Advances in leprosy immunology and the field application: a gap to bridge

Advances concerning the hosts' immune response to Mycobacterium leprae infection have focused on elucidating the immune pathomechanisms involved, with the hope that predictive diagnostic and prognostic parameters (biomarkers) for field use would emerge; however, improvements in our understanding of the immunologic responses to this complex disease have, to date, somewhat failed to provide the effective and robust methods for improving its predictive diagnosis in the field situation, particularly in those patients suffering from paucibacillary disease. In this contribution we have attempted to review some of the advances both in the immunology and immunopathology of leprosy, and also highlight the limited clusters of immune parameters that are now available. Most importantly, we point out the limitations that still prevail in the provision of effective biomarkers in the field situation for either: (1) the diagnosis of indeterminate disease, (2) predictive diagnosis of individuals developing reactional states, (3) monitoring efficacy of treatment, or (4) monitoring treatment of reactional state

Reduced expression of mir15a in the blood of patients with oral squamous cell carcinoma is associated with tumor staging

MicroRNAs (miRNAs) mirl 5a and let7a are iMportant regulators of bcl-2, ras and c-myc proteins Considering that these miRNAs are commonly altered in many human cancers and that these proteins are reported to be altered in oral squamous cell carcinoma (OSCC), we investigated them in a set of OSCC cases \u27I he miRNAs as well as the proteins were evaluated in the tumor and blood of 20 patients by real-time quantitative PCR and iMmunohistochemistry, respectively The expression of nfirl5a and bcl-2 proteins in the tumors was not associated with each other or with tumor staging On the other hand, we found reduced expression of this miRNA in the blood of patients with an advanced stage of OSCC and with lymph node metastasis The expression of let7a in the tumor and blood was not associated with tumor size lymph node metastasis, tumor staging and immunoexpression of ras and c-myc proteins In conclusion, the present study shows that reduced expression of Mir15a is associated with OSCC stagin

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Retos para la integración social de los pobres en América Latina

En América Latina continúan en marcha procesos económicos, políticos y culturales que reproducen o incrementan la pobreza, la desigualdad y la exclusión social. Sin embargo, en el ámbito de las políticas sociales, la mayoría de los gobiernos de la región mantienen un enfoque minimalista. Cada vez es más evidente que la ecuación liberalización de la economía + crecimiento económico promovido exclusivamente por actores privados + políticas sociales fundamentalmente residuales no sólo no han disminuido significativamente los rezagos sociales heredados del pasado, sino que ha generado nuevas formas de pobreza, desigualdad, descalificación y exclusión. A pesar de ello, la intención de este libro no es documentar la crisis del paradigma de bienestar residual que ahora es hegemónico, ni realizar un recuento de daños. Intentamos contribuir a trascender la fragmentación de la discusión académica reinante, dedicada frecuentemente a impugnar índices de pobreza, a mostrar dinámicas sectoriales o a levantar la bandera por nuevos programas sociales diseñados para paliar situaciones de emergencia. El Grupo Pobreza y Políticas Sociales de CLACSO propone en esta obra algunos enfoques conceptuales más integrales, interdisciplinarios y comparativos, que ponen en el centro de la agenda académica la superación de la pobreza y la integración socioeconómica. Los temas centrales abordados aquí son: la dinámica del cambio de paradigmas, regímenes de bienestar y políticas sociales en la región; la interacción entre procesos de estabilización, ajuste, integración regional y pobreza; y algunos aspectos puntuales de la política social urbana, la vivienda y la pobreza en tres países de la región.Reconocimientos | 13 Introducción Carlos Barba Solano | 15 Parte I Paradigmas, regímenes de bienestar y políticas sociales en transición Anete Brito Leal Ivo La agudización del conflicto distributivo en la base: el nuevo tratamiento de la política social focalizada | 27 Carlos Barba Solano Reforma social y ciudadanía social en América Latina durante los años noventa: una perspectiva comparada | 51 Carmen Midaglia Entre la tradición, la modernización ingenua y los intentos de refundar la casa: la reforma social en el Uruguay de las últimas tres décadas | 85 Enrique Valencia Crecimiento, política social y pobreza en Corea del Sur y México | 109 Laura Golbert Los olvidados de la política social | 155 Parte II Procesos de ajuste e integración y pobreza Alicia Puyana y José Romero El sector agropecuario mexicano bajo el Tratado de Libre Comercio de América del Norte. La pobreza y la desigualdad se intensifican, crece la migración | 187 Carlos Larrea Crisis, dolarización y pobreza en el Ecuador | 215 Parte III Política social urbana, vivienda y pobreza Alicia Ziccardi Políticas de inclusión social de la Ciudad de México | 237 Carlos Fidel, Cristina Farías y Raúl Di Tomaso Rasgos de las insuficiencias urbanas y habitacionales en el partido de Quilmes, Argentina | 259 María Elena Ducci La política habitacional como instrumento de desintegración social. Efectos de una política de vivienda exitosa | 293 Vania Salles y María de la Paz López Viviendas pobres en México: un estudio desde la óptica de género | 311 Parte IV Enfoques sobre pobreza rural Salomón Nahmad, Tania Carrasco y Elena Nava Elementos para la construcción de una tipología de la pobreza rural en México | 351 Gustavo Verduzco Igartúa Trayectorias laborales del proletariado rural: estudio de caso en una zona del centro de México | 37

Reprogramming iPSCs to study age-related diseases: models, therapeutics, and clinical trials

The unprecedented rise in life expectancy observed in the last decades is leading to a global increase in the ageing population, and age-associated diseases became an increasing societal, economic, and medical burden. This has boosted major efforts in the scientific and medical research communities to develop and improve therapies to delay ageing and age-associated functional decline and diseases, and to expand health span. The establishment of induced pluripotent stem cells (iPSCs) by reprogramming human somatic cells has revolutionised the modelling and understanding of human diseases. iPSCs have a major advantage relative to other human pluripotent stem cells as their obtention does not require the destruction of embryos like embryonic stem cells do, and do not have a limited proliferation or differentiation potential as adult stem cells. Besides, iPSCs can be generated from somatic cells from healthy individuals or patients, which makes iPSC technology a promising approach to model and decipher the mechanisms underlying the ageing process and age-associated diseases, study drug effects, and develop new therapeutic approaches. This review discusses the advances made in the last decade using iPSC technology to study the most common age-associated diseases, including age-related macular degeneration (AMD), neurodegenerative and cardiovascular diseases, brain stroke, cancer, diabetes, and osteoarthritis.ALG-01-0145-FEDER-072586info:eu-repo/semantics/publishedVersio

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013