Association of TNF-\u3b1, CTLA4, and PTPN22 polymorphisms with type 1 diabetes and other autoimmune diseases in Brazil

Type 1 diabetes mellitus (T1D) is a complex disorder characterized by an autoimmune response against human pancreatic beta-cells. Patients with T1D can also develop a response toward one or more other factors, such as in autoimmune thyroiditis (AITD) and celiac disease (CD). In the presence of T1D + AITD, the patient is diagnosed with autoimmune polyglandular syndrome type III (APSIII); patients with APSIII may also present with CD. These diseases have a strong genetic component and share many susceptibility genes, suggesting potentially overlapping pathogenic pathways. Polymorphisms in the TNF-\u3b1(rs1800629), CTLA-4 (rs231775), and PTPN22 (rs2476601) genes have been previous associated with T1D; however, there is no consensus regarding their role in T1D and scarce literature focusing on AIDT and/or CD. Thus, we analyzed these genetic variants in 205 Northeast Brazilian patients with T1D and with/without AITD and/or CD, and in 308 healthy controls. The PTPN22 gene variants were associated with T1D susceptibility and APSIII [odds ratio (OR) = 2.57 and 2.77, respectively]. CTLA4 rs231775 and TNF-\u3b1rs1800629 were not associated with T1D onset in the Brazilian population. However, when comparing APSIII individuals in the T1D only group, we observed an association of the TNF-\u3b1SNP in the allelic (P = 0.0442; OR = 0.44) and dominant models (P = 0.0387; OR = 0.40). This study reinforces the importance of CTLA-4 and other variants in unraveling the pathogenic mechanisms of T1D in different populations and in understanding their relationships with the development of other T1D-related autoimmune diseases

Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers

BACKGROUND: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated. OBJECTIVE: To identify predictive genetic markers of immune response to ART. METHODS: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure. RESULTS: Male patients were overrepresented in non-responder group (p=0.01). Non-responders also started with lower absolute CD4+ T cell counts (p<0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p=0.04), rs1128503 (ABCB1) A allele (p=0.03) and rs707265 (CYP2B6) A allele (p=0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p=0.004) and rs4646437 (CYP3A4) A allele (p=0.04). CONCLUSION: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response

LITTER PRODUCTION AND DECOMPOSITION IN AREAS OF SECONDARY FOREST, PLANTATION OF SABI\uc1 ( Mimosa caesalpiniaefolia Benth. ) AND PLANTATION OF ANDIROBA ( Carapa guianensis Aubl. ) IN FLONA M\uc1RIO XAVIER, RJ

Este trabalho teve como objetivo avaliar o aporte e a decomposi\ue7\ue3o da serapilheira em \ue1reas de floresta secund\ue1ria espont\ue2nea, plantio de sabi\ue1 (Mimosa caesalpiniaefolia Benth.) e plantio de andiroba (Carapa guianensis Aubl.). Para avalia\ue7\ue3o do aporte de serapilheira, foram instalados dez coletores c\uf4nicos sendo o aporte avaliado durante o per\uedodo de outubro de 2003 a setembro de 2004. Posteirormente, foi feita a quantifica\ue7\ue3o dos macronutrientes (N, P e K). A avalia\ue7\ue3o da taxa de decomposi\ue7\ue3o foi realizada utilizando-se o m\ue9todo dos litter bags . A \ue1rea de plantio de andiroba aportou a maior quantidade de serrapilheira 9,20 Mg ha-1,sendo seguida pelo plantio de sabi\ue1 com 9,06 Mg ha-1 e pela floresta secund\ue1ria espont\ue2nea 7,63 Mg ha-1 por ano. A serapilheira das \ue1reas de plantio de sabi\ue1 e do plantio de andiroba apresentou maiores valores de nitrog\ueanio e f\uf3sforo que a \ue1rea de floresta secund\ue1ria. A velocidade de decomposi\ue7\ue3o da serapilheira foi maior nas \ue1reas de plantio de sabi\ue1 e andiroba, podendo tal comportamento ter sido influenciado pelo maior conte\ufado de nitrog\ueanio na serapilheira. O f\uf3sforo foi o nutriente que apresentou maior velocidade de libera\ue7\ue3o.This study evaluated litter production and decomposition in areas of spontaneous secondary forest, sabi\ue1 (Mimosa caesalpiniaefolia Benth.) and andiroba (Carapa guianensis Aubl.) plantation. For litter contribution evaluation, 10 conical collectors were installed, and the contribution was evaluated from October, 2003 to September, 2004. N, P and K contents were quantified in litter. To evaluate decomposition, rate litter bags method was used. In the andiroba plantation area, it was observed the higher litter amount 9,20 Mg ha-1, followed by the sabia plantation with 9,06 Mg ha-1 and spontaneous secondary forest 7,63 Mg ha-1. Sabi\ue1 and andiroba litter presented larger nitrogen and phosphorus values in relation to the secondary forest area. Litter decomposition rate was faster in sabi\ue1 and andiroba areas. This behavior might be influenced by larger nitrogen content in the litter. Phosphorus was the nutrient that presented the higher liberation rate

A rapid screening of ancestry for genetic association studies in an admixed population from Pernambuco, Brazil

Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time

Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III

Type 1 diabetes mellitus (T1D) is an organ-specific autoimmune disease characterized by T-cell mediated self-destruction of insulin-producing \u3b2 cells in the pancreas. T1D patients are prone to develop other glandular autoimmune disorders, such as autoimmune thyroid disease that occurs simultaneously with autoimmune polyglandular syndrome type III (APSIII). Signal transducer and activator of transcription 4 (STAT4) is a well-known regulator of proinflammatory cytokines, and interferon-induced with helicase C domain 1 (IFIH1) is activated in the interferon type I response. Both genes have been examined separately in autoimmune diseases and, in this study, we assessed their joint role in T1D and APSIII. We conducted a case-control study, enrolling 173 T1D patients and 191 healthy controls from northeastern Brazil, to assess the distribution of the rs7574865 and rs3024839 SNPs in STAT4 and the rs3747517 and rs1990760 SNPs in IFIH1 in T1D and APSIII patients. Additionally, we conducted a meta-analysis with the rs7574865 SNP in STAT4 (1392 T1D patients and 1629 controls) and the rs1990760 SNP in IFIH1 (25092 T1D patients and 28544 controls) to examine their association with T1D. Distribution of STAT4 and IFIH1 allelic frequencies did not show statistically significant differences between T1D patients and controls in our study population; however, the meta-analysis indicated that SNPs in STAT4 and IFIH1 are associated with T1D worldwide. Our findings indicate that although STAT4 and IFIH1 SNPs are not associated with T1D in a Brazilian population, they might play a role in susceptibility to T1D on a larger worldwide scale

TECHNICAL AND ECONOMIC VIABILITY OF COMMERCIAL PLANTATIONS IN AREAS ACCIDENTS IN SOUTH OF THE ESP\ucdRITO SANTO STATE, BRAZIL

Esta pesquisa objetivou realizar uma an\ue1lise t\ue9cnica e econ\uf4mica da implanta\ue7\ue3o e manuten\ue7\ue3o de plantios de eucalipto em \ue1reas com topografia acidentada no sul do Esp\uedrito Santo. O trabalho foi executado em pequenas propriedades rurais. Foram analisados o rendimento, a produtividade e os custos envolvidos nas atividades. De acordo com os resultados, a opera\ue7\ue3o de capina qu\uedmica manual obteve o maior rendimento (0,191 hectare/hora) e a atividade de replantio obteve o menor (0,008 hectare/hora). Quanto aos custos operacionais, as opera\ue7\uf5es realizadas durante o preparo do solo para o plantio tiveram o maior custo (32%), seguido das atividades de manuten\ue7\ue3o (27%), atividades pr\ue9vias de preparo da \ue1rea (22%) e plantio (19%).This research aimed to carry out a technical and economic analysis of the deployment and maintenance of eucalyptus crops on areas with steep topography, in small farms in south 'Esp\uedrito Santo' state, Brazil. The yield, the productivity of operations and the costs involved in activities were analyzed. According to the results, the operation of chemical weed control manual had the highest yield (0.191 ha hour-1) and the activity of replanting had the lowest (0.008 ha hour-1). Concerned to the operation costs, the operations during the soil preparation for planting had the highest cost (32%), followed by maintenance activities (27%), previous activities of preparation of the area (22%) and plantation (19%)

The fraction of cancer attributable to ways of life, infections, occupation, and environmental agents in Brazil in 2020

Many human cancers develop as a result of exposure to risk factors related to the environment and ways of life. The aim of this study was to estimate attributable fractions of 25 types of cancers resulting from exposure to modifiable risk factors in Brazil. The prevalence of exposure to selected risk factors among adults was obtained from population-based surveys conducted from 2000 to 2008. Risk estimates were based on data drawn from metaanalyses or large, high quality studies. Population-attributable fractions (PAF) for a combination of risk factors, as well as the number of preventable deaths and cancer cases, were calculated for 2020. The known preventable risk factors studied will account for 34% of cancer cases among men and 35% among women in 2020, and for 46% and 39% deaths, respectively. The highest attributable fractions were estimated for tobacco smoking, infections, low consumption of fruits and vegetables, excess weight, reproductive factors, and physical inactivity. This is the first study to systematically estimate the fraction of cancer attributable to potentially modifiable risk factors in Brazil. Strategies for primary prevention of tobacco smoking and control of infection and the promotion of a healthy diet and physical activity should be the main priorities in policies for cancer prevention in the country. \ua9 2016 Azevedo e Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Mixed connective tissue disease: state of the art on clinical practice guidelines

Mixed connective tissue disease (MCTD) is a complex overlap disease with features of different autoimmune connective tissue diseases (CTDs) namely systemic sclerosis, poly/dermatomyositis and systemic lupus erythematous in patients with antibodies targeting the U1 small nuclear ribonucleoprotein particle. In this narrative review, we summarise the results of a systematic literature research which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. Since no specific CPGs on MCTD were found, other CPGs developed for other CTDs were taken into consideration in order to discuss what can be applied to MCTD even if designed for other diseases. Three major objectives were proposed for the future development of CPGs: MCTD diagnosis (diagnostic criteria), MCTD initial and follow-up evaluations, MCTD treatment. Early diagnosis, epidemiological data, assessment of burden of disease and QOL aspects are among the unmet needs identified by patient

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). METHODS/DESIGN: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure 6430 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. DISCUSSION: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration metho

Correlated long-range mixed-harmonic fluctuations measured in pp, p+Pb and low-multiplicity Pb+Pb collisions with the ATLAS detector

For abstract see published article