Cytokine storm modulation in COVID-19: a proposed role for vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i)

A dysregulated immune response characterized by the hyperproduction of several pro-inflammatory cytokines (a.k.a. 'cytokine storm') plays a central role in the pathophysiology of severe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this Perspective article we discuss the evidence for synergistic anti-inflammatory and immunomodulatory properties exerted by vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors, the latter being a class of antihyperglycemic agents used for the treatment of Type 2 diabetes, which have also been reported as immunomodulators. Then, we provide the rationale for investigation of vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i) as an immunomodulation strategy to ratchet down the virulence of SARS-CoV-2, prevent disease progression and modulate the cytokine storm in COVID-19

The Insulin Journey in the Human Body

Insulin represents the paramount anabolic hormone and the master regulator of glucose, lipid, and protein metabolism. This chapter describes the sequential stages of the physiologic journey of insulin in the human body, from its synthesis/secretion to its action in peripheral tissues and, ultimately, to its clearance and degradation. These stages include i) insulin synthesis and release from pancreatic beta cells; ii) insulin first-pass metabolism and partial clearance in the liver; iii) insulin action on the vasculature and exit from the capillary beds; iv) insulin action in peripheral and central target tissues (skeletal muscle, adipose tissue, liver, and central nervous system); and v) final insulin degradation in the kidney. Each of these stages is regulated by complex intracellular mechanisms that take place in different tissues and allow for the anabolic actions of insulin. Understanding the abovementioned stages is pivotal to comprehending the clinical consequences of impaired insulin secretion and action, as defects in one or more of these stages can be associated with the development of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. Additionally, a thorough knowledge of the insulin bodily journey can assist clinicians in therapeutic decision-making for diabetic patients on exogenous insulin therapy in different clinical settings

Independent Candidaturas in Mexico: A Paradoxical Experience

El objetivo de este artículo es evaluar el desempeño electoral de las candidaturas independientes en México a partir de su adopción en el año 2014. En específico, este trabajo analiza sus fundamentos jurídicos, sus requisitos legales y económicos (en comparación con las candidaturas tradicionales de los candidatos de los partidos políticos). En la segunda parte del trabajo se analiza el desempeño electoral de los candidatos independientes en los procesos electorales llevados a cabo en los años 2015 y 2016. Finalmente, se proponen algunas conclusiones que giran en torno a una cuestión central: a pesar de que las candidaturas independientes se introdujeron con la finalidad de estimular la participación ciudadana, han recibido poco apoyo electoral y, en general, han sido utilizadas de forma creciente por políticos vinculados a los partidos tradicionales que desean emprender una carrera política personal.The aim this paper is to evaluate the performance of the independent candidates in Mexico, since its legal adoption in 2014. Specifically, this paper analyses its legal foundations, the legal and the economic requirements –compared to the traditional candidacies of the political parties. The second part of the paper analyses the performance of the independent candidates in the electoral processes carried out in the years 2015, 2016 and 2017. Finally, some conclusions are proposed that revolve around a central question: although the Independents candidacies were introduced with the aim of stimulating the citizen participation, they have received generally a minor electoral support, and they have been increasingly used by politicians linked to traditional parties who wish to begin a personal political career

Long-term metformin therapy and vitamin B12 deficiency: an association to bear in mind

To date, metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile. Indeed, metformin is the most widely used oral insulin-sensitizing agent, being prescribed to more than 100 million people worldwide, including patients with prediabetes, insulin resistance, and polycystic ovary syndrome. However, over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency. Of note, evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status. Vitamin B12 (also referred to as cobalamin) is a water-soluble vitamin that is mainly obtained from animal-sourced foods. At the cellular level, vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection. Thus, vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities (e.g., megaloblastic anemia and formation of hypersegmented neutrophils), progressive axonal demyelination and peripheral neuropathy. Nevertheless, no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy, and vitamin B12 deficiency remains frequently unrecognized in such individuals. Therefore, in this "field of vision" article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients, which could serve as a practical guide for identifying individuals at high risk for this condition. Moreover, we discuss additional relevant topics related to this field, including: (1) The lack of consensus about the exact definition of vitamin B12 deficiency; (2) The definition of reliable biomarkers of vitamin B12 status; (3) Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis; and (4) Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency. Finally, we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency, particularly when this condition is induced by metformin

Evaluación del servicio de préstamo de e-readers en el Centro de Información de la Universidad Peruana de Ciencias Aplicadas

Publicación a texto completo no autorizada por el autorSeñala que, con la aparición de internet, la industria editorial hace un giro hacia el modelo de edición digital. Muchas editoriales empiezan a producir libros en versión digital a la par que aparecen en el mercado una nueva generación de dispositivos o lectores de libros digitales, los denominados E-Readers, que incorporan una serie de avances tecnológicos, como la tinta electrónica, conexión a internet, audio, etc., que a la vez son muy populares entre los jóvenes y personas que consumen información en formato digital y que han crecido rodeados de pantallas, videojuegos, celulares, los llamados nativos digitales. El libro electrónico corresponde a la tercera ola de la revolución digital luego de los documentos en CD-ROM y las bases de datos de artículos de revistas académicas y científicas. La aparición del libro electrónico y la generación de información digital han hecho que las bibliotecas cambien su rol de custodia de la información a facilitadoras al acceso a la información. Es en este sentido, que tanto los libros electrónicos como los dispositivos de lectura tienen mayor presencia en las aulas y muchos programas pilotos se están desarrollando en numerosos centros universitarios, muchas bibliotecas han empezado a prestar lectores de libros digitales como el Kindle como parte de sus servicios. Bajo este contexto, el Centro de Información de la Universidad Peruana de Ciencias Aplicadas (UPC), decide implementar a partir del 2010 el servicio de préstamo de E-Readers, seleccionando para este propósito el Kindle Global de Amazon (versión 2), como parte de sus servicios, teniendo en cuenta su relación con el tema de lectura y la compra de libros que se realiza a través de Amazon, convirtiéndose en la primera biblioteca del país en ofrecer este servicio. El presente trabajo de investigación es una evaluación del servicio de préstamo de libros electrónico a través de los E-Readers

Trabajo de titulación previo a la obtención del título de Ingeniero en Sistemas

El objetivo principal de este proyecto es la reestructuración de la base de datos e interfaces en aplicación web de ventas e implementación del servicio de geo ubicación para la empresa “LABORATORIO GENESIS” de la de la ciudad de Ambato, ya que por el momento el sistema informático actual no es amigable con el usuario, retrasa el proceso de ventas y su ubicación. En el proyecto se abarca el problema que existe en la empresa a causa de la utilización de métodos obsoletos y escasez de tecnologías de la información. También se incluye la modalidad, técnicas e instrumentos de investigación. Así mismo se conglomera el desarrollo de la reestructuración del sistema informático actual y la geo ubicación para lo cual se utilizó como metodología técnica XP. Por último, se ha planteado las conclusiones y recomendaciones. Los resultados preliminares que se pudo observar fueron, agilidad en el proceso de ventas y su ubicación de forma oportuna, por lo que se evidenció un cambio significativo y positivo en la gestión de las ventas para la empresa. Se recomienda respaldar la base datos con regularidad, mínimo semanalmente; dado que es información con alto grado de sensibilidad

LIFE-THREATENING HYPOCALCEMIA IN A PATIENT WITH HIGHLY SUSPECTED OSTEOMALACIA: A CASE REPORT

ABSTRACT: Objective: Osteomalacia is a metabolic bone disease characterized by impaired mineralization with increased non-mineralized osteoid tissue, increased frailty, and reduced bone mineral density. A common cause of osteomalacia in adults and the elderly is severe deficiency of vitamin D, which leads to chronic hypocalcemia, hypophosphatemia, and secondary hyperparathyroidism. The objective of this case report is to describe an unusual clinical presentation of osteomalacia, consisting of life-threatening acute hypocalcemia.Methods: Clinical, laboratory, and imaging data are presented.Results: We report the case of a 65-year-old man that showed symptoms and signs of severe and prolonged hypocalcemia due to unrecognized vitamin D deficiency. He presented at the emergency room reporting abdominal pain and vomiting since the evening before. Blood tests showed increased levels of rhabdomyolysis markers, severe hypocalcemia, hypophosphatemia, hypomagnesemia, normal renal function, elevated levels of alkaline phosphatase, extremely high levels of parathyroid hormone, and hypovitaminosis D. Radiological skeletal features of bone demineralization and bone abnormalities suggestive of osteomalacia were additionally detected. Other secondary causes of hypocalcemia were excluded. Clinical and biochemical resolution were progressively obtained only after an intramuscular loading dose of cholecalciferol was added to the standard calcium intravenous replacement therapy.Conclusion: This case report shows that osteomalacia consequent to a severe vitamin D deficiency can present with acute symptoms and signs of severe hypocalcemia requiring hospital admission. In such cases, vitamin D administration, and not intensive calcium supplementation alone, is essential to achieve clinical resolution of symptoms and normalization of mineral metabolism parameters.Abbreviations: 25-OH-D 25-hydroxyvitamin D CT computed tomography IV intravenous PTH parathyroid hormon

Desarrollo de un sistema embebido para el control de un autoclave mediante aplicación Android para el Hospital Provincial General Docente de Riobamba a través de la empresa Multiservicios Coestra.

El trabajo de titulación tuvo como objetivo principal desarrollar una aplicación para el monitoreo y control de un autoclave (esterilizador). La aplicación de monitoreo denominada Sistema de Monitoreo de Autoclave (SIMA). Para la recolección de información se realizaron entrevistas y se aplicaron encuestas, el desarrollo de la aplicación se realizó mediante la metodología ágil SCRUM. Para la elaboración de la aplicación se emplearon herramientas de desarrollo como LabView, App Inventor, para crear las pantallas de usuario y administrador del monitoreo y control en tiempo real del autoclave (esterilizador), para el monitoreo se utilizaron dispositivos electrónicos como Arduino Uno, modulo Bluetooth y el sensor PT100. Se analizó bibliografía comprobada en la integración y comunicación de dispositivo Bluetooth con Arduino para el monitoreo mediante la PC y dispositivo móvil. Para la comprobación de la aplicación desarrollada se realizó la instalación en la PC y en un teléfono móvil que cuente con sistema operativo Android para la manipulación y monitoreo del autoclave (esterilizador). Para obtener resultados de usabilidad del sistema se aplicó una capacitación al gerente general de la empresa Multiservicios COESTRA y a los empleados en el área de esterilización del Hospital General Docente de Riobamba, para la evaluación de la usabilidad de se estudió la norma ISO IEC 9126 3, a partir de la cual se estableció un test para verificar el cumplimiento de la norma, para ello se realizó un simulacro y se concluyó que la comprensión de la aplicación tiene un nivel de aceptación del 84.3% de aceptación y un nivel de desacuerdo de un 15.7%, de esta manera se concluye que la aplicación cumple con los objetivos planteados en el trabajo de titulación, que el sistema es totalmente usable. Se recomienda comprobar y verificar la seguridad de la información de futuras aplicaciones web haciendo uso de las métricas internas basadas en la norma ISO IEC 9126 3.This investigation aims to develop an application for the monitoring and control of an autoclave (sterilizer) named Sterilizer Monitoring System (SMS). Interviews and surveys were used to gather information. In addition, the Agile SCRUM methodology was used to develop application. We used Labview to make this application, App Inventor to create the screen of user and administrator of the monitoring and control in real time of autoclave (sterilizer), electronic devices as Arduino One, Bluetooth module and sensor PT100 were used for monitoring. We analyzed verified bibliography about integration and communication of Bluetooth device with Arduino to monitor by PC and in a mobile with Android operative system for manipulating and monitoring of autoclave (sterilizer). The general manager of the Multi services COESTRA enterprise and the employees of sterilization area at Hospital General Docente Riobamba were trained to get results of usability. To evaluate usability we studied ISO IEC 9126 3 norm making a test to verify the accomplishment of the norm. A simulation was carried out to know that it is comprehensive application with 84.3% of level of acceptance 15.7%, of level of disagreement. It is concluded that the application meet the objectives proposed in this investigation and that the system is usable entirely. It is recommended to test and to verify the information of future web applications by using the internal metrics based on ISO IEC 9126 3 norm

A comparison between some fracture modelling approaches in 2D LEFM using finite elements

[EN] The finite element method has been widely used to solve different problems in the field of fracture mechanics. In the last two decades, new methods have been developed to improve the accuracy of the solution in 2D linear elastic fracture mechanics problems, such as the extended finite element method (XFEM) or the phantom node method (PNM). The goal of this work is to quantify the differences between some numerical approaches: standard finite element method (FEM), mechanical property degradation, interelemental crack method with multi-point constraints, XFEM and PNM. We explain the different techniques analysed together with their advantages and disadvantages. We compare these numerical techniques to model fracture using problems of reference with known solutions, evaluating their behaviour in terms of convergence with respect to the element size and accuracy of the stress intensity factor (SIF), stresses ahead the crack tip and crack propagation prediction. Some of the new techniques have shown a better accuracy in SIF calculation or stress fields ahead the crack tip and other lead to high errors in local results estimations. However, all methods reviewed here can predict crack propagation for the problems of reference of this work, showing good accuracy in crack orientation prediction.The authors gratefully acknowledge the funding support received from the Spanish Ministerio de Ciencia, Innovacion y Universidades and the FEDER operation program in the framework of the projects DPI2017-89197-C2-1-R and DPI2017-89197-C2-2-R and the FPI subprograms BES-2014-068473 and BES-2015-072070. The financial support of the Generalitat Valenciana through the Programme PROMETEO 2016/007 is also acknowledged.Marco, M.; Infante-García, D.; Belda, R.; Giner Maravilla, E. (2020). A comparison between some fracture modelling approaches in 2D LEFM using finite elements. 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