Substrate Availability and Utilization During Sub-maximal Exercise in the Elderly

Aging is associated with a decline in physiological capacity and metabolic function, leading to increased risk for chronic conditions such as insulin resistance and diabetes. Reduced ability to utilize fatty acids in the elderly has been linked to increased fat deposition within skeletal muscle. However, intramuscular triglyceride (IMTG) content and its relation to substrate oxidation has not been clearly established in older individuals. The two main purposes of the present investigation were 1.) to compare IMTG stores in the elderly with a younger group of men and women and 2.) to examine the relationship between substrate content and utilization during an acute sub-maximal bout of exercise in the elderly. A total of thirteen sedentary, healthy older men (5) and women (8) aged 67 + 3 yrs were matched for gender and percent body fat with a younger, control group (age=39 + 6 yrs) for IMTG comparison. Fat free mass (FFM), body mass index (BMI), weight, and height were not significantly different between the old and young and ORO staining from vastus lateralis muscle obtained by percutaneous needle biopsy revealed no statistically significant differences between the two groups. Sixteen sedentary elderly men (5) and women (11) were given constant infusions of 13C palmitate and d2 glucose during 60 minutes of cycle ergometry exercise at ~58% VO2peak to assess substrate utilization during exercise. There was a significant negative correlation between IMTG content by Oil Red O staining and total fatty acid oxidation (rho= -0.5989; p=0.03) and IMTG content and oxidative capacity of muscle (rho= -0.6485; p=0.04) induced by sub-maximal exercise. Oxidative capacity of muscle was not associated with rates of NPFA oxidation during sub-maximal exercise. Fitness was marginally correlated with fasting insulin levels (rho= -0.4857; p=0.056) and HOMA IR (rho= -0.4441; p=0.085). In summary, IMTG content was not higher in this group of sedentary elderly compared to younger individuals, but higher IMTG content was associated with decreased fat oxidation during sub-maximal exercise in this group. In addition, higher fitness predicted more favorable trends for markers of insulin resistance

False recognition in a mouse model of Alzheimer's disease: rescue with sensory restriction and memantine.

Alzheimer's disease is commonly regarded as a loss of memory for past events. However, patients with Alzheimer's disease seem not only to forget events but also to express false confidence in remembering events that have never happened. How and why false recognition occurs in such patients is currently unknown, and treatments targeting this specific mnemonic abnormality have not been attempted. Here, we used a modified object recognition paradigm to show that the tgCRND8 mouse-which overexpresses amyloid β and develops amyloid plaques similar to those in the brains of patients with Alzheimer's disease-exhibits false recognition. Furthermore, we found that false recognition did not occur when tgCRND8 mice were kept in a dark, quiet chamber during the delay, paralleling previous findings in patients with mild cognitive impairment, which is often considered to be prodromal Alzheimer's disease. Additionally, false recognition did not occur when mice were treated with the partial N-methyl-d-aspartic acid receptor antagonist memantine. In a subsequent experiment, we found abnormally enhanced N-methyl-d-aspartic acid receptor-dependent long-term depression in these mice, which could be normalized by treatment with memantine. We suggest that Alzheimer's disease typical amyloid β pathology leads to aberrant synaptic plasticity, thereby making memory representations more susceptible to interfering sensory input, thus increasing the likelihood of false recognition. Parallels between these findings and those from the literature on Alzheimer's disease and mild cognitive impairment suggest a mechanism underlying false recognition in these patients. The false recognition phenomenon may provide a novel paradigm for the discovery of potential therapies to treat the mnemonic dysfunction characteristic of this disease

Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice

Abstract Background Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. Methods/Design "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). Discussion This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857http://deepblue.lib.umich.edu/bitstream/2027.42/78264/1/1472-6963-10-280.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78264/2/1472-6963-10-280.pdfPeer Reviewe

TESS Discovery of an ultra-short-period planet around the nearby M dwarf LHS 3844

Data from the newly-commissioned \textit{Transiting Exoplanet Survey Satellite} (TESS) has revealed a "hot Earth" around LHS 3844, an M dwarf located 15 pc away. The planet has a radius of $1.32\pm 0.02$ $R_\oplus$ and orbits the star every 11 hours. Although the existence of an atmosphere around such a strongly irradiated planet is questionable, the star is bright enough ($I=11.9$, $K=9.1$) for this possibility to be investigated with transit and occultation spectroscopy. The star's brightness and the planet's short period will also facilitate the measurement of the planet's mass through Doppler spectroscopy.Comment: 10 pages, 4 figures. Submitted to ApJ Letters. This letter makes use of the TESS Alert data, which is currently in a beta test phase, using data from the pipelines at the TESS Science Office and at the TESS Science Processing Operations Cente

Relationships between physical activity across lifetime and health outcomes in older adults: Results from the NuAge cohort

Abstract: Objectives: This study aims to (1) describe participation in four physical activity (PA) domains across life and (2) examine the influence of PA during adolescence, early, mid-life, and later adulthood on health variables at older age. Design: Retrospective, observational, population-based cohort. Setting: Longitudinal study Nutrition as a Determinant of Successful Aging study ParticipantS: 1 378 healthy older adults (667 men; 711 women; aged 67-84 yrs at baseline) Measurements: Using a modified version of the interviewer-administered Lifetime Total Physical Activity Questionnaire (LTPAQ) and life events calendar to facilitate the recall, participants reported the frequency, duration, and intensity of occupational (OPA), commuting (CPA), household (HPA), and leisure time (LTPA) they participated in at the ages of 15, 25, 45, and 65 years and at the first follow-up (aged 68-85 yrs at follow-up). Fat mass, lean body mass, body mass index, waist to hip ratio, fasting glucose, systolic and diastolic blood pressures, self-reported chronic diseases, and socio-demographic were assessed at baseline. Results: Changes in PA differed across sex and PA domain. However, there was a general decline in all PA domains among both sexes after the age of 65. In multiple regression analyses, current LTPA was systematically associated with more favorable waist to hip ratio and fat mass in both sexes, whereas CPA, OPA, and HPA across life were not consistently associated with health variables. Conclusion: PA domains during adolescence, early adulthood, and mid-life were not directly related to health variables at older age, while current LTPA was, suggesting it is never too late to start

Methane-derived authigenic carbonates from the northern Gulf of Mexico and their relation to gas hydrates

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Geochemical Exploration 95 (2007): 1-15, doi:10.1016/j.gexplo.2007.05.011.Authigenic carbonates were sampled in piston cores collected from both the Tunica Mound and the Mississippi Canyon area on the continental slope of the northern Gulf of Mexico during a Marion Dufresne cruise in July 2002. The carbonates are present as hardgrounds, porous crusts, concretions or nodules and shell fragments with or without carbonate cements. Carbonates occurred at gas venting sites which are likely to overlie gas hydrates bearing sediments. Electron microprobe, X-ray diffraction (XRD) and thinsection investigations show that these carbonates are high-Mg calcite (6 - 21 mol % MgCO3), with significant presence of framboidal pyrite. All carbonates are depleted in 13C (δ13C = -61.9 to -31.5 ‰ PDB) indicating that the carbon is derived mainly from anaerobic methane oxidation (AMO). Age estimates based on 14C dating of shell fragments and on regional sedimentation rates indicate that these authigenic carbonates formed within the last 1,000 yr in the Mississippi Canyon and within 5,500 yr at the Tunica Mound. The oxygen isotopic composition of carbonates ranges from +3.4 to +5.9 ‰ PDB. Oxygen isotopic compositions and Mg2+ contents of carbonates, and present in-situ temperatures of bottom seawater/sediments, show that some of these carbonates, especially from a core associated with underlying massive gas hydrates precipitated in or near equilibrium with bottom-water. On the other hand, those carbonates more enriched in 18O are interpreted to have precipitated from 18O-rich fluids which are thought to have been derived from the dissociation of gas hydrates. The dissociation of gas hydrates in the northern Gulf of Mexico within the last 5,500 yr may be caused by nearby salt movement and related brines.Financial support for this work was provided by the Grant-in-Aid from the Ministry of Education and Science and the Research Grant from JAPEX

Exercise recommendations for people with bone metastases: Expert consensus for healthcare providers and clinical exercise professionals

Purpose: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. Methods: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. Results: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. Conclusion: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases

Exercise for individuals with bone metastases: A systematic review

Background Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This systematic review summarizes the safety, feasibility and efficacy of exercise in controlled trials that include individuals with bone metastases. Methods MEDLINE, Embase, Pubmed, CINAHL, PEDro and CENTRAL databases were searched up to July 16, 2020. Results A total of 17 trials were included incorporating aerobic exercise, resistance exercise or soccer interventions. Few (n=4, 0.5%) serious adverse events were attributed to exercise participation, with none related to bone metastases. Mixed efficacy results were found, with exercise eliciting positive changes or no change. The majority of trials included an element of supervised exercise instruction (n=16, 94%) and were delivered by qualified exercise professionals (n=13, 76%). Conclusions Exercise appears safe and feasible for individuals with bone metastases when it includes an element of supervised exercise instruction

Exercise Recommendation for People With Bone Metastases: Expert Consensus for Health Care Providers and Exercise Professionals

PURPOSE:Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion.METHODS:The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement.RESULTS:Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential.CONCLUSION:Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases