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Objective: To establish whether positive affect (PA) is uniquely associated with loneliness and other social functioning variables beyond negative affect (NA) among older adults.Methods: Four hundred and twenty-eight participants (aged 60+ years old, 82% White, and 48% female) were recruited using random digit-dialing and completed scales for loneliness (UCLA Loneliness Scale), companionship (PROMIS scale), satisfaction with discretionary social activities (PROMIS scale), PA (Center for Epidemiologic Studies [CES] Happiness Scale), and NA (CES-Depression scale and Brief Symptom Inventory-Anxiety Subscale).Results: Multiple linear regression models found PA to be a significant predictor of lower loneliness where the effect of PA on loneliness is dependent on the level of NA; a large effect size at the mean level of NA, which becomes attenuated when NA increases. Although the direction of effect of PA on loneliness will change for NA > 5.10, which is 5 standard deviations away from 0, based on the model estimates, the percent of subjects with this large NA levels is practically 0. Thus, higher PA is associated with lower loneliness, however this effect is attenuated for larger NA. Similarly, multiple linear regression models found that companionship was associated with PA and NA where the effect of PA is dependent on the level of NA; a medium effect size at the mean level of NA, which becomes attenuated when NA increases. As in the case of loneliness, the direction of effect of PA on companionship will change for NA > 3.52, which is 3.5 standard deviation away from 0, based on the model estimates, but the percent of subjects with this large NA levels is practically 0. Thus, higher PA is associated with increased companionship, aand this effect is attenuated with greater NA. Satisfaction with social activities was associated with PA only (medium effect size).Conclusion: Results suggest PA appears to be uniquely associated with social functioning among older adults. These findings support the potential for treatments that target PA to decrease loneliness among older adults, or vice versa. [ABSTRACT FROM AUTHOR]

Alterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD. In a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0–4, 44 patients had an NAS of 5–8 or liver cirrhosis (LCI), 37 patients had F0–F1 fibrosis, and 36 patients had F2–F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles. Patients with NAFLD and NAS 5–8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0–4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5–8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91–0.99) and F2–F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80–0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity. In a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies patients with severe NAFLD and fibrosis more accurately than models based only on clinical or bacterial data. [ABSTRACT FROM AUTHOR]

Type 2 Diabetes mellitus is associated with aging and shortened telomere length. Telomerase replaces lost telomeric repeats at the ends of chromosomes and is necessary for the replicative immortality of cells. Aspirin and the n3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are commonly used therapies in people with type 2 diabetes for reducing cardiovascular disease events, though their relation to telomerase activity is not well studied. We explored the effects of aspirin, EPA + DHA, and the combined effects of aspirin and EPA + DHA treatment on telomerase activity in 30 adults with diabetes mellitus. EPA and DHA ingestion alone increased telomerase activity then a decrease occurred with the addition of aspirin consumption. Crude (F-stat = 2.09, p = 0.13) and adjusted (F-stat = 2.20, p = 0.14) analyses of this decrease showed signs of a trend. These results suggest that aspirin has an adverse effect on aging in diabetics who have relatively high EPA and DHA ingestion. [ABSTRACT FROM AUTHOR]

Objective: To examine associations of sociodemographic and clinical factors with cognitive, physical, and mental health among independent living older adults in a continuing care senior housing community (CCSHC).Methods: This was a cross-sectional study at the independent living sector of a CCSHC in San Diego County, California. Participants included English-speaking adults aged 65-95 years, of which two-thirds were women. Of the 112 subjects recruited, 104 completed basic study assessments. The authors computed composite measures of cognitive, physical, and mental health. The authors also assessed relevant clinical correlates including psychosocial factors such as resilience, loneliness, wisdom, and social support.Results: The CCSHC residents were similar to a randomly selected community-based sample of older adults on most standardized clinical measures. In the CCSHC, physical health correlated with both cognitive function and mental health, but there was no significant correlation between cognitive and mental health. Cognitive function was significantly associated with physical mobility, satisfaction with life, and wisdom, whereas physical health was associated with age, self-rated physical functioning, mental well-being, and resilience. Mental health was significantly associated with income, optimism, self-compassion, loneliness, and sleep disturbances.Conclusion: Different psychosocial factors are significantly associated with cognitive, physical, and mental health. Longitudinal studies of diverse samples of older adults are necessary to determine risk factors and protective factors for specific domains of health. With rapidly growing numbers of older adults who require healthcare as well as supportive housing, CCSHCs will become increasingly important sites for studying and promoting the health of older adults. [ABSTRACT FROM AUTHOR]

Objectives: Persons with schizophrenia, and women in particular, are at high risk for sleep disturbances and inflammatory activation. The sleep-inflammation link has been reported to be stronger in women within the general population. This study sought to examine the sleep-inflammation link in persons with schizophrenia and its relationship with demographic, clinical and cognitive variables.Design: Cross-sectional case-control study.Participants: Community-dwelling outpatients with schizophrenia (N=144, 46% women) and non-psychiatric comparison (NC) participants (N=134, 52% women), age 26-65 years.Measurements: Reported sleep disturbances (sleep quality and duration), and mental and physical health were assessed. Cognitive assessments included executive functioning (Delis-Kaplan Executive Function System) and global cognitive functioning (Telephone Interview for Cognitive Status - modified.) Inflammatory biomarkers included pro-inflammatory cytokines [high sensitivity C-Reactive Protein (hs-CRP), Interleukin (IL)-6, Tumor Necrosis Factor-α (TNF-α)] and an anti-inflammatory cytokine (IL-10).Results: The schizophrenia group had longer sleep duration, worse sleep quality, and increased levels of hs-CRP, IL-6, and TNF-α compared to NCs. Women with schizophrenia were less likely to have good sleep quality and had elevated levels of hs-CRP and IL-6 compared to men with schizophrenia. In the schizophrenia group, worse sleep quality and global cognitive functioning were associated with higher hs-CRP and IL-6 levels. Female sex and younger age were also associated with higher hs-CRP levels.Conclusions: Sleep disturbances and increased inflammation, which were common in schizophrenia, were associated in persons with schizophrenia. Moreover, women with schizophrenia had worse sleep quality and inflammation than men. Further examination of the sleep-inflammation links, their contribution to clinical outcomes, and sex-specific factors is warranted. [ABSTRACT FROM AUTHOR]

Background/synopsis Low-dose aspirin is an effective drug for the prevention of cardiovascular disease (CVD) events but individuals with diabetes mellitus can be subject to ‘aspirin resistance’. Thus, aspirin's effect in these individuals is controversial. Higher blood levels of seafood-derived omega-3 polyunsaturated fatty acids (ω3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also have beneficial effects in reducing risk of CVD events but few studies have examined the interaction of plasma EPA and DHA with aspirin ingestion. Objective/purpose Our study examined the combinatory effects of EPA, DHA, and aspirin ingestion on HDL-cholesterol (HDL-C) and apoA-I exchange (shown to be associated with CVD event risk). Methods 30 adults with Type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 consecutive days, EPA+DHA (2.6 g/day) for 28 days, then both for 7 days. Plasma was collected at baseline and at 5 subsequent visits including 4 h after each aspirin ingestion. Mixed model methods were used to determine HDL-C-concentrations and apoA-I exchange compared to the baseline visit values. LOWESS curves were used for non-linear analyses of outcomes to help discern change patterns, which was followed by piecewise linear functions for formal testing of curvilinear relationships. Results Significant changes (p < 0.05) compared to baseline in both HDL-C-concentrations and apoA-I exchange were present at different times. After 7 days of aspirin-only ingestion, apoA-I exchange was significantly modified by increasing levels of DHA concentration, with increased apoA-I exchange observed up until log(DHA) of 4.6 and decreased exchange thereafter (p = 0.03). These LOWESS curve effects were not observed for EPA or HDL-C (p > 0.05). Aspirin's effects on apoA-I exchange were the greatest when EPA or DHA concentrations were moderate compared to high or low. Comparison of EPA, DHA, and EPA+DHA LOWESS curves, demonstrated that the majority of the effect is due to DHA. Conclusion Our results strongly suggest that plasma concentrations of EPA and DHA influence aspirin effects on lipid mediators of CVD event risk where their concentrations are most beneficial when moderate, not high or low. These effects on HDL-C cholesterol and apoA-I exchange are novel. Personalized dosing of DHA in those who take aspirin may be a beneficial option for patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

The article discusses research which was conducted to investigate the effectiveness of a psychotherapeutic intervention designed for older adults at risk for suicide. Researchers evaluated the intervention with 17 English speaking adults aged 60 and older. They found that the intervention led to significant reductions in suicide ideation, death ideation, and depressive symptom severity and significant improvements in psychological well being.

• Aspirin's cardiovascular effects in the Framingham Study differ by plasma levels of EPA and DHA. • Events in those not taking aspirin with EPA and DHA in the second lowest quintile were reduced. • Events in those taking aspirin with EPA and DHA in the second lowest quintile were increased. • A personalized approach to both aspirin use and omega-3 supplementation may be needed. The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect of aspirin combined with a particular n3 fatty acid level present in each individual. RBC EPA+DHA, arachidonic acid (AA) and docosapentaenoic acid (DPA) were measured in 2500 participants without known CVD in the Framingham Heart Study. We then tested for interactions with reported aspirin use (1004 reported use and 1494 did not) on CVD outcomes. The median follow-up was 7.2 years. Having RBC EPA+DHA in the second quintile (4.2–4.9% of total fatty acids) was associated with significantly reduced risk for future CVD events (relative to the first quintile, <4.2%) in those who did not take aspirin (HR 0.54 (0.30, 0.98)), but in those reporting aspirin use, risk was significantly increased (HR 2.16 (1.19, 3.92)) in this quintile. This interaction remained significant when adjusting for confounders. Significant interactions were also present for coronary heart disease and stroke outcomes using the same quintiles. Similar findings were present for EPA and DHA alone but not for DPA and AA. There is a complex interaction between aspirin use and RBC EPA+DHA levels on CVD outcomes. This suggests that aspirin use may be beneficial in one omega-3 environment but harmful in another, implying that a personalized approach to both aspirin use and omega-3 supplementation may be needed. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This paper is aimed to develop and validate the hypertension scale of the system of Quality of Life Instruments for Chronic Diseases, QLICD-HY. Methods: The QLICD-HY instrument was developed based on programmed decision procedures with multiple nominal and focus group discussions and pilot testing. A total of 157 inpatients with hypertension were used to provide the data measuring QOL three times before and after treatment. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation and factor analyses, and t-tests. Results: Correlation and factor analyses confirmed good construct validity and criterion-related validity when using Short Form (36) Health Survey (SF-36) as a criterion. Test–retest reliability coefficients (Pearson r and intra-class correlation (ICC)) for the overall instrument score and all domains except for the hypertension-specific domain (SPD) (0.75) were higher than 0.80 with a range of 0.75–0.91; the internal consistency α for all domains except for the hypertension-specific domain (0.66) was higher than 0.70. The overall score and scores for most facets within each domain except for the social domain (SOD) had statistically significant changes (t-tests) after treatment with moderate effect sizes. Conclusion: QLICD-HY has good validity, reliability, responsiveness and can be used as the quality-of-life instrument for patients with hypertension. [Copyright &y& Elsevier]

• A lifestyle composite of smoking, alcohol consumption, diet, physical activity, and social engagement at age 40 was associated with accelerated brain aging in old age. • Brain aging and AD-brain signature in old age were worse among participants with lower age 20 cognitive ability. • Lower cognitive ability predicted better brain outcomes if lifestyle was favorable, but high cognitive ability predicted better brain outcomes regardless of lifestyle. • Favorable early midlife lifestyle may be protective against neurodegeneration and dementia risk especially among adults with lower cognitive ability. • Efforts at prevention could be prioritized earlier in midlife. We examined the influence of lifestyle on brain aging after nearly 30 years, and tested the hypothesis that young adult general cognitive ability (GCA) would moderate these effects. In the community-dwelling Vietnam Era Twin Study of Aging (VETSA), 431 largely non-Hispanic white men completed a test of GCA at mean age 20. We created a modifiable lifestyle behavior composite from data collected at mean age 40. During VETSA, MRI-based measures at mean age 68 included predicted brain age difference (PBAD), Alzheimer's disease (AD) brain signature, and abnormal white matter scores. There were significant main effects of young adult GCA and lifestyle on PBAD and the AD signature (p s ≤ 0.012), and a GCA-by-lifestyle interaction on both (p s ≤ 0.006). Regardless of GCA level, having more favorable lifestyle behaviors predicted less advanced brain age and less AD-like brain aging. Unfavorable lifestyles predicted advanced brain aging in those with lower age 20 GCA, but did not affect brain aging in those with higher age 20 GCA. Targeting early lifestyle modification may promote dementia risk reduction, especially among lower reserve individuals. [ABSTRACT FROM AUTHOR]

Cognitive change in people with schizophrenia (PwS) is challenging to assess, but important to understand. Previous studies with limited age ranges and follow-up were subject to practice effects. Controlling for practice effects in a well-established cohort, we examined executive functioning trajectories and their association with inflammatory biomarkers, hypothesizing that PwS will have worsening executive functioning over time compared to non-psychiatric comparison participants (NCs), predicted by higher baseline inflammation with a stronger relationship in PwS than NCs. Executive functioning was assessed in 350 participants (n = 186 PwS, 164 NCs) at 12–16-month intervals (0 to 7 follow-up visits). Inflammatory biomarkers at baseline included high sensitivity C-Reactive Protein (hs-CRP), Interferon-gamma, Tumor Necrosis Factor (TNF)-alpha, and Interleukin(IL)-6, −8, and − 10. Executive functioning trajectories across diagnostic groups were estimated using a linear mixed-effects model controlling for age, sex, race/ethnicity, and education level, with additional models to assess prediction by baseline inflammation. Over 4.4 years average follow-up, improvements in executive functioning were attenuated in PwS and older participants. Controlling for practice effects negated improvements, revealing declines among highly educated participants regardless of diagnosis. Higher baseline hs-CRP predicted worse executive functioning only among NCs, while TNF-alpha was predictive of change in all participants only after controlling for practice effects. Only the main effect of hs-CRP on executive function was significant after adjusting for multiple comparisons. None of the other inflammatory biomarkers predicted executive functioning or trajectories of performance among study participants. Systemic inflammation as reflected by baseline inflammatory biomarker levels did not predict longitudinal declines in executive functioning. Additional studies examining the temporal dynamics of inflammation and cognition in PwS will help further clarify their relationship and associated mechanisms. • Higher baseline TNF-alpha predicted worse cognition over 4.4 years, but not after controlling for multiple comparisons. • After controlling for practice effects, people with schizophrenia did not have accelerated decline in executive functioning. • Older age and less education were associated with worse cognitive functioning. [ABSTRACT FROM AUTHOR]

Wisdom has gained increasing interest among researchers as a personality trait relevant to well-being and mental health. We previously reported development of a new 24-item San Diego Wisdom Scale (SD-WISE), with good to excellent psychometric properties, comprised of six subscales: pro-social behaviors, emotional regulation, self-reflection (insight), tolerance for divergent values (acceptance of uncertainty), decisiveness, and social advising. There is controversy about whether spirituality is a marker of wisdom. The present cross-sectional study sought to address that question by developing a new SD-WISE subscale of spirituality and examining its associations with various relevant measures. Data were collected from a national-level sample of 1,786 community-dwelling adults age 20–82 years, as part of an Amazon M-Turk cohort. Participants completed the 24-item SD-WISE along with several subscales of a commonly used Brief Multidimensional Measure of Religiousness/Spirituality, along with validated scales for well-being, resilience, happiness, depression, anxiety, loneliness, and social network. Using latent variable models, we developed a Spirituality subscale, which demonstrated acceptable psychometric properties including a unidimensional factor structure and good reliability. Spirituality correlated positively with age and was higher in women than in men. The expanded 28-item, 7-subscale SD-WISE total score (called the Jeste-Thomas Wisdom Index or JTWI) demonstrated acceptable psychometric properties. The Spirituality subscale was positively correlated with good mental health and well-being, and negatively correlated with poor mental health. However, compared to other components of wisdom, the Spirituality factor showed weaker (i.e., small-to-medium vs. medium-to-large) association with the SD-WISE higher-order Wisdom factor (JTWI). Similar to other components as well as overall wisdom, spirituality is significantly associated with better mental health and well-being, and may add to the predictive utility of the total wisdom score. Spirituality is, however, a weaker contributor to overall wisdom than components like pro-social behaviors and emotional regulation. Longitudinal studies of larger and more diverse samples are needed to explore mediation effects of these constructs on well-being and health. [ABSTRACT FROM AUTHOR]

• Fecal levels of C. albicans and ECE1 are increased in patients with alcoholic hepatitis. • Candidalysin enhances ethanol-induced liver disease and is associated with higher mortality in mice. • Candidalysin damages hepatocytes in a dose-dependent manner. • Candidalysin is associated with the severity of liver disease and mortality in patients with alcoholic hepatitis. Alcohol-associated liver disease is a leading indication for liver transplantation and a leading cause of mortality. Alterations to the gut microbiota contribute to the pathogenesis of alcohol-associated liver disease. Patients with alcohol-associated liver disease have increased proportions of Candida spp. in the fecal mycobiome, yet little is known about the effect of intestinal Candida on the disease. Herein, we evaluated the contributions of Candida albicans and its exotoxin candidalysin in alcohol-associated liver disease. C. albicans and the extent of cell elongation 1 (ECE1) were analyzed in fecal samples from controls, patients with alcohol use disorder and those with alcoholic hepatitis. Mice colonized with different and genetically manipulated C. albicans strains were subjected to the chronic-plus-binge ethanol diet model. Primary hepatocytes were isolated and incubated with candidalysin. The percentages of individuals carrying ECE1 were 0%, 4.76% and 30.77% in non-alcoholic controls, patients with alcohol use disorder and patients with alcoholic hepatitis, respectively. Candidalysin exacerbates ethanol-induced liver disease and is associated with increased mortality in mice. Candidalysin enhances ethanol-induced liver disease independently of the β-glucan receptor C-type lectin domain family 7 member A (CLEC7A) on bone marrow-derived cells, and candidalysin does not alter gut barrier function. Candidalysin can damage primary hepatocytes in a dose-dependent manner in vitro and is associated with liver disease severity and mortality in patients with alcoholic hepatitis. Candidalysin is associated with the progression of ethanol-induced liver disease in preclinical models and worse clinical outcomes in patients with alcoholic hepatitis. Candidalysin is a peptide toxin secreted by the commensal gut fungus Candida albicans. Candidalysin enhances alcohol-associated liver disease independently of the β-glucan receptor CLEC7A on bone marrow-derived cells in mice without affecting intestinal permeability. Candidalysin is cytotoxic to primary hepatocytes, indicating a direct role of candidalysin on ethanol-induced liver disease. Candidalysin might be an effective target for therapy in patients with alcohol-associated liver disease. [ABSTRACT FROM AUTHOR]

Persons with schizophrenia and schizoaffective disorder (PwS) have high rates of cardiometabolic pathology that contributes to premature mortality. Adiponectin is a metabolic hormone affecting insulin sensitivity and inflammation, and is active in the brain. High-molecular weight (HMW) adiponectin is considered a more sensitive marker of metabolic dysfunction than total adiponectin, but has been poorly studied in schizophrenia. This was a cross-sectional study of 100 PwS, age range 26–68 years (46 women), and 93 age- and sex-comparable non-psychiatric comparison (NC) subjects. Assessments included measures of psychopathology, physical health, cognitive function, and circulating biomarkers of metabolic dysfunction (HMW adiponectin, lipids, insulin resistance) and inflammation (high-sensitivity C-reactive protein or hs-CRP, Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10). HMW adiponectin levels were lower in PwS compared to NCs. Lower HMW adiponectin levels were associated with higher body mass index (BMI), higher Framingham risk for coronary heart disease, higher number of metabolic syndrome criteria, greater insulin resistance, lower HDL cholesterol, and higher hs-CRP in both groups. Only in PwS, lower HMW adiponectin correlated with younger age. In the best-fit regression models of HMW adiponectin, lower levels were associated with lower HDL cholesterol and minority race/ethnicity in both groups; but with younger age, non-smoking, higher insulin resistance, and a diagnosis of schizoaffective disorder only among PwS, and with male sex, better cognitive functioning, and higher hs-CRP levels in NCs only. HMW adiponectin may be a promising biomarker of cardiometabolic health, especially among PwS. Adiponectin is a potential target for lifestyle and pharmacological interventions. Research on the possible role of HMW adiponectin in modifying cardiometabolic pathology in schizophrenia is needed. • High-molecular weight adiponectin is understudied in schizophrenia. • Schizophrenia patients have lower adiponectin levels than non-psychiatric controls. • Adiponectin may be a promising biomarker of cardio-metabolic health in schizophrenia. [ABSTRACT FROM AUTHOR]