996 resultados para Gh-deficient Adults
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OBJECTIVE: Prospective data on the association between resistin levels and cardiovascular disease (CVD) events are sparse with conflicting results. METHODS: We studied 3044 aged 70-79 years from the Health, Aging, and Body Composition Study. CVD events were defined as coronary heart disease (CHD) or stroke events. «Hard » CHD events were defined as CHD death or myocardial infarction. We estimated hazard ratio (HR) and 95% confidence intervals (CI) according to the quartiles of serum resistin concentrations and adjusted for clinical variables, and then further adjusted for metabolic disease (body mass index, fasting plasma glucose, abdominal visceral and subcutaneous adipose tissue, leptin, adiponectin, insulin) and inflammation (C-reactive protein, interleukin-6, tumor necrosis factors-α). RESULTS: During a median follow-up of 10.1 years, 559 patients had « hard » CHD events, 884 CHD events and 1106 CVD Events. Unadjusted incidence rate for CVD events was 36.6 (95% CI 32.1-41.1) per 1000 persons-year in the lowest quartile and 54.0 per 1000 persons-year in the highest quartile (95% CI 48.2-59.8, P for trend < 0.001). In the multivariate models adjusted for clinical variables, HRs for the highest vs. lowest quartile of resistin was 1.52 (95% CI 1.20-1.93, P < 0.001) for « Hard » CHD events, 1.41 (95% CI 1.16-1.70, P = 0.001) for CHD events and 1.35 (95% CI 1.14-1.59, P = 0.002) for CVD events. Further adjustment for metabolic disease slightly reduced the associations while adjustment for inflammation markedly reduced the associations. CONCLUSIONS: In older adults, higher resistin levels are associated with CVD events independently of clinical risk factors and metabolic disease markers, but markedly attenuated by inflammation.
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QUESTIONS UNDER STUDY: As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. METHODS: We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. RESULTS: A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS: There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.
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BACKGROUND: The burden of asthma on patients and healthcare systems is substantial. Interventions have been developed to overcome difficulties in asthma management. These include chronic disease management programmes, which are more than simple patient education, encompassing a set of coherent interventions that centre on the patients' needs, encouraging the co-ordination and integration of health services provided by a variety of healthcare professionals, and emphasising patient self-management as well as patient education. OBJECTIVES: To evaluate the effectiveness of chronic disease management programmes for adults with asthma. SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, MEDLINE (MEDLINE In-Process and Other Non-Indexed Citations), EMBASE, CINAHL, and PsycINFO were searched up to June 2014. We also handsearched selected journals from 2000 to 2012 and scanned reference lists of relevant reviews. SELECTION CRITERIA: We included individual or cluster-randomised controlled trials, non-randomised controlled trials, and controlled before-after studies comparing chronic disease management programmes with usual care in adults over 16 years of age with a diagnosis of asthma. The chronic disease management programmes had to satisfy at least the following five criteria: an organisational component targeting patients; an organisational component targeting healthcare professionals or the healthcare system, or both; patient education or self-management support, or both; active involvement of two or more healthcare professionals in patient care; a minimum duration of three months. DATA COLLECTION AND ANALYSIS: After an initial screen of the titles, two review authors working independently assessed the studies for eligibility and study quality; they also extracted the data. We contacted authors to obtain missing information and additional data, where necessary. We pooled results using the random-effects model and reported the pooled mean or standardised mean differences (SMDs). MAIN RESULTS: A total of 20 studies including 81,746 patients (median 129.5) were included in this review, with a follow-up ranging from 3 to more than 12 months. Patients' mean age was 42.5 years, 60% were female, and their asthma was mostly rated as moderate to severe. Overall the studies were of moderate to low methodological quality, because of limitations in their design and the wide confidence intervals for certain results.Compared with usual care, chronic disease management programmes resulted in improvements in asthma-specific quality of life (SMD 0.22, 95% confidence interval (CI) 0.08 to 0.37), asthma severity scores (SMD 0.18, 95% CI 0.05 to 0.30), and lung function tests (SMD 0.19, 95% CI 0.09 to 0.30). The data for improvement in self-efficacy scores were inconclusive (SMD 0.51, 95% CI -0.08 to 1.11). Results on hospitalisations and emergency department or unscheduled visits could not be combined in a meta-analysis because the data were too heterogeneous; results from the individual studies were inconclusive overall. Only a few studies reported results on asthma exacerbations, days off work or school, use of an action plan, and patient satisfaction. Meta-analyses could not be performed for these outcomes. AUTHORS' CONCLUSIONS: There is moderate to low quality evidence that chronic disease management programmes for adults with asthma can improve asthma-specific quality of life, asthma severity, and lung function tests. Overall, these results provide encouraging evidence of the potential effectiveness of these programmes in adults with asthma when compared with usual care. However, the optimal composition of asthma chronic disease management programmes and their added value, compared with education or self-management alone that is usually offered to patients with asthma, need further investigation.
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BACKGROUND: Delirium is an acute cognitive impairment among older hospitalized patients. It can persist until discharge and for months after that. Despite proof that evidence-based nursing interventions are effective in preventing delirium in acute hospitals, interventions among home-dwelling older patients is lacking. The aim was to assess feasibility and acceptability of a nursing intervention designed to detect and reduce delirium in older adults after discharge from hospital. METHODS: Randomized clinical pilot trial with a before/after design was used. One hundred and three older adults were recruited in a home healthcare service in French-speaking Switzerland and randomized into an experimental group (EG, n = 51) and a control group (CG, n = 52). The CG received usual homecare. The EG received usual homecare plus five additional nursing interventions at 48 and 72 h and at 7, 14 and 21 days after discharge. These interventions were tailored for detecting and reducing delirium and were conducted by a geriatric clinical nurse (GCN). All patients were monitored at the start of the study (M1) and throughout the month for symptoms of delirium (M2). This was documented in patients' records after usual homecare using the Confusion Assessment Method (CAM). At one month (M2), symptoms of delirium were measured using the CAM, cognitive status was measured using the Mini-Mental State Examination (MMSE), and functional status was measured using Katz and Lawton Index of activities of daily living (ADL/IADL). At the end of the study, participants in the EG and homecare nurses were interviewed about the acceptability of the nursing interventions and the study itself. RESULTS: Feasibility and acceptability indicators reported excellent results. Recruitment, retention, randomization, and other procedures were efficient, although some potentially issues were identified. Participants and nurses considered organizational procedures, data collection, intervention content, the dose-effect of the interventions, and methodology all to be feasible. Duration, patient adherence and fidelity were judged acceptable. Nurses, participants and informal caregivers were satisfied with the relevance and safety of the interventions. CONCLUSIONS: Nursing interventions to detect/improve delirium at home are feasible and acceptable. These results confirm that developing a large-scale randomized controlled trial would be appropriate. TRIAL REGESTRATION: ISRCTN registry no: 16103589 - 19 February 2016.
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BACKGROUND & AIMS: It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS: Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS: Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS: In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.
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NLRC5, a member of the NOD-like receptor (NLR) protein family, has recently been characterized as the master transcriptional regulator of MHCI molecules in lymphocytes, in which it is highly expressed. However, its role in activated dendritic cells (DCs), which are instrumental to initiate T cell responses, remained elusive. We show in this study that, following stimulation of DCs with inflammatory stimuli, not only did NLRC5 level increase, but also its importance in directing MHCI transcription. Despite markedly reduced mRNA and intracellular H2-K levels, we unexpectedly observed nearly normal H2-K surface display in Nlrc5(-/-) DCs. Importantly, this discrepancy between a strong intracellular and a mild surface defect in H2-K levels was observed also in DCs with H2-K transcription defects independent of Nlrc5. Hence, alongside with demonstrating the importance of NLRC5 in MHCI transcription in activated DCs, we uncover a general mechanism counteracting low MHCI surface expression. In agreement with the decreased amount of neosynthesized MHCI, Nlrc5(-/-) DCs exhibited a defective capacity to display endogenous Ags. However, neither T cell priming by endogenous Ags nor cross-priming ability was substantially affected in activated Nlrc5(-/-) DCs. Altogether, these data show that Nlrc5 deficiency, despite significantly affecting MHCI transcription and Ag display, is not sufficient to hinder T cell activation, underlining the robustness of the T cell priming process by activated DCs.
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BACKGROUND: The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). METHODS: We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 10(10) viral particles), low-dose vaccine (2·5 × 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027. FINDINGS: Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 μg/mL (95% CI 41·1-63·3) in the high-dose group, 44·9 μg/mL (25·8-56·3) in the low-dose group, and 5·2 μg/mL (3·5-7·6) in the placebo group, with respective response rates of 96% (95% CI 85·7-99·5), 96% (86·5-99·5), and 5% (0·1-24·9). Geometric mean concentrations decreased by day 180 to 25·5 μg/mL (95% CI 20·6-31·5) in the high-dose group, 22·1 μg/mL (19·3-28·6) in the low-dose group, and 3·2 μg/mL (2·4-4·9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31 (61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses. INTERPRETATION: ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), through the EU Horizon 2020 Research and Innovation Programme.
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Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.
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El setembre del 2000 vam crear el grup de recerca interuniversitari GRE (Grup de Recerca en Envelliment) en el si de la FPCE Blanquerna. Aquest grup està format per professors d'aquesta Facultat i per professors del grup GIG (Grup d'Investigació en Gerontologia) de la Universitat de Barcelona, amb ànim d'investigar sobre la gent gran i la seva qualitat de vida. Som conscients que el canvi demogràfic de la població marcarà el s.XXI. Com han esmentat diferents mitjans de comunicació, un terç de la població espanyola tindrà més de 65 anys l'any 2020. És palès que, en les properes dècades, el nombre de persones grans augmentarà als països desenvolupats, ateses les millores del nivell de vida i la reducció de la taxa de natalitat; per tant, pensem que és un encert estratègic i una visió de futur desenvolupar iniciatives dirigides a conèixer i abordar les necessitats psíquiques i socials de les persones grans.
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L’article s’obre amb una reflexió genèrica sobre la funció tutorial en l’ensenyament de llengües en entorns virtuals. A continuació s’analitza l’acció docent tutorial, els seus rols, funcions i tasques: en primer lloc, en l’autoconeixement inicial, la creació de comunitat i l’acció docent; seguidament, en relació amb l’actuació estratègica dels aprenents, i, finalment, en la incentivació, dinamització i facilitació de l’activitat col·laborativa.
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The human language-learning ability persists throughout life, indicating considerable flexibility at the cognitive and neural level. This ability spans from expanding the vocabulary in the mother tongue to acquisition of a new language with its lexicon and grammar. The present thesis consists of five studies that tap both of these aspects of adult language learning by using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) during language processing and language learning tasks. The thesis shows that learning novel phonological word forms, either in the native tongue or when exposed to a foreign phonology, activates the brain in similar ways. The results also show that novel native words readily become integrated in the mental lexicon. Several studies in the thesis highlight the left temporal cortex as an important brain region in learning and accessing phonological forms. Incidental learning of foreign phonological word forms was reflected in functionally distinct temporal lobe areas that, respectively, reflected short-term memory processes and more stable learning that persisted to the next day. In a study where explicitly trained items were tracked for ten months, it was found that enhanced naming-related temporal and frontal activation one week after learning was predictive of good long-term memory. The results suggest that memory maintenance is an active process that depends on mechanisms of reconsolidation, and that these process vary considerably between individuals. The thesis put special emphasis on studying language learning in the context of language production. The neural foundation of language production has been studied considerably less than that of perceptive language, especially on the sentence level. A well-known paradigm in language production studies is picture naming, also used as a clinical tool in neuropsychology. This thesis shows that accessing the meaning and phonological form of a depicted object are subserved by different neural implementations. Moreover, a comparison between action and object naming from identical images indicated that the grammatical class of the retrieved word (verb, noun) is less important than the visual content of the image. In the present thesis, the picture naming was further modified into a novel paradigm in order to probe sentence-level speech production in a newly learned miniature language. Neural activity related to grammatical processing did not differ between the novel language and the mother tongue, but stronger neural activation for the novel language was observed during the planning of the upcoming output, likely related to more demanding lexical retrieval and short-term memory. In sum, the thesis aimed at examining language learning by combining different linguistic domains, such as phonology, semantics, and grammar, in a dynamic description of language processing in the human brain.
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Background: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, insulin resistance, impaired glucose tolerance, hypertension and dyslipidemia. The prevalence of MetS is increasing worldwide in all age groups. MetS is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. Aims: The aim of the present study was to investigate the prevalence, secular trends and childhood predictors of MetS in young adults. Furthermore, the relations between MetS and subclinical atherosclerosis were studied and whether apolipoproteins (apo) B and A-I, C-reactive protein (CRP) and type II secretory phospholipase A2 (sPLA2) were associated with MetS, and to what extent the atherogenicity of MetS was explained by these factors. Participants and Methods: The present thesis is part of the large scale population-based, prospective study, the Cardiovascular Risk in Young Finns Study. The first cross-sectional study was conducted in 1980 and included 3,596 participants aged 3-18 years. Carotid and brachial ultrasound studies were performed for 2,283 of these participants in 2001 and 2,200 of these participants in 2007. Results: The overall prevalence of MetS in young adults aged 24-39 years in 2001 was 10-15 % and 6 years later in 30-45 year-old adults it was 15-23 % depending on the MetS definition used. Between the years 1986 and 2001, MetS prevalence increased from 1.0 % to 7.5 % (p<0.0001) in 24-year-old participants that was mostly driven by the increased central obesity. Participants with MetS had increased carotid intima-media thickness (cIMT) and decreased carotid elasticity compared to those without the syndrome. Impaired brachial flow-mediated dilatation (FMD) was not related to MetS but it modified the relationship between MetS and cIMT (P for interaction 0.023). High levels of apoB, CRP, sPLA2 and low levels of apoA-I associated with MetS in young adults. In prospective analysis both MetS and high apoB predicted (P<0.0001) incident high cIMT, defined as cIMT>90th percentile and/or plaque. The association between MetS and incident high cIMT was attenuated by ~40 % after adjustment with apoB. Conclusions: MetS is common in young adults and increases with age. Screening for risk factors, especially obesity, at an early life stage could help identify children and adolescents at increased risk of developing MetS and cardiovascular disease later in life. MetS identifies a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MetS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis. In addition, the atherogenicity of MetS in this population assessed by incident high cIMT appears to be substantially mediated by elevated apoB.
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OBJECTIVE: to determine the prevalence of radiographic signs of femoroacetabular impingement (FAI) in asymptomatic adults and correlate them with data from physical examinations. METHODS: We conducted a cross-sectional study with 82 asymptomatic volunteers, 164 hips, between 40 and 60 years of age, selected by convenience. They were submitted to anamnesis and clinical examination of the hip, anteroposterior (AP) pelvis radiographs with three incidences, Dunn 45° and Lequesne false profile of each hip, to measure the variables. We measured the alpha angle, anterior offset of the femoral neck, cervical diaphyseal angle, CE angle of Wiberg, acetabular index, Sharp angle, and the crossing, ischial spine and posterior wall signs. RESULTS: our sample consisted of 66% women, mean age of 50.4 years. The average alpha angle was 45.10°, SD=8.6. One quarter of the hips showed alpha angle greater than or equal to 50°; among men the prevalence was 34%, and among women, 11%. We found indicative radiographic signs of femoroacetabular impingement in 42.6% of hips, whether femoral or acetabular, and the increased alpha angle was related to the decrease in hip internal rotation (p<0.001). CONCLUSION: the radiographic findings of femoroacetabular impingement in asymptomatic patients were frequent in the studied sample. The increase in alpha angle was associated with decreased internal rotation.