Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormone-binding globulin affect these age trends remain poorly understood, and ...were examined in men of the Framingham Heart Study.
Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation.
There were 1,461 eligible men (mean age ±SD 61.1±9.5 years and body mass index BMI 28.8±4.5kg/m(2)). Total estradiol and estrone were positively associated with age, but free estradiol was negatively associated with age. Age-related increase in total estrone was greater than that in total estradiol. Estrone was positively associated with smoking, BMI, and testosterone, and total and free estradiol with diabetes, BMI, testosterone, and comorbid conditions; additionally, free estradiol was associated negatively with smoking. Collectively, age, BMI, testosterone, and other health and behavioral factors explained only 18% of variance in estradiol, and 9% of variance in estrone levels. Men in the highest quintile of estrone levels had significantly higher age and BMI, and a higher prevalence of smoking, diabetes, and cardiovascular disease than others, whereas those in the highest quintile of estradiol had higher BMI than others.
Total estrone and estradiol levels in men, measured using liquid chromatography tandem mass spectrometry, revealed significant age-related increases that were only partially accounted for by cross-sectional differences in BMI, diabetes status, and other comorbidities and health behaviors. Longitudinal studies are needed to confirm these findings.
•Integrating genetic analyses, clinical testing and MRI (PNS/CNS).•Early stages of pain development in a group with confirmed neuropathic pain.•MRI changes in peripheral nerve fibers resulting from ...ankle sprain.
The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system.
Beam tests of a large-scale TORCH time-of-flight demonstrator Hancock, T.H.; Bhasin, S.; Blake, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2020, Letnik:
958
Journal Article
Recenzirano
Odprti dostop
The TORCH time-of-flight detector is designed to provide particle identification in the momentum range 2−10GeV∕c over large areas. The detector exploits prompt Cherenkov light produced by charged ...particles traversing a 10mm thick quartz plate. The photons propagate via total internal reflection and are focused onto a detector plane comprising position-sensitive Micro-Channel Plate Photo-Multiplier Tubes (MCP-PMT) detectors. The goal is to achieve a single-photon timing resolution of 70ps, giving a timing precision of 15ps per charged particle by combining the information from around 30 detected photons. The MCP-PMT detectors have been developed with a commercial partner (Photek Ltd, UK), leading to the delivery of a square tube of active area 53×53mm2 with a granularity of 8×128pixels equivalent. A large-scale demonstrator of TORCH, having a quartz plate of dimensions 660×1250×10mm3 and read out by a pair of MCP-PMTs with custom readout electronics, has been verified in a test beam campaign at the CERN PS. Preliminary results indicate that the required performance is close to being achieved. The anticipated performance of a full-scale TORCH detector at the LHCb experiment is presented.
TORCH is a time-of-flight detector designed to perform particle identification over the momentum range 2–10 GeV/c for a 10 m flight path. The detector exploits prompt Cherenkov light produced by ...charged particles traversing a quartz plate of 10mm thickness. Photons are then trapped by total internal reflection and directed onto a detector plane instrumented with customised position-sensitive Micro-Channel Plate Photo-Multiplier Tube (MCP-PMT) detectors. A single-photon timing resolution of 70ps is targeted to achieve the desired separation of pions and kaons, with an expectation of around 30 detected photons per track. Studies of the performance of a small-scale TORCH demonstrator with a radiator of dimensions 120×350×10mm3 have been performed in two test-beam campaigns during November 2017 and June 2018. Single-photon time resolutions ranging from 104.3ps to 114.8ps and 83.8ps to 112.7ps have been achieved for MCP-PMTs with granularity 4 × 64 and 8 × 64 pixels, respectively. Photon yields are measured to be within ∼10% and ∼30% of simulation, respectively. Finally, the outlook for future work with planned improvements is presented.
Maternal Low-Protein Diet or Hypercholesterolemia Reduces Circulating Essential Amino Acids and Leads to Intrauterine Growth
Restriction
Kum Kum S. Bhasin 1 ,
Atila van Nas 2 ,
Lisa J. Martin 2 ,
...Richard C. Davis 1 ,
Sherin U. Devaskar 3 and
Aldons J. Lusis 1 2 4
1 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
2 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California
3 Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
4 Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California,
Los Angeles, California
Corresponding author: Aldons J. Lusis, jlusis{at}mednet.ucla.edu
Abstract
OBJECTIVE— We have examined maternal mechanisms for adult-onset glucose intolerance, increased adiposity, and atherosclerosis using two
mouse models for intrauterine growth restriction (IUGR): maternal protein restriction and hypercholesterolemia.
RESEARCH DESIGN AND METHODS— For these studies, we measured the amino acid levels in dams from two mouse models for IUGR: 1 ) feeding C57BL/6J dams a protein-restricted diet and 2 ) feeding C57BL/6J LDL receptor–null (LDLR −/− ) dams a high-fat (Western) diet.
RESULTS— Both protein-restricted and hypercholesterolemic dams exhibited significantly decreased concentrations of the essential amino
acid phenylalanine and the essential branched chain amino acids leucine, isoleucine, and valine. The protein-restricted diet
for pregnant dams resulted in litters with significant IUGR. Protein-restricted male offspring exhibited catch-up growth by
8 weeks of age and developed increased adiposity and glucose intolerance by 32 weeks of age. LDLR −/− pregnant dams on a Western diet also had litters with significant IUGR. Male and female LDLR −/− Western-diet offspring developed significantly larger atherosclerotic lesions by 90 days compared with chow-diet offspring.
CONCLUSIONS— In two mouse models of IUGR, we found reduced concentrations of essential amino acids in the experimental dams. This indicated
that shared mechanisms may underlie the phenotypic effects of maternal hypercholesterolemia and maternal protein restriction
on the offspring.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 10 December 2008.
K.K.S.B., A.v.N., and L.J.M. are joint first authors of this work.
K.K.S.B. is currently affiliated with Kaiser Permanente Hospital, Bellflower, California.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
Accepted November 26, 2008.
Received October 26, 2007.
DIABETES
Human body can be viewed simplistically as being composed of fat-free and fat mass. With more sophisticated techniques, body composition can be broken down into fat mass, skeletal muscle mass, ...nonmuscle lean mass, visceral mass and bone mineral content. Similarly, it is possible to obtain estimates of total body water and intracellular and extracellular water contents. Regardless of the model of body composition assessment, it is evident that androgens are important determinants of body composition; there is no body compartment that is not directly or indirectly affected by androgens. The effects of androgens on skeletal muscle mass have received the greatest attention in recent literature; however, growing body of evidence suggests that androgens also regulate fat mass, bone mineral content, nonmuscle soft tissues and body water.
In spite of the widespread abuse of androgenic steroids by athletes and recreational body-builders, the effects of these agents on athletic performance and physical function remain poorly understood. ...Experimentally induced androgen deficiency is associated with a loss of fat-free mass; conversely, physiologic testosterone replacement of healthy, androgen-deficient men increases fat-free mass and muscle protein synthesis. Testosterone supplementation of HIV-infected men with low testosterone levels and of older men with normally low testosterone concentrations also increases muscle mass. However, we do not know whether physiologic testosterone replacement can improve physical function and health-related quality of life, and reduce the risk of falls and disability in older men or those with chronic illness. Testosterone increases maximal voluntary strength in a dose-dependent manner and thus might improve performance in power-lifting events. However, testosterone has not been shown to improve performance in endurance events. The mechanisms by which testosterone increases muscle mass are not known, but probably involve alterations in the expression of multiple muscle growth regulators.
Androgens are involved in the development of several tissues, including prostate, skeletal muscle, bone marrow, hair follicles, and brain. Most of the biological effects of the androgens are mediated ...through an intracellular transcription factor, the androgen receptor (AR) at the level of gene regulation. Several types of mutations in the AR gene have been linked to endocrine dysfunctions. The expansion of CAG codon repeat, coding for a polyglutamine (PolyQ) tract in the N-terminal domain is one such mutation. The polyQ chain length impacts AR's ability to interact with critical coregulators, which in turn modulates its transcriptional efficacy. Pathologic manifestations of variations in polyQ chain length have been associated with prostate cancer susceptibility, and the Spinal and Bulbar Muscular Atrophy (SBMA), a neurodegenerative disease. In this review article, we discuss multiple aspects of the role of polyQ chain length in the actions of the AR, their importance in prostate cancer development and progression, and SBMA with an aim to understand the underlying mechanisms involved in these diseases, which can be targeted for future therapeutic approaches.
Sarcopenia and frailty represent two burdensome conditions, contributing to a broad spectrum of adverse outcomes. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force ...met virtually in September 2021 to discuss the challenges in the development of drugs for sarcopenia and frailty. Lifestyle interventions are the current mainstay of treatment options in the prevention and management of both conditions. However, pharmacological agents are needed for people who do not respond to lifestyle modifications, for those who are unable to adhere, or for whom such interventions are inaccessible/unfeasible. Preliminary results of ongoing trials were presented and discussed. Several pharmacological candidates are currently under clinical evaluation with promising early results, but none have been approved for either frailty or sarcopenia. The COVID-19 pandemic has reshaped how clinical trials are conducted, in particular by enhancing the usefulness of remote technologies and assessments/interventions.
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