Genetic diversity of dengue virus serotypes 1 and 2 in the State of Paraná, Brazil, based on a fragment of the capsid/premembrane junction region

INTRODUCTION: The precise identification of the genetic variants of the dengue virus is important to understand its dispersion and virulence patterns and to identify the strains responsible for epidemic outbreaks. This study investigated the genetic variants of the capsid-premembrane junction region fragment in the dengue virus serotypes 1 and 2 (DENV1-2). METHODS: Samples from 11 municipalities in the State of Paraná, Brazil, were provided by the Central Laboratory of Paraná. They were isolated from the cell culture line C6/36 (Aedes albopictus) and were positive for indirect immunofluorescence. Ribonucleic acid (RNA) extracted from these samples was submitted to the reverse transcription polymerase chain reaction (RT-PCR) and nested PCR. RESULTS: RT-PCR revealed that 4 of the samples were co-infected with both serotypes. The isolated DENV-1 sequences were 95-100% similar to the sequences of other serotype 1 strains deposited in GenBank. Similarly, the isolated DENV-2 sequences were 98-100% similar to other serotype 2 sequences in GenBank. According to our neighbor-joining tree, all strains obtained in this study belonged to genotype V of DENV-1. The DENV-2 strains, by contrast, belonged to the American/Asian genotypes. CONCLUSIONS: The monitoring of circulating strains is an important tool to detect the migration of virus subtypes involved in dengue epidemics.

Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis

INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.

Evaluation of natural foci of Panstrongylus megistus in a forest fragment in Porto Alegre, State of Rio Grande do Sul, Brazil

Introduction Panstrongylus megistus is commonly found in wild environments of the State of Rio Grande do Sul, Brazil. The aim of this study was to characterize the network of refuges used by triatomine in a forest fragment of Porto Alegre and to identify Trypanosoma cruzi infection, associated hosts and the epidemiological importance of both hosts and triatomines. Methods Techniques including the spool-and-line method and active searching (transects) were used to identify natural foci. Results The food source for each triatomine was determined using the precipitin test, and the infection of marsupials was determined by xenodiagnosis. A total of 33 adults (domestic environment) and 27 nymphs (wild environment) of P. megistus were found in addition to 43 Didelphis albiventris specimens. The infection rates of triatomine adults, triatomine nymphs and opossums with T. cruzi I were 64%, 73% and 69%, respectively. Birds, rodents and opossums were the main resources used by triatomine. Conclusions This work presents the first characterization of a natural focus of P. megistus in Rio Grande do Sul. The natural characteristics of this focus and its implication in the transmission of T. cruzi are discussed.

Length and caliber of the rectosigmoid colon among patients with Chagas disease and controls from areas at different altitudes

Introduction In this study, we investigated radiological changes in the sigmoid colon in chagasic patients by comparing their colon lengths and caliber with those of non-chagasic living in the same region and non-chagasic living at high altitudes. Methods A total of 317 individuals were evaluated using clinical, serological and radiological methods and divided into three groups: 1) one hundred and nine non-chagasic individuals from Uberaba, Brazil; 2) sixty-one non-chagasic from Puno, Peru; 3) one hundred forty-seven chagasics examined in Uberaba, being 62 without megacolon (3A), 72 with megacolon (3B) and 13 with doubtful diagnosis of megacolon (3C). Results In group 2, the sigmoid colon had a significantly larger caliber (p=0.001) and the rectosigmoid colon was longer (p<0.001) than group 1. In subgroup 3A, the sigmoid colon (p<0.001) and rectum (p<0.001) had a significantly larger caliber and the rectosigmoid was longer (p<0.001) than that of the non-chagasic individuals. In subgroup 3B, the rectosigmoid was longer in all patients, and the caliber of the sigmoid was significantly larger than that of subjects in subgroups 3A and 3C (p<0.001). Conclusions Morphometric analysis confirms that Chagas disease may increase the caliber and length of the rectosigmoid. Our results suggest that altitude, ethnicity and diet may have influenced the size and length of the rectosigmoid of andean patients.

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

^a Introduction Interleukin (IL)-18 is a well-known major proinflammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited. Methods This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples. Results In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients. Conclusions The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients.

The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

AbstractINTRODUCTION:Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients.METHODS:Genomic deoxyribonucleic acid from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was genotyped to determine the presence of human platelet antigens-1, -3, or -5 polymorphisms. Fibrosis progression was evaluated using the Metavir scoring system, and the patients were assigned to two groups, namely, G1 that comprised patients with F1, portal fibrosis without septa, or F2, few septa (n = 23) and G2 that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13). Fisher's exact test was utilized to determine possible associations between the human platelet antigen polymorphisms and fibrosis progression.RESULTS:There were no deviations from the Hardy-Weinberg equilibrium in the human platelet antigen systems evaluated. Statistically significant differences were not observed between G1 and G2 with respect to the distributions of the allelic and genotypic frequencies of the human platelet antigen systems.CONCLUSION:The greater stimulation of hepatic stellate cells by the human immunodeficiency virus and, consequently, the increased expression of transforming growth factor beta can offset the effect of human platelet antigen polymorphism on the progression of fibrosis in patients coinfected with the human immunodeficiency virus-1 and the hepatitis C virus.

Can body traits, other than wings, reflect the flight ability of Triatominae bugs?

Abstract: INTRODUCTION : Insects of the subfamily Triatominae are vectors of Trypanosoma cruzi , the Chagas disease parasite, and their flying behavior has epidemiological importance. The flying capacity is strikingly different across and within Triatominae species, as well as between sexes or individuals. Many Triatoma infestans individuals have wings but no flying muscles. In other Triatominae species, no clear relationships were found between wing length and flying behavior. If wing presence or size is not reflective of the flying behavior, which other parts of the body could be considered as reliable markers of this important function? METHODS : The genus Mepraia has exceptional characteristics with invariably wingless females and wingless or winged males. We calculated the porous surface exposed to odorant molecules to estimate the olfactory capacity of Mepraia spinolai . The head shape and thorax size were estimated using the geometric morphometric approach and traditional morphometric techniques, respectively. RESULTS : Alary polymorphism in M. spinolai was significantly associated with consistent modification of the thorax size, head shape, and notable change in the estimated olfactory capacity. The macropterous individuals had a larger olfactory surface and thorax size and significantly different head shape compared to those of the micropterous individuals. CONCLUSIONS: We concluded that these structural changes could be associated with the flying potential of Triatominae. Thus, morphological attributes not found on wings could help determine the likely flying potential of the bugs.

The role of arl13b in cilia length regulation and in zebrafish development

RESUMO: Arl13b é uma importante proteína ciliar, presente em cílios primários e cílios móveis. Ratinhos mutantes para Arl13b têm comprimento dos cílios reduzido e defeitos nos B-túbulos dos cílios. Como consequência destes fenótipos, deficiências na Arl13b originam, em modelos animais, várias doenças congénitas, incluindo problemas no estabelecimento do eixo esquerda-direita, malformações cerebrais e deformações corporais. Nos seres humanos, deficiências na Arl13b levam a uma doença crónica congénita chamada Síndrome de Joubert. Por outro lado, a sobreexpressão de Arl13b origina cílios mais longos, no entanto existe uma ausência da caracterização dos fenótipos celulares e durante o desenvolvimento embrionário. Neste trabalho, quisemos explorar o efeito da sobre-expressão de Arl13b em embriões de peixezebra. Descobrimos que, ao nível ciliar, a sobre-expressão de Arl13b nas células aumenta o comprimento ciliar em cílios primários e móveis, no entanto, a esses cílios falta adequada acetilação da alfa-tubulina no citoesqueleto feito por microtúbulos. Os nossos resultados mostraram que esse efeito é específico de Arl13b sobre-expressão e quando se manipularam as enzimas responsáveis pela acetilação (Mec17) e pela de-acetilação (HDAC6) encontrámos uma sinergia potencial com ambas. Testámos ainda, que o aumento no comprimento ciliar não estava causalmente relacionado com a falta de acetilação, ou seja, os cílios com menos acetilação não eram necessariamente os mais longos. Também mostrámos que a sobre-expressão de Arl13b é capaz de restaurar o comprimento dos cílios em mutantes com cílios curtos e como isso pode ser explorado para um futuro potencial papel terapêutico para Arl13b. Em seguida, foi avaliado o impacto do aumento da quantidade de Arl13b no desenvolvimento embrionário do peixe-zebra. Observou-se que a sobre-expressão de Arl13b apresentava fenótipos muito fracos, quando comparados com a perda de função dos mutantes de Arl13b. Focados no inesperado fenótipo leve no estabelecimento do eixo esquerda-direita abordámos a questão através do estabelecimento de uma colaboração com matemáticos, descobrimos que os cílios mais longos que potencialmente têm a capacidade de movimentar mais fluido são atenuados por amplitudes de batimento menores, e, como resultado, estes longos cílios não prejudicam o movimento do fluido e consequentemente não afetam o estabelecimento dos padrões de esquerda-direita. Sugerimos assim que a Arl13b é um regulador chave, do comprimento ciliar. Descobrimos uma nova interação com as enzimas de acetilação/de-acetilação e levantamos novas hipóteses quanto aos mecanismos moleculares da função da Arl13b. Propomos um novo modelo para o mecanismo molecular da Arl13b na regulação do comprimento dos cílios onde podemos integrar os nossos resultados com os relatados na literatura. Este trabalho adiciona mais conhecimento para o mecanismo de ação da Arl13b e, portanto, fornece uma importante contribuição para o campo da investigação em cílios.---------------------------------------------------------------------------------------------------------------------- ABSTRACT: Arl13b is an important ciliary protein, present in primary and motile cilia. arl13b-/- mouse mutants have reduced cilia length and cilia B-tubule defects. As a consequence of these phenotypes, Arl13b loss of function animal models suffer from several congenital disorders including left-right problems, brain malformations and body deformations. In humans Arl13b depletion leads to a congenital chronic disease called Joubert Syndrome. On the other hand, overexpressing Arl13b leads to longer cilia but the characterization of the cellular and developmental phenotypes was missing. In this work we explore the effect of Arl13b overexpression in zebrafish embryos. We found that, at the ciliary level, Arl13b overexpression from 1 cell stage produces longer primary and motile cilia, but these cilia lack proper alpha tubulin acetylation of their microtubule cytoskeleton. Our results showed that this effect is specific from Arl13b overexpression and when we manipulated the enzymes responsible for acetylation, Mec17, and de-acetylation, HDAC6, we found a potential synergy of both mec17 knockdown and HDAC6 activity with Arl13b overexpression. We tested that the ciliary increase in length was not causally related to the lack of acetylation, meaning the more de-acetylated cilia were not necessarily the longer ones. We also showed that Arl13b overexpression is able to restore cilia length in short cilia mutants and how that may be explored to a potential future therapeutic role for Arl13b. Next, we evaluated the impact of increasing the amount of Arl13b in zebrafish embryonic development. We observed that Arl13b overexpression presented very mild phenotypes when compared to the loss of function mutants. We focused on the unexpected left-right mild phenotype and by establishing a mathematical modeling collaboration, we found out that the longer cilia generated force was attenuated by smaller beating amplitudes, and as a result, these long cilia were not impairing the cilia generated flow and the establishment of left-right patterning. We suggest that Arl13b is one key cilia length regulator. We disclosed a novel interaction with the acetylation / de-acetylation enzymes and raised new hypothesis as to the mechanisms of Arl13b function. We propose a new model for the Arl13b molecular mechanism of cilia length regulation where we integrate our findings with those reported in the literature. This work adds more knowledge to the Arl13b mechanism of action and therefore provides an important contribution to the cilia research field.

Using data mining for prediction of hospital length of stay: an application of the CRISP-DM Methodology

Hospitals are nowadays collecting vast amounts of data related with patient records. All this data hold valuable knowledge that can be used to improve hospital decision making. Data mining techniques aim precisely at the extraction of useful knowledge from raw data. This work describes an implementation of a medical data mining project approach based on the CRISP-DM methodology. Recent real-world data, from 2000 to 2013, were collected from a Portuguese hospital and related with inpatient hospitalization. The goal was to predict generic hospital Length Of Stay based on indicators that are commonly available at the hospitalization process (e.g., gender, age, episode type, medical specialty). At the data preparation stage, the data were cleaned and variables were selected and transformed, leading to 14 inputs. Next, at the modeling stage, a regression approach was adopted, where six learning methods were compared: Average Prediction, Multiple Regression, Decision Tree, Artificial Neural Network ensemble, Support Vector Machine and Random Forest. The best learning model was obtained by the Random Forest method, which presents a high quality coefficient of determination value (0.81). This model was then opened by using a sensitivity analysis procedure that revealed three influential input attributes: the hospital episode type, the physical service where the patient is hospitalized and the associated medical specialty. Such extracted knowledge confirmed that the obtained predictive model is credible and with potential value for supporting decisions of hospital managers.

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR?=?0.81; 95% CI: 0.72-0.92; p?=?0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR?=?1.19; 95% CI: 0.63-2.24; ptrend ?=?0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

On the length of bank-firm relationships: an empirical application to a major French bank

NIPE - WP 01/ 2016

Effect of the alkyl chain length of the ionic liquid anion on polymer electrolytes properties

New polymer electrolytes (PEs) based on chitosan and three ionic liquid (IL) families ([C2mim][CnSO3], [C2mim][CnSO4] and [C2mim][diCnPO4]) were synthesized by the solvent casting method. The effect of the length of the alkyl chain of the IL anion on the thermal, morphological and electrochemical properties of the PEs was studied. The solid polymer electrolytes (SPE) membranes were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), polarized optical microscopy (POM), atomic force microscopy (AFM), complex impedance spectroscopy (ionic conductivity) and cyclic voltammetry (CV). The obtained results evidenced an influence of the alkyl chain length of the IL anion on the temperature of degradation, birefringence, surface roughness and ionic conductivity of the membranes. The DSC, XRD and CV results showed independency from the length of the IL-anion-alkyl chain. The PEs displayed an predominantly amorphous morphology, a minimum temperature of degradation of 135 °C, a room temperature (T = 25 °C) ionic conductivity of 7.78 × 10−4 S cm−1 and a wide electrochemical window of ∼ 4.0 V.

Association study of the Ile349val polymorphism of the gene ADH1C and alcohol dependence

OBJECTIVE: The aim of this study was to investigate the polymorphism Ile349Val of the enzyme alcohol dehydrogenase ADH1C gene among individuals with alcohol dependence syndrome (ADS) attending Alcoholics Anonymous (AA) meetings. METHODS: A total of 120 subjects residing in Rio de Janeiro city participated in this study. Subjects were divided into two groups: a group consisting of 54 individuals from the ADS group and 66 individuals that declared not having any alcohol dependence (control group). DNA was extracted from mouth epithelial cells by phenol-chloroform method and further submitted to amplification by polymerase chain reaction (PCR). RESULTS: Our results did not show differences between the genotypes of control individuals and ADS subjects. Nevertheless, we found increased rates of alcoholism in families of ADS subjects as compared to controls. CONCLUSIONS: Our results did not show any genotype difference on the ADH1C gene when control and AA genotypes are compared.

Monitoring for a decidable fragment of MTL-∫

Temporal logics targeting real-time systems are traditionally undecidable. Based on a restricted fragment of MTL-R, we propose a new approach for the runtime verification of hard real-time systems. The novelty of our technique is that it is based on incremental evaluation, allowing us to e↵ectively treat duration properties (which play a crucial role in real-time systems). We describe the two levels of operation of our approach: offline simplification by quantifier removal techniques; and online evaluation of a three-valued interpretation for formulas of our fragment. Our experiments show the applicability of this mechanism as well as the validity of the provided complexity results.

Ischemic heart disease. Hospitalization, length of stay and expenses in Brazil from 1993 to 1997

OBJECTIVE: To identify characteristics of the hospitalizations due to ischemic heart disease (IHD) made by the Single Health System -- "Sistema Único de Saúde (SUS) in Brazil from 1993 to 1997. METHODS: The information used came from records of permissions for hospitalization due to IHD (diseases codified from 410 to 414 by the International Disease Classification -- 9th Revision) furnished by the data bank DATASUS. The material studied was classified according to age, sex and length of hospitalization of the patients, and expenses to the system for IHD. RESULTS: IHD represents 1.0% of total hospitalizations. Angina pectoris was the most frequent type, occurring in 53.3% of the cases, followed by acute myocardial infarct (26.6%). This later was more frequent in men and angina in women . The majority of patients with IHD stayed hospitalized from 5 to 8 days. In the years of 1997 the expenses due to hospital treatment for IHD reach to 0.01% of Brazil's Gross Internal Product. In the studied period (1993-1997), IHD was responsible by 1.0% of hospitalizations, however it was 3.3% of the expenses of SUS. CONCLUSION: IHD is an important cause of hospitalization by the SUS; it has a rather high cost, indicating the need for preventive measures aimed at reducing exposure to risk factors and to decrease the incidence of this group of diseases in the nation.