IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.

While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.

SEOM-GEMCAD-TTD clinical guideline for the diagnosis and treatment of gastric cancer (2023).

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, the incidence is lower and GC represents the tenth most frequent tumor and the seventh cause of cancer mortality. Molecular biology knowledge allowed to better profile patients for a personalized therapeutic approach. In the localized setting, the multidisciplinary team discussion is fundamental for planning the therapeutic approach. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors, and chemoradiation + surgery + adjuvant immunotherapy for the GEJ are current standards. For the metastatic setting, biomarker profiling including Her2, PD-L1, MSS status is needed. Chemotherapy in combination with checkpoint inhibitors had improved the outcomes for patients with PD-L1 expression. Her2 positive patients should receive antiHer2 therapy added to chemotherapy. We describe the different evidences and recommendations based on the literature.

Inhibition of Crif1 protects fatty acid-induced POMC neuron-like cell-line damage by increasing CPT-1 function.

Hypothalamic proopiomelanocortin (POMC) neurons are sensors of signals that reflect the energy stored in the body. Inducing mild stress in proopiomelanocortin neurons protects them from the damage promoted by the consumption of a high-fat diet, mitigating the development of obesity; however, the cellular mechanisms behind these effects are unknown. Here, we induced mild stress in a proopiomelanocortin neuron cell line by inhibiting Crif1. In proopiomelanocortin neurons exposed to high levels of palmitate, the partial inhibition of Crif1 reverted the defects in mitochondrial respiration and ATP production; this was accompanied by improved mitochondrial fusion/fission cycling. Furthermore, the partial inhibition of Crif1 resulted in increased reactive oxygen species production, increased fatty acid oxidation, and reduced dependency on glucose for mitochondrial respiration. These changes were dependent on the activity of CPT-1. Thus, we identified a CPT-1-dependent metabolic shift toward greater utilization of fatty acids as substrates for respiration as the mechanism behind the protective effect of mild stress against palmitate-induced damage of proopiomelanocortin neurons.NEW & NOTEWORTHY Saturated fats can damage hypothalamic neurons resulting in positive energy balance, and this is mitigated by mild cellular stress; however, the mechanisms behind this protective effect are unknown. Using a proopiomelanocortin cell line, we show that under exposure to a high concentration of palmitate, the partial inhibition of the mitochondrial protein Crif1 results in protection due to a metabolic shift warranted by the increased expression and activity of the mitochondrial fatty acid transporter CPT-1.

Delphi consensus for the third-line treatment of metastatic colorectal cancer.

PURPOSE: The optimal drug regimen and sequence are still unknown for patients with metastatic colorectal cancer (mCRC) who are candidates for third-line (3L) or subsequent treatment. The aim of this study is to know the opinion of experts on the most appropriate treatment options for mCRC in 3L and to clarify certain clinical decisions in Spain. METHODS: Using a modified Delphi method, a group of experts discussed the treatment in 3L of patients with mCRC and developed a questionnaire with 21 items divided into 5 sections. RESULTS: After 2 rounds, the 67 panelists consulted agreed on 17 items (81%). They considered that the main objective of 3L is to equally increase survival and improve patients' quality of life (QoL), but preferably the QoL. It was agreed that patients with mCRC in 3L prefer to receive active versus symptomatic treatment. Panelists considered trifluridine/tipiracil (FTD/TPI) to be the best oral treatment available to them in 3L. In patients with MSI-H or dMMR and BRAF V600E, the panelists mostly prefer targeted treatments. Panelists agreed the use of a therapeutic sequence that not only increases outcomes but also allows patients to be treated later. Finally, it was agreed that FTD/TPI has a mechanism of action that allows it to be used in patients refractory to previous treatment with 5-fluorouracil. CONCLUSION: The experts agreed with most of the proposed items on 3L treatment of mCRC, prioritizing therapeutic options that increase survival and preserve QoL, while facilitating the possibility that patients can continue to be treated later.

Segmented neutrophil-to-monocyte ratio and systemic immune-inflammation index associated with the severity and functional prognosis of acute ischemic stroke.

PURPOSE/AIM OF THE STUDY: To identify the inflammation indexes associated with the severity and functional prognosis in ischemic stroke. MATERIAL AND METHODS: A prospective study was conducted with ischemic stroke cases included in the i-ReNe clinical registry. Patients were divided into groups according to the severity on admission measured by the National Institutes of Health Stroke Scale (NIHSS) and the functional prognosis at 30 and 90 days of discharge measured by the modified Rankin Scale (mRS). RESULTS: We included 145 patients with a mean age of 61.5 ± 12.75, 97 (66.9%) were men. The leukocyte and neutrophil counts, Neutrophil-to-Lymphocyte ratio (NLR), Derived Neutrophil-to-Lymphocyte ratio (dNLR), Platelet-to-Lymphocyte ratio (PLR), Segmented Neutrophil-to-Monocyte ratio (SeMo ratio), and Systemic Immune-inflammation index (SII) were higher in moderate-to-severe stroke (NIHSS ≥6). NLR, PLR, SeMo ratio, and SII were higher in the group with severe disability and death at 30 days (mRS ≥4). In the multiple logistic regression analyses, SeMo ratio >14.966 and SII >623.723 were associated with moderate-to-severe stroke (NIHSS ≥6). In addition, SeMo ratio >7.845 was associated with severe disability and death at 30 days (mRS ≥4). CONCLUSIONS: Systemic inflammation indexes could be rapid and low-cost markers used in the initial evaluation of ischemic stroke, whose values could help to stratify patients according to their severity and functional prognosis. This is the first study to establish a relationship between ischemic stroke and the SeMo ratio.

Hantavirus in Panama: Twenty Years of Epidemiological Surveillance Experience.

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999-2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4-5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide.

The impact of a story on learning ketone body metabolism.

Biochemistry is a core subject in the cross-disciplinary training on Biotechnology engineering courses. Metabolic pathways teaching has traditionally integrated hands-on laboratory experiences and traditional lectures, which detail a large number of reactions at a molecular level, their enzymes and regulation. The current scenario of Covid-19 outbreak have motivated the development of complementary tools that expand the horizon of metabolism teaching. In this study, we employed a story-based methodology to strengthen the metabolic pathways learning and to measure students' perception. Specifically, a peer-reviewed tale describing the ketone body metabolism was used during five semesters as a didactic strategy to teach this biochemical process. A questionnaire assessed the students' understanding and acceptance of the methodology (n = 83). Our findings showed that a high proportion of students (83.13%) were able to relate the story to the topics studied in the classroom (ketogenesis and ketolysis). On the other hand, they were satisfied and suggested that such methodology is effective and fun. In summary, most of the survey responses related to acceptance of story-based strategy ranged from 72% to 97%. Collectively, these results indicated that the story is appropriate to decomplex pathways, becoming a simple tool for driving motivation, learning and engagement of students. The narrative represents a bridge to connect the intriguing series of chemical reactions involved in the anabolism and degradation of 3-hydroxybutyrate (3-OHB), acetoacetate, and acetone with previously learned knowledge, emotions, and key concepts. In conclusion, the tale was useful to decode ketone body-related pathways and making metabolism learning more interesting and easier.

Resilience of environment, infrastructure, communities, and governance in Puerto Rico after Hurricane Maria and the need for community empowerment to develop decentralized, nature-based solutions to sustainability.

Collapse of electric and water infrastructure throughout Puerto Rico with Hurricane Maria is well documented but assessment of interactions among environment, infrastructure, and society is lacking. A classification system is developed to assess the resilience of each component based on principles of ecosystem responses to long-term and unexpected environmental change. All infrastructure sectors have experienced long-term decline because of a patch and stabilize approach that excludes strengthen and innovate. Maria was the tipping point for system collapse. The weakest sector, however, is governance and an inability to change direction from traditional centralized, engineered approaches incapable of meeting current or projected changes in resource availability and societal needs. The two most resilient sectors are environment and human communities. Their strong interrelationship is key to developing decentralized, nature-based solutions to address immediate and projected threats to resiliency and sustainability of communities in Puerto Rico. Still in its infancy, community ownership of the water-energy-food Nexus shows a great promise for island.

An experimental protocol for molecular biology lab at an Amazonian University.

Laboratory-based practical classes are an essential component in teaching molecular biology for undergraduate students. Universidad Regional Amazonica Ikiam is a higher education institution located in the Ecuadorian Amazon rainforest, a high biodiversity place, including amphibians. Based on this, we have established a practical molecular biology program with eight sessions that contextualize the biodiverse surroundings of the University. This program stimulates synchronization of information between theory and practice and improves research skills. During these sessions, students are motivated to identify and characterize antimicrobial peptides from Ecuadorian frog skin secretions, using molecular biology techniques and biochemistry and microbiology knowledge. This practical course was held twice with a total of 56 students from the fifth semester of the biotechnology engineering. The evaluation of the practical program was carried out through a questionnaire applied to students using the Likert scale. Overall, this form of teaching had high receptivity and presented benefits for student learning. Interestingly, 80% of respondents strongly agreed that this course provided tools and knowledge for the development of their undergraduate dissertation. Therefore, practical courses tailored to the student's context can stimulate student learning and interest. Additionally, this experimental methodology is interdisciplinary and can be applied to other research fields and subjects.

SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021).

Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.

Modeling the sulfamethoxazole degradation by active chlorine in a flow electrochemical reactor.

The aim of this study is to propose a continuous physicochemical model accounting for the active chlorine production used to degrade recalcitrant sulfamethoxazole (SMX) in an electrochemical flow reactor. The computational model describes the fluid mechanics and mass transfer occurring in the re/actor, along with the electrode kinetics of hydrogen evolution reaction arising on a stainless steel cathode, and the chloride oxidation on a DSA. Specifically, the anodic contributions assume the heterogeneous nature of the adsorbed chlorine species formed on this surface, which are a model requirement to correctly define the experimental reactor performance and degradation efficiency of the contaminant. The experimental validation conducted at different applied current densities, volumetric flows, and chloride concentrations is adequately explained by the model, thus evidencing some of the phenomena controlling the electrocatalytic chlorine production for environmental applications. The best conditions to eliminate the SMX are proposed based on the theoretical analysis of the current efficiency calculated with the model, and experimentally confirmed. The use of the Ti/RuO2-ZrO2-Sb2O3 anode at the bench scale improves the SMX removal by using electro-generated chlorine species adsorbed on its surface, which remarkably increases the oxidation potential of the system along with chlorine desorbed from the electrode. This is a technological innovation concerning other mediated oxidation methods entirely using oxidants in solution.

Particle image velocimetry and digital image correlation for determining the elasticity modulus in wood

Several non-destructive testing techniques have been improved and tested in recent years. The non-destructive testing techniques using particle image velocimetry (PIV) and digital image correlation (DIC) differ from conventional testing techniques, as they allow making measurements indirectly. In this study, the elastic modulus in wood beams of Eucalyptus grandis and Pinus oocarpa were determined using PIV and DIC. The application of PIV and DIC techniques occurred during the static bending tests, when the displacements were also measured by the conventional method. The applied load values allowed calculating the elasticity modulus. In all regions of analysis, the mean values of the elasticity modulus found by the DIC, PIV and conventional method are statistically equivalent. It is concluded that the PIV and DIC testing techniques can be used to determine mechanical properties of wood.

Fighting Against Stroke in Latin America: A Joint Effort of Medical Professional Societies and Governments.

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments.

Psychosocial impact on health-related and non-health related university students during the COVID-19 pandemic. Results of an electronic survey.

INTRODUCTION: The current SARS-CoV-2 pandemic has caused feelings of anxiety, confusion, and panic among the world population. Due to these psychological changes resulting from the stress produced by the disease, we sought to investigate the psychological impact of the pandemic on the university student community. MATERIAL AND METHODS: 1,283 students were surveyed, of which 1,149 students were selected. The majority of the subjects were female, and the overall average age was of 20 years. They were provided with an 82-question online questionnaire divided into four sections; looking for the prevalence of significant symptomatology of major depression and generalised anxiety using the PHQ-9 and GAD-7 scales; and factors that potentially affect the mental health of our university population. RESULTS: We found a high prevalence of significant depression (47.08%) and anxiety (27.06%) symptomatology, considering a score of 10 or more as cut-off point. There was no significant difference in depression and anxiety symptomatology between the health-care students and non-health-care students. CONCLUSIONS: Our results, together with what is observed in the literature, allow us to conclude that the college student population has a high risk of mental illness, and these should be taken into consideration for the search of effective strategies for detection and control of mental health illnesses. Undoubtedly, the COVID-19 pandemic is a red flag that shows the need to upgrade mental health programmes in universities and to validate virtual instruments.

Psychosocial impact on health-related and non-health related university students during the COVID-19 pandemic. Results of an electronic survey / Impacto psicosocial en estudiantes universitarios de ciencias de la salud y otros durante la pandemia de COVID-19. Resultados de una encuesta electrónica

ABSTRACT Introduction: The current SARS-CoV-2 pandemic has caused feelings of anxiety, confusion, and panic among the world population. Due to these psychological changes resulting from the stress produced by the disease, we sought to investigate the psychological impact of the pandemic on the university student community. Material and methods: 1,283 students were surveyed, of which 1,149 students were selected. The majority of the subjects were female, and the overall average age was of 20 years. They were provided with an 82-question online questionnaire divided into four sections; looking for the prevalence of significant symptomatology of major depression and generalised anxiety using the PHQ-9 and GAD-7 scales; and factors that potentially affect the mental health of our university population. Results: We found a high prevalence of significant depression (47.08%) and anxiety (27.06%) symptomatology, considering a score of 10 or more as cut-off point. There was no significant difference in depression and anxiety symptomatology between the health-care students and non-health-care students. Conclusions: Our results, together with what is observed in the literature, allow us to conclude that the college student population has a high risk of mental illness, and these should be taken into consideration for the search of effective strategies for detection and control of mental health illnesses. Undoubtedly, the COVID-19 pandemic is a red flag that shows the need to upgrade mental health programmes in universities and to validate virtual instruments.

RESUMEN Introducción y objetivos: La actual pandemia de SARS-CoV-2ha causado sentimientos de ansiedad, confusión y pánico entre la población mundial. Debido a estos cambios psi cológicos derivados del estrés que produce la enfermedad, se buscó investigar el impacto psicológico de la pandemia en la comunidad estudiantil universitaria. Material y métodos: Se encuestó a 1.283 estudiantes, de los que se seleccionó a 1.149. La mayoría eran mujeres y la media de edad fue 20 anos. Se les proporcionó un cuestionario en línea de 82 preguntas divididas en 4 secciones para indagar la prevalencia de síntomas signi ficativos de depresión mayor y ansiedad generalizada utilizando las escalas PHQ-9 y GAD-7, además factores que pueden afectar a la salud mental de nuestra población universitaria. Resultados: Se halló una alta prevalencia de síntomas significativos de depresión (47,08%) y ansiedad (27,06%), considerando como umbral un total de 10 o más puntos. No hubo difer encias significativas entre los estudiantes relacionados con la salud y los no relacionados con la salud. Conclusiones: Nuestros resultados, en conjunto con lo observado en la literatura, muestran que la comunidad universitaria es una población en riesgo de enfermedades mentales, por lo que el Gobierno debería considerar la creación de estrategias efectivas para la detección de problemas de salud mental; sin duda alguna, la actual pandemia de COVID-19 es un foco rojo sobre las necesidad de mejores programas de salud mental en universidades y validación de instrumentos virtuales.