878 resultados para Age-related diseases


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Rhodnius ecuadoriensis is the second most important vector of Chagas Disease (CD) in Ecuador. The objective of this study was to describe (and compare) the life cycle, the feeding and defecation patterns under laboratory conditions of two populations of this specie [from the provinces of Manabí (Coastal region) and Loja (Andean region)]. Egg-to-adult (n = 57) development took an average of 189.9 ± 20 (Manabí) and 181.3 ± 6.4 days (Loja). Mortality rates were high among Lojan nymphs. Pre-feeding time (from contact with host to feeding initiation) ranged from 4 min 42 s [nymph I (NI)] to 8 min 30 s (male); feeding time ranged from 14 min 45 s (NI)-28 min 25 s (male) (Manabí) and from 15 min 25 s (NI)-28 min 57 s (nymph V) (Loja). The amount of blood ingested increased significantly with instar and was larger for Manabí specimens (p < 0.001). Defecation while feeding was observed in Manabí specimens from stage nymph III and in Lojan bugs from stage nymph IV. There was a gradual, age-related increase in the frequency of this behaviour in both populations. Our results suggest that R. ecuadoriensis has the bionomic traits of an efficient vector of Trypanosoma cruzi. Together with previous data on the capacity of this species to infest rural households, these results indicate that control of synanthropic R. ecuadoriensis populations in the coastal and Andean regions may have a significant impact for CD control in Ecuador and Northern Peru.

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Motor inhibitory control plays a central role in adaptive behaviors during the entire lifespan. Inhibitory motor control refers to the ability to stop all (global) or a part (selective) of a planned or ongoing motor action. Although the neural processing underlying the global inhibitory control has received much attention from cognitive neuroscientists, brain modulations that occur during selective inhibitory motor control remain unknown. The aim of the present thesis is to investigate the spatio-temporal brain processes of selective inhibitory motor control in young and old adults using high-density electroencephalography. In the first part, we focus on early (preparatory period) spatio-temporal brain processes involved in selective and global inhibitory control in young (study I) and old adults (study II) using a modified Go/No-go task. In study I, we distinguished global from selective inhibition in the early attentional stage of inhibitory control and provided neurophysiological evidence in favor of the combination model. In study II, we showed an under-recruitment of neural resources associated with preservation of performance in old adults during selective inhibition, suggesting efficient cerebral and behavioral adaptations to environmental changes. In the second part, we investigate beta oscillations in the late (post-execution period) spatio-temporal brain processes of selective inhibition during a motor Switching task (i.e., tapping movement from bimanual to unimanual) in young (study III) and old adults (study IV). In study III, we identified concomitant beta synchronization related (i) to sensory reafference processes, which enabled the stabilization of the movement that was perturbed after switching, and (ii) to active inhibition processes that prevented movement of the stopping hand. In study IV, we demonstrated a larger beta synchronization in frontal and parietal regions in old adults compared to young adults, suggesting age-related brain modulations in active inhibition processes. Apart from contributing to a basic understanding of the electrocortical dynamics underlying inhibitory motor control, the findings of the present studies contribute to knowledge regarding the further establishment of specific trainings with aging. -- Le contrôle de l'inhibition motrice joue un rôle central dans les adaptations comportementales quel que soit l'âge. L'inhibition motrice se réfère à la capacité à arrêter entièrement (globale) ou en partie (sélective) une action motrice planifiée ou en cours. Bien que les processus neuronaux sous-jacents de l'inhibition globale aient suscité un grand intérêt auprès des neurosciences cognitives, les modulations cérébrales dans le contrôle de l'inhibition motrice sélective sont encore peu connues. Le but de cette thèse est d'étudier les processus cérébraux spatio-temporels du contrôle de l'inhibition motrice sélective chez les adultes jeunes et âgés en utilisant l'électroencéphalogramme à haute densité. Dans la première partie, nous comparons les processus cérébraux spatio-temporels précoces (préparation motrice) de l'inhibition sélective et globale chez des adultes jeunes (étude I) et âgés (étude II) en utilisant une tâche Go/No-go modifiée. Dans l'étude I, nous avons distingué l'inhibition globale et sélective au niveau des processus attentionnels précoces du contrôle de l'inhibition et nous avons apporté des preuves neurophysiologiques de l'existence d'un modèle de combinaison. Dans l'étude II, nous avons montré une sous-activation neuronale associée à un maintien de la performance dans l'inhibition sélective chez les adultes âgés, suggérant des adaptations cérébrales et comportementales aux contraintes environnementales. Dans la seconde partie, nous examinons les processus cérébraux spatio-temporels tardifs (post-exécution motrice) de l'inhibition sélective pendant une tâche de Switching (tapping bimanuel vers un tapping unimanuel) chez des adultes jeunes (étude III) et âgés (étude IV). Dans l'étude III, nous avons distingué des synchronisations beta liées (i) au traitement des réafférences sensorielles permettant de stabiliser le mouvement perturbé après le switching, et (ii) aux processus d'inhibition active afin d'empêcher les mouvements de la main arrêtée. Dans l'étude IV, cette synchronisation beta était plus forte dans les régions frontales et pariétales chez les âgés par rapport aux jeunes adultes suggérant des modulations cérébrales de l'inhibition active avec l'âge. Outre la contribution fondamentale sur la compréhension des dynamiques électrocorticales dans le contrôle de l'inhibition motrice, les résultats de ces études contribuent à développer les connaissances pour la mise en place de programmes d'entraînements adaptés aux personnes âgées.

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Purpose: In this study, we investigated the expression of the gene encoding beta-galactosidase (Glb)-1-like protein 3 (Glb1l3), a member of the glycosyl hydrolase 35 family, during retinal degeneration in the retinal pigment epithelium (RPE)-specific 65-kDa protein knockout (Rpe65(-/-)) mouse model of Leber congenital amaurosis (LCA). Additionally, we assessed the expression of the other members of this protein family, including beta-galactosidase-1 (Glb1), beta-galactosidase-1-like (Glb1l), and beta-galactosidase-1-like protein 2 (Glb1l2).Methods: The structural features of Glb1l3 were assessed using bioinformatic tools. mRNA expression of Glb-related genes was investigated by oligonucleotide microarray, real-time PCR, and reverse transcription (RT) -PCR. The localized expression of Glb1l3 was assessed by combined in situ hybridization and immunohistochemistry.Results: Glb1l3 was the only Glb-related member strongly downregulated in Rpe65(-/-) retinas before the onset and during progression of the disease. Glb1l3 mRNA was only expressed in the retinal layers and the RPE/choroid. The other Glb-related genes were ubiquitously expressed in different ocular tissues, including the cornea and lens. In the healthy retina, expression of Glb1l3 was strongly induced during postnatal retinal development; age-related increased expression persisted during adulthood and aging.Conclusions: These data highlight early-onset downregulation of Glb1l3 in Rpe65-related disease. They further indicate that impaired expression of Glb1l3 is mostly due to the absence of the chromophore 11-cis retinal, suggesting that Rpe65 deficiency may have many metabolic consequences in the underlying neuroretina.

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Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.

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The present study investigates developmental changes in selective inhibition of symmetric movements with a lateralized switching task from bimanual to unimanual tapping in typically developing (TD) children and with Developmental Coordination Disorder (DCD) from 7 to 10 years old. Twelve right-handed TD children and twelve gender-matched children with DCD and probable DCD produce a motor switching task in which they have (1) to synchronize with the beat of an auditory metronome to produce bimanual symmetrical tapping and (2) to selectively inhibit their left finger's tapping while continuing their right finger's tapping and conversely. We assess (1) the development of the capacity to inhibit the stopping finger (number of supplementary taps after the stopping instruction) and (2) the development of the capacity to maintain the continuing finger (changes in the mean tempo and its variability for the continuing finger's tapping) and (3) the evolution of performance through trials. Results indicate that (1) TD children present an age-related increase in the capacity to inhibit and to maintain the left finger's tapping, (2) DCD exhibits persistent difficulties to inhibit the left finger's tapping, and (3) both groups improve their capacity to inhibit the left finger's movements through trials. In conclusion, the lateralized switching task provides a simple and fine tool to reveal differences in selective inhibition of symmetric movements in TD children and children with DCD. More theoretically, the specific improvement in selective inhibition of the left finger suggests a progressive development of inter-hemispheric communication during typical development that is absent or delayed in children with DCD.

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.

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Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associated SLC6A8. Here, we identified a second creatine transporter (CRT2) known as monocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, Slc16a12 knockout (KO) rats have elevated creatine levels in urine. Transport activity and expression characteristics of the two creatine transporters are distinct. CRT2 (MCT12)-mediated uptake of creatine was not sensitive to sodium and chloride ions or creatine biosynthesis precursors, breakdown product creatinine or creatine phosphate. Increasing pH correlated with increased creatine uptake. Michaelis-Menten kinetics yielded a Vmax of 838.8 pmol/h/oocyte and a Km of 567.4 µm. Relative expression in various human tissues supports the distinct mutation-associated phenotypes of the two transporters. SLC6A8 was predominantly found in brain, heart and muscle, while SLC16A12 was more abundant in kidney and retina. In the lens, the two transcripts were found at comparable levels. We discuss the distinct, but possibly synergistic functions of the two creatine transporters. Our findings infer potential preventive power of creatine supplementation against the most prominent age-related vision impaired condition.

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This study was designed to investigate personality development with children aged 8 to 12. For this purpose, Children's self-perceptions were compared to parent's ratings. 506 children and their parents completed a selection of 38 questions from the Hierarchical Personality Inventory for Children (HiPIC). Results showed an age-related increase in the structural congruence of children's ratings compared to parents' ratings and a highly significant increase in the reliabilities of both parents' and children's assessments. The mean correlation between the children's self-descriptions and parents' ratings were higher for Conscientiousness and Imagination than for Extraversion, Benevolence and Emotional Stability and significantly increased with the children's age. Mean-levels decreased with age for Imagination in parents' ratings and for Benevolence, Conscientiousness, and Imagination, in children's ratings. This study showed that personality development from 8 to 12 years goes along with an increase in the agreement between the children's self-perceptions and the parents' perceptions of the children's personality.

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Charcot-Marie-Tooth disease type 2A is an autosomal dominant axonal form of peripheral neuropathy caused by mutations in the mitofusin 2 gene. Mitofusin 2 encodes a mitochondrial outer membrane protein that participates in mitochondrial fusion in mammalian cells. How mutations in this protein lead to Charcot-Marie-Tooth disease type 2A pathophysiology remains unclear. We have generated a transgenic mouse expressing either a mutated (R94Q) or wild-type form of human mitofusin 2 in neurons to evaluate whether the R94Q mutation was sufficient for inducing a Charcot-Marie-Tooth disease type 2A phenotype. Only mice expressing mitofusin 2(R94Q) developed locomotor impairments and gait defects thus mimicking the Charcot-Marie-Tooth disease type 2A neuropathy. In these animals, the number of mitochondria per axon was significantly increased in the distal part of the sciatic nerve axons with a diameter smaller than 3.5 microm. Importantly, the analysis of R94Q transgenic animals also revealed an age-related shift in the size of myelinated axons leading to an over-representation of axons smaller than 3.5 microm. Together these data suggest a link between an increased number of mitochondria in axons and a shift in axonal size distribution in mitofusin 2(R94Q) transgenic animals that may contribute to their neurological phenotype.

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RésuméL'origine de l'obésité, qui atteint des proportions épidémiques, est complexe. Elle est liée au mode de vie et au comportement des individus par rapport à l'activité physique, expression des choix individuels et de l'interaction avec l'environnement. Les mesures du comportement au niveau de l'activité physique des individus face à leur environnement, la répartition des types d'activité physique, la durée, la fréquence, l'intensité, et la dépense énergétique sont d'une grande importance. Aujourd'hui, il y a un manque de méthodes permettant une évaluation précise et objective de l'activité physique et du comportement des individus. Afin de compléter les recherches relatives à l'activité physique, à l'obésité et à certaines maladies, le premier objectif du travail de thèse était de développer un modèle pour l'identification objective des types d'activité physique dans des conditions de vie réelles et l'estimation de la dépense énergétique basée sur une combinaison de 2 accéléromètres et 1 GPS. Le modèle prend en compte qu'une activité donnée peut être accomplie de différentes façons dans la vie réelle. Les activités quotidiennes ont pu être classées en 8 catégories, de sédentaires à actives, avec une précision de 1 min. La dépense énergétique a pu peut être prédite avec précision par le modèle. Après validation du modèle, le comportement des individus de l'activité physique a été évalué dans une seconde étude. Nous avons émis l'hypothèse que, dans un environnement caractérisé par les pentes, les personnes obèses sont tentées d'éviter les pentes raides et de diminuer la vitesse de marche au cours d'une activité physique spontanée, ainsi que pendant les exercices prescrits et structurés. Nous avons donc caractérisé, par moyen du modèle développé, le comportement des individus obèses dans un environnement vallonné urbain. La façon dont on aborde un environnement valloné dans les déplacements quotidiens devrait également être considérée lors de la prescription de marche supplémentaire afin d'augmenter l'activité physique.SummaryOrigin of obesity, that reached epidemic proportion, is complex and may be linked to different lifestyle and physical activity behaviour. Measurement of physical activity behaviour of individuals towards their environment, the distribution of physical activity in terms of physical activity type, volume, duration, frequency, intensity, and energy expenditure is of great importance. Nowadays, there is a lack of methods for accurate and objective assessment of physical activity and of individuals' physical activity behaviour. In order to complement the research relating physical activity to obesity and related diseases, the first aim of the thesis work was to develop a model for objective identification of physical activity types in real-life condition and energy expenditure based on a combination of 2 accelerometers and 1 GPS device. The model takes into account that a given activity can be achieved in many different ways in real life condition. Daily activities could be classified in 8 categories, as sedentary to active physical activity, within 1 min accuracy, and physical activity patterns determined. The energy expenditure could be predicted accurately with an accuracy below 10%. Furthermore, individuals' physical activity behaviour is expression of individual choices and their interaction with the neighbourhood environment. In a second study, we hypothesized that, in an environment characterized by inclines, obese individuals are tempted to avoid steep positive slopes and to decrease walking speed during spontaneous outdoor physical activity, as well as during prescribed structured bouts of exercise. Finally, we characterized, by mean of the developed model, the physical activity behaviour of obese individuals in a hilly urban environment. Quantifying how one tackles hilly environment or avoids slope in their everyday displacements should be also considered while prescribing extra walking in free-living conditions in order to increase physical activity.

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The vascular effects of angiotensin converting enzyme inhibitors are mediated by the inhibition of the dual action of angiotensin converting enzyme (ACE): production of angiotensin II and degradation of bradykinin. The deleterious effect of converting enzyme inhibitors (CEI) on neonatal renal function have been ascribed to the elevated activity of the renin-angiotensin system. In order to clarify the role of bradykinin in the CEI-induced renal dysfunction of the newborn, the effect of perindoprilat was investigated in anesthetized newborn rabbits with intact or inhibited bradykinin B2 receptors. Inulin and PAH clearances were used as indices of GFR and renal plasma flow, respectively. Perindoprilat (20 microg/kg i.v.) caused marked systemic and renal vasodilation, reflected by a fall in blood pressure and renal vascular resistance. GFR decreased, while urine flow rate did not change. Prior inhibition of the B2 receptors by Hoe 140 (300 microg/kg s.c.) did not prevent any of the hemodynamic changes caused by perindoprilat, indicating that bradykinin accumulation does not contribute to the CEI-induced neonatal renal effects. A control group receiving only Hoe 140 revealed that BK maintains postglomerular vasodilation via B2 receptors in basal conditions. Thus, the absence of functional B2 receptors in the newborn was not responsible for the failure of Hoe 140 to prevent the perindoprilat-induced changes. Species- and/or age-related differences in the kinin-metabolism could explain these results, suggesting that in the newborn rabbit other kininases than ACE are mainly responsible for the degradation of bradykinin.

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This adult cohort determined the incidence and patients' short-term outcomes of severe traumatic brain injury (sTBI) in Switzerland and age-related differences. A prospective cohort study with a follow-up at 14 days was performed. Patients ≥16 years of age sustaining sTBI and admitted to 1 of 11 trauma centers were included. sTBI was defined by an Abbreviated Injury Scale of the head (HAIS) score >3. The centers participated from 6 months to 3 years. The results are presented as percentages, medians, and interquartile ranges (IQRs). Subgroup analyses were performed for patients ≤65 years (younger) and >65 (elderly). sTBI was observed in 921 patients (median age, 55 years; IQR, 33-71); 683 (74.2%) were male. Females were older (median age, 67 years; IQR, 42-80) than males (52; IQR, 31-67; p<0.00001). The estimated incidence was 10.58 per 100,000 inhabitants per year. Blunt trauma was observed in 879 patients (95.4%) and multiple trauma in 283 (30.7%). Median Glasgow Coma Score (GCS) on the scene was 9 (IQR 4-14; 8 in younger, 12 in elderly) and in emergency departments 5 (IQR, 3-14; 3 in younger, 8 in elderly). Trauma mechanisms included the following: 484 patients with falls (52.6%; younger, 242 patients [50.0%]; elderly, 242 [50.0%]), 291 with road traffic accidents (31.6%; younger, 237 patients [81.4%]; elderly, 54 [18.6%]), and 146 with others (15.8%). Mortality was 30.2% (24.5% in younger, 40.9% in elderly). Median GCS at 14 days was 15 (IQR, 14-15) without differences among subgroups. Estimated incidence of sTBI in Switzerland was low, age was high, and mortality considerable. The elderly had higher initial GCS and a higher death rate, but high GCS at 14 days.

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Some of the elements that characterize the globalization of food and agriculture are industrialization and intensification of agriculture and liberalization of agricultural markets, that favours elongation of the food chain and homogenization of food habits (nutrition transition), among other impacts. As a result, the probability of food contamination has increased with the distance and the number of “hands" that may contact the food (critical points); the nutritional quality of food has been reduced because of increased transport and longer periods of time from collection to consumption; and the number of food-related diseases due to changes in eating patterns has increased. In this context, there exist different agencies and regulations intended to ensure food safety at different levels, e.g. at the international level, Codex Alimentarius develops standards and regulations for the marketing of food in a global market. Although governments determine the legal framework, the food industry manages the safety of their products, and thus, develops its own standards for their marketing, such as the Good Agricultural Practices (GAP) programs. The participation of the private sector in the creation of regulatory standards strengthens the free trade of food products, favouring mostly large agribusiness companies. These standards are in most cases unattainable for small producers and food safety regulations are favouring removal of the peasantry and increase concentration and control in the food system by industrial actors. Particularly women, who traditionally have been in charge of the artisanal transformation process, can be more affected by these norms than men. In this project I am analysing the impcact of food safety norms over small farms, based on the case of artisanal production made by women in Spain.

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PURPOSE: Negative lifestyle factors are known to be associated with increased cardiovascular risk (CVR) in children, but research on their combined impact on a general population of children is sparse. Therefore, we aimed to quantify the combined impact of easily assessable negative lifestyle factors on the CVR scores of randomly selected children after 4 years. METHODS: Of the 540 randomly selected 6- to 13-year-old children, 502 children participated in a baseline health assessment, and 64% were assessed again after 4 years. Measures included anthropometry, fasting blood samples, and a health assessment questionnaire. Participants scored one point for each negative lifestyle factor at baseline: overweight; physical inactivity; high media consumption; little outdoor time; skipping breakfast; and having a parent who has ever smoked, is inactive, or overweight. A CVR score at follow-up was constructed by averaging sex- and age-related z-scores of waist circumference, blood pressure, glucose, inverted high-density lipoprotein, and triglycerides. RESULTS: The age-, sex-, pubertal stage-, and social class-adjusted probabilities (95% confidence interval) for being in the highest CVR score tertile at follow-up for children who had at most one (n = 48), two (n = 64), three (n = 56), four (n = 41), or five or more (n = 14) risky lifestyle factors were 15.4% (8.9-25.3), 24.3% (17.4-32.8), 36.0% (28.6-44.2), 49.8% (38.6-61.0), and 63.5% (47.2-77.2), respectively. CONCLUSIONS: Even in childhood, an accumulation of negative lifestyle factors is associated with higher CVR scores after 4 years. These negative lifestyle factors are easy to assess in clinical practice and allow early detection and prevention of CVR in childhood.

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This is a critical review of the medical, ethical, judicial and financial aspects of the so called "social freezing", the cryopreservation of a woman's oocytes for non-medical purposes. The possibility of storing the eggs of fertile women in order to prevent age-related fertility decline is being widely promoted by fertility centres and the lay press throughout the world. Research data has shown that social freezing should ideally be performed on women around 25 years of age in order to increase their chances of a future pregnancy. In reality, it is mostly performed after the age of 35. Unfortunately, social freezing is in general not a solution for the underlying societal problems to fit in with professionally active women and having children. It only delays the existing problems. Furthermore, it creates a lot of potential new problems. A great deal more should be undertaken to offer real solutions to the underlying societal problems which are in part: pre-school education, care in the event of childhood illness, and the many weeks of school holidays, acceptance of professionally active women having children, and more job offers with a workload <100%.). Furthermore, society should be informed about the decreasing chances of pregnancy with increasing maternal (and paternal) age as well as the increasing risks of miscarriage and obstetric/neonatal complications. Detailed information for woman considering social freezing is crucial. Every doctor, proposing social freezing to his patients, should be up to date with all these details. Follow-up studies on the outcome of these children are needed.