New statistical perspectives on the secretory patterns of both luteinizing hormone (LH) and testosterone (T) may prove useful in further understanding the aging process, and possibly ultimately in improving the diagnosis and treatment of spermatogenetic failure and loss of sexual interest. We examined serum concentration time-series for LH and T in 14 young (21-34 years of age) and 11 aged (62-74 years of age) healthy men. For each subject, blood samples were obtained at 2.5-min intervals during a sleep period, with an average sampling duration of 7 hr. For each of LH and T, we used the model-independent statistic approximate entropy (ApEn) to quantify the irregularity of the serum concentration time-series; to quantify joint LH-T secretory asynchrony, we employed the recently introduced cross-ApEn. Although mean (and SD) LH and T concentrations were indistinguishable in the two age groups (P > 0.25), for LH, aged subjects had greater ApEn values (1.525 ؎ 0.221) than younger individuals (1.207 ؎ 0.252), P < 0.003, indicating more irregular secretion in the older cohort. For T, aged subjects also had greater ApEn values (1.622 ؎ 0.120) than younger counterparts (1.384 ؎ 0.228), P < 0.004. In young, but not older men, ApEn(T) significantly exceeded ApEn(LH), P < 0.02. Aged subjects had greater cross-ApEn values (1.961 ؎ 0.121) than younger subjects (1.574 ؎ 0.249), P < 10 ؊4 , with nearly 100% sensitivity and specificity, indicating greater LH-T asynchrony in the older group. In conjunction with previous findings of greater irregularity of growth hormone release with increasing age, we propose that increased secretory irregularity with advancing age may be a widespread hormonal phenomenon. Finally, theoretically, we clarify the need for quantifications such as ApEn and cross-ApEn via a study of a ''variable lag'' pulsatile process, and empirically note the potential wide applicability of cross-ApEn to quantify asynchrony in interconnected (hormonal) networks.Greater understanding of the evolution of the hypothalamopituitary-testicular axis with aging is of vital importance both scientifically, in elucidating the physiology of reproductive capacity, and clinically, in assessing, e.g., a loss of libido or decreased reproductive performance. In recent years, there has been considerable study of luteinizing hormone (LH) and testosterone (T) serum concentration time-series in both younger and older males to develop such understanding, and to determine whether a hypothesized male climacteric (or so-called andropause) at least partially analogous to menopause in the female exists, and if so, in what precise sense. Such studies have evaluated changes in (i) mean concentrations of total and free T, and LH and the ratio of biological to immunological (B͞I) LH activity (1-6); (ii) ''near-term'' (circhoral) pulsatility characteristics of LH and T, via changes in mean frequencies and amplitudes (7-10); (iii) ''longer term,'' i.e., nyctohemeral characteristics of LH and T release (1). While considerable insight has alre...

Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs.

In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of the IL6R SNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm.

Testosterone supplementation may improve rehabilitation outcomes in ill older men.

Cognitive difficulties manifested by the growing elderly population with cirrhosis could be amnestic (memory-related) or non-amnestic (memory-unrelated). The underlying neuro-biological and gut-brain changes are unclear in this population. We aimed to define gut-brain axis alterations in elderly cirrhotics compared to non-cirrhotic individuals based on presence of cirrhosis and on neuropsychological performance. Age-matched outpatients with/without cirrhosis underwent cognitive testing (amnestic/non-amnestic domains), quality of life (HRQOL), multi-modal MRI (fMRI go/no-go task, volumetry and MR spectroscopy), blood (inflammatory cytokines) and stool collection (for microbiota). Groups were studied based on cirrhosis/not and also based on neuropsychological performance (amnestic-type, amnestic/non-amnestic-type and unimpaired). Cirrhotics were impaired on non-amnestic and selected amnestic tests, HRQOL and systemic inflammation compared to non-cirrhotics. Cirrhotics demonstrated significant changes on MR spectroscopy but not on fMRI or volumetry. Correlation networks showed that Lactobacillales members were positively while Enterobacteriaceae and Porphyromonadaceae were negatively linked with cognition. Using the neuropsychological classification amnestic/non-amnestic-type individuals were majority cirrhosis and had worse HRQOL, higher inflammation and decreased autochthonous taxa relative abundance compared to the rest. This classification also predicted fMRI, MR spectroscopy and volumetry changes between groups. We conclude that gut-brain axis alterations may be associated with the type of neurobehavioral decline or inflamm-aging in elderly cirrhotic subjects.

Committee on the Conduct of Human Research, and Veterans Affairs Medical Center Research and Development Committee. We studied a total of 33 healthy male volunteers, namely 17 young (age 20-40 yr) and 16 older (age 60-82 yr) men. Health was affirmed by detailed medical history, physical examination, and screening blood tests of hepatic, renal, metabolic, hematological, and endocrine function (2, 3, 15, 18). Exclusion criteria included the use of prescription medications; drug, alcohol, narcotic, or cigarette abuse; acute or chronic organic or psychiatric illness; recent transmeridian travel (more than Abbreviations: ApEn, Approximate entropy; CI, confidence interval.

Young healthy men were studied during brief treatment with prednisone to determine the rapidity of the effects of glucocorticoids on serum osteocalcin. Seven subjects were given 60 mg of prednisone orally at 8 a.m. on 5 consecutive days. Serum osteocalcin fell to 68% of the pretreatment level within 24 hours after the first dose was administered (p less than 0.01) and reached a nadir of 37% of baseline between 48 and 96 hours after treatment was begun (p less than 0.005). When prednisone was discontinued, serum osteocalcin returned promptly to pretreatment levels. Similar, though less marked, effects were found with lower doses of prednisone. Serum osteocalcin was not different from baseline after 5 mg of prednisone in five subjects, but after treatment of five subjects each with 10, 15, or 20 mg of prednisone, osteocalcin levels were 83%, 78%, and 74% of baseline, respectively (p less than 0.05). Serum osteocalcin levels fell rapidly with glucocorticoid administration, indicating that the effects of glucocorticoids on bone cells may be demonstrated long before clinical evidence of osteoporosis becomes apparent.

BackgroundWhile adherence to healthful dietary patterns has been associated with a lower risk of coronary artery disease (CAD) in the general population, limited data are available among US veterans. We tested the hypothesis that adherence to Dietary Approach to Stop Hypertension (DASH) food pattern is associated with a lower risk of developing CAD among veterans.Methods and ResultsWe analyzed data on 153 802 participants of the Million Veteran Program enrolled between 2011 and 2016. Information on dietary habits was obtained using a food frequency questionnaire at enrollment. We used electronic health records to assess the development of CAD during follow‐up. Of the 153 802 veterans who provided information on diet and were free of CAD at baseline, the mean age was 64.0 (SD=11.8) years and 90.4% were men. During a mean follow‐up of 2.8 years, 5451 CAD cases occurred. The crude incidence rate of CAD was 14.0, 13.1, 12.6, 12.3, and 11.1 cases per 1000 person‐years across consecutive quintiles of Dietary Approach to Stop Hypertension score. Hazard ratios (95% confidence interval) for CAD were 1.0 (ref), 0.91 (0.84–0.99), 0.87 (0.80–0.95), 0.86 (0.79–0.94), and 0.80 (0.73–0.87) from the lowest to highest quintile of Dietary Approach to Stop Hypertension score controlling for age, sex, body mass index, race, smoking, exercise, alcohol intake, and statin use (P linear trend, <0.0001).ConclusionsOur data are consistent with an inverse association between Dietary Approach to Stop Hypertension diet score and incidence of CAD among US veterans.