Cholera with severe renal failure in an Italian tourist returning from Cuba, July 2013

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Epidemiology of Strongyloides stercoralis in northern Italy: Results of a multicentre case-control study, February 2013 to July 2014

Strongyloides stercoralis is a soil-transmitted helminth widely diffused in tropical and subtropical regions of the world. Autochthonous cases have been also diagnosed sporadically in areas of temperate climate. We aimed at defining the epidemiology of strongyloidiasis in immigrants and Italians living in three northern Italian Regions. Screening for S. stercoralis infection was done with serology, confirmation tests were a second serological method or stool agar culture. A case-control approach was adopted and patients with a peripheral eosinophil count 65 500/mcL were classified as cases. Of 2,701 individuals enrolled here 1,351 were cases and 1,350 controls; 86% were Italians, 48% women. Italians testing positive were in 8% (97/1,137) cases and 1% (13/1,178) controls (adjusted odds ratio (aOR) 8.2; 95% confidence interval (CI): 4.5-14.8), while positive immigrants were in 17% (36/214) cases and in 2% (3/172) controls (aOR 9.6; 95% CI: 2.9-32.4). Factors associated with a higher risk of infection for all study participants were eosinophilia (p < 0.001) and immigration (p = 0.001). Overall, strongyloidiasis was nine-times more frequent in individuals with eosinophilia than in those with normal eosinophil count

Generalized Fourier Integral Operators on spaces of Colombeau type

Generalized Fourier integral operators (FIOs) acting on Colombeau algebras are defined. This is based on a theory of generalized oscillatory integrals (OIs) whose phase functions as well as amplitudes may be generalized functions of Colombeau type. The mapping properties of these FIOs are studied as the composition with a generalized pseudodifferential operator. Finally, the microlocal Colombeau regularity for OIs and the influence of the FIO action on generalized wave front sets are investigated. This theory of generalized FIOs is motivated by the need of a general framework for partial differential operators with non-smooth coefficients and distributional data

Chagas disease in Italy: breaking an epidemiological silence

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Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations

The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs. We solved co-crystal structures of both VRK1 and VRK2 bound to BI-D1870 and of VRK1 bound to two broad-spectrum inhibitors. These structures revealed that both VRKs can adopt a P-loop folded conformation, which is stabilized by different mechanisms on each protein. Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2

Biochemical evaluation of a series of synthetic chalcone and hydrazide derivatives as novel inhibitors of cruzain from Trypanosoma cruzi

Chagas’ disease, a parasitic infection widely distributed throughout Latin America, is a major public health problem with devastating consequences in terms of human morbidity and mortality. The enzyme cruzain is the major cysteine protease from Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas’ disease, and has been selected as an attractive target for the development of novel trypanocidal drugs. In the present work, we describe the synthesis and inhibitory effects of a series of thirty-three chalcone and seven hydrazide derivatives against the enzyme cruzain from T. cruzi. Most of the compounds showed promising in vitro inhibition (IC50 values in the range of 20-60 μM), which suggest the potential of these compounds as lead candidates for further development. Twelve compounds have not been reported before, and four of them (7, 13, 16 e 18) are among the most potent inhibitors of the series.A doença de Chagas, uma infecção parasitária amplamente distribuída na América Latina, é um problema grave de saúde pública com conseqüências devastadoras em termos de morbidade e mortalidade humana. A enzima cruzaína é a principal cisteíno protease do Trypanosoma cruzi, agente etiológico da tripanossomíase Americana ou doença de Chagas, e foi selecionada como alvo atrativo para o desenvolvimento de novos fármacos tripanocidas. No presente trabalho, a síntese e os efeitos inibitórios de uma série de trinta e três chalconas e sete hidrazidas são descritos contra a enzima cruzaína de T.cruzi. A maioria dos compostos mostraram inibição promissora in vitro (valores de IC50 na faixa de 20-60 μM), o que sugere o potencial desses compostos como candidatos a líderes para contínuo desenvolvimento. Doze compostos são inéditos, sendo que quatro destes (7, 13, 16 e 18) estão entre os inibidores mais potentes da série.CNPqFAPESPCAPE

Gevrey local solvability in locally integrable structures

We consider a locally integrable real-analytic structure, and we investigate the local solvability in the category of Gevrey functions and ultradistributions of the complex d' naturally induced by the de Rham complex. We prove that the so-called condition Y(q) on the signature of the Levi form, for local solvability of d' u=f, is still necessary even if we take f in the classes of Gevrey functions and look for solutions u in the corresponding spaces of ultradistributions.Comment: 12 page

A large-scale species level dated angiosperm phylogeny for evolutionary and ecological analyses.

Phylogenies are a central and indispensable tool for evolutionary and ecological research. Even though most angiosperm families are well investigated from a phylogenetic point of view, there are far less possibilities to carry out large-scale meta-analyses at order level or higher. Here, we reconstructed a large-scale dated phylogeny including nearly 1/8th of all angiosperm species, based on two plastid barcoding genes, matK (incl. trnK) and rbcL. Novel sequences were generated for several species, while the rest of the data were mined from GenBank. The resulting tree was dated using 56 angiosperm fossils as calibration points. The resulting megaphylogeny is one of the largest dated phylogenetic tree of angiosperms yet, consisting of 36,101 sampled species, representing 8,399 genera, 426 families and all orders. This novel framework will be useful for investigating different broad scale research questions in ecological and evolutionary biology

Structural Changes of the Paraflagellar Rod during Flagellar Beating in Trypanosoma cruzi

, the agent of Chagas disease, is a protozoan member of the Kinetoplastidae family characterized for the presence of specific and unique structures that are involved in different cell activities. One of them is the paraflagellar rod (PFR), a complex array of filaments connected to the flagellar axoneme. Although the function played by the PFR is not well established, it has been shown that silencing of the synthesis of its major proteins by either knockout of RNAi impairs and/or modifies the flagellar motility.Here, we present results obtained by atomic force microscopy (AFM) and transmission electron microscopy (TEM) of replicas of quick-frozen, freeze-fractured, deep-etched and rotary-replicated cells to obtain detailed information of the PFR structures in regions of the flagellum in straight and in bent state. The images obtained show that the PFR is not a fixed and static structure. The pattern of organization of the PFR filament network differs between regions of the flagellum in a straight state and those in a bent state. Measurements of the distances between the PFR filaments and the filaments that connect the PFR to the axoneme as well as of the angles between the intercrossed filaments supported this idea.Graphic computation based on the information obtained allowed the proposal of an animated model for the PFR structure during flagellar beating and provided a new way of observing PFR filaments during flagellar beating

Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry

<p>Abstract</p> <p>Background</p> <p>Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence <it>in situ </it>hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings.</p> <p>Methods</p> <p>One hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio ≥ 2 were considered positive for gene amplification.</p> <p>Results</p> <p>The c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no gene amplification. However, all cases with gene amplification were positive (3+) by immunohistochemistry. According to univariate analysis, there was a significant difference (p = 0.003) in survival rates when cases with and without HER-2/neu amplification were compared.</p> <p>Conclusion</p> <p>Our data demonstrate the correspondence between gene amplification and protein expression of HER-2/neu. Gene amplification is an indicator of poor prognosis in ESCC.</p