Modelos de composición corporal basados en antropometría: revisión sistemática de literatura / Body composition models based on anthropometry: systematic literature review

La determinación de la composición corporal se realiza a través de métodos de medición que requieren el uso de equipos especializados de difícil adquisición y manipulación. Por esta razón, diferentes autores han desarrollado modelos matemáticos para su cálculo. El objetivo de esta revisión fue analizar los trabajos realizados en modelos matemáticos para la determinación de variables de composición corporal a partir de medidas antropométricas, respondiendo las siguientes preguntas: ¿cuál es la variable corporal que el modelo predice?, ¿cuáles son las variables de entrada para el desarrollo del modelo?, ¿cómo es la tipificación de pacientes en cada modelo?, ¿qué método de análisis de datos es utilizado? y ¿cómo se evaluó el modelo? Se limitó la búsqueda a las revistas que se encuentran en los repositorios de las áreas de Medicina, Enfermería, Bioquímica, Biología, Salud, Farmacología, Inmunología, Ingeniería y Matemáticas. Se encontraron 424 artículos que se redujeron a 30 al aplicar el proceso de revisión sistemática de literatura. Se observa que los estudios analizados se orientan a la predicción de variables relacionadas con la masa grasa corporal. Los resultados de evaluación encontrados para masa libre de grasa, masa grasa y tasa metabólica basal difieren dependiendo de la técnica de comparación y los segmentos corporales analizados. La evaluación se basa principalmente en correlación intraclase, correlación de Pearson y el coeficiente de determinación (r2 ) y se denota una buena correlación para la población objeto de estudio. (AU)

The body composition determination is carried out through measurement methods that require the use of specialized equipment that is difficultto acquire and manipulate. Therefore, different authors have developed mathematical models for its calculation. The target of this review was toanalyze the work carried out on mathematical models of body composition variables from different anthropometric measurements, answeringthe following questions: what is the corporal variable that the model predicts?, what are the input variables for model development?, how is thepatients typification in each model?, what data analysis method has been used?, and how has been the model evaluated? The search was limited to journals found in repositories in the areas of Medicine, Nursing, Biochemistry, Biology, Health, Pharmacology, Immunology, Engineering, and Mathematics. Four hundred and twenty-four articles were found, which were reduced to 30 by applying the systematic literature review process. The analyzed studies are oriented to the prediction of variables related to body fat mass. The evaluation results found for fat-free mass, fat mass and metabolic rate differ according to the comparison technique and the body segments analyzed. The evaluation is mainly based on the intraclass correlation, the Pearson correlation and the coefficient of determination (r2 ), and they present a good correlation for the population under study. (AU)

[Body composition models based on anthropometry, systematic literature review]. / Modelos de composición corporal basados en antropometría: revisión sistemática de literatura.

Introduction: The body composition determination is carried out through measurement methods that require the use of specialized equipment that is difficult to acquire and manipulate. Therefore, different authors have developed mathematical models for its calculation. The target of this review was to analyze the work carried out on mathematical models of body composition variables from different anthropometric measurements, answering the following questions: what is the corporal variable that the model predicts?, what are the input variables for model development?, how is the patients typification in each model?, what data analysis method has been used?, and how has been the model evaluated? The search was limited to journals found in repositories in the areas of Medicine, Nursing, Biochemistry, Biology, Health, Pharmacology, Immunology, Engineering, and Mathematics. Four hundred and twenty-four articles were found, which were reduced to 30 by applying the systematic literature review process. The analyzed studies are oriented to the prediction of variables related to body fat mass. The evaluation results found for fat-free mass, fat mass and metabolic rate differ according to the comparison technique and the body segments analyzed. The evaluation is mainly based on the intraclass correlation, the Pearson correlation and the coefficient of determination (r2), and they present a good correlation for the population under study.

Introducción: La determinación de la composición corporal se realiza a través de métodos de medición que requieren el uso de equipos especializados de difícil adquisición y manipulación. Por esta razón, diferentes autores han desarrollado modelos matemáticos para su cálculo. El objetivo de esta revisión fue analizar los trabajos realizados en modelos matemáticos para la determinación de variables de composición corporal a partir de medidas antropométricas, respondiendo las siguientes preguntas: ¿cuál es la variable corporal que el modelo predice?, ¿cuáles son las variables de entrada para el desarrollo del modelo?, ¿cómo es la tipificación de pacientes en cada modelo?, ¿qué método de análisis de datos es utilizado? y ¿cómo se evaluó el modelo? Se limitó la búsqueda a las revistas que se encuentran en los repositorios de las áreas de Medicina, Enfermería, Bioquímica, Biología, Salud, Farmacología, Inmunología, Ingeniería y Matemáticas. Se encontraron 424 artículos que se redujeron a 30 al aplicar el proceso de revisión sistemática de literatura. Se observa que los estudios analizados se orientan a la predicción de variables relacionadas con la masa grasa corporal. Los resultados de evaluación encontrados para masa libre de grasa, masa grasa y tasa metabólica basal difieren dependiendo de la técnica de comparación y los segmentos corporales analizados. La evaluación se basa principalmente en correlación intraclase, correlación de Pearson y el coeficiente de determinación (r2) y se denota una buena correlación para la población objeto de estudio.

CRISPRi screening reveals regulators of tau pathology shared between exosomal and vesicle-free tau.

The aggregation of the microtubule-associated protein tau is a defining feature of Alzheimer's disease and other tauopathies. Tau pathology is believed to be driven by free tau aggregates and tau carried within exosome-like extracellular vesicles, both of which propagate trans-synaptically and induce tau pathology in recipient neurons by a corrupting process of seeding. Here, we performed a genome-wide CRISPRi screen in tau biosensor cells and identified cellular regulators shared by both mechanisms of tau seeding. We identified ANKLE2, BANF1, NUSAP1, EIF1AD, and VPS18 as the top validated regulators that restrict tau aggregation initiated by both exosomal and vesicle-free tau seeds. None of our validated hits affected the uptake of either form of tau seeds, supporting the notion that they operate through a cell-autonomous mechanism downstream of the seed uptake. Lastly, validation studies with human brain tissue also revealed that several of the identified protein hits are down-regulated in the brains of Alzheimer's patients, suggesting that their decreased activity may be required for the emergence or progression of tau pathology in the human brain.

A Narrative Review of the Pathophysiology and Treatment of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic autosomal dominant disorder of the heart muscle that is characterized by left ventricular hypertrophy and sudden cardiac death. It is the most common inherited cardiac disease. HCM is defined by sarcomeric mutations that result in fibrosis of the heart, affecting contraction. In most cases, clinical presentations can range from asymptomatic to systolic and diastolic ventricular dysfunction, arrhythmias, and sudden cardiac death. Some histopathologic features typical of the disease are changes in myocyte disarray and myocardial fibrosis. Mutations in the ß-myosin heavy chain and myosin-binding protein C have been identified as the cause of the disease. The goals of pharmacological therapy as well as nonpharmacological therapy are to alleviate the symptoms and to prevent sudden cardiac death. Anatomical defects are treated primarily by surgical intervention, whereas other issues such as hypercontractility are treated with pharmacotherapy. In this article, we review the pathophysiology and treatment options for HCM.

A concerning trend in geriatric pharmacy that merits evidence-based intervention.

The effects of polypharmacy on geriatric populations are an emerging concern that merits more exploration. The primary goal of this review was to evaluate the current body of knowledge on polypharmacy and explore the preventive and corrective measures to avoid negative outcomes. Even if a medication has an appropriate indication, polypharmacy in the geriatric population is associated with an increased risk of drug-drug or drug-condition interactions. Recent efforts to prevent polypharmacy include the development of interprofessional teams in clinics dedicated to medication review and reconciliation, deprescription plans aimed to safely discontinue potentially inappropriate medications, and inpatient screening tools that provide prescribing recommendations. In conclusion, polypharmacy affects a high percentage of the geriatric population. Current efforts to address and prevent polypharmacy are ongoing but have not been widely adopted.

Miocinas: su rol en la obesidad y en las enfermedades cardiometabólicas / Myokines: their role in obesity and cardiometabolic diseases

Resumen Introducción: La obesidad es uno de los principales problemas de salud pública en el mundo. Se considera detonante de múltiples enfermedades cardiometabólicas, como el infarto agudo de miocardio, la hipertensión arterial, la diabetes mellitus tipo 2 y el accidente isquémico cerebral. Es interesante conocer diversos factores fisiopatológicos que no dependen solo de la adiposidad, sino también de la masa muscular. Al entender que el músculo como órgano endocrino corresponde al 40% del peso corporal, las miocinas, como sustancias propias de este órgano liberadas desde la contracción, cobran importancia por su efecto antiinflamatorio y cardioprotector, y suponen un esfuerzo mayor para, a partir de su comprensión, realizar una prescripción adecuada del ejercicio. Objetivo: Estudiar las funciones de las miocinas como sustancias reguladoras de diversos procesos metabólicos, fundamentales en la homeostasis corporal. Método: Se hizo una revisión de tema, resultado de la revisión crítica de la literatura disponible sobre las miocinas, sus funciones y los efectos de la actividad física y el ejercicio en su liberación y acción. Conclusiones: El estudio de las miocinas viene en aumento y cobra relevancia clínica. Los efectos antiinflamatorios y cardioprotectores de las miocinas dependen del tipo de entrenamiento y de las cargas aplicadas al músculo una vez ha sido sometido a diferentes tipos de estímulo (aeróbico/anaeróbico, fuerza). Por tanto, la prescripción correcta del ejercicio es crucial en la modulación de estos mediadores: la optimización de su efecto, el acondicionamiento físico y el mantenimiento del peso adecuado.

Abstract Introduction: Obesity is one of the main public health problems worldwide being considered as a trigger for multiple cardiometabolic diseases such as acute myocardial infarction, high blood pressure, type 2 diabetes mellitus, cerebral ischemic accident among others. For this reason, it is of interest to know the various pathophysiological factors which depend not only on adiposity but also on muscle mass. Taking into account that the muscle as an endocrine organ corresponds to 40 % of the body weight, the importance that myokines charge as substances of this organ with an anti-inflammatory and cardioprotective character and which are released from muscle contraction is an additional study to perform an adequate Prescription of the exercise. Objective: To study the functions of myokines as regulatory substances in various metabolic processes, being essential in body homeostasis. Method: It is presented a topic review article, the result of a critical review of the available literature on myokines, their functions and the effects of physical activity and exercise on their release and action. Conclusions: that the study of myokines is increasing and is becoming more important clinical. The anti-inflammatory and cardioprotective effects of myokines depend on the type of training and loads applied to the muscle once subjected to different types of stimulation (aerobic/anaerobic, strength). Therefore, the proper prescription of exercise becomes crucial in the physical conditioning and in the maintenance of the appropriate weight.

Exosomal and vesicle-free tau seeds-propagation and convergence in endolysosomal permeabilization.

In Alzheimer's disease (AD), ß-amyloid peptides aggregate to form amyloid plaques, and the microtubule-associated protein tau forms neurofibrillary tangles. However, severity and duration of AD correlate with the stereotypical emergence of tau tangles throughout the brain, suggestive of a gradual region-to-region spreading of pathological tau. The current notion in the field is that misfolded tau seeds propagate transsynaptically and corrupt the proper folding of soluble tau in recipient neurons. This is supported by accumulating evidence showing that in AD, functional connectivity and not proximity predicts the spreading of tau pathology. Tau seeds can be found in two flavors, vesicle-free, that is, naked as in oligomers and fibrils, or encapsulated by membranes of secreted vesicles known as exosomes. Both types of seeds have been shown to propagate between interconnected neurons. Here, we describe potential ways of how their propagation can be controlled in several subcellular compartments by manipulating mechanisms affecting production, neuron-to-neuron transmission, internalization, endosomal escape, and autophagy. We emphasize that although vesicle-free tau seeds and exosomes differ, they share the ability to trigger endolysosomal permeabilization. Such a mechanistic convergence in endolysosomal permeabilization presents itself as a unique opportunity to target both types of tau seeding. We discuss the cellular response to endolysosomal damage that might be key to control permeabilization, and the significant overlap in the seeding mechanism of proteopathic agents other than tau, which suggests that targeting the endolysosomal pathway could pave the way toward developing broad-spectrum treatments for neurodegenerative diseases.

Vortex clustering, polarisation and circulation intermittency in classical and quantum turbulence.

The understanding of turbulent flows is one of the biggest current challenges in physics, as no first-principles theory exists to explain their observed spatio-temporal intermittency. Turbulent flows may be regarded as an intricate collection of mutually-interacting vortices. This picture becomes accurate in quantum turbulence, which is built on tangles of discrete vortex filaments. Here, we study the statistics of velocity circulation in quantum and classical turbulence. We show that, in quantum flows, Kolmogorov turbulence emerges from the correlation of vortex orientations, while deviations-associated with intermittency-originate from their non-trivial spatial arrangement. We then link the spatial distribution of vortices in quantum turbulence to the coarse-grained energy dissipation in classical turbulence, enabling the application of existent models of classical turbulence intermittency to the quantum case. Our results provide a connection between the intermittency of quantum and classical turbulence and initiate a promising path to a better understanding of the latter.

Effect of Steel Fibre Reinforcement on Flexural Fatigue Behaviour of Notched Structural Concrete.

One of the biggest challenges in facilitating the installation of concrete is the development of fibre-reinforced concrete. Although nowadays fibre reinforced concrete is relatively common, it is still necessary to deepen in the study on its behaviour, especially regarding its fatigue behaviour. This paper proposes a new methodology to analyse the bending fatigue behaviour of notched test specimens. From these tests, it was possible to verify that, despite carrying out the tests with load control, the presence of fibres extends the fatigue life of the concrete after cracking. This effect is of great importance since during the extra lifetime with the cracked concrete, the damage to the concrete will be evident and the corresponding maintenance measures can be carried out. Regarding the analysis of the results, in addition to obtaining a traditional S-N curve, two new criteria have been applied, namely energy and notch growth. From these two new approaches, it was possible to determine critical energy values that can be used as predictive indicators of the collapse of the element. Moreover, from the notch growth analysis, it was possible to determine crack growth rate as a function of the stress conditions for the concrete and the specific geometry. From the comparison among the results obtained from the different tests, a limit cracking index of 0.05 mm can be defined.

Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol.

The microtubule-associated protein tau has a critical role in Alzheimer's disease and other tauopathies. A proposed pathomechanism in the progression of tauopathies is the trans-synaptic spreading of tau seeds, with a role for exosomes which are secretory nanovesicles generated by late endosomes. Our previous work demonstrated that brain-derived exosomes isolated from tau transgenic rTg4510 mice encapsulate tau seeds with the ability to induce tau aggregation in recipient cells. We had also shown that exosomes can hijack the endosomal pathway to spread through interconnected neurons. Here, we reveal how tau seeds contained within internalized exosomes exploit mechanisms of lysosomal degradation to escape the endosome and induce tau aggregation in the cytosol of HEK293T-derived 'tau biosensor cells'. We found that the majority of the exosome-containing endosomes fused with lysosomes to form endolysosomes. Exosomes induced their permeabilization, irrespective of the presence of tau seeds, or whether the exosomal preparations originated from mouse brains or HEK293T cells. We also found that permeabilization is a conserved mechanism, operating in both non-neuronal tau biosensor cells and primary neurons. However, permeabilization of endolysosomes only occurred in a small fraction of cells, which supports the notion that permeabilization occurs by a thresholded mechanism. Interestingly, tau aggregation was only induced in cells that exhibited permeabilization, presenting this as an escape route of exosomal tau seeds into the cytosol. Overexpression of RAB7, which is required for the formation of endolysosomes, strongly increased tau aggregation. Conversely, inhibition of lysosomal function with alkalinizing agents, or by knocking-down RAB7, decreased tau aggregation. Together, we conclude that the enzymatic activities of lysosomes permeabilize exosomal and endosomal membranes, thereby facilitating access of exosomal tau seeds to cytosolic tau to induce its aggregation. Our data underscore the importance of endosomal membrane integrity in mechanisms of cellular invasion by misfolded proteins that are resistant to lysosomal degradation.

Fyn Kinase Controls Tau Aggregation In Vivo.

Alzheimer's disease (AD) is a proteinopathy exhibiting aggregation of ß-amyloid (Aß) as amyloid plaques and tau as neurofibrillary tangles (NFTs), whereas primary tauopathies display only a tau pathology. Aß toxicity is mediated by Fyn kinase in a tau-dependent process; however, whether Fyn controls tau pathology in diseases that lack Aß pathology remains unexplored. To address this, we generate the Tg/Fyn-/- mouse, which couples mutant tau overexpression with Fyn knockout. Surprisingly, Tg/Fyn-/- mice exhibit a near-complete ablation of NFTs, alongside reduced tau hyperphosphorylation, altered tau solubility, and diminished synaptic tau accumulation. Furthermore, Tg/Fyn-/- brain lysates elicit less tau seeding in tau biosensor cells. Lastly, the fibrillization of tau is boosted by its pseudophosphorylation at the Fyn epitope Y18. Together, this identifies Fyn as a key regulator of tau pathology independently of Aß-induced toxicity and thereby represents a potentially valuable therapeutic target for not only AD but also tauopathies more generally.

The abundance of false killer whale, Pseudorca crassidens (Cetartiodactyla: Delphinidae) in coastal waters of Golfo Dulce and Osa Peninsula, Costa Rica

Introduction: False killer whale (Pseudorca crassidens) is a tropical and subtropical social species that live in groups with individuals of mixed ages and sex classes. False killer whales have been documented since the late 1990s in Southwestern Costa Rica. Objective: To estimate the abundance of false killer whales in Osa Peninsula waters. Methods: Cetacean surveys off the Osa Peninsula Waters (OPW), Costa Rica, yielded opportunistic encounters with false killer whales in Drake Bay and Caño Island (2001-2019) and observations during formal surveys in Golfo Dulce (2005-2015). Photo-identification data was analyzed using capture-mark-recapture models in the study area, through an open population (POPAN) framework, considering the effect of time on the parameters apparent survival and capture probability, producing an abundance estimate for a superpopulation in the entire study area. Results: False killer whale abundance in OPW is characterized by a small population size of no more than 100 individuals, complemented by a very low probability of encounter and a contrasting high apparent survival. Conclusions: This population estimate should be taken as conservative, however, the small population size of less than 100 individuals should be considered vulnerable, in contrast to the increasing anthropogenic impacts in the coastal seascape. We argue the potential occurrence of population units along the coastal seascape of the Pacific littoral and oceanic island-associated units at Isla del Coco.

Introducción: La falsa orca es una especie gregaria tropical y subtropical, que vive en grupos con individuos de diferentes clases de edad y sexo. La falsa orca ha sido documentada en el sur-oeste de Costa Rica desde finales de los 90s. Objetivo: Evaluar el uso de hábitat de la especie en términos de abundancia. Métodos: Observaciones en campo para cetáceos en aguas de la Península de Osa (APO), incluyen encuentros oportunísimos en Bahía de Drake y la Isla del Caño (2001-2019), así como observaciones directas de Pseudorca crassidens, durante muestreos formales en Golfo Dulce (2005-2015). Se analizaron datos sobre foto-identificación utilizando modelos de marcaje captura y recaptura, considerando un enfoque para población abierta (POPAN), el cual considera el efecto del tiempo en los parámetros demográficos: supervivencia aparente (ф) y probabilidad de captura (P), produciendo un estimado de abundancia que comprende toda la superpoblación en el área de estudio. Resultados: La abundancia de la falsa orca en APO se caracteriza por un tamaño poblacional pequeño, de menos de 100 individuos, que se complementa por una muy baja probabilidad de captura, en contraste con una supervivencia aparente alta. Conclusión: Este estimado debe tratarse como conservativo, no obstante, el pequeño número poblacional, de menos de 100 individuos debe considerarse como vulnerable, en contraste con el incremento del impacto antropogénico del paisaje marino costero. Se discute la posible presencia de unidades poblacionales en el paisaje costero del litoral Pacífico y de unidades oceánicas asociadas a la Isla del Coco.

Counterflow-Induced Inverse Energy Cascade in Three-Dimensional Superfluid Turbulence.

Finite-temperature quantum turbulence is often described in terms of two immiscible fluids that can flow with a nonzero-mean relative velocity. Such out-of-equilibrium state is known as counterflow superfluid turbulence. We report here the emergence of a counterflow-induced inverse energy cascade in three-dimensional superfluid flows by performing extensive numerical simulations of the Hall-Vinen-Bekarevich-Khalatnikov model. As the intensity of the mean counterflow is increased, an abrupt transition, from a fully three-dimensional turbulent flow to a quasi-two-dimensional system exhibiting a split cascade, is observed. The findings of this work could motivate new experimental settings to study quasi-two-dimensional superfluid turbulence in the bulk of three-dimensional experiments. They might also find applications beyond superfluids in systems described by more than one fluid component.

Obesidad: un problema en la atención de Covid-19 atención de Covid-19 / Obesity: a problem in Covid-19 care

Actualmente el mundo atraviesa una de las peores crisis a nivel salud secundario a la infección por un nuevo coronavirus de alta transmisibilidad y mortalidad, que ha impactado múltiples aspectos. Se ha establecido de forma general que la severidad de la infección está asociada con edad avanzada y comorbilidades como hipertensión y diabetes. Por otro lado, la obesidad en este momento representa una de las mayores amenazas del sector salud, por su gran relación con morbimortalidad a nivel cardiometabólico, esto conlleva a un alto costo de la enfermedad. Este artículo busca alertar sobre lo que han llamado algunos expertos el "choque de dos pandemias", esto dado al aumento de la prevalencia de obesidad a nivel mundial, donde nuestro país no está exento, que podría relacionarse con un número mayor de personas vulnerables a la infección por COVID-19 y sus complicaciones respiratorias y de esta manera evitar desenlaces catastróficos.

Currently the world is going through one of the worst health crises secondary to the infection by a new highly transmissible and deadly coronavirus, which has impacted multiple aspects. It has been generally established that the severity of the infection is associated with old age and comorbidities such as hypertension and diabetes. On the other hand, obesity at this time represents one of the greatest threats to the health sector, due to its strong relationship with morbidity and mortality at the cardiometabolic level which leads to a high cost of the disease. This article seeks to warn about what some experts have called the "clash of two pandemics", this given the increasing prevalence of obesity worldwide, where our country is not exempt, which could be related with a greater number of people vulnerable to COVID-19 infection and related respiratory complications and thus avoid catastrophic outcomes.

Calidad de vida relacionada con la salud en población víctima del conflicto armado en Colombia / Quality of life related to health in the population victims of the armed conflict in Colombia

Resumen Este artículo describió la calidad de vida relacionada con la salud en población víctima del conflicto armado colombiano. El estudio fue de tipo cuantitativo, descriptivo y transversal, con un diseño no experimental. La muestra estuvo constituida por 265 personas, a las cuales se les aplicó una ficha de datos sociodemográficos y el cuestionario SF-36. Los resultados muestran que el tipo de hecho victimizante que más se presenta es el desplazamiento forzado con un 96,6 %; la mayoría de las víctimas son mujeres, con un 72,1 %, las cuales tienen una menor percepción de calidad de vida en salud en comparación con los hombres. En general, los participantes presentan una baja percepción en la dimensión del rol emocional, mientras que se tiene una buena percepción en la dimensión relacionada con la función social. Los resultados sugieren realizar nuevas investigaciones para profundizar la relación existe entre el rol emocional y la función social, y se diferencie entre población clínica y no clínica.

Abstract In the present research the quality of life related to health was described in population victims of the Colombian armed conflict. The study was of quantitative,descriptive and transversal type, with a non-experimental design. The sample consisted of 265 people, who were given a socio-demographic data sheet and the SF-36 Questionnaire. The results show that the type of victimization that presents the most is forced displacement with 96.6% and there is a high score in lathes to Quality of Life related to the social function dimension. The results suggest establishing the relationship between emotional role and social function and the differentiation between clinical and nonclinical populations in future studies.

Acercamiento multifactorial a la fisiopatología de la obesidad. Modelo de abordaje COD2 / A multi-factor approach to the physiopathology of obesity: COD2 model

La obesidad en este momento representa una de las peores amenazas del sector salud. El acelerado aumento de la prevalencia y mortalidad a causa de enfermedades cardiovasculares establece un precedente histórico como problema de salud pública mundial. La elevada incidencia de obesidad y enfermedades crónicas ha llevado a múltiples áreas de la salud a entender y buscar un detonante claro que explique esta patología. Existen numerosas causas que explican su comportamiento agresivo, progresivo y crónico. Sin embargo, ninguna de ellas satisface como el solo factor desencadenante que ofrezca un tratamiento único que genere una reducción de su rápida expansión. En este artículo se buscan explicar las principales causas relacionadas con esta entidad así como los mecanismos que lo demuestran, para lograr entender el abordaje adecuado de los pacientes que acuden buscando el manejo de la obesidad (modelo COD2).

Obesity is currently considered as one of the major life-threatening conditions affecting the healthcare system. The accelerated increase in prevalence and mortality due to cardiovascular diseases establishes an historical precedent as a global public health issue. The increased incidence of obesity and chronic diseases, has led multiple health researchers to try to identify a clear triggering factor contributing to obesity. There are numerous causes which explain its aggressive, progressive and chronic behavior. However, they do not satisfactorily elucidate a unique triggering factor which would determine a unique treatment to help decelerate its rapid expansion. This article seeks to explain the major causal factors and mechanisms leading to obesity, in order to find the most appropriate approach for obese patients seeking treatment options (COD2 model).

Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons.

In Alzheimer disease and related disorders, the microtubule-associated protein tau aggregates and forms cytoplasmic lesions that impair neuronal physiology at many levels. In addition to affecting the host neuron, tau aggregates also spread to neighboring, recipient cells where the misfolded tau aggregates, in a manner similar to prions, actively corrupt the proper folding of soluble tau, and thereby impair cellular functions. One vehicle for the transmission of tau aggregates are secretory nanovesicles known as exosomes. Here, we established a simple model of a neuronal circuit using a microfluidics culture system in which hippocampal neurons A and B were seeded into chambers 1 and 2, respectively, extending axons via microgrooves in both directions and thereby interconnecting. This system served to establish two models to track exosome spreading. In the first model, we labeled the exosomal membrane by coupling tetraspanin CD9 with either a green or red fluorescent tag. This allowed us to reveal that interconnected neurons exchange exosomes only when their axons extend in close proximity. In the second model, we added exosomes isolated from the brains of tau transgenic rTg4510 mice (i.e. exogenous, neuron A-derived) to neurons in chamber 1 (neuron B) interconnected with neuron C in chamber 2. This allowed us to demonstrate that a substantial fraction of the exogenous exosomes were internalized by neuron B and passed then on to neuron C. This transportation from neuron B to C was achieved by a mechanism that is consistent with the hijacking of secretory endosomes by the exogenous exosomes, as revealed by confocal, super-resolution and electron microscopy. Together, these findings suggest that fusion events involving the endogenous endosomal secretory machinery increase the pathogenic potential and the radius of action of pathogenic cargoes carried by exogenous exosomes.

Amyloid-ß and tau complexity - towards improved biomarkers and targeted therapies.

Most neurodegenerative diseases are proteinopathies, which are characterized by the aggregation of misfolded proteins. Although many proteins have an intrinsic propensity to aggregate, particularly when cellular clearance systems start to fail in the context of ageing, only a few form fibrillar aggregates. In Alzheimer disease, the peptide amyloid-ß (Aß) and the protein tau aggregate to form plaques and tangles, respectively, which comprise the histopathological hallmarks of this disease. This Review discusses the complexity of Aß biogenesis, trafficking, post-translational modifications and aggregation states. Tau and its various isoforms, which are subject to a vast array of post-translational modifications, are also explored. The methodological advances that revealed this complexity are described. Finally, the toxic effects of distinct species of tau and Aß are discussed, as well as the concept of protein 'strains', and how this knowledge can facilitate the development of early disease biomarkers for stratifying patients and validating new therapies. By targeting distinct species of Aß and tau for therapeutic intervention, the way might be paved for personalized medicine and more-targeted treatment strategies.