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

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

Detecting multiple DNA human profile from a mosquito blood meal

Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals

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

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Ant species (Hymenoptera, Formicidae) from the seasonally dry tropical forest of northeastern Brazil: a compilation from field surveys in Bahia and literature records

Ant species (Hymenoptera, Formicidae) from the seasonally dry tropical forest of northeastern Brazil: a compilation from field surveys in Bahia and literature records. The Caatingas occur predominantly in northeastern Brazil and comparatively it is the biome that received less attention than any other ecosystem in Brazil, representing the region where invertebrate groups are less known. We present here the first list of ant species of the Caatingas, compiling information from the literature, from a study of samples preserved in alcohol in the Laboratory of Entomology (Universidade Estadual de Feira de Santana), and from a field survey conducted in Milagres, Bahia, submitting standardized 1-m² samples of the leaf-litter to Winkler extractors. Summing all information, 11 subfamilies, 61 genera and 173 species (plus one subspecies) of ants are recognized in the biome. This species number does not consider morphospecies that could not be named due to the lack of reliable recent taxonomic information for some Neotropical ant genera. The list presented here for ant species of the Caatingas is therefore underestimated, but it is relevant because it allows the identification of areas to be sampled in order to improve our knowledge of the diversity of ants in this biome

A catalogue of the Pseudomyrmecinae ants type specimens (Hymenoptera, Formicidae) deposited in the Museu de Zoologia da Universidade de S\ue3o Paulo, Brazil

This catalogue lists the type specimens of 37 species of Pseudomyrmecinae ants deposited in the Hymenoptera Formicidae collection of the Museu de Zoologia da Universidade de São Paulo, which holds types of the only two genera that occur in the Neotropics, Pseudomyrmex Lund and Myrcidris Ward. We record the label information, condition of the specimens, nomenclatural changes, type status, and provide an index of the listed taxa.<br>Este catálogo lista espécimes tipos de 37 espécies de formigas Pseudomyrmecinae depositadas na coleção de Formicidae da seção de Hymenoptera do Museu de Zoologia da Universidade de São Paulo, e que pertencem aos dois gêneros que ocorrem na Região Neotropical, Pseudomyrmex Lund e Myrcidris Ward. São apresentados os dados dos rótulos, estado de conservação dos exemplares, mudanças nomenclaturais, status taxonômicos e um índice para os táxons catalogados

Catalogue of " poneromorph" ant type specimens (Hymenoptera, Formicidae) deposited in the Museu de Zoologia da Universidade de S\ue3o Paulo, Brazil

The present catalogue lists the type specimes of 112 nominal " poneromorph" ant species housed in the Formicidae collection of the Hymenoptera laboratory, Museu de Zoologia da Universidade de São Paulo (MZSP). The catalogue includes types of Amblyoponinae, Ectatomminae, Heteroponerinae, Ponerinae, and Proceratiinae, that is, all poneromorph (sensu Bolton, 2003) but for the monotypic Paraponerinae, of which the collection bears no type specimens. We present here information on type categories (holotype, paratype, syntype, lectotype, and paralectotype), label data, nomenclatural changes since the original description and type specimens conservation status. At last we present indexes for the taxa names presented.O presente catálogo lista os espécimes-tipo de 112 espécies nominais de formigas poneromorfas depositados no Laboratório de Hymenoptera do Museu de Zoologia da Universidade de São Paulo (MZSP). O catálogo inclui tipos das subfamílias poneromorfas (no sentido de Bolton, 2003), isto é, Amblyoponinae, Ectatomminae, Heteroponerinae, Ponerinae e Proceratiinae, exceto Paraponerinae, monotípica, não representada nesta coleção por espécimes-tipo. Aqui são apresentadas informações sobre as categorias dos tipos de poneromorfos na coleção do MZSP (holótipo, parátipo, síntipo, lectótipo e paralectótipo), além de dados do rótulo, mudanças nomenclaturais desde a publicação original e uma breve avaliação sobre o estado de conservação dos espécimes. Por último, apresentamos índices para os taxons aqui catalogados

The type specimens of "dorylomorph" ants (Hymenoptera, Formicidae: Aenictinae, Ecitoninae, Cerapachyinae, Leptanilloidinae) deposited in the Museu de Zoologia da Universidade de S\ue3o Paulo, Brazil

The present catalogue lists the "dorylomorph" ant types (Aenictinae: Aenictus; Cerapachyinae: Acanthostichus and Cerapachys; Ecitoninae: Eciton, Labidus, Neivamyrmex and Nomamyrmex; and Leptanilloidinae: Asphinctanilloides and Leptanilloides) housed in the Formicidae collection of the Hymenoptera laboratory, Museu de Zoologia da Universidade de São Paulo (MZSP), Brazil. In total, the collection includes types of 141 nominal species, of which 56 are still valid. The majority of types of dorylomorph species in the MZSP collection are syntypes (67 species), but there are as well 13 species represented by holotypes only, 17 by holotypes and paratypes, 43 species by paratypes only, and one species by a paralectotype. We record the label information, condition of the specimens, nomenclatural changes, type status, and provide indexes of the listed taxa