998 resultados para Population-pharmacokinetics Pop-PK
Resumo:
Fifty-five clinical and environmental Aspergillus fumigatus isolates from Mexico, Argentina, France and Peru were analyzed to determine their genetic variability, reproductive system and level of differentiation using amplified fragment length polymorphism markers. The level of genetic variability was assessed by measuring the percentage of polymorphic loci, number of effective alleles, expected heterozygocity and by performing an association index test (I A). The degree of genetic differentiation and variation was determined using analysis of molecular variance at three levels. Using the paired genetic distances, a dendrogram was built to detect the genetic relationship among alleles. Finally, a network of haplotypes was constructed to determine the geographic relationship among them. The results indicate that the clinical isolates have greater genetic variability than the environmental isolates. The I A of the clinical and environmental isolates suggests a recombining population structure. The genetic differentiation among isolates and the dendrogram suggest that the groups of isolates are different. The network of haplotypes demonstrates that the majority of the isolates are grouped according to geographic origin.
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This study describes major electrocardiogram (ECG) measurements and diagnoses in a population of African individuals; most reference data have been collected in Caucasian populations and evidence exists for interethnic differences in ECG findings. This study was conducted in the Seychelles islands (Indian Ocean) and included 709 black individuals (343 men and 366 women) aged 25 to 64 years randomly selected from the general population. Resting ECG were recorded by using a validated ECG unit equipped with a measurement and interpretation software (Cardiovit AT-6, Schiller, Switzerland). The epidemiology of 14 basic ECG measurements, 6 composite criteria for left ventricular hypertrophy and 19 specific ECG diagnoses including abnormal rhythms, conduction abnormalities, repolarization abnormalities, and myocardial infarction were examined. Substantial gender and age differences were found for several ECG parameters. Moreover, tracings recorded in African individuals of the Seychelles differed from those collected similarly in Caucasian populations in many respects. For instance, heart rate was approximately 5 beats per minute lower in the African individuals than in selected Caucasian populations, prevalence of first degree atrio-ventricular block was especially high (4.8%), and the average Sokolow-Lyon voltage was markedly higher in African individuals of the Seychelles compared with black and white Americans. The integrated interpretation software detected "old myocardial infarction" in 3.8% of men and 0% of women and "old myocardial infarction possible" in 6.1% and 3%, respectively. Cardiac infarction injury scores are also provided. In conclusion, the study provides reference values for ECG findings in a specific population of people of African descent and stresses the need to systematically consider gender, age, and ethnicity when interpreting ECG tracings in individuals.
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Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35–64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 μg/d respectively. Approximately, 32 % of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.
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Objective: To determine the values of, and study the relationships among, central corneal thickness (CCT), intraocular pressure (IOP), and degree of myopia (DM) in an adult myopic population aged 20 to 40 years in Almeria (southeast Spain). To our knowledge this is first study of this kind in this region. Methods: An observational, descriptive, cross-sectional study was done in which a sample of 310 myopic patients (620 eyes) aged 20 to 40 years was selected by gender- and age-stratified sampling, which was proportionally fixed to the size of the population strata for which a 20% prevalence of myopia, 5% epsilon, and a 95% confidence interval were hypothesized. We studied IOP, CCT, and DM and their relationships by calculating the mean, standard deviation, 95% confidence interval for the mean, median, Fisher’s asymmetry coefficient, range (maximum, minimum), and the Brown-Forsythe’s robust test for each variable (IOP, CCT, and DM). Results: In the adult myopic population of Almeria aged 20 to 40 years (mean of 29.8), the mean overall CCT was 550.12 μm. The corneas of men were thicker than those of women (P = 0.014). CCT was stable as no significant differences were seen in the 20- to 40-year-old subjects’ CCT values. The mean overall IOP was 13.60 mmHg. Men had a higher IOP than women (P = 0.002). Subjects over 30 years (13.83) had a higher IOP than those under 30 (13.38) (P = 0.04). The mean overall DM was −4.18 diopters. Men had less myopia than women (P < 0.001). Myopia was stable in the 20- to 40-year-old study population (P = 0.089). A linear relationship was found between CCT and IOP (R2 = 0.152, P ≤ 0.001). CCT influenced the IOP value by 15.2%. However no linear relationship between DM and IOP, or between CCT and DM, was found. Conclusions: CCT was found to be similar to that reported in other studies in different populations. IOP tends to increase after the age of 30 and is not accounted for by alterations in CCT values.
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The variation with latitude of incidence and mortality for cutaneous malignant melanoma (CMM) in the non-Maori population of New Zealand was assessed. For those aged 20 to 74 years, the effects of age, time period, birth-cohort, gender, and region (latitude), and some interactions between them were evaluated by log-linear regression methods. Increasing age-standardized incidence and mortality rates with increasing proximity to the equator were found for men and women. These latitude gradients were greater for males than females. The relative risk of melanoma in the most southern part of New Zealand (latitude 44 degrees S) compared with the most northern region (latitude 36 degrees S) was 0.63 (95 percent confidence interval [CI] = 0.60-0.67) for incidence and 0.76 (CI = 0.68-0.86) for mortality, both genders combined. The mean percentage change in CMM rates per degree of latitude for males was greater than those reported in other published studies. Differences between men and women in melanoma risk with latitude suggest that regional sun-behavior patterns or other risk factors may contribute to the latitude gradient observed.
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Hearing loss in Meniere's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, wed genotyped three functional variants of NOS1 (rs41279104,rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets(273 patients in total) and 550 controls. A third cohort of American patients was genotyped as replication cohort for the CCTTT repeat. Neither allele nor genotype frequencies of rs41279104 and rs2682826 were associated with MD, although longer alleles of the cytosine-adenosine microsatellite repeat were marginally significant (corrected p = 0.05) in the Mediterranean cohort but not in a second Galicia cohort. Shorter numbers of the CCTTT repeat in NOS2A were significantly more frequent in Galicia controls (OR = 0.37 [CI, 0.18-0.76], corrected p =0.04), but this finding could not be replicated in Mediterranean or American case-control populations. Meta-analysis did not support an association between CCTTT repeats and risk for MD. Severe hearing loss (>75 dB) was also not associated with any functional variants studied. Functional variants of NOS1 and and NOS2A do not confer susceptibility for MD.
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Previous studies have reported genetic differences between wild-caught sylvatic, domestic and laboratory pop-ulations of several Triatominae species. The differences between sylvatic and laboratory colonies parallel are similar to the differences observed between sylvatic and domestic populations. Laboratory colonies are frequently used as references for field populations, but the consequences of founder events on the genetic makeup of laboratory or domestic populations are rarely quantified. Our goal was to quantify the genetic change in Rhodnius pallescens populations artificially submitted to founder effects via laboratory colonization. We compared the genetic makeup of two sylvatic populations and their laboratory descendants using a panel of 10 microsatellite markers. Both sylvatic populations were initially collected from palm trees, but the colonies differed in the number of founder insects and amount of time kept in the laboratory. We evaluated allelic polymorphism, differences between expected and observed heterozygosity, estimates of population differentiation (Fst) and inbreeding (Fis, Fit) and cluster analyses based on Nei's distances. We found a unique genetic structure for each sample population, with significant differentiation between the field insects and each of the laboratory generations. These analyses showed strong founder effects and showed that genetic drift had led to a genetic equilibrium over several generations of isolation. Our results suggest that laboratory colonies of R. pallescens have a different genetic structure than their wild relatives and similar processes likely affect other Triatominae laboratory stocks.
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BACKGROUND: This study is aimed to assess the prevalence of awareness, treatment and control of high blood pressure (HBP) and associated factors in a Swiss city. DESIGN: Population-based cross-sectional study of 6182 participants (52.5% women) aged 35-75 years living in Lausanne, Switzerland. METHODS: HBP was defined as blood pressure >/=140/90 mmHg or current antihypertensive medication. RESULTS: The overall prevalence of HBP was 36% (95% confidence interval: 35-38%). Among participants with HBP, 63% were aware of it. Among participants aware of HBP, 78% were treated, and among those treated, 48% were controlled (BP <140/90 mmHg). In multivariate analysis, HBP prevalence was associated with older age, male sex, low educational level, high alcohol intake, awareness of diabetes or dyslipidaemia, obesity and parental history of myocardial infarction. HBP awareness was associated with older age, female sex, awareness of diabetes or dyslipidaemia, obesity and parental history of myocardial infarction. HBP control was associated with younger age, higher educational level and no alcohol intake. Alone or in combination, sartans were the most often prescribed antihypertensive medication category (41%), followed by diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium channel blockers. Only 31% of participants treated for HBP were taking >/=2 antihypertensive medications. CONCLUSION: Although more than half of all participants with HBP were aware and more than three-quarters of them received a pharmacological treatment, less than half of those treated were adequately controlled.
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The investigation of the genetic variation and population structure of Chrysomya species is of great interest for both basic and applied research. However, very limited genetic information is available for this genus across its geographical distribution. Here, we describe 12 polymorphic microsatellite loci isolated from Chrysomya putoria with expected heterozygosities ranging from 0.1402-0.8312. These markers are of potential applied interest for forensic entomologists and for the characterisation of the genetic structure of C. putoria from recently colonised regions, with great promise for understanding the colonisation dynamics and spread of the genus Chrysomya in the New World.
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BACKGROUND The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The CD209 gene is located in a region linked previously to IBD and a CD209 functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this CD209 variant in IBD susceptibility. METHODS We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using chi2 tests. RESULTS No association between CD209 and UC or CD was observed initially. However, stratification of UC patients by HLA-DR3 status, a strong protective allele, showed that carriage of the CD209_G allele could increase susceptibility in the subgroup of HLA-DR3-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04-3.02, vs. controls). CONCLUSION A functional variant in the CD209 gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in HLA-DR3-positive individuals but further studies are necessary.
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In the present paper, we evaluate the relationship between climate variables and population density of Lutzomyia longipalpis in Montes Claros, an area of active transmission of American visceral leishmaniasis (AVL) in Brazil. Entomological captures were performed in 10 selected districts of the city, between September 2002-August 2003. A total of 773 specimens of L. longipalpiswere captured in the period and the population density could be associated with local climate variables (cumulative rainfall, average temperature and relative humidity) through a mathematical linear model with a determination coefficient (Rsqr) of 0.752. Although based on an oversimplified statistical analysis, as far as the vector is concerned, this approach showed to be potentially useful as a starting point to guide control measures for AVL in Montes Claros.
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Strong reciprocity, defined as a predisposition to help others and to punish those that are not helping, has been proposed as a potent force leading to the evolution of cooperation and altruism. However, the conditions under which strong reciprocity might be favored are not clear. Here we investigate the selective pressure on strong reciprocity by letting both limited dispersal (i.e., spatial structure) and recombination between helping and punishment jointly determine the evolutionary dynamics of strong reciprocity. Our analytical model suggests that when helping and punishment are perfectly linked traits (no recombination occurring between them), strong reciprocity can spread even when the initial frequency of strong reciprocators is close to 0 in the population (i.e., a rare mutant can invade). By contrast, our results indicate that when recombination can occur between helping and punishment (i.e., both traits coevolve) and is stronger than selection, punishment is likely to invade a population of defectors only when it gives a direct fitness benefit to the actor. Overall, our results delineate the conditions under which strong reciprocity is selected for in a spatially structured population and highlight that the forces behind its evolution involves kinship (be it genetic or cultural).
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Although the genome of Trypanosoma cruzi has been completely sequenced, little is known about its population structure and evolution. Since 1999, two major evolutionary lineages presenting distinct epidemiological characteristics have been recognised: T. cruzi I and T. cruzi II. We describe new and important aspects of the population structure of the parasite, and unequivocally characterise a third ancestral lineage that we propose to name T. cruzi III. Through a careful analysis of haplotypes (blocks of genes that are stably transmitted from generation to generation of the parasite), we inferred at least two hybridisation events between the parental lineages T. cruzi II and T. cruzi III. The strain CL Brener, whose genome was sequenced, is one such hybrid. Based on these results, we propose a simple evolutionary model based on three ancestral genomes, T. cruzi I, T. cruzi II and T. cruzi III. At least two hybridisation events produced evolutionarily viable progeny, and T. cruzi III was the cytoplasmic donor for the resulting offspring (as identified by the mitochondrial clade of the hybrid strains) in both events. This model should be useful to inform evolutionary and pathogenetic hypotheses regarding T. cruzi.
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Introduction: Bien que l'imatinib (Glivec®) ait révolutionné le traitement de la leucémie myéloïde chronique (LMC) et des tumeurs stromales d'origine digestive (GIST), ses relations pharmacocinétique-pharmacodynamique (PK-PD) ont été peu étudiées. De par ses caractéristiques pharmacocinétiques (PK), ce médicament pourrait toutefois représenter un candidat à un programme de suivi thérapeutique (TDM). Objectif: Cette étude observationnelle visait à explorer ces relations PK-PD, et à évaluer l'influence spécifique du génotype de la tumeur dans la population GIST. Méthode: Des données de 59 patients ont été collectées durant une étude pharmacocinétique précédente. Sur la base du modèle de population développé alors, les paramètres PK ont été obtenus par estimation bayésienne et ont permis d'estimer l'exposition au médicament (AUC; aire sous la courbe). Les paramètres se rapportant à la fraction libre de l'imatinib ont été déduits d'un modèle intégrant les taux plasmatiques d'alpha1-glycoprotéine acide. L'association entre l'AUC (ou la clairance) et la réponse ou la toxicité a été explorée par régression logistique. L'influence du génotype de la tumeur (gène KIT) sur la réponse a également été évaluée chez des patients GIST. Résultats: L'exposition du médicament totale et libre est corrélée au nombre d'effets indésirables (ex: OR 2.9 ± 0.6 pour un accroissement d'AUC d'un facteur 2; p<0.001). Une relation avec la réponse n'est par contre pas évidente (les bons répondeurs recevant souvent des doses plus faibles que les mauvais répondeurs). Cependant, chez les patients GIST, une AUC libre plus élevée prédit une meilleure réponse (OR 1.9 ± 0.6; p<0.001), notamment chez les patients présentant des mutations sur l'exon 9 du gène cible KIT (ou un gène wild-type). Un tel profile génétique est connu pour diminuer la sensibilité à l'imatinib, par opposition à des mutations sur l'exon 11. Discussion-conclusion: Ces résultats, associés à la grande variabilité PK observée, représentent des arguments pour évaluer, pour l'imatinib, le bénéfice d'un programme de TDM. Nos données suggèrent également qu'une stratification des patients selon le génotype de la tumeur est important.