999 resultados para Inhibiting factors
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Despite a common disorder population-based data on gastro-esophageal reflux disease (GERD) in Bangladesh is lacking. This epidemiological study was designed to determine the prevalence of GERD and its association with lifestyle factors. This population-based cross-sectional study was done by door to door interview of randomly selected persons in both urban and rural areas of North Eastern part of Bangladesh by using a validated questionnaire. A cutoff point 3 was chosen as a valid and reliable scale to confirm GERD. Statistical analysis was done by SPSS-12 version and the level of significance was set at P < or = 0.05. A total of 2000 persons with an age range of 15 to 85 years were interviewed; 1000 subjects from urban area and 1000 from rural area. Among the study subjects 1064 were male and 936 were female. A total of 110 persons (5.5%) were found to have GERD symptoms and among them 47 were men and 67 were women. The monthly, weekly and daily prevalence of heart-burn and or acid regurgitation was 5.5%, 5.25% and 2.5% respectively. Female sex, increased age and lower level of education were significantly associated with GERD symptoms. Prevalence was found more among city dwellers (approximately 6.0% versus 4.8%), married (6.23%, n = 86), widowed/widowers (16.83%, n = 17) and day labourer (8.78%). Level of education inversely influenced the prevalence. No significant association of GERD was found with body mass index (BMI) and smoking. Prevalence of GERD in North-Eastern part of Bangladesh was lower than that of western world. Prevalence was found higher in urban population, women, married, widowed/widowers and in poor an dilliterate persons. BMI and smoking had no significant association with GERD.
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Abstract : The term "muscle disuse" is often used to refer collectively to reductions in neuromuscular activity as observed with sedentary lifestyles, reduced weight bearing, cancer, chronic obstructive pulmonary disease, chronic heart failure, spinal cord injury, sarcopenia or exposure to microgravity (spaceflight). Muscle disuse atrophy, caused by accelerated proteolysis, is predominantly due to the activation of the ATP-dependent ubiquitin (Ub) proteasome pathway. The current advances in understanding the molecular factors contributing to the Ub-dependent proteolysis process have been made mostly in rodent models of human disease and denervation with few investigations performed directly in humans. Recently, in mice, the genes Atrogin-1 and MuRF1 have been designated as primary candidates in the control of muscle atrophy. Additionally, the decreased activity of the Akt/GSK-3ß and Akt/mTOR pathways has been associated with a reduction in protein synthesis and contributing to skeletal muscle atrophy. Therefore, it is now commonly accepted that skeletal muscle atrophy is the result of a decreased protein synthesis concomitant with an increase in protein degradation (Glass 2003). Atrogin-1 and MuRF1 are genes expressed exclusively in muscle. In mice, their expression has been shown to be directly correlated with the severity of atrophy. KO-mice experiments showed a major protection against atrophy when either of these genes were deleted. Skeletal muscle hypertrophy is an important function in normal postnatal development and in the adaptive response to exercise. It has been shown, in vitro, that the activation of phosphatidylinositol 3-kinase (PI-3K), by insulin growth factor 1 (IGF-1), stimulates myotubes hypertrophy by activating the downstream pathways, Akt/GSK-3ß and Akt/mTOR. It has also been demonstrated in mice, in vivo, that activation of these signalling pathways causes muscle hypertrophy. Moreover, the latter were recently proposed to also reduce muscle atrophy by inhibiting the FKHR mediated transcription of several muscle atrophy genes; Atrogin-1 and MuRF1. Therefore, these targets present new avenues for developing further the understanding of the molecular mechanisms involved in both skeletal muscle atrophy and hypertrophy. The present study proposed to investigate the regulation of the Akt/GSK-3ß and Akt/mTOR signalling pathways, as well as the expression levels of the "atrogenes", Atrogin-1 and MuRF1, in four human models of skeletal muscle atrophy. In the first study, we measured the regulation of the Akt signalling pathway after 8 weeks of both hypertrophy stimulating resistance training and atrophy stimulation de-training. As expected following resistance training, muscle hypertrophy and an increase in the phosphorylation status of the different members of the Akt pathway was observed. This was paralleled by a concomitant decrease in FOXO1 nuclear protein content. Surprisingly, exercise training also induced an increase in the, expression of the atrophy genes and proteins involved in the ATP-dependant ubiquitin-proteasome system. On the opposite, following the de-training period a muscle atrophy, relative to the post-training muscle size, was measured. At the same time, the phosphorylation levels of Akt and GSK-3ß were reduced while the amount of FOXO1 in the nucleus increased. After the atrophy phase, there was also a reduction in Atrogin-1 and MuRF1 contents. In this study, we demonstrate for the first time in healthy human skeletal muscle, that the regulation of Akt and its downstream targets GSK-3ß, mTOR and FOXO1 are associated with both thé skeletal muscle hypertrophy and atrophy processes. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of both upper and lower motor neurons, which leads to severe muscle weakness and atrophy. All measurements were performed in biopsies from 22 ALS patients and 16 healthy controls. ALS patients displayed an increase in Atrogin-1 mRNA and protein content which was associated with a decrease in Akt activity. However there was no difference in the mRNA and phospho-protein content of FOXO1, FOXO3a, p70S6K and GSK-3ß. The transcriptional regulation of human Atrogin-1 may be controlled by an Akt-mediated transcription factor other than FKHR or via an other signalling pathway. Chronic complete spinal cord injury (SCI) is associated with severe muscle atrophy which is linked to co-morbidity factors such as diabetes, obesity, lipid disorders and cardiovascular diseases. Molecular mechanisms associated with chronic complete SCI-related muscle atrophy are not well understood. The aim of the present study was to determine if there was an increase in catabolic signalling targets such as Atrogin-1, MuRF1, FOXO and myostatin, and decreases in anabolic signalling targets such as IGF, Akt, GSK-3ß, mTOR, 4E-BP1 and p-70S6K in chronic complete SCI patients. All measurements were performed in biopsies taken from 8 complete chronic SCI patients and 7 age matched healthy controls. In SCI patients when compared with controls, there was a significant reduction in mRNA levels of Atrogin1, MuRF1 and Myostatin. Protein levels for Atrogin-1, FOX01 and FOX03a were also reduced. IGF-1 and both phosphorylated GSK-3ß and 4E-BP1 were decreased; the latter two in an Akt and mTOR independent manner, respectively. Reductions in Atrogin-1, MuRF1, FOXO and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. The downregulation of signalling proteins regulating anabolism such as IGF, GSK3ß and 4E-BP1 would reduce the ability to increase protein synthesis rates in this chronic state of muscle wasting. The molecular mechanisms controlling age-related skeletal muscle loss in humans are poorly understood. The present study aimed to investigate the regulation of several genes and proteins involved in the activation of key signalling pathways promoting muscle hypertrophy such as GH/STAT5/IGF, IGF/Akt/GSK-3ß/4E-BP1 and muscle atrophy such as TNFα/SOCS3 and Akt/FOXO/Atrogin-1 or MuRF1 in muscle biopsies from 13 young and 16 elderly men. In the older, as compared with the young subjects, TNFα and SOCS-3 were increased while growth hormone receptor protein (GHR) and IGF-1 mRNA were both decreased. Akt protein levels were increased however no change in phosphorylated Akt content was observed. GSK-3ß phosphorylation levels were increased while 4E-BP1 was not changed. Nuclear FKHR and FKHRL1 protein levels were decreased, with no changes in their atrophy target genes, Atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signalling proteins such as GHR, IGF and Akt. TNFα, SOCS-3 and myostatin are potential candidates influencing this anabolic perturbation. In conclusion our results support those obtained in rodent or ín vitro models, and demonstrate Akt plays a pivotal role in the control of muscle mass in humans. However, the Akt phosphorylation status was dependant upon the model of muscle atrophy as Akt phosphorylation was reduced in all atrophy models except for SCI. Additionally, the activity pattern of the downstream targets of Akt appears to be different upon the various human models. It seems that under particular conditions such as spinal cord injury or sarcopenia, .the regulation of GSK-3ß, 4eBP1 and p70S6K might be independent of Akt suggesting alternative signalling pathways in the control of these the anabolic response in human skeletal muscle. The regulation of Atrogin-1 and MuRF1 in some of our studies has been shown to be also independent of the well-described Akt/FOXO signalling pathway suggesting that other transcription factors may regulate human Atrogin-1 and MuRF1. These four different models of skeletal muscle atrophy and hypertrophy have brought a better understanding concerning the molecular mechanisms controlling skeletal muscle mass in humans.
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The present work was carried out in a watercress garden in Alto da Boa Vista, in the city of Rio de Janeiro, Brazil. The investigation was carried out in two phases. The first one (1985-86) involved the sampling of Biomphalaria tenegophila in two areas to determine its relative populational densities. The results showed that the populations presented similar densities and dynamics. The second phase (1988-89) involved the study of the influence of some environmental factors on the establishment of B. tenagophila in watercress garden. Two factors were identified as responsible for the establishment of B. tenagophila in the garden: (1) the quality of the water entering the irrigation system, to which domestic sewage is added, and (2) alterations in the nature of the substrate, due to inadequate fertilization techniques, which employ organic matter from adjacent pigsties. Aquatic plants and hydrological parameters of the irrigation system were subsidiary factors to the establishment of B. tenagophila in the garden.
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The purpose of this study was to assess the long-term outcomes of patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) without Five-Factor Score (FFS)-defined poor-prognosis factors (FFS=0) and enrolled in a prospective clinical trial. Patients were followed (2005-2012) under routine clinical care in an extended study and data were recorded prospectively. Long-term survival, disease-free survival (DFS), relapses, therapeutic responses and sequelae were analyzed. Mean±SD follow-up was 98.2±41.9months. After having initially received glucocorticoids (GC) alone, according to the study protocol, 82% (97/118) patients achieved remission but 18% (21/118) required ≥1 immunosuppressant(s) (IS) before 19/21 achieved remission. Two patients died before entering remission. After remission, 53% (61/116) patients relapsed 25.6±27.9months after starting treatment. The 5- and 8-year overall survival rates were 93% and 86%, respectively, with no difference between PAN and MPA, and between relapsers and nonrelapsers. DFS was shorter for MPA than PAN patients (P=0.02). Throughout follow-up, 47% of patients required ≥1 IS. At the last follow-up visit, 44% were still taking GC and 15% IS. The mean vasculitis damage index score was 1.9±1.9; the most frequent sequelae were peripheral neuropathy, hypertension and osteoporosis. For PAN or MPA patients without poor-prognosis factors at diagnosis and treated initially with GC alone, long-term survival was excellent. However, relapses remained frequent, requiring IS introduction for nearly half of the patients. To lower the frequencies of relapses and sequelae remains a challenge for FFS=0 PAN and MPA patients.
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Background¦The outcome after primary percutaneous coronary intervention (pPCI) for STElevation¦Myocardial Infarction (STEMI) is strongly affected by time delays. In thepresent study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients from a well-defined region of the French part of Switzerland.¦Method¦A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analyzed for the following socioeconomic factors: level of education, gender, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment by fibrinolysis or patients immediately referred for CABG.¦Therefore, 352 patients were finally included.¦Results¦At one year, there was no difference in mortality amongst the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly higher for patients with a low level of education, Swiss citizens and non-married patients with median differences of 40 minutes, 48 minutes, and 60 minutes, respectively (p<0.05).¦Nevertheless, no difference was found regarding in-hospital management and clinical outcome.¦Conclusion¦This study demonstrates that symptom-to-first-medical-contact time is higher amongst people with a lower educational level, Swiss-citizens, and non-married people. Because of the low mortality rate in general, these differences in time delays did not affect clinical outcomes. Still, primary prevention measures should particularly focus on these vulnerable populations.
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Strains of Vibrio parahaemolyticus, Vibrio fluvialis and Vibrio mimicus isolated from seafood and seawater were examined for characteristics related to infectivity, such as enzymatic activity and animal assays. All strains hydrolysed DNA, starch, gelatin and chitin. Variable results were obtained with the haemolysin, chondroitin, collagen, elastin and lecithin tests. Production of thermostable direct haemolysin by V. parahaemolyticus was detected in 7.1% strains derived from seafood and 2%from seawater. In the animal assays, strains of V. fluvialis showed positive results at skin PF (75%), mouse lethality (100%), but no fluid accumulation in the suckling mice model was noted. Concerning V. mimicus, results showed skin PF (100%), mouse lethality (100%) and fluid accumulation in suckling mice (66.6%).
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Variations in the rate of predation of the waterbugs Sphaerodema annulatum and S. rusticum on the snails Lymnaea (Radix) luteola have been noted in respect to the morphs of the waterbugs, size of the prey individuals, densities of prey and predators, temperature and surface area of the waterbody concerned and the seasons. Consumption rate was highest (7.2 and 2.2 individuals per day per individual of S. annulatum and S. rusticum, respectively) in prereproductive ages of the waterbugs. This was followed by a gradual decline with the increase in age of the predators. The consumption rate was gradually higher with the increase of temperature from 20 °C to 35 °C. The bugs failed to survive beyond 35 days at 35 °C. Though the bugs prey upon the snails of all sizes preference for 6.5 ÷ 4.5 mm to 8 ÷ 5 mm individuals by S. annulatum and for 5 ÷ 3 mm to 6.5 ÷ 4.5 mm individuals belonged to 3 ÷ 2 - 4 ÷ 3 mm size group maximum when supplied separately. The rate of predation gradually declined with the rise of predator's desity irrespective of waterbug species. Predation rate increased with increasing prey density. This was level off when the prey snails were 1100 and 700 in number for S. annulatum and S. rusticum respectively. An adult S. annulatum and S. rusticum consumed 5.04, 3.7, 1.43 and 3.36, 2.49, 1.04 snails per day respectively in summer, monsoon and winter.
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Purpose: To assess the prevalence of four self-reported cardiovascular risk factors (CV RFs: smoking, hypertension, dyslipidaemia and diabetes) and their reported management in seven Swiss regions (Léman, MiUelland, Zurich, North-West Switzerland, Oriental Switzerland, Central Switzerland and Tessin). Methods: National health interview survey conducted in 2007 in a representative sample of the Swiss population (17,879 subjects). Age-adjusted data on prevalence of self-reported CV RFs, treatment among participants reporting a RF, control of RFs among treated participants and CV RF screening in the last 12 months levels were computed after weighting. Results: The prevalence of hypertension was highest in North-West Switzerland (27.3%) and lowest in Central Switzerland (21.0%, p<0.001). Antihypertensive treatment was highest in Léman region (62.7%) and lowest in Oriental Switzerland (55.2%, p<0.001). Screening was higher in Tessin (89.3%) and lowest in Léman region (81.8%, p<0.001). Prevalence of dyslipidaemia was highest in Tessin and Léman region (20.7% and 20.1 %, respectively) and lowest in Oriental Switzerland (14.5%, p<0.001). Lipid-Iowering treatment was highest in Tessin and Léman region (44.3% each) and lowest in Central Switzerland (30.7%, p<0.001). Dyslipidaemia screening was highest in Tessin (76.6%) and lowest in Central Switzerland (58.6%, p<0.001). Prevalence of diabetes was highest in North-West Switzerland (5.4%) and lowest in Central Switzerland (3.3%, p<0.05). Diabetes screening was highest in Tessin (78.1%) and lowest in Oriental Switzerland (64.0%, p<0.001). Conversely, no between-region differences were found for hypertension or dyslipidaemia control (see table). Conclusion: there are significant differences between the Swiss regions in self-reported prevalence and management of CV RFs. Screening is beUer in Tessin than in the other regions.
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OBJECTIVE: The present study aimed to measure the prevalence of adult attention deficit hyperactivity disorder (ADHD) in a large, representative sample of young Swiss men and to assess factors associated with this disorder. METHODS: Our sample consisted of 5656 Swiss men (mean age 20 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed with the World Health Organization (WHO) adult ADHD Self Report Screener (ASRS). Logistic regression analyses were conducted to assess the association between ADHD and several socio-demographic, clinical and familial factors. RESULTS: The prevalence of ADHD was 4.0%, being higher in older and French-speaking conscripts. A higher prevalence also was identified among men whose mothers had completed primary or high school/university and those with a family history of alcohol or psychiatric problems. Additionally, adults with ADHD demonstrated impairment in their professional life, as well as considerable mental health impairment. CONCLUSION: Our results demonstrate that ADHD is common among young Swiss men. The impairments in function and mental health we observed highlight the need for further support and interventions to reduce burden in affected individuals. Interventions that incorporate the whole family also seem crucial.
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Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems, and aberrant Notch signaling is associated with tumorigenesis. The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin. Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1-/- embryos die during gestation. Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin.
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Sera from 29 individuals residing in a malaria-endemic region of Colombia were evaluated by an inhibition assay for their capacity to retard the growth of Plasmodium falciparum in vitro. The inhibitory activity was found to be independent of antibody activity. Furthermore, the degree of inhibition of parasite development was variable, depending on the parasite isolate used for the assay and the season of malaria transmission. We selected sera with high inhibitory activity and carried out partial analytical characterization by anion exchange fast protein liquid chromatography (FPLC) to identify the chemical nature of the inhibitory factor(s). The results suggested that the in vitro inhibitory activity might result from the additive effect of different molecules. It appears that these molecules could be non-specifically induced by stimulation of the immune system, they seem to play a role in the immunity to malaria.
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La predicció del grau d’adaptació de les persones que ingressen als centres penitenciaris és un element clau per poder minimitzar problemes regimentals i, alhora, facilitar el procés de rehabilitació. Els elements predictors es poden fonamentar en variables psicomètriques (mesurades mitjançant qüestionaris psicològics) i també en judicis tècnics professionals, basats en l’acumulació d’experiència obtinguda pel treball. En aquesta investigació, es validen dos qüestionaris psicomètrics que poden ser útils per predir el grau d’adaptació regimental: un de personalitat, el CPS (Cuestionario de Personalidad Situacional) i l’altre d’impulsivitat, el BARRAT (BIS-11). Els resultats demostren que les variables del CPS prediuen millor el comportament conflictiu, mentre que la impulsivitat mesurada pel BARRAT prediu millor el comportament adaptat. També es validen els criteris tècnics psicològic (judici tècnic emès per part del psicòleg) i criminològic (judici tècnic emès per part del jurista criminòleg). El pas següent ha estat fer una validació creuada que consisteix en la comparació mútua entre el criteris psicomètrics i els tècnics, per veure quines variables són finalment seleccionades de cara a la predicció de la variable més rellevant de l’adaptació regimental: haver tingut o no una regressió de grau de tractament penitenciari. Els resultats demostren que no hi ha una superioritat dels criteris psicomètrics sobre els criteris tècnics i que no estan oposats, sinó que es reforcen mútuament per millorar la predicció del grau d’adaptació regimental. El poder predictiu de les variables seleccionades és encara més alt quan es tracta de predir l’adaptació al règim penitenciari dels interns primaris (els que ingressen per primera vegada a la presó) que quan es refereix als reincidents. D’altra banda, s’ha baremat el qüestionari d’impulsivitat de BARRAT (BIS-11) en població penitenciària per convertir-lo en una eina de pronòstic, tant de comportament regimental com de reincidència penal.