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Background: While the gut microbiota is relatively stable through adulthood, its composition is influenced by various host and environmental factors, including changes in health, gastrointestinal processes (e.g., transit time, gastric acidity), medication use, and diet. The association of habitual diet, in the form of a posteriori-derived dietary patterns, and microbiota composition has not been adequately studied, particularly in older men., Objective: The objective was to investigate the association of dietary patterns with the composition and diversity of the gut bacterial microbiota in community-dwelling, older men., Methods: This cross-sectional study included 517 men who were participants in the Osteoporotic Fractures in Men (MrOS) Study (≥65 y of age at baseline in 2000-2002) and who provided a stool sample and completed an FFQ at MrOS Visit 4 in 2014-2016. Dietary patterns were derived by factor analysis. 16S ribosomal RNA target gene sequencing was performed and taxonomy assignments were derived using the Greengenes database. Linear regression and permutational multivariate analysis of variance (PERMANOVA) considered variations in alpha and beta diversity by dietary pattern, and a model that implements a 0-inflated Gaussian distribution of mean group abundance for each taxa (metagenomeSeq) assessed taxonomic variations by dietary pattern., Results: In multivariable-adjusted models, greater adherence to the Western pattern was positively associated with families Mogibacteriaceae and Veillonellaceae and genera Alistipes, Anaerotruncus, CC-115, Collinsella, Coprobacillus, Desulfovibrio, Dorea, Eubacterium, and Ruminococcus, while greater adherence to the prudent pattern was positively associated with order Streptophyta, family Victivallaceae, and genera Cetobacterium, Clostridium, Faecalibacterium, Lachnospira, Paraprevotella, and Veillonella. The relative abundance of the dominant gut bacterial phyla, Bacteroidetes and Firmicutes, did not differ between participants with greater adherence to the Western pattern, compared with those with greater adherence to the prudent pattern. Dietary patterns were not associated with measures of alpha diversity, but beta diversity measures were significantly associated with both Western and prudent patterns., Conclusions: We observed significant associations between dietary patterns and measures of gut microbial composition in this sample of community-dwelling, older men., (Copyright © American Society for Nutrition 2019.)

Background: The purpose of this study is to evaluate the utility of vasoactive-inotropic score (VIS) in predicting outcomes after left ventricular assist device (LVAD) implantation and explore possible mechanisms of post-operative hemodynamic instability., Methods: Retrospective review was performed in 418 consecutive patients with LVAD implantation. VIS was calculated as dopamine + dobutamine + 10 × milrinone + 100 × epinephrine + 100 × norepinephrine (all μg/kg/min) + 10000 × vasopressin (U/kg/min) after initial stabilization in the operating room and upon arrival at the intensive care unit. The primary outcome was in-hospital mortality. The secondary outcomes were a composite of in-hospital mortality, delayed right ventricular assist device (RVAD) implantation, and continuous renal replacement therapy. The pre-operative biomarkers of inflammation, oxidative stress, endotoxemia and gut-derived metabolite trimethylamine-N-oxide (TMAO) were measured in a subset of 61 patients., Results: Median VIS was 20.0 (interquartile range 13.3-27.9). VIS was an independent predictor of in-hospital mortality (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03-1.09, p < 0.001) and composite outcome (OR 1.03, 95% CI 1.01-1.06, p = 0.008). In-hospital mortality increased for each VIS quartile (0% vs 3.9% vs 7.6% vs 12.3%, p = 0.002). VIS was superior to other established LVAD risk models as a predictor of in-hospital mortality (area under the curve 0.73, 95% CI 0.64-0.82). The optimal cut-off point for VIS as a predictor of in-hospital mortality was 20. Pre-operative hemoglobin level was the only independent predictor of VIS ≥ 20 (p = 0.003). Patients with a high VIS were more likely to have elevated TMAO pre-operatively (53.6% vs 25.8%, p = 0.03)., Conclusions: A high post-operative VIS is associated with adverse in-hospital outcomes and is a better predictor of in-hospital mortality compared with existing LVAD risk models. Whether early hemodynamic stabilization using RVAD may benefit patients with a high VIS remains to be investigated., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Rheumatoid arthritis (RA) conveys an increased risk of cardiovascular disease (CVD), making it imperative that traditional CVD risk factors are well controlled. This study compared blood pressure (BP) trends over 13 years among patients with seropositive RA and patients without RA who received care within a large health care system in Minnesota., Methods: This retrospective cohort study compared 774 patients with seropositive RA and 3254 patients without RA who were matched on sex and year of birth (±5 years) and observed between 2005 and 2017. Generalized estimating equation models were used for longitudinal analyses, with adjustment for demographics, body mass index, smoking status, Charlson Comorbidity Index, number of BP measurements, and number of antihypertensive and oral glucocorticoid medications., Results: Patients both with and without RA had a mean age of 55 and were predominately female (78% with RA; 79% without RA). The mean follow-up was 6.3 (SD 3.4) years for patients with RA and 7.2 (SD 3.3) years for patients without RA. Overall, systolic BP, diastolic BP, and the number of prescribed antihypertensive medications did not differ between groups. Patients with RA were more likely to be current smokers compared with patients without RA (23% vs 11%; P < 0.01) and were less likely to have serum lipid measurements (75% vs 85%; P < 0.01)., Conclusion: BP was similarly controlled in patients with seropositive RA and patients without RA. However, diastolic BP in patients with RA was trending up in most recent years. Patients with RA were also more likely to smoke compared with controls and were less likely to have serum lipid measurements., (© 2019 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Purpose: The weathering hypothesis states that chronic exposure to social and economic disadvantage leads to accelerated decline in physical health outcomes and could partially explain racial disparities in a wide array of health conditions. This systematic review summarizes the literature empirically testing the weathering hypothesis and assesses the quality of the evidence regarding weathering as a determinant of racial disparities in health., Methods: Databases (Web of Science, Ovid MEDLINE, PubMed, and Embase) were searched for studies published in English up to July 1, 2017. Studies that tested the weathering hypothesis for any physical health outcome and included at least one socially or economically disadvantaged group (e.g., Blacks) for whom the weathering hypothesis applies were assessed for eligibility. Threats to validity were assessed using the Quality in Prognostic Studies tool., Results: The 41 included studies were rated as having overall good methodological quality. Most studies found evidence in support of the weathering hypothesis, although the magnitude of support varied by the health outcome and population studied., Conclusions: Future evaluations of the weathering hypothesis should include an examination of additional health outcomes and interrogate mechanisms that could link weathering to poor health., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Elevated blood pressure (BP) has been linked to adverse events during left ventricular assist device support. In this study we investigated the association between outpatient BP and stroke or suspected pump thrombosis among HeartMate II (HMII) recipients., Methods: We retrospectively studied 220 HMII patients. Serial outpatient BP measurements were averaged. Patients were categorized by: (1) mean arterial pressure (MAP), high (>90 mm Hg) vs intermediate (80 mm Hg ≤ MAP ≤ 90 mm Hg) vs low (<80 mm Hg); (2) systolic BP (SBP), high (≥101 mm Hg, median) vs low; and (3) pulse pressure (PP), high (≥22 mm Hg, median) vs low. To assess visit-to-visit BP variability, patients were divided in quartiles of standard deviation of MAP and SBP. The primary end-point was the composite of stroke or suspected pump thrombosis., Results: The risk for the primary end-point was increased in the high MAP group (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.49 to 5.05, vs intermediate MAP; and 6.73, 1.9 to 23.9, vs low MAP). MAP had higher predictive value for the primary end-point compared with SBP (p = 0.05). Patients with high SBP had a higher rate of stroke (HR 2.8, 95% CI 1.09 to 7.17, vs low SBP). The combination of high SBP and low PP was associated with the highest risk for stroke. The lowest quartile of visit-to-visit MAP variability was associated with the highest risk for the primary end-point., Conclusions: Elevated outpatient BP is associated with increased risk for stroke or suspected pump thrombosis in HMII recipients. Reduced PP and low visit-to-visit BP variability may confer additional risk., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Antimicrobial peptides (AMPs) are a diverse family of peptides that defend the mucosal surfaces of the oral cavity and other locations. Many AMPs have multiple functions and properties that influence aspects of innate defense and colonization by microorganisms. The human oral cavity is home to the second-most diverse microbiome, and the health of the mouth is influenced by the presence of these bacteria as well as by extrinsic factors such as periodontitis and smoking. This study hypothesized that the AMP profile is different in the presence of extrinsic factors and that this would also be reflected in the bacteria present. The AMP profile was analyzed by quantitative selected-reaction-monitoring mass spectrometry analysis and 40 bacterial species were quantified by DNA-DNA hybridization in saliva donated by 41 individuals. Periodontal status was assessed through dental examination and smoking status through medical charting. Periodontal health (in nonsmokers) was associated with a higher abundance of ribonuclease 7, protachykinin 1, β-defensin 128, lipocalin 1, bactericidal permeability-increasing protein fold-containing family B member 3, and bone-marrow proteoglycan. Nonsmoking periodontal disease was associated with an abundance of neutrophil defensin 1 and cathelicidin. However, 7 AMPs were overabundant in periodontal disease in smokers: adrenomedullin, eosinophil peroxidase, 3 different histones, myeloperoxidase, and neutrophil defensin 1. There were no differentially abundant AMPs in smokers versus nonsmokers with periodontal health. Correlation network inference of healthy nonsmokers, healthy smokers, nonsmoking periodontitis, or smoking periodontitis donors demonstrated very different networks growing in complexity with increasing numbers of stressors. The study highlights the importance of the interaction between the oral cavity and its resident microbiota and how this may be influenced by periodontal disease and smoking., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Objectives: To determine the relationship between objectively measured physical activity (PA) and the gut microbiome among community-dwelling older men., Design: Cross-sectional study., Setting: Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16)., Participants: Eligible men (n=373, mean age 84 y) included participants with 5-day activity assessment with at least 90% wear time and analyzed stool samples., Measurements: PA was measured with the SenseWear Pro3 Armband and stool samples analyzed for 16S v4 rRNA marker genes using Illumina MiSeq technology. Armband data together with sex, height, and weight were used to estimate total steps, total energy expenditure, and level of activity. 16S data was analyzed using standard UPARSE workflow. Shannon and Inverse Simpson indices were measures of (within-participant) α-diversity. Weighted and unweighted Unifrac were measures of (between-participant) β-diversity. We used linear regression analysis, principal coordinate analysis, zero-inflated Gaussian models to assess association between PA and α-diversity, β-diversity, and specific taxa, respectively, with adjustments for age, race, BMI, clinical center, library size, and number of chronic conditions., Results: PA was not associated with α-diversity. There was a slight association between PA and β-diversity (in particular the second principal coordinate). Compared to those who were less active, those who had higher step counts had higher relative abundance of Cetobacterium and lower relative abundance of taxa from the genera Coprobacillus, Adlercreutzia, Erysipelotrichaceae CC-115 after multivariable adjustment including age, BMI, and chronic conditions. There was no consistent pattern by phylum., Conclusion: There was a modest association between levels of PA and specific gut microbes among community-dwelling older men. The observed associations are consistent with the hypothesis that underlying health status and composition of the host microbiome are related., Competing Interests: Drs. Langsetmo, Orwoll, Ensrud, Cauley, and Shikany have received NIH funding as noted above. Dr. Langsetmo reports grants from Abbott outside the submitted work. Dr. Johnson reports personal fees from Nestlé Health Science, grants from General Mills Inc., outside the submitted work. Dr. Orwoll reports grants from Lilly, grants from Nordic Biosciences, grants from Mereo Biopharma, other from Bayer, outside the submitted work. Drs. Ryan Demmer, Fino, Hoffman, Shmagel, Meyer have no disclosures.

Aim: To cross-sectionally analyse the submucosal microbiome of peri-implantitis (PI) lesions at different severity levels., Materials and Methods: Microbial signatures of 45 submucosal plaque samples from untreated PI lesions obtained from 30 non-smoking, systemically healthy subjects were assessed by 16s sequencing. Linear mixed models were used to identify taxa with differential abundance by probing depth, after correction for age, gender, and multiple samples per subject. Network analyses were performed to identify groups of taxa with mutual occurrence or exclusion. Subsequently, the effects of peri-implant probing depth on submucosal microbial dysbiosis were calculated using the microbial dysbiosis index., Results: In total, we identified 337 different taxa in the submucosal microbiome of PI. Total abundance of 12 taxa correlated significantly with increasing probing depth; a significant relationship with lower probing depth was found for 16 taxa. Network analysis identified two mutually exclusive complexes associated with shallow pockets and deeper pockets, respectively. Deeper peri-implant pockets were associated with significantly increased dysbiosis., Conclusion: Increases in peri-implant pocket depth are associated with substantial changes in the submucosal microbiome and increasing levels of dysbiosis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background:: Cardiogenic shock following acute myocardial infarction (AMI-CS) portends a poor prognosis. Short-term mechanical circulatory support devices (MCSDs) provide hemodynamic support for patients with cardiogenic shock but predictors of survival and the ability to wean from short-term MCSDs remain largely unknown., Methods:: All patients > 18 years old treated at our institution with extra-corporeal membrane oxygenation or short-term surgical ventricular assist device for AMI-CS were studied. We collected acute myocardial infarction details with demographic and hemodynamic variables. Primary outcomes were survival to discharge and recovery from MCSD (i.e. survival without heart replacement therapy including durable ventricular assist device or heart transplant)., Results:: One hundred and twenty-four patients received extra-corporeal membrane oxygenation or short-term surgical ventricular assist device following acute myocardial infarction from 2007 to 2016; 89 received extra-corporeal membrane oxygenation and 35 short-term ventricular assist device. Fifty-five (44.4%) died in the hospital and 69 (55.6%) survived to discharge. Twenty-six (37.7%) required heart replacement therapy (four transplant, 22 durable ventricular assist device) and 43 (62.3%) were discharged without heart replacement therapy. Age and cardiac index at MCSD implantation were predictors of survival to discharge; patients over 60 years with cardiac index <1.5 l/min per m 2 had a low likelihood of survival. The angiographic result after revascularization predicted recovery from MCSD (odds ratio 9.00, 95% confidence interval 2.45-32.99, p=0.001), but 50% of those optimally revascularized still required heart replacement therapy. Cardiac index predicted recovery from MCSD among this group (odds ratio 4.06, 95% confidence interval 1.45-11.55, p=0.009)., Conclusion:: Among AMI-CS patients requiring short-term MCSDs, age and cardiac index predict survival to discharge. Angiographic result and cardiac index predict ventricular recovery but 50% of those optimally revascularized still required heart replacement therapy.

Previous studies on the association between number of children and carotid intima-media thickness (cIMT) were limited to Western populations. Pregnancy in women is associated with physiologic changes that may influence the risk of cardiovascular disease. Comparing the association between number of children and cIMT in men and women can provide insights on whether the association may be due to pregnancy. We investigated the association between number of children and cIMT among 718 female (mean age 37.5 years) and 417 male participants (mean age 41.3 years), randomly selected from the Health Effect of Arsenic Longitudinal Study (HEALS), a population-based cohort study in Bangladesh. Multivariate linear regression was used to assess the association and to control for education attainment, history of diabetes, age, smoking, betel use, BMI, systolic blood pressure, and diastolic blood pressure. The average number of children was 4.43 for women and 3.74 for men. There were no nulliparous women. We observed a positive association between number of children and cIMT in women. Mean cIMT increased by 4.5 μm (95% CI, 0.8-8.1) per increment of one birth (P = 0.02). Compared to women with two children, cIMT in women with 4 children and ≥5 children was 23.6μm (95%CI, 2.6-44.7; P = 0.03) and 25.1 μm (95%CI, 3.5-46.6; P = 0.02) greater, respectively. The association was not modified by BMI, SBP, betel use or age. Data in men showed no evidence of association (P = 0.4). The finding suggests a role of high parity in atherosclerosis in women of a low-income, high parity population., Competing Interests: The authors have declared that no competing interests exist.

Background: Widespread availability of rapid diagnostic testing for respiratory viruses allows more in-depth studies of human parainfluenza viruses (HPIV)., Objectives: This study aimed to assess seasonality of HPIV types 1-4, clinical outcomes by HPIV type, and risk factors for illness severity., Patients/methods: This retrospective study was performed from January 2013 to December 2015 in children and adults with HPIV, detected by multiplex reverse transcription polymerase chain reaction, participating in a community surveillance study of acute respiratory infections (ARIs) in New York City and patients admitted to a tertiary care center in the same neighborhood. Seasonality trends by HPIV type were compared between the community and hospital groups. The associations between HPIV type, demographics, clinical characteristics, and illness severity were assessed., Results: HPIV was detected in 69 (4%) of 1753 community surveillance participants (median age 9.2 years) and 680 hospitalized patients (median age 6.8 years). Seasonality for HPIV types 1-3 agreed with previously described patterns; HPIV-4 occurred annually in late summer and fall. In the community cohort, 22 (32%) participants sought medical care, 9 (13%) reported antibiotic use, and 20 (29%) reported ≥1 day of missed work or school. Among hospitalized patients, 24% had ≥4 chronic conditions. Multivariable ordinal logistic regression demonstrated that increased severity of illness was significantly associated with HPIV-4 and chronic cardiovascular and respiratory conditions in children and with age ≥65 years and chronic respiratory conditions in adults., Conclusions: HPIV-4 presented late summer and early fall annually and was associated with increased severity of illness in hospitalized children., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley &Sons Ltd.)

Objective: We investigated the hypothesis that childhood obesity is a risk factor for sensorineural hearing loss (SNHL) independent of other metabolic risk factors., Study Design: A complex, multistage, stratified geographic area design for collecting representative data from noninstitutionalized US population., Methods: A total of 5,638 adolescents between age 12 and 19 from the NHANES database (2005-2010) were studied. Subjects with body mass index >= 95th percentile were classified as obese. SNHL was defined as average pure-tone greater than 15 dB HL for 0.5, 1, and 2 kHz or 3, 4, 6, and 8 kHz in at least 1 ear. Multivariable logistic regression models assessed incident hearing loss odds across obese patients in comparison with normal weight individuals (5th-85th percentile). Multivariable models included age, sex, socioeconomic status, race, smoke exposure, high density lipoprotein level, triglyceride level, elevated blood pressure measurement, hemoglobin A1C level, and C-reactive protein level., Results: The rate of SNHL was 21.5% in obese and 13.44% in normal weight adolescents (p < 0.0001). In multivariable analyses, obesity was associated with 1.73-fold increase in the odds of SNHL (95% CI: 1.25-2.40, p value = 0.006). Potentially confounding and mediating factors had minimal effect on the odds of SNHL in obese study participants (OR range of 1.69-1.75, all p values <= 0.01)., Conclusions: Obesity is associated with higher prevalence of SNHL in adolescents independent of other potential risk factors. Future longitudinal investigations and mechanistic studies are warranted.

Objectives: To determine whether asthma hospitalisations of children and adults in the five boroughs of New York City are correlated with influenza hospitalisations temporally and spatially., Design: A longitudinal ecological study., Inclusion Criteria: We reviewed the Statewide Planning and Research Cooperative System's records of hospitalisations in Manhattan, Bronx, Queens, Brooklyn and Staten Island from 2002 to 2012. All hospitalisations with a primary diagnosis of either asthma or influenza were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes., Methods: A time-series regression analysis was performed using aggregate monthly counts of influenza hospitalisations as predictors of asthma hospitalisations. Time-series regression models were also applied to different age groups and boroughs to examine the magnitude of influenza and asthma correlations across strata. The per cent excess risk was also calculated across age groups and boroughs., Results: Time-series analysis of the overall population revealed a significant positive correlation between influenza and asthma hospitalisations (p=0.011). When stratifying by age, there was a significant positive correlation between asthma and influenza hospitalisations for individuals 18 and older (p<0.01), and no significant correlation found for age groups younger than 18. Percentages of excess risk of influenza-related asthma hospitalisations also increased with increasing age with adults 18-44, 45-64 and 65+ having excess risk percentages of 2.9%, 3.4% and 4%, respectively. Time-series analysis by location revealed positive significant correlations between asthma and influenza hospitalisations in Brooklyn (p=0.03) and Manhattan (p<0.01). Manhattan and Brooklyn had a 2.5% and 1.6%, respectively, percentage of excess risk of influenza-related asthma hospitalisations., Conclusion: Influenza and asthma hospitalisations are significantly associated at the population level among adults. These associations vary by age and geographical location. Influenza prevention strategies targeting adult populations, particularly individuals living in Manhattan and Brooklyn, have the potential for meaningful reduction of influenza-related asthma hospitalisations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Periodontitis is strongly associated with diabetes and is increasingly shown to be associated with other glycemic abnormalities. Vitamin D is postulated to have both anti-inflammatory and antimicrobial activity. Therefore, our aim was to investigate the joint effects of both serum 25-hydroxyvitamin D 3 and total 25-hydroxyvitamin D with periodontitis on homeostatic model assessment for insulin resistance (HOMA-IR), pre-diabetes, and type 2 diabetes., Research Design and Methods: Using data from the 2009-2010 National Health and Nutrition Examination Survey, the sample was restricted to adults over 30 years of age, who were eligible for oral health examination, and had vitamin D, fasting glucose and insulin measures. The analytic sample includes those with (n=1631) and without (n=1369) type 2 diabetes. Using survey logistic multivariable regression analysis, we examined the following joint effects: (1) vitamin D insufficiency (<50 nmol/L) and moderate to severe periodontitis (VD+PD+); (2) vitamin D insufficiency and mild to no periodontitis (VD+PD-); and (3) vitamin D sufficiency ) (>50 nmol/L) and periodontitis (VD-PD+), and compared these groups with the doubly unexposed reference group (VD-PD-)., Results: Consistently, the joint effects of vitamin D 3 insufficiency and total vitamin D insufficiency with periodontitis (VD+PD+) were significantly associated with diabetes: OR=2.83 (95% CI 1.34 to 5.96) and OR=1.98 (95% CI 1.04 to 3.76), respectively. However, the joint effects of vitamin D 3 insufficiency and periodontitis were attenuated for HOMA-IR 4.17: OR=1.57 (95% CI 0.97 to 2.55). Pre-diabetes was not associated with either joint effects., Conclusion: In this cross-sectional, nationally representative sample, the joint effects of vitamin D and periodontitis appear to differ for HOMA-IR, pre-diabetes and diabetes., Competing Interests: Competing interests: None declared.

Background: Among adults, depressive symptoms are associated with higher rates of cardiovascular disease; however, the evidence is mixed regarding the association between depressive symptoms and hypertension, especially among young adults. The deleterious effects of some antidepressant medications on blood pressure may contribute to mixed findings., Methods: Adolescents enrolled in Add Health (N = 11,183) (1994-2008) completed an abbreviated Center for Epidemiologic Studies Depression Scale at three waves (mean ages, 16, 22, and 29). Antidepressant use was measured at age 22 and at age 29. Hypertension at age 29 was defined as measured systolic blood pressure of 140 mm Hg or greater, diastolic blood pressure of 90 mm Hg or greater, or staff-inventoried anti-hypertensive medication use., Results: The prevalence of hypertension at age 29 was 20%. High depressive symptoms in adolescence or young adulthood were not associated with hypertension in young adulthood. Antidepressant use at age 29 was associated with increased prevalence of hypertension (prevalence ratio [PR], 1.4; 95% CI, 1.2, 1.7) and an interaction with sex was observed (PRMen, 1.6; 95% CI, 1.2, 2.0; PRWomen, 1.2; 95% CI, 0.89, 1.6; pinteraction = 0.0227). Selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor antidepressant use were associated with hypertension (PRSSRI, 1.3; 95% CI, 1.0, 1.6; PRnon-SSRI, 1.6; 95% CI, 1.2, 2.1)., Conclusions: In this sample, antidepressant use, but not depressive symptoms, was associated with hypertension in young adulthood. Further research is recommended to examine joint and independent relationships between depression and antidepressant use and hypertension among young adults. See video abstract at, http://links.lww.com/EDE/B355.

Introduction: There are known racial differences in cardiovascular health behaviors, including smoking, physical activity, and diet quality. A better understanding of these differences may help identify intervention targets for reducing cardiovascular disease disparities. This study examined whether socioeconomic, psychosocial, and neighborhood environmental factors, in isolation or together, mediate racial differences in health behaviors., Methods: Participants were 3,081 men and women from the Coronary Artery Risk Development in Young Adults study who were enrolled in 1985-1986 (Year 0) and completed a follow-up examination in 2015-2016 (Year 30). A health behavior score was created at Years 0, 7, 20, and 30 using smoking, physical activity, and diet assessed that year. The race difference in health behavior score was estimated using linear regression in serial cross-sectional analyses. Mediation analyses computed the proportion of the race and health behavior score association attributable to socioeconomic, psychosocial, and neighborhood factors., Results: Data analysis conducted in 2016-2017 found that blacks had significantly lower health behavior scores than whites across 30 years of follow-up. Individual socioeconomic factors mediated 48.9%-70.1% of the association between race and health behavior score, psychosocial factors 20.3%-30.0%, and neighborhood factors 22.1%-41.4% (p<0.01 for all)., Conclusions: Racial differences in health behavior scores appear to be mediated predominately by correspondingly large differences in socioeconomic factors. This study highlights the profound impact of socioeconomic factors, which are mostly not under an individual's control, on health behaviors. Policy action targeting socioeconomic factors may help reduce disparities in health behaviors., (Copyright © 2018 American Journal of Preventive Medicine. All rights reserved.)

Measurement and characterization of the human microbiome in large population-based human studies has recently become a reality secondary to technological advances in high-throughput DNA sequencing. These advances bring new challenges and knowledge gaps for study planning, data analysis, and interpretation that are novel to large-scale epidemiologic studies. In this issue of the Journal, Sinha et al. (Am J Epidemiol. 2018;187(6):1282-1290) have provided data with which to inform statistical power and sample size requirements for microbiome studies in population-based settings. This work serves as a helpful starting point for study planning while also serving as a springboard for discussion regarding additional considerations for improving microbiome research. This commentary emphasizes the importance of selecting microbiome metrics appropriate for the biological hypothesis under investigation, as well as the need for new analytical tools that can better capitalize on the unique yet rich information contained in microbiome data sets.

Background: Gastrointestinal bleeding (GIB) is a frequent cause of re-admission in patients with continuous-flow left ventricular assist devices (CF-LVADs) and is associated with multiple endoscopic procedures and high resource utilization. Our aim was to determine the diagnostic and therapeutic yield of endoscopy and to develop a more cost-effective approach for the management of GIB in CF-LVAD recipients., Methods: We retrospectively reviewed 428 patients implanted with a CF-LVAD between 2009 and 2016 at the Columbia University Medical Center and identified those hospitalized for GIB. Patients were categorized into upper GIB (UGIB), lower GIB (LGIB) and occult GIB (OGIB), based on clinical presentation., Results: Eighty-seven CF-LVAD patients underwent a total of 164 GIBs, resulting in 239 endoscopies. Index presentation was consistent with UGIB in 30 (34.5%), LGIB in 19 (21.8%) and OGIB in 38 (43.7%) patients. On the first GIB, 147 endoscopies localized a bleeding source in 49 (30%), resulting in 24 (16.3%) endoscopic interventions. Of 45 lesions identified, arteriovenous malformations (AVMs) were the most common (22, 48.9%). A gastric or small bowel source (HR 2.8, p = 0.003) and an endoscopic intervention (HR 1.9, p = 0.04) predicted recurrent GIB. The proposed algorithm may reduce the number of endoscopic procedures by 45% and costs by 35%., Conclusions: Occult GIB is the most common presentation in CF-LVAD patients and carries the lowest diagnostic and therapeutic yield of endoscopy. Performing an intervention was among the strongest predictors of recurrent GIB. Our proposed algorithm may decrease the number of low-yield procedures and improve resource utilization., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized., Methods: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children's hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression., Results: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9-13.1) and cardiovascular (OR = 3.9; 95% CI, 1.6-9.5), genetic/congenital (OR = 2.8; 95% CI, 1.1-7.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7-12.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1-7.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types., Conclusions: Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.

Background: Diabetes and periodontitis are chronic non-communicable diseases independently associated with mortality and have a bidirectional relationship., Aims: To update the evidence for their epidemiological and mechanistic associations and re-examine the impact of effective periodontal therapy upon metabolic control (glycated haemoglobin, HbA1C)., Epidemiology: There is strong evidence that people with periodontitis have elevated risk for dysglycaemia and insulin resistance. Cohort studies among people with diabetes demonstrate significantly higher HbA1C levels in patients with periodontitis (versus periodontally healthy patients), but there are insufficient data among people with type 1 diabetes. Periodontitis is also associated with an increased risk of incident type 2 diabetes., Mechanisms: Mechanistic links between periodontitis and diabetes involve elevations in interleukin (IL)-1-β, tumour necrosis factor-α, IL-6, receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio, oxidative stress and Toll-like receptor (TLR) 2/4 expression., Interventions: Periodontal therapy is safe and effective in people with diabetes, and it is associated with reductions in HbA1C of 0.27-0.48% after 3 months, although studies involving longer-term follow-up are inconclusive., Conclusions: The European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) report consensus guidelines for physicians, oral healthcare professionals and patients to improve early diagnosis, prevention and comanagement of diabetes and periodontitis., (Copyright © 2017 John Wiley & Sons A/S, Elsevier B.V. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate whether coeliac disease (CD) was associated with periodontitis among a nationally representative sample of US adults., Materials and Methods: The National Health and Nutrition Examination Survey (NHANES) 2009-2012 enrolled 6,661 subjects with full-mouth periodontal examination and serological testing for antitissue transglutaminase (tTg) and antiendomysial (EMA) antibodies. CD was defined as (i) self-reported physician diagnosis while on a gluten-free diet; or (ii) tTg levels >10.0 U/ml and positive EMA results. Positive serology without self-reported diagnosis was defined as undiagnosed CD (UdxCD). Periodontitis was defined according to the CDC/AAP definition. Multivariable linear and logistic models were used to regress the mean probing depth (PD) or attachment loss (AL) outcomes across CD categories (none, diagnosed and undiagnosed)., Results: The prevalence of moderate/severe periodontitis and diagnosed/undiagnosed CD was 40% and 0.74%, respectively. Mean AL was lower among those with CD although results were not statistically significant (p = .67). The odds of periodontitis among individuals with diagnosed and undiagnosed CD were: 0.5(0.22, 1.16) and 0.62(0.1, 3.75), respectively. Mean PD levels among those without CD or with diagnosed or undiagnosed CD were 1.49 ± 0.02, 1.36 ± 0.11 and 1.31 ± 0.11 (p = .03)., Conclusion: CD is associated with modestly lower levels of mean PD but was not associated with mean AL or periodontitis. Larger studies are necessary to enhance precision and strengthen conclusions., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Apolipoprotein E (APOE) polymorphism has previously been associated with carotid intima-media thickness (cIMT) in predominantly Caucasian populations. We sought to test the strength of the relationship between APOE-ε4 carrier status and subclinical atherosclerosis in a tri-ethnic population with a large Hispanic representation., Methods: We assessed the association between APOE polymorphism and cIMT and plaque burden among 1243 stroke-free individuals (mean age 69 years, 65% Hispanic, 18% black, 17% white) using a sequence of multivariable regression models., Results: After adjusting for demographics, vascular risk factors and plasma low-density lipoprotein (LDL) levels, APOE-ε4 carrier status was positively associated with cIMT (mean difference, .013 mm; 95% confidence interval, .003-.023 mm). The APOE-ε4 association with cIMT appeared to be segment-specific with greater differences in IMT between APOE-ε4 carriers and noncarriers in the common carotid artery (CCA, .014 mm) and bifurcation (.017 mm) than in the internal carotid artery (ICA) IMT (.007 mm). This relationship was not modified by race-ethnicity. Presence of diabetes modified the ε4-cIMT relationship in CCA (P = .045) and ICA (P = .046). APOE-ε4 carrier status was not associated with plaque presence or plaque area., Conclusions: APOE-ε4 carriers had elevated cIMT independent of demographics and vascular risk factors including LDL levels. Diabetes was an effect modifier of the relationship between APOE-ε4 and IMT, such that ε4 carriers with diabetes had greater IMT in the CCA and ICA than those without diabetes. The APOE-IMT relationship was not modified by race-ethnicity., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Surgical site infections (SSIs) following spine surgery in children and adolescents with nonidiopathic scoliosis are associated with increased morbidity and health care costs. Potentially modifiable risk factors for SSIs merit additional study in this population., Methods: A single-center, retrospective cohort study was performed from August 2008 through December 2013 in children and adolescents undergoing surgery for nonidiopathic scoliosis to determine the trends in SSI rate and causative microorganisms. A standardized perioperative antimicrobial prophylaxis regimen was developed from September-October 2008. Potential risk factors for SSIs were assessed by multivariable analysis using Poisson regression models. Fusion procedures and growing construct procedures were analyzed separately., Results: In all, 268 patients underwent 536 surgical procedures of whom 192 underwent 228 fusion procedures, 89 underwent 308 growing construct procedures, and 13 underwent both procedures during the study period. Twenty-one SSIs (3.9% of surgical procedures and 7.8% of patients) occurred within 90 days of surgery, 17 SSIs occurred after fusion procedures (4.5% of procedures and 8.9% of patients), and 4 SSIs occurred after growing construct procedures (1.3% of procedures and 4.5% of patients). There were 9 polymicrobial SSIs (42.9%). Of the 31 bacterial pathogens isolated, 48% were Gram-negative organisms. Among patients undergoing fusion procedures, SSIs were associated with underdosing of preoperative cefazolin [relative risk (RR)=4.99; 95% confidence interval (CI), 1.89-17.43; P=0.012] and tobramycin (RR=5.86; 95% CI, 1.90-18.06; P=0.002), underdosing of intraoperative (RR=5.65; 95% CI, 2.13-14.97; P=0.001) and postoperative (RR=3.86; 95% CI, 1.20-12.40; P=0.023) tobramycin, and any preoperative or intraoperative underdosing (RR=4.89; 95% CI, 1.70-14.12; P=0.003), after adjustment for duration of surgery. No factors were associated with SSIs in those undergoing growing construct procedures. During the study period, the SSIs rate declined (P<0.0001)., Conclusions: Underdosing of tobramycin and preoperative cefazolin were associated with an increased SSI risk among patients undergoing fusion procedures. Future multicenter studies should further investigate the generalizability of these findings., Level of Evidence: Level II-retrospective study.

Objectives: This study sought to determine if the presence of implantable cardioverter-defibrillators (ICD) provided a mortality benefit during continuous-flow left ventricular assist device (LVAD) support., Background: An ICD decreases mortality in selected patients with advanced heart failure and have been associated with reduced mortality in patients with pulsatile LVAD. However, it is unclear whether that benefit extends to patients with a contemporary continuous-flow LVAD., Methods: Propensity score matching was used to generate a cohort of patients with similar baseline characteristics. The primary outcome was freedom from death during LVAD support. Secondary endpoints included freedom from unexpected death, likelihood of transplantation and recovery, and adverse events., Results: Among 16,384 eligible patients in the Interagency Registry for Mechanically Assisted Circulatory Support registry, 2,209 patients with an ICD and 2,209 patients without one had similar propensity scores and were included. The presence of an ICD was associated with an increased mortality risk (hazard ratio: 1.20; 95% confidence interval [CI]: 1.04 to 1.39; p = 0.013) and an increased risk of unexpected death during device support (HR: 1.33; 95% CI: 1.03 to 1.71; p = 0.03). Patients with an ICD were more likely to undergo transplantation (HR: 1.16; 95% CI: 0.99 to 1.35; p = 0.06) and less likely to have LVAD explant for recovery (HR: 0.53, 95% CI: 0.29 to 0.98; p = 0.04). Patients with an ICD had a higher rate of treated ventricular arrhythmias (rate ratio: 1.27; 95% CI: 1.10 to 1.48; p = 0.001) and rehospitalization (rate ratio: 1.08; 95% CI: 1.04 to 1.12; p < 0.0001), but rates of hemorrhagic stroke were similar (rate ratio: 1.01; 95% CI: 0.81 to 1.26; p = 0.98)., Conclusions: Among patients with a continuous flow LVAD, the presence of an ICD was not associated with reduced mortality., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is uncertainty regarding the prevalence of psychiatric illnesses in patients with celiac disease (CD) and people who avoid gluten (PWAG) without a diagnosis of CD., Participants and Methods: We obtained data from 22 274 participants from the 2009-2014 National Health and Nutrition Examination Survey to compare the prevalence of depression, insomnia, quality-of-life variables, and psychotropic medication use in CD participants and PWAGs to controls. We used multivariable logistic regression to assess for independent associations between CD/PWAG status and the outcomes of these variables., Results: Depression was present in 8.2% of controls compared with 3.9% of participants with CD (P=0.18) and 2.9% of PWAGs (P=0.002). After adjustment for age, sex, race, income, and access to healthcare, PWAGs maintained lower odds of depression compared with controls (odds ratio=0.25; 95% confidence interval: 0.12-0.51; P=0.0001). The prevalence estimates of sleep difficulty among controls (27.3%) compared to participants with CD or PWAGs were 37.7% (P=0.15) and 34.1% (P=0.11). Those with diagnosed CD had increased odds of sleep difficulty (odds ratio=2.41; 95% confidence interval 1.04-5.60), but this was no longer significant after multivariable adjustment (P=0.17)., Conclusion: Among a nationally representative US sample, participants with CD overall showed no increased odds of depression or sleep difficulty. PWAGs showed lower odds of depression compared with controls. Future research should investigate the relationship between a diagnosis of CD and the development of psychiatric conditions.

Beginning in 2002, New York City (NYC) implemented numerous policies and programs targeting cardiovascular disease (CVD) risk factors. Using death certificates, we analyzed trends in NYC-specific and US mortality rates from 1990 to 2011 for all causes, any CVD, atherosclerotic CVD (ACVD), coronary artery disease (CAD), and stroke. Joinpoint analyses quantified annual percent change (APC) and evaluated whether decreases in CVD mortality accelerated after 2002 in either NYC or the total US population. Our analyses included 1,149,217 NYC decedents. The rates of decline in mortality from all causes, any CVD, and stroke in NYC did not change after 2002. Among men, the decline in ACVD mortality accelerated during 2002-2011 (APC = -4.8%, 95% confidence interval (CI): -6.1, -3.4) relative to 1990-2001 (APC = -2.3%, 95% CI: -3.1, -1.5). Among women, ACVD rates began declining more rapidly in 1993 (APC = -3.2%, 95% CI: -3.8, -2.7) and again in 2006 (APC = -6.6%, 95% CI: -8.9, -4.3) as compared with 1990-1992 (APC = 1.6%, 95% CI: -2.7, 6.0). In the US population, no acceleration of mortality decline was observed in either ACVD or CAD mortality rates after 2002. Relative to 1990-2001, atherosclerotic CVD and CAD rates began to decline more rapidly during the 2002-2011 period in both men and women-a pattern not observed in the total US population, suggesting that NYC initiatives might have had a measurable influence on delaying or reducing ACVD mortality., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent studies have suggested that epigenetic alterations, particularly DNA methylation, play a crucial role in the pathogenesis of insulin resistance. Folate is a key source of the one-carbon group for DNA methylation, whereas the association and mechanistic linkage between folate status and insulin resistance remains unclear with very limited experimental support. We performed a cross-sectional study of 1530 nondiabetic adults in the 2011-2012 National Health and Nutrition Examination Survey (NHANES). We examined associations between serum folate and insulin resistance using multiple linear regression models adjusted for potential confounders. We detected a significant inverse relationship for serum folate, where a 25% increase in serum folate was associated with a 3.06% (95% CI, -4.72, -1.37) and 2.77% (95% CI, -4.36, -1.77) decline in HOMA-IR and insulin respectively, and a 2.55% (95% CI, 0.93, 4.21) increase in G/I ratio. Our findings demonstrate that serum folate was inversely associated with insulin resistance in U.S. nondiabetic adults.

Background: Implantable cardioverter defibrillators (ICDs) provide a significant mortality benefit for appropriately selected patients with advanced heart failure. ICDs are associated with a mortality benefit when used in patients with a pulsatile left ventricular assist device (LVAD). It is unclear whether patients with a continuous-flow LVAD (CF-LVAD) derive the same benefit. We sought to determine if the presence of an ICD provided a mortality benefit during CF-LVAD support as a bridge to transplantation., Methods: Patients were identified in the United Network for Organ Sharing (UNOS) registry who underwent LVAD implantation as bridge to transplantation between May 2004 and April 2014, with follow-up through June 2014. Primary outcome was freedom from death while on CF-LVAD support with adjustment for complications requiring UNOS listing status upgrade. Secondary end-points included freedom from delisting while on CF-LVAD support and incidence of transplantation., Results: The study cohort comprised 2,990 patients, and propensity score matching identified 1,012 patients with similar propensity scores. There was no difference in survival during device support between patients with and without an ICD (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.66-2.17; p = 0.55). Adjusting for device complications requiring a UNOS listing status upgrade had minimal influence (HR = 1.11; 95% CI, 0.60-2.05; p = 0.74). There was no increased risk of delisting owing to being too sick for patients with an ICD (HR = 1.08; 95% CI, 0.63-1.86; p = 0.78). Likewise, the probability of transplantation was similar (HR = 1.05; 95% CI, 0.87-1.27; p = 0.62)., Conclusions: Among patients bridged to transplantation with a CF-LVAD, the presence of an ICD did not reduce mortality., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Endothelin-1 (ET-1) is a pivotal mediator of vasoconstriction and inflammation in congestive states such as heart failure (HF) and chronic kidney disease (CKD). Whether peripheral venous congestion (VC) increases plasma ET-1 at pressures commonly seen in HF and CKD patients is unknown. We seek to characterize whether peripheral VC promotes time- and dose-dependent increases in plasma ET-1 and whether these changes are sustained after decongestion. We used a randomized, cross-over design in 20 healthy subjects (age 30 ± 7 years). To experimentally model VC, venous pressure was increased to either 15 or 30 mmHg (randomized at first visit) above baseline by inflating a cuff around the subject's dominant arm; the nondominant arm served as a noncongested control. We measured plasma ET-1 at baseline, after 20, 60 and 120 min of VC, and finally at 180 min (60 min after cuff release and decongestion). Plasma ET-1 progressively and significantly increased over 120 min in the congested arm relative to the control arm and to baseline values. This effect was dose-dependent: ET-1 increased by 45% and 100% at VC doses of 15 and 30 mmHg, respectively ( P  <   0.05), and declined after 60 min of decongestion though remaining significantly elevated compared to baseline. In summary, peripheral VC causes time- and dose-dependent increases in plasma ET-1. Of note, the lower dose of 15 mmHg (more clinically relevant to HF and CKD patients) was sufficient to raise ET-1. These findings support the potentially contributory, not merely consequential, role of VC in the pathophysiology of HF and CKD., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Inflammation might link microbial exposures to insulin resistance. We investigated the cross-sectional association between periodontal microbiota, inflammation and insulin resistance., Methods: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 152 diabetes-free adults (77% female) aged 20-55 years (mean = 34 ± 10). Three hundred and four subgingival plaque samples were analysed using the Human Oral Microbe Identification Microarray to measure the relative abundances of 379 taxa. C-reactive protein, interleukin-6, tumour necrosis factor-α and adiponectin were assessed from venous blood and their z-scores were summed to create an inflammatory score (IS). Insulin resistance was defined via the HOMA-IR. Associations between the microbiota and both inflammation and HOMA-IR were explored using multivariable linear regressions; mediation analyses assessed the proportion of the association explained by inflammation., Results: The IS was inversely associated with Actinobacteria and Proteobacteria and positively associated with Firmicutes and TM7 (p-values < 0.05). Proteobacteria levels were associated with insulin resistance (p < 0.05). Inflammation explained 30-98% of the observed associations between levels of Actinobacteria, Proteobacteria or Firmicutes and insulin resistance (p-values < 0.05). Eighteen individual taxa were associated with inflammation (p < 0.05) and 22 with insulin resistance (p < 0.05). No findings for individual taxa met Bonferroni-adjusted statistical significance., Conclusion: Bacterial measures were related to inflammation and insulin resistance among diabetes-free adults., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Serum lactate dehydrogenase (LDH) is the standard measure for detection of hemolysis and thus surveillance for device thrombosis in patients on continuous-flow left ventricular assist device (CF-LVAD) support. Significant hemolysis has been defined as LDH ≥600 IU/L. However, LDH testing requires phlebotomy, precluding frequent home monitoring. Simple dipstick urinalysis (UA) for urine hemoglobin (U-Hb) overcomes this limitation. This study correlated U-Hb and LDH levels and evaluated the performance of UA for detection of significant hemolysis in patients with CF-LVADs., Methods: U-Hb and LDH were measured concurrently 956 times in 221 patients with CF-LVADs. Statistics were computed to determine accuracy of UA in detecting LDH ≥600 IU/L, with a positive result being any detected U-Hb. All analyses were performed with and without excluding for 1) conditions associated with tissue damage, which are known to increase LDH, and 2) suspected or confirmed urinary tract infections or hematuria, which are known to cause hemoglobinuria for reasons other than hemolysis., Results: Mean LDH for absent/mild/severe U-Hb was 360 IU/L/467 IU/L IU/L/777 IU/L without exclusions, 354 IU/L/444 IU/L IU/L/651 IU/L after excluding non-hemolytic LDH elevations, 370 IU/L/513 IU/L IU/L/1,357 IU/L after excluding urinary tract infections and hematuria, and 367 IU/L/470 IU/L IU/L/1,217 IU/L when both exclusions applied (all p < 0.001). Absent U-Hb had a negative predictive value for LDH ≥600 IU/L of >90% for all analyses., Conclusions: Serum LDH is significantly associated with U-Hb levels. Absence of U-Hb appears to efficiently exclude significant hemolysis in patients with CF-LVADs. Because it can be performed by patients at home, hemoglobinuria monitoring may enable more intense surveillance and earlier diagnosis of device thrombosis., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Today, -omics analyses, including the systematic cataloging of messenger RNA and microRNA sequences or DNA methylation patterns in a cell population, organ, or tissue sample, allow for an unbiased, comprehensive genome-level analysis of complex diseases, offering a large advantage over earlier "candidate" gene or pathway analyses. A primary goal in the analysis of these high-throughput assays is the detection of those features among several thousand that differ between different groups of samples. In the context of oral biology, our group has successfully utilized -omics technology to identify key molecules and pathways in different diagnostic entities of periodontal disease.A major issue when inferring biological information from high-throughput -omics studies is the fact that the sheer volume of high-dimensional data generated by contemporary technology is not appropriately analyzed using common statistical methods employed in the biomedical sciences.In this chapter, we outline a robust and well-accepted bioinformatics workflow for the initial analysis of -omics data generated using microarrays or next-generation sequencing technology using open-source tools. Starting with quality control measures and necessary preprocessing steps for data originating from different -omics technologies, we next outline a differential expression analysis pipeline that can be used for data from both microarray and sequencing experiments, and offers the possibility to account for random or fixed effects. Finally, we present an overview of the possibilities for a functional analysis of the obtained data.

Background: Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF., Methods: In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years., Results: The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years., Conclusions: Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients., (© 2016 American Association for Clinical Chemistry.)

Importance: Murine studies reveal that sympathetic nervous system activation leads to decreased bone mass. Stimulant medications used to treat attention-deficit/hyperactivity disorder (ADHD) increase sympathetic tone and may affect bone remodeling. Because bone mass accrual is completed by young adulthood, assessing stimulant effects on bone density in growing children is of critical importance., Objective: To investigate associations between stimulant use and bone mass in children and adolescents., Design, Setting, and Participants: This cross-sectional analysis used data collected from January 1, 2005, to December 31, 2010, from the National Health and Nutrition Examination Survey (NHANES) database. NHANES is a series of cross-sectional, nationally representative health and nutrition surveys of the US population. All children, adolescents, and young adults aged 8 to 20 years with dual-energy x-ray absorptiometry (DXA), anthropometric, demographic, and prescription medication use data were eligible for participation. Of the 6489 respondents included in the multivariable linear regression analysis, 159 were stimulant users and 6330 were nonusers. Data were analyzed from October 8, 2015, to December 31, 2016., Exposures: Stimulant use, determined by questionnaires administered via interview., Main Outcomes and Measures: The association between stimulant use and total femur, femoral neck, and lumbar spine bone mineral content (BMC) and bone mineral density (BMD) was assessed using DXA., Results: Study participants included 6489 NHANES participants with a mean (SD) age of 13.6 (3.6) years. Stimulant use was associated with lower bone mass after adjustment for covariates. Mean lumbar spine BMC was significantly lower in stimulant users vs nonusers (12.76 g; 95% CI, 12.28-13.27 g vs 13.38 g; 95% CI, 13.26-13.51 g; P = .02), as was mean lumbar spine BMD (0.90 g/cm2; 95% CI, 0.87-0.94 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .03) and mean femoral neck BMC (4.34 g; 95% CI, 4.13-4.57 g vs 4.59 g; 95% CI, 4.56-4.62 g; P = .03). Mean BMD of the femoral neck (0.88 g/cm2; 95% CI, 0.84-0.91 g/cm2 vs 0.91 g/cm2; 95% CI, 0.90-0.91 g/cm2; P = .08) and total femur (0.94 g/cm2; 95% CI, 0.90-0.99 g/cm2 vs 0.99 g/cm2; 95% CI, 0.98-0.99 g/cm2; P = .05) were also lower in stimulant users vs nonusers. Participants treated with stimulants for 3 months or longer had significantly lower lumbar spine BMD (0.89 g/cm2; 95% CI, 0.85-0.93 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .02) and BMC (12.71 g; 95% CI, 12.14-13.32 g vs 13.38 g; 95% CI, 13.25-13.51 g; P = .03) and femoral neck BMD (0.87 g/cm2; 95% CI, 0.74-0.83 g/cm2 vs 0.91 g/cm2; 95% CI, 0.83-0.84 g/cm2; P = .048) than nonusers., Conclusions and Relevance: Children and adolescents reporting stimulant use had lower DXA measurements of the lumbar spine and femur compared with nonusers. These findings support the need for future prospective studies to examine the effects of stimulant use on bone mass in children.

Aim: To evaluate the relationship between periodontal diseases and subclinical atherosclerosis in a younger and lean South Asian population., Methods: We conducted a cross-sectional study in 917 subjects (mean age 46 years and mean body mass index 21.1 kg/m 2 ) from the Health Effects of Arsenic Longitudinal Study in Bangladesh. Multivariate linear regression models were used to assess the associations between multiple clinical measures of periodontal diseases and carotid intima-media thickness (IMT)., Results: Mean attachment loss (AL) and percentage of sites with AL ≥ 4 mm (% AL ≥ 4) were associated with increased IMT. The IMT was 20.0-μm (95% CI: 2.2, 37.8) and 26.5-μm (95% CI: 8.9, 44.1) higher in subjects in the top quartile of mean AL (>3.72 mm) and % AL ≥ 4 (>58.4%), respectively, compared to those in the bottom quartile. In a subset of 366 subjects, mean AL was positively associated with plasma levels of matrix metalloproteinase-9 (p < 0.05) and soluble intercellular adhesion molecule-1 (p < 0.01)., Conclusions: Attachment loss was associated with subclinical atherosclerosis in this young and lean Bangladeshi population. Future prospective studies are needed to confirm this association., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Alterations in the microbiome, including the periodontal microbiome, may be a risk factor for rheumatoid arthritis (RA). Most studies that have analyzed this association are relatively small, focus primarily on a single periodontal pathogen (Porphyromonas gingivalis), and are not population based. This study was undertaken to investigate the association between elevated serum levels of IgG antibodies to 19 periodontal species and the prevalence of rheumatoid factor (RF) in a large nationally representative sample of adults., Methods: The Third National Health and Nutrition Examination Survey (NHANES-III) is a cross-sectional sample of the noninstitutionalized US population (n = 33,994). Our study population included all dentate participants who were 60 years and older, did not have RA as defined by a modified version of the American College of Rheumatology 1987 criteria, and had complete data for both serum IgG antibodies against periodontal bacteria and serum RF antibody titer (n = 2,461)., Results: Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) summarizing the relationship between the 19 periodontal serum IgG antibodies and RF seropositivity ranged from 0.53 (95% CI 0.29-0.97) to 1.27 (95% CI 0.79-2.06), and 17 of the 19 observed ORs were <1.0. The ORs for RF seropositivity among participants with elevated Prevotella intermedia (0.53 [95% CI 0.29-0.97]) and Capnocytophaga ochracea (0.54 [0.31-0.95]) IgG levels were statistically significant., Conclusion: Our findings indicate that elevated levels of IgG antibodies to periodontal bacteria are mostly unassociated with RF seropositivity in the nationally representative NHANES-III. Elevated levels of antibodies to P intermedia and C ochracea are associated with lower odds of RF seropositivity., Competing Interests: We have no financial conflict of interest to report., (© 2016, American College of Rheumatology.)

Background: We examined the relationship between glucose homeostasis and comprehensive measures of cardiac structure and function among a representative sample of US Hispanics., Methods and Results: ECHO-SOL (Echocardiographic Study of Latinos), an echocardiographic ancillary study of the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), enrolled 1818 Hispanic/Latino men (43%) and women (57%) aged ≥45 years (mean=56). Glucose intolerance was defined as follows: (1) prediabetes: hemoglobin (HbA1c) ≥5.7 and <6.5% and (2) diabetes mellitus: fasting plasma glucose ≥126 mg/dL, 2-hour postload glucose ≥200 mg/dL, HbA1c ≥6.5%, or hypoglycemic agent use. Uncontrolled diabetes mellitus was defined as HbA1c ≥7.0%. Insulin resistance was defined using the homeostatic model assessment for insulin resistance. Echocardiography examinations assessed left ventricular structure and systolic/diastolic function. Multivariable linear and logistic regression models were used. Prediabetes prevalence was 42%, and diabetes mellitus prevalence was 28% (47% uncontrolled). Glucose intolerance was associated with increased left ventricular posterior wall and interventricular septal and relative wall thicknesses (all P<0.05), reduced ejection fraction (P<0.01), reduced stroke and end-diastolic volumes (both P<0.001), decreased peak E' velocity (lateral and septal P<0.001), and increased E/E' ratio (lateral and septal P<0.01). The odds ratios (95% confidence intervals) for diastolic dysfunction among individuals with prediabetes and diabetes mellitus (versus diabetes mellitus free) were 1.36 (0.96-1.9) and 1.90 (1.3-2.8), respectively(P=0.006). Results were consistent for uncontrolled diabetes mellitus versus diabetes mellitus. Homeostatic model assessment for insulin resistance was associated with increased E/E' (P<0.001), and greater relative wall thickness and septal thickness (both P<0.05); lower stroke volume (P<0.0001); and lower peak lateral and septal E' velocities (both P<0.01)., Conclusions: Glucose intolerance and insulin resistance are associated with unfavorable cardiac structure and function, particularly worsened measures of diastolic function, even before the development of diabetes mellitus., (© 2016 American Heart Association, Inc.)

Analytic approaches confined to fold-change comparisons of gene expression patterns between states of health and disease are unable to distinguish between primary causal disease drivers and secondary noncausal events. Genome-wide reverse engineering approaches can facilitate the identification of candidate genes that may distinguish between causal and associative interactions and may account for the emergence or maintenance of pathologic phenotypes. In this work, we used the algorithm for the reconstruction of accurate cellular networks (ARACNE) to analyze a large gene expression profile data set (313 gingival tissue samples from a cross-sectional study of 120 periodontitis patients) obtained from clinically healthy (n = 70) or periodontitis-affected (n = 243) gingival sites. The generated transcriptional regulatory network of the gingival interactome was subsequently interrogated with the master regulator inference algorithm (MARINA) and gene expression signature data from healthy and periodontitis-affected gingiva. Our analyses identified 41 consensus master regulator genes (MRs), the regulons of which comprised between 25 and 833 genes. Regulons of 7 MRs (HCLS1, ZNF823, XBP1, ZNF750, RORA, TFAP2C, and ZNF57) included >500 genes each. Gene set enrichment analysis indicated differential expression of these regulons in gingival health versus disease with a type 1 error between 2% and 0.5% and with >80% of the regulon genes in the leading edge. Ingenuity pathway analysis showed significant enrichment of 36 regulons for several pathways, while 6 regulons (those of MRs HCLS1, IKZF3, ETS1, NHLH2, POU2F2, and VAV1) were enriched for >10 pathways. Pathways related to immune system signaling and development were the ones most frequently enriched across all regulons. The unbiased analysis of genome-wide regulatory networks can enhance our understanding of the pathobiology of human periodontitis and, after appropriate validation, ultimately identify target molecules of diagnostic, prognostic, or therapeutic value., (© International & American Associations for Dental Research 2016.)

Although depression symptoms have been associated with type 2 diabetes mellitus (T2DM) among adults, little is known about the association of adolescent-onset depression and development of T2DM in young adulthood and whether the association differs by sex. We examined the association between high levels of depressive symptoms in adolescence and T2DM in adulthood in the National Longitudinal Study of Adolescent to Adult Health (n = 12,657). Adolescents completed the 20-item version of Center for Epidemiologic Studies Depression Scale during wave 1 (mean age, 16 years) and the 10-item version during follow-up (mean age, 29 years). A high level of depressive symptoms was defined as a score of 16 or higher on the 20-item version or 11 or higher on the 10-item version. T2DM was identified 13 years after baseline on the basis of either a glycated hemoglobin concentration of at least 6.5% or use of hypoglycemic medication (with or without insulin). Participants who reported taking insulin alone were classified as having type 1 diabetes mellitus and excluded. In models adjusted for demographic characteristics, women were at a higher risk of developing T2DM if they experienced high levels of depressive symptoms during both adolescence and adulthood (odds ratio = 1.96, 95% confidence interval: 1.23, 3.11) than were those who did not experience a high level of symptoms at either time point. No statistically significant associations were noted among men (odds ratio = 0.46, 95% confidence interval: 0.20, 1.05)., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Carotid intima-media thickness (IMT) is a validated surrogate marker of preclinical atherosclerosis and is predictive of cardiovascular morbidity and mortality. Research on the association between IMT and diet, however, is lacking, especially in low-income countries or low-BMI populations., Design: Cross-sectional analysis. Dietary intakes were measured using a validated, thirty-nine-item FFQ at baseline cohort recruitment. IMT measurements were obtained from 2010-2011., Setting: Rural Bangladesh., Subjects: Participants (n 1149) randomly selected from the Health Effects of Arsenic Longitudinal Study, an ongoing, population-based, prospective cohort study established in 2000. Average age at IMT measurement was 45·5 years., Results: Principal component analysis of reported food items yielded a 'balanced' diet, an 'animal protein' diet and a 'gourd and root vegetable' diet. We observed a positive association between the gourd/root vegetable diet and IMT, as each 1 sd increase in pattern adherence was related to a difference of 7·74 (95 % CI 2·86, 12·62) μm in IMT (P<0·01), controlling for age, sex, total energy intake, smoking status, BMI, systolic blood pressure and diabetes mellitus diagnoses. The balanced pattern was associated with lower IMT (-4·95 (95 % CI -9·78, -0·11) μm for each 1sd increase of adherence; P=0·045)., Conclusions: A gourd/root vegetable diet in this Bangladeshi population positively correlated with carotid IMT, while a balanced diet was associated with decreased IMT., Competing Interests: Conflict of interests There were no conflicts of interests.

Objective: Periodontal infections have been linked to cardiovascular disease, including atherosclerosis, and systemic inflammation has been proposed as a possible mediator. Secretory phospholipase A2 (s-PLA2) and Lipoprotein-associated PLA2 (Lp-PLA2) are inflammatory enzymes associated with atherosclerosis. No data are available on the association between oral microbiota and PLA2s. We studied whether a relationship exists between periodontal microbiota and the activities of these enzymes., Methods: The Oral Infection and Vascular Disease Epidemiology Study (INVEST) collected subgingival biofilms and serum samples from 593 dentate men and women (age 68.7 ± 8.6 years). 4561 biofilm samples were collected in the two most posterior teeth of each quadrant (average 7/participant) for quantitative assessment of 11 bacterial species using DNA-DNA checkerboard hybridization. Mean concentration of s-PLA2 and activities of s-PLA2 and Lp-PLA2 were regressed on tertiles of etiologic dominance (ED). ED is defined as the level of presumed periodontopathic species/combined level of all eleven species measured, and represents the relative abundance of periodontopathic organisms. Analyses were adjusted for age, sex, race/ethnicity, education, smoking, BMI, diabetes, LDL cholesterol and HDL cholesterol, and systolic blood pressure., Results: Higher levels of s-PLA2 activity were observed across increasing tertiles of etiologic dominance (0.66 ± 0.04 nmol ml(-1) min(-1), 0.73 ± 0.04 nmol ml(-1) min(-1), 0.89 ± 0.04 nmol ml-1 min-1; p < 0.001), with also a trend of association between Lp-PLA2 activity and ED (p = 0.07), while s-PLA2 concentration was unrelated to ED., Conclusion: Increasingly greater s-PLA2 activity at higher tertiles of etiologic dominance may provide a mechanistic explanatory link of the relationship between periodontal microbiota and vascular diseases. Additional studies investigating the role of s-PLA2 are needed., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Context: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed medications to treat depression and anxiety. SSRIs exert their effects by inhibiting the serotonin transporter and modulating extracellular serotonin levels, a neurotransmitter that has been shown to affect bone metabolism in animals. Studies in adults suggest a negative association between SSRI use and bone mineral density (BMD), greater rates of bone loss with SSRI use and increased risk of fractures. However, the results on bone mass have been inconsistent. Furthermore, there is a dearth of studies examining an association between SSRI use and bone mass in the pediatric and adolescent age group., Objective: To investigate associations between SSRI use and bone mass in adolescents., Design: Cross-sectional analysis of data from the 2005-2010 National Health and Nutrition Examination Study (NHANES)., Participants: 4303 NHANES participants aged 12-20 years. The mean age was 15.65±2.42 years., Main Outcomes: Total femur, femoral neck and lumbar spine bone mineral content (BMC) and BMD assessed via dual-energy X-ray absorptiometry (DXA)., Results: 62 out of 4303 subjects used SSRIs. SSRI use was an independent predictor of bone mass after adjusting for age, gender, height and weight Z score, socioeconomic status, physical activity, serum cotinine level and race/ethnicity. After multivariable adjustment, total femur BMC was 8.8% lower among SSRI users versus non-users (mean difference 2.98 g, SE±0.105 g, p=0.0006), while total femur BMD was 6.1% lower (mean difference 0.06 g/cm2, SE±0.002 g/cm2, p=0.016). Femoral neck BMC and BMD and lumbar spine BMC were similarly negatively associated with SSRI use. Compared to nonusers, lumbar spine BMC was 7% lower among SSRI users (mean difference 0.97 g, SE±0.048g, p=0.02) and BMD was 3.2% lower (mean difference 0.03 g/cm2, SE±0.015 g/cm2, p=0.09). Sub-analysis of those individuals treated for more than 6 months yield similar results. Finally, the association of SSRIs with bone mass persisted after excluding individuals with Body Mass Index (BMI) less than 5th percentile thus accounting for the possible confounding effect of anorexia nervosa, which can be treated with SSRIs., Conclusion: In this NHANES study, adolescents treated with SSRIs had lower DXA measurements of the total femur and lumbar spine compared to SSRI non-users. These findings support the need for future prospective studies to examine the effects of SSRI use on bone mass in adolescents., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P = 0.23. Higher colonization levels of specific periodontal microbiota are associated with higher prediabetes prevalence among diabetes-free adults., (© International & American Associations for Dental Research.)

Venous congestion and endothelial and neurohormonal activation are known to occur in acute decompensated heart failure (ADHF), yet the temporal role of these processes in the pathophysiology of decompensation is not fully understood. Conventional wisdom presumes congestion to be a consequence of worsening cardiovascular function; however, the biomechanically driven effects of venous congestion are biologically plausible contributors to ADHF that remain largely unexplored in vivo. Recent experimental evidence from human models suggests that fluid accumulation and venous congestion are not simply consequences of poor cardiovascular function, but rather are fundamental pro-oxidant, pro-inflammatory, and hemodynamic stimuli that contribute to acute decompensation. The latest advances in the monitoring of volume status using implantable devices allow for the detection of venous congestion before symptoms arise. This may ultimately lead to improved treatment strategies including not only diuretics, but also specific, adjuvant interventions to counteract endothelial and neurohormonal activation during early preclinical decompensation.

In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device implantation HTN as a potential predictor of adverse CF-LVAD outcomes. HTN among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard noninvasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-cuff deflation system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may (1) consider potential mechanisms relating HTN to poor outcomes, (2) realize that HTN management is a stated goal despite scarce evidence, and (3) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward.

Background: Depression and anxiety have been inconsistently associated with diabetes. Sex differences in the biological and behavioral correlates of these forms of distress could partially explain these inconsistencies. We investigated sex-specific associations between depression/anxiety symptoms and diabetes in two separate samples., Methods: The First National Health and Nutrition Examination Survey enrolled 3233 participants aged 25 to 74 years from 1971 to 1974. Depression and anxiety symptoms were measured via General Well Being schedule subscales. Incident diabetes for 17 years was defined by the following: a) death certificate, b) participant self-report, or c) health care facility discharge. The Detroit Neighborhood Health Study enrolled 1054 participants 18 years or older from 2008 to 2010. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 assessed depression and anxiety. Participants' self-reported physician-diagnosed prevalent diabetes., Results: In the First National Health and Nutrition Examination Survey, the risk ratio (RR; 95% confidence interval) for incident diabetes among men with high versus low anxiety symptoms was 0.85 (0.56-1.29) and that among women was 2.19 (1.17-4.09; p for interaction = .005). RRs comparing high versus low depressive symptoms for men and women were 0.69 (0.43-1.100) and 2.11 (1.06-4.19); p for interaction = .007. In the Detroit Neighborhood Health Study, the RRs for prevalent diabetes comparing those with high versus low anxiety symptoms were 0.24 (0.02-2.42) for men and 1.62 (0.61-4.32) for women (p for interaction = < .001), whereas RRs for depression were 1.30 (0.46-3.68) for men and 2.32 (1.10-4.89) for women (p for interaction = .16)., Conclusions: In two separate samples, depressive symptoms were related to increased diabetes risk among women but not men. Although less robust, findings for anxiety were differentially associated with diabetes by sex.

Aim: Low-dose aspirin has been hypothesized as being a potential host modulatory agent for periodontitis treatment. We investigated the relationship between low-dose aspirin use and periodontitis prevalence in the continuous National Health and Nutrition Examination Survey, 2011-2012., Methods: We analysed n = 2335 adult men and women who received a full-mouth periodontal examination and responded to an aspirin use questionnaire. Periodontal disease was defined as severe, moderate or mild according to established case definitions. Mean full-mouth probing depth, attachment loss and tooth loss were also considered. Low-dose aspirin was defined by any self-reported, physician prescribed aspirin use of ≤162 mg/day., Results: Participants had mean age (SE) 55.8 years (0.42). The prevalences of periodontitis and low-dose aspirin use were 49.5% and 25% respectively. In multivariable logistic regression models controlling for age, sex, race, socioeconomic variables and comorbidities, the odds ratios [95%CI] for moderate or severe periodontitis among low-dose aspirin users (versus non-users) were: 0.91 [0.56-1.50] and 1.06 [0.74-1.50] respectively. Results were unchanged among participants without diabetes or coronary heart disease., Conclusions: Within the limitations of this cross-sectional study we conclude that low-dose aspirin is not associated with prevalent periodontal status in a nationally representative sample of US adults., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)