A prospective study on the dynamics of the clinical and immunological evolution of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region

This prospective study was carried out from October 2003 to December 2005 and involved a cohort of 946 individuals of both genders, aged 1-89 years, from an endemic area for American visceral leishmaniasis (AVL), in Para State, Brazil. The aim of the study was to analyze the dynamics of the clinical and immunological evolution of human Leishmania ( L.) infantum chagasi infection represented by the following clinical-immunological profiles: asymptomatic infection (AI); symptomatic infection (SI = AVL); subclinical oligosymptomatic infection (SOI); subclinical resistant infection (SRI); and indeterminate initial infection (III). Infection diagnosis was determined by the indirect fluorescent antibody test and leishmanin skin test. In total, 231 cases of infection were diagnosed: the AI profile was the most frequent (73.2%), followed by SRI (12.1%), III (9.9%), SI (2.6%) and SOI (2.2%). The major conclusion regarding evolution dynamics was that the III profile plays a pivotal role from which the cases evolve to either the resistant, SRI and AI, or susceptible, SOI and SI, profiles; only one of the 23 III cases evolved to SI, while most evolved to either SRI (nine cases) or SOI (five cases) and eight cases remained as III. (C) 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals

Background: Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai`s portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals. Methods: In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses. Results: The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group. Conclusions: Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces. (C) 2009 Elsevier Inc. All rights reserved.

Effects of Salivary Gland Homogenate from Wild-Caught and Laboratory-Reared Lutzomyia longipalpis on the Evolution and Immunomodulation of Leishmania (Leishmania) amazonensis Infection

We investigated the effects of Lutzomyia longipalpis salivary glands homogenate of wild-caught and laboratory-reared vectors on the lesion evolution and immunomodulation of the infection caused by Leishmania (Leishmania) amazonensis. To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were inoculated Subcutaneously into the hind footpads or into the ear dermis with 10(6) promastigotes in the presence or not of SGH from wild-caught and laboratory-colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co-inoculated with wild-caught SGH, as the parasitism and the infiltration of macrophages at the inoculation site. Wild-caught SGH also determined lower production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory-reared SGH. Our findings address a probable bias by using SGH from laboratory-colonized sand flies instead of wild-caught vector SGH in studies concerning saliva effects. A possible mild influence of sand fly saliva in natural infections caused by Leishmania is also speculated, as infection is transmitted by wild and not by laboratory-reared vectors.

Gambling in Brazil Lifetime prevalences and socio-demographic correlates

Gambling has experienced world-wide growth The current study is the first national survey into household gambling conducted in a developing country The sample was a three-stage probabilistic one designed to cover individuals 14 years old or older of both genders and from all regions of the national territory 325 census sectors were visited including rural areas DSM-IV-based instruments were used to assess problem and pathological gambling individuals were asked to estimate their monthly gambling expenditure The lifetime prevalences were pathological gambling 1 0% and problem gambling 1 3% Maximum gambling expenditure corresponded to 5 4% of the household income for social gamblers 16 9% for problem gamblers and 20 0% for pathological gamblers The male female ratio among adults for pathological gambling was 3 2 1 The data suggest the existence of two subgroups of pathological gamblers one younger (33 9 +/- 4 19) and severe (7 or more DSM-IV criteria) another older (47 8 +/- 6 01) and less severe (5-6 criteria) In a multinomial logistic regression problematic gambling was associated with gender age education employment region of origin and living in metropolitan areas The data suggest that feeling active and socially inserted protects against problematic gambling Individuals who are young male unemployed or not currently pursuing further education may be at special risk for severe pathological gambling (C) 2010 Elsevier Ireland Ltd All rights reserved

Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS-II study, 2007 to 2008

BACKGROUND: The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics. STUDY DESIGN AND METHODS: Data were extracted from the blood center, compiled in a data warehouse, and analyzed. Population data were obtained from the Brazilian census. RESULTS: During 2007 to 2008, there were 615,379 blood donations from 410,423 donors. A total of 426,142 (69.2%) were from repeat (Rpt) donors and 189,237 (30.8%) were from first-time (FT) donors. Twenty percent of FT donors returned to donate in the period. FT donors were more likely to be younger, and Rpt donors were more likely to be community donors. All were predominantly male. Replacement donors still represent 50% of FT and 30% of Rpt donors. The mean percentage of the potentially general population who were donors was approximately 1.2% for the three centers (0.7, 1.5, and 3.1%). Adjusting for the catchment`s area, the first two were 2.1 and 1.6%. CONCLUSIONS: Donors in the three Brazilian centers tended to be younger with a higher proportion of males than in the general population. Donation rates were lower than desirable. There were substantial differences in sex, age, and community/replacement status by center. Studies on the safety, donation frequencies, and motivations of donors are in progress to orient efforts to enhance the availability of blood.

Evolution of Laparoscopic Colorectal Surgery in Brazil Results of 4744 Patients From the National Registry

Background: Since its introduction, laparoscopic colorectal surgery has raised intense debate and controversies regarding its safety and effectiveness. Methods: This multicentric registry reports the experience of 28 Brazilian surgical teams specializing in laparoscopic colorectal surgery. Results: Between 1992 and 2007, 4744 patients (1994 men-42% and 2750 women-58%) were operated upon, with ages ranging from 13 to 94 years (average 57.5y). Benign diseases were diagnosed in 2356 patients (49.6%). Most diseases were located in 50.7% of the left and sigmoid colon, 28.2% in the rectum and anal canal. 8.0% in the right colon, and diffuse 7.0%. There were 181 (3.8%) intraoperative complications (from 0% to 14%). There were 261 (5.5%) reported conversions to laparotomy (from 0% to 16.5%), mainly during the early experience (n = 119 - 59.8%). Postoperative complications were registered in 683 (14.5%) patients (from 5.0% to 50%). Mortality occurred in 43 patients (0.8%). Surgeons who performed less than 50 cases reported similar rates of intraoperative (4.2% vs. 3.8%,- P = 0.7), postoperative complications (20.8% vs. 14.3%; P = 0.07), and mortality (1.0% vs. 0.9%; P = 0.5) but the conversion rate was higher (10.4% vs. 5.4%; P = 0.04). Two thousand three hundred and eighty-nine (50.4%) malignant tumors were operated upon, and histologic classification showed 2347 (98%) adenocarcinomas, 30 (0.6%) spinocelular carcinomas, and 12 (0.2%) other histologic types. Tumor recurrence rate was 16.3% among patients followed more than I year. After an average follow-Lip of 52 months, 19 (0.8%) parietal recurrences were reported, 18 of which were in port sites and I in a patient with disseminated disease. There was no incisional recurrence in the ports used to withdraw the pathologic specimen. Compared with other registries, there was a 75% increase in the number of groups pet-forming laparoscopic colorectal surgery and a decrease in conversions (from 10.5%. to 5.5%) and mortality (from 1.5% to 0.9%) rates. Conclusions: (1) The number of patients operated upon increased expressively during the last years; (2) operative indications for benign and malignant diseases were similar, and diverticular disease of the colon comprised 40% of the benign ones; (3) conversion and mortality rates decreased over time; (4) Surgeon`s experience did not influence the complication rates, but was associated with a lower conversion; and (5) oncologic outcome expressed by recurrence rates showed results similar to those reported in conventional surgery.

High rates of molecular evolution in hantaviruses

Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae, and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10(-7) nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the 3 rodent subfamilies: Araraquara virus ( Sigmodontinae), Dobrava virus ( Murinae), Puumala virus ( Arvicolinae), and Tula virus ( Arvicolinae). Our results reveal that hantaviruses exhibit shortterm substitution rates of 10(-2) to 10(-4) substitutions/site/year and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent-hantavirus codivergence suggests that the codivergence hypothesis may need to be reevaluated.

Glomerular Nucleus of the Weakly Electric Fish, Gymnotus sp.: Cytoarchitecture, Histochemistry, and Fiber Connections-Insights from Neuroanatomy to Evolution and Behavior

The present study provides a detailed description of morphological and hodological aspects of the glomerular nucleus in the weakly electric fish Gymnotus sp., and explores the evolutionary and functional implications flowing from this analysis. The glomerular nucleus of Gymnotus shows numerous morphological similarities with the glomerular nucleus of percomorph fish, although cytoarchitectonically simpler. In addition, congruence of the histochemical acetylcholinesterase (AChE) distribution with cytoarchitectonic data suggests that the glomerular nucleus, together with the ventromedial cell group of the medial subdivision of the preglomerular complex (PGm-vmc) rostrally, and the subglomerular nucleus (as identified by Maler et al. [1991] J Chem Neuroanat 4:1-38) caudally, may form a distinct longitudinally organized glomerular complex. Our results show that an important source of sensory afferents to the glomerular nucleus originates in the pretectal and electrosensorius nuclei. The glomerular nucleus in turn projects to the hypothalamus (inferior lobe and anterior hypothalamus), to the anterior tuberal nucleus, and to the medial region of the preglomerular nucleus (PGm). These data suggest that visual and electrosensory information reach the glomerular nucleus and are relayed to the hypothalamus and, via PGm, to the pallium. Such connections are similar to those of the glomerular nucleus in percomorphs and the posterior pretectal nucleus in osteoglossomorph, esocids, and salmonids, where they comprise one component of a visual processing pathway. In Gymnotiform fish, however, the pretectal region that projects to the glomerular nucleus is dominated by electrosensory input (visual input is minor), which is consistent with the dominant role of electroreception in these fish. J. Comp. Neurol. 519:1658-1676, 2011. (c) 2011 Wiley-Liss, Inc.

Migration in Afro-Brazilian Rural Communities: Crossing Demographic and Genetic Data

Many studies have used genetic markers to understand global migration patterns of our species. However, there are only few studies of human migration on a local scale. We, therefore, researched migration dynamics in three Afro-Brazilian rural communities, using demographic data and ten Ancestry Informative Markers. In addition to the description of migration and marriage structures, we carried out genetic comparisons between the three populations, as well as between locals and migrants from each community. Genetic admixture analyses were conducted according to the gene-identity method, with Sub-Saharan Africans, Amerindians, and Europeans as parental populations. The three analyzed Afro-Brazilian rural communities consisted of 16% to 30% of migrants, most of them women. The age pyramid revealed a gap in the segment of men aged between 20 to 30 yrs. While endogamous marriages predominated, exogamous marriages were mainly patrilocal. Migration dynamics are apparently associated with matrimonial customs and other social practices of such communities. The impact of migration upon the populations` genetic composition was low but showed an increase in European alleles with a concomitant decrease in the Amerindian contribution. Admixture analysis evidenced a higher African contribution to the gene pool of the studied populations, followed by the contribution of Europeans and Amerindians, respectively.

The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

Blood Cardioplegia with N-Acetylcysteine May Reduce Coronary Endothelial Activation and Myocardial Oxidative Stress

Objectives: The aim of this prospective study was to compare the efficacy of intermittent antegrade blood cardioplegia with or without n-acetylcysteine (NAC) in reducing myocardial oxidative stress and coronary endothelial activation. Methods: Twenty patients undergoing elective isolated coronary artery bypass graft surgery were randomly assigned to receive intermittent antegrade blood cardioplegia (32 degrees C-34 degrees C) with (NAC group) or without (control group) 300 mg of NAC. For these 2 groups we compared clinical outcome, hemodynamic evolution, systemic plasmatic levels of troponin I, and plasma concentrations of malondialdehyde (MDA) and soluble vascular adhesion molecule 1 (sVCAM-1) from coronary sinus blood samples. Results: Patient demographic characteristics and operative and postoperative data findings in both groups were similar. There was no hospital mortality. Comparing the plasma levels of MDA 10 min after the aortic cross-clamping and of sVCAM-1 30 min after the aortic cross-clamping period with the levels obtained before the aortic clamping period, we observed increases of both markers, but the increase was significant only in the control group (P=.039 and P=.064 for MDA; P=.004 and P=.064 for sVCAM- 1). In both groups there was a significant increase of the systemic serum levels of troponin I compared with the levels observed before cardiopulmonary bypass (P<.001), but the differences between the groups were not significant (P=.570). Conclusions: Our investigation showed that NAC as an additive to blood cardioplegia in patients undergoing on-pump coronary artery bypass graft surgery may reduce oxidative stress and the resultant coronary endothelial activation.

Thermostable variants of the recombinant xylanase A from Bacillus subtilis produced by directed evolution show reduced heat capacity changes

Directed evolution techniques have been used to improve the thermal stability of the xylanase A from Bacillus subtilis (XylA). Two generations of random mutant libraries generated by error prone PCR coupled with a single generation of DNA shuffling produced a series of mutant proteins with increasing thermostability. The most Thermostable XylA variant from the third generation contained four mutations Q7H, G13R, S22P, and S179C that showed an increase in melting temperature of 20 degrees C. The thermodynamic properties Of a representative subset of nine XylA variants showing a range of thermostabilities were measured by thermal denaturation as monitored by the change in the far ultraviolet circular dichroism signal. Analysis of the data from these thermostable variants demonstrated a correlation between the decrease in the heat capacity change (Delta C(p)) with an increase in the midpoint of the transition temperature (T(m)) on transition from the native to the unfolded state. This result could not be interpreted within the context of the changes in accessible surface area of the protein on transition from the native to unfolded states. Since all the mutations are located at the surface of the protein, these results suggest that an explanation of the decrease in Delta C(p) on should include effects arising from the prot inlsolvent interface.

Experimental autoimmune encephalomyelitis evolution was not modified by multiple infections with Strongyloides venezuelensis

P>According to the hygiene hypothesis, the increased incidence of allergic and autoimmune diseases in developed countries is mainly explained by the decreased contact between the human population and certain environmental agents as lactobacillus, mycobacteria and helminths. In this study, we evaluated the effect of multiple infections with Strongyloides venezuelensis on the development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Multiple infections before EAE induction were not able to change the evolution of the disease. No alterations were observed in weight loss, clinical score and inflammation intensity at the central nervous system. The presence of significant levels of parasite-specific IgG1 but not IgG2b suggested a Th2 polarization. However, the percentage and absolute number of CD4+CD25+Foxp3+ T cells were not changed, being their levels in the spleen and lymph nodes of infected rats comparable to the ones found in normal animals. These results suggest that a Th2-polarized response without concomitant expansion of Foxp3+ regulatory T cells was not able to modify EAE progression. Even though these results do not threaten the hygiene hypothesis, they suggest that this paradigm might be an oversimplification. They also emphasize the need of a study to compare the immunoregulatory ability associated with different helminth spp.

Temporal evolution of epithelial, vascular and interstitial lung injury in an experimental model of idiopathic pulmonary fibrosis induced by butyl-hydroxytoluene

This study was undertaken to test whether the structural remodelling of pulmonary parenchyma can be sequentially altered in a model and method that demonstrate the progression of the disease and result in remodelling within the lungs that is typical of idiopathic pulmonary fibrosis. Three groups of mice were studied: (i) animals that received 3-5-di-tert-butyl-4-hydroxytoluene (BHT) and were killed after 2 weeks (early BHT = 9); (ii) animals that received BHT and were killed after 4 weeks (late BHT = 11); (iii) animals that received corn oil solution (control = 10). The mice were placed in a ventilated Plexiglas chamber with a mixture of pure humidified oxygen and compressed air. Lung histological sections underwent haematoxylin-eosin, immunohistochemistry (epithelial, endothelial and immune cells) and specific staining (collagen/elastic fibres) methods for morphometric analysis. When compared with the control group, early BHT and late BHT groups showed significant decrease of type II pneumocytes, lower vascular density in both and higher endothelial activity. CD4 was increased in late BHT compared with early and control groups, while CD8, macrophage and neutrophil cells were more prominent only in early BHT. The collagenous fibre density were significantly higher only in late BHT, whereas elastic fibre content in late BHT was lower than that in control group. We conclude that the BHT experimental model is pathologically very similar to human usual interstitial pneumonia. This feature is important in the identification of animal models of idiopathic pulmonary fibrosis that can accurately reflect the pathogenesis and progression of the human disease.

Modeling the Dynamics of Viral Evolution Considering Competition Within Individual Hosts and at Population Level: The Effects of Treatment

We consider two viral strains competing against each other within individual hosts (at cellular level) and at population level (for infecting hosts) by studying two cases. In the first case, the strains do not mutate into each other. In this case, we found that each individual in the population can be infected by only one strain and that co-existence in the population is possible only when the strain that has the greater basic intracellular reproduction number, R (0c) , has the smaller population number R (0p) . Treatment against the one strain shifts the population equilibrium toward the other strain in a complicated way (see Appendix B). In the second case, we assume that the strain that has the greater intracellular number R (0c) can mutate into the other strain. In this case, individual hosts can be simultaneously infected by both strains (co-existence within the host). Treatment shifts the prevalence of the two strains within the hosts, depending on the mortality induced by the treatment, which is, in turn, dependent upon the doses given to each individual. The relative proportions of the strains at the population level, under treatment, depend both on the relative proportions within the hosts (which is determined by the dosage of treatment) and on the number of individuals treated per unit time, that is, the rate of treatment. Implications for cases of real diseases are briefly discussed.