Evaluation of four molecular methods for the diagnosis of tuberculosis in pulmonary and blood samples from immunocompromised patients

The present study analysed the concordance among four different molecular diagnostic methods for tuberculosis (TB) in pulmonary and blood samples from immunocompromised patients. A total of 165 blood and 194 sputum samples were collected from 181 human immunodeficiency virus (HIV)-infected patients with upper respiratory complaints, regardless of suspicious for TB. The samples were submitted for smear microscopy, culture and molecular tests: a laboratory-developed conventional polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) and the Gen-Probe and Detect-TB Ampligenix kits. The samples were handled blindly by all the technicians involved, from sample processing to results analysis. For sputum, the sensitivity and specificity were 100% and 96.7% for qPCR, 81.8% and 94.5% for Gen-Probe and 100% and 66.3% for Detect-TB, respectively. qPCR presented the best concordance with sputum culture [kappa (k) = 0.864)], followed by Gen-Probe (k = 0.682). For blood samples, qPCR showed 100% sensitivity and 92.3% specificity, with a substantial correlation with sputum culture (k = 0.754) and with the qPCR results obtained from sputum of the corresponding patient (k = 0.630). Conventional PCR demonstrated the worst results for sputa and blood, with a sensitivity of 100% vs. 88.9% and a specificity of 46.3% vs. 32%, respectively. Commercial or laboratory-developed molecular assays can overcome the difficulties in the diagnosis of TB in paucibacillary patients using conventional methods available in most laboratories.

The prominent role of neutrophils during the initial phase of infection by Leishmania parasites.

Neutrophils are rapidly and massively recruited to the site of Leishmania inoculation, where they phagocytose the parasites, some of which are able to survive within these first host cells. Neutrophils can thus provide a transient safe shelter for the parasites, prior to their entry into macrophages where they will replicate. In addition, neutrophils release and synthesize rapidly several factors including cytokines and chemokines. The mechanism involved in their rapid recruitment to the site of parasite inoculation, as well as the putative consequences of their massive presence on the microenvironment of the focus of infection will be discussed in the context of the development of the Leishmania-specific immune response.

Impaired expression of NADH dehydrogenase subunit 1 and PPARgamma coactivator-1 in skeletal muscle of ZDF rats: restoration by troglitazone.

Type 2 diabetes has been related to a decrease of mitochondrial DNA (mtDNA) content. In this study, we show increased expression of the peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target genes involved in fatty acid metabolism in skeletal muscle of Zucker Diabetic Fatty (ZDF) (fa/fa) rats. In contrast, the mRNA levels of genes involved in glucose transport and utilization (GLUT4 and phosphofructokinase) were decreased, whereas the expression of pyruvate dehydrogenase kinase 4 (PDK-4), which suppresses glucose oxidation, was increased. The shift from glucose to fatty acids as the source of energy in skeletal muscle of ZDF rats was accompanied by a reduction of subunit 1 of complex I (NADH dehydrogenase subunit 1, ND1) and subunit II of complex IV (cytochrome c oxidase II, COII), two genes of the electronic transport chain encoded by mtDNA. The transcript levels of PPARgamma Coactivator 1 (PGC-1) showed a significant reduction. Treatment with troglitazone (30 mg/kg/day) for 15 days reduced insulin values and reversed the increase in PDK-4 mRNA levels, suggesting improved insulin sensitivity. In addition, troglitazone treatment restored ND1 and PGC-1 expression in skeletal muscle. These results suggest that troglitazone may avoid mitochondrial metabolic derangement during the development of diabetes mellitus 2 in skeletal muscle.

Role of CCR5 genetic polymorphisms in clinical and histological outcomes of hepatitis C

Background: The CCR5 32-base deletion (CCR5D32), which results into the expression of a non-functioning receptor, has been associated with H CV c learance a nd may influence fibrosis progression i n hepatitis C . We a ssessed t he link between C CR5D32 and c linical outcomes o f HCV. Methods: Genomic D NA was isolated and analyzed b y PCR to i dentify C CR5D32 in 1 303 anti-HCV-positive persons (161 clearers and 1142 chronically infected, 1007 with a liver biopsy). Results: Overall, 200 (15.3%) w ere heterozygote a nd 16 (1.2%) homozygote for CCR5D32. H CV c learance (by univariate) was associated with m ale sex (OR 0.633, 9 5% C I 0.428-0.935, P=0.022), HCV acquisition by blood transfusion (OR 0.360, 95% CI 0.175-0.741, P =0.0056), polymorphisms at IL28B rs12979860 ( OR 0.482, 9 5% C I 0.277-0.839, P =0.0098) a nd rs8099917 ( OR 0.291, 95% CI 0.167-0.508, P=0.000014), but not with CCR5D32. However, CCR5D32 was associated with spontaneous HCV clearance when the 482 females only w ere considered, although the number of homozygotes was small (1/427 chronic vs 3/51 clearers) (OR 24.56, 95% C I 12.5-241.4, P =0.006). T he CCR5D32 deletion was not associated with liver grading and staging scores, fibrosis progression rate, or t herapy response. Conclusions: At v ariance w ith a p revious report (Nattermann et a l, 2011), suggesting that a n on-functional CCR5 m ay hamper H CV clearance, C CR5D32 appeared to b e associated with an increased spontaneous eradication in women (but not men). Given the small number of CCR5D32 homozygote persons, these data need further validation.

Better 6 months outcome for steroid refractory ulcerative colitis with infliximab rescue therapy compared to tacrolimus or cyclosporine: a Swiss IBD cohort retrospective analysis

BACKGROUND: C iclosporine ( CsA), Tacrolimus (Tcl) and Infliximab (IFX) are effective rescue therapies in steroidrefractory ulcerative colitis (UC). Comparative studies are however m issing. M ETHOD: T his i s the retrospective analysis of treatment outcome for oral Tcl (n=27, initially 0.05mg/Kg twice daily, aiming for serum trough levels of 5-10 n g/mL), i ntravenous C sA ( n=23, 2 mg/kg/daily a nd then o ral CsA 5mg/kg/daily) and IFX ( n=43, 5 mg/kg intravenously at week 0, 2, 6 and then every 8 weeks) in patients with s teroid r efractory moderate to s evere UC enrolled i n the SWISS IBD cohort s tudy. After successful rescue therapy with Tcl o r C sA, t hiopurine m aintenance therapy or maintenance therapy with Tcl (in Tcl pretreated patients) was introduced. The endpoints analyzed steroid free r emission r ate (on the basis of m odified Truelove- Witts severity index (MTWSI)) and number of colectomies after 6 m onths. R ESULTS: A t 6 months, 26% ( 7/27) o f patients treated with T cl r emained i n steroid free remission (MTWSI score ≤4) compared to 30 % (7/23) on 18 droplets to the same extend under the linoleic acid treat, whereas lipid hydrolysis or loss was significantly increased in Huh-7 WT cells after 24h. Conclusions: Chronic alcohol feeding in obese, insulin-resistant rats exerts significant and synergistic effects on PNPLA3 mRNA expression, which correlated with triglyceride content. In v itro experiments suggest that PNPLA3 expression depends on the t ypes of d ietary f atty acids with polyunsaturated fatty a cids i nducing a nd monounsaturated fatty a cids inhibiting PNPLA3 mRNA. I148M polymorphism of PNPLA3 l eads to attenuation o f lipolytic processes resulting in fat accumulation in the cell. 20 CsA and 58% ( 27/41) o f patients t reated w ith IFX ( Tcl & CsA vs I FX p = 0 .018). S ignificant m ore patients had primary non response, loss of response or severe adverse events i n the CsA cohort ( 61%, 1 4/23) c ompared to Tcl cohort (33.3 % , 9/27), and IFX cohort (30%, 1 3/43) (p= 0.037). Colectomy rate was significantly higher after CsA (17.4 %, 4/23) compared to Tcl (3.7 %, 1/27) or IFX (2.3 %, 1/43) (p= 0.047).CONCLUSION: After s ix m onth, rescue therapy with I FX h ad t he l owest c olectomy r ate, significantly h igher steroid free r emission rate, a nd t he lowest rate of non-response, loss of response and severe adverse events compared to CsA or Tcl rescue treatment.

Las posiciones de los diferentes grupos políticos israelíes sobre la resolución de la situación de los refugiados

La cuestión de los refugiados palestinos es uno de los asuntos clave para alcanzar una resolución firme del conflicto palestino-israelí. Para ello debe resolverse la situación de los cientos de miles de palestinos que fueron expulsados y/o huyeron con la guerra de 1948, y sus descendientes, que hoy suman casi 5 millones. En el proceso de paz, este es uno de los asuntos que ni siquiera fue tenido en cuenta con la profundidad que lo requiere. Los palestinos se acogen a la resolución 194 de la Asamblea de Naciones Unidas y reivindican el Derecho al Retorno. Pero del lado israelí tres argumentos ponen en duda este derecho al retorno: A) El asunto de la responsabilidad en la huida/expulsión de cientos de miles de palestinos de sus hogares. B) La «necesidad» existencial de ser un estado de mayoría judía, que el retorno podría poner en cuestión. C) El hecho de que Israel ya acogió a cientos de miles de judíos originarios de los países árabes. Analizaremos cómo los partidos políticos israelíes tratan este asunto, y cómo los «nuevos historiadores israelíes» pueden ayudar a cambiar el punto de vista israelí al poner en cuestión la narrativa sionista de la guerra del 48.

Improved accuracy of co-morbidity coding over time after the introduction of ICD-10 administrative data.

BACKGROUND: Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges.METHODS: Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities.RESULTS: For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven.CONCLUSIONS: Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system.

Mutation analysis of the ATP7B gene in a new group of Wilson's disease patients: contribution to diagnosis.

Wilson's disease (WD), an autosomal recessive disorder of copper transport with a broad range of genotypic and phenotypic characteristics, results from mutations in the ATP7B gene. Herein we report the results of mutation analysis of the ATP7B gene in a group of 118 Wilson disease families (236 chromosomes) prevalently of Italian origin. Using DNA sequencing we identified 83 disease-causing mutations. Eleven were novel, while twenty one already described mutations were identified in new populations in this study. In particular, mutation analysis of 13 families of Romanian origin showed a high prevalence of the p.H1069Q mutation (50%). Detection of new mutations in the ATP7B gene in new populations increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.

Iowa Department of Commerce - Division of Banking, Agency Performance Plan

Annual Report, Agency Performance Plan

[Archives de la parole]. , Fragment de la messe grecque melchite arabe / M. Alexis Ben Kori, voix. Chanson arabe [O Mijana, O vents, passez sur ceux que j'aime] / M. Alexis Ben Kori, chant

Enregistrement : Paris, Université de Paris, La Sorbonne, 04-02-1914