1000 resultados para 146-891A


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BACKGROUND: In Switzerland, intravenous drug use (IDU) accounts for 80% of newly acquired hepatitis C virus (HCV) infections. Early HCV treatment has the potential to interrupt the transmission chain and reduce morbidity/mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programs are often insufficiently screened and treated. OBJECTIVE/METHODS: With the aim to improve HCV management in IDUs, we conducted a cross sectional chart review in three opioid substitution programs in St. Gallen (125 methadone and 71 heroin recipients). Results were compared with another heroin substitution program in Bern (202 patients) and SCCS/SHCS data. RESULTS: Among the methadone/heroin recipients in St. Gallen, diagnostic workup of HCV was better than expected: HCV/HIV-status was unknown in only 1% (2/196), HCV RNA was not performed in 9% (13/146) of anti-HCV-positives and the genotype missing in 15% (12/78) of HCV RNA-positives. In those without spontaneous clearance (two thirds), HCV treatment uptake was 23% (21/91) (HIV-: 29% (20/68), HIV+: 4% (1/23)), which was lower than in methadone/heroin recipients and particularly non-IDUs within the SCCS/SHCS, but higher than in the, mainly psychiatrically focussed, heroin substitution program in Bern (8%). Sustained virological response (SVR) rates were comparable in all settings (overall: 50%, genotype 1: 35-40%, genotype 3: two thirds). In St. Gallen, the median delay from the estimated date of infection (IDU start) to first diagnosis was 10 years and to treatment was another 7.5 years. CONCLUSIONS: Future efforts need to focus on earlier HCV diagnosis and improvement of treatment uptake among patients in drug substitution programs, particularly if patients are HIV-co-infected. New potent drugs might facilitate the decision to initiate treatment.

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Abstract Sex-determining systems often undergo high rates of turnover but for reasons that remain largely obscure. Two recent evolutionary models assign key roles, respectively, to sex-antagonistic (SA) mutations occurring on autosomes and to deleterious mutations accumulating on sex chromosomes. These two models capture essential but distinct key features of sex-chromosome evolution; accordingly, they make different predictions and present distinct limitations. Here we show that a combination of features from the two models has the potential to generate endless cycles of sex-chromosome transitions: SA alleles accruing on a chromosome after it has been co-opted for sex induce an arrest of recombination; the ensuing accumulation of deleterious mutations will soon make a new transition ineluctable. The dynamics generated by these interactions share several important features with empirical data, namely, (i) that patterns of heterogamety tend to be conserved during transitions and (ii) that autosomes are not recruited randomly, with some chromosome pairs more likely than others to be co-opted for sex.

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Objective: Enhanced Recovery After Surgery (ERAS) clinical pathways in¦colorectal surgery are known to reduce postoperative complications leading¦to shortened hospital stay. However, the implementation of such an ERAS¦pathway requires time and financial investment. This study evaluates whether¦the savings related to the reduction in the length of stay (LOS) outweigh the¦costs of implementing an ERAS pathway.¦Methods: An ERAS pathway was implemented in our institution for colorectal¦surgery. The first 50 consecutive patients subjected to this ERAS pathway¦(ERAS group) were compared to 50 consecutive patients that were operated one¦year before its introduction (control group). Primary LOS, readmission within¦30 days, and total costs based on costs per day were compared. The mean costs¦per day were: 3,263 CHF for intensive care, 1,152 CHF for intermediate care,¦and 728 CHF for basic care.¦Results: Primary LOS was shorter in the ERAS group than in the control¦group: median 7 (interquartile range 5-12·25) versus 10 (7-18) days (P =¦0·0025). The readmission within 30 postoperative days was similar in both¦groups (2 patients each). In the ERAS group, the added primary LOS was¦485 days (379 in basic care, 99 in intermediate care, 7 in intensive care) compared¦to 706 days in the control group (533 in basic care, 146 in intermediate care,¦27 in intensive care). The total costs were significantly lower for the 50 ERAS¦patients compared to the control group: 412,801 CHF versus 644,317 CHF (P <¦0·01). Investments required for the 50 first ERAS patients were approximately¦83,544 CHF, including 348 working hours as well a full-time ERAS dedicated¦nurse. The overall cost saving was approximately 2,959 CHF per patient.¦Conclusion: Implementation of an ERAS pathway significantly reduced LOS¦after colorectal surgery. The financial investment to introduce and maintain¦such a pathway is clearly inferior to the cost-saving of reduced hospital stay.

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INTRODUCTION: Currently, there is no reliable method to differentiate acute from chronic carotid occlusion. We propose a novel CTA-based method to differentiate acute from chronic carotid occlusions that could potentially aid clinical management of patients. METHODS: We examined 72 patients with 89 spontaneously occluded extracranial internal carotids with CT angiography (CTA). All occlusions were confirmed by another imaging modality and classified as acute (imaging <1 week of presumed occlusion) orchronic (imaging >4 weeks), based on circumstantial clinical and radiological evidence. A neuroradiologist and a neurologist blinded to clinical information determined the site of occlusion on axial sections of CTA. They also looked for (a) hypodensity in the carotid artery (thrombus), (b) contrast within the carotid wall (vasa vasorum), (c) the site of the occluded carotid, and (d) the "carotid ring sign" (defined as presence of a and/or b). RESULTS: Of 89 occluded carotids, 24 were excluded because of insufficient circumstantial evidence to determine timing of occlusion, 4 because of insufficient image quality, and 3 because of subacute timing of occlusion. Among the remaining 45 acute and 13 chronic occlusions, inter-rater agreement (kappa) for the site of proximal occlusion was 0.88, 0.45 for distal occlusion, 0.78 for luminal hypodensity, 0.82 for wall contrast, and 0.90 for carotid ring sign. The carotid ring sign had 88.9% sensitivity, 69.2% specificity, and 84.5% accuracy to diagnose acute occlusion. CONCLUSION: The carotid ring sign helps to differentiate acute from chronic carotid occlusion. If further confirmed, this information may be helpful in studying ischemic symptoms and selecting treatment strategies in patients with carotid occlusions.

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FGFR1 mutations have been identified in both Kallmann syndrome and normosmic HH (nIHH). To date, few mutations in the FGFR1 gene have been structurally or functionally characterized in vitro to identify molecular mechanisms that contribute to the disease pathogenesis. We attempted to define the in vitro functionality of two FGFR1 mutants (R254W and R254Q), resulting from two different amino acid substitutions of the same residue, and to correlate the in vitro findings to the patient phenotypes. Two unrelated GnRH deficient probands were found to harbor mutations in FGFR1 (R254W and R254Q). Mutant signaling activity and expression levels were evaluated in vitro and compared to a wild type (WT) receptor. Signaling activity was determined by a FGF2/FGFR1 dependent transcription reporter assay. Receptor total expression levels were assessed by Western blot and cell surface expression was measured by a radiolabeled antibody binding assay. The R254W maximal receptor signaling capacity was reduced by 45% (p<0.01) while R254Q activity was not different from WT. However, both mutants displayed diminished total protein expression levels (40 and 30% reduction relative to WT, respectively), while protein maturation was unaffected. Accordingly, cell surface expression levels of the mutant receptors were also significantly reduced (35% p<0.01 and 15% p<0.05, respectively). The p.R254W and p.R254Q are both loss-of-function mutations as demonstrated by their reduced overall and cell surface expression levels suggesting a deleterious effect on receptor folding and stability. It appears that a tryptophan substitution at R254 is more disruptive to receptor structure than the more conserved glutamine substitution. No clear correlation between the severity of in vitro loss-of-function and phenotypic presentation could be assigned.

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There has been an increase in the incidence of carcinoma of the tongue, particularly among alcohol and tobacco non-users. However, the number of studies that would allow a better understanding of etiological factors and clinical features, particularly in the Portuguese population, is very limited. This study was based on patients with squamous cell carcinoma of the anterior two thirds of the tongue that were treated at the Department of Head and Neck Surgery of the ¿Instituto Portugues de Oncologia de Lisboa - Francisco Gentil" IPOLFG) in Lisbon, Portugal, between January 1, 2001 and December 31, 2009. The patients were divided in alcohol and tobacco users and non-users in order to evaluate the differences between these 2 groups based on gender, age, tumor location, denture use, and tumor size, metastasis and stage. Of the 354 cases, 208 were users and 146 were non-users. The main location in both groups was the lateral border of the tongue. Denture use showed no significant effect in both study groups. It was possible to conclude that patients who did not drink or smoke were older and presented with smaller tumor size, lower incidence of ganglion metastasis and lower tumor stage compared with alcohol and tobacco users.

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Monalysin was recently described as a novel pore-forming toxin (PFT) secreted by the Drosophila pathogen Pseudomonas entomophila. Recombinant monalysin is multimeric in solution, whereas PFTs are supposed to be monomeric until target membrane association. Monalysin crystals were obtained by the hanging-drop vapour-diffusion method using PEG 8000 as precipitant. Preliminary X-ray diffraction analysis revealed that monalysin crystals belonged to the monoclinic space group C2, with unit-cell parameters a = 162.4, b = 146.2, c = 144.4 Å, β = 122.8°, and diffracted to 2.85 Å resolution using synchrotron radiation. Patterson self-rotation analysis and Matthews coefficient calculation indicate that the asymmetric unit contains nine copies of monalysin. Heavy-atom derivative data were collected and a Ta6Br14 cluster derivative data set confirmed the presence of ninefold noncrystallographic symmetry.

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O objetivo deste trabalho foi avaliar os efeitos da aplicação de 0, 20 e 40 Mg ha-1 de lodo de esgoto, na presença e ausência de fertilizante mineral (NPK) na fertilidade e nos teores de metais pesados de um Argissolo Vermelho-Amarelo distrófico, cultivado com cana-de-açúcar. Amostras de solo foram coletadas aos 146, 272 e 484 dias após o plantio da cultura de cana-de-açúcar e foram submetidas à análise de fertilidade pelo método do Instituto Agronômico de Campinas, incluindo a determinação do S, Cr, Cd, Cu, Fe, Mn, Pb e Zn. O lodo de esgoto diminuiu a acidez do solo e forneceu Ca, P, S e Zn, principalmente. Seus efeitos foram de curta duração, restringindo-se a um ano agrícola. Os teores dos metais pesados das amostras de solo tratado foram maiores que os da testemunha, mas menores que os valores considerados perigosos ao ambiente.

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The incomplete Evros ophiolites in NE Greece form a NE-SW-oriented discontinuous belt in the Alpine orogen of the north Aegean. Field data, petrology and geochemistry are presented here for the intrusive section and associated mafic dykes of these ophiolites. Bodies of high-level isotropic gabbro and plagiogranite in the ophiolite suite are cross-cut by NE-SW-trending boninitic and tholeiitic-boninitic affinity dykes, respectively. The dykes fill tensile fractures or faults, which implies dyke emplacement in an extensional tectonic regime. The tholeiitic-transitional boninitic gabbro is REE- and HFS-depleted relative to N-MORB, indicating derivation from melting of a refractory mantle peridotite source. Associated boninitic dykes are slightly LREE-enriched, showing mineral and whole-rock geochemistry similar to the gabbro. The plagiogranite is a strongly REE-enriched high-silica trondhjemite, with textures and composition typical for an oceanic crust differentiate. Plagiogranite-hosted tholeiitic and transitional boninitic dykes are variably REE-enriched. Geochemical modelling indicates origin of the plagiogranite by up to 75% fractional crystallization of basaltic magma similar to that producing the associated tholeiitic dykes. All mafic rocks have high LILE/HFSE ratios and negative Ta-Nb-Ti and Ce anomalies, typical for subduction zone-related settings. The mafic rocks show a similar trace-element character to the mafic lavas of an extrusive section in Bulgaria, suggesting they both form genetically related intrusive and extrusive suites of the Evros ophiolites. The field occurrence, the structural context, the petrology and geochemical signature of the studied magmatic assemblage provide evidence for its origin in a proto-arc (fore-arc) tectonic setting, thus tracing the early stages of the tectono-magmatic evolution of Jurassic arc-marginal basin system that has generated the supra-subduction type Evros ophiolites.

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BACKGROUND: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. METHODS: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. RESULTS: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03-1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00-1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91-1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91-1.31; p = 0.355). CONCLUSION: This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age. Birth Defects Research (Part A), 100:695-702, 2014. © 2014 Wiley Periodicals, Inc.

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Breastfeeding is considered the ideal way of providing young infants with the required nutrients for healthy growth and development. An increase in the prevalence and duration of breastfeeding has been observed over the last years in response to promotion campaigns. When a medicamentous treatment is started, discontinuation of breastfeeding is often proposed, for fear of harmful consequences for the infant. Nevertheless such a decision is not unimportant, and it appears that many drugs can actually be used during breastfeeding without significant risk. An assessment of the real risk incurred by exposed children makes it possible to avoid unnecessary discontinuations of breastfeeding. This article aims to review the facts needed to assess amount of drug exposure to the child and to list the few drugs associated with significant effects on the nursing infant.