Comparación de la agudeza visual en visión de cerca y visión de lejos bajo diferentes iluminaciones en una muestra de población infantil

OBJECTIU Analitzar els valors de la agudesa visual (AV) en una població jove i sana, en funció dels tipus de color de la llum que incideixen sobre l’optotip (vermell, blau, verd i blanc) i la distància d’observació (lluny-prop). A més a més, es farà una comparació amb els resultats obtinguts amb altres estudis científics. METODOLOGIA L’estudi s’ha realitzat amb una mostra de 10 pacients, 5 dones y 5 homes, amb un rang d’edats entre els 9 y 16 anys. La part experimental s’ha dut a terme en un banc òptic i el procés de muntatge es divideix en 3 parts: creació e impressió de l’optotip, calibratge de les llums LED i el muntatge final. El procediment es el següent: es col·loca l’optotip a 33 cm del subjecte, que estarà col·locat en una mentonera, i s’il·lumina l’optotip mitjançant les quatre il·luminats LED. Anotarem en cada cas la màxima agudesa visual que aconsegueix l’observador, tant per visió propera com per visió llunyana. Per tant, s’obtindrà 8 mesures totals per subjecte. CONCLUSIÓ La millor AV s'obté amb el LED verd i el blanc, ja que les imatges amb les dues llums s'enfocaran sobre la retina. L'AV amb la llum vermella és similar a les AV amb la llum verda i blanca, ja que amb longituds d’ona llarga l'ull actua com si fos hipermetrop i podrà compensar mitjançant l'acomodació la falta de potència. En canvi, la llum blava provoca un efecte de miopia, la qual no podrà ser compensada pel sistema visual. Per tant, l'aberració cromàtica si afecta el rendiment visual

Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle

The cell wall of Mycobacterium tuberculosis is composed of diverse glycolipids which potentially interact with the human immune system. To overcome difficulties in obtaining pure compounds from bacterial extracts, we recently synthesized three forms of mycobacterial diacyltrehalose (DAT) that differ in their fatty acid composition, DAT1, DAT2, and DAT3. To study the potential recognition of DATs by human T cells, we treated the lipid-binding antigen presenting molecule CD1b with synthetic DATs and looked for T cells that bound the complex. DAT1- and DAT2-treated CD1b tetramers were recognized by T cells, but DAT3-treated CD1b tetramers were not. A T cell line derived using CD1b-DAT2 tetramers showed that there is no cross-reactivity between DATs in an IFN-γ release assay, suggesting that the chemical structure of the fatty acid at the 3-position determines recognition by T cells. In contrast with the lack of recognition of DAT3 by human T cells, DAT3, but not DAT1 or DAT2, activates Mincle. Thus, we show that the mycobacterial lipid DAT can be both an antigen for T cells and an agonist for the innate Mincle receptor, and that small chemical differences determine recognition by different parts of the immune system

A TCR beta-Chain Motif Biases toward Recognition of Human CD1 Proteins

High-throughput TCR sequencing allows interrogation of the human TCR repertoire, potentially connecting TCR sequences to antigenic targets. Unlike the highly polymorphic MHC proteins, monomorphic Ag-presenting molecules such as MR1, CD1d, and CD1b present Ags to T cells with species-wide TCR motifs. CD1b tetramer studies and a survey of the 27 published CD1b-restricted TCRs demonstrated a TCR motif in humans defined by the TCR β-chain variable gene 4-1 (TRBV4-1) region. Unexpectedly, TRBV4-1 was involved in recognition of CD1b regardless of the chemical class of the carried lipid. Crystal structures of two CD1b-specific TRBV4-1+ TCRs show that germline-encoded residues in CDR1 and CDR3 regions of TRBV4-1–encoded sequences interact with each other and consolidate the surface of the TCR. Mutational studies identified a key positively charged residue in TRBV4-1 and a key negatively charged residue in CD1b that is shared with CD1c, which is also recognized by TRBV4-1 TCRs. These data show that one TCR V region can mediate a mechanism of recognition of two related monomorphic Ag-presenting molecules that does not rely on a defined lipid Ag

Multimodal memory T cell profiling identifies a reduction in a polyfunctional Th17 state associated with tuberculosis progression

Mycobacterium tuberculosis (M.tb) results in 10 million active tuberculosis (TB) cases and 1.5 million deaths each year, making it the world's leading infectious cause of death. Infection leads to either an asymptomatic latent state or TB disease. Memory T cells have been implicated in TB disease progression, but the specific cell states involved have not yet been delineated because of the limited scope of traditional profiling strategies. Furthermore, immune activation during infection confounds underlying differences in T cell state distributions that influence risk of progression. Here, we used a multimodal single-cell approach to integrate measurements of transcripts and 30 functionally relevant surface proteins to comprehensively define the memory T cell landscape at steady state (i.e., outside of active infection). We profiled 500,000 memory T cells from 259 Peruvians > 4.7 years after they had either latent M.tb infection or active disease and defined 31 distinct memory T cell states, including a CD4+CD26+CD161+CCR6+ effector memory state that was significantly reduced in patients who had developed active TB (OR = 0.80, 95% CI: 0.73-0.87, p = 1.21 x 10-6). This state was also polyfunctional; in ex vivo stimulation, it was enriched for IL-17 and IL-22 production, consistent with a Th17-skewed phenotype, but also had more capacity to produce IFNgamma than other CD161+CCR6+ Th17 cells. Additionally, in progressors, IL-17 and IL-22 production in this cell state was significantly lower than in non-progressors. Reduced abundance and function of this state may be an important factor in failure to control M.tb infection. ### Competing Interest Statement The authors have declared no competing interest

Comparación de la agudeza visual en visión de cerca y visión de lejos bajo diferentes iluminaciones en una muestra de población infantil

OBJECTIU Analitzar els valors de la agudesa visual (AV) en una població jove i sana, en funció dels tipus de color de la llum que incideixen sobre l’optotip (vermell, blau, verd i blanc) i la distància d’observació (lluny-prop). A més a més, es farà una comparació amb els resultats obtinguts amb altres estudis científics. METODOLOGIA L’estudi s’ha realitzat amb una mostra de 10 pacients, 5 dones y 5 homes, amb un rang d’edats entre els 9 y 16 anys. La part experimental s’ha dut a terme en un banc òptic i el procés de muntatge es divideix en 3 parts: creació e impressió de l’optotip, calibratge de les llums LED i el muntatge final. El procediment es el següent: es col·loca l’optotip a 33 cm del subjecte, que estarà col·locat en una mentonera, i s’il·lumina l’optotip mitjançant les quatre il·luminats LED. Anotarem en cada cas la màxima agudesa visual que aconsegueix l’observador, tant per visió propera com per visió llunyana. Per tant, s’obtindrà 8 mesures totals per subjecte. CONCLUSIÓ La millor AV s'obté amb el LED verd i el blanc, ja que les imatges amb les dues llums s'enfocaran sobre la retina. L'AV amb la llum vermella és similar a les AV amb la llum verda i blanca, ja que amb longituds d’ona llarga l'ull actua com si fos hipermetrop i podrà compensar mitjançant l'acomodació la falta de potència. En canvi, la llum blava provoca un efecte de miopia, la qual no podrà ser compensada pel sistema visual. Per tant, l'aberració cromàtica si afecta el rendiment visual

High prevalence and heterogeneity of Dysglycemia in patients with tuberculosis from Peru: a prospective cohort study

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-29T11:51:28Z No. of bitstreams: 1 Calderon, R. High....pdf: 2042526 bytes, checksum: 3f541403ffb4892d058d895c77a33074 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-29T12:12:29Z (GMT) No. of bitstreams: 1 Calderon, R. High....pdf: 2042526 bytes, checksum: 3f541403ffb4892d058d895c77a33074 (MD5)Made available in DSpace on 2019-10-29T12:12:29Z (GMT). No. of bitstreams: 1 Calderon, R. High....pdf: 2042526 bytes, checksum: 3f541403ffb4892d058d895c77a33074 (MD5) Previous issue date: 2019-01-11Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica (CONCYTEC-Peru) / Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (FONDECYT, Convenio 175–2015). The work from BBA was supported by intramural research program from FIOCRUZ, by the National Institutes of Health (U01AI115940 and U01AI069923) and by the Departamento de Ciência e Tecnologia (DECIT) - Secretaria de Ciência e Tecnologia (SCTIE) – Ministério da Saúde (MS), Brazil (25029.000507/2013–07). MBA receives a fellowship from the Fundação de Amparo à Pesquisa da Bahia (FAPESB). BBA is a senior scientist from the Conselho Nacional de Desenvolvimento Científico e Tecnológico.Socios en Salud Sucursal Peru. Lima, Peru / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Socios en Salud Sucursal Peru. Lima, Peru.Socios en Salud Sucursal Peru. Lima, Peru.Socios en Salud Sucursal Peru. Lima, Peru.Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Harvard Medical School / Department of Global Health and Social Medicine. Boston, MA, USA.Socios en Salud Sucursal Peru. Lima, Peru / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Universidade de Salvador. Salvador, BA, Brasil /Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.The accuracy of different laboratory tests for diagnosis of diabetes mellitus (DM) and prediabetes (preDM) in populations exposed to tuberculosis (TB) remains poorly understood. Here, we examined the prevalence of DM and preDM in TB affected people in Lima, Peru. Methods: A prospective cohort study of patients affected TB and their household contacts (HHC), was conducted between February and November 2017 in Lima, Peru. Fasting plasma glucose (FPG), HbA1c and oral glucose tolerance test (OGTT) were used to detect DM and preDM in a prospective cohort of TB patients (n = 136) and household contacts (n = 138). Diagnostic performance of the laboratory tests was analyzed. Potential effects of sociodemographic and clinical factors on detection of dysglycemia were analyzed. Results: In TB patients, prevalence of DM and preDM was 13.97 and 30.88% respectively. Lower prevalence of both DM (6.52%) and preDM (28.99%) were observed in contacts. FPG, HbA1c and OGTT had poor agreement in detection of preDM in either TB cases or contacts. TB-DM patients had substantially lower hemoglobin levels, which resulted in low accuracy of HbA1c-based diagnosis. Classic sociodemographic and clinical characteristics were not different between TB patients with or without dysglycemia. Conclusion: High prevalence of DM and preDM was found in both TB patients and contacts in Lima. Anemia was strongly associated with TB-DM, which directly affected the diagnostic performance of HbA1c in such population

Severe pulmonary radiological manifestations are associated with a distinct biochemical profile in blood of tuberculosis patients with dysglycemia

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2020-03-13T13:02:25Z No. of bitstreams: 1 Ponce, N.B. Severe....pdf: 2056545 bytes, checksum: cc833879bc0e28b6d17d3a4cab72ba40 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2020-03-13T13:22:44Z (GMT) No. of bitstreams: 1 Ponce, N.B. Severe....pdf: 2056545 bytes, checksum: cc833879bc0e28b6d17d3a4cab72ba40 (MD5)Made available in DSpace on 2020-03-13T13:22:44Z (GMT). No. of bitstreams: 1 Ponce, N.B. Severe....pdf: 2056545 bytes, checksum: cc833879bc0e28b6d17d3a4cab72ba40 (MD5) Previous issue date: 2020-01-14Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica (CONCYTEC-Peru) / Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (FONDECYT, Convenio 173–2015). MBA receives a fellowship from the Fundação de Amparo à Pesquisa da Bahia (FAPESB).Socios En Salud Sucursal Peru. Lima, Peru / Universidad Nacional Mayor de San Marcos. Lima, Peru.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Socios En Salud Sucursal Peru. Lima, Peru.Socios En Salud Sucursal Peru. Lima, Peru / Universidad Nacional Mayor de San Marcos. Lima, Peru / Harvard Medical School. Brigham and Women’s Hospital. Division of Rheumatology, Inflammation, and Immunity. Boston, MA, USA.Socios En Salud Sucursal Peru. Lima, Peru.Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Universidade Salvador. Salvador, BA, Brasil.Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Universidade Salvador. Salvador, BA, Brasil.Socios En Salud Sucursal Peru. Lima, PeruUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Universidade Salvador. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Socios En Salud Sucursal Peru. Lima, Peru / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.Diabetes mellitus (DM) is thought to affect tuberculosis (TB) clinical presentation and treatment response. Whether DM impacts radiological manifestations of pulmonary TB is still not clear. This study investigated the impact of glycemic status on radiological manifestations of pulmonary TB cases and its relationship with concentration of biochemical parameters in peripheral blood. Methods: A retrospective cross-sectional study used data from 132 microbiologically confirmed pulmonary TB patients from Lima, Peru, evaluated in a previous investigation performed between February and December 2017. Chest radiographs were analyzed by a radiologist and a pulmonologist. Radiographic lesions were identified as cavities, alveolar infiltrates and fibrous tracts. Hyperglycemia in TB patients was identified by use of fasting plasma glucose, HbA1c and oral glucose tolerance test. Clinical, biochemical and hematological parameters were also analyzed. Results: TB patients with hyperglycemia presented more frequently with cavities, alveolar infiltrates and fibrous tracts than those with normoglycemia. Hierarchical clustering analysis indicated that patients with more diverse and higher number of lung lesions exhibited a distinct laboratorial profile characterized by heightened white blood cell counts and circulating levels of total cholesterol, triglycerides and transaminases and simultaneously low levels of albumin and hemoglobin. Multivariable regression analyses adjusted for age, sex, prior TB, hemoglobin levels and acid-fast bacilli ≥2+ in sputum smears, demonstrated that presence of prediabetes or diabetes in TB patients was associated with increased odds of having 3 pulmonary lesion types (p = 0.003 and p < 0.01 respectively) or ≥ 4 lesions (p = 0.001 and p = 0.01 respectively). Conclusion: Hyperglycemia (both DM and prediabetes) significantly affected the presentation of radiographic manifestations and the number of lesions in pulmonary TB patients as well as the biochemical profile in peripheral blood

CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State

The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysis of T cell clones suggested that semi-invariant TCRs exist in the CD1b system, but their prevalence in humans is not known. Here we used CD1b tetramers loaded with mycolic acid or glucose monomycolate to study polyclonal T cells from 150 Peruvian subjects. We found that CD1b tetramers loaded with mycolic acid or glucose monomycolate antigens stained TRAV1-2+ GEM T cells or TRBV4-1+ LDN5-like T cells in the majority of subjects tested, at rates ~10-fold lower than NKT cells. Thus, GEM T cells and LDN5-like T cells are a normal part of the human immune system. Unlike prior studies measuring MHC- or CD1b-mediated activation, this large-scale tetramer study found no significant differences in rates of CD1b tetramer-mycobacterial lipid staining of T cells among subjects with Mtb exposure, latent Mtb infection or active tuberculosis (TB) disease. In all subjects, including 'uninfected' subjects, CD1b tetramer+ T cells expressed memory markers at high levels. However, among controls with lower mycobacterial antigen exposure in Boston, we found significantly lower frequencies of T cells staining with CD1b tetramers loaded with mycobacterial lipids. These data link CD1b-specific T cell detection to mycobacterial exposure, but not TB disease status, which potentially explains differences in outcomes among CD1-based clinical studies, which used control subjects with low Mtb exposure