Transcriptomic analysis of the hepatic response to stress in the red cusk-eel (Genypterus chilensis): Insights into lipid metabolism, oxidative stress and liver steatosis

Indexación: Scopus.Teleosts exhibit a broad divergence in their adaptive response to stress, depending on the magnitude, duration, and frequency of stressors and the species receiving the stimulus. We have previously reported that the red cusk-eel (Genypterus chilensis), an important marine farmed fish, shows a physiological response to stress that results in increased skeletal muscle atrophy mediated by over-expression of components of the ubiquitin proteasome and autophagy-lysosomal systems. To better understand the systemic effects of stress on the red cusk-eel metabolism, the present study assessed the transcriptomic hepatic response to repetitive handling-stress. Using high-Throughput RNA-seq, 259 up-regulated transcripts were found, mostly associated with angiogenesis, gluconeogenesis, and triacylglyceride catabolism. Conversely, 293 transcripts were down-regulated, associated to cholesterol biosynthesis, PPARα signaling, fatty acid biosynthesis, and glycolysis. This gene signature was concordant with hepatic metabolite levels and hepatic oxidative damage. Moreover, the increased plasmatic levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase) and AP (alkaline phosphatase), as well as liver histology suggest stress-induced liver steatosis. This study offers an integrative molecular and biochemical analysis of the hepatic response to handling-stress, and reveals unknown aspects of lipid metabolism in a non-model teleost.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.017644

Trametinib Induces the Stabilization of a Dual GNAQ p.Gly48Leu- and FGFR4 p.Cys172Gly-Mutated Uveal Melanoma. The Role of Molecular Modelling in Personalized Oncology.

We report a case of an uveal melanoma patient with GNAQ p.Gly48Leu who responded to MEK inhibition. At the time of the molecular analysis, the pathogenicity of the mutation was unknown. A tridimensional structural analysis showed that Gα <sub>q</sub> can adopt active and inactive conformations that lead to substantial changes, involving three important switch regions. Our molecular modelling study predicted that GNAQ p.Gly48Leu introduces new favorable interactions in its active conformation, whereas little or no impact is expected in its inactive form. This strongly suggests that GNAQ p.Gly48Leu is a possible tumor-activating driver mutation, consequently triggering the MEK pathway. In addition, we also found an FGFR4 p.Cys172Gly mutation, which was predicted by molecular modelling analysis to lead to a gain of function by impacting the Ig-like domain 2 folding, which is involved in FGF binding and increases the stability of the homodimer. Based on these analyses, the patient received the MEK inhibitor trametinib with a lasting clinical benefit. This work highlights the importance of molecular modelling for personalized oncology

Nivel de sesgos cognitivos de representatividad y confirmación en estudiantes de Psicología de tres universidades del Bío-Bío

Cognitive biases are unreasonable ways of making decisions, often in a one-sided way. The objective of this research was to describe the level of representativeness and confirmation biases in Chilean psychology students, in order to know how this phenomenon occurs. The participants were 198 psychology students from three universities in southern Chile. The instrument was based on two cognitive tasks derived from Kanheman and Tversky. The data were analyzed through descriptive statistics and mean differences. The results indicate a high level of biases in the groups of students, in the two tasks evaluated; the representativeness bias presents differences among universities only in sub-task 1, as well as in task 2, related to confirmation bias. Likewise, there are differences in representation bias according to age and sex. The need to strengthen reasoning skills in the initial training of future psychologists, in order to improve skills related to decision making in the professional field is concluded.Los sesgos cognitivos son formas no razonadas de tomar decisiones, a menudo de manera parcializada. El objetivo de esta investigación fue describir el nivel de sesgos de representatividad y confirmación en estudiantes de psicología chilenos, para conocer cómo se presenta este fenómeno. Los participantes fueron 198 estudiantes de psicología, de tres universidades del sur de Chile. El instrumento se basó en dos tareas cognitivas derivadas de Kanheman y Tversky; se analizaron los datos con estadística descriptiva y diferencias de medias. Los resultados indican alto nivel de sesgos en los grupos de estudiantes, en las dos tareas evaluadas; el sesgo de representatividad presenta diferencias entre universidades, solo en la subtarea 1, así como en la tarea 2, relacionada con sesgo de confirmación; así mismo se observan diferencias en sesgo de representación según edad y sexo. Se concluye la necesidad de fortalecer habilidades de razonamiento en la formación inicial de los futuros psicólogos y psicólogas, con la finalidad de mejorar las habilidades relacionadas con la toma de decisiones en el campo profesional

EDUEST@DISTICA UN MEDIADOR DIDACTICO PARA LA ENSEÑANZADE LA ESTADISTICA EN LA EDUCACION SUPERIOR ANGOLANA

En el presente trabajo se explica el uso de un mediador didáctico para la enseñanza de la Estadística en la Educación Superior en Angola y tiene como propósito contribuir a resolver las insuficiencias que se manifiestan en el aprendizaje de los estudiantes, en este nivel de enseñanza la poca existencia de bibliografía relacionada con los temas objeto de estudio en la asignatura, el poco dominio de la informática que les dificulta la búsqueda de información sobre esta materia, las insuficiencias en la argumentación para emitir juicios valorativos en la asignatura y tomar decisiones acertadas en la solución de problemas profesionales. La aplicación «Esduest@distica» constituye un material bibliográfico de fácil manejo e instalación, la misma puede ser usada por cualquier institución educativa para la enseñanza aprendizaje  de la Estadística de forma amena y sencilla

Nivel de sesgos cognitivos de representatividad y confirmación en estudiantes de Psicología de tres universidades del Bío-Bío

Cognitive biases are unreasonable ways of making decisions, often in a one-sided way. The objective of this research was to describe the level of representativeness and confirmation biases in Chilean psychology students, in order to know how this phenomenon occurs. The participants were 198 psychology students from three universities in southern Chile. The instrument was based on two cognitive tasks derived from Kanheman and Tversky. The data were analyzed through descriptive statistics and mean differences. The results indicate a high level of biases in the groups of students, in the two tasks evaluated; the representativeness bias presents differences among universities only in sub-task 1, as well as in task 2, related to confirmation bias. Likewise, there are differences in representation bias according to age and sex. The need to strengthen reasoning skills in the initial training of future psychologists, in order to improve skills related to decision making in the professional field is concluded.Los sesgos cognitivos son formas no razonadas de tomar decisiones, a menudo de manera parcializada. El objetivo de esta investigación fue describir el nivel de sesgos de representatividad y confirmación en estudiantes de psicología chilenos, para conocer cómo se presenta este fenómeno. Los participantes fueron 198 estudiantes de psicología, de tres universidades del sur de Chile. El instrumento se basó en dos tareas cognitivas derivadas de Kanheman y Tversky; se analizaron los datos con estadística descriptiva y diferencias de medias. Los resultados indican alto nivel de sesgos en los grupos de estudiantes, en las dos tareas evaluadas; el sesgo de representatividad presenta diferencias entre universidades, solo en la subtarea 1, así como en la tarea 2, relacionada con sesgo de confirmación; así mismo se observan diferencias en sesgo de representación según edad y sexo. Se concluye la necesidad de fortalecer habilidades de razonamiento en la formación inicial de los futuros psicólogos y psicólogas, con la finalidad de mejorar las habilidades relacionadas con la toma de decisiones en el campo profesional

Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany.

Talimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%. The aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting. Based on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36-95 years) treated with T-VEC during the period from May 2016 to January 2020. 88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1-65), an average of 11 doses (range: 1-36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%). This real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs

Ophrys fusca and Ophrys dyris (Orchidaceae) – constancy of tetraploidy amongst populations in Central Portugal

Ophrys is amongst the best known orchid genera and is an established system for the study of pollinatormediated floral evolution. Two species, Ophrys fusca s.l. and Ophrys dyris (= O. omegaifera subsp. dyris) belonging to Ophrys section Pseudophrys are the focus of this study. In the context of an integrative study of morphological and genetic diversity of O. fusca and O. dyris, genome size (GS) and cytotype diversity were surveyed from Portuguese populations. Flow cytometry methods were used to assess GS, and subsequently determine the ploidy level of 67 specimens, including the species and putative hybrids. Cytotypes were also confirmed based on chromosome counts from the roots of two specimens, one of each species. Constancy of nuclear DNA content (1C = 11.19 pg) and ploidy level (2n =4x = 72, 74) was documented among all the individuals analysed. Implications are considered, in terms of interpreting the origin and predicting the persistence of putative hybrids

Testing a Model of Care for Patients on Immune Checkpoint Inhibitors Based on Electronic Patient-Reported Outcomes: Protocol for a Randomized Phase II Controlled Trial.

Management of severe symptomatic immune-related adverse events (IrAEs) related to immune checkpoint inhibitors (ICIs) can be facilitated by timely detection. As patients face a heterogeneous set of symptoms outside the clinical setting, remotely monitoring and assessing symptoms by using patient-reported outcomes (PROs) may result in shorter delays between symptom onset and clinician detection. We assess the effect of a model of care for remote patient monitoring and symptom management based on PRO data on the time to detection of symptomatic IrAEs from symptom onset. The secondary objectives are to assess its effects on the time between symptomatic IrAE detection and intervention, IrAE grade (severity), health-related quality of life, self-efficacy, and overall survival at 6 months. For this study, 198 patients with cancer receiving systemic treatment comprising ICIs exclusively will be recruited from 2 Swiss university hospitals. Patients are randomized (1:1) to a digital model of care (intervention) or usual care (control group). Patients are enrolled for 6 months, and they use an electronic app to complete weekly Functional Assessment of Cancer Therapy-General questionnaire and PROMIS (PROs Measurement Information System) Self-Efficacy to Manage Symptoms questionnaires. The intervention patient group completes a standard set of 37 items in a weekly PROs version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire, and active symptoms are reassessed daily for the first 3 months by using a modified 24-hour recall period. Patients can add items from the full PRO-CTCAE item library to their questionnaire. Nurses call patients in the event of new or worsening symptoms and manage them by using a standardized triage algorithm based on the United Kingdom Oncology Nursing Society 24-hour triage tool. This algorithm provides guidance on deciding if patients should receive in-person care, if monitoring should be increased, or if self-management education should be reinforced. The Institut Suisse de Recherche Expérimentale sur le Cancer Foundation and Kaiku Health Ltd funded this study. Active recruitment began since November 2021 and is projected to conclude in November 2023. Trial results are expected to be published in the first quarter of 2024 and will be disseminated through publications submitted at international scientific conferences. This trial is among the first trials to use PRO data to directly influence routine care of patients treated with ICIs and addresses some limitations in previous studies. This trial collects a wider spectrum of self-reported symptom data daily. There are some methodological limitations brought by changes in evolving treatment standards for patients with cancer. This trial's results could entail further academic discussions on the challenges of diagnosing and managing symptoms associated with treatment remotely by providing further insights into the burden symptoms represent to patients and highlight the complexity of care procedures involved in managing symptomatic IrAEs. ClinicalTrials.gov NCT05530187; https://www.clinicaltrials.gov/study/NCT05530187. DERR1-10.2196/48386

Iberoamerican network of medicine post-consumption programs: past, present and future

La contaminación por residuos farmacéuticos es una preocupación a nivel mundial. Diversos estudios han demostrado el efecto deletéreo que estos productos ocasionan sobre los ecosistemas en general, incluyendo los seres humanos. Entre las estrategias propuestas para mitigar esta problemática figuran los programas de gestión posconsumo de medicamentos, basados, en su mayoría, en conceptos de Responsabilidad Social Empresaria, Economía Circular y Logística Inversa. De tales programas se destacan cuatro, que han sido instalados con éxito, en Colombia (Punto Azul), España (SIGRE), México (SINGREM) y Portugal (VALORMED). En forma conjunta integran la Red Iberoamericana de Programas Posconsumo de Medicamentos. En este trabajo se brinda un panorama de los orígenes de estos programas, su situación actual y las proyecciones futuras.A contaminação por resíduos farmacêuticos é uma preocupação mundial. Vários estudos têm mostrado o efeito deletério que esses produtos causam nos ecossistemas em geral, inclusive no ser humano. Entre as estratégias propostas para mitigar esse problema estão os programas de gestão de medicamentos pós-consumo, em sua maioria baseados nos conceitos de Responsabilidade Social Corporativa, Economia Circular e Logística Reversa. Destacam-se quatro desses programas, implantados com sucesso na Colômbia (Punto Azul), Espanha (SIGRE), México (SINGREM) e Portugal (VALORMED). Juntos, eles compõem a Rede Ibero-Americana de Programas Pós-Consumo de Medicamentos. Este artigo fornece uma visão geral sobre as origens desses programas, sua situação atual e projeções futuras.Contamination by pharmaceuticals is a worldwide concern. Several studies have shown the deleterious effect that these products cause to ecosystems, including human beings. Among the strategies proposed to mitigate this problem are postconsumer drug management programs, mostly based on the concepts of Corporate Social Responsibility, Circular Economy, and Reverse Logistics. Four of these programs stand out, which have been successfully installed in Colombia (Punto Azul), Spain (SIGRE), Mexico (SINGREM) and Portugal (VALORMED). Together they conform the Ibero-American Network of Post-Consumer Drug Programs. This paper provides an overview of the origins of these programs, their current situation, and future projections.Fil: Aedo, José A.. Sistema Nacional de Gestión de Residuos de Envases y Medicamentos; MéxicoFil: Figueiredo, Luis. Sociedade Gestora de Resíduos de Embalagens e Medicamentos; PortugalFil: González Vidal, Noelia Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Control de Calidad de Medicamentos; Argentina. Sociedad Iberoamericana de Salud Ambiental; ArgentinaFil: Mampasso, Juan C.. Medicamento y Medio Ambiente; EspañaFil: Pinzon Ramirez, J.c.. Corporación Punto Azul; ColombiaFil: Trujillo Sanchez, J.e.. Corporación Punto Azul; Colombi