Moléculas coestimulatórias na leishmaniose visceral

Visceral leishmaniasis (VL) is endemic in many countries, including Brazil. The protozoan Leishmania infantum, is the etiological agent of VL, and is transmitted by the bite of female sandflies during the blood meal. The majority of subjects when exposed to the parasite do not develop the disease, because of development of Th1 cellular responses. Those who have develop signs of VL such as fever, weight loss, hepatosplenomegaly, have impairment of the cellular immune response, specific to the Leishmania antigens. We evaluated whether the specififc anergy during symptomatic VL, may be associated with changes in T cells costimulatory molecules or their ligands in CD14+ monocytes. There is an increase in CTLA-4 porcentage on CD4+ T lymphocytes (p=0.001) and ICOS on CD4+ and CD8+ T cells (p=0.002 to CD4+ and p=0.003 to CD8+), after stimulation by soluble Leishmania antigen (SLA) during active visceral leishmaniasis, and that there is a higher percentage of these molecules ex vivo, when comparing symptomatic to recovered individuals (p=0.04 to CTLA-4 in CD4+, and p=0.001 to ICOS in CD4+ and p=0.026 to CD8+). Moreover, we found a high gene expression of CTLA-4, OX-40 and ICOS during active VL. CD40, CD80, CD86, HLA-DR and ICOSL molecules do not suffer changes during disease. There is IFN-γ production by the peripheral blood cells, after SLA stimulation, by peripheral blood cells in symptomatic subjects; however, there is a decrease of the ratio IFN-γ/IL-10, which is reversed after clinical recovery. The impairment of some costimulatory molecules pathways during symptomatic VL could inhibit the ability of phagocytes to kill Leishmania and could facilitate their survival and the proliferation inside macrophages.

miRNAS circulantes como biomarcadores para fibrilação atrial aguda

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Some non-coding RNAs (miRNAs) have been involved in regulatory activity in arrhythmogenesis, targeting genes that contribute to the development of AF. The present study aimed to evaluate the expression of candidate miRNAs in plasma from patients with AF and new-onset AF and its application as future markers for diagnosis and monitoring of disease. miR-21, miR-133a, miR-133b, miR-150, miR-328 and miR-499 were selected as targets in this study through a prior literature review. They were isolated from plas-ma of individuals aged from 20 to 85 years old with AF (n = 17), new-onset AF (n = 5) and without AF (n = 15), where the latter was the control group. The results were ana-lyzed by Real-Time PCR (RT-PCR) with miScript SYBR Green PCR. We observed that miR-21, miR-133b, miR-328 and miR-499 had different levels of expression be-tween the three groups (p <0.05). Increased expression of miR-21 (0.6-fold), miR-133b (1.4-fold), miR-328 (2.0-fold) and miR-499 (2.3-fold) in patients with new-onset AF when compared to AF and control subjects. The miR-133a and miR-150 expression did not differ among the groups. miR-21, miR-133b, miR-328 and miR-499 may be potential biomarkers for AF as well as for new-onset AF, for monitoring and for the di-agnosis. These findings may contribute to the understanding of the process that trig-gers AF and suggest application these molecules as future biomarkers for AF.

miRNAS circulantes como biomarcadores para fibrilação atrial aguda

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Some non-coding RNAs (miRNAs) have been involved in regulatory activity in arrhythmogenesis, targeting genes that contribute to the development of AF. The present study aimed to evaluate the expression of candidate miRNAs in plasma from patients with AF and new-onset AF and its application as future markers for diagnosis and monitoring of disease. miR-21, miR-133a, miR-133b, miR-150, miR-328 and miR-499 were selected as targets in this study through a prior literature review. They were isolated from plas-ma of individuals aged from 20 to 85 years old with AF (n = 17), new-onset AF (n = 5) and without AF (n = 15), where the latter was the control group. The results were ana-lyzed by Real-Time PCR (RT-PCR) with miScript SYBR Green PCR. We observed that miR-21, miR-133b, miR-328 and miR-499 had different levels of expression be-tween the three groups (p <0.05). Increased expression of miR-21 (0.6-fold), miR-133b (1.4-fold), miR-328 (2.0-fold) and miR-499 (2.3-fold) in patients with new-onset AF when compared to AF and control subjects. The miR-133a and miR-150 expression did not differ among the groups. miR-21, miR-133b, miR-328 and miR-499 may be potential biomarkers for AF as well as for new-onset AF, for monitoring and for the di-agnosis. These findings may contribute to the understanding of the process that trig-gers AF and suggest application these molecules as future biomarkers for AF.

Variabilidade genética de Leishmania spp. circulantes entre seres humanos e cães e infecção de flebotomíneos em áreas endêmicas para as leishmanioses no Rio Grande do Norte

Leishmania infantum is the main etiologic agent of visceral leishmaniasis in the New World. The pattern of distribution of leishmaniasis has changed substantially and has presented an emerging profile within the periphery of the Large Urban Centers. Leishmania infection can compromise skin, mucosa and viscera. Only 10% of the individuals infected develop the disease and 90% of human infection is asymptomatic. The main factors involved in the development of the disease are the host immune response, the vector’s species and the parasite’s genetic content. The sequencing of Leishmania isolated seeks to increase the understanding of the symptoms of individuals. The aim of this study was to evaluate the genetic diversity of circulating Leishmania strains among humans, and symptomatic and asymptomatic, and dogs from endemic areas of Rio Grande do Norte State and analyze sandflies from endemic areas for cutaneous and visceral disease. The genetic variability was evaluated by the use of markers hsp70 , ITS1 and a whole genome sequencing was also carried out. The amplified hsp70 and ITS1 of samples were analyzed and assembled using a Phred / Phrap package. The dendograms were constructed using the same methodology, but adding 500 bootstraps, followed by inferences on the relationships between Leishmania variants. The sequences of the 20 Brazilian isolates were mapped to the reference genome L. infantum JPCM5, using the Bowtie2 program and the identification of 36 contigs. The information of the valid SNPs were used in the PCA. SNPs were visualized by Geneious 7.1 and IGV. The genome annotations were transferred to their respective chromosomes and displayed on Geneious. The matching sequences of all chromosomes were aligned using Mauve. The phylogenetic trees were calculated according to maximum likelihood and JTT models. Sandflies were analyzed by PCR for the identification of Leishmania infection, a blood meal source and GAPDH sand fly. As a result, hsp70 and ITS1 were not capable of identifying genetic variability among human isolates from symptomatic and asymptomatic, and dogs. The complete sequencing of the 20 Brazilian isolates revealed a strong similarity between the circulating Leishmania strains in Rio Grande do Norte. The isolates collected in the city of Natal from humans and canines remained grouped in all analyzes, suggesting that there is genotypic and geographic proximity among the isolates. The isolated samples in the 1990s had a higher genotypic diversity when compared to freshly isolated samples. All isolates presented 36 chromosomes with variable ploidy among them, no correlation was found between the number of amastina genes copies, gp63, A2 and SSG with such clinic forms. In general, we did not find correlation between symptomatic and asymptomatic clinical forms and the gene content of the Brazilian isolates of Leishmania. 34,28% of the sandflies collected in the upper west region were L. longipalpis and the main sources of blood meal were humans, dogs and chickens.

Variabilidade genética de Leishmania spp. circulantes entre seres humanos e cães e infecção de flebotomíneos em áreas endêmicas para as leishmanioses no Rio Grande do Norte

Leishmania infantum is the main etiologic agent of visceral leishmaniasis in the New World. The pattern of distribution of leishmaniasis has changed substantially and has presented an emerging profile within the periphery of the Large Urban Centers. Leishmania infection can compromise skin, mucosa and viscera. Only 10% of the individuals infected develop the disease and 90% of human infection is asymptomatic. The main factors involved in the development of the disease are the host immune response, the vector’s species and the parasite’s genetic content. The sequencing of Leishmania isolated seeks to increase the understanding of the symptoms of individuals. The aim of this study was to evaluate the genetic diversity of circulating Leishmania strains among humans, and symptomatic and asymptomatic, and dogs from endemic areas of Rio Grande do Norte State and analyze sandflies from endemic areas for cutaneous and visceral disease. The genetic variability was evaluated by the use of markers hsp70 , ITS1 and a whole genome sequencing was also carried out. The amplified hsp70 and ITS1 of samples were analyzed and assembled using a Phred / Phrap package. The dendograms were constructed using the same methodology, but adding 500 bootstraps, followed by inferences on the relationships between Leishmania variants. The sequences of the 20 Brazilian isolates were mapped to the reference genome L. infantum JPCM5, using the Bowtie2 program and the identification of 36 contigs. The information of the valid SNPs were used in the PCA. SNPs were visualized by Geneious 7.1 and IGV. The genome annotations were transferred to their respective chromosomes and displayed on Geneious. The matching sequences of all chromosomes were aligned using Mauve. The phylogenetic trees were calculated according to maximum likelihood and JTT models. Sandflies were analyzed by PCR for the identification of Leishmania infection, a blood meal source and GAPDH sand fly. As a result, hsp70 and ITS1 were not capable of identifying genetic variability among human isolates from symptomatic and asymptomatic, and dogs. The complete sequencing of the 20 Brazilian isolates revealed a strong similarity between the circulating Leishmania strains in Rio Grande do Norte. The isolates collected in the city of Natal from humans and canines remained grouped in all analyzes, suggesting that there is genotypic and geographic proximity among the isolates. The isolated samples in the 1990s had a higher genotypic diversity when compared to freshly isolated samples. All isolates presented 36 chromosomes with variable ploidy among them, no correlation was found between the number of amastina genes copies, gp63, A2 and SSG with such clinic forms. In general, we did not find correlation between symptomatic and asymptomatic clinical forms and the gene content of the Brazilian isolates of Leishmania. 34,28% of the sandflies collected in the upper west region were L. longipalpis and the main sources of blood meal were humans, dogs and chickens.

Análise da expressão dos receptores HER-2 e sua correlação clínica em pacientes com neoplasia gástrica do setor de Oncologia do Hospital de Clínicas da Universidade Federal de Uberlândia-UFU

Introduction: Gastric cancer is currently the fourth higher cancer mortality rate among men in the world and the fifth among women, despite the progressive advances in oncology. The identification of tumor receptors and the development of target-drugs to block them has contributed to increased survival and quality of life of patients, but it becomes important to know the tumor profile of the population being treated, avoiding burdening treatment with examinations and treatments that are not cost-effective. Objective: To evaluate the profile of the population with gastric cancer treated in five years at the Clinical Hospital of the Federal University of Uberlândia and verify the correlation between overexpression of HER-2 receptor with an unfavorable prognosis. Methods: 203 records with gastric cancer were selected through the system database, attending a five-year period, of which 117 paraffin blocks were available for immunohistochemical assessment of HER2 receptor. Results: 2.6% of tumors showed overexpression of HER2, considering for this study two crosses as positive. There was no statistically significant difference in correlation between expression of the HER2 receptor with age, gender, tumor grade, local involvement, Lauren classification, Borrmann classification or staging. Conclusion: For this studied population, we can conclude that there is no need to employ HER2 blockers with high cost as a target-therapy in patients with gastric cancer, since no clinical benefit probably will be obtained due to a low percentage of these patients that demonstrated superexpression of this receptor or even there is no patients with gastric cancer with superexpression of HER2 with more than three crosses of positivity in immunochemistry

Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH-adapted killifish.

Acute exposures to some individual polycyclic aromatic hydrocarbons (PAHs) and complex PAH mixtures are known to cause cardiac malformations and edema in the developing fish embryo. However, the heart is not the only organ impacted by developmental PAH exposure. The developing brain is also affected, resulting in lasting behavioral dysfunction. While acute exposures to some PAHs are teratogenically lethal in fish, little is known about the later life consequences of early life, lower dose subteratogenic PAH exposures. We sought to determine and characterize the long-term behavioral consequences of subteratogenic developmental PAH mixture exposure in both naive killifish and PAH-adapted killifish using sediment pore water derived from the Atlantic Wood Industries Superfund Site. Killifish offspring were embryonically treated with two low-level PAH mixture dilutions of Elizabeth River sediment extract (ERSE) (TPAH 5.04 μg/L and 50.4 μg/L) at 24h post fertilization. Following exposure, killifish were raised to larval, juvenile, and adult life stages and subjected to a series of behavioral tests including: a locomotor activity test (4 days post-hatch), a sensorimotor response tap/habituation test (3 months post hatch), and a novel tank diving and exploration test (3months post hatch). Killifish were also monitored for survival at 1, 2, and 5 months over 5-month rearing period. Developmental PAH exposure caused short-term as well as persistent behavioral impairments in naive killifish. In contrast, the PAH-adapted killifish did not show behavioral alterations following PAH exposure. PAH mixture exposure caused increased mortality in reference killifish over time; yet, the PAH-adapted killifish, while demonstrating long-term rearing mortality, had no significant changes in mortality associated with ERSE exposure. This study demonstrated that early embryonic exposure to PAH-contaminated sediment pore water caused long-term locomotor and behavioral alterations in killifish, and that locomotor alterations could be observed in early larval stages. Additionally, our study highlights the resistance to behavioral alterations caused by low-level PAH mixture exposure in the adapted killifish population. Furthermore, this is the first longitudinal behavioral study to use killifish, an environmentally important estuarine teleost fish, and this testing framework can be used for future contaminant assessment.

The Role of Dopaminergic Systems in the Neurobehavioral Teratology of Organophosphates in Zebrafish

Background: Organophosphate (OP) pesticides are well-known developmental neurotoxicants that have been linked to abnormal cognitive and behavioral endpoints through both epidemiological studies and animal models of behavioral teratology, and are implicated in the dysfunction of multiple neurotransmitters, including dopamine. Chemical similarities between OP pesticides and organophosphate flame retardants (OPFRs), a class of compounds growing in use and environmental relevance, have produced concern regarding whether developmental exposures to OPFRs and OP pesticides may share behavioral outcomes, impacts on dopaminergic systems, or both. Methods: Using the zebrafish animal model, we exposed developing fish to two OPFRs, TDCIPP and TPHP, as well as the OP pesticide chlorpyrifos, during the first 5 days following fertilization. From there, the exposed fish were assayed for behavioral abnormalities and effects on monoamine neurochemistry as both larvae and adults. An experiment conducted in parallel examined how antagonism of the dopamine system during an identical window of development could alter later life behavior in the same assays. Finally, we investigated the interaction between developmental exposure to an OPFR and acute dopamine antagonism in larval behavior. Results: Developmental exposure to all three OP compounds altered zebrafish behavior, with effects persisting into adulthood. Additionally, exposure to an OPFR decreased the behavioral response to acute D2 receptor antagonism in larvae. However, the pattern of behavioral effects diverged substantially from those seen following developmental dopamine antagonism, and the investigations into dopamine neurochemistry were too variable to be conclusive. Thus, although the results support the hypothesis that OPFRs, as with OP pesticides such as chlorpyrifos, may present a risk to normal behavioral development, we were unable to directly link these effects to any dopaminergic dysfunction.

Investigating bias in recreational fishing surveys: Fishers listed in public telephone directories fish similarly to their unlisted counterparts

Several recent offsite recreational fishing surveys have used public landline telephone directories as a sampling frame. Sampling biases inherent in this method are recognised, but are assumed to be corrected through demographic data expansion. However, the rising prevalence of mobile-only households has potentially increased these biases by skewing raw samples towards households that maintain relatively high levels of coverage in telephone directories. For biases to be corrected through demographic expansion, both the fishing participation rate and fishing activity must be similar among listed and unlisted fishers within each demographic group. In this study, we tested for a difference in the fishing activity of listed and unlisted fishers within demographic groups by comparing their avidity (number of fishing trips per year), as well as the platform used (boat or shore) and species targeted on their most recent fishing trip. 3062 recreational fishers were interviewed at 34 tackle stores across 12 residential regions of Queensland, Australia. For each fisher, data collected included their fishing avidity, the platform used and species targeted on their most recent trip, their gender, age, residential region, and whether their household had a listed telephone number. Although the most avid fishers were younger and less likely to have a listed phone number, cumulative link models revealed that avidity was not affected by an interaction of phone listing status, age group and residential region (p > 0.05). Likewise, binomial generalized linear models revealed that there was no interaction between phone listing, age group and avidity acting on platform (p > 0.05), and platform was not affected by an interaction of phone listing status, age group, and residential region (p > 0.05). Ordination of target species using Bray-Curtis dissimilarity indices found a significant but irrelevant difference (i.e. small effect size) between listed and unlisted fishers (ANOSIM R < 0.05, p < 0.05). These results suggest that, at this time, the fishing activity of listed and unlisted fishers in Queensland is similar within demographic groups. Future research seeking to validate the assumptions of recreational fishing telephone surveys should investigate fishing participation rates of listed and unlisted fishers within demographic groups.

Representaciones sociales sobre proyección social de docentes y estudiantes de los programas de la facultad de ciencias económicas y sociales Universidad de La Salle 2013

Tesis (Trabajadora Social).-- Universidad de La Salle. Facultad de Ciencias Económicas y sociales. Programa de Trabajo Social, 2014

One-year follow-up of the nutritional status of patients undergoing liver transplantation

Background: Choosing the method of nutritional assessment is essential for proper follow-up of the nutritional status of patients undergoing liver transplantation. Objectives: Evaluate and compare the nutritional status of cirrhotic patients before and after liver transplantation over a year by different methods of nutritional assessment. Methods: Patients undergoing liver transplantation were assessed in five phases: pre-transplant, 1, 3, 6 and 12 months after transplantation at the hospital Santa Casa de Misericordia de Porto Alegre, RS, Brazil. The methods used for nutritional assessment were anthropometry, grip strength of the non-dominant hand (HGS) by dynamometry, thickness of the adductor pollicis muscle (APM) and phase angle (PA) by bioelectrical impedance analysis (BIA). In all evaluations, the same measurements were taken. Results: Evaluations were performed in 22 patients. Methods that showed a higher prevalence of malnourished patients before transplantation were PA by BIA (25%), arm muscle circumference (AMC) (21.9%) and arm circumference (AC) (18.8%). When comparing the nutritional status of patients during follow-up, there was a significant difference only in the evaluation methods AC, triceps skinfold thickness and PA by BIA. At the end, the methods of nutritional assessment were compared again. They showed a significant statistical difference, with HGS being the best method for detecting malnutrition. Conclusions: In conclusion, it is suggested that the method PA by BIA could be widely used with this population since the results are consistent with other findings in the literature and they are significant, reliable, and reproducible.

Potencial de acúmulo de massa e nutrientes e estádio mais adequado de manejo do sorgo-forrageiro em sistemas de transição agroecológica.

2014

Milho cultivado em sucessão a adubos verdes em sistemas sob bases agroecológicas.

2015

Enquadramento dos corpos hídricos subterrâneos do Distrito Federal : parâmetros hidrogeoquímicos e ambientais

Dissertação (mestrado)—Universidade de Brasília, Instituto de Geociências, 2016.