Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients

Background: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. Methods: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. Conclusions: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. Trial registration: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited

EDUCACIÓN AMBIENTAL Y SOCIEDAD. SABERES LOCALES PARA EL DESARROLLO Y LA SUSTENTABILIDAD

Este texto contribuye al análisis científico de varias áreas del conocimiento como la filosofía social, la patología, la educación para el cuidado del medio ambiente y la sustentabilidad que inciden en diversas unidades de aprendizaje de la Licenciatura en Educación para la Salud y de la Maestría en Sociología de la SaludLas comunidades indígenas de la sierra norte de Oaxaca México, habitan un territorio extenso de biodiversidad. Sin que sea una área protegida y sustentable, la propia naturaleza de la región ofrece a sus visitantes la riqueza de la vegetación caracterizada por sus especies endémicas que componen un paisaje de suma belleza

Libro: Las Ciencias Políticas y Sociales ante Contingencias de Amplio Impacto. Incógnitas y Propuestas

Ciencia Política, Administración Pública, Política y Gobierno, y Políticas Públicas. Licencia Creative Commons License 3.0 Reconocimiento-No Comercial-Sin Obras Derivadas. Usted es libre de copiar, distribuir y comunicar públicamente la obra bajo las condiciones siguientes: Reconocimiento - Debe reconocer los créditos de la obra de la manera especificada por el autor o el licenciador (pero no de una manera que sugiera que tiene su apoyo o apoyan el uso que hace de su obra). No comercial - No puede utilizar esta obra para fines comerciales. Sin obras derivadas - No se puede alterar, transformar o generar una obra derivada a partir de esta obra.Se analizan desde una perspectiva internacional a interdisciplinaria las vertientes, problemas, incógnitas y propuestas ante una nueva realidad o normalidad, resultado y consecuencia de la pandemia que se vive de manera contemporánea, de tal manera que la problematización abordada realimente propuestas, acciones y rutas adecuadas y satisfactorias que permitan la construcción de futuros promisorios.Academia Internacional de Ciencias Político-Administrativas y Estudios de Futuro, A.C. (IAPAS por sus siglas en inglés)

The European Eel NCCβ Encodes for an Electroneutral NaCl Cotransporter That Is Not Sensitive to Thiazide Diuretics

The renal thiazide-sensitive NaCl cotransporter (NCC) in mammalian nephron plays a key role in salt transport of the distal convoluted tubule and thus in modulation of arterial blood pressure and potassium secretion. Only one gene encoding NCC has been described in mammals. However, in the teleost European eel, two genes encoding putative isoforms of NCC were identified: NCCα, from kidney, and NCCβ from intestine. For the NCCα the identify degree with flounder, rat and human NCC is 70, 65, and 45%, respectively and for the NCCβ is 55, 55, and 43, respectively. No functional characterization of these variants has been reported. By RT-PCR we cloned the full-length cDNA of eel NCCβ isoform and inserted into the Xenopus expression vector pgh19. The insert contains 3437 bp, with an open reading frame of 3132, encoding a 1043 amino acid protein. Functional expression was assessed in Xenopus oocytes, microinjected with 10 ng of cRNA in vitro transcribed from NCCβ cDNA, by measuring the tracer 22Na+ uptake. Rat NCC was used as a control signal. Our results revealed that injection of oocytes with NCCβ cRNA induced the appearance of Na+ uptake mechanism that is fully dependent on extracellular Cl-, constituting a NaCl cotransporter. However, in strict contrast to rat NCC, eel NCCβ is not inhibited by thiazide type diuretics. In addition, it is also not stimulated by WNK3 kinase that is a powerful activator of mammalian NCC. We conclude that NCCβ encodes a non-thiazide sensitive NaCl cotransporter

Structure-function relationships in the sodium chloride cotransporter

The thiazide sensitive Na+:Cl− cotransporter (NCC) is the principal via for salt reabsorption in the apical membrane of the distal convoluted tubule (DCT) in mammals and plays a fundamental role in managing blood pressure. The cotransporter is targeted by thiazide diuretics, a highly prescribed medication that is effective in treating arterial hypertension and edema. NCC was the first member of the electroneutral cation-coupled chloride cotransporter family to be identified at a molecular level. It was cloned from the urinary bladder of the Pseudopleuronectes americanus (winter flounder) 30 years ago. The structural topology, kinetic and pharmacology properties of NCC have been extensively studied, determining that the transmembrane domain (TM) coordinates ion and thiazide binding. Functional and mutational studies have discovered residues involved in the phosphorylation and glycosylation of NCC, particularly on the N-terminal domain, as well as the extracellular loop connected to TM7-8 (EL7-8). In the last decade, single-particle cryogenic electron microscopy (cryo-EM) has permitted the visualization of structures at high atomic resolution for six members of the SLC12 family (NCC, NKCC1, KCC1-KCC4). Cryo-EM insights of NCC confirm an inverted conformation of the TM1-5 and TM6-10 regions, a characteristic also found in the amino acid-polyamine-organocation (APC) superfamily, in which TM1 and TM6 clearly coordinate ion binding. The high-resolution structure also displays two glycosylation sites (N-406 and N-426) in EL7-8 that are essential for NCC expression and function. In this review, we briefly describe the studies related to the structure-function relationship of NCC, beginning with the first biochemical/functional studies up to the recent cryo-EM structure obtained, to acquire an overall view enriched with the structural and functional aspects of the cotransporter

Servicio de diagnóstico y tratamiento de enfermedades vasculares mediante procedimientos angiográficos en el Centro de Especialidades Médicas Intervencionistas – CEMI

The aim of this business plan was to demonstrate the technical and economic feasibility in the implementation of the diagnosis and treatment service of vascular diseases for rescue of the diabetic foot through outpatient angiographic procedures at the Centro de Especialidades Médicas Intervencionistas - CEMI located in the city of Lima. In this regard, there is an unmet demand and a business opportunity, which will be met through a cost leadership strategy. The value proposition is a timely service, quality, high technology and recognized doctors. The potential market, with 48 IAFAS, is a total of 4 196 insured with diabetic foot. The business model will be based on agreements and contracts with these Health care financing sources. It is also expected, as part of the non-financial strategic objectives, to retain 95% of the clients, use the installed capacity over than 75% and maintain connection between different Health professional asocciated with diabetes specialization and, community. According to economic and financial analysis, an initial investment of S/ 4 831 045.70, 40% financed at 5 years and 60% assumed by the partners, is required. In ten years, this project will create an Economic Net Present Value (NPV) of 28,015,047.31 and an Internal Rate of Return (IRR) of 60%. Financially, it will generate an Increasing Net Present Value (NPV) of 17 687 598.28 and an Incremental Internal Return Rate (IRR) of 78%. All of the above indicates that it is a good investment, with a stable model and controllable risks.Trabajo de investigaciónEl presente plan de negocio tuvo como objetivo demostrar la viabilidad técnica y económica de la implementación del servicio de diagnóstico y tratamiento de enfermedades vasculares para el rescate del pie diabético mediante procedimientos angiográficos ambulatorios en el Centro de Especialidades Médicas Intervencionistas – CEMI ubicado en la ciudad de Lima. Al respecto, existe una demanda no satisfecha y una oportunidad de negocio, que será atendida por medio de una estrategia de liderazgo en costos. La propuesta de valor es un servicio oportuno, de calidad, alta tecnología y médicos reconocidos. El mercado potencial, con 48 IAFAS, es de un total de 4 196 asegurados con pie diabético. El modelo de negocios se basará en convenios y contratos con dichas IAFAS. También se espera, como parte de los objetivos estratégicos no financieros, fidelizar al 95% de los clientes, usar la capacidad instalada a más del 75% y mantener nexos con los diferentes profesionales de la salud asociados a la subespecialidad en diabetes y la comunidad. Según el análisis económico y financiero, se requiere una inversión inicial de S/ 4 831 045,70, 40% financiada a 5 años y 60% asumida por los socios. A los 10 años este proyecto creará un Valor Presente Neto Económico (VPNE) de 28 015 047,31 y una Tasa Interna de Retorno (TIR) de 60%. Financieramente, generará un Valor Presente Neto Incremental (VPNI) de 17 687 598,28 y una Tasa Interna de Retorno Incremental (TIRI) de 78%. Todo lo anterior indica que se trata de una buena inversión, con un modelo estable y riesgos controlables

Servicio de diagnóstico y tratamiento de enfermedades vasculares mediante procedimientos angiográficos en el Centro de Especialidades Médicas Intervencionistas – CEMI

El presente plan de negocio tuvo como objetivo demostrar la viabilidad técnica y económica de la implementación del servicio de diagnóstico y tratamiento de enfermedades vasculares para el rescate del pie diabético mediante procedimientos angiográficos ambulatorios en el Centro de Especialidades Médicas Intervencionistas – CEMI ubicado en la ciudad de Lima. Al respecto, existe una demanda no satisfecha y una oportunidad de negocio, que será atendida por medio de una estrategia de liderazgo en costos. La propuesta de valor es un servicio oportuno, de calidad, alta tecnología y médicos reconocidos. El mercado potencial, con 48 IAFAS, es de un total de 4 196 asegurados con pie diabético. El modelo de negocios se basará en convenios y contratos con dichas IAFAS. También se espera, como parte de los objetivos estratégicos no financieros, fidelizar al 95% de los clientes, usar la capacidad instalada a más del 75% y mantener nexos con los diferentes profesionales de la salud asociados a la subespecialidad en diabetes y la comunidad. Según el análisis económico y financiero, se requiere una inversión inicial de S/ 4 831 045,70, 40% financiada a 5 años y 60% asumida por los socios. A los 10 años este proyecto creará un Valor Presente Neto Económico (VPNE) de 28 015 047,31 y una Tasa Interna de Retorno (TIR) de 60%. Financieramente, generará un Valor Presente Neto Incremental (VPNI) de 17 687 598,28 y una Tasa Interna de Retorno Incremental (TIRI) de 78%. Todo lo anterior indica que se trata de una buena inversión, con un modelo estable y riesgos controlables.The aim of this business plan was to demonstrate the technical and economic feasibility in the implementation of the diagnosis and treatment service of vascular diseases for rescue of the diabetic foot through outpatient angiographic procedures at the Centro de Especialidades Médicas Intervencionistas - CEMI located in the city of Lima. In this regard, there is an unmet demand and a business opportunity, which will be met through a cost leadership strategy. The value proposition is a timely service, quality, high technology and recognized doctors. The potential market, with 48 IAFAS, is a total of 4 196 insured with diabetic foot. The business model will be based on agreements and contracts with these Health care financing sources. It is also expected, as part of the non-financial strategic objectives, to retain 95% of the clients, use the installed capacity over than 75% and maintain connection between different Health professional asocciated with diabetes specialization and, community. According to economic and financial analysis, an initial investment of S/ 4 831 045.70, 40% financed at 5 years and 60% assumed by the partners, is required. In ten years, this project will create an Economic Net Present Value (NPV) of 28,015,047.31 and an Internal Rate of Return (IRR) of 60%. Financially, it will generate an Increasing Net Present Value (NPV) of 17 687 598.28 and an Incremental Internal Return Rate (IRR) of 78%. All of the above indicates that it is a good investment, with a stable model and controllable risks.Trabajo de investigació

Nature’s Contributions to People in Vulnerability Studies When Assessing the Impact of Climate Change on Coastal Landscapes

The geographic landscape is a recurrent unit of analysis in vulnerability studies. Single descriptions are often used to show the elements exposed in these landscapes. However, the concept requires specifying the components of the landscape and its functioning as a unit. Thus, the purpose of this research was to use the analysis of Nature’s Contributions to People (NCP) to describe the global contribution of landscape elements to human activities, prioritizing the units in which the effects of climate change may imply greater impacts on the human population. For this, we analyzed six categories of nature’s contributions applied to the landscape units in a fragment of the Mexican Pacific coast. The units with mangrove cover had the highest nature contributions. It is expected that the application of this approach in the exposure component of vulnerability studies will allow a better understanding of the non-return relationship and the search for adaptive nature-based solutions