421 research outputs found
A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing
Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox
Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed
Ejercicio dosis-respuesta de la pendiente V? E / V?CO 2 en mujeres posmenopáusicas en el estudio DREW
Purpose: Being overweight/obese, having hypertension, and being postmenopausal are risk factors for the development of congestive heart failure (CHF). A characteristic of CHF is an abnormal V?E/V?CO2 slope, which is predictive of mortality in patients with CHF. Although the V?E/V?CO2 slope is well established in CHF patients, little is known regarding interventions for 'at-risk' populations. Methods: We examined the V?E/V?CO2 slope in 401 sedentary, overweight, moderately hypertensive women randomized to 6 m of nonexercise (control) or 4 kcal·kg?1·wk?1 (KKW), 8 KKW, or 12 KKW of exercise at an intensity corresponding to 50% of baseline V?O2max. We examined trends in exercise treatment dose versus change in mean V?E/V?CO2 slope using a linear regression model (KKW vs V?E/V?CO2 slope) and a linear mixed model. Results: Regression analysis showed a significant trend for a reduction in the V?E/V?CO2 slope from baseline (mean ± SD: 32.6 ± 6.3; P < 0.004). When expressed as mean change (95% confidence interval (CI)) from baseline, we observed significant reductions in the V?E/V?CO2 slope for the 8-KKW (?1.14; 95% CI, ?1.5 to ?0.2) and 12-KKW (?1.67; 95% CI, ?2.3 to ?0.3) groups. No significant effect was noted for the 4-KKW (?0.4; 95% CI, ?1.2 to 0.15) group. Conclusion: Moderate-intensity aerobic exercise at doses of 8 KKW or greater seems to present an adequate dose of exercise to promote small but significant reductions in the V?E/V?CO2 slope in postmenopausal women who exhibit risk factors associated with the development of CHF
Developing a framework for the analysis of power through depotentia
Stakeholder participation in tourism policy-making is usually perceived as providing a means of empowerment. However participatory processes drawing upon stakeholders from traditionally empowered backgrounds may provide the means of removing empowerment from stakeholders. Such an outcome would be in contradiction to the claims that participatory processes improve both inclusivity and sustainability. In order to form an understanding of the sources through which empowerment may be removed, an analytical perspective has been developed deriving from Lukes�s views of power dating from 1974. This perspective considers the concept of depotentia as the removal of �power to� without speculating upon the underlying intent and also provides for the multidimensionality of power to be examined within a single study. The application of this analytical perspective has been tested upon findings of the government-commissioned report of the Countryside and Community Research Unit in 2005. The survey and report investigated the progress of Local Access Forums in England created in response to the Countryside and Rights of Way Act 2000. Consideration of the data from this perspective permits the classification of individual sources of depotentia which can each be addressed and potentially enable stakeholder groups to reverse loss of empowerment where it has occurred
Mean Profiles of the NEO Personality Inventory
The Revised NEO Personality Inventory (NEO-PI-R, Costa & McCrae, 1992) and its latest version, the NEO-PI-3, were designed to measure 30 distinctive personality traits, which are grouped into Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness domains. The mean self-rated NEO-PI-R scores for 30 subscales have been reported for 36 countries or cultures (McCrae, 2002, Appendix 1). As a follow-up, this study reports the mean scores of the NEO-PI-R/3 for 71,334 participants from 76 samples and 62 different countries or cultures and 37 different languages. Mean differences in personality traits across countries and cultures were about 8 times smaller than differences between any two individuals randomly selected from any of these samples. Nevertheless, systematic differences can be observed in the aggregate personality profiles, in which Anglophonic and Nordic countries are distinguished from the rest of the world. This study provides further evidence that country/culture mean scores in personality are replicable and can provide reliable information about personality dispositions
Graphical Elicitation of a Prior Distribution for a Clinical Trial
1 online resource (PDF, 27 pages
Tau isoform-specific enhancement of L-type calcium current and augmentation of afterhyperpolarization in rat hippocampal neurons
Accumulation of tau is observed in dementia, with human tau displaying 6 isoforms grouped by whether they display either 3 or 4 C-terminal repeat domains (3R or 4R) and exhibit no (0N), one (1N) or two (2N) N terminal repeats. Overexpression of 4R0N-tau in rat hippocampal slices enhanced the L-type calcium (Ca(2+)) current-dependent components of the medium and slow afterhyperpolarizations (AHPs). Overexpression of both 4R0N-tau and 4R2N-tau augmented Ca(V)1.2-mediated L-type currents when expressed in tsA-201 cells, an effect not observed with the third 4R isoform, 4R1N-tau. Current enhancement was only observed when the pore-forming subunit was co-expressed with Ca(V)β3 and not Ca(V)β2a subunits. Non-stationary noise analysis indicated that enhanced Ca(2+) channel current arose from a larger number of functional channels. 4R0N-tau and Ca(V)β3 were found to be physically associated by co-immunoprecipitation. In contrast, the 4R1N-tau isoform that did not augment expressed macroscopic L-type Ca(2+) current exhibited greatly reduced binding to Ca(V)β3. These data suggest that physical association between tau and the Ca(V)β3 subunit stabilises functional L-type channels in the membrane, increasing channel number and Ca(2+) influx. Enhancing the Ca(2+)-dependent component of AHPs would produce cognitive impairment that underlie those seen in the early phases of tauopathies
PGC1α
PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α −1 nucleosome (−1N) position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the −1N position revealed that those individuals with a −1N phased further upstream from the transcriptional start site (UP) expressed lower levels of NTPGC1α than those with the −1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and −1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133
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