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The advent of super‐resolution microscopy allowed for new insights into cellular and physiological processes of normal and diseased cells. In this study, we report for the first time on the super‐resolved DNA structure of buccal cells from patients with Alzheimer's disease (AD) versus age‐ and gender‐matched healthy, non‐caregiver controls. In this super‐resolution study cohort of 74 participants, buccal cells were collected and their spatial DNA organization in the nucleus examined by 3D Structured Illumination Microscopy (3D‐SIM). Quantitation of the super‐resolution DNA structure revealed that the nuclear super‐resolution DNA structure of individuals with AD significantly differs from that of their controls (p

Cells arrested in mitosis by inactivation of the APC/C complex sometimes manage to exit mitosis in a process called mitotic slippage, which helps cancer cells circumvent chemotherapy drugs. Balachandran et al. show that mitotic slippage occurs as a result of targeting of cyclin B1 for degradation by the ligase CRL2ZYG11., The anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase is known to target the degradation of cyclin B1, which is crucial for mitotic progression in animal cells. In this study, we show that the ubiquitin ligase CRL2ZYG-11 redundantly targets the degradation of cyclin B1 in Caenorhabditis elegans and human cells. In C. elegans, both CRL2ZYG-11 and APC/C are required for proper progression through meiotic divisions. In human cells, inactivation of CRL2ZYG11A/B has minimal effects on mitotic progression when APC/C is active. However, when APC/C is inactivated or cyclin B1 is overexpressed, CRL2ZYG11A/B-mediated degradation of cyclin B1 is required for normal progression through metaphase. Mitotic cells arrested by the spindle assembly checkpoint, which inactivates APC/C, often exit mitosis in a process termed “mitotic slippage,” which generates tetraploid cells and limits the effectiveness of antimitotic chemotherapy drugs. We show that ZYG11A/B subunit knockdown, or broad cullin–RING ubiquitin ligase inactivation with the small molecule MLN4924, inhibits mitotic slippage in human cells, suggesting the potential for antimitotic combination therapy.

To critically analyze appropriate clinical studies to assess the relationship between health conditions and the frequency of private prayer. Private prayer is defined as individuals praying for themselves.Using PubMed and other search engines, we identified over 300 articles reporting relationships between prayer and health conditions. We identified 41 observational clinical studies that evaluated the relationship between private prayer and health conditions. Prayer scores of 5 to 1 were assigned to studies, with 5 being private prayer for health and 1 being prayer in combination with meditation or Bible study. Frequency scores ranged from 3 to 1 with 3 being twice daily or more and 0 when frequency was not assessed. Studies were ranked from 8 to 1 based on the sum of Prayer and Frequency Scores.Twenty-one studies had Prayer-Frequency scores of 5 to 8, indicating that they evaluated private prayer (praying for one's own health) of suitable frequency in association with health conditions. Nine of 11 studies indicated that private prayer was associated with a significantly lower prevalence of depression (P value,0.01). Optimism as well as coping were significantly improved by prayer in four studies (P value, P 0.01). In 10 studies of mental health conditions-including anxiety and confusion-there was a significant benefit associated with prayer (P 0.01), In the reviewed studies, prayer did not have a significant effect on physical health or blood pressure.The reported observational studies suggest that frequent private prayer is associated with a significant benefit for depression, optimism, coping, and other mental health conditions such as anxiety. Controlled clinical trials are required to critically assess the associations of private prayer and health conditions.

We develop a condition on a closed curve on a surface or in a 3-manifold that implies that the length function associated to the curve on the space of all hyperbolic structures on the surface or in the 3-manifold (respectively) completely determines the curve. Specifically, for an orientable surfaceSof negative Euler characteristic, we extend the known result that simple curves have this property to curves with self-intersection number one (with one exceptional case arising from hyperellipticity that we describe completely). For a large class of hyperbolizable 3-manifolds, we show that curves freely homotopic to simple curves on ∂Mhave this property.

Just as the type and duration of physical activity can have variable effects on the glucose levels and other cardiometabolic parameters among patients with type 2 diabetes mellitus (T2DM), so can the types of foods have variable effects as well. This 12-week randomized study of 51 study participants evaluated the impact of routine consumption of dark raisins versus alternative processed snacks on glucose levels and other cardiovascular risk factors among patients with type T2DM. In this study, compared to alternative processed snacks, those who consumed raisins had a significant 23% reduction in postprandial glucose levels (P = 0.024). Also compared to snacks, those who consumed raisins had a 19% reduction in fasting glucose and 0.12% reduction in hemoglobin A1c, although these latter findings did not achieve statistical significance. Regarding blood pressure, compared to alternative processed snacks, those who consumed raisins had a significant 8.7 mmHg reduction in systolic blood pressure (P = 0.035) (7.5% [P = 0.031]) but did not experience a significant reduction in diastolic blood pressure. Compared to alternative processed snacks, those who consumed raisins did not have a significant improvement in body weight, body mass index, waist circumference, fasting insulin, homeostatic model assessment of insulin resistance, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL), triglyceride, or non-HDL cholesterol levels. Overall, these data support raisins as a healthy alternative compare to processed snacks in patients with T2DM.

This study validates and expands on our previous work that assessed three-dimensional (3D) nuclear telomere profiling in buccal cells of Alzheimer's disease (AD) patients and non-AD controls (Mathur et al., J Alzheimers Dis 39, 35-48, 2014). While the previous study used age- and gender-matched caregiver controls, the current study consented a new cohort of 44 age- and gender-matched healthy non-caregiver controls and 44 AD study participants. 3D telomeric profiles of buccal cells of AD patients and their non-AD controls were examined with participant information blinded to the analysis. In agreement with our previous study, we demonstrate that 3D telomeric profiles allow for the distinction between AD and non-AD individuals. This validation cohort provides an indication that the total number of 3D telomeric signals and their telomere lengths may be a suitable biomarker to differentiate between AD and non-AD and between mild, moderate, and severe AD. Further studies with larger sample sizes are required to move this technology further toward the clinic.

Aims: Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial. Methods: A battery of neuropsychological tests (digit span, digit symbol substitution (DSym), and Trails-making Part B (TMT-B)) was administered at baseline in ~1700 participants and repeated at year 5. Thirty-six risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses.Results: The mean age-adjusted, DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized intensive glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = -0.028; P = 0.0057), lower baseline diastolic blood pressure (beta = 0.028; P < 0.001), and baseline calcium channel blocker medication use (beta = -0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic blood pressure. Baseline thiazide diuretic use (beta= -0.549; P =0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic blood pressure-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride- lowering (P = 0.045) and decline in digit symbol substitution task performance.Conclusions: A five-year period of randomized intensive glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic blood pressure as well as plasma triglycerides were modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes.