The administration of multipotent stromal cells at precancerous stage precludes tumor growth and epithelial dedifferentiation of oral squamous cell carcinoma

Multipotent stromal cells (MSCs) are envisioned as a powerful therapeutic tool. As they home into tumors, secrete trophic and vasculogenic factors, and suppress immune response their role in carcinogenesis is a matter of controversy. Worldwide oral squamous cell carcinoma (OSCC) is the fifth most common epithelial cancer. Our aim was to determine whether MSC administration at precancerous stage modifies the natural progression of OSCC. OSCC was induced in Syrian hamsters by topical application of DMBA in the buccal pouch. At papilloma stage, the vehicle or 3 × 106 allogenic bone marrow-derived MSCs were locally administered. Four weeks later, the lesions were studied according to: volume, stratification (histology), proliferation (Ki-67), apoptosis (Caspase 3 cleaved), vasculature (ASMA), inflammation (Leukocyte infiltrate), differentiation (CK1 and CK4) and gene expression profile (mRNA). Tumors found in individuals that received MSCs were smaller than those presented in the vehicle group (87 ± 80 versus 54 ± 62 mm3, p < 0.05). The rate of proliferation was two times lower and the apoptosis was 2.5 times higher in lesions treated with MSCs than in untreated ones. While the laters presented dedifferentiated cells, the former maintained differentiated cells (cytokeratin and gene expression profile similar to normal tissue). Thus, MSC administration at papilloma stage precludes tumor growth and epithelial dedifferentiation of OSCC.Fil: Bruna, Flavia Alejandra. Universidad del Desarrollo; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Arango Rodríguez, Martha. Universidad del Desarrollo; ChileFil: Plaza, Anita. Universidad del Desarrollo; ChileFil: Espinoza, Iris. Universidad del Desarrollo; ChileFil: Conget, Paulette. Universidad del Desarrollo; Chil

Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry.

International audienceBACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients. METHODS: COPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)). RESULTS: Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7). CONCLUSIONS: COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients

Impacto familiar de la eutanasia: Un estudio de caso en Soria

INTRODUCCIÓN. Durante los últimos años la discusión en torno a la eutanasia ha adquirido una relevancia sin precedentes. La intervención enfermera no está definida de forma clara en la Ley Orgánica de Regulación de la Eutanasia a pesar de la importancia en su implicación. La esclerosis lateral amiotrófica es una enfermedad grave que a menudo lleva a considerar la solicitud de eutanasia. Esta decisión implica también a la familia que es la principal responsable de su atención hasta el final de su vida. OBJETIVO. Analizar el impacto familiar en situaciones donde se contempla la eutanasia, desde la perspectiva familiar de los pacientes solicitantes. METODOLOGÍA. El estudio de caso requiere una metodología mixta, con una toma de contexto a partir de una revisión bibliográfica y un análisis cualitativo del caso. DISCUSIÓN. El sufrimiento del familiar viene marcado por sentimientos de ambivalencia e injusticia. La relación de cuidado se caracteriza por un cuidado transpersonal compasivo, proporcionado también por la enfermera. Además, el duelo del postcuidador refleja un vacío emocional y la falta de rutinas relacionadas con la atención de su ser querido. Las actitudes familiares hacia el final de la vida revelan la aceptación de la eutanasia como parte de una filosofía compartida. El equipo sanitario ofrece apoyo profesional (informativo y emocional destacando la empatía) durante todo el proceso. CONCLUSIONES. Los familiares de los pacientes que solicitan la eutanasia enfrentan una compleja mezcla de emociones y conflictos internos. La relación cuidador-paciente se caracteriza por un vínculo transpersonal y compasivo que garantice un contexto eutanásico de bienestar, en el que el paciente se sienta cómodo expresando sus opiniones, al que se suma la enfermera. El equipo sanitario debe ofrecer una atención integral, antes y después de la prestación de ayuda para morir.Grado en Enfermerí

Design and Baseline Characteristics of Participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) Trial of Dulaglutide's Cardiovascular Effects

DigitalThe aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.Ciencias Médicas y de la Salu

Omental adipose tissue is a more suitable source of canine Mesenchymal stem cells

Background: Mesenchymal Stem Cells (MSCs) are a promising therapeutic tool in veterinary medicine. Currently the subcutaneous adipose tissue is the leading source of MSCs in dogs. MSCs derived from distinct fat depots have shown dissimilarities in their accessibility and therapeutic potential. The aims of our work were to determine the suitability of omental adipose tissue as a source of MSCs, according to sampling success, cell yield and paracrine properties of isolated cells, and compared to subcutaneous adipose tissue. Results: While sampling success of omental adipose tissue was 100% (14 collections from14 donors) for subcutaneous adipose tissue it was 71% (10 collections from 14 donors). MSCs could be isolated from both sources. Cell yield was significantly higher for omental than for subcutaneous adipose tissue (38 ± 1 vs. 30 ± 1 CFU-F/g tissue, p < 0.0001). No differences were observed between sources regarding cell proliferation potential (73 ± 1 vs. 74 ± 1 CDPL) and cell senescence (at passage 10, both cultures presented enlarged cells with cytoplasmic vacuoles and cellular debris). Omental- and subcutaneous-derived MSCs expressed at the same level bFGF, PDGF, HGF, VEGF, ANG1 and IL-10. Irrespective of the source, isolated MSCs induced proliferation, migration and vascularization of target cells, and inhibited the activation of T lymphocytes. Conclusion: Compared to subcutaneous adipose tissue, omental adipose tissue is a more suitable source of MSCs in dogs. Since it can be procured from donors with any body condition, its collection procedure is always feasible, its cell yield is high and the MSCs isolated from it have desirable differentiation and paracrine potentials.Fil: Bahamondes, Francisca. Universidad de Chile; Chile. Universidad del Desarrollo; ChileFil: Flores, Estefania. Universidad de Chile; ChileFil: Cattaneo, Gino. Universidad de Chile; ChileFil: Bruna, Flavia Alejandra. Universidad del Desarrollo; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Conget, Paulette. Universidad del Desarrollo; Chil

Diabetes associated with HNF1B: Beyond Occam’s razor—a case report

This report presents a clinical case of diabetes associated with HNF1B in a patient who was initially enrolled in a clinical trial for type 1 diabetes (T1D) and received immunosuppressive treatment for four years. At the time, knowledge of monogenic diabetes was limited, leading to diagnoses that did not account for these genetic forms. This case also highlights the broad phenotypic spectrum of these genetic alterations and emphasizes the importance of considering this diagnosis even in the absence of a clear family histor

Oportunidades de aprendizaje de la práctica pedagógica en el campus universitario: planificación, ejecución y contribución en la formación profesional de futuros docentes

La formación inicial docente busca enseñar a enseñar. Para ello, se ha propuesto que los programas incorporen formalmente instancias de comprensión y entrenamiento en prácticas pedagógicas, tanto en las asignaturas como en terreno. Este estudio tiene como objetivo explorar la planificación, ejecución y contribución a la formación profesional de la incorporación de oportunidades de aprendizaje de la práctica pedagógica (OAP) en asignaturas impartidas en el campus universitario. Para ello, se realizó un estudio descriptivo en tres programas de formación docente: educación de párvulos, básica y media. Primero, se identificaron las OAP planificadas analizando las calendarizaciones de 72 asignaturas. Luego, se examinó la percepción al respecto de las OAP ejecutadas encuestando a 231docentes en formación. Finalmente, se indagó sobre la contribución de las OAP a la formación profesional entrevistando a 8 docentes en formación. Las OAP más planificadas por los formadores de docentes fueron planificar experiencias de aprendizaje y simular lo que hace un docente durante una experiencia de aprendizaje. Esta última fue la OAP más frecuentemente ejecutada por los docentes en formación, quienes reconocen que las simulaciones les permiten: 1) aplicar los contenidos, 2) aprender de los errores, 3) ejercitar el monitoreo metacognitivo y la autoevaluación y 4) aproximarse a la complejidad de la enseñanza. Los hallazgos de esta investigación pueden ser utilizados por las instituciones formadoras para fundamentar la incorporación y diseñar la implementación de la enseñanza de las OAP desde el primer año del trayecto formativo, haciendo un énfasis particular en la simulación de lo que hace un docente antes y durante una experiencia de aprendizaje

El tratamiento adecuado en pacientes con SAHS (Síndrome de Apnea Hipoapnea del Sueño) que sufren un ictus, ¿protege de reinfartos cerebrales durante el año siguiente al ictus?

Introducción: el ictus representa la tercera causa de muerte y la primera causa de invalidez en adultos. Los Trastornos Respiratorios durante el Sueño y, concretamente, el Síndrome de Apnea Hipoapnea del Sueño (SAHS) está emergiendo como uno de los más importantes factores de riesgo para la enfermedad cardiovascular en general, y para el ictus en particular. Objetivo: el objetivo de este estudio es valorar si el uso correcto de CPAP disminuye la tasa de reinfartos cerebrales durante el primer año tras sufrir un ictus. Metodología: se trata de un estudio descriptivo, retrospectivo. Se incluyeron los pacientes con diagnóstico de ictus que ingresaron entre el 1 de Enero de 2008 y el 30 de Marzo de 2011 y que tenían entre los diagnósticos secundarios SAHS (Síndrome de Apnea Hipoapnea del Sueño) en tratamiento con CPAP. Se observó la tasa de reinfarto durante el primer año tras el ictus. Se registraron además las variables clásicas en relación con el riesgo de ictus. El método estadístico utilizado han sido tablas cruzadas de contigencia para el análisis proporcional, junto con el uso de la “chi-cuadrado”. Resultados y conclusiones; en nuestro estudio, la tasa de reinfarto cerebral tras un ictus en pacientes con SAHS en el primer año tras el ictus, fue del 13,4%. Del total de la muestra, un 19,6 % (N= 19) estaban tratados correctamente con CPAP, siendo la tasa de reinfarto cerebral durante el primer año en este grupo del 0%, mientras que la tasa de reinfartos entre los no tratados correctamente con CPAP fue del 16.6 % (N=13). Parece existir una mayor tasa de reinfartos en mayores de 80 años y en alcohólicos, siendo estos últimos, los menos cumplidores. Este estudio nos sugiere que el uso adecuado de CPAP, en pacientes que sufren un ictus y padecen SAHS, disminuye la tasa de reinfartos cerebrales durante el primer año tras sufrir un ictus. Para consolidar firmemente estos resultados, sería interesante realizar estudios prospectivos e investigar estrategias de mejorar el cumplimiento del CPAP

Accuracy of Continuous Glucose Monitoring before, during, and after Aerobic and Anaerobic Exercise in Patients with Type 1 Diabetes Mellitus

[EN] Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of CGM in the context of exercise is addressed. Six adults performed aerobic and anaerobic exercise sessions and used two Medtronic Paradigm Enlite-2 sensors under closed-loop therapy. CGM readings were compared with plasma glucose during different periods: one hour before exercise, during exercise, and four hours after the end of exercise. In aerobic sessions, the median absolute relative difference (MARD) increased from 9.5% before the beginning of exercise to 16.5% during exercise (p < 0.001), and then decreased to 9.3% in the first hour after the end of exercise (p < 0.001). For the anaerobic sessions, the MARD before exercise was 15.5% and increased without statistical significance to 16.8% during exercise realisation (p = 0.993), and then decreased to 12.7% in the first hour after the cessation of anaerobic activities (p = 0.095). Results indicate that CGM might present lower accuracy during aerobic exercise, but return to regular operation a few hours after exercise cessation. No significant impact for anaerobic exercise was found.This project was partially supported by the Spanish Government through grants DPI2013-46982-C2-1-R, DPI2013-46982-C2-2-R, DPI2016-78831-C2-1-R, and DPI2016-78831-C2-2-R, and by the National Council of Technological and Scientific Development, CNPq Brazil through grants 202050/2015-7 and 207688/2014-1.Biagi, L.; Bertachi, A.; Quirós, C.; Giménez, M.; Conget, I.; Bondía Company, J.; Vehí, J. (2018). Accuracy of Continuous Glucose Monitoring before, during, and after Aerobic and Anaerobic Exercise in Patients with Type 1 Diabetes Mellitus. Biosensors. 8(1):1-8. https://doi.org/10.3390/bios8010022S188

Hypoglycemia prevention and user acceptance of an insulin pump system with predictive low glucose management

Background: The MiniMed 640G sensor-augmented insulin pump system (Medtronic, Inc., Northridge, CA) can automatically suspend insulin delivery in advance of predicted hypoglycemia and restart it upon recovery. The aims of this analysis were to determine the rate at which predicted hypoglycemia was avoided with this strategy, as well as to assess user acceptance of the system and its insulin management features. Subjects and Methods: Forty subjects with type 1 diabetes used the system for 4 weeks. We retrospectively evaluated performance of the system, using downloaded pump and sensor data, and evaluated user acceptance via questionnaires. Results: There were 2,322 suspend before low events (2.1 per subject-day). The mean (± SD) duration of pump suspension events was 56.4 ± 9.6 min, and the mean subsequent sensor glucose (SG) nadir was 71.8 ± 5.2 mg/dL. SG values following 1,930 (83.1%) of the predictive suspensions did not reach the preset low limit. Nadir SG values of ≤50 and ≤60 mg/dL were seen in 207 (8.9%) and 356 (15.3%) of the predictive suspensions, respectively. Blood glucose (BG) and SG values before and during the study were comparable (P &gt; 0.05). The mean absolute relative difference between paired SG and BG values was 10.9 ± 13.8%. Subjects felt confident using the system, agreed that it helped protect them from hypoglycemia, and wished to continue using it. Conclusions: Automatic insulin pump suspension as implemented in the MiniMed 640G system can help patients avoid hypoglycemia, without significantly increasing hyperglycemia.</p