300 resultados para Not-for-profit


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The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and ~30% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a 'global' NF-kB negative regulator, in 1 of 12 splenic marginal zone lymphoma. To investigate further whether deregulation of the NF-kB pathway plays a role in the pathogenesis of splenic marginal zone lymphoma, we screened several NF-kB regulators for genetic changes by PCR and sequencing. Somatic mutations were found in A20 (6/46=13%), MYD88 (6/46=13%), CARD11 (3/34=8.8%), but not in CD79A, CD79B and ABIN1. Interestingly, these genetic changes are largely mutually exclusive from each other and MYD88 mutation was also mutually exclusive from 7q deletion. These results strongly suggest that deregulation of the TLR (toll like receptor) and BCR (B-cell receptor) signalling pathway may play an important role in the pathogenesis of splenic marginal zone lymphoma.

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Hepatitis D virus (HDV) is a subviral agent which depends on the envelope proteins (HBsAg) of hepatitis B virus (HBV). Therefore, hepatitis D is observed only in patients infected with HBV. Chronic hepatitis D is the least frequent albeit most severe form of chronic viral hepatitis. A resurgence of chronic hepatitis D has been observed in Northern and Central Europe, mainly due to immigration of patients from regions with high prevalence. Every HBsAg-positive patient should be screened for concurrent HDV infection. Standard treatment consists of pegylated interferon-alpha for at least one year. Sustained virological response rates are approximately 20%. Liver transplantation should be considered in patients with advanced cirrhosis or limited hepatocellular carcinoma. Preventive measures for hepatitis D are the same as for hepatitis B.

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QUESTION UNDER STUDY: Thirty-day readmissions can be classified as potentially avoidable (PARs) or not avoidable (NARs) by following a specific algorithm (SQLape®). We wanted to assess the financial impact of the Swiss-DRG system, which regroups some readmissions occurring within 18 days after discharge within the initial hospital stay, on PARs at our hospital. METHODS: First, PARs were identified from all hospitalisations recorded in 2011 at our university hospital. Second, 2012 Swiss-DRG readmission rules were applied, regrouped readmissions (RR) were identified, and their financial impact computed. Third, RRs were classified as potentially avoidable (PARRs), not avoidable (NARRs), and others causes (OCRRs). Characteristics of PARR patients and stays were retrieved, and the financial impact of PARRS was computed. RESULTS: A total of 36,777 hospitalisations were recorded in 2011, of which 3,140 were considered as readmissions (8.5%): 1,470 PARs (46.8%) and 1,733 NARs (53.2%). The 2012 Swiss-DRG rules would have resulted in 910 RRs (2.5% of hospitalisations, 29% of readmissions): 395 PARRs (43% of RR), 181 NARRs (20%), and 334 OCRRs (37%). Loss in reimbursement would have amounted to CHF 3.157 million (0.6% of total reimbursement). As many as 95% of the 395 PARR patients lived at home. In total, 28% of PARRs occurred within 3 days after discharge, and 58% lasted less than 5 days; 79% of the patients were discharged home again. Loss in reimbursement would amount to CHF 1.771 million. CONCLUSION: PARs represent a sizeable number of 30-day readmissions, as do PARRs of 18-day RRs in the 2012 Swiss DRG system. They should be the focus of attention, as the PARRs represent an avoidable loss in reimbursement.

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The hypothesis of ecological divergence giving rise to premating isolation in the face of gene flow is controversial. However, this may be an important mechanism to explain the rapid multiplication of species during adaptive radiation following the colonization of a new environment when geographical barriers to gene flow are largely absent but underutilized niche space is abundant. Using cichlid fish, we tested the prediction of ecological speciation that the strength of premating isolation among species is predicted by phenotypic rather than genetic distance. We conducted mate choice experiments between three closely related, sympatric species of a recent radiation in Lake Mweru (Zambia/DRC) that differ in habitat use and phenotype, and a distantly related population from Lake Bangweulu that resembles one of the species in Lake Mweru. We found significant assortative mating among all closely related, sympatric species that differed phenotypically, but none between the distantly related allopatric populations of more similar phenotype. Phenotypic distance between species was a good predictor of the strength of premating isolation, suggesting that assortative mating can evolve rapidly in association with ecological divergence during adaptive radiation. Our data also reveals that distantly related allopatric populations that have not diverged phenotypically, may hybridize when coming into secondary contact, e.g. upon river capture because of diversion of drainage systems.

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Missed appointments represent an important medical and economical issue. Few studies on the subject are reported in the literature, particularly regarding adolescents. Our aim was to characterize missed and cancelled appointments in a multidisciplinary outpatient clinic for adolescents, to assess the effectiveness of a policy aimed at reducing missed appointments by introducing payment for those missed appointments not cancelled in advance, and to compare the rates between staff and resident physicians. A total of 32,816 consultations (representing 35 patients aged 12-20 years, 82.4% females) between 1999 and 200 were analysed. The missed appointment rate was 11.8% whilst another 10.9% were cancellations. Females cancelled more than males (11.3% vs. 8.4%, AOR 1.31, 99% CI 1.08-1.59), but there was no difference for missed appointments (11.6% vs. 12.3%, AOR 0.88, 99% CI 0.61-1.08). April and June to October (vacation months) were associated with more missed appointments. Globally mornings had higher rates of missed appointments than afternoons (13.6% vs. 11.2%, AOR 1.25, 99% CI 1.11-1.40). There was a slight difference in missed appointment rates between staff physicians and residents (10.4%; 11.8%, AOR 1.20, 99% CI 1.08-1.33). Missed appointment rates before and after the new policy on missed appointments were similar (1999-2003: 11.9%; 2004-2006: 11.6%, AOR 0.96, 99% CI 0.83-1.10). Conversely, cancellation rates increased from 8.4% (1999-2003) to 14.5% (2004-2006) (AOR 1.83, 99% CI 1.63-2.05). Attendance rates among adolescents show variations depending on vacation and school hours. Being attentive to these factors could help prevent missed appointments. Although having to pay for missed appointments does not increase attendance, it increases cancellations with the advantage that the appointment can be rescheduled.

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The effect of high antigen dose on the activation of cytochrome c peptide-primed lymph node cells was determined in several strains of mice by a limiting dilution analysis. It was found that proliferation of cytochrome c peptide-specific T cells was completely inhibited at high antigen concentration in C57BL/6 but only partially in DBA mice and had no effect in SJL mice. Clones derived from DBA mice showed a differential capacity to be inhibited by high antigen dose. On the other hand, interleukin 2 production by these clones was not impaired regardless of the antigen concentrations used.

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PURPOSE: Not in Education, Employment, or Training (NEET) youth are youth disengaged from major social institutions and constitute a worrying concern. However, little is known about this subgroup of vulnerable youth. This study aimed to examine if NEET youth differ from other contemporaries in terms of personality, mental health, and substance use and to provide longitudinal examination of NEET status, testing its stability and prospective pathways with mental health and substance use. METHODS: As part of the Cohort Study on Substance Use Risk Factors, 4,758 young Swiss men in their early 20s answered questions concerning their current professional and educational status, personality, substance use, and symptomatology related to mental health. Descriptive statistics, generalized linear models for cross-sectional comparisons, and cross-lagged panel models for longitudinal associations were computed. RESULTS: NEET youth were 6.1% at baseline and 7.4% at follow-up with 1.4% being NEET at both time points. Comparisons between NEET and non-NEET youth showed significant differences in substance use and depressive symptoms only. Longitudinal associations showed that previous mental health, cannabis use, and daily smoking increased the likelihood of being NEET. Reverse causal paths were nonsignificant. CONCLUSIONS: NEET status seemed to be unlikely and transient among young Swiss men, associated with differences in mental health and substance use but not in personality. Causal paths presented NEET status as a consequence of mental health and substance use rather than a cause. Additionally, this study confirmed that cannabis use and daily smoking are public health problems. Prevention programs need to focus on these vulnerable youth to avoid them being disengaged.

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Rapport de synthèse : Introduction : le vieillissement cutané est un processus biologique complexe auquel participe une exposition excessive au rayonnement ultraviolet du soleil. En particulier, les longueurs d'onde des rayons ultraviolets A et B (UV-A et UV-B) peuvent induire une augmentation de la synthèse de protéases, comme la métalloprotéinase matricielle 1 (MMP-1), qui est impliquée dans le processus de vieillissement. La thermothérapie par infrarouges, dont les longueurs d'onde sont plus longues que celles des UV, est largement utilisée à des fins thérapeutiques ou cosmétiques. Or, il a été démontré que les infrarouges en filtration aqueuse (IRFA) pouvaient induire une augmentation de la production de MMP-1 et par conséquent être nocifs. Il serait donc intéressant d'évaluer les effets des IRFA au niveau cellulaire et moléculaire. But Expérimental : étudier les effets des lampes à infrarouges en filtration aqueuse utilisées en clinique sur des fibroblastes cutanés humains en culture, afin d'analyser l'expression du gène codant pour la protéine MMP-1. Méthode : des fibroblastes cutanés humain ont été irradiés d'une part avec approximativement 88% d'IRFA (780-1400 nm) et 12% de lumière rouge (LR, 665-780 nm) avec 380 mW/cm2 IRFA(+LR) (333 mW/cm2 IRFA) et d'autre part avec des UV-A comme contrôle. Des courbes de survie cellulaire ont été établies après une exposition allant de 15 minutes à 8 heures au IRFA(+LR) (340-10880 J/cm2 wIRA(+RL), 300-9600 J/cm2 wIRA) ou de 15 à 45 minutes aux UV-A(+BL) (25-75 J/cm2 UV-A(+BL). L'induction de l'ARNm du gène de la MMP-1 a été analysé dans les fibroblastes cutanés humain à deux températures physiologiques (30°C et 37°C) lors d'expositions uniques de 15 à 60 minutes aux IRFA(+LR) (340-1360 J/cm2 IRFA(+LR), 300-1200 J/cm2 IRFA) ou de 30 minutes aux UV-A(+BL) (50 J/cm2 UVA(+BL)). De plus, nous avons effectué des irradiations répétées, une a chaque passage cellulaire jusqu'au passage. 10 de 15 minutes d'IRFA(+LR) 340 J/cm2 IRFA(+LR), 300 J/cm2 IRFA) . Résultats : une exposition unique aux UV-A (+BL) entraîne chez des fibroblastes cutanés humains une augmentation de la mort cellulaire, ainsi qu'une forte augmentation de l'expression du gène codant pour la MMP-1. L'augmentation mise en évidence pour cet ARNm varie en fonction de la technique utilisée : elle est de 11 ± 1 fois par RT-PCR classique, de 76 ± 2 fois par RT-PCR quantitative à 30°C, et de 75 ± 1 fois par RT-PCR quantitative à 37°C. Par contre, une exposition unique ou répétée aux IRFA (+LR) n'induit aucune augmentation de la mort cellulaire, ni de l'expression de l'ARNm de la MMP-1 chez ces fibroblastes. Conclusions : les résultats de cette étude montrent que, contrairement aux rayons ultraviolets, les IRFA (+LR) ne semblent impliqués ni dans le vieillissement, ni dans la mort cellulaire, même utilisés à des doses très élevées. Ces résultats sont en accord avec certaines investigations in vivo montrant une induction de MMP-1 par des UV et non des infrarouges. Ces dernières études suggèrent d'ailleurs plutôt un rôle protecteur des IRFA (+LR).

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INTRODUCTION: Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region is robustly associated with smoking quantity. Conversely, the association between one of the most significant single nucleotide polymorphisms (SNPs; rs1051730 within the CHRNA3 gene) with perceived difficulty or willingness to quit smoking among current smokers is unknown. METHODS: Cross-sectional study including current smokers, 502 women, and 552 men. Heaviness of smoking index (HSI), difficulty, attempting, and intention to quit smoking were assessed by questionnaire. RESULTS: The rs1051730 SNP was associated with increased HSI (age, gender, and education-adjusted mean ± SE: 2.6 ± 0.1, 2.2 ± 0.1, and 2.0 ± 0.1 for AA, AG, and GG genotypes, respectively, p < .01). Multivariate logistic regression adjusting for gender, age, education, leisure-time physical activity, and personal history of cardiovascular or lung disease showed rs1051730 to be associated with higher smoking dependence (odds ratio [OR] and 95% CI for each additional A-allele: 1.38 [1.11-1.72] for smoking more than 20 cigarette equivalents/day; 1.31 [1.00-1.71] for an HSI ≥5 and 1.32 [1.05-1.65] for smoking 5 min after waking up) and borderline associated with difficulty to quit (OR = 1.29 [0.98-1.70]), but this relationship was no longer significant after adjusting for nicotine dependence. Also, no relationship was found with willingness (OR = 1.03 [0.85-1.26]), attempt (OR = 1.00 [0.83-1.20]), or preparation (OR = 0.95 [0.38-2.38]) to quit. Similar findings were obtained for other SNPs, but their effect on nicotine dependence was no longer significant after adjusting for rs1051730. Conclusions: These data confirm the effect of rs1051730 on nicotine dependence but failed to find any relationship with difficulty, willingness, and motivation to quit.

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CONTEXT: Several genetic risk scores to identify asymptomatic subjects at high risk of developing type 2 diabetes mellitus (T2DM) have been proposed, but it is unclear whether they add extra information to risk scores based on clinical and biological data. OBJECTIVE: The objective of the study was to assess the extra clinical value of genetic risk scores in predicting the occurrence of T2DM. DESIGN: This was a prospective study, with a mean follow-up time of 5 yr. SETTING AND SUBJECTS: The study included 2824 nondiabetic participants (1548 women, 52 ± 10 yr). MAIN OUTCOME MEASURE: Six genetic risk scores for T2DM were tested. Four were derived from the literature and two were created combining all (n = 24) or shared (n = 9) single-nucleotide polymorphisms of the previous scores. A previously validated clinic + biological risk score for T2DM was used as reference. RESULTS: Two hundred seven participants (7.3%) developed T2DM during follow-up. On bivariate analysis, no differences were found for all but one genetic score between nondiabetic and diabetic participants. After adjusting for the validated clinic + biological risk score, none of the genetic scores improved discrimination, as assessed by changes in the area under the receiver-operating characteristic curve (range -0.4 to -0.1%), sensitivity (-2.9 to -1.0%), specificity (0.0-0.1%), and positive (-6.6 to +0.7%) and negative (-0.2 to 0.0%) predictive values. Similarly, no improvement in T2DM risk prediction was found: net reclassification index ranging from -5.3 to -1.6% and nonsignificant (P ≥ 0.49) integrated discrimination improvement. CONCLUSIONS: In this study, adding genetic information to a previously validated clinic + biological score does not seem to improve the prediction of T2DM.

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Astrocytes are the most abundant glial cell type in the brain. Although not apposite for long-range rapid electrical communication, astrocytes share with neurons the capacity of chemical signaling via Ca(2+)-dependent transmitter exocytosis. Despite this recent finding, little is known about the specific properties of regulated secretion and vesicle recycling in astrocytes. Important differences may exist with the neuronal exocytosis, starting from the fact that stimulus-secretion coupling in astrocytes is voltage independent, mediated by G-protein-coupled receptors and the release of Ca(2+) from internal stores. Elucidating the spatiotemporal properties of astrocytic exo-endocytosis is, therefore, of primary importance for understanding the mode of communication of these cells and their role in brain signaling. We here take advantage of fluorescent tools recently developed for studying recycling of glutamatergic vesicles at synapses (Voglmaier et al., 2006; Balaji and Ryan, 2007); we combine epifluorescence and total internal reflection fluorescence imaging to investigate with unprecedented temporal and spatial resolution, the stimulus-secretion coupling underlying exo-endocytosis of glutamatergic synaptic-like microvesicles (SLMVs) in astrocytes. Our main findings indicate that (1) exo-endocytosis in astrocytes proceeds with a time course on the millisecond time scale (tau(exocytosis) = 0.24 +/- 0.017 s; tau(endocytosis) = 0.26 +/- 0.03 s) and (2) exocytosis is controlled by local Ca(2+) microdomains. We identified submicrometer cytosolic compartments delimited by endoplasmic reticulum tubuli reaching beneath the plasma membrane and containing SLMVs at which fast (time-to-peak, approximately 50 ms) Ca(2+) events occurred in precise spatial-temporal correlation with exocytic fusion events. Overall, the above characteristics of transmitter exocytosis from astrocytes support a role of this process in fast synaptic modulation.

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The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumour necrosis factor receptor superfamily (TNFRSF) and all primary viral strains tested to date use CD134 for infection. To investigate the effect of the natural ligand for CD134 on FIV infection, feline CD134L was cloned and expressed in soluble forms. However, in contrast to murine or human CD134L, soluble feline CD134L (sCD134L) did not bind to CD134. Receptor-binding activity was restored by enforced covalent trimerisation following the introduction of a synthetic trimerisation domain from tenascin (TNC). Feline and human TNC-CD134Ls retained the species-specificity of the membrane-bound forms of the ligand while murine TNC-CD134L displayed promiscuous binding to feline, human or murine CD134. Feline and murine TNC-CD134Ls were antagonists of FIV infection; however, potency was both strain-specific and substrate-dependent, indicating that the modulatory effects of endogenous sCD134L, or exogenous CD134Lbased therapeutics, may vary depending on the viral strain.