Search

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women's Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through 2018. We conducted a mediation analysis to examine depressive symptoms as a potential mediator and further examined effect modification by age and race and ethnicity. Incident HF requiring hospitalization was the main outcome. Social isolation was a composite variable based on marital/partner status, religious ties, and community ties. Depressive symptoms were assessed using CES-D (Center for Epidemiology Studies-Depression). Over a median follow-up of 15.0 years, we analyzed data from 36 457 women, and 2364 (6.5%) incident HF cases occurred; 2510 (6.9%) participants were socially isolated. In multivariable analyses adjusted for sociodemographic, behavioral, clinical, and general health/functioning; socially isolated women had a higher risk of incident HF than nonisolated women (HR, 1.23; 95% CI, 1.08-1.41). Adding depressive symptoms in the model did not change this association (HR, 1.22; 95% CI, 1.07-1.40). Neither race and ethnicity nor age moderated the association between social isolation and incident HF. Conclusions Socially isolated older women are at increased risk for developing HF, independent of traditional HF risk factors. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00000611.

BackgroundCognitive impairment and decline may signal the increased risk of incident cardiovascular disease (CVD). We examined associations of global cognitive function, as measured by the Modified Mini-Mental State Examination (3MS) and changes in 3MS over time, with incident CVD, individual CVD outcomes, CVD death, and all-cause mortality.MethodsA total of 5,596 women (≥ 60) from the Women's Health Initiative Memory Study free of CVD at baseline were followed for an average of 7.1 years. The 3MS was measured at baseline and annually thereafter. Cox proportional hazards regressions were used to model associations between baseline 3MS and changes in 3MS and time to events.ResultsIn the fully-adjusted models for every 5-point lower baseline 3MS score, the risk was 12% greater for incident CVD, 37% for HF, 35% for CVD death, and 24% for all-cause mortality. No significant relationships were found for coronary heart disease (CHD), angina, stroke/transient ischemic attack (TIA), or coronary revascularization. When change in 3MS was added as a time-varying covariate in the fully-adjusted models, for every 1-point/year greater decline in 3MS, the risk was 4% greater for incident CVD, 10% for CHD, 9% for Stroke/TIA, 17% for CVD death, and 13% for all-cause mortality.ConclusionsIn older women free of prevalent CVD at baseline, lower baseline global cognitive function or decline in global cognitive function over time, increased risk of incident CVD, CVD death, and all-cause mortality.

INTRODUCTION: Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI). METHODS: The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area Deprivation Index (ADI) rank with measures of cardiometabolic health and cognition among Wake Forest (WF) Alzheimer's Disease Research Center (ADRC) participants, with and without MCI. RESULTS: ADI was positively associated with blood pressure and cardiometabolic index (CMI), and negatively associated with global and Preclinical Alzheimer's Cognitive Composite (PACC5) scores, in cognitively unimpaired (CU) individuals. ADI was only positively associated with hemoglobin A1c (HbA1c) in MCI. DISCUSSION: Neighborhood disadvantage is associated more strongly with measures of cardiometabolic health and cognition among CU individuals rather than MCI. These findings demonstrate a need for structural solutions to address social determinants of health in an attempt to reduce cardiometabolic and cognitive risks. [ABSTRACT FROM AUTHOR]

Introduction: This study presents a rare case of multiple evanescent white dot syndrome (MEWDS) with atypical electrooculogram (EOG) findings, as well as abnormal en-face images of minimum intensity projection (Min-IP) and the en-face inner segment/outer segment-ellipsoid complex. Methods: A 25-year-old female patient presented with painless visual impairment and photopsia in her right eye for a duration of two days. Multimodal imaging was employed including color fundus photography (CFP), fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA), and en-face images of Min-IP and the en-face inner segment/outer segment-ellipsoid complex were performed. Results: In the right eye, multifocal small white spots were observed surrounding the posterior pole and optic disc of retina with the granular appearance of the fovea. FAF displayed of hyperfluorescence. SD-OCT appearance of MEWDS demonstrated primarily disrupted ellipsoid zone (EZ), photoreceptor outer segments, and interdigitation zone (IZ) complex within the fovea. The en-face images of the inner segment/outer segment-ellipsoid complex and Min-IP exhibited hyperreflective spots in the right eye. In the left eye, interestingly, hyperreflective spots were also observed on the en-face image of the inner segment/outer segment-ellipsoid complex. EOG revealed an Arden ratio of 2.5 for the right eye, while the left eye exhibited an Arden ratio of 1.7. Conclusion: The en-face image of the inner segment/outer segment-ellipsoid complex in MEWDS exhibits aberrant features and it is noteworthy that a similar alteration may occur in the fellow eye. Further investigation is required to explore the relationship between MEWDS and EOG. The en-face images of the inner segment/outer segment-ellipsoid complex and Min-IP may help to elucidate the pathogenesis of MEWDS. [ABSTRACT FROM AUTHOR]

Abstract Background Dendritic cells (DC) play a central role in primary immune responses and become potent stimulators of the adaptive immune response after undergoing the critical process of maturation. Understanding the dynamics of DC maturation would provide key insights into this important process. Time course microarray experiments can provide unique insights into DC maturation dynamics. Replicate experiments are necessary to address the issues of experimental and biological variability. Statistical methods and averaging are often used to identify significant signals. Here a novel strategy for filtering of replicate time course microarray data, which identifies consistent signals between the replicates, is presented and applied to a DC time course microarray experiment. Results The temporal dynamics of DC maturation were studied by stimulating DC with poly(I:C) and following gene expression at 5 time points from 1 to 24 hours. The novel filtering strategy uses standard statistical and fold change techniques, along with the consistency of replicate temporal profiles, to identify those differentially expressed genes that were consistent in two biological replicate experiments. To address the issue of cluster reproducibility a consensus clustering method, which identifies clusters of genes whose expression varies consistently between replicates, was also developed and applied. Analysis of the resulting clusters revealed many known and novel characteristics of DC maturation, such as the up-regulation of specific immune response pathways. Intriguingly, more genes were down-regulated than up-regulated. Results identify a more comprehensive program of down-regulation, including many genes involved in protein synthesis, metabolism, and housekeeping needed for maintenance of cellular integrity and metabolism. Conclusions The new filtering strategy emphasizes the importance of consistent and reproducible results when analyzing microarray data and utilizes consistency between replicate experiments as a criterion in both feature selection and clustering, without averaging or otherwise combining replicate data. Observation of a significant down-regulation program during DC maturation indicates that DC are preparing for cell death and provides a path to better understand the process. This new filtering strategy can be adapted for use in analyzing other large-scale time course data sets with replicates.

Abstract Background Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene expression associated with different developmental stages to each other to study patterns of long-term developmental gene regulation. We use tools from functional data analysis to study dynamic changes by relating temporal gene expression profiles of different developmental stages to each other. Results We demonstrate that functional regression methodology can pinpoint relationships that exist between temporary gene expression profiles for different life cycle phases and incorporates dimension reduction as needed for these high-dimensional data. By applying these tools, gene expression profiles for pupa and adult phases are found to be strongly related to the profiles of the same genes obtained during the embryo phase. Moreover, one can distinguish between gene groups that exhibit relationships with positive and others with negative associations between later life and embryonal expression profiles. Specifically, we find a positive relationship in expression for muscle development related genes, and a negative relationship for strictly maternal genes for Drosophila, using temporal gene expression profiles. Conclusion Our findings point to specific reactivation patterns of gene expression during the Drosophila life cycle which differ in characteristic ways between various gene groups. Functional regression emerges as a useful tool for relating gene expression patterns from different developmental stages, and avoids the problems with large numbers of parameters and multiple testing that affect alternative approaches.

Objective To assess the long-term effects of an intensive lifestyle intervention on physical function using a randomized post-test design in the Look AHEAD trial. Methods Overweight and obese (BMI ≥ 25 kg m−2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes ( n = 964) at four clinics in Look AHEAD, a trial evaluating an intensive lifestyle intervention (ILI) designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including an expanded short physical performance battery (SPPBexp), 20-m and 400-m walk, and grip and knee extensor strength 8 years post-randomization, during the trial's weight maintenance phase. Results Eight years post-randomization, individuals randomized to ILI had better SPPBexp scores [adjusted mean (SE) difference: 0.055 (0.022), P = 0.01] and faster 20-m and 400-m walk speeds [0.032 (0.012) m s−1, P = 0.01, and 0.025 (0.011) m s−1, P = 0.02, respectively] compared to those randomized to DSE. Achieved weight loss greatly attenuated the group differences in physical function, and the intervention effect was no longer significant. Conclusions An intensive lifestyle intervention has long-term benefits for mobility function in overweight and obese middle-aged and older individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Poor oral health influences the dietary quality of older individuals. The objective of the present study was to relate the number of teeth to adherence to the 2005 Dietary Guidelines for Americans among an ethnically diverse sample of older adults. Design: A block cluster design was used to obtain a sample of older adults. Data were weighted to census data for ethnicity and gender. Dietary intakes were assessed using an FFQ and converted into Healthy Eating Index-2005 (HEI-2005) scores. Setting: Two counties in North Carolina, USA, with large African-American and American Indian populations. Subjects: Community-dwelling older adults (N 635). Results: Three hundred and twenty-six participants had severe tooth loss (0-10 teeth remaining), compared with 305 participants with 111 teeth. After controlling for socio-economic factors, those with 0-10 teeth had lower total HEI-2005 scores and consumed less Total Fruit, Meat and Beans, and Oils, and more energy from Solid Fat, Alcohol and Added Sugar, compared with those with 111 teeth. Less than 1% of those with 0-10 teeth and 4% of those with 111 teeth met overall HEI-2005 recommendations. Those with 0-10 teeth were less likely to eat recommended amounts of Total Vegetables, Dark Green and Orange Vegetables, and energy from Solid Fat, Alcohol and Added Sugar. Conclusions: Older adults with severe tooth loss are less likely than those with moderate to low tooth loss to meet current dietary recommendations. Nutrition interventions for older adults should take oral health status into consideration and include strategies that specifically address this as a barrier to healthful eating. [ABSTRACT FROM AUTHOR]

Background: Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke., Objective: The present study represents the first multi-center effort to measure cortical reorganization induced by CIMT in subjects who are in the subacute stage of recovery., Methods: A total of 30 stroke subjects in the subacute phase (>3 and <9 months poststroke) were recruited and randomized into experimental (receiving CIMT immediately after baseline evaluation) and control (receiving CIMT after 4 months) groups. Each subject was evaluated using transcranial magnetic stimulation (TMS) at baseline, 2 weeks after baseline, and at 4-month follow-up (ie, after CIMT in the experimental groups and before CIMT in the control groups). The primary clinical outcome measure was the Wolf Motor Function Test., Results: Both experimental and control groups demonstrated improved hand motor function 2 weeks after baseline. The experimental group showed significantly greater improvement in grip force after the intervention and at follow-up (P = .049). After adjusting for the baseline measures, the experimental group had an increase in the TMS motor map area compared with the control group over a 4-month period; this increase was of borderline significance (P = .053)., Conclusions: Among subjects who had a stroke within the previous 3 to 9 months, CIMT produced statistically significant and clinically relevant improvements in arm motor function that persisted for at least 4 months. The corresponding enlargement of TMS motor maps, similar to that found in earlier studies of chronic stroke subjects, appears to play an important role in CIMT-dependent plasticity.