Thalidomide modulates Mycobacterium leprae-induced NF-κB pathway and lower cytokine response

AbstractIt is widely accepted that tumor necrosis factor alpha (TNF-α) plays a critical role in the development of tissue and nerve damage in leprosy and during the reactional episodes of acute inflammation. Thalidomide (N-α-phthalimidoglutarimide), a drug used to treat leprosy reaction, modulates immune response, inhibits inflammation and NF-κB activity. Here we investigated whether thalidomide inhibits NF-κB activation induced by Mycobacterium leprae, p38 and ERK1/2 MAPK activation. EMSA and supershift assays were performed to investigate NF-κB activation in response to M. leprae and its modulation following in vitro treatment with thalidomide. Luciferase assay was assayed in transfected THP-1 cells to determine NF-κB transcriptional activity. Flow cytometry and immunofluorescence were used to investigate p65 accumulation in the nucleus. Immunoblotting was used to investigate p38 and ERK1/2 phosphorylation. Following activation of PBMC and monocytes with M. leprae, the formation and nuclear localization of NF-κB complexes composed mainly of p65/p50 and p50/p50 dimers was observed. Induction of NF-κB activation and DNA binding activity was inhibited by thalidomide. The drug also reduced M. leprae-induced TNF-α production and inhibited p38 and ERK1/2 activation. Definition of the activation mechanisms in cells stimulated with M. leprae can lead to the development of new therapy applications to modulate NF-κB activation and to control the inflammatory manifestations due to enhanced TNF-α response as observed in leprosy and in leprosy reactions

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Factores asociados al abandono y al fallecimiento por casos de tuberculosis farmacorresistente (TBFR), atendidos en un centro de referencia en Río de Janeiro, Brasil

Submitted by Regiane Silva ([email protected]) on 2018-07-24T13:41:22Z No. of bitstreams: 1 Fatores associados ao abandono e ao óbito de casos de tuberculose drogarresistente (TBDR).pdf: 589134 bytes, checksum: f17a38577065beecbaa49df728525ca6 (MD5)Approved for entry into archive by Regiane Silva ([email protected]) on 2018-07-24T18:14:54Z (GMT) No. of bitstreams: 1 Fatores associados ao abandono e ao óbito de casos de tuberculose drogarresistente (TBDR).pdf: 589134 bytes, checksum: f17a38577065beecbaa49df728525ca6 (MD5)Made available in DSpace on 2018-07-24T18:14:54Z (GMT). No. of bitstreams: 1 Fatores associados ao abandono e ao óbito de casos de tuberculose drogarresistente (TBDR).pdf: 589134 bytes, checksum: f17a38577065beecbaa49df728525ca6 (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Rio de Janeiro, RJ, Brasil.A tuberculose drogarresistente (TBDR) representa hoje uma grave ameaça aos avanços no controle da tuberculose (TB) no Brasil e no mundo. Neste estudo, investigam-se fatores associados ao abandono e ao óbito de casos em tratamento para TBDR, em um centro de referência terciária do Município do Rio de Janeiro, Brasil. Trata-se de um estudo de coorte retrospectiva, a partir dos casos notificados no Sistema de Informação de Tratamentos Especiais de Tuberculose (SITETB), no período de 1o de janeiro de 2012 a 31 de dezembro de 2013. Um total de 257 pacientes foi notificado no SITETB e iniciou o tratamento para TBDR. Desse total, 139 (54,1%) tiveram sucesso terapêutico como desfecho, 54 (21%) abandonaram o tratamento e 21 (8,2%) evoluíram para óbito. Após análise de regressão logística multinomial múltipla, a faixa etária acima de cinquenta anos foi observada como único fator de proteção ao abandono, ao passo que ter menos de oito anos de escolaridade e reingresso após abandono foram considerados como fatores de risco. Reingresso após abandono, recidiva e falência indicaram fatores de risco. Nossos dados reforçam a concepção de que o abandono do tratamento de tuberculose resistente é um sério problema de saúde pública, sendo necessário um adequado acompanhamento no tratamento de pacientes com esse histórico e com baixa escolaridade. Além disso, uma rede de apoio social ao paciente é imprescindível para que desfechos desfavoráveis sejam evitados.Drug-resistant tuberculosis (DR-TB) poses a serious threat to tuberculosis (TB) control in Brazil and worldwide. The current study investigated factors associated with loss to follow-up and death in the course of treatment for DR-TB in a tertiary reference center in the city of Rio de Janeiro, Brazil. This was a retrospective cohort study of cases reported to the Information System on Special Treatments for Tuberculosis (SITETB) from January 1, 2012, to December 31, 2013. A total of 257 patients were reported to the SITETB and initiated treatment for DR-TB. Of this total, 139 (54.1%) achieved treatment success as the outcome, 54 (21%) were lost to follow-up, and 21 (8.2%) died. Following a multiple multinomial logistic regression analysis, the age bracket older than 50 years was the only protective factor against loss to follow-up, whereas less than eight years of schooling and reentry after loss to follow-up were considered risk factors. Reentry after loss to followup, relapse, and treatment failure appeared as risk factors. Our data reinforce the concept that loss to follow-up in drug-resistant tuberculosis is a serious public health problem, and that adequate follow-up of treatment is necessary in patients with this history and low schooling. A social support network for patients is also indispensable for avoiding unfavorable outcomes.La tuberculosis farmacorresistente (TBFR) representa hoy una grave amenaza para los avances en el control de la tuberculosis (TB) en Brasil y en el mundo. En este estudio, se investigan factores asociados al abandono y al óbito de casos en tratamiento para TBDR, dentro de un centro de referencia de carácter terciario del municipio de Río de Janeiro, Brasil. Se trata de un estudio de cohorte retrospectiva, a partir de los casos notificados en el Sistema de Información de Tratamientos Especiales de Tuberculosis (SITETB), durante el período del 1 de enero de 2012 al 31 de diciembre de 2013. Un total de 257 pacientes fue notificado en el SITETB y comenzó el tratamiento para TBDR. De ese total, 139 (un 54,1%) tuvieron éxito terapéutico como desenlace, 54 (un 21%) abandonaron el tratamiento y un 21 (8,2%) evolucionaron hacia óbito. Tras el análisis de regresión logística multinomial múltiple, la franja de edad por encima de cincuenta años se observó como el único factor de protección al abandono, al mismo tiempo que tener menos de ocho años de escolaridad y reingresar en el sistema educativo tras el abandono fueron considerados como factores de riesgo. Reingreso tras abandono, recidiva e insolvencia indicaron factores de riesgo. Nuestros datos refuerzan la concepción de que el abandono del tratamiento de tuberculosis resistente es un serio problema de salud pública, siendo necesario un adecuado acompañamiento en el tratamiento de pacientes con este historial y con baja escolaridad. Además, una red de apoyo social entorno al paciente es imprescindible para que los desenlaces desfavorables sean evitados

First detection of Mycobacterium triplex in Latin America

In this study we describe the first isolation of Mycobacterium triplex in Latin America. This species causes infections in humans, with very few reports from around the world. We isolated two sputum specimens of a patient with a 6-year history of human immunodeficiency and tuberculosis treatment failure. All tests used confirmed M. triplex and the patient responded well to drug therapy for 18 months

Whole genome sequence of Mycobacterium kansasii isolates of the genotype 1 from Brazilian patients with pulmonary disease demonstrates considerable heterogeneity.

Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil

Testiradan toimintavarmuuden parantaminen

Työntarkoituksena oli parantaa katsastusaseman, sään vaihteluille alttiina olevan, testiradan toimintavarmuutta ja lisätä mittatarkkuutta, sekä toistomahdollisuutta muuttuvista keliolosuhteista huolimatta. Testiradan korjauksen kohteena olevat osat olivat heilahduksenvaimentimien testauslaite ja jarrudynamometri. Työssä käsiteltiin kyseisten mittalaitteiden toimintaperiaatteita, sekä niiden käytöstä aiheutuvaa kulumista. Varsinainen työ oli näiden mittalaitteiden kulumisesta aiheutuneiden mahdollisten mittaustarkkuuteen vaikuttavien tekijöiden poistaminen tai ainakin mittatarkkuuden heikkenemisen minimointi. Lisäksi tavoitteena oli parantaa laitteiden huollettavuutta, sekä pidentää niiden käyttöikää. Parannusten jälkeiseen laitteiston toimivuuteen oltiin tyytyväisiä. Joitain kulumisen mukanaan tuomia mahdollisia puutteita tai uusia parannuskohteita ei korjauksen jälkeen pystytty arvioimaan lyhyestä seurantajaksosta johtuen.The aim of the work was to improve inspection station`s reliability of the test track. It is exposed to variable weather conditions and sometimes in harsh Finnish winter, reliability of measuring and testing brakes and shock absorbers is at stakes. Main goal is to minimize this risk of measuring errors and make testing repeatability higher. Parts of the test track that were repaired were brake dynamometer and shock absorber tester. During this work, basic principles of how these instruments work are explained. Also the most common problems caused by wearing are presented and showed how they can be repaired. Or at least minimize the defect of the wear. Reliability and maintainability should be increased by these repairing’s. After repairs, functionality of the gadgets increased and reliability should come to higher level. Despite lack of time, during following period of surveying the most of the units of measure were just like they should have been after the repairs