Screening for tuberculosis and prediction of disease in Portuguese healthcare workers

<p>Abstract</p> <p>Introduction</p> <p>Results of systematic screening of healthcare workers (HCWs) for tuberculosis (TB) with the tuberculin skin test (TST) and interferon-γ release assays (IGRA) in a Portuguese hospital from 2007 to 2010 are reported.</p> <p>Methods</p> <p>All HCWs are offered screening for TB. Screening is repeated depending on risk assessment. TST and QuantiFERON Gold In-Tube (QFT) are used simultaneously. X-ray is performed when TST is > 10 mm, IGRA is positive or typical symptoms exist.</p> <p>Results</p> <p>The cohort comprises 2,889 HCWs. TST and IGRA were positive in 29.5%, TST-positive but IGRA-negative results were apparent in 43.4%. Active TB was diagnosed in twelve HCWs - eight cases were detected during screening and four cases were predicted by IGRA as well as by TST. However, the progression rate in IGRA-positive was higher than in TST-positive HCWs (0.4% vs. 0.2%, p-value 0.06).</p> <p>Conclusions</p> <p>The TB burden in this cohort was high (129.8 per 100,000 HCWs). However, the progression to active TB after a positive TST or positive IGRA was considerably lower than that reported in literature for close contacts in low-incidence countries. This may indicate that old LTBI prevails in these HCWs.</p

Rare nuclearities in Ni(II) cluster chemistry: an unprecedented {Ni12} nanosized cage from the use of N-naphthalidene-2-amino-5-chlorobenzoic acid.

The self-assembly reaction between NiI2, benzoic acid (PhCO2H) and the Schiff base chelate, N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in the presence of the organic base triethylamine (NEt3), has resulted in the isolation and the structural, spectroscopic, and physicochemical characterization of the dodecanuclear [Ni12I2(OH)6(O2CPh)5(nacb)5(H2O)4(MeCN)4]I (1) cluster compound in ~30%yield. Complex 1 has a cage-like conformation, comprising twelvedistorted, octahedral NiII ions that are bridged by five 3-OH, one -OH, an I in 55% occupancy, five PhCO2 groups (under the 1: 1: , 1: 2: 3 and 2: 2: 4 modes), and the naphthoxido and carboxylato O-atoms of five doubly deprotonated nacb2 groups. The overall {Ni12} cluster exhibits a nanosized structure with a diameter of ~2.5 nm and its metallic core can be conveniently described as a series of nine edge- or vertex-sharing {Ni3} triangular subunits. Complex 1 is the highest nuclearity coordination compound bearing the nacbH2 chelate, and a rare example of polynuclear NiII complex containing coordinating I ions. Direct current (DC) magnetic susceptibility studies revealed the presence of predominant antiferromagnetic exchange interactions between the NiII ions, while photophysical studies of 1 in the solid-state showed a cyan-to-green centered emission at 520 nm, upon maximum excitation at 380 nm. The reported results demonstrate the rich coordination chemistry of the deprotonated nacb2 chelate in the presence of NiII metal ions, and the ability of this ligand to adopt a variety of di erent bridging modes, thus fostering the formation of high-nuclearity molecules with rare, nanosized dimensions and interesting physical (i.e., magnetic and optical) properties

Hierarchical characterization of complex networks

While the majority of approaches to the characterization of complex networks has relied on measurements considering only the immediate neighborhood of each network node, valuable information about the network topological properties can be obtained by considering further neighborhoods. The current work discusses on how the concepts of hierarchical node degree and hierarchical clustering coefficient (introduced in cond-mat/0408076), complemented by new hierarchical measurements, can be used in order to obtain a powerful set of topological features of complex networks. The interpretation of such measurements is discussed, including an analytical study of the hierarchical node degree for random networks, and the potential of the suggested measurements for the characterization of complex networks is illustrated with respect to simulations of random, scale-free and regular network models as well as real data (airports, proteins and word associations). The enhanced characterization of the connectivity provided by the set of hierarchical measurements also allows the use of agglomerative clustering methods in order to obtain taxonomies of relationships between nodes in a network, a possibility which is also illustrated in the current article.Comment: 19 pages, 23 figure

Predicting progression of mild cognitive impairment to dementia using neuropsychological data: a supervised learning approach using time windows

Background: Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages. In this paper, we propose a Time Windows approach to predict conversion to dementia, learning with patients stratified using time windows, thus fine-tuning the prognosis regarding the time to conversion. Methods: In the proposed Time Windows approach, we grouped patients based on the clinical information of whether they converted (converter MCI) or remained MCI (stable MCI) within a specific time window. We tested time windows of 2, 3, 4 and 5 years. We developed a prognostic model for each time window using clinical and neuropsychological data and compared this approach with the commonly used in the literature, where all patients are used to learn the models, named as First Last approach. This enables to move from the traditional question "Will a MCI patient convert to dementia somewhere in the future" to the question "Will a MCI patient convert to dementia in a specific time window". Results: The proposed Time Windows approach outperformed the First Last approach. The results showed that we can predict conversion to dementia as early as 5 years before the event with an AUC of 0.88 in the cross-validation set and 0.76 in an independent validation set. Conclusions: Prognostic models using time windows have higher performance when predicting progression from MCI to dementia, when compared to the prognostic approach commonly used in the literature. Furthermore, the proposed Time Windows approach is more relevant from a clinical point of view, predicting conversion within a temporal interval rather than sometime in the future and allowing clinicians to timely adjust treatments and clinical appointments.FCT under the Neuroclinomics2 project [PTDC/EEI-SII/1937/2014, SFRH/BD/95846/2013]; INESC-ID plurianual [UID/CEC/50021/2013]; LASIGE Research Unit [UID/CEC/00408/2013

Avaliação de assimetria hemisférica funcional em pacientes com doença de Alzheimer

Introdução: as assimetrias cerebrais constituem aspectos fundamentais para a organização funcional e o processamento cognitivo. Estudos prévios têm reportado que alterações no padrão de assimetria hemisférica existentes em algumas patologias reduzem a eficiência no processamento de informação. Objetivos: avaliar a assimetria hemisférica funcional a partir de padrões de homofilia e heterofilia; analisar a assimetria da conectividade funcional de redes dinâmicas em portadores de Alzheimer. Metodologia: foram construídas redes funcionais dinâmicas do córtex cerebral de pacientes com diferentes níveis de Alzheimer (muito leve, leve e moderado a grave) e do grupo de controle a partir de EEG (19 eletrodos, Sistema 10-20). Tais redes foram geradas a partir do método de associação sincronização por motifs e representadas através de grafos variantes no tempo e de redes estáticas agregadas. Essas redes foram avaliadas por meio de índices de assimetria e conectividade. Resultados: os resultados mostram uma tendência à redução da homofilia com a progressão da enfermidade, quando se compara ao controle, além de um leve aumento do índice para o último estágio, se comparado aos estágios iniciais da doença. A assimetria para a conectividade funcional, por sua vez, mostrou uma propensão a maior conectividade para o hemisfério direito, salvo para o estágio moderado a grave. Conclusão: embora os resultados não tenham apresentado diferenças significativas, eles indicam tendências de alteração no padrão de homofilia e na assimetria da conectividade funcional em redes funcionais dinâmicas de pacientes com Alzheimer.

Disrupted murine gut-to-human liver signaling alters bile acid homeostasis in humanized mouse liver models

The humanized liver mouse model is being exploited increasingly for human drug metabolism studies. However, its model stability, intercommunication between human hepatocytes and mouse nonparenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expressions have not been investigated. We examined these issues in FRGN [fumarylacetoacetate hydrolase (Fah2/2), recombination activating gene 2 (Rag22/2), and interleukin 2 receptor subunit gamma (IL-2rg 2/2) triple knockout] on nonobese diabetic (NOD) background] and chimeric mice: mFRGN and hFRGN (repopulated withmouse or human hepatocytes, respectively). hFRGN mice showed markedly higher levels of liver cholesterol, biliary bilirubin, and bile acids (liver, bile, and plasma; mainly human forms, but also murine bile acids) but lower transforming growth factor beta receptor 2 (TGFBR2) mRNA expression levels (10%) in human hepatocytes and other proliferative markers in mouse nonparenchymal cells (Tgf-1) and cholangiocytes [plasma membrane-bound, G protein-coupled receptor for bile acids (Tgr5)], suggestive of irregular regeneration processes in hFRGN livers. Changes in gene expression in murine intestine, kidney, and brain of hFRGN mice, in particular, induction of intestinal farnesoid X receptor (Fxr) genes: fibroblast growth factor 15 (Fgf15), mouse ileal bile acid binding protein (Ibabp), small heterodimer partner (Shp), and the organic solute transporter alpha (Osta), were observed. Proteomics revealed persistence of remnant murine proteins (cyotchrome P450 7α-hydroxylase (Cyp7a1) and other enzymes and transporters) in hFRGN livers and suggest the likelihood ofmouse activity.When comparedwith normal human liver tissue, hFRGN livers showed lower SHP mRNA and higher CYP7A1 (300%) protein expression, consequences of tb- and ta-muricholic acid-mediated inhibition of the FXR-SHP cascade and miscommunication between intestinal Fgf15 and human liver fibroblast growth factor receptor 4 (FGFR4), as confirmed by the unchanged hepatic pERK/total ERK ratio. Dysregulation of hepatocyte proliferation and bile acid homeostasis in hFRGN livers led to hepatotoxicity, gallbladder distension, liver deformity, and other extrahepatic changes, making questionable the use of the preparation for drug metabolism studies

Chromosomal evidence for a putative cryptic species in the Gymnotus carapo species-complex (Gymnotiformes, Gymnotidae)

<p>Abstract</p> <p>Background</p> <p>In this study we examined the karyotypes of morphologically indistinguishable populations of the electric knifefish <it>Gymnotus carapo sensu stricto </it>from the Eastern Amazon of Brazil. These were identified unambiguously on the basis of external morphology, meristics, and pigmentation.</p> <p>Results</p> <p>Specimens from one of five localities exhibited a karyotype previously not documented for <it>Gymnotus </it>species in the Amazon basin: 2n = 40 (34M/SM+6ST/A). Samples from the other four localities exhibited a different karyotype: 2n = 42 (30M/SM+12ST/A), which we had previously described. Specimens from all five localities presented constitutive heterochromatin in the centromeric region of almost all chromosomes, including in the distal and interstitial regions. Staining with 4'6-Diamidino-2-phenylindole revealed C-positive banding. In both karyotypes the Nucleolar Organizer Region (NOR) was located on the short arm of pair 20, and Chromomycin A₃stained the NORs. Fluorescent <it>in situ </it>hybridization with telomeric probes showed an Interstitial Telomeric Sequence (ITS) in the proximal short arm of a metacentric pair in the 2n = 40 karyotype.</p> <p>Conclusion</p> <p>The difference between the two karyotypes on the diploid number and chromosome morphology can be explained by rearrangements of the fusion-fission type and also by pericentric inversions. The presence of ITS in a metacentric pair of the 2n = 40 karyotype suggests that the difference in the diploid number of the karyotypes results from a fusion. The consistent 2n = 42 karyotype at four localities suggests an interbreeding population. However, because fusion-fission and pericentric inversions of this nature typically result in reproductive isolation, we speculate that the form with the 2n = 40 karyotype is a different species to that of the 2n = 42 form. Nonetheless, we did not observe evident differences in external morphology, meristics and pigmentation between the two forms, which suggest that they represent cryptic sympatric species in the <it>G. carapo </it>species complex. We speculate that the chromosomal speciation occurred recently, allowing insufficient time for the fixation of other differences following post-zygotic isolation.</p

Extragalactic Background Light Inferred from AEGIS Galaxy SED-type Fractions

The extragalactic background light (EBL) is of fundamental importance both for understanding the entire process of galaxy evolution and for gamma-ray astronomy, but the overall spectrum of the EBL between 0.1-1000 microns has never been determined directly from galaxy spectral energy distribution (SED) observations over a wide redshift range. The evolving, overall spectrum of the EBL is derived here utilizing a novel method based on observations only. This is achieved from the observed evolution of the rest-frame K-band galaxy luminosity function up to redshift 4 (Cirasuolo et al. 2010), combined with a determination of galaxy SED-type fractions. These are based on fitting SWIRE templates to a multiwavelength sample of about 6000 galaxies in the redshift range from 0.2 to 1 from the All-wavelength Extended Groth Strip International Survey (AEGIS). The changing fractions of quiescent galaxies, star-forming galaxies, starburst galaxies and AGN galaxies in that redshift range are estimated, and two alternative extrapolations of SED-types to higher redshifts are considered. This allows calculation of the evolution of the luminosity densities from the UV to the IR, the evolving star formation rate density of the universe, the evolving contribution to the bolometric EBL from the different galaxy populations including AGN galaxies and the buildup of the EBL. Our EBL calculations are compared with those from a semi-analytic model, from another observationally-based model and observational data. The EBL uncertainties in our modeling based directly on the data are quantified, and their consequences for attenuation of very high energy gamma-rays due to pair production on the EBL are discussed. It is concluded that the EBL is well constrained from the UV to the mid-IR, but independent efforts from infrared and gamma-ray astronomy are needed in order to reduce the uncertainties in the far-IR.Comment: 25 pages, 18 figures, 4 tables; accepted for publication in MNRAS on September 3, 2010. Online material available at http://side.iaa.es/EB