Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is the most common malignant primary brain tumor. Despite aggressive multimodality treatment it remains one of the most challenging and intractable cancers (1]. While current standard of care treatment for GBM is maximal safe surgical resection, systemic chemotherapy with Temozolimide (TMZ), and radiation therapy, the current prognosis of GBM patients remains poor, with a median overall survival of 12–15 months (2, 3). Therefore, other treatments are needed to provide better outcomes for GBM patients. Immunotherapy is one of the most promising new cancer treatment approaches. Immunotherapy drugs have obtained regulatory approval in a variety of cancers including melanoma (4), Hodgkin lymphoma (5), and non-small cell lung cancer (6). The basis of immunotherapy in cancer treatment is linked to stimulating the immune system to recognize cancer cells as foreign, thereby leading to the eventual elimination of the tumor. One form of immunotherapy utilizes vaccines that target tumor antigens (7), while other approaches utilize T-cells in patients to stimulate them to attack tumor cells (8). Despite intensive efforts all approaches have not been overtly successful (9), suggesting that we need to better understand the underlying biology of tumor cells and their environment as they respond to immunotherapy. Recent studies have elucidated epigenetic pathway regulation of GBM tumor expansion (10), suggesting that combined epigenetic pathway inhibition with immunotherapy may be feasible. In this review, we discuss current GBM clinical trials and how immune system interactions with epigenetic pathways and signaling nodes can be delineated to uncover potential combination therapies for this incurable disease

El rol del Terapeuta Ocupacional en la prevención primaria de obesidad en niños y niñas entre seis meses y dos años

Tesis (Magíster en Terapia Ocupacional, Mención Salud Física)La presente investigación busca conocer el rol de la Terapia Ocupacional en la prevención primaria de obesidad en niños y niñas entre seis meses y dos años, por medio de una investigación cualitativa que permite obtener información desde la perspectiva de los Terapeutas Ocupacionales entrevistados. La relevancia de la investigación radica en que la obesidad infantil es un campo escasamente abordado por los Terapeutas Ocupacionales, tanto en su formación como en su ejercicio, a pesar de relacionarse con aspectos ocupacionales esenciales de la Terapia Ocupacional y donde ésta podría aportar estableciéndose los niños y niñas con obesidad como un campo de intervención de la profesión. La investigación revela el rol actual y el rol esperado de los y las Terapeutas Ocupacionales en relación al contexto, hábitos y desempeño ocupacional respecto de la obesidad infantil, que permite respaldar la idea propuesta sobre la pertinencia y necesidad de la participación de estos profesionales en equipos que aborden, desde la prevención y promoción, la obesidad infantil

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial

BACKGROUND: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation. METHODS: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase I and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase II. RESULTS: Twenty-six patients were enrolled and followed for a median 15.1 months (7.3‒19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase II dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). CONCLUSIONS: Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population

Assessment of reliability and validity of the Spanish version of the Nursing Students’ Perception of Instructor Caring (S-NSPIC)

The care that clinical instructors demonstrate to students is essential for their education, considering the strong impact it has on their future relationships with patients, relatives, and other health professionals. Nursing Students’ Perceptions of Instructor Caring (NSPIC) is an instrument designed to assess nursing students’ perceptions of instructor’s caring behaviors. A trans-cultural, conceptual, and psychometric validation study was conducted with 315 nursing students at the University of Seville during their clinical practices in three regional hospitals. The NSPIC was translated and adapted to Spanish. The content validity was established by a panel of experts. To assess concurrent validity the culturally adapted Spanish version of the Clinical Placement Evaluation Tool (CPET) was used as a gold standard. The construct validity was determined by an exploratory factor analysis to identify the internal structure of the NSPIC-S. The internal consistency was established by Cronbach’s α and the intra-observer reliability for each item was established by test-retest. The content validity index varied between 0.53 and 0.93 and the correlation to the CPET was moderate. The factor analysis revealed a structure of five factors, one of which differed from the original scale. The value of Cronbach’s α was 0.95 and intraclass correlation coefficients varied between 0.5 and 0.89. Our study provided a culturally adapted version of the NSPIC, valid and reliable to be used in the Spanish context, the NSPIC-S

Implementation and evaluation of a dynamic contrast enhanced mr perfusion protocol for glioblastoma using a 0.35T mri-Linac system

MRI-linear accelerator (MRI-Linac) systems allow for daily tracking of MRI changes during radiotherapy (RT). Since one common MRI-Linac operates at 0.35T, there are efforts towards developing protocols at that field strength. In this study we demonstrate the implementation of a post-contrast 3DT1-weighted (3DT1w) and dynamic contrast enhancement (DCE) protocol to assess glioblastoma response to RT using a 0.35T MRI-Linac. The protocol implemented was used to acquire 3DT1w and DCE data from a flow phantom and two patients with glioblastoma (a responder and a non-responder) who underwent RT on a 0.35T-MRI-Linac. The detection of post-contrast enhanced volumes was evaluated by comparing the 3DT1w images from the 0.35T-MRI-Linac to images obtained using a 3T-standalone scanner. The DCE data were tested temporally and spatially using data from the flow phantom and patients. K-trans maps were derived from DCE at three time points (a week before treatment: Pre RT, four weeks through treatment: Mid RT, and three weeks after treatment: Post RT) and were validated with patients treatment outcomes. The 3D-T1 contrast enhancement volumes were visually and volumetrically similar (+/- 0.6-3.6%) between 0.35T MRI-Linac and 3T. DCE images showed temporal stability, and associated K-trans maps were consistent with patient response to treatment. On average, K-trans values showed a 54% decrease and 8.6% increase for a responder and non-responder respectively when Pre RT and Mid RT images were compared. Our findings support the feasibility of obtaining post-contrast 3DT1w and DCE data from patients with glioblastoma using a 0.35T MRI-Linac system

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial

Brain penetration; Mutant; OlutasidenibPenetració cerebral; Mutant; OlutasidenibPenetración cerebral; Mutante; OlutasidenibBackground Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation. Methods This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase I and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase II. Results Twenty-six patients were enrolled and followed for a median 15.1 months (7.3‒19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase II dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). Conclusions Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.This study was funded by Forma Therapeutics, Inc., Watertown, MA, USA

Analytical tools for the multiplex rapid detection of SARS-CoV-2

There is a high demand for analytical tools that can readily be applied to effectively diagnose the Covid-19 but also to carry out screening and surveillance detection with enough frequency to get the transmission rates under control and thus help to timely tackling the disease. On the one hand, high throughput analytical benchtop approaches are still highly demanding for accelerating diagnostics. Such platforms are required to show multiplexed capabilities while in turn reducing the turnaround times of currently applied techniques such as the RT-PCR gold standard. On the other hand, massive screening and surveillance protocols still require for effective tools at the point of need that could reliably detect the virus in individuals after being exposed or the likelihood of being immunized after suffering from the disease. The rapid detection of coronavirus biomarkers, including RNA as well as spike and nucleocapsid proteins in nasopharyngeal and oropharyngeal samples, together with host biomarkers such as immunoglobulins and cytokines in serum has been addressed in this work. We aim to produce tools that provided with a global response to the diagnosis, prognosis and follow-up of the disease (Figure 1). All the biocomponents and corresponding bioassay protocols required for measuring these biomarkers have been tailored made and implemented in three different platforms. A calorimetric device based on a lateral flow assay format [1, 2] and a multiplex electrochemical platform comprising an electrochemical transducer array and a paper microfluidic component [3] have been adapted to produce tools to be used at the point of care. Likewise, a fluorescence microarray platform has been set up with the potential for high-throughput screening by recording molecular signatures thanks to the its multiplexing and miniaturization capabilities. REFERENCES [1] E. Polo et al. PCT, ES2013/070549 [2] E. Polo et al. Chem. Commun., 49 (2013) 3676 [3] C. Fernández-Sánchez et al. Application no. EP20382721.

Salud de los trabajadores

Actividad física y su relación con los factores de riesgo cardiovascular de carteros chilenosAnálisis de resultados: riesgos psicosociales en el trabajo Suceso-Istas 21 en Cesfam QuellónAusentismo laboral por enfermedades oftalmológicas, Chile 2009Brote de diarreas por norovirus, posterremoto-tsunami, Constitución, Región del MauleCalidad de vida en profesionales de la salud pública chilenaCaracterización del reposo laboral en personal del SSMN durante el primer semestre de 2010Concentración de nicotina en pelo en trabajadores no fumadores expuestos a humo de tabaco ambientalCondiciones de trabajo y bienestar/malestar docente en profesores de enseñanza media de SantiagoDisfunción auditiva inducida por exposición a xilenoErgonomía aplicada al estudio del síndrome de dolor lumbar en el trabajoEstimación de la frecuencia de factores de riesgo cardiovascular en trabajadores de una empresa mineraExposición a plaguicidas inhibidores de la acetilcolinesterasa en Colombia, 2006-2009Factores de riesgo y daños de salud en conductores de una empresa peruana de transporte terrestre, 2009Las consecuencias de la cultura en salud y seguridad ocupacional en una empresa mineraPercepción de cambios en la práctica médica y estrategias de afrontamientoPercepción de la calidad de vida en la Universidad del BiobíoPesos máximos aceptables para tareas de levantamiento manual de carga en población laboral femeninaRiesgo coronario en trabajadores mineros según la función de Framingham adaptada para la población chilenaTrastornos emocionales y riesgo cardiovascular en trabajadores de la salu

Envejecimiento de la población

•Actividades básicas de la vida diaria en personas mayores y factores asociados •Asociación entre depresión y posesión de mascotas en personas mayores •Calidad de vida en adultos mayores de Santiago aplicando el instrumento WHOQOL-BREF •Calidad de vida en usuarios con enfermedad de Parkinson, demencia y sus cuidadores, comuna de Vitacura •Caracterización de egresos hospitalarios de adultos mayores en Puerto Natales (2007-2009) •Comportamiento de las patologías incluidas como GES para el adulto mayor atendido en un Cesfam •Contribución de vitaminas y minerales a las ingestas recomendadas diarias en ancianos institucionalizados de Madrid •Estado de salud oral del paciente inscrito en el Programa de Visita Domiciliaria •Evaluación del programa de discapacidad severa en Casablanca con la matriz de marco lógico •Factores asociados a satisfacción vital en una cohorte de adultos mayores de Santiago, Chile •Pauta instrumental para la identificación de riesgos para el adulto mayor autovalente, en su vivienda •Perfil farmacológico del paciente geriátrico institucionalizado y posibles consecuencias en el deterioro cognitivo •Programa de cuidados paliativos y alivio del dolor en Puerto Natales •Rehabilitación mandibular implantoprotésica: efecto en calidad de vida relacionada con salud bucal en adultos mayores •Salud bucodental en adultos mayores autovalentes de la Región de Valparaíso •Transición epidemiológica y el estudio de carga de enfermedad en Brasi