This study of loneliness across adult lifespan examined its associations with sociodemographics, mental health (positive and negative psychological states and traits), subjective cognitive ...complaints, and physical functioning.
Analysis of cross-sectional data.
340 community-dwelling adults in San Diego, California, mean age 62 (SD = 18) years, range 27-101 years, who participated in three community-based studies.
Loneliness measures included UCLA Loneliness Scale Version 3 (UCLA-3), 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation Scale, and a single-item measure from the Center for Epidemiologic Studies Depression (CESD) scale. Other measures included the San Diego Wisdom Scale (SD-WISE) and Medical Outcomes Survey- Short form 36.
Seventy-six percent of subjects had moderate-high levels of loneliness on UCLA-3, using standardized cut-points. Loneliness was correlated with worse mental health and inversely with positive psychological states/traits. Even moderate severity of loneliness was associated with worse mental and physical functioning. Loneliness severity and age had a complex relationship, with increased loneliness in the late-20s, mid-50s, and late-80s. There were no sex differences in loneliness prevalence, severity, and age relationships. The best-fit multiple regression model accounted for 45% of the variance in UCLA-3 scores, and three factors emerged with small-medium effect sizes: wisdom, living alone and mental well-being.
The alarmingly high prevalence of loneliness and its association with worse health-related measures underscore major challenges for society. The non-linear age-loneliness severity relationship deserves further study. The strong negative association of wisdom with loneliness highlights the potentially critical role of wisdom as a target for psychosocial/behavioral interventions to reduce loneliness. Building a wiser society may help us develop a more connected, less lonely, and happier society.
Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already ...collected and analysed before accepting manuscripts for publication. In this report, post hoc power analysis for retrospective studies is examined and the informativeness of understanding the power for detecting significant effects of the results analysed, using the same data on which the power analysis is based, is scrutinised. Monte Carlo simulation is used to investigate the performance of posthoc power analysis.
Statistical methods for analysis of survey data have been developed to facilitate research. More recently, Lumley and Scott (2013) developed an approach to extend the Mann‐Whitney‐Wilcoxon (MWW) rank ...sum test to survey data. Their approach focuses on the null of equal distribution. In many studies, the MWW test is called for when two‐sample t‐tests (with or without equal variance assumed) fail to provide meaningful results, as they are highly sensitive to outliers. In such situations, the null of equal distribution is too restrictive, as interest lies in comparing centers of groups. In this article, we develop an approach to extend the MWW test to survey data to test the null of equal mean rank. Although not as popular as the mean and median, the mean rank is also a meaningful measure of the center of a distribution and is the same as the median for a symmetric distribution. We illustrate the proposed approach and show major differences with Lumley and Scott's alternative using both real and simulated data.
How and when education improves cognitive capacity is an issue of profound societal importance. Education and later-life education-related factors, such as occupational complexity and engagement in ...cognitive-intellectual activities, are frequently considered indices of cognitive reserve, but whether their effects are truly causal remains unclear. In this study, after accounting for general cognitive ability (GCA) at an average age of 20 y, additional education, occupational complexity, or engagement in cognitive-intellectual activities accounted for little variance in late midlife cognitive functioning in men age 56–66 (n = 1009). Age 20 GCA accounted for 40% of variance in the same measure in late midlife and approximately 10% of variance in each of seven cognitive domains. The other factors each accounted for <1% of the variance in cognitive outcomes. The impact of these other factors likely reflects reverse causation—namely, downstream effects of early adult GCA. Supporting that idea, age 20 GCA, but not education, was associated with late midlife cortical surface area (n = 367). In our view, the most parsimonious explanation of our results, a meta-analysis of the impact of education, and epidemiologic studies of the Flynn effect is that intellectual capacity gains due to education plateau in late adolescence/early adulthood. Longitudinal studies with multiple cognitive assessments before completion of education would be needed to confirm this speculation. If cognitive gains reach an asymptote by early adulthood, then strengthening cognitive reserve and reducing later-life cognitive decline and dementia risk may really begin with improving educational quality and access in childhood and adolescence.
Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality
. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated ...liver disease. The gut microbiota promotes ethanol-induced liver disease in mice
, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis
-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.
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•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.
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.
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).
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.
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.
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.
Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol‐related liver ...disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal‐specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti–Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90‐day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11‐8.82; P = 0.031). Conclusion: Patients with alcohol‐associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.
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