Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases

Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option

Social media in cardiology: Reasons to learn how to use it

Social media has changed the way we learn, educate, and interact with our peers. The dynamic nature of social media and their immediate availability through our portable devices (smartphones, tablets, smartwatches, etc.) is quickly transforming the way we participate in society. The scope of these digital tools is broad as they deal with many different aspects: Teaching and learning, case discussion, congresses coverage, peer to peer interaction, research are examples worth mentioning. The scientific societies considered more innovative, are promoting these tools between their members. These new concepts need to be known by the cardiologists to stay updated, as countless information is moving rapidly through these channels. We summarize the main reasons why learning how to use these tools to be part of the conversation is essential for the cardiologist in training or fully stablished

Prognostic value of discharge heart rate in acute heart failure patients: More relevant in atrial fibrillation?

Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results: The mean age of the study population was 72+/-12years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR)=1.182, confidence interval (CI) 95% 1.024-1.366, p=0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR=1.276, CI 95% 1.115-1.459, p</=0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients

Employment generation by small firms in Spain

Despite the relevance in terms of policy, we still know little in Spain about where and by whom jobs are created, and how that is affecting the size distribution of firms. The main innovation of this paper is to use a rich database that overcomes the problems encountered by other firm-level studies to shed some light on the employment generation of small firms in Spain. We find that small firms contribute to employment disproportionately across all sectors of the economy although the difference between their employment and job creation share is largest in the manufacturing sector. The job creators in that sector are both new and established firms whereas only new small firms outperform their larger counterparts in the service sector. The large annual job creation of the small firm size class is shifting the firm size distribution towards the very small production units, although not uniformly across industries of different technology intensit

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Estudo comparativo entre m?todos de dosagem de concreto autoadens?vel

Made available in DSpace on 2015-04-14T13:58:44Z (GMT). No. of bitstreams: 1 434471.pdf: 3846522 bytes, checksum: 31c7bc9b2eae0d1e9d61a544fa33a3ab (MD5) Previous issue date: 2011-08-29A introdu??o do concreto autoadens?vel (CAA), primeiramente buscando sanar o problema da redu??o de m?o de obra qualificada no Jap?o, apresentou diversas oportunidades de melhoria de qualidade e produtividade na ind?stria da constru??o. Pesquisadores, desde ent?o, v?m desenvolvendo trabalhos a fim de compreender e tornar a dosagem experimental do CAA t?o clara e sistem?tica como a do concreto convencional. No Brasil, os m?todos experimentais de dosagem de CAA podem ser divididos em dois grupos. Os m?todos do primeiro grupo baseiam-se na adi??o de agregados e avaliam a mistura desde a etapa de formula??o da pasta at? o ajuste final do concreto. O segundo grupo avalia o concreto como um todo e utiliza conceitos do m?todo IPT/EPUSP de Helene e Terzian (1992). Na presente pesquisa foram comparados os m?todos de dosagem de CAA de Tutikian e Dal Molin (2007) e Alencar e Helene (2006), ambos pertencentes ao segundo grupo, e um CAA obtido atrav?s de metodologia desenvolvida neste trabalho. Todos os CAAs foram dosados com areia fina e para cada m?todo foi dosado uma fam?lia composta por tr?s tra?os-base. Para a obten??o do CAA resultante, foram utilizados conceitos dos m?todos CIENTEC e IPT/EPUSP de Helene e Terzian (1992), al?m de considerar o teor de argamassa seca e o teor de aditivo superplastificante em rela??o ao cimento vari?vel para cada tra?o-base de uma mesma fam?lia. Os resultados dos ensaios de trabalhabilidade, no estado fresco, e de resist?ncia ? compress?o, absor??o de ?gua por imers?o e por capilaridade, no estado endurecido, assim como o custo por m? de concreto, demonstraram que o desempenho do CAA desenvolvido neste trabalho ? consoante ou superior aos demais m?todo

Potencial de pr?cticas y sistemas silvopastoriles para las acciones nacionales apropiadas de mitigaci?n (NAMA) para el sector ganadero de Honduras

Tesis (maestr?a) - CATIE, Turrialba (Costa Rica), 2019El objetivo del presente estudio fue evaluar el potencial de pr?cticas y sistemas silvopastoriles para las acciones nacionales apropiadas de mitigaci?n (NAMA) para el sector ganadero de Honduras. Las pr?cticas y sistemas silvopastoriles (SPP) evaluadas fueron pasturas mejoradas, cercas vivas, ?rboles dispersos en potreros y bancos forrajeros. Para esto se realizaron entrevistas con productores y recolecci?n de datos en campo, para estimar el carbono almacenado, las emisiones de gases de efecto invernadero por estas pr?cticas, y conocer la relaci?n costo-efectividad de las pr?cticas y sistemas silvopastoriles incorporadas en fincas ganaderas usando como muestra 20 fincas ganaderas de doble prop?sito agrup?ndolas seg?n la presencia de pr?cticas y/sistemas silvopastoriles dentro de las fincas. Se realizaron comparaciones entre las agrupaciones de fincas con la prueba estad?stica LSD Fisher a trav?s del an?lisis de la varianza (ANAVA), para conocer si exist?an diferencias significativas en las pr?cticas y/o sistemas silvopastoriles referentes a captura de carbono y emisiones en las fincas ganaderas. Se encontr? rango de almacenamiento de carbono en cercas vivas con edad de 3 a?os entre 1.0 - 6.8 t/km, en ?rboles dispersos en potreros 0.32 - 2.7 t/ha de carbono almacenado. En pasturas mejoradas se documentaron valores de biomasa almacenada de 9.50 ? 11.70 t/ha y en los bancos forrajeros de gram?neas de 7.8 ? 10.3 t/ha. Resultados de las fincas en estudio en cuanto a emisiones de gases de efecto invernadero determinaron que la fermentaci?n ent?rica ocup? el porcentaje m?s alto como fuente de emisi?n seguidos del esti?rcol y la fertilizaci?n, pues el promedio de emisiones en estas fincas fluct?a entre 3.59 y 7.25 t CO2e/ha/a?o, y para la producci?n de 1 kg de leche las emisiones producidas est?n entre 1.48 y 4.15 t CO2e. En promedio, el costo de implementaci?n para bancos forrajeros US$549.64, para las pasturas mejoras de 442.71. US$/ha y para las cercas vivas de 102 US$/ha. El an?lisis de costo-efectividad refleja que las cercas vivas es la actividad con la cual los costos por almacenar 1 tonelada de carbono es m?s econ?mico ya que su cuant?a en este estudio fue de US$ 15.00 t/a?o, seguido de las pasturas mejoradas US$51.13 t/a?o. Los bancos forrajeros de gram?neas mostraron valores de US$ 67.05 t/a?o. Se logr? aportar recomendaciones t?cnicas para la adopci?n de estas pr?cticas y/o sistemas silvopastoriles como apoyo a la NAMA de ganader?a sostenible de Honduras, que su objetivo principal es frenar el impacto de la ganader?a al cambio clim?tico a trav?s de los gases de efecto invernadero.CATIE (Centro Agron?mico Tropical de Investigaci?n y Ense?anza

Liquid Biopsy: A New Tool for Overcoming CDKi Resistance Mechanisms in Luminal Metastatic Breast Cancer

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2- BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi), in combination with an aromatase inhibitor or fulvestrant, have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all of the patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms that underlie this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease, and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We mainly focus on those studies that describe the possible resistance mechanisms in circulating tumour-derived material