Mycobacterium tuberculosis multi-drug-resistant strain M induces IL-17+ IFNγ- CD4+ T cell expansion through an IL-23 and TGF-β-dependent mechanism in patients with MDR-TB tuberculosis

We have previously reported that T cells from patients with multidrug-resistant tuberculosis (MDR-TB) express high levels of IL-17 in response to the MDR strain M(Haarlem family) of Mycobacterium tuberculosis (M.tuberculosis). Herein, we explore the pathways involved in the induction of h17 cells in MDR-TB patients and healthy tuberculin reactors (PPD+HD) by the M strain and the laboratory strain H37Rv. Our results show that IL-1β and IL-6 are crucial for the H37Rv and M-induced expansion of IL-17+IFNγ¯ and IL-17+IFNγ+ in CD4+ T cells from MDR-TB and PPD+HD. IL-23 plays an ambiguous role in Th1 and Th17 profiles: alone, IL-23 is responsible for M.tuberculosis induced IL-17 and IFNγ expression in CD4+ T cells from PPD+HD whereas, together with TGF-β, it promotes IL-17+IFNγ¯ expansion in MDR-TB. In fact, spontaneous and M.tuberculosis-induced TGF-β secretion is increased in cells from MDR-TB being theM strain the highest inducer. Interestingly, TLR-2 signaling mediates the expansion of IL-17+IFNγ¯ cells and the enhancement of latency-associated protein (LAP) expression in CD14+ and CD4+ T cells from MDR-TB, which suggests that M strain promotes IL-17+IFNγ¯ T cells through a strong TLR-2-dependent TGF-β production by antigenpresenting cells and CD4+ T cells. Finally, CD4+ T cells from MDR-TB patients infected with MDR Haarlem strains show higher IL-17+IFNγ¯ and lower IL-17+IFNγ+ levels than LAM-infected patients. The present findings deepen our understanding on the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M.tuberculosis strain on the ex vivo Th17 response.Fil: Basile, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Kviatcovsky, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Romero, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Monteserin, Johana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Ritacco, Gloria Viviana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: López, Beatriz. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Sabio y García, Carmen Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: García, A.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas “Dr. Francisco Javier Muñiz”; ArgentinaFil: Vescovo, M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas “Dr. Francisco Javier Muñiz”; ArgentinaFil: Gonzalez Montaner, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas “Dr. Francisco Javier Muñiz”; ArgentinaFil: Palmero, Domingo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas “Dr. Francisco Javier Muñiz”; ArgentinaFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16(+) monocyte population via the IL-10/STAT3 axis

The human CD14+ monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16+ monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by theCD16+CD163+MerTK+pSTAT3+ phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16+CD163+MerTK+pSTAT3+ cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16+CD163+MerTK+pSTAT3+ monocyte-to-macrophage differentiation program and its potential as a target for TB therapy,and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoringof treatment efficacy.Fil: Lastrucci, Claire. Centre National de la Recherche Scientifique; FranciaFil: Bénard, Alan. Centre National de la Recherche Scientifique; FranciaFil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pingris, Karine. Centre National de la Recherche Scientifique; FranciaFil: Souriant, Shanti. Centre National de la Recherche Scientifique; FranciaFil: Poincloux, Renaud. Centre National de la Recherche Scientifique; FranciaFil: Al Saati, Talal. Inserm; FranciaFil: Rasolofo, Voahangy. Pasteur Institute in Antananarivo; MadagascarFil: González Montaner, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Inwentarz, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Moraña, Eduardo José. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Kondova, Ivanela. Biomedical Primate Research Centre; Países BajosFil: Verreck, Franck A. W.. Biomedical Primate Research Centre; Países BajosFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Neyrolles, Olivier. Centre National de la Recherche Scientifique; FranciaFil: Maridonneau Parini, Isabel. Centre National de la Recherche Scientifique; FranciaFil: Lugo Villarino, Geanncarlo. Centre National de la Recherche Scientifique; FranciaFil: Cougoule, Celine. Centre National de la Recherche Scientifique; Franci

estudos artísticos

A revista Gama, Estudos Artísticos estabeleceu-se como um instrumento para a disseminação do conhecimento em torno da arte e da cultura numa perspetiva que se crê inovadora, e que nos caracteriza: estudar arte e artistas através do olhar formado e privilegiado dos companheiros de profissão. Artistas estudam outros artistas. A revista Gama pertence assim a um projeto de resistência: resistência ao centrismo do artworld, ao esmagamento pelos discursos dominantes, às lógicas de reprodução da legitimação instituída. Há uma característica que prevalece em todos os 28 artigos reunidos na presente edição: a reflexão informada sobre autores e obras de arte, que propõe novas leituras e novas redes de conhecimento. Todas juntas constituem um tecido que descobre sentidos, na sua integração global na nova paisagem cultural.info:eu-repo/semantics/publishedVersio

Dime corazón, ¿qué sabes de tu enfermedad y qué te gustaría saber?

• Introduction: Heart failure (HF) has become an important and increasing health problem in developed countries, due to, specially, the ageing of the population. In our country it is the first cause of hospital admissions in people over 65 and the third cause of cardiovascular mortality. • Aims: To know how much information patients have about their pathology. To detect improving areas as well as strong areas in nurse-directed education. To obtain a higher autonomy and quality of life on HF patients, reducing their mortality. • Materials and method: HF patients admitted in our ward are interviewed in order to detect how much they know about their disease, in December 2008. Bibliographical revision. Analysis of clinical-statistical information on admitted patients during 2007 with HF diagnosis. • Results: 284 HF patients were admitted, 48 were readmitted. Survey: 25 people. Average age: 73,12 years old. Knowledge of pharmacological treatment: Most of them didn’t know about treatment indications and nobody of them knew something about adverse effects. 76% never got any nursing medical education. 40 % knows about symptoms of alarm. 48% take a low salt diet. Educational interests: 52%: cause of their disease and risk factors. 64%: exacerbation of the disease. 56%: Diet. The educational interests of patients and informal carers differed between them. Conclusions: An important lack of knowledge of HF is detected in our patients and carers. It becomes important to involve both groups (patients and carers) on heart failure education, being the final objective to get a better quality of life.• Introducción: La insuficiencia cardiaca (IC) se ha convertido en un importante y creciente problema de salud en los países desarrollados debido, principalmente, al envejecimiento de la población. En nuestro país supone la principal causa de ingreso hospitalario en mayores de 65 años y la tercera causa de mortalidad cardiovascular. • Objetivos: Conocer qué grado de información tienen los pacientes sobre su patología. Detectar áreas de mejora y áreas fuertes en la educación sanitaria de enfermería. Mejorar la autonomía y calidad de vida de los pacientes con IC, disminuyendo la morbilidad. • Material y método: Se encuesta a los pacientes ingresados con IC en nuestra unidad para detectar el grado de conocimiento sobre su enfermedad, en diciembre del 2008. Revisión bibliográfica. Análisis de los datos clínicos-estadísticos de los ingresados en el 2007 con el diagnóstico de IC. • Resultados: Ingresaron por IC 284, 48 reingresaron. Encuesta: 25 personas. Edad media: 73,12 años. Conocimiento sobre tratamiento farmacológico: La mayoría desconocía las indicaciones del tratamiento y un 100% los efectos adversos. Un 76% no habían recibido nunca educación sanitaria de enfermería. El 40% conoce los síntomas de alarma. El 48% realiza dieta hiposódica. Intereses educacionales: 52%: causas de su enfermedad y factores de riesgo. 64%: reagudizaciones. 56%.: Dieta. Los intereses educacionales de los pacientes y cuidadores informales diferían. • Conclusiones: Se detecta un déficit importante de conocimiento sobre la IC en nuestros pacientes y cuidadores. Importante implicar a los dos grupos (pacientes y cuidadores), en la educación sanitaria, siendo el objetivo final la mejora de la calidad de vida

Nuevos retos en la atención de enfermería en el paciente crónico con insuficiencia cardíaca

• Introduction: HF is a high prevalence condition that causes negative consequences on life quality on people who suffers the disease. Patients expectations on health service has evolved, from a paternalist approach, to an holistic one. Patientnurse relationship is charged with emotions. Patients, being at a more vulnerable state, feel lots of negative emotions, expecting from nursing staff care that preserves their dignity. • Aims: Reflect on our role as nurses providing care for HF patients. Do a critical judgement on our daily performance as an opportunity to improve practise. • Material and method: Literature review. Reflect on how we want to provide our services and how the therapeutic relationship with patients should be. Group meetings. Sharing and discussing ideas. • Results: “... On our hospitals we do not always have time, due to many different issues, to provide a good quality holistic care to patients. This means that we only provide clinical care on the acute state of the condition...” “... The main carer is not involved on HF education, and when the patient is discharged, is the main carer the one who is going to be looking after the patient...” “... All our efforts are nothing if we do not involve patients on their health process...” • Conclusions: Nursing staff is responsible not only for providing care for these patients, but also should help them to cope with disability, respecting their believes, and giving respond to educational needs. It is a challenge for nurses to develop pathways and teaching sessions on the wards. We think it is important to reflect on our daily practise in order to advance on the care that is being delivered.• Introducción: La IC es un síndrome de alta prevalencia; provoca consecuencias negativas en la calidad de vida de quien las padece. La demanda sanitaria del paciente ha evolucionado, desde una perspectiva paternalista, hacia una holística. La relación enfermera-paciente está cargada de emociones. El paciente es más vulnerable, siente una pléyade de emociones negativas, esperando de nosotras un trato que preserve su dignidad. • Objetivos: Reflexionar sobre nuestro papel como enfermeras en la atención al paciente crónico con IC. Realizar un juicio crítico sobre nuestro quehacer diario como área de mejora. • Material y metodología: Estudio cualitativo. Revisión bibliográfica. Autorreflexión sobre cómo queremos trabajar y cómo tiene que ser la relación con el enfermo. Reuniones de grupo. Puesta en común. • Resultados: “… En nuestro medio hospitalario, no siempre tenemos tiempo, debido a múltiples factores, para prestar una atención integral de calidad a los pacientes, quedándonos sólo en la prestación asistencial en el cuadro agudo…. ” “… No se implica, en la educación sanitaria, al cuidador informal, cuando sobre éste recae el cuidado al alta del paciente…”. “… De nada sirven todos nuestros esfuerzos, si al paciente no le hacemos partícipe de su proceso de salud…” • Conclusiones: Las enfermeras tenemos la responsabilidad no sólo de prestar asistencia, sino que también tenemos que ayudar a afrontar la incapacidad, respetar sus valores y creencias, atendiendo a sus necesidades educativas. Es un reto para las enfermeras elaborar guías y sesiones de educación sanitaria en las unidades de hospitalización Creemos importante reflexionar sobre nuestro trabajo diario para dar un paso más en los cuidados prestados

Cuidados paliativos en insuficiencia cardiaca (IC ) ¿podemos hacer más?

� Introduction: Heart failure (HF) is a serious condition equivalent to a malignant disease in terms of symptom burden and mortality. Its palliative care is underdeveloped despite being (together with optimal treatment) necessary to achieve an adequate control of symptoms and patient comfort. � Objectives: To assess the current situation of palliative care in HF. To evaluate the efficacy of nursing care regarding the control of symptoms in patients with terminal HF. To identify weak areas in order to improve the care of patients with end-stage HF. � Material and methods: Descriptive, retrospective study. Data were obtained from medical and nursery records of patients who died in our hospital with a diagnosis of HF during the period 2008/09. � Results: NIC quantification: � NIC 2080 Management of fluids and electrolytes 70,9% � NIC 6680 Monitorization of vital signs 100% � NIC 1400 Management of pain 90.9% � NIC 5290 Grieve support 5.5% � NIC 5420 Spiritual support 38.2% NOC comparison by means of the McNemar-Bowker test. � NOC 0400 Effectiveness of heart pump p<0.001 � NOC 1302 Facing of problems p= 0.317 � NOC 1307 Providing a good death p =0.035 � NOC 2001 Emotional health p=0.368 � Conclusions: Hospital care for patients with end-stage HF focuses on solving acute symptoms, leaving the psychosocial and spiritual needs of the patients and their families aside. Patients are not evaluated as a whole. It is necessary to coordinate health care professionals from different areas to reduce a fragmentation in the care of the patients and to improve the patient support and continuity of care� Introducción: La insuficiencia cardiaca (IC) es una afección grave equivalente a una enfermedad maligna en términos de carga de síntomas y mortalidad. Los cuidados paliativos están poco desarrollados en la IC, a pesar de ser, junto al tratamiento médico óptimo, necesarios para el adecuado control de síntomas y conseguir el máximo bienestar del paciente. � Objetivos: Conocer la realidad asistencial de la prestación de cuidados paliativos en IC. Evaluar la eficacia de los cuidados de enfermería respecto al control de síntomas en el paciente terminal con IC. Identificar áreas débiles y de mejora en el cuidado al paciente con IC terminal. � Material y métodos: Estudio descriptivo, retrospectivo. Se recogen datos de historias clínicas, planes de cuidados y evolutivos de enfermería, de pacientes fallecidos con diagnóstico principal de insuficiencia cardiaca, durante los años 2008-09. � Resultados: Cuantificación de NIC en patrones alterados: � NIC 2080 Manejo de líquidos, electrolítos 70,9% � NIC 6680 Monitorización signos vitales 100% � NIC 1400 Manejo del dolor 90.9% � NIC 5290 Facilitar el duelo 5.5% � NIC 5420 Apoyo espiritual 38.2% Comparación de NOC mediante la prueba de McNemar-Bowker. � NOC 0400 Efectividad bomba cardiaca, p<0.001 � NOC 1302 Afrontamiento problemas p= 0.317 � NOC 1307 Muerte digna p =0.135 � NOC 2001 Salud espiritual p=0.368 � Conclusiones: La atención hospitalaria al paciente con IC terminal se centra en la resolución del cuadro agudo y en el alivio de síntomas físicos, relegando las necesidades psicosociales y espirituales y la atención al duelo y a las familias. No se tiene una percepción holística del paciente como un todo. Es necesaria la coordinación entre profesionales de los diferentes nivel

Mycobacterium tuberculosis Triggers Apoptosis in Peripheral Neutrophils Involving Toll-Like Receptor 2 and p38 Mitogen Protein Kinase in Tuberculosis Patients

Polymorphonuclear neutrophils (PMN) exposed to Mycobacterium tuberculosis display bactericidal responses and produce inflammatory proteins. This PMN-mediated inflammatory response is regulated by an activation of the apoptotic program, which collaborates to avoid tissue injury. In vitro, circulating PMN from patients with tuberculosis (TB) show an increased spontaneous apoptosis, and M. tuberculosis-induced activation accelerates the PMN apoptosis. In this study, we evaluated the mechanisms involved in spontaneous and M. tuberculosis-induced apoptosis. We demonstrate that apoptosis of PMN is not induced by lipoarabinomannan or by a whole-cell lysate of M. tuberculosis and that neither tumor necrosis factor alpha nor CD11b, CD14, and Fcγ receptors are involved. Apoptosis of PMN from patients with active TB (TB-PMN) is induced by the interaction with the whole M. tuberculosis via Toll-like receptor 2 (TLR2), and, in contrast to spontaneous apoptosis, it involves the p38 mitogen-activated protein kinase (MAPK) pathway. These results correlate with a high expression of phosphorylated p38 (p-p38) in circulating TB-PMN and with the ability of M. tuberculosis to induce in vitro the expression of p-p38 in PMN. Therefore, when the bacterial burden is low, TB-PMN could be detecting nonopsonized M. tuberculosis via TLR2, leading to the activation of the p38 MAPK pathway, which in turn would induce PMN activation and apoptosis. This mechanism needs further confirmation at the site of infection

IL-9 promotes anti-Mycobacterium leprae cytotoxicity: involvement of IFNγ

Interleukin 9 (IL-9) is a T-cell derived factor preferentially expressed by CD4+ Th2 cells and it has been characterized both in human and murine systems. It is a pleiotropic cytokine with multiple functions on cells of the lymphoid, myeloid and mast cell lineages, as well as on lung epithelial cells. Other activities described for IL-9 support its contribution to asthma and its important role in helminthic infections, where a Th2 response can be protective and IL-9 enhances resistance or is responsible for elimination of the nematode. Nevertheless, until recently there were no studies on its role in bacterial infections in man. We have demonstrated that cytokines can modulate the specific cytotoxicity generation in peripheral blood mononuclear cells from leprosy patients and normal controls. In the present report we studied the effect of IL-9 in this experimental model. Our results indicate that IL-9 can counteract the negative effect mediated by IL-4 on the generation of M. leprae-induced cytotoxic T lymphocytes. Moreover, it can increase this lytic activity in controls and enhance the stimulatory effect of IL-2 or IL-6 in cells from leprosy patients and controls. IL-9 is also able to revert the inhibitory effect of IL-10 and IL-13 on the M. leprae-induced cytotoxic activity. Although the exact mechanism of action of IL-9 remains to be determined, interferon gamma seems to be required for the effect of IL-9 in this experimental model. These data suggest that IL-9 may have an atypical Th2 behaviour and play a role in the modulation of the immune response to mycobacterial infections