Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing

Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit

Medida del gasto cardiaco

Uno de los campos más amplios y poco explotados en nuestro medio para realizar investigación aplicada, es el de la Ingeniería Biomédica. En él se pueden enfocar los esfuerzos en la adquisición, tratamiento y análisis de biopotenciales (señales biológicas), al igual que en el diseño, construcción y puesta a punto de equipos y sistemas Software/Hardware de uso específico en Medicina.El presente trabajo MEDIDA DEL GASTO CARDIACO es buen ejemplo de ello. Con pocos recursos, y gran dedtcactón , los autores han pretendido desde el comienzo de su realización presentar un prototipo de bajo costo y versatilidad. respetando los índices de seguridad. robustez y calidad de un sistema tradicional

Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show ALDH(high)CD44(+) phenotype and sphere-forming capacity

BACKGROUND Conventional chemotherapy in malignant pleural mesothelioma (MPM) has minimal impact on patient survival due to the supposed chemoresistance of cancer stem cells (CSCs). We sought to identify a sub-population of chemoresistant cells by using putative CSC markers, aldehyde dehydrogenase (ALDH) and CD44 in three MPM cell lines; H28, H2052 and Meso4. METHODS The Aldefluor assay was used to measure ALDH activity and sort ALDH(high) and ALDH(low) cells. Drug-resistance was evaluated by cell viability, anchorage-independent sphere formation, flow-cytometry and qRT-PCR analyses. RESULTS The ALDH(high) - and ALDH(low) -sorted fractions were able to demonstrate phenotypic heterogeneity and generate spheres, the latter being less efficient, and both showed an association with CD44. Cis- diamminedichloroplatinum (II) (cisplatin) treatment failed to reduce ALDH activity and conferred only a short-term inhibition of sphere generation in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines. Induction of drug sensitivity by an ALDH inhibitor, diethylaminobenzaldehyde (DEAB) resulted in significant reductions in cell viability but not a complete elimination of the sphere-forming cells, suggestive of the presence of a drug-resistant subpopulation. At the transcript level, the cisplatin + DEAB-resistant cells showed upregulated mRNA expression levels for ALDH1A2, ALDH1A3 isozymes and CD44 indicating the involvement of these markers in conferring chemoresistance in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines. CONCLUSIONS Our study shows that ALDH(high) CD44(+) cells are implicated in conveying tolerance to cisplatin in the three MPM cell lines. The combined use of CD44 and ALDH widens the window for identification and targeting of a drug-resistant population which may improve the current treatment modalities in mesothelioma

Seroprevalence and Risk Factors Associated with Leishmania Infection in Dogs from Portugal

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Formulación de proyecto para la creación de planta de tratamiento de residuos aprovechables industriales generado por empresas metalmecánicas en la zona industrial de la ciudad de Bogotá.

Este proyecto busca establecer la viabilidad técnica y económica de una empresa que gestione los residuos generados por la industria, específicamente la industria metalmecánica en el sector de la zona industrial de Montevideo. Las actividades que se realizarán en la empresa serán la recolección de los materiales generados en las empresas metalúrgicas, principalmente metales, plásticos, madera, papel y cartón. Se realizará el transporte hasta la planta de acopio donde se harán las actividades de clasificación que comprende la limpieza, selección y empaque. El material plástico tendrá un proceso adicional que será el peletizado. Una vez el material esté listo en su proceso se realizara la venta a otras industrias como materia prima para sus procesos y finalmente la entrega en las instalaciones del cliente.This project seeks to establish the Technical and Economic Feasibility of a company that manages the waste generated by them, specifically in the metalworking industry of the industrial area of ​​Montevideo Bogotá

Resumen Analítico Especializado Empresa Agroautonoma

El mundo empresarial hoy en día se rige de diferentes maneras dentro de cada compañía, donde es importante resaltar que la innovación forma parte del crecimiento de las organizaciones siendo este un factor favorable para la economía del mundo, es así que mediante el crecimiento exponencial de las empresas la RSE forma parte de la responsabilidad que adquieren las compañías con sus directivos y sus grupos de colaboradores; es así que se busca conocer el grado de compromiso de los participantes de la empresa que trabajan en las actividades directa o indirectamente ya que ellos son parte fundamental de la implementación de los programas sociales y cuidado ambiental en la organización. La planeación estratégica es fundamental si queremos que nuestra compañía no solo conquiste los mercados nacionales sino internacionales, además logre posicionarse y mantenerse. Queda claro que todo debe ir acompañado de grandes estrategias de protección a los recursos naturales y comunicación estratégica con los grupos de colaboradores que le permitan tener un estatus social responsable, pretendemos que AGROAUTONOMA se convierta en una empresa auto sostenible con gran proyección financiera y gran responsabilidad social y ambiental.The business world today is governed in different ways within each company, where it is important to highlight that innovation is part of the growth of organizations, this being a favorable factor for the world economy, it is thus through the exponential growth of companies. companies CSR is part of the responsibility that companies acquire with their managers and their groups of collaborators; Thus, it is sought to know the degree of commitment of the participants of the company who work in the activities directly or indirectly since they are a fundamental part of the implementation of social programs and environmental care in the organization. Strategic planning is essential if we want our company not only to conquer national but international markets, as well as to position and maintain itself. It is clear that everything must be accompanied by great strategies for the protection of natural resources and strategic communication with the groups of collaborators that allow it to have a responsible social status, we want AGROAUTONOMA to become a self-sustainable company with great financial projection and great responsibility social and environmental

Risk factors for one-year mortality in hospitalized adults with severe covid-19 comment

As the body''s immunity declines with age, elderly-hospitalized patients due to COVID-19 might be at higher mortality risk. Therefore, the aim of this prospective study was to examine the possible risk factors (demographic, social or comorbidities) most associated with mortality one-year after diagnosis of COVID-19. Routine data were collected from a cohort of hospitalized adults with severe COVID-19. The primary endpoint was mortality at one-year after diagnosis of COVID-19. We used a Cox proportional hazard model to estimate the hazard ratios (HRs) for both all-cause and specific cardiorespiratory mortality. A fully adjusted model included sex, socioeconomic status, institutionalization status, disability, smoking habit, and comorbidities as confounders. A total of 368 severe cases hospitalized on average 67.3 +/- 15.9 years old were included. Participants aged >= 71 years had significantly higher HRs for all-cause mortality (adjusted HRs = 2.86, 95%CI: 2.01-4.07) and cardiorespiratory mortality (adjusted HRs = 2.86, 95%CI: 1.99-4.12). The association between age and mortality after diagnosis of COVID-19 due to both all-causes and cardiorespiratory mortality showed a consistent dose-response fashion. Institutionalization, disability, and socioeconomic status also showed a significant association with mortality. In conclusion, aging itself was the most important risk factor associated with mortality one year after diagnosis of COVID-19. People with disabilities, institutionalized or low socioeconomic status are significantly more likely to die after COVID-19

Stony Coral Tissue Loss Disease and Other Diseases Affect Adults and Recruits of Major Reef Builders at Different Spatial Scales in the Dominican Republic

Monitoring programs can help understand coral disease dynamics. Here, we present results from a national program in the Dominican Republic (DR) aimed at evaluating coral diseases 3 times a year following a nested spatial design. Prevalence of coral diseases in DR varied from sites to regions, suggesting that disease dynamics can be driven by local processes and/or across larger spatial scales. Three diseases were common: Dark Spot (DSD), Yellow Band (YBD) and Stony Coral Tissue Loss Disease (SCTLD). DSD and YBD were more prevalent across the western coast (north and south), whereas SCTLD was restricted for the study period to the northern coast. SCTLD has become endemic in the northwestern coast, epizootic in the northeastern, and absent in other sites across DR. SCTLD prevalence in the northwest was below 10% across sites, whereas in the northeast it varied from 2.13±3.69% (mean± sd) to 38.7±13.55% in Galeras and from 1.9±0.99% to 38.5±19.8% in Samaná. Over 10 coral species were affected by SCTLD in DR, with Pseudodiploria spp, Dendrogyra cylindrus, Eusmilia fastigiata, Siderastrea siderea, Montastraea cavernosa and Meandrina spp, being the most susceptible. We observed SCTLD affecting recruits and juvenile corals with 5% prevalence on average. Furthermore, we observed Oreaster reticulatus climbing on 1% healthy and 27% SCTLD P. strigosa colonies in Samaná. We conclude that SCTLD is a serious problem in DR, producing rapid loss of coral cover of major reef builders that are locally used for propagation efforts. This monitoring plan will provide future insights to design more effective disease responses

An SVM-Based classifier for estimating the state of various rotating components in agro-industrial machinery with a vibration signal acquired from a single point on the machine chassis

The goal of this article is to assess the feasibility of estimating the state of various rotating components in agro-industrial machinery by employing just one vibration signal acquired from a single point on the machine chassis. To do so, a Support Vector Machine (SVM)-based system is employed. Experimental tests evaluated this system by acquiring vibration data from a single point of an agricultural harvester, while varying several of its working conditions. The whole process included two major steps. Initially, the vibration data were preprocessed through twelve feature extraction algorithms, after which the Exhaustive Search method selected the most suitable features. Secondly, the SVM-based system accuracy was evaluated by using Leave-One-Out cross-validation, with the selected features as the input data. The results of this study provide evidence that (i) accurate estimation of the status of various rotating components in agro-industrial machinery is possible by processing the vibration signal acquired from a single point on the machine structure; (ii) the vibration signal can be acquired with a uniaxial accelerometer, the orientation of which does not significantly affect the classification accuracy; and, (iii) when using an SVM classifier, an 85% mean cross-validation accuracy can be reached, which only requires a maximum of seven features as its input, and no significant improvements are noted between the use of either nonlinear or linear kernels

Biophysical and lipidomic biomarkers of cardiac remodeling post-myocardial infarction in humans

Few studies have analyzed the potential of biophysical parameters as markers of cardiac remodeling post-myocardial infarction (MI), particularly in human hearts. Fourier transform infrared spectroscopy (FTIR) illustrates the overall changes in proteins, nucleic acids and lipids in a single signature. The aim of this work was to define the FTIR and lipidomic pattern for human left ventricular remodeling post-MI. A total of nine explanted hearts from ischemic cardiomyopathy patients were collected. Samples from the right ventricle (RV), left ventricle (LV) and infarcted left ventricle (LV INF) were subjected to biophysical (FTIR and differential scanning calorimetry, DSC) and lipidomic (liquid chromatography–high-resolution mass spectrometry, LC–HRMS) studies. FTIR evidenced deep alterations in the myofibers, extracellular matrix proteins, and the hydric response of the LV INF compared to the RV or LV from the same subject. The lipid and esterified lipid FTIR bands were enhanced in LV INF, and both lipid indicators were tightly and positively correlated with remodeling markers such as collagen, lactate, polysaccharides, and glycogen in these samples. Lipidomic analysis revealed an increase in several species of sphingomyelin (SM), hexosylceramide (HexCer), and cholesteryl esters combined with a decrease in glycerophospholipids in the infarcted tissue. Our results validate FTIR indicators and several species of lipids as useful markers of left ventricular remodeling post-MI in humans