Infecção natural por tripanosomatídeos (Kinetoplastida: Trypanosomatidae) em Lutzomyia umbratilis (Diptera: Psychodidae) em áreas de leishmaniose tegumentar americana no Amazonas, Brasil

Durante o período de 2002 a 2003 foram realizadas coletas de flebotomíneos em duas áreas do estado do Amazonas (Base de treinamento militar - BI1 e Tarumã Mirim). Nessas coletas foram capturadas um total de 1.440 fêmeas de Lutzomyia (Nyssomyia) umbratilis. Lu.umbratilis é a principal responsável pela transmissão da Leishmaniose Tegumentar Americana (LTA) ao norte do Rio Amazonas. Do total coletado apenas 15 espécimens (ou 1,04%) apresentaram infecção natural por tripanosomatídeos, sendo 12 na BI1 e 3 em Tarumã-Mirim. Isso representou uma taxa de infecção de 1,66% (12 dos 720 capturados em BI1) e 0,42% (3 dos 720 em Tarumã-Mirim). Estes resultados confirmam as informações prévias por outros autores de reduzidos valores de infecção natural por tripanosomatídeos em flebotomíneos, mesmo em áreas altamente endêmicas para leishmaniose.During the period of 2002 to 2003, there were collected sand flies in two areas of Amazon State (Forest Combat Training Base - BI1 and Tarumã-Mirim). Were collected the 1440 L. (Nyssomyia) umbratilis female. Lu. umbratilis is the main responsible for the transmission of American Tegumentary Leishmaniasis (ATL) in the northern of Amazon River. Only 15 specimens (or 1,04%) presented natural infection with trypanosomatids, being 12 at Bl1 and 3 at Tarumã-Mirim. The infection rate was 1,66% (12 of the 720 collected at BI1) and 0,42% (3 of the 720 at Tarumã-Mirim). These results confirm the previous informations described by other authors that insects have low rates of natural infection by trypanosomatids even in high endemic areas for Leishmaniasis

Pharmacologic regimens for knee osteoarthritis prevention: can they be cost-effective?

We sought to determine the target populations and drug efficacy, toxicity, cost, and initiation age thresholds under which a pharmacologic regimen for knee osteoarthritis (OA) prevention could be cost-effective

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The modified Delphi method. An approach from the Soft Systems Methodology [El método delphi modificado. Un acercamiento desde la metodología de sistemas suaves]

The article presents a revision of a state of the art related to the Delphi method, its definitions, characteristics and applications. Based on this revision, its problems were identified, and one of them related to the non-structure structuring of problems of human activity was analyzed. With the end of complementing the analysis, a case of the application of soft system methodology was made, conceived in the 1960's by Peter Checkland in a Doctoral dissertation related to the Delphi method and its alignment with an innovation strategy in the frame of a management innovation model; with the purpose of generating a solved problem. Amongst the main conclusions, the advantages of the use of a soft system methodology were highlighted to help the improvement of non-structured human activity with the Delphi method, and its alignment with the company's innovation strategy in the frame of innovation management models. Also, the possibility of complementing the soft system methodology with priority surveys to obtain expert opinion related with the components of a Doctoral dissertation

Metodologias para obtenção de resistência e/ou tolerância da soja à ferrugem-asiática

Os objetivos deste trabalho foram complementar os estudos dos mecanismos genéticos da resistência e tolerância da soja à ferrugem-asiática e sugerir metodologias de melhoramento que permitam o acúmulo de genes maiores e menores. Seis experimentos foram realizados durante três safras em Londrina, PR, de 2005/06 a 2007/08, envolvendo cinco parentais e as gerações derivadas F2, F3 e F4. Foi utilizado o delineamento inteiramente casualizado, com parcelas em covas. As metodologias propostas foram planejadas para superar as dificuldades do melhorista em selecionar genes menores na presença de genes maiores. Isto é resolvido conduzindo populações segregantes F2, F3 e F4 numerosas para melhorar as chances de encontrar recombinações favoráveis e submetendo-as à pressão do patógeno para aumentar a frequência de genótipos resistentes/tolerantes na população F4 ou F5 quando plantas individuais serão selecionadas para formação de progênies. Consequentemente, a frequência de progênies F5 ou F6 superiores possuidoras de alelos nos genes menores e maiores também será aumentada