Contact tracing investigation after professional exposure to tuberculosis in a Swiss hospital using both tuberculin skin test and IGRA.

SETTING: A 950 bed teaching hospital in Switzerland. AIM: To describe the result of a contact investigation among health care workers (HCW) and patients after exposure to a physician with smear-positive pulmonary tuberculosis in a hospital setting using standard tuberculin skin tests (TST) and Interferon-gamma release assay (IGRA). METHOD: HCW with a negative or unknown TST at hiring had a TST two weeks after the last contact with the index case (T0), repeated six weeks later if negative (T6). All exposed HCW had a T-SPOT.TB at T0 and T6. Exposed patients had a TST six weeks after the last contact, and a T-SPOT.TB if the TST was positive. RESULTS: Among 101 HCW, 17/73 (22%) had a positive TST at T0. TST was repeated in 50 at T6 and converted from negative to positive in eight (16%). Twelve HCW had a positive T-SPOT.TB at T0 and ten converted from negative to positive at T6. Seven HCW with a positive T-SPOT.TB reverted to negative at T6 or at later controls, most of them with test values close to the cut-off. Among 27 exposed patients tested at six weeks, ten had a positive TST, five of them confirmed by a positive T-SPOT.TB. CONCLUSIONS: HCW tested twice after exposure to a case of smear-positive pulmonary TB demonstrated a possible conversion in 10% with T-SPOT and 16% with TST. Some T-SPOT.TB reverted from positive to negative during the follow-up, mostly tests with a value close to the cut-off. Due to the variability of the test results, it seems advisable to repeat the test with values close to the cut-off before diagnosing the presence of a tuberculous infection

Xcd - Modular, Realizable Software Architectures

Connector-Centric Design (Xcd) is centred around a new formal architectural description language, focusing mainly on complex connectors. Inspired by Wright and BIP, Xcd aims to cleanly separate in a modular manner the high-level functional, interaction, and control system behaviours. This can aid in both increasing the understandability of architectural specifications and the reusability of components and connectors themselves. Through the independent specification of control behaviours, Xcd allows designers to experiment more easily with different design decisions early on, without having to modify the functional behaviour specifications (components) or the interaction ones(connectors). At the same time Xcd attempts to ease the architectural specification by following (and extending) a Design-by-Contract approach, which is more familiar to software developers than process algebras like CSP or languages like BIP that are closer to synchronous/hardware specification languages. Xcd extends Design-by-Contract (i) by separating component contracts into functional and interaction sub-contracts, and (ii) by allowing service consumers to specify their own contractual clauses. Xcd connector specifications are completely decentralized, foregoing Wright’s connector glue, to ensure their realizability by construction

MODELO DE ATENCIÓN DEL CÁNCER EN LA INFANCIA Y ADOLESCENCIA

La atención integral de niños y adolescentes con cáncer es uno de los grandes desafíos para el sistema de salud pública de nuestros países donde el cáncer infantil representa un problema de salud pública y un problema social. El cáncer pediátrico en Paraguay, un país de escasos recursos, es un problema social y de salud pública por las consecuencias que se infringen a los pacientes, sus familias, las comunidades y los sistemas de salud. Un modelo descentralizado con clínicas más cercanas y dedicadas a cuidados primarios y referencias de niños con diagnóstico potencial de cáncer mejoraron el acceso a cuidados especializados y seguimiento del cáncer. Estas clínicas, implementadas dentro de los hospitales regionales de los sistemas nacionales de salud, ofrecen soluciones sostenibles y efectivas para un mejor acceso y seguimiento del cuidado de los niños con cáncer. El análisis de los desafíos, el éxito y la rentabilidad de estas clínicas regionales de cáncer pediátrico para referencias y seguimiento, permite sugerir un modelo óptimo para tales clínicas en entornos de bajos ingresos. Este modelo podría ser replicado para el cuidado de otras enfermedades y en otros grupos de edad. Presentamos aquí el resultado de la evaluación de los resultados de los pacientes de las cuatro clínicas regionales desde su implementación inicial

Borrelia burgdorferi EbfC defines a newly-identified, widespread family of bacterial DNA-binding proteins

The Lyme disease spirochete, Borrelia burgdorferi, encodes a novel type of DNA-binding protein named EbfC. Orthologs of EbfC are encoded by a wide range of bacterial species, so characterization of the borrelial protein has implications that span the eubacterial kingdom. The present work defines the DNA sequence required for high-affinity binding by EbfC to be the 4 bp broken palindrome GTnAC, where ‘n’ can be any nucleotide. Two high-affinity EbfC-binding sites are located immediately 5′ of B. burgdorferi erp transcriptional promoters, and binding of EbfC was found to alter the conformation of erp promoter DNA. Consensus EbfC-binding sites are abundantly distributed throughout the B. burgdorferi genome, occurring approximately once every 1 kb. These and other features of EbfC suggest that this small protein and its orthologs may represent a distinctive type of bacterial nucleoid-associated protein. EbfC was shown to bind DNA as a homodimer, and site-directed mutagenesis studies indicated that EbfC and its orthologs appear to bind DNA via a novel α-helical ‘tweezer’-like structure

Development of a diagnostic protocol for dizziness in elderly patients in general practice: a Delphi procedure

<p>Abstract</p> <p>Background</p> <p>Dizziness in general practice is very common, especially in elderly patients. The empirical evidence for diagnostic tests in the evaluation of dizziness is scarce. Aim of our study was to determine which set of diagnostic tests should be part of a diagnostic protocol for evaluating dizziness in elderly patients in general practice.</p> <p>Methods</p> <p>We conducted a Delphi procedure with a panel of 16 national and international experts of all relevant medical specialities in the field of dizziness. A selection of 36 diagnostic tests, based on a systematic review and practice guidelines, was presented to the panel. Each test was described extensively, and data on test characteristics and methodological quality (assessed with the Quality Assessment of Diagnostic Accuracy Studies, QUADAS) were presented. The threshold for in- or exclusion of a diagnostic test was set at an agreement of 70%.</p> <p>Results</p> <p>During three rounds 21 diagnostic tests were selected, concerning patient history (4 items), physical examination (11 items), and additional tests (6 items). Five tests were excluded, although they are recommended by existing practice guidelines on dizziness. Two tests were included, although several practice guidelines question their diagnostic value. Two more tests were included that have never been recommended by practice guidelines on dizziness.</p> <p>Conclusion</p> <p>In this study we successfully combined empirical evidence with expert opinion for the development of a set of diagnostic tests for evaluating dizziness in elderly patients. This comprehensive set of tests will be evaluated in a cross-sectional diagnostic study.</p

Activation and modulation of antiviral and apoptotic genes in pigs infected with classical swine fever viruses of high, moderate or low virulence

The immune response to CSFV and the strategies of this virus to evade and suppress the pigs’ immune system are still poorly understood. Therefore, we investigated the transcriptional response in the tonsils, median retropharyngeal lymph node (MRLN), and spleen of pigs infected with CSFV strains of similar origin with high, moderate, and low virulence. Using a porcine spleen/intestinal cDNA microarray, expression levels in RNA pools prepared from infected tissue at 3 dpi (three pigs per virus strain) were compared to levels in pools prepared from uninfected homologue tissues (nine pigs). A total of 44 genes were found to be differentially expressed. The genes were functionally clustered in six groups: innate and adaptive immune response, interferon-regulated genes, apoptosis, ubiquitin-mediated proteolysis, oxidative phosphorylation and cytoskeleton. Significant up-regulation of three IFN-γ-induced genes in the MRLNs of pigs infected with the low virulence strain was the only clear qualitative difference in gene expression observed between the strains with high, moderate and low virulence. Real-time PCR analysis of four response genes in all individual samples largely confirmed the microarray data at 3 dpi. Additional PCR analysis of infected tonsil, MRLN, and spleen samples collected at 7 and 10 dpi indicated that the strong induction of expression of the antiviral response genes chemokine CXCL10 and 2′–5′ oligoadenylate synthetase 2, and of the TNF-related apoptosis-inducing ligand (TRAIL) gene at 3 dpi, decreased to lower levels at 7 and 10 dpi. For the highly and moderately virulent strains, this decrease in antiviral and apoptotic gene expression coincided with higher levels of virus in these immune tissues

Global gene expression profiling of myeloid immune cell subsets in response to in vitro challenge with porcine circovirus 2b

Compelling evidence suggests that the early interaction between porcine circovirus 2 (PCV-2) and the innate immune system is the key event in the pathogenesis of Post-Weaning Multisystemic Wasting Syndrome (PMWS). Furthermore, PCV2 has been detected in bone-marrow samples, potentially enabling an easy spread and reservoir for the virus. To assess the gene-expression differences induced by an in-vitro PCV2b infection in different three different myeloid innate immune cell subsets generated from the same animal, we used the Agilent Porcine Gene Expression Microarray (V2). Alveolar macrophages (AMØs), monocyte-derived dendritic cells (MoDCs) and bone-marrow cells (BMCs) were generated from each animal, and challenged with a UK-isolate of a PCV2 genotype b-strain at a MOI of 0.5. Remarkably, analysis showed a highly distinct and cell-type dependent response to PCV2b challenge. Overall, MoDCs showed the most marked response to PCV2b challenge in vitro and revealed a key role for TNF in the interaction with PCV2b, whereas only few genes were affected in BMCs and AMØs. These observations were further supported by an enrichment of genes in the downstream NF-κB Signalling pathway as well as an up regulation of genes with pro-apoptotic functions post-challenge. PCV2b challenge increases the expression of a large number of immune-related and pro-apoptotic genes mainly in MoDC, which possibly explain the increased inflammation, granulomatous inflammation and lymphocyte depletion seen in PMWS-affected pigs

Efecto de enfermedades del fuste en Eucalyptus globulus.

El alto valor de la madera de Eucalyplus globulus para la producción de pulpa y papel ha llevado a que esta especie sea, con más de 200 mil hectáreas, la especieforestal más plantada en Uruguay. En general se reconoce que E. globulus es una especie exigente desde el punto de vista climático y que es susceptible a diversas enfermedades y plagas. Sin embargo, tanto la adaptación a las diterentes zonas, como la susceptibilidad a enfermedades, varían marcadamente con la fuente de semilla utilizada. En el presente trabajo se analiza el efecto de enfermedades que afectan el fuste sobre el crecimiento y la capacidad de rebrote post cosecha, evaluado en un ensayo instalado en el departamento de Lavalleja

Daños provocados por enfermedades foliares y por heladas en E. globulus : I. Efecto fenotípico sobre el comportamiento productivo posterior

Eucalyptus globulus es la especie forestal de mayor área plantada en Uruguay, existiendo en la actualidad más de 250 mil hectáreas de plantaciones. Sin embargo, debido al efecto combinado de diversos factores (falta de adaptación a las condiciones agro-ecológicas de algunas regiones, susceptibilidad a varias enfermedades y utilización de fuentes de semilla inadecuadas), la productividad de esta especie ha sido en general bastante inferior a lo esperado. Si bien se reconoce que los problemas sanitarios son una de las principales limitantes productivas, las pérdidas económicas provocadas por diferentes enfermedades aún no han sido cuantificadas. El presente trabajo realiza un aporte en este sentido mediante el análisis del efecto que diferentes niveles de daño foliar tienen sobre parámetros productivos. El estudio se realizó en un test genético en el cual en el primer año se cuantificó el daño provocado por enfermedades y por heladas, mientras que al tercer año se evaluó el crecimiento en diámetro y la sobrevivencia. Los resultados de dicha evaluación permitieron comprobar que un alto nivel de daño foliar, tanto de manchas como de defoliación, puede provocar hasta un 40% de reducción en el crecimiento en diámetro al tercer año. A su vez, el porcentaje de mortalidad hasta el tercer año de los árboles que presentaron altos niveles de daño foliar puede llegar al 90%. El daño provocado por heladas durante el primer invierno también tiene un marcado efecto sobre el comportamiento posterior, con pérdidas de crecimiento en diámetro para los niveles más altos de daño de hasta un 57% y una mortalidad hasta el tercer año que puede llegar al 80%