Relationship between self-declared ethnicity, mitochondrial haplogroup and genomic ancestry in individuals from southeast of Brazil

Em populações onde há um alto grau de miscigenação, como no Brasil, o uso exclusivo de informações da etnia auto-declarada não é um bom método de classifi cação étnica. Neste trabalho, nós avaliamos a relação entre as etnias auto-declaradas com ancestralidade genômica e haplogrupos mitocondriais em 492 indivíduos do Sudeste Brasileiro. Haplogrupos mitocondriais foram obtidos pela análise das regiões hipervariáveis do DNA mitocondrial (mtDNA) e a ancestralidade genômica foi obtida utilizando 48 marcadores autossômicos informativos de ancestralidade (AIM). Dos 492 indivíduos, 74,6% se auto-declararam brancos, 13,8% pardos e 10,4% pretos. Em relação aos haplogrupos mitocondriais, 46,3% apresentaram mtDNA Africano e a maior contribuição de ancestralidade genômica foi Europeia (57,4%). Quando realizamos a distribuição do mtDNA e ancestralidade genômica de acordo com as etnias auto-declaradas, dos 367 indivíduos auto-declarados brancos, encontramos 37,6% com mtDNA Africano, sendo observado maior contribuição de ancestralidade Europeia (63,3%). Dos 68 indivíduos auto-declarados pardos, 25% apresentaram mtDNA Ameríndio e pouca diferen-ça na contribuição de ancestralidade Europeia e Africana. Dos 51 indivíduos auto-declarados pretos, 80,4% apresentaram mtDNA Africano e maior contribuição de ancestralidade Africana (55,6%). A população brasileira apresenta uma uniformidade de ancestralidade genômica Ameríndia, e apenas o uso de marcadores genéticos (autossômico e mitocondrial) foi capaz de capturar essa informação. Sugerimos que estudos epidemiológicos façam o uso associado destes métodos, pois poderiam fornecer informações complementares.In populations where there is a high degree of admixture, as in Brazil, the sole use of ethnicity self-declaration information is not a good method of ethnic classifi cation. We evaluate the relationship between self-declared ethnicities with genomic ancestry and mitochondrial haplogroups in 492 individuals from Southeastern Brazil. Mitochondrial haplogroups were obtained by analyzing the hypervariable regions of mitochondrial DNA (mtDNA) and genomic ancestry was obtained using 48 autosomal ancestry informative markers (AIM). Of the 492 individuals, 74.6% self-declared as white, 13.8% as Brown and 10.4% as Black. In relation of mtDNA haplogroups, 46.3% presented African mtDNA and the major genomic ancestry was European (57.4%). When we performed the distribution of mtDNA and genomic ancestry according to the self-declared ethnicities, from 367 individuals self-declared white, 37.6% showed African mtDNA, and had a higher contribution of European ancestry (63.3%). The 68 individuals self-declared brown, 25% showed Amerindian mtDNA and few differences in the averages contribution of European and African ancestries. Those 51 subjects self-declared black, 80.4% had African mtDNA and the main contribution of African ancestry (55.6%). The Brazilian population had a very uniform degree of Amerindian genomic ancestry, and only by using genetic markers (autosomal and mitochondrial) we were able to capture this information. Epidemiological studies should use the association of these methods to provide complementary information

Collapsing Glomerulopathy. A Treatable Disease?

Renal disease is a relatively common complication in human immunodeficiency virus (HIV) infected patients and has become the fourth leading cause of death in AIDS individuals, immediately following septicaemia, pneumonia and hepatic disease. HIV associated nephropathy, HIV associated immune complex renal disease and HIV associated thrombotic microangiopathy are the main causes of chronic renal failure in this population. The authors report a case of a 44 year-old black male, HIV 1 infected with low CD4 count, admitted to the nephrology department with non nephrotic proteinuria and renal failure. Renal biopsy revealed a focal segmental glomerulosclerosis collapsing variant. The patient was treated with highly active antiretroviral therapy and an ACE inhibitor and, at 3 months of follow-up, has recovered his renal function. This case illustrates the efficacy of highly active antiretroviral therapy (HAART) on HIV associated nephropathy. Prospective studies are needed to evaluate HAART in the treatment of HIV associated nephropathies

Removal of diethyltoluamide, paracetamol, caffeine and triclosan from natural water by photo-Fenton process using powdered zero-valent iron

The removal of four pharmaceuticals and personal care products (PPCPs), namely diethyltoluamide (DEET), paracetamol (PAR), caffeine (CAF) and triclosan (TCS) (at a spiked concentration of 25 μg/L), from natural water using the photo (UVC)-Fenton (powdered zero-valent iron, pZVI) process was investigated. The results show that a molar ratio of H2O2/pZVI of 2.0, pZVI concentration of 22.4 mg/L and pH of 3.0 maximised the removal of the target compounds at 71.1%, 100%, 64.2% and 87.1%, for DEET, PAR, CAF and TCS, respectively, after 30 min in Fenton (pZVI) process. When this process was coupled with UVC radiation, 29.6%, 80.3%, 3.1% and 88.4% of DEET, PAR, CAF and TCS, respectively, were removed within the first minute, and 99.0%, 100%, 99.5% and 100%, respectively, were removed after 30 min. The pseudo first-order kinetic model best fitted the degradation data of DEET, PAR and CAF (1–20 min); and because 80% of TCS and PAR degraded within the first minutes, it is suggested to explore the kinetics during the initial period. Characterisations of pZVI after the photo-Fenton (pZVI) process indicated the corrosion of the surface of iron powder and the presence of iron oxides and iron hydroxides. Lower removals of nitrate (35–50%), phosphate (<35%) and total organic carbon (TOC, <18%) were observed, which may be attributed to the small H2O2/pZVI dosage used. Results of this investigation show that the photo-Fenton (pZVI) process has potential for efficient and cost-effective removal of PPCPs

Five-year review of an international clinical research-training program

The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008-2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background

Gene-gene interaction affects coronary artery disease risk.

Introdução: Existem vários estudos que comparam doentes coronários e controlos, no sentido de determinar quais os polimorfismos que apresentam risco acrescido de doença das artérias coronárias (DC). Os seus resultados têm sido muitas vezes contraditórios, mas apresentam uma limitação suplementar: avaliam os polimorfismos um a um, quando na natureza os polimorfismos não existem isolados. Põe-se a questão se serão mais importantes associações de polimorfismos mutados no mesmo gene ou em genes diferentes. Objectivo: Com o presente trabalho pretendemos avaliar o risco da associação de polimorfismos em termos de aparecimento de DC no mesmo gene ou em genes diferentes. Metodologia: Estudámos em 298 doentes coronários e 298 controlos sãos o risco associado aos polimorfismos (genótipos considerados de risco), DD da Enzima de Converaão da Angiotensina (ECA) I/D; GG da ECA 8, MM do Angiotensinogénio (AGT) 174; TT do AGT 235; TT da Metiltetrahidrofolato Reductase (MTHFR) 677; AA da MTHFR 1298;RR da Paraoxonase1 (PON1) 192 e MM da PON1 55. Posteriormente avaliámos o risco ligado às associações no mesmo gene (DD da ECA + GG da ECA 8; MM do AGT174 + TT do AGT 235; TT da MTHFR 677 + AA da MTHFR 1298). Finalmente, nos polimorfismos que isoladamente apresentavam significância, avaliámos o risco das associações de polimorfismos a níveis funcionais diferentes (ECA + AGT; ECA + MTHFR; ECA + PON1. Finalmente através de um modelo de regressão logística fomos determinar quais as variáveis que se relacionavam de forma significativa e independente com a DC. Resultados: Os polimorfismos isolados como: ECA DD [P<0.0001], ECA 8 GG [P=0,023], e MTHFR 1298 AA [P=0,049]), apresentaram uma frequência mais elevada nos casos, associando-se de forma significativa ao grupo com DC. A associação de polimorfismos no mesmo gene não teve efeito sinergístico ou aditivo e não aumentou o risco de DC. A associação polimórfica em genes diferentes aumentou o risco de DC quando comparada com o risco do polimorfismo isolado. No caso da associação da ECA DD ou ECA 8 GG com a PON1 192 RR, o risco quadruplicou (OR passou de 1,8 para 4,2). Após regressão logística o hábito tabágico, a história familiar, o fibrinogénio, diabetes, a associação ECA DD ou ECA 8 GG com a MTHFR 1298 AA e a interacção ECA DD ou ECA 8 GG com a PON1 192 RR permaneceram na equação, mostrando ser factores de risco independente para DC. Conclusões: A associação de polimorfismos mutados no mesmo gene nunca aumentou o risco do polimorfismo isolado. A associação com interacção de polimorfismos mutados em genes diferentes, pertencentes a sistemas fisiopatológicos e enzimáticos diferentes, esteve sempre associada a maior risco do que cada polimorfismo por si. Este trabalho levanta, pela primeira vez, a possibilidade de tentativa de compreensão do risco genético coronário em conjunto e não de cada polimorfismo por si.INTRODUCTION: Various studies have compared coronary artery disease (CAD) patients with controls in order to determine which polymorphisms are associated with a higher risk of disease. The results have often been contradictory. Moreover, these studies evaluated polymorphisms in isolation and not in association, which is the way they occur in nature. OBJECTIVE: Our purpose was to evaluate the risk of CAD in patients with associated polymorphisms in the same gene or in differen genes. METHODS: We evaluated the risk associated with ACE DD, ACE 8 CC, ACT 174MM, AGT 235TT, MTHFR 677TT, MTHFR 1298AA, PON1 192RR and PON1 55MM in 298 CAD patients and 298 healthy individuals. We then evaluated the risk of associated polymorphisms in the same gene (ACE DD + ACE 8GG; AGT 174MM + AGT 235TT; MTHFR 677TT + MTHFR 1298AA). Finally, for the isolated polymorphisms which were significant, we evaluated the risk of polymorphism associations at different functional levels (ACE + AGT; ACE + MTHFR; ACE + PON1). Multiple logistic regression was used to identify independent risk factors for CAD. RESULTS: Isolated polymorphisms including ACE DD(p < 0.0001), ACE 8 gg (p=0.023), and MTHFR 1298AA (p = 0.049) presented with a significantly higher frequency in the CAD group. An association of polymorphisms in the same gene did not have an additive or synergistic effect, nor did it increase the risk of CAD. Polymorphic associations in different genes increased the risk of CAD, compared with the isolated polymorphisms. The association of ACE DD or ACE 8 GG with PON1 192RR increased the risk of CA fourfold (1.8 to 4.2). After logistic regression analysis, current smoking, family history, fibrinogen, diabetes, and the ACE DD or ACE 8 GG + MTHFR 1298AA and ACE DD or ACE 8 GG + PON1 192RR associations remained in the, model and proved to be independent predictors of CAD. CONCLUSIONS: The association of polymorphisms in the same gene did not increase the risk of the isolated polymorphism. The association of polymorphisms in genes belonging to different enzyme systems was always linked to increased risk compared to the isolated polymorphisms. This study may contribute to a better understanding of overall genetic risk for CAD rather than that associated with each polymorphism in isolation.info:eu-repo/semantics/publishedVersio

Spreading Patterns of the Influenza A (H1N1) Pandemic

We investigate the dynamics of the 2009 influenza A (H1N1/S-OIV) pandemic by analyzing data obtained from World Health Organization containing the total number of laboratory-confirmed cases of infections - by country - in a period of 69 days, from 26 April to 3 July, 2009. Specifically, we find evidence of exponential growth in the total number of confirmed cases and linear growth in the number of countries with confirmed cases. We also find that, i) at early stages, the cumulative distribution of cases among countries exhibits linear behavior on log-log scale, being well approximated by a power law decay; ii) for larger times, the cumulative distribution presents a systematic curvature on log-log scale, indicating a gradual change to lognormal behavior. Finally, we compare these empirical findings with the predictions of a simple stochastic model. Our results could help to select more realistic models of the dynamics of influenza-type pandemics

Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle

Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a pair of isolated flat electronic bands and forms a strongly correlated electronic platform. Here, we use scanning tunneling microscopy to probe local properties of highly tunable twisted bilayer graphene devices and show that the flat bands strongly deform when aligned with the Fermi level. At half filling of the bands, we observe the development of gaps originating from correlated insulating states. Near charge neutrality, we find a previously unidentified correlated regime featuring a substantially enhanced flat band splitting that we describe within a microscopic model predicting a strong tendency towards nematic ordering. Our results provide insights into symmetry breaking correlation effects and highlight the importance of electronic interactions for all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page

Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade