Physical Activity and Public Health in Older Adults: Recommendation From the American College of Sports Medicine and the American Heart Association

Objective - To issue a recommendation on the types and amounts of physical activity needed to improve and maintain health in older adults. Participants - A panel of scientists with expertise in public health, behavioral science, epidemiology, exercise science, medicine, and gerontology. Evidence - The expert panel reviewed existing consensus statements and relevant evidence from primary research articles and reviews of the literature. Process: After drafting a recommendation for the older adult population and reviewing drafts of the Updated Recommendation from the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) for Adults, the panel issued a final recommendation on physical activity for older adults. Summary - The recommendation for older adults is similar to the updated ACSM/AHA recommendation for adults, but has several differences including: the recommended intensity of aerobic activity takes into account the older adult\u27s aerobic fitness; activities that maintain or increase flexibility are recommended; and balance exercises are recommended for older adults at risk of falls. In addition, older adults should have an activity plan for achieving recommended physical activity that integrates preventive and therapeutic recommendations. The promotion of physical activity in older adults should emphasize moderate-intensity aerobic activity, muscle-strengthening activity, reducing sedentary behavior, and risk management

Groundwater Development in Arid Basins

Summary: Groundwater development frequently provides a means whereby tremendous new economic opportunities are opened up. If supplies are overdrawn (mined) the ensuing regional economy may be able to affort replacements from more costly sources. In the United States the Salt River Valley of Arizona and the valleys of California provide examples. Two cases are treated in this paper, Israel and West Pakistan. In Israel, besides furnishing more than half of the basic source of water suppply, groundwater development provides opportunity for both quantity and quality management, which makes possible use of surface supplies and reclaimed sewage as firm rather than marginal sources. This development will permit the total water resources of this small country, where agricultural production ranks among the world\u27s most efficient, to be utilized effectively down to almost the last drop by the mid 1970\u27s. Israel must then look to desalted water from the sea for further expansion of its overall water supply. In West Pakistan a combination of level terrain and leaky canals since about 1890 led to threatened waterlogging and salinity of more than 25 million acreas of irrigated land, even though supplies were less than half adequate for good productivity. By the 1950\u27s low yields and increasing population threatened starvation. However, initiation of groundwater development, first by the government and later by pricate entreprise, has, since 1960, let to construction of 3,500 governmental tube wells of about 3 cfs capacity and 30,000 private tube wells of slightly less than 1 cfs capacity. Results have been dramatic. Agricultural production and use of fertilizer are rapidly increasing, and opening of well development of pricate enterprise is providing the irrigator with benefits of free competition for his water custom which he did not previously enjoy. Ultimately, besides providing full supplies for an estimated 26 to 30 million acrea, drainage and salinity problems will be mitigated if about 50 million acre-feet are pumped each year from groundwater including about 28 million acre-feet to be mined from a reserve of about 1,900 million acre-feet. With some difficult surface storage development due to terrain, mining may eventually be reduced. Through an eventual technological solution for the continuing overdraft is not now in sight, perhaps an economy may be built which can affort such a solution when the time comes

Beyond gene-disease validity: capturing structured data on inheritance, allelic-requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions

Background: As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings. Methods: We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. Results: For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. Conclusions: Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing

MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload.

Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly. Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening

The effects of acute exercise on subsequent cigarette smoking

The present study was conducted to examine the effects of acute aerobic exercise on smoking behavior. On alternate days, 10 healthy young smokers were subjected to half an hour of sustained high exercise (about 56% of maximum work capacity) or of low exercise (about 28% of maximum, simulating normal daytime activity). During the high-exercise condition, there were pronounced increases in physiological markers of physical activity such as mean work, heart rate, and lactic acid as well as elevations in circulating hormones (norepinephrine, epinephrine, and immunoreactive beta-endorphin and cortisol) known to be affected by vigorous exercise. Despite a trend toward decreased desire for cigarettes after the high exercise condition, there were no differences in plasma nicotine levels following the smoking of a usual-brand cigarette 35 min later. The sustained effects of the two exercise conditions were also similar: plasma cotinine levels 24 hr later (reflecting nicotine intake over the entire exercise day) revealed no significant differences between hight and low exercise.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44810/1/10865_2004_Article_BF00846420.pd

Neuronal Nitric Oxide Synthase-Rescue of Dystrophin/Utrophin Double Knockout Mice does not Require nNOS Localization to the Cell Membrane

Survival of dystrophin/utrophin double-knockout (dko) mice was increased by muscle-specific expression of a neuronal nitric oxide synthase (nNOS) transgene. Dko mice expressing the transgene (nNOS TG+/dko) experienced delayed onset of mortality and increased life-span. The nNOS TG+/dko mice demonstrated a significant decrease in the concentration of CD163+, M2c macrophages that can express arginase and promote fibrosis. The decrease in M2c macrophages was associated with a significant reduction in fibrosis of heart, diaphragm and hindlimb muscles of nNOS TG+/dko mice. The nNOS transgene had no effect on the concentration of cytolytic, CD68+, M1 macrophages. Accordingly, we did not observe any change in the extent of muscle fiber lysis in the nNOS TG+/dko mice. These findings show that nNOS/NO (nitric oxide)-mediated decreases in M2c macrophages lead to a reduction in the muscle fibrosis that is associated with increased mortality in mice lacking dystrophin and utrophin. Interestingly, the dramatic and beneficial effects of the nNOS transgene were not attributable to localization of nNOS protein at the cell membrane. We did not detect any nNOS protein at the sarcolemma in nNOS TG+/dko muscles. This important observation shows that sarcolemmal localization is not necessary for nNOS to have beneficial effects in dystrophic tissue and the presence of nNOS in the cytosol of dystrophic muscle fibers can ameliorate the pathology and most importantly, significantly increase life-span

Meta-analysis of genome-wide association studies for extraversion:Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes