335 research outputs found
Daily physical activity and macronutrient distribution of low-calorie diets jointly affect body fat reduction in obese women.
Inadequate dietary patterns and sedentary lifestyles are believed to be important factors in predisposing people to obesity. This study analyzed the potential interaction between habitual physical activity and the carbohydrate (CHO)-fat
distribution in 2 hypocaloric diets and the impact of such interplay on body composition changes. Forty healthy obese women, 20â50 years old, were randomly assigned to a high- or low-CHO energy-restricted diet, which was low or high in fat, respectively, during 10 weeks. Baseline and final measurements were performed to assess dietary habits, resting metabolic rate, and body composition changes. Physical activity was measured with a triaxial accelerometer and with a questionnaire. There were no significant differences in anthropometric and metabolic variables between both dietary groups at
baseline. However, there was a positive correlation between total free-living physical activity and arm muscle preservation
after 10 weeks (r = 0.371; p = 0.024). Interestingly, an interaction between macronutrient (CHOâfat distribution) intake
and physical activity was found, since less-active subjects with a high-CHOâlow-fat diet showed a greater fat loss than those more active with a lower-CHOâhigh-fat diet, whereas more-active subjects with a high-CHOâlow-fat diet showed a smaller fat loss than those receiving a low-CHOâhigh-fat diet. Physical activity and the macronutrient content of energyrestricted diets, when designed to promote body fat mass reduction, should be considered together to better predict the outcome
Genetic Characterization of Cancer of Unknown Primary Using Liquid Biopsy Approaches
Cancers of unknown primary (CUPs) comprise a heterogeneous group of rare metastatic tumors whose primary site cannot be identified after extensive clinical\u2013pathological investigations. CUP patients are generally treated with empirical chemotherapy and have dismal prognosis. As recently reported, CUP genome presents potentially druggable alterations for which targeted therapies could be proposed. The paucity of tumor tissue, as well as the difficult DNA testing and the lack of dedicated panels for target gene sequencing are further relevant limitations. Here, we propose that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) could be used to identify actionable mutations in CUP patients. Blood was longitudinally collected from two CUP patients. CTCs were isolated with CELLSEARCH\uae and DEPArrayTM NxT and Parsortix systems, immunophenotypically characterized and used for single-cell genomic characterization with Ampli1TM kits. Circulating cell-free DNA (ccfDNA), purified from plasma at different time points, was tested for tumor mutations with a CUP-dedicated, 92-gene custom panel using SureSelect Target Enrichment technology. In parallel, FFPE tumor tissue was analyzed with three different assays: FoundationOne CDx assay, DEPArray LibPrep and OncoSeek Panel, and the SureSelect custom panel. These approaches identified the same mutations, when the gene was covered by the panel, with the exception of an insertion in APC gene. which was detected by OncoSeek and SureSelect panels but not FoundationOne. FGFR2 and CCNE1 gene amplifications were detected in single CTCs, tumor tissue, and ccfDNAs in one patient. A somatic variant in ARID1A gene (p.R1276 17) was detected in the tumor tissue and ccfDNAs. The alterations were validated by Droplet Digital PCR in all ccfDNA samples collected during tumor evolution. CTCs from a second patient presented a pattern of recurrent amplifications in ASPM and SEPT9 genes and loss of FANCC. The 92-gene custom panel identified 16 non-synonymous somatic alterations in ccfDNA, including a deletion (I1485Rfs 1719) and a somatic mutation (p. A1487V) in ARID1A gene and a point mutation in FGFR2 gene (p.G384R). Our results support the feasibility of non-invasive liquid biopsy testing in CUP cases, either using ctDNA or CTCs, to identify CUP genetic alterations with broad NGS panels covering the most frequently mutated genes
Genomic analysis of diet composition finds novel loci and associations with health and lifestyle
We conducted genome-wide association study (GWAS) meta-analyses of relative caloric intake from fat,
protein, carbohydrates and sugar in over 235,000 individuals. We identified 21 approximately
independent lead SNPs. Relative protein intake exhibits the strongest relationships with poor health,
including positive genetic associations with obesity, type 2 diabetes, and heart disease ( â 0.15 â
0.5). Relative carbohydrate and sugar intake have negative genetic correlations with waist circumference,
waist-hip ratio, and neighborhood poverty (|| â 0.1 â 0.3). Overall, our results show that the relative
intake of each macronutrient has a distinct genetic architecture and pattern of genetic correlations
suggestive of health implications beyond caloric content
Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study
Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration. The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40â80â
years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300â
mg twice daily or placebo added to usual COPD therapy for 12â
months. The primary outcome was the number of acute exacerbations during the study. In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8â
years, forced expiratory volume in 1â
s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus. 1.13 exacerbations·patientâ1·yearâ1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patientâ1·yearâ1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patientâ1·yearâ1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63â
days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation. In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups
Validation of the Spanish version of the physical activity questionnaire used in the Nursesâ Health Study and the Health Professionalsâ Follow-up Study
Objective: The objective of this analysis was to test the validity of the estimates of
energy expenditure and sedentary lifestyle obtained through a self-administered
questionnaire of physical activity for Spanish-speaking people adapted from US
questionnaires (Nursesâ Health Study and Health Professionalsâ Follow-up Study)
using a triaxial accelerometer (RT3 Triaxial Research Tracker) as the reference.
Design and setting: Validation study, calculating the non-parametric correlation
coefficients between the level of physical activity and sedentary lifestyle collected by
the self-administered questionnaire and the triaxial accelerometer measurements.
Percentage of misclassification and kappa coefficients were also calculated.
Subjects: The study population consisted of a sample of 40 obese women who were
participants of the SUN (Seguimiento Universidad de Navarra) project (a prospective cohort study among Spanish university alumni). They were selected because of their peculiar metabolic characteristics, in the search for a sub-optimal scenario for validity.
Results: Physical activity during leisure time (estimated as MET-h week21) derived
from the self-administered questionnaire moderately correlated with kcal day21
assessed through the accelerometer (Spearmanâs r ÂŒ 0.507, 95% confidence interval (CI) 0.232, 0.707). The Spearman correlation between the ratio of sedentary lifestyle to physical activity obtained through the questionnaire and the direct estimation (RT3) was 20.578 (95% CI 20.754, 20.325). The kappa index was 0.25 (P ÂŒ 0.002)
when assessing the cross-classification into quintiles and 0.41 for the dichotomous
estimation of a sedentary lifestyle. Only 2.5% of participants were misclassified by the questionnaire more than two quintiles apart from the estimates of the RT3.
Conclusions: The moderate values obtained for correlation in a sub-optimal scenario
for validity and the low percentage of extreme misclassification suggest the validity of the questionnaire to assess physical activity in Spanish-speaking women aged 20â50 years
Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes
Foregoing researches made on the N/OFQ system brought up a possible role for this system in cardiovascular regulation. In this study we examined how N/OFQ levels of the blood plasma changed in acute cardiovascular diseases. Three cardiac patient groups were created: enzyme positive acute coronary syndrome (EPACS, n = 10), enzyme negative ACS (ENACS, n = 7) and ischemic heart disease (IHD, n = 11). We compared the patients to healthy control subjects (n = 31). We found significantly lower N/OFQ levels in the EPACS [6.86 (6.21â7.38) pg/ml], ENACS [6.97 (6.87â7.01) pg/ml and IHD groups [7.58 (7.23â8.20) pg/ml] compared to the control group [8.86 (7.27â9.83) pg/ml]. A significant correlation was detected between N/OFQ and white blood cell count (WBC), platelet count (PLT), creatine kinase (CK), glutamate oxaloacetate transaminase (GOT) and cholesterol levels in the EPACS group.Decreased plasma N/OFQ is closely associated with the presence of acute cardiovascular disease, and the severity of symptoms has a significant negative correlation with the N/OFQ levels. We believe that the rate of N/OFQ depression is in association with the level of ischemic stress and the following inflammatory response. Further investigations are needed to clarify the relevance and elucidate the exact effects of the ischemic stress on the N/OFQ system
Human Rights and the Pink Tide in Latin America : Which Rights Matter?
Latin America witnessed the election of ânew Leftâ governments in the early 21 st century that, in different ways, sought to open a debate about alternatives to paradigms of neoliberal development. What has this meant for the way that human rights are understood and for patterns of human rights compliance? Using qualitative and quantitative evidence, this article discusses how human rights are imagined and the compliance records of new Left governments through the lens of the three âgenerationsâ of human rights â political and civil, social and economic, and cultural and environmental rights. The authors draw in particular on evidence from Andean countries and the Southern Cone. While basic civil and individual liberties are still far from guaranteed, especially in the Andean region, new Left countries show better overall performances in relation to socio-economic rights compared to the past and to other Latin American countries. All new Left governments also demonstrate an increasing interest in âthird generationâ (cultural and environmental) rights, though this is especially marked in the Andean Left. The authors discuss the tensions around interpretations and categories of human rights, reflect on the stagnation of first generation rights and note the difficulties associated with translating second and third generation rights into policy
Evaluation of the impact of orally administered carbohydrates on postprandial blood glucose levels in different pre-clinical models
ABSTRACT We developed a pre-clinical model in which to evaluate the impact of orally administered carbohydrates on postprandial blood glucose levels. For this purpose, we compared the effects of different carbohydrates with well-established glycemic indexes. We orally administered (gavage) increasing amounts (0.2, 0.4, 0.6, 0.8, and 1.0 g/kg) of sucrose and lactose to rats which had been fasted for 6 h or 15 h, respectively. In part of the experiments we administered frutose (gavagem). Three different models were compared for measuring postprandial blood glucose levels: a) evaluation of interstitial glucose concentrations by using a real time continuous glucose monitoring system; b) evaluation of glucose levels in blood obtained from the rat tail; c) evaluation of serum glucose levels in blood collected after decapitation. Our results showed that blood obtained from the tails of 15-h fasted rats was the best model in which to evaluate the effect of carbohydrates on postprandial blood glucose levels
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