Major Challenges in clinical management of TB/HIV coinfected patients in Eastern Europe compared with Western Europe and Latin America

Objectives: rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and methods: between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results: significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00-4.09), prior anti-TB treatment (3.42 (1.88-6.22)), and living in EE (7.19 (3.28-15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90-96% in other regions (p<0.0001). Conclusions: in EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART

Early lung cancer detection using spiral computed tomography and positron emission tomography

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions

High major histocompatibility complex class I polymorphism despite bottlenecks in wild and domesticated populations of the zebra finch ()

Background Two subspecies of zebra finch, Taeniopygia guttata castanotis and T. g. guttata are native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system. Results Despite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies. Conclusions Despite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences

Halorhabdus tiamatea: Proteogenomics and glycosidase activity measurements identify the first cultivated euryarchaeon from a deep-sea anoxic brine lake as potential polysaccharide degrader.

Euryarchaea from the genus Halorhabdus have been found in hypersaline habitats worldwide, yet are represented by only two isolates: Halorhabdus utahensis AX-2T from the shallow Great Salt Lake of Utah, and Halorhabdus tiamatea SARL4BT from the Shaban deep-sea hypersaline anoxic lake (DHAL) in the Red Sea. We sequenced the H. tiamatea genome to elucidate its niche adaptations. Among sequenced archaea, H. tiamatea features the highest number of glycoside hydrolases, the majority of which were expressed in proteome experiments. Annotations and glycosidase activity measurements suggested an adaptation towards recalcitrant algal and plant-derived hemicelluloses. Glycosidase activities were higher at 2% than at 0% or 5% oxygen, supporting a preference for low-oxygen conditions. Likewise, proteomics indicated quinone-mediated electron transport at 2% oxygen, but a notable stress response at 5% oxygen. Halorhabdus tiamatea furthermore encodes proteins characteristic for thermophiles and light-dependent enzymes (e.g. bacteriorhodopsin), suggesting that H. tiamatea evolution was mostly not governed by a cold, dark, anoxic deep-sea habitat. Using enrichment and metagenomics, we could demonstrate presence of similar glycoside hydrolase-rich Halorhabdus members in the Mediterranean DHAL Medee, which supports that Halorhabdus species can occupy a distinct niche as polysaccharide degraders in hypersaline environments

CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions

CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. CD47, also called integrin-associated protein, has been demonstrated to associate in cis with β1 and β3 integrins. Here we test the hypothesis that CD47 regulates adhesive functions of T-cell α4β1 (VLA-4) and αLβ2 (LFA-1) in in vivo and in vitro models of inflammation. Intravital microscopy studies reveal that CD47(−/−) Th1 cells exhibit reduced interactions with wild-type (WT) inflamed cremaster muscle microvessels. Similarly, murine CD47(−/−) Th1 cells, as compared with WT, showed defects in adhesion and transmigration across tumor necrosis factor-α (TNF-α)–activated murine endothelium and in adhesion to immobilized intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion protein 1 (VCAM-1) under flow conditions. Human Jurkat T-cells lacking CD47 also showed reduced adhesion to TNF-α–activated endothelium and ICAM-1 and VCAM-1. In cis interactions between Jurkat T-cell β2 integrins and CD47 were detected by fluorescence lifetime imaging microscopy. Unexpectedly, Jurkat CD47 null cells exhibited a striking defect in β1 and β2 integrin activation in response to Mn(2+) or Mg(2+)/ethylene glycol tetraacetic acid treatment. Our results demonstrate that CD47 associates with β2 integrins and is necessary to induce high-affinity conformations of LFA-1 and VLA-4 that recognize their endothelial cell ligands and support leukocyte adhesion and transendothelial migration

Methyl 2-benzyl-5-[1-(4-methoxy­phen­yl)-4-oxo-3-phenyl­azetidin-2-yl]-4-nitro-3-phenyl­pyrrolidine-2-carboxyl­ate

In the title mol­ecule, C35H33N3O6, the pyrrolidine ring adopts a twist conformation. The mol­ecules are paired into centrosymmetric dimers by weak inter­molecular C—H⋯O hydrogen bonds. The dimers inter­act further again via C—H⋯O hydrogen bonds and N—H⋯O intramolecular interaction also stabilize the crystal packing

Desenvolvimento de competências sociais através de jogos e danças do mundo em crianças de 5 anos

Introducción: La innovación en educación cada vez está más a la orden del día, evolucionando acorde con lo que demanda la sociedad actual, sin embargo, a la hora de innovar en la evaluación de los resultados no encontramos demasiada relevancia. Existen multitud de herramientas que nos permiten realizar evaluaciones de manera más rápida, dinámica y motivante, que hacen este proceso más ameno. Objetivos: Esta propuesta formativa persigue el objetivo de que los participantes descubran nuevas herramientas y aplicaciones tecnológicas para el proceso de evaluación del alumnado y aprendan a utilizarlas en la asignatura de Educación Física, pero también aplicable a otras materias. Métodos: Esta formación se llevará a cabo a través de diferentes sesiones en las cuales a través del aprendizaje cooperativo y la puesta en práctica aprenderán a utilizar herramientas como iDoceo, Socrative y Plickers. Conclusiones: Resulta indispensable que el docente continúe formándose de manera constante, aprendiendo nuevas estrategias y actualizándose conforme lo requiera el contexto en el que se encuentra. A través de estas herramientas conseguimos que se motive tanto el alumnado como el profesorado, al realizar las evaluaciones de forma más rápida y dinámico y haciendo a los estudiantes partícipes del proceso.Introduction: Innovation in education is becoming more and more the order of the day, evolving in accordance with what today's society demands, however, when it comes to innovating in the evaluation of results, we do not find much relevance. There are many tools that allow us to carry out evaluations in a faster, more dynamic and motivating way, which make this process more enjoyable. Aim: This training proposal pursues the objective that the participants discover new technological tools and applications for the student evaluation process and learn to use them in the subject of Physical Education, but also applicable to other subjects. Methods: This training will be carried out through different sessions in which, through cooperative learning and putting into practice, they will learn to use tools such as iDoceo, Socrative and Plickers. Conclusions: It is essential that the teacher continue to train constantly, learning new strategies and updating as required by the context in which they find themselves. Through these tools we manage to motivate both students and teachers, by carrying out assessments more quickly and dynamically and by involving students in the process.Introdução: A inovação na educação está cada vez mais na ordem do dia, evoluindo de acordo com o que a sociedade atual exige, porém, quando se trata de inovar na avaliação de resultados, não encontramos muita relevância. Existem muitas ferramentas que permitem realizar avaliações de forma mais rápida, dinâmica e motivadora, o que torna esse processo mais prazeroso. Objectivos: Esta proposta de formação persegue o objetivo de que os participantes conheçam novas ferramentas e aplicações tecnológicas para o processo de avaliação dos alunos e aprendam a utilizá-las na disciplina de Educação Física, mas também aplicáveis a outras disciplinas. Métodos: Esta formação será realizada através de diferentes sessões em que, através da aprendizagem cooperativa e da prática, aprenderão a utilizar ferramentas como iDoceo, Socrative e Plickers. Conclusões: É fundamental que o professor continue se capacitando constantemente, aprendendo novas estratégias e se atualizando conforme exige o contexto em que se encontra. Através destas ferramentas conseguimos motivar alunos e professores, fazendo avaliações de forma mais rápida e dinâmica e envolvendo os alunos no processo