Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142052/1/jper0257.pd

Association Between Metabolic Syndrome and Periodontal Disease Measures in Postmenopausal Women: The Buffalo OsteoPerio Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141377/1/jper1489.pd

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing

Association of Plasma 25â Hydroxyvitamin D Concentrations and Pathogenic Oral Bacteria in Postmenopausal Females

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141146/1/jper0944.pd

Parameterizing and Validating Existing Algorithms for Identifying Out-of-Bed Time Using Hip-Worn Accelerometer Data from Older Women

Objective: To parameterize and validate two existing algorithms for identifying out-of-bed time using 24-hour hip-worn accelerometer data from older women. Approach: Overall, 628 women (80±6 years old) wore ActiGraph GT3X+ accelerometers 24 hours/day for up to 7 days and concurrently completed sleep-logs. Trained staff used a validated visual analysis protocol to measure in-bed periods on accelerometer tracings (criterion). The Tracy and McVeigh algorithms were adapted for optimal use in older adults. A training set of 314 women was used to choose two key thresholds by maximizing the sum of sensitivity and specificity for each algorithm and data (vertical axis, VA, and vector magnitude, VM) combination. Data from the remaining 314 women were then used to test agreement in waking wear time (i.e., out-of-bed time while wearing the accelerometer) by computing sensitivity, specificity, and kappa comparing the algorithm output with the criterion. Waking wear time-adjusted means of sedentary time, light-intensity physical activity (light PA) and moderate-to-vigorous-intensity physical activity (MVPA) were then estimated and compared. Main results: Waking wear time agreement with the criterion was high for Tracy_VA, Tracy_VM, McVeigh_VA, and highest for McVeigh_VM. Compared to the criterion, McVeigh_VM had mean sensitivity=0.92, specificity=0.87, kappa=0.80, and overall mean difference (±SD) of -0.04±2.5 hours/day. Minutes of sedentary time, light PA, and MVPA adjusted for waking wear time using the criterion measure and McVeigh_VM were not statistically different (p \u3e0.43 | all). Significance: The McVeigh algorithm with optimal parameters using VM performed best compared to criterion sleep-log assisted visual analysis and is suitable for automated identification of waking wear time in older women when visual analysis is not feasible

Modifying effect of obesity on the association between sitting time and incident diabetes in post-menopausal women

Objective: To evaluate the association between self-reported daily sitting time and the incidence of type II diabetes in a cohort of postmenopausal women. Design and Methods Women (N = 88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes over 14.4 years follow-up. Results: Each hour of sitting time was positively associated with increased risk of diabetes (Risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤ 7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet and alcohol intake) and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations. Conclusion: Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women— a population already at high risk of the disease

Association Between Annual Visit-to-Visit Blood Pressure Variability and Stroke in Postmenopausal Women: Data From the Women's Health Initiative

Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exist as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58228 postmenopausal women enrolled in the Women's Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the SD for the participant's mean systolic blood pressure (SBP) across visits (SD) and about the participant's regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared with the lowest quartile (referent) were 1.39 (1.03–1.89) for quartile 2, 1.52 (1.13–2.03) for quartile 3, and 1.72 (1.28–2.32) for quartile 4 (P trend <0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (P trend <0.001). The associations did not differ by stroke type (ischemic versus hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP

Post-diagnosis body mass index and mortality among women diagnosed with endometrial cancer: Results from the Women\u27s Health Initiative.

Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women\u27s Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55-1.91). Our study does not support the hypothesis that higher BMI after endometrial cancer diagnosis is associated with poorer survival

Vitamin D Status and 5â Year Changes in Periodontal Disease Measures Among Postmenopausal Women: The Buffalo OsteoPerio Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141463/1/jper1321.pd