Observed Changes in Risk during Naturopathic Treatment of Hypertension

Few outcome assessments are published from complementary and alternative medicine (CAM) practices. We aimed to describe patient and practice characteristics of ND care for hypertension (HTN), quantify changes in blood pressure (BP), and evaluate the proportion achieving control of HTN during care. A retrospective, observational study of ND practice in HTN was performed in an outpatient clinic in WA State. Eighty-five charts were abstracted for the final analysis. At initiation of care, the mean patient age was 61 years, with 51% having stage 2 HTN, despite common use of anti-hypertensive medications (47%). Patients with both stage 1 and stage 2 HTN appeared to improve during care, with stage 2 patients achieving mean reductions of −26 mmHg (P < .0001) and −11 mmHg (P < .0001) in systolic BP (SBP) and diastolic BP (DBP), respectively. The proportion of patients achieving control (<140/90 mmHg) in both SBP and DBP was increased significantly from 14 to 44% (P < .033), although the statistical significance was not maintained upon correction for multiple comparisons. BP appears to improve during ND care for HTN, in a high-risk population. Randomized trials are warranted

Physical Activity, Physical Fitness, and Leukocyte Telomere Length: The Cardiovascular Health Study.

INTRODUCTION: The influence of physical activity (PA) and physical fitness (PF) at older ages on changes in telomere length (TL)--repetitive DNA sequences that may mark biologic aging--is not well-established. Few prior studies (mainly cross-sectional) have been conducted in older adults, and few studies have evaluated PF. METHODS: We investigated cross-sectional and prospective associations of PA and PF with leukocyte TL among 582 older adults (mean ± SD age, 73 ± 5 yr at baseline) in the Cardiovascular Health Study, with serial TL measures and PA and PF assessed multiple times. Cross-sectional associations were assessed using multivariable repeated-measures regression, in which cumulatively averaged PA and PF measures were related to TL. Longitudinal analyses assessed cumulatively averaged PA and PF against later changes in TL, and changes in cumulatively averaged PA and PF against changes in TL. RESULTS: Cross-sectionally, greater walking distance and chair test performance, but not other PA and PF measures, were each associated with longer TL (P trend = 0.007 and 0.04, respectively). In longitudinal analyses, no significant associations of baseline PA and PF with change in TL were observed. In contrast, changes in leisure-time activity and chair test performance were each inversely associated with changes in TL. CONCLUSIONS: Cross-sectional analyses suggest that greater PA and PF are associated with longer TL. Prospective analyses show that changes in PA and PF are associated with differences in changes in TL. Even later in life, changes in certain PA and PF measures are associated with changes in TL, suggesting that leisure-time activity and fitness could reduce leukocyte telomere attrition among older adults.This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant U01HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Luisa Soares-Miranda is supported by the Portuguese Foundation of Science and Technology (FCT), SFRH/BPD/76947/2011, PTDC/DES/099018/2008 - FCT/FCOMP-01- 0124-FEDER-009573, and The Research Centre in Physical Activity Health and Leisure is supported by UID/DTP/00617/2013. Dr Imamura received support from the Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/5).This is the author accepted manuscript. The final version is available from Wolters Kluwer via http://dx.doi.org/10.1249/MSS.000000000000072

Alcohol consumption and leukocyte telomere length.

The relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation

Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

Objective: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. Methods: Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥ 65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. Results: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. Interpretation: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses

Mice Engrafted with Human Fetal Thymic Tissue and Hematopoietic Stem Cells Develop Pathology Resembling Chronic Graft-versus-Host Disease

AbstractChronic graft-versus-host disease (cGVHD) is a significant roadblock to long-term hematopoietic stem cell (HSC) transplantation success. Effective treatments for cGVHD have been difficult to develop, in part because of a paucity of animal models that recapitulate the multiorgan pathologies observed in clinical cGVHD. Here we present an analysis of the pathology that occurs in immunodeficient mice engrafted with human fetal HSCs and implanted with fragments of human fetal thymus and liver. Starting at time points generally later than 100 days post-transplantation, the mice developed signs of illness, including multiorgan cellular infiltrates containing human T cells, B cells, and macrophages; fibrosis in sites such as lungs and liver; and thickened skin with alopecia. Experimental manipulations that delayed or reduced the efficiency of the HSC engraftment did not affect the timing or progression of disease manifestations, suggesting that pathology in this model is driven more by factors associated with the engrafted human thymic organoid. Disease progression was typically accompanied by extensive fibrosis and degradation of the thymic organoid, and there was an inverse correlation of disease severity with the frequency of FoxP3+ thymocytes. Hence, the human thymic tissue may contribute T cells with pathogenic potential, but the generation of regulatory T cells in the thymic organoid may help to control these cells before pathology resembling cGVHD eventually develops. This model thus provides a new system to investigate disease pathophysiology relating to human thymic events and to evaluate treatment strategies to combat multiorgan fibrotic pathology produced by human immune cells

The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and [alpha]-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a [beta]-sheet arrangement reminiscent of the [beta]-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods

Kidney Function and Cognitive Health in Older Adults: The Cardiovascular Health Study

Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study, recruited from 4 U.S. communities, and studied from 1992 - 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFR[subscript cys]). Cognitive function was assessed using the Modified Mini-Mental State Exam and the Digit Symbol Substitution Test administered up to 7 times during annual visits. There was an association between eGFR[subscript cys] and change in cognitive function after adjustment for confounders; persons with eGFR[subscript cys] < 60 ml/min/1.73m² had a 0.64 (95% confidence interval: 0.51, 0.77) point/year faster decline in Modified Mini-Mental State Exam score and a 0.42 (95% confidence interval: 0.28, 0.56) point/year faster decline in Digit Symbol Substitution Test score compared with persons with eGFR[subscript cys] ≥ 90 ml/min/1.73m². Additional adjustment for intermediate cardiovascular events modestly impacted these associations. Participants with eGFR[subscript cys] < 60 ml/min/1.73m² had fewer cognitive impairment-free life-years on average compared with those with eGFR[subscript cys] ≥ 90 ml/min/1.73m², independent of confounders and mediating cardiovascular events (-0.44, 95% confidence interval: -0.62, -0.26). Older adults with reduced kidney function are at increased risk of worsening cognitive function.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the author(s) and published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. It can be found at: http://aje.oxfordjournals.org/Keywords: stroke, aging, myocardial infarction, successful aging, chronic kidney disease, cognitive function, prospective study, congestive heart failur