Skeletal Muscle Mitochondrial Function/Dysfunction and Type 2 Diabetes

“Let food be your medicine and medicine be your food” stated Hippocrates, the father of Western medicine, in 400 B.C. This statement was based on the belief that food was able to influence disease, a concept that was revived several times in later years by painters, writers, scientists, and philosophers. One such philosopher, Ludwig Feuerbach, famously wrote in his 1863-4 essay “man is what he eats” introducing the idea that if we want to improve the spiritual conditions of people we must first improve their material conditions (Feuerbach, 2003). However, for years his warnings remained unheeded, at least in Western countries, in contrast to the teachings of Indian and Chinese medicine which for millennia have argued that a living organism has to assume a healthy diet. Like diet, physical activity has been also considered an important starting point for people's health. Hippocrates wrote in his book Regimen "if we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health" (Hippocrates, 1955). Our knowledge about the links between diet, exercise, and disease has vastly increased since Hippocrates time. A healthy lifestyle based on diet and physical activity is now considered the keystone of disease prevention and the basis for a healthy aging. However, modern society has created conditions with virtually unrestricted access to food resources and reduced physical activity, resulting in a positive overall energy balance. This is far from the environment of our ”hunter-gathered ancestros” whose genes were modulated over thousands of years adapting our metabolism to survive when food was scarce and maximizing energy storage when food became available. In terms of evolution, this radical and sudden lifestyle change in modern society has led to a dramatic increase in the incidence of metabolic diseases including obesity and type 2 diabetes mellitus (T2DM). It seems clear that the development of T2DM has a genetic component that becomes obvious when individuals are exposed to western lifestyle. However, environment plays a critical role in the incidence of the disease being obesity the main etiological cause of T2DM. Thus, modest weight loss is enough for obese glucose intolerant subjects to prevent the development of T2DM (National Task Force on the Prevention and Treatment of Obesity, 2000)..

Long-term assessment of the translocation of an endangered primate into an agroforestry system

Translocation is increasingly being used as a conservation tool in wildlife management, but long-term assessments of the animals’ establishment in the new habitat are rarely done. In addition, finding protected areas for translocations can often be a limitation, but habitat patches managed for productive purposes could potentially be used for translocations. Here, we present a translocation case study of the Endangered Mexican howler monkey Alouatta palliata mexicana into a forest fragment managed as an agroforest in the Los Tuxtlas Biosphere Reserve (Mexico). We compared the behavior of the translocated focal group 6 yr after translocation with that ob - served 1 yr after translocation (Year 1 vs. Year 6), and with reference parameters for conserved forest. We also examined the 14 yr trajectory of the translocated population through published data. We found that in Year 6, monkeys spent less time on locomotion and more time consuming fruit than in Year 1. The focal group in Year 6 had doubled its activity area compared to Year 1. All behavioral parameters during Year 6 were similar to those reported for the species in conserved forest. During the first 14 yr, the translocated population increased at a rate of 1.29 ind. yr−1. We conclude that this translocation succeeded in establishing a thriving population and that certain agroforestry systems may be adequate habitat for primate translocations. We also discuss how the translocation of howler monkeys into defaunated habitats might help restore ecological functions associated with these primates, such as the dispersal of large-seeded plants. Long-term information on successful primate translocations has high practical value for designing adequate conservation strategies in anthropogenic landscapes

Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance

Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown. Here, we show that mitochondria-ER contacts in anorexigenic pro-opiomelanocortin (POMC) neurons in the hypothalamus are decreased in diet-induced obesity. POMC-specific ablation of Mfn2 resulted in loss of mitochondria-ER contacts, defective POMC processing, ER stress-induced leptin resistance, hyperphagia, reduced energy expenditure, and obesity. Pharmacological relieve of hypothalamic ER stress reversed these metabolic alterations. Our data establish MFN2 in POMC neurons as an essential regulator of systemic energy balance by fine-tuning the mitochondrial-ER axis homeostasis and function. This previously unrecognized role for MFN2 argues for a crucial involvement in mediating ER stress-induced leptin resistance

Molecular modulators of celastrol as the keystones for its diverse pharmacological activities

© 2018 The Authors In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development

Transdisciplinary studies in socio-ecosystems: Theoretical considerations and its application in Latin American contexts

Debido a limitaciones para abordar la complejidad de la relación sociedad-naturaleza, los esfuerzos para solucionar los problemas ambientales han sido en general infructuosos. Aquí proponemos que el enfoque holístico de “socio-ecosistema” por parte de la academia, podría contribuir a disminuir estas limitaciones desde la adopción de cuatro cambios: i) ontológico, que presenta el concepto de “socio-ecosistemas”; ii) epistemológico, que propone a la transdisciplina como la forma de entenderlos, iii) metodológico, que sugiere intervenir en ellos de forma participativa y adaptativa y, iv) cambios institucionales que facilitarían la adopción de esta propuesta. Este planteamiento se complementa con la descripción de una experiencia transdiciplinaria en la cuenca del río San Juan Zitácuaro, México, en el contexto de un curso internacional de manejo de socio-ecosistemas.Given the difficulties to approach the complex relationship bettween society and nature, efforts to solve environmental problems have generally been unsuccessful. Here we suggest that a hollistic “socio-ecosystem” approach by the sciencies could help diminish these difficulties by embracing four kinds of changes: i) ontological, which introduces the concept of “socio-ecosystem”; ii) epistemological, which proposes transdiscipline as the way to understand them, iii) metholodogical, which suggests that in intervention in them must be participatory and adaptive, iv) institutional changes that would facilitate the adoption of this approach. This is then followed by a description of a transdisciplinary work experience in the Zitácuaro river basin, in Mexico, in the context of an international course on socio-ecosystem management.Fil: Ortega Uribe, Tamara. Universidad de Chile; ChileFil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Villarroel Torrez, Daniel. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piaz, Agustín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica ; ArgentinaFil: Vallejos, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Saenz Ceja, Jesús Eduardo. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Gallego, Federico. Universidad de la República. Facultad de Ciencias; UruguayFil: Franquesa Soler, Monserrat. Instituto de Ecología; MéxicoFil: Calzada Peña, Leonardo. Universidad Nacional Autónoma de México; MéxicoFil: Espinosa Mellado, Noelia. Universidad de la Armada; MéxicoFil: Fiestas Flores, Jerico. Instituto de Estudios Peruanos; PerúFil: Gill Mairhofer, Luis R.. Ministerio de la Defensa Pública; ParaguayFil: González Espino, Zarahí. Instituto Superior de Tecnologías y Ciencias Aplicadas. Facultad de Medio Ambiente. Departamento de Meteorología; CubaFil: Luna Salguero, Betsabé Montserrat. Sociedad de Historia Natural Niparajá; MéxicoFil: Martinez Peralta, Claudia María. Comisión de Ecología y Desarrollo Sustentable del Estado de Sonora. Dirección General de Conservación; MéxicoFil: Ochoa, Olivia. Universidad Nacional Autónoma de México; MéxicoFil: Pérez Volkow,Lucía. No especifica;Fil: Sala, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Sánchez Rose, Isabelle. Universidad Central de Venezuela; VenezuelaFil: Weeks, Madeline. University of Cambridge; Reino UnidoFil: Ávila García, Daniela. Universidad Nacional Autónoma de México; MéxicoFil: García Reyes, Isabel Bueno. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Carmona, Alejandra. Universidad Austral de Chile. Instituto de Economía Agraria; ChileFil: Castro Videla, Fernando Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan; ArgentinaFil: Ferrer Gonzalez, César Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Frank Buss, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: López Carapia, Gabriela. Universidad Nacional Autónoma de México; MéxicoFil: Núñez Cruz, Martha. Universidad Nacional Autónoma de México; MéxicoFil: Taboada Hermoza, Rossi. Universidad Nacional Mayor de San Marcos; PerúFil: Benet, Daniel. Alternare A. C.; MéxicoFil: Venegas, Ysmael. Alternare A. C.; MéxicoFil: Balvanera, Patricia. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Mwampamba, Tuyeni H.. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Lazos Chavero, Elena. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Noellemeyer, Elke Johanna. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maass, Manuel. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; Méxic

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery