Lung immune signatures define two groups of end-stage IPF patients

BackgroundThe role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial.MethodsTo investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters.ResultsWe identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities.ConclusionsIn end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored

Propuesta estratégica de mejora en la implementación de los estándares mínimos del sistema de gestión de la seguridad y salud en el trabajo (SG-SST) en la empresa cooasucol para el primer semestre del 2019

El desarrollo del siguiente trabajo pretende presentar el plan de mejoramiento diseñado para la compañía COOSUACOL , el cual permita fortalecer las fallas encontradas en la matriz de análisis y calificación realizada frente a la implementación de estándares mínimos del Sistema de Gestión de Seguridad y Salud en el Trabajo (SG_SST). El enfoque planteado esta en cumplir con la legislación vigente planteada en: decreto 1443 de Junio de 2014 (Implementación del SG-SST), decreto 1072 del 2015 (único reglamentario del sector trabajo), el Decreto 171 de 2016 (prorroga implementación SG-SST), el Decreto 052 de 2017 (transición para la implementación de SGSST) y por último la una de las más relevantes, la resolución 0312 del 2019 (Dicta los estándares mínimos del SG-SST), Para el desarrollo de la propuesta, la metodología empleada es con base en la investigación cualitativa, la cual propone realizar atreves de mejoras que se fortalezca la salud y seguridad en el Trabajo en unión con el área de Talento Humano de la compañía.The development of the following work intends to present the improvement plan designed for the company COOSUACOL, which allows to strengthen the failures found in the analysis and qualification matrix carried out against the implementation of minimum standards of the Occupational Health and Safety Management System (SG_SST). The proposed approach is to comply with the current legislation proposed in: Decree 1443 of June 2014 (Implementation of the SG-SST), Decree 1072 of 2015 (only regulation of the labor sector), Decree 171 of 2016 (extends SG-SST implementation ), Decree 052 of 2017 (transition for the implementation of SGSST) and finally one of the most relevant, resolution 0312 of 2019 (Dictates the minimum standards of the SG-SST), For the development of the proposal, the methodology used is based on qualitative research, which proposes to make improvements that strengthen the health and safety at Work in conjunction with the area of ​​Human Talent of the company

Avaliação de um extrato vegetal na dieta sobre o comportamento produtivo de suínos estressados pelo calor

The exposure of pigs to heat stress (HS) affects the integrity of intestinal epithelia, compared to thermal neutral (TN) pigs, partially due to overproduction of free radicals. Herbal extracts (HE) from Capsicum spp., Pipper nigrum y Zingiber officinales possess antioxidant activity. The effect of adding this HE to the diet was analyzed on performance of 42 pigs (27±3 kg). The treatments were: TN-C, TN pigs with control diet, TN-P, pigs with control diet plus 0.02% HE; HS-C, HS pigs with control diet; and HS-P, HS pigs with control diet plus 0.02% HE. The experiment consisted of two periods; in period 1, all pigs were adapted to the control diet during 8 days under TN conditions, followed by a 7-day experimental period. Daily weight gain and feed intake were higher (P <0.05), and feed conversion ratio tended (P<0.10) to improve in HS-HE pigs compared to HS-C pigs. In conclusion, adding HE to the diet can improve some productive parameters in pigs exposed to HS conditions.La exposición de cerdos a estrés por calor (EC), en comparación con termo neutralidad (TN) afecta la integridad del epitelio intestinal, en parte debido a la sobreproducción de radicales libres. Extractos de hierbas (EH) como Capsicum spp., Pipper nigrum y Zingiber officinales poseen actividad antioxidante. Se evaluó el efecto de adicionar un extracto EH a la dieta en el desempeño productivo de 42 cerdos (27±3 kg) en EC. Los tratamientos fueron: TN-T, cerdos en TN alimentados con dieta testigo; EC-T y EC-EH, cerdos en EC alimentados con dieta testigo sin o con 0.2 % de EH. El experimento consistió de dos periodos; en periodo 1, todos los cerdos tuvieron 8 días de adaptación a la dieta testigo en TN, seguido del periodo experimental de 7 días. La ganancia de peso y consumo de alimento fueron mayores (P <0.05), y la conversión alimenticia tendió a ser mejor (P<0.10) en cerdos EC-EH que en cerdos EC-T. En conclusión, la adición del EH puede contribuir a mejorar algunos parámetros productivos cuando los cerdos están expuestos a EC.A exposição de suínos ao estresse térmico (CE), em comparação com a termoneutralidade (TN), afeta a integridade do epitélio intestinal, em parte devido à superprodução de radicais livres. Extratos de ervas (EH) como Capsicum spp., Pipper nigrum e Zingiber officinales possuem atividade antioxidante. Avaliou-se o efeito da adição de extrato de EH à dieta sobre o desempenho produtivo de 42 suínos (27±3 kg) em EC. Os tratamentos foram: TN-T, suínos em TN alimentados com dieta controle; EC-T e EC-EH, suínos em EC alimentados com dieta controle sem ou com 0,2% de EH. O experimento consistiu em dois períodos; No período 1, todos os suínos tiveram 8 dias de adaptação à dieta controle em TN, seguido do período experimental de 7 dias. O ganho de peso e o consumo de ração foram maiores (P < 0,05) e a conversão alimentar tendeu a ser melhor (P < 0,10) em porcos EC-EH do que em porcos EC-T. Em conclusão, a adição de EH pode contribuir para melhorar alguns parâmetros produtivos quando os suínos são expostos a CE

Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis

Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer.International Agency for Research on Cance

A Critical Review of Biomarkers Used for Monitoring Human Exposure to Lead: Advantages, Limitations, and Future Needs

Lead concentration in whole blood (BPb) is the primary biomarker used to monitor exposure to this metallic element. The U.S. Centers for Disease Control and Prevention and the World Health Organization define a BPb of 10 μg/dL (0.48 μmol/L) as the threshold of concern in young children. However, recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 μg/dL, suggesting that there is no safe level of exposure. It appears impossible to differentiate between low-level chronic Pb exposure and a high-level short Pb exposure based on a single BPb measurement; therefore, serial BPb measurements offer a better estimation of possible health outcomes. The difficulty in assessing the exact nature of Pb exposure is dependent not so much on problems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments (i.e., cycling of Pb between bone, blood, and soft tissues). If we are to differentiate more effectively between Pb stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of internal Pb dose have yet been accepted by the scientific community as a reliable substitute for a BPb measurement. This review focuses on the limitations of biomarkers of Pb exposure and the need to improve the accuracy of their measurement. We present here only the traditional analytical protocols in current use, and we attempt to assess the influence of confounding variables on BPb levels. Finally, we discuss the interpretation of BPb data with respect to both external and endogenous Pb exposure, past or recent exposure, as well as the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe