advantage to improve data utility. In conclusion, biases in miRNA abundance are heavily influenced by the kit used for library preparation, suggesting that comparisons of datasets prepared by different procedures should be made with caution. This article is intended to assist researchers select the most appropriate kit for their experimental conditions.

Medical and psychosocial outcomes of youth with psychogenic nonepileptic seizures: An observational study.

BACKGROUND: Few studies have examined both medical and psychosocial outcomes of youth with psychogenic nonepileptic seizures (PNES). The current observational study aimed to fill this gap by examining changes in seizure frequency, school absences, emergency department (ED) visits, psychological functioning, and health-related quality of life (HRQoL) in youth attending a clinic for brief treatment of PNES. METHODS: Nineteen youth with PNES and their families presented to an integrated clinic and received psychoeducation and recommendations by medical and mental health professionals. Patients returned to the clinic, on average six months later, for follow-up. Parent proxy-report and self-report measures of psychological functioning and HRQoL were collected at each visit, and medical data were extracted from patient charts. RESULTS: Forty-six percent of youth in the study experienced a reduction in seizure frequency, and 58% reported improvements in school attendance. Emergency department visits decreased by over 50%, and significant improvements in parent proxy-report of depression and HRQoL were observed. CONCLUSIONS: Results provide valuable information regarding the clinical profiles of youth with PNES and demonstrate the possibility for improved medical and psychosocial prognoses in response to psychoeducation and treatment guidance. Information obtained in this study may aid in the design of future clinical trials and research, assisting in the development of appropriate interventions.

Reduced expression of ribosomal proteins relieves microRNA-mediated repression.

MicroRNAs (miRNAs) regulate physiological and pathological processes by inducing posttranscriptional repression of target messenger RNAs (mRNAs) via incompletely understood mechanisms. To discover factors required for human miRNA activity, we performed an RNAi screen using a reporter cell line of miRNA-mediated repression of translation initiation. We report that reduced expression of ribosomal protein genes (RPGs) dissociated miRNA complexes from target mRNAs, leading to increased polysome association, translation, and stability of miRNA-targeted mRNAs relative to untargeted mRNAs. RNA sequencing of polysomes indicated substantial overlap in sets of genes exhibiting increased or decreased polysomal association after Argonaute or RPG knockdowns, suggesting similarity in affected pathways. miRNA profiling of monosomes and polysomes demonstrated that miRNAs cosediment with ribosomes. RPG knockdowns decreased miRNAs in monosomes and increased their target mRNAs in polysomes. Our data show that most miRNAs repress translation and that the levels of RPGs modulate miRNA-mediated repression of translation initiation.

Association Between Depressive Symptoms and Incident Cardiovascular Diseases.

Importance: It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs). Objective: To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. Design, Setting, and Participants: A pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162 036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401 219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. Exposures: Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; ≥16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; ≥3 indicates possible depressive disorder). Main Outcomes and Measures: Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported. Results: Among 162 036 participants from the ERFC (73%, women; mean age at baseline, 63 years [SD, 9 years]), 5078 CHD and 3932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% CI, 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10 000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401 219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years [SD, 8 years]), 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10 000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. Conclusions and Relevance: In a pooled analysis of 563 255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.

Multicenter Evaluation of Circulating Plasma MicroRNA Extraction Technologies for the Development of Clinically Feasible Reverse Transcription Quantitative PCR and Next-Generation Sequencing Analytical Work Flows.

BACKGROUND: In human body fluids, microRNA (miRNA) can be found as circulating cell-free miRNA (cfmiRNA), as well as secreted into extracellular vesicles (EVmiRNA). miRNAs are being intensively evaluated as minimally invasive liquid biopsy biomarkers in patients with cancer. The growing interest in developing clinical assays for circulating miRNA necessitates careful consideration of confounding effects of preanalytical and analytical parameters. METHODS: By using reverse transcription quantitative real-time PCR and next-generation sequencing (NGS), we compared extraction efficiencies of 5 different protocols for cfmiRNA and 2 protocols for EVmiRNA isolation in a multicentric manner. The efficiency of the different extraction methods was evaluated by measuring exogenously spiked cel-miR-39 and 6 targeted miRNAs in plasma from 20 healthy individuals. RESULTS: There were significant differences between the tested methods. Although column-based extraction methods were highly effective for the isolation of endogenous miRNA, phenol extraction combined with column-based miRNA purification and ultracentrifugation resulted in lower quality and quantity of isolated miRNA. Among all extraction methods, the ubiquitously expressed miR-16 was represented with high abundance when compared with other targeted miRNAs. In addition, the use of miR-16 as an endogenous control for normalization of quantification cycle values resulted in a decreased variability of column-based cfmiRNA extraction methods. Cluster analysis of normalized NGS counts clearly indicated a method-dependent bias. CONCLUSIONS: The choice of plasma miRNA extraction methods affects the selection of potential miRNA marker candidates and mechanistic interpretation of results, which should be done with caution, particularly across studies using different protocols.

Nurse practitioner primary care organizational climate questionnaire: Item response theory and differential item functioning.

AIMS AND OBJECTIVES: To validate Nurse Practitioner Primary Care Organizational Climate Questionnaire (NP-PCOCQ) items using item response theory (IRT) models and conduct differential item functioning (DIF) analysis to test the item functioning among nurse practitioners (NPs) practicing in different U.S. states with variable regulations governing NP practice. BACKGROUND: Nurse Practitioner Primary Care Organizational Climate Questionnaire is the only NP-specific tool measuring NP work environment and is being used in different U.S. states with variable NP scope of practice regulations and internationally to produce evidence about NP work environments within their organisations. DESIGN: Cross-sectional survey design was used to collect data from 278 primary care NPs in New York (NY) and 314 NPs in Massachusetts (MA). METHODS: NPs completed the 29-item NP-PCOCQ. Data collection involved an online survey in NY and a mail survey in MA in 2012. We used Samejima's graded response model for IRT and ordinal logistic regression for DIF analysis. A STROBE checklist was completed. RESULTS: IRT models yielded discrimination parameters ranging from 0.98-4.65 in NY and 1.25-6.94 in MA. Item difficulty parameters were within -3 to +3 range, suggesting a fair range of item difficulties exist in the scale. Only five of the 29 items on NP-PCOCQ exhibited DIF, suggesting some other state-related factor besides the measured construct influenced item responses; thus, the items were removed. CONCLUSION: Our findings indicate that a shortened, 24-item NP-PCOCQ is capable of measuring organisational climate of NPs practicing in different U.S. states. NP-PCOCQ can be used in future research to measure NP work environment. RELEVANCE TO CLINICAL PRACTICE: The tool can also be used by practice administrators to assess NP work environment and identify deficiencies to address them. This evidence about NP work environment can be used by practice administrators to promote favourable work environments for NPs to deliver high-quality care.

N-of-1 Randomized Intervention Trials in Health Psychology: A Systematic Review and Methodology Critique.

Background: Single-patient, multiple cross-over designs (N-of-1 or single-case randomized clinical trials) with systematic data collection on treatment effects may be useful for increasing the precision of treatments in health psychology. Purposes: To assess the quality of the methods and statistics, describe interventions and outcomes, and explore the heterogeneity of treatment effect of health psychology N-of-1 trials. Methods: We conducted a systematic review of N-of-1 trials from electronic database inception through June 1, 2015. Potentially relevant articles were identified by searching the biomedical electronic databases Ovid, MEDLINE, EMBASE, all six databases in the Cochrane Library, CINAHL, and PsycINFO, and conference proceedings, dissertations, ongoing studies, Open Grey, and the New York Academy's Grey Literature Report. Studies were included if they had health behavior or psychological outcomes and the order of interventions was randomized. We abstracted study characteristics and analytic methods and used the Consolidated Standards of Reporting Trials extension for reporting N-of-1 trials as a quality checklist. Results: Fifty-four N-of-1 trial publications composed of 1,193 participants were included. Less than half of these (36%) reported adequate information to calculate the heterogeneity of treatment effect. Nearly all (90%) provided some quantitative information to determine the superior treatment; 79% used an a priori statistical cutoff, 12% used a graph, and 10% used a combination. Conclusions: N-of-1 randomized trials could be the next major advance in health psychology for precision therapeutics. However, they must be conducted with more methodologic and statistical rigor and must be transparently and fully reported.

Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study.

MicroRNAs are important negative regulators of protein-coding gene expression and have been studied intensively over the past years. Several measurement platforms have been developed to determine relative miRNA abundance in biological samples using different technologies such as small RNA sequencing, reverse transcription-quantitative PCR (RT-qPCR) and (microarray) hybridization. In this study, we systematically compared 12 commercially available platforms for analysis of microRNA expression. We measured an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples and synthetic spikes from microRNA family members with varying homology. We developed robust quality metrics to objectively assess platform performance in terms of reproducibility, sensitivity, accuracy, specificity and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which help to guide informed selection of a quantitative microRNA gene expression platform for particular study goals.

Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (ß ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (ß = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (ß = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (ß = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (ß = 0.046 ± 0.01, P = 2.2 × 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

Neighborhood matters: the impact of Hispanic ethnic density on future depressive symptoms 1-year following an ACS event among Hispanic patients.

The Ethnic Density hypothesis posits that living around others from similar ethnic backgrounds reduces the risk of adverse mental health outcomes such as depression. Contrary to this hypothesis, previous work has shown that Hispanic ethnic density is cross-sectionally associated with increased depressive symptom severity among patients hospitalized with an acute coronary syndrome (ACS; myocardial infarction or unstable angina pectoris). To date, no study has examined the prospective association of Hispanic ethnic density on long-term depressive symptom severity following an acute medical event. We prospectively assessed the impact of Hispanic ethnic density on depressive symptoms, 1-year following an ACS event, among Hispanic adult patients. We tested the non-linear association between ethnic density and depressive symptoms to account for inconsistent findings on the ethnic density hypothesis. At the time of an index ACS event (i.e., baseline, N = 326) and 1-year later (N = 252), Hispanic patients from the Prescription Usage, Lifestyle, and Stress Evaluation prospective cohort study completed the Beck Depression Inventory as a measure of depressive symptom severity. Hispanic ethnic density was defined by the percentage of Hispanic residents within each patient's census tract using data extracted from the American Community Survey Census (2010-2013). Covariates included baseline demographic factors (age, gender, English fluency, education, nativity status), cardiovascular factors (Charlson comorbidity index, left ventricular ejection fraction, Global Registry of Acute Coronary Events 6-month prognostic risk score), and neighborhood factors (residential density, income, and percentage of households receiving public assistance). In an adjusted multivariable linear regression analysis there was a significant curvilinear association between Hispanic ethnic density and depressive symptom severity at 1 year. As Hispanic ethnic density increased from low to moderate density, there was an increase in depressive symptoms, but depressive symptoms slightly declined in census tracts with the highest density of Hispanics. Furthermore, gender significantly moderated the relation between Hispanic ethnic density and 1-year depressive symptom severity, such that Hispanic ethnic density was significantly associated with increased depressive symptom severity for female Hispanic patients with ACS, but not for male Hispanic patients. Previous research suggests that ethnic density may be protective against depression in Hispanic enclaves; however, our findings suggest a non-linear ethnic density effect and an overall more complex association between ethnic density and depression. These data add to a growing body of literature on the effects of sociodemographic and contextual factors on health.

Association of social support during emergency department evaluation for acute coronary syndrome with subsequent posttraumatic stress symptoms.

We examined the associations of different aspects of social support during emergency department (ED) evaluation for an acute cardiac event with perceptions of threat in the ED and subsequent posttraumatic stress symptoms (PSS) in 484 patients. Participants were enrolled in the ED where they reported on their perceptions of threat in the ED. Social support in the ED and PSS were assessed at inpatient bedside or by telephone a median of 3 days later. Positive aspects of social support were not associated with subsequent PSS. Anxiety-provoking social support was significantly associated with increased PSS at follow-up. Greater ED threat perception partially mediated that relationship.