Single versus tandem autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma and high-risk cytogenetics. A retrospective, open-label study of the PETHEMA/Spanish Myeloma Group (GEM)

Tandem ASCT has been suggested as a valid approach to improve the prognosis of patients with MM and HR cytogenetic. In this observational, retrospective study, 213 patients with newly diagnosed MM and HR cytogenetic in 35 hospitals from the Spanish Myeloma Group underwent single or tandem ASCT between January 2015 and December 2019 after induction with VTD/VRD. HR cytogenetic was defined as having ≥1 of the following: del17p, t(4;14), t(14;16) or gain 1q21. More patients in the tandem group had R-ISS 3 and >1 cytogenetic abnormality at diagnosis. With a median follow-up of 31 months (range, 10–82), PFS after single ASCT was 41 months versus 48 months with tandem ASCT (p = 0.33). PFS in patients with del17p undergoing single ASCT was 41 months, while 52% of patients undergoing tandem ASCT were alive and disease free at 48 months. In conclusion, tandem ASCT partly overcomes the bad prognosis of HR cytogenetic

Increased Lysis of Stem Cells but Not Their Differentiated Cells by Natural Killer Cells; De-Differentiation or Reprogramming Activates NK Cells

The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-γ were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells. Moreover, NK cells were found to lyse human Mesenchymal Stem Cells (hMSCs), human dental pulp stem cells (hDPSCs) and human induced pluripotent stem cells (hiPSCs) significantly more than their differentiated counterparts or parental lines from which they were derived. It was also found that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 in monocytes significantly augmented NK cell cytotoxicity and secretion of IFN-γ. Taken together, these results suggest that stem cells are significant targets of the NK cell cytotoxicity. However, to support differentiation of a subset of tumor or healthy untransformed primary stem cells, NK cells may be required to lyse a number of stem cells and/or those which are either defective or incapable of full differentiation in order to lose their cytotoxic function and gain the ability to secrete cytokines (split anergy). Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats

9 páginas -- PAGS nros. 1180-1188Diabetologia June 2005, Volume 48, Issue 6, pp 1180-1188 Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats T. Teruel, R. Hernandez, E. Rial, A. Martin-Hidalgo, M. Lorenzo … show all 5 hide » Download PDF (326 KB) » View Article Abstract Aims/hypothesis Although thiazolidinediones are now widely used to treat type 2 diabetes, their mechanism of action remains largely unknown. They are agonists for the transcription factor PPARγ, and in addition to their insulin-sensitising effects, they can promote adipogenesis and control gene expression in adipose tissues. We have explored the effect of rosiglitazone on insulin-mediated induction of pivotal genes involved in lipid metabolism and thermogenesis in brown fat. The genes studied were: (1) lipoprotein lipase (lpl), which is involved in lipid uptake; (2) hormone-sensitive lipase (hsl), which mobilises fatty acids from stored triglycerides; (3) fatty acid synthase (fas), which regulates de novo lipogenesis; and (4) the uncoupling proteins (ucp) 1 and 3, which control thermogenesis. Methods We used fetal rat primary brown adipocytes cultured with insulin, rosiglitazone or both combined. Then, we studied gene expression by northern and western blotting, as well as ‘run-on’ and gel-shift assays to identify binding of potential transcription factors to the fas promoter. Results Exposure to rosiglitazone for 24 h induced ucp-1, lpl and hsl gene expression and when rosiglitazone was combined with insulin a synergistic effect on lpl and ucp-3 mRNA expression was produced. These effects were consistent with increased LPL and HSL activities as well as respiration rates, mainly in response to exogenous palmitate. In contrast, treatment with rosiglitazone did not alter FAS mRNA basal levels but prevented the induction elicited by insulin in a time- and dose-dependent manner. Correspondingly diminished FAS protein levels and activity, as well as cellular lipid content, were observed, indicating an antilipogenic action of rosiglitazone in brown adipocytes. Furthermore, rosiglitazone impaired insulin increase in the FAS transcription rate by antagonising insulin-induced binding of upstream stimulatory factors to the E-box consensus sequence in the FAS promoter and insulin-induced binding of activating protein-1Conclusions/interpretation Rosiglitazone prevents insulin-induced up-regulation of the main lipogenic enzyme but increases the expression of those enzymes involved in lipid uptake and mobilisation, favouring fatty acid utilisation through uncoupled respirationThis work was supported by Grant BMC2002-01322 (Direccion General de Investigacion Cientifica, MCYT, Spain). We are also grateful for the support of COST B17 Action on ‘Insulin resistance, obesity and diabetes mellitus in the elderly’ (European Commission), and of Red de grupos de Diabetes Mellitus G03/212 (Instituto de Salud Carlos III, MSC, SpainPeer reviewe

Instrucciones prácticas en el arte de escribir, reducidas a cinco diálogos entre maestro y discípulo, que para imponer y perfeccionar en sus reglas a los jóvenes aplicados de la nación española

Grab. xil. del imp. en port.Las il. son grab. xil. a toda plan

Improving sleep quality, daytime sleepiness, and cognitive function in patients with dementia by therapeutic exercise and NESA neuromodulation: a multicenter clinical trial

Multicenter study[Abstract] Dementia is a progressive decline in cognitive functions caused by an alteration in the pattern of neural network connections. There is an inability to create new neuronal connections, producing behavioral disorders. The most evident alteration in patients with neurodegenerative diseases is the alteration of sleep-wake behavior. The aim of this study was to test the effect of two non-pharmacological interventions, therapeutic exercise (TE) and non-invasive neuromodulation through the NESA device (NN) on sleep quality, daytime sleepiness, and cognitive function of 30 patients diagnosed with dementia (non-invasive neuromodulation experimental group (NNG): mean ± SD, age: 71.6 ± 7.43 years; therapeutic exercise experimental group (TEG) 75.2 ± 8.63 years; control group (CG) 80.9 ± 4.53 years). The variables were evaluated by means of the Pittsburg Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Mini-Cognitive Exam Test at four different times during the study: at baseline, after 2 months (after completion of the NNG), after 5 months (after completion of the TEG), and after 7 months (after 2 months of follow-up). Participants in the NNG and TEG presented significant improvements with respect to the CG, and in addition, the NNG generated greater relevant changes in the three variables with respect to the TEG (sleep quality (p = 0.972), daytime sleepiness (p = 0.026), and cognitive function (p = 0.127)). In conclusion, with greater effects in the NNG, both treatments were effective to improve daytime sleepiness, sleep quality, and cognitive function in the dementia population

ANTECEDENTES PSICOLÓGICOS DE LA COMUNICACIÓN

El artículo aborda los antecedentes psicológicos de la categoría comunicación desde diferentes posiciones. Se explica la concepción de la psicología no marxista acerca de la comunicación y la concepción de los psicólogos marxistas. Se analiza el lugar que ocupa la categoría comunicación en la teoría de la personalidad

Conexión didáctica y organizativa : preescolar y ciclo inicial

Trabajo realizado en el marco de un seminario o grupo de trabajo del CEP de Melilla. Con el objeto de fundamentar teóricamente metodologías, materiales y actividades en conexión con el ciclo inicial de EGB, y a partir del trabajo en grupo de los educadores, que considera algo imprescindible dentro de la escuela infantil y del ciclo inicial, estudia detalladamente la fundamentación teórica e implicaciones pedagógicas de todos aquellos aspectos que son fundamentales para seguir una línea coherente en pre-escolar y ciclo inicial, con vistas a un nuevo currículum.AndalucíaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5; 28014 Madrid; Tel. +34917748000; [email protected]

¿Y las Universidades qué? Universidad Abierta: algo más que Gobierno Abierto y Open Data

[ES] El Gobierno Abierto y los valores que representa (transparencia, participación y rendición de cuentas) están generando un creciente interés entre las administraciones públicas. La Universidad, como una de las grandes instituciones de la sociedad contemporánea, no se escapa de esta tendencia al alza. Si bien aún son tímidos los pasos que se dan en este sentido, el movimiento open cada vez inunda más la gestión y la investigación universitarias. Algo que, como se muestra en este artículo, tiene una enorme relevancia para avanzar en la mejora de la calidad en los servicios que prestan.Solís Cabrera, FM.; Álvarez Sánchez, D.; Marín Garcia, MD.; Peset Mancebo, MF.; Ferrer Sapena, A.; Teruel Doñate, E. (2014). ¿Y las Universidades qué? Universidad Abierta: algo más que Gobierno Abierto y Open Data. Actualidad Administrativa. (7/8):841-849. http://hdl.handle.net/10251/52285S8418497/