Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC.

Severe cases of COVID-19 are characterized by development of acute respiratory distress syndrome (ARDS). Water accumulation in the lungs is thought to occur as consequence of an exaggerated inflammatory response. A possible mechanism could involve decreased activity of the epithelial Na+ channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na+ reabsorption could contribute to lung edema due to reduced alveolar fluid clearance. This hypothesis is based on the observation of the presence of a novel furin cleavage site in the S protein of SARS-CoV-2 that is identical to the furin cleavage site present in the alpha subunit of ENaC. Proteolytic processing of αENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and αENaC for furin-mediated cleavage in SARS-CoV-2-infected cells may negatively affect channel activity. Here we present experimental evidence showing that coexpression of the S protein with ENaC in a cellular model reduces channel activity. In addition, we show that bidirectional competition for cleavage by furin-like proteases occurs between 〈ENaC and S protein. In transgenic mice sensitive to lethal SARS-CoV-2, however, a significant decrease in gamma ENaC expression was not observed by immunostaining of lungs infected as shown by SARS-CoV2 nucleoprotein staining.

KS-WNK1 is Required for the Renal Response to Extreme Changes in Potassium Intake.

KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest that it could play a role in regulating potassium renal excretion by modulating the activity of the Na+-Cl- cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low potassium diet. In this study, we investigated the role of KS-WNK1 in regulating potassium excretion under extreme changes in potassium intake. After following a zero-potassium diet (0KD) for 10 days, KS-WNK1-/- mice had lower plasma levels of K+ and Cl-, while exhibiting higher urinary excretion of Na+, Cl-, and K+ compared to KS-WNK1+/+ mice. After 10 days of 0KD or normal-potassium diet (NKD), all mice were challenged with a high-potassium diet (HKD). Plasma K+ levels markedly increased after the HKD challenge only in mice previously fed with 0KD, regardless of genotype. KSWNK1+/+ mice adapt better to HKD-challenge than KS-WNK1-/- mice after a potassium-retaining state. The difference in the pNCC/NCC ratio between KS-WNK1+/+ and KS-WNK1-/- mice after 0KD and HKD indicates a role for KS-WNK1 in both, NCC phosphorylation and dephosphorylation. These observations show that KS-WNK1 helps the DCT to respond to extreme changes in potassium intake, such as those occurring in wildlife.

Arginine vasopressin regulates the renal Na+-Cl- and Na+-K+-Cl- cotransporters through with-no-lysine kinase 4 and inhibitor 1 phosphorylation.

Vasopressin regulates water homeostasis via the V2 receptor in the kidney at least in part through protein kinase A (PKA) activation. Vasopressin, through an unknown pathway, upregulates the activity and phosphorylation of Na+-Cl- cotransporter (NCC) and Na+-K+-2Cl- cotransporter 2 (NKCC2) by Ste20-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1), which are regulated by the with-no-lysine kinase (WNK) family. Phosphorylation of WNK4 at PKA consensus motifs may be involved. Inhibitor 1 (I1), a protein phosphatase 1 (PP1) inhibitor, may also play a role. In human embryonic kidney (HEK)-293 cells, we assessed the phosphorylation of WNK4, SPAK, NCC, or NKCC2 in response to forskolin or desmopressin. WNK4 and cotransporter phosphorylation were studied in desmopressin-infused WNK4-/- mice and in tubule suspensions. In HEK-293 cells, only wild-type WNK4 but not WNK1, WNK3, or a WNK4 mutant lacking PKA phosphorylation motifs could upregulate SPAK or cotransporter phosphorylation in response to forskolin or desmopressin. I1 transfection maximized SPAK phosphorylation in response to forskolin in the presence of WNK4 but not of mutant WNK4 lacking PP1 regulation. We observed direct PP1 regulation of NKCC2 dephosphorylation but not of NCC or SPAK in the absence of WNK4. WNK4-/- mice with desmopressin treatment did not increase SPAK/OSR1, NCC, or NKCC2 phosphorylation. In stimulated tubule suspensions from WNK4-/- mice, upregulation of pNKCC2 was reduced, whereas upregulation of SPAK phosphorylation was absent. These findings suggest that WNK4 is a central node in which kinase and phosphatase signaling converge to connect cAMP signaling to the SPAK/OSR1-NCC/NKCC2 pathway.NEW & NOTEWORTHY With-no-lysine kinases regulate the phosphorylation and activity of the Na+-Cl- and Na+-K+-2Cl- cotransporters. This pathway is modulated by arginine vasopressin (AVP). However, the link between AVP and WNK signaling remains unknown. Here, we show that AVP activates WNK4 through increased phosphorylation at putative protein kinase A-regulated sites and decreases its dephosphorylation by protein phosphatase 1. This work increases our understanding of the signaling pathways mediating AVP actions in the kidney.

Caracterización del bienestar en hogares mexicanos de niñas y niños con diarrea, Ensanut Continua 2022.

OBJETIVO: Analizar el nivel de bienestar en los hogares mexicanos de niñas y niños menores de cinco años que presentaron enfermedad diarreica aguda (EDA) en las últimas dos semanas en México, según la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. La encuesta se realizó entre julio y diciembre de 2022. Variable dependiente: ocurrencia de EDA. Variable independiente: nivel de bienestar de los hogares. Se realizó análisis bivariado y regresiones logísticas crudas y ajustadas. RESULTADOS: Se estima que 9.4% de los menores de cinco años presentaron EDA, de quienes 76.4% (IC95%: 69.0,82.5) pertenecía a hogares con nivel de bienestar bajo-medio. La EDA fue más frecuente en los niños y niñas de un año de edad (razón de momios ajustada [RMa] 3.00; IC95%: 1.76,5.11), en comparación con quienes tenían menor edad y en los hogares donde el agua para beber no es tratada (RMa 2.13; IC95%: 1.11,4.08). CONCLUSIONES: Se requiere fortalecer las medidas sanitarias preventivas de EDA en niñas y niños de un año de edad, principalmente implementar acciones para asegurar la disponibilidad de agua potable o el tratamiento adecuado para beberla, y planear, ejecutar y evaluar acciones de política pública integrales y multisectoriales para coadyuvar en garantizar el derecho humano a la salud durante la niñez.

Cobertura de vacunación en niños, niñas y adolescentes en México.

OBJETIVO: Describir las coberturas de vacunación en 2022 en niñas, niños y en adolescentes, así como comparar las prevalencias observadas con los datos de la Encuesta Nacional de Salud y Nutrición 2021 (Ensanut 2021). Material y métodos. Análisis de datos obtenidos de la Ensanut 2022. RESULTADOS: En los niños menores de cinco años, las coberturas de vacuna con Bacilo de Calmette y Guérin (BCG), hepatitis B, pentavalente o hexavalente, neumocócica, antirotavirus y triple viral (SRP) fueron de 78.5% (IC95%: 70.8,84.6), 65.1% (IC95%: 58.4,71.2), 69.0% (IC95%: 61.8,75.4), 88.0% (IC95%: 83.0,91.7), 81.6% (IC95%: 75.7,86.2) y 61.8% (IC95%: 55.6,67.6), respectivamente. Al primer y segundo año de vida, 42.6% (IC95%: 34.3,51.4) y 26.6% (IC95%: 22.1,31.5) habían recibido el esquema correspondiente. Se redujo la cobertura estimada para primera dosis de SRP 72.6% (IC95%: 67.5,77.1) vs. 61.8% (IC95%: 55.6,67.5). En adolescentes, el antecedente de vacunación contra VPH, hepatitis B, tétanos y doble viral (SR) lo refirieron en 43.7% (IC95%: 39.9,47.6), 31.8% (IC95%: 29.8,34.0), 38.5% (IC95%: 35.9,41.2) y 32.6% (IC95%: 30.15,35.1). Conclusión. No se alcanza la meta de cobertura de 90% para ningún inmunógeno investigado. La cobertura para primera dosis de SRP se ha reducido.

Porcentaje de infección respiratoria aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de infección respiratoria aguda (IRA) en menores de cinco años en las últimas dos semanas en México, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. Se analizaron datos de la Ensanut Continua 2022. RESULTADOS: El porcentaje de IRA fue de 27.6% (IC95%: 25.2,30.1). La prevalencia fue mayor en el primer tercil socioeconómico (44.1% [IC95%: 38.0,50.4]). El signo de alarma IRA más identificado fue "verse más enfermo" 33.0% (IC95%: 30.1,36.0) y el menos identificado fue "salir pus del oído" (1.5% [IC95%: 0.9,2.7]). CONCLUSIONES: Las IRA afectan cerca de una tercera parte de los niños y las niñas menores de cinco años en México, particularmente de los hogares con menores capacidades económicas. Es necesario fortalecer las estrategias de prevención, entre ellas la vacunación, el control y la promoción de la salud.

Porcentaje de enfermedad diarreica aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de enfermedad diarreica aguda (EDA) en menores de cinco años en las últimas dos semanas, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022. Material y métodos. Se analizaron los datos de menores de cinco años incluidos en la Encuesta Nacional de Salud y Nutrición Continua 2022 respecto a la EDA en las últimas dos semanas. Se compararon los datos con los de ediciones previas de la encuesta. RESULTADOS: El porcentaje de EDA en México fue de 9.4% (IC95%: 7.9,11.2), similar al de 2000, con diferencias por grupo etario. Durante el episodio de EDA, 38.7% (IC95%: 27.7,51.0) de las personas cuidadoras ofrecen menor cantidad de alimentos a la habitual. CONCLUSIONES: El elevado porcentaje de EDA en menores de cinco años en México en el 2022 evidencia la necesidad de fortalecer estrategias de prevención y promoción de la salud.

Vacunación en adultos y adultos mayores en México.

OBJETIVO: Estimar la prevalencia del antecedente de vacunación en adultos de 20 a 59 años y mayores de 60 años mediante autorreporte. Material y métodos. Análisis de datos obtenidos de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). RESULTADOS: El 27.4% de los adultos de 20-39 años refirió haber recibido vacuna doble viral (sarampión y rubeola [SR]) y 57.3% de adultos de 20-59 años cualquier vacuna con toxoide tetánico (Td) en los últimos diez años. En mujeres de 29 a 49 años, 18.7% (IC95%: 17.0,20.5) y 58.46% (IC95%: 56.2,60.7) habían sido vacunadas con vacuna SR y Td, respectivamente. En mayores de 60 años, 48.8% (IC95%: 45.9,51.7), 24.4% (IC95%: 22.2,26.8) y 49.1% (IC95%: 46.1,52.2) informaron haber recibido cualquier vacuna conteniendo Td, vacuna antineumococo y vacuna antiinfluenza estacional desde septiembre del año anterior a la encuesta, respectivamente. Conclusión. Los resultados de este estudio muestran que una proporción considerable de adultos, mujeres en edad fértil y adultos mayores no estaban protegidos contra enfermedades prevenibles por vacunación en 2022.

Exploración del discurso de los enfermos crónicos sobre la legalización de la muerte asistida / Exploring the Discourse of Chronically-Ill Patients about the Legalization of Medically-Assisted Death / Exploração do discurso dos doentes crônicos sobre a legalização da morte medicamente assistida

Introducción: las enfermedades crónicas van en aumento e implican múltiples consecuencias que, en un determinado momento, con el paso de los años, pueden llegar a un estado terminal de la enfermedad. El objetivo de este estudio fue analizar el discurso de enfermos crónicos sobre la muerte digna, la eutanasia y el suicidio médicamente asistido para visibilizar la necesidad de la regulación de la muerte digna. Materiales y métodos: se llevó a cabo una investigación cualitativa que se inserta dentro del paradigma del construccionismo social, mediante entrevistas a enfermos crónicos de la Ciudad de México, utilizando una guía semiestructurada. Se empleó el análisis del discurso para encontrar convergencias y diferencias en los discursos. Resultados: se entrevistaron siete personas vía telefónica de enero a marzo del 2022. Las principales enfermedades fueron: lupus, cáncer, artritis, diabetes y ovarios poliquísticos. Los discursos convergen hacia una muerte digna sin dolor, sufrimiento, tranquila y en casa. Coinciden sus discursos en legalizar la eutanasia y el suicidio médicamente asistido; sin embargo, hay divergencias en cuanto a solicitarlas. Conclusiones: la experiencia de la enfermedad crónica es un factor importante para aceptar en un futuro la muerte médicamente asistida, sin ser una carga para otros y evitar el dolor y sufrimiento al final de la vida. La religión influye en las decisiones, pero se puede observar una mayor apertura para aceptar la legalización de la muerte médicamente asistida.

Introduction: Chronic diseases are increasing in frequency and entail multiple consequences that can eventually lead to death. The study aim was to analyze the discourse of chronically-ill patients on death with dignity, euthanasia, and medically-assisted suicide to highlight the need for regulation of death with dignity. Materials and Methods: A qualitative study was conducted within the paradigm of social constructionism. A semi-structured guide was used to conduct interviews with chronically-ill patients in Mexico City. Discourse analysis was performed to identify convergences and differences in the discourses. Results: Seven interviews were conducted by telephone from January to March 2022. The main diseases of the interviewees were lupus, cancer, arthritis, diabetes, and polycystic ovaries. The discourses converged toward a preference for dignified death without pain or suffering that was calm, and occurred at home. The discourses included the topics of legalizing euthanasia and medically-assisted suicide, but the patients differed on whether or not these should be requested. Conclusions: The experience of chronic illness was an important factor in accepting medically-assisted death for the patients, who did not wish to be a burden on others and wanted to avoid pain and suffering at the end of their lives. Religion influenced the patients' decisions, but there was openness to accepting legalization of medically-assisted death.

Introdução: a incidência das doenças crônicas vem aumentando, e têm múltiplas consequências que num determinado momento, ao longo dos anos, podem chegar a um estado terminal da doença. O objetivo deste estudo foi analisar o discurso de pessoas com doenças crônicas sobre morte digna, eutanásia e suicídio medicamente assistido para tornar visível a necessidade de regulamentar a morte digna. Materiais e métodos: foi realizada uma pesquisa qualitativa que se insere no paradigma do construcionismo social. Entrevistas com pacientes crônicos na Cidade do México foram realizadas usando um guia semiestruturado. A análise do discurso foi utilizada para encontrar convergências e divergências nos discursos. Resultados: foram realizadas sete entrevistas por telefone no período de janeiro a março de 2022. As principais doenças foram lúpus, câncer, artrite, diabetes e ovários policísticos. Os discursos convergem para uma morte digna sem dor, sofrimento, tranquila e em casa. Seus discursos coincidem na legalização da eutanásia e do suicídio medicamente assistido; entretanto, há divergências quanto à sua solicitação. Conclusões: a experiência da doença crônica é um fator importante para aceitar a morte medicamente assistida no futuro, sem ser um fardo para os outros e evitando a dor e o sofrimento no final da vida. A religião influencia nas decisões, mas observase uma maior abertura para aceitar a legalização da morte medicamente assistida.

Practical considerations for accurate determination of free thyroxine by equilibrium dialysis.

Background: Free thyroxine (FT4) measurement is one of the most requested tests in patient care for diagnosing and treating thyroid-related illnesses. Equilibrium dialysis (ED) is considered the "gold standard" for FT4 measurement; however, several factors have a profound effect on the reliability of FT4 assays and require special consideration. Methods: In the current study, we focused on evaluating critical factors that could contribute to reporting errors, such as adsorption of thyroxine (T4) to labware surfaces, stability of serum samples, stock solutions, and calibrator storage conditions, as well as the solvents used to prepare T4 solutions. Results: The adsorption of T4 in ethanolic solutions and dialysates to labware surfaces can be reduced with the careful selection of pipette tips, test tubes, and 96-well plates. Adding pH modifiers to neat T4 solutions can improve its stability. FT4 in serum samples remains stable after exposure to four freeze-thaw cycles, 5 °C for 18-20 h, or -70 °C for a minimum of three years. Conclusion: The presented study has demonstrated that the loss of analyte due to pre-analytical and analytical factors during operation of the FT4 reference measurement procedure (RMP) can be minimized by careful selection of all labware for sample preparation. It was found that the accuracy and imprecision of FT4 assays can be influenced by different types of dialysis devices, but acceptable alternatives to ED membranes were identified. This study demonstrates approaches to establish a FT4 method that is independent from specific suppliers and addresses critical pre-analytical and analytical factors important for FT4 measurements.

Water reclamation from anodizing wastewaters by removing reactive silica with adsorption and precipitation methods.

Water stress is a current environmental menace mainly driven by over exploitation of aquifers, which is triggering poor water quality with high concentration of minerals in extracted groundwater. Particularly, silica is widespread in natural water supplies due to weathering processes of silicates occurring in contact with water, light, air, and other factors. However, due to groundwater over extraction the concentration of silica has increased during the last years in aquifer reservoirs from Aguascalientes State (México). In this context, it is very important to note that the removal of silica compounds from water is challenging and different methods can be used to avoid embedding problems in different industries. In the present work, the removal of reactive silica from synthetic solutions as well as from real wastewaters from an industrial anodizing process was studied using adsorption and chemical precipitation methods. Twelve commercial materials of different nature were used for adsorption tests, while seven precipitant agents were applied in the precipitation experiments. Adsorption tests were performed in batch systems with constant stirring at 30 °C and at different pH values (7 and 9). Precipitation experiments were carried out in batch systems and the best conditions for silica removal were found using an L9 orthogonal array of the Taguchi method employing molar ratio, pH of wastewater, stirring time and temperature as experimental factors. Adsorption results showed that Ferrolox (Iron (III) hydroxide-base adsorbent) was the most efficient sorbent for reactive silica removal from synthetic solutions and the anodizing wastewater. Also, the reactive silica adsorption was higher at pH 9 as compared to that measured at pH 7 and the adsorbed quantity at pH 9 was 16.22 and 11.25 mg/g for the synthetic solution and anodizing wastewater, respectively. According to molecular simulation, the main interaction between Ferrolox and silica species was related to the formation of hydroxo-complexes and to the interaction of Fe with oxygen of silica species. Additionally, magnesium chloride was the best precipitating reagent for reactive silica achieving up to 87% removal. According to ANOVA analysis of Taguchi method, pH was the most influential factor during the precipitation of reactive silica with a variance value of 81.42, while values lower than 3 were obtained for the rest of parameters. Overall, the present work is reporting for the first time the removal of reactive silica from anodizing wastewaters with promising results that can be implemented at full scale for water reclamation, which may significantly contribute to manage water reservoir in the region sustainably.

Evaluating the impact of mobility in COVID-19 incidence and mortality: A case study from four states of Mexico.

Introduction: The COVID-19 pandemic in Mexico began at the end of February 2020. An essential component of control strategies was to reduce mobility. We aimed to evaluate the impact of mobility on COVID- incidence and mortality rates during the initial months of the pandemic in selected states. Methods: COVID-19 incidence data were obtained from the Open Data Epidemiology Resource provided by the Mexican government. Mobility data was obtained from the Observatory for COVID-19 in the Americas of the University of Miami. We selected four states according to their compliance with non-pharmaceutical interventions and mobility index. We constructed time series and analyzed change-points for mobility, incidence, and mortality rates. We correlated mobility with incidence and mortality rates for each time interval. Using mixed-effects Poisson models, we evaluated the impact of reductions in mobility on incidence and mortality rates, adjusting all models for medical services and the percentage of the population living in poverty. Results: After the initial decline in mobility experienced in early April, a sustained increase in mobility followed during the rest of the country-wide suspension of non-essential activities and the return to other activities throughout mid-April and May. We identified that a 1% increase in mobility yielded a 5.2 and a 2.9% increase in the risk of COVID-19 incidence and mortality, respectively. Mobility was estimated to contribute 8.5 and 3.8% to the variability in incidence and mortality, respectively. In fully adjusted models, the contribution of mobility to positive COVID-19 incidence and mortality was sustained. When assessing the impact of mobility in each state compared to the state of Baja California, increased mobility conferred an increased risk of incident positive COVID-19 cases in Mexico City, Jalisco, and Nuevo León. However, for COVID-19 mortality, a differential impact of mobility was only observed with Jalisco and Nuevo León compared to Baja California. Conclusion: Mobility had heterogeneous impacts on COVID-19 rates in different regions of Mexico, indicating that sociodemographic characteristics and regional-level pandemic dynamics modified the impact of reductions in mobility during the COVID-19 pandemic. The implementation of non-pharmaceutical interventions should be regionalized based on local epidemiology for timely response against future pandemics.

Multiple molecular mechanisms are involved in the activation of the kidney sodium-chloride cotransporter by hypokalemia.

Low potassium intake activates the kidney sodium-chloride cotransporter (NCC) whose phosphorylation and activity depend on the With-No-Lysine kinase 4 (WNK4) that is inhibited by chloride binding to its kinase domain. Low extracellular potassium activates NCC by decreasing intracellular chloride thereby promoting chloride dissociation from WNK4 where residue L319 of WNK4 participates in chloride coordination. Since the WNK4-L319F mutant is constitutively active and chloride-insensitive in vitro, we generated mice harboring this mutation that displayed slightly increased phosphorylated NCC and mild hyperkalemia when on a 129/sv genetic background. On a low potassium diet, upregulation of phosphorylated NCC was observed, suggesting that in addition to chloride sensing by WNK4, other mechanisms participate which may include modulation of WNK4 activity and degradation by phosphorylation of the RRxS motif in regulatory domains present in WNK4 and KLHL3, respectively. Increased levels of WNK4 and kidney-specific WNK1 and phospho-WNK4-RRxS were observed in wild-type and WNK4L319F/L319F mice on a low potassium diet. Decreased extracellular potassium promoted WNK4-RRxS phosphorylation in vitro and ex vivo as well. These effects might be secondary to intracellular chloride depletion, as reduction of intracellular chloride in HEK293 cells increased phospho-WNK4-RRxS. Phospho-WNK4-RRxS levels were increased in mice lacking the Kir5.1 potassium channel, which presumably have decreased distal convoluted tubule intracellular chloride. Similarly, phospho-KLHL3 was modulated by changes in intracellular chloride in HEK293 cells. Thus, our data suggest that multiple chloride-regulated mechanisms are responsible for NCC upregulation by low extracellular potassium.

The European and Japanese eel NaCl cotransporters ß exhibit chloride currents and are resistant to thiazide type diuretics.

The thiazide-sensitive Na+-Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule, and the inhibition of its function with thiazides is widely used for the treatment of arterial hypertension. In mammals and teleosts, NCC is present as one ortholog that is mainly expressed in the kidney. One exception, however, is the eel, which has two genes encoding NCC. The eNCCα is located in the kidney and eNCCß, which is present in the apical membrane of the rectum. Interestingly, the European eNCCß functions as a Na+-Cl- cotransporter that is nevertheless resistant to thiazides and is not activated by low-chloride hypotonic stress. However, in the Japanese eel rectal sac, a thiazide-sensitive NaCl transport mechanism has been described. The protein sequences between eNCCß and jNCCß are 98% identical. Here, by site-directed mutagenesis, we transformed eNCCß into jNCCß. Our data showed that jNCCß, similar to eNCCß, is resistant to thiazides. In addition, both NCCß proteins have high transport capacity with respect to their renal NCC orthologs and, in contrast to known NCCs, exhibit electrogenic properties that are reduced when residue I172 is substituted by A, G, or M. This is considered a key residue for the chloride ion-binding sites of NKCC and KCC. We conclude that NCCß proteins are not sensitive to thiazides and have electrogenic properties dependent on Cl-, and site I172 is important for the function of NCCß.

La importancia de implementar y difundir la Ley de Voluntad Anticipada en México

Propósito/Contexto. Identificar mediante un cuestionario si personas con diferentes características sociodemográficas que viven en la República Mexicana conocen la importancia de la Ley de Voluntad Anticipada (LVA). Metodología/Enfoque. Se realizó un estudio cuantitativo observacional, descriptivo y transversal. También se llevó a cabo una encuesta de opinión a la población general con una representatividad a nivel nacional, el margen de error fue de +/- 3,46 % con un nivel de confianza del 95 %. Resultados/Hallazgos. El 49,6 % de las personas encuestadas desconocen la LVA y el 41,4 % considera que ayudaría a tener una muerte digna. En cuanto a la pregunta de si en su estado existe esta ley, el 63 % opina que no lo sabe y respecto a la pregunta de si en el estado en el que viven es necesario implementarla, el 41,3 % está totalmente de acuerdo. Discusión/Conclusiones/Contribuciones. En este estudio se observó que la población no tiene información acerca de esta ley y expresa su interés en conocer y en afirmar que están de acuerdo con una muerte digna, evitar el sufrimiento y el dolor.

Purpose/Context. Identify through a questionnaire if people with different sociodemographic characteristics living in the Mexican Republic know the importance of the Advance Will Law (LVA). Methodology/Approach. An observational, descriptive, cross-sectional quantitative study was performed. An opinion survey of the general population was carried out with a national representation; the margin of error was +/- 3.46% with a confidence level of 95%. Results/Findings. 49.6% of the people surveyed do not know the LVA and 41.4% consider that it would help people to have a dignified death. As for the question of whether this law exists in their state, 63% think they do not know; and regarding the question of whether in the state in which they live it is necessary to implement the LVA, 41.3% totally agree. Discussion/Conclusions/Contributions. In this study it was observed that the population does not have information about this law and expresses their interest in knowing and affirming that they agree with a dignified death, avoiding suffering and pain.

Objetivo/Contexto. O objetivo deste artigo é identificar, mediante um questionário, se pessoas com diferentes características sociodemográficas que vivem na República Mexicana, conhecem a importância da Lei de Vontade Antecipada (LVA). Metodologia/Abordagem. Realizou-se um estudo quantitativo observacional, descritivo, transversal. Foi realizado um inquérito de opinião à população em geral com uma representatividade a nível nacional; a margem de erro foi de +/-3,46 %, com um nível de confiança de 95 %. Resultados/Conclusões. O 49,6 % das pessoas entrevistadas desconhecem a LVA e 41,4 % consideram que isso ajudaria a ter uma morte digna. No que se refere à questão de saber se a lei existe no seu Estado, o 63% consideram que não sabem; e no que se refere à questão de saber se, no Estado-Membro em que vivem, é necessário implementá-la, 41,3% concordam plenamente. Discussão/Conclusões/Contribuições. Neste estudo observou-se que a população não tem informação sobre esta lei e expressa seu interesse em conhecer e em afirmar que estão de acordo com uma morte digna, evitar o sofrimento e a dor.

Comunicación médico-paciente en enfermos de cáncer en etapa terminal: una visión desde la experiencia de los familiares / Doctor-Patient Communication in End-Stage Cancer Patients: a View From the Experience of Family / Comunicação médico-paciente em pacientes com câncer em estágio terminal: uma perspectiva a partir da experiência de familiares

Resumen: Uno de los elementos prioritarios en la ética médica es la relación médico-paciente. La comunicación es fundamental para que los enfermos y sus familiares puedan tomar decisiones al final de la vida. El objetivo del artículo es conocer, a partir de la experiencia de los familiares de los enfermos de cáncer en etapa terminal, la información oportuna que proporciona el médico sobre el pronóstico y las condiciones del enfermo para tomar decisiones que alivien las molestias o el sufrimiento. Se llevó a cabo un estudio cualitativo que parte del paradigma hermenéutico fenomenológico, el cual permite conocer la percepción que tienen las personas del mundo en el cual viven y el significado que le dan. Se entrevistó a once familiares y cuidadores primarios y se utilizó el análisis temático y el método de van Manen. La experiencia de los familiares muestra que algunos enfermos no recibieron información acerca de su condición y pronóstico. Se puede concluir que algunos de los médicos necesitan capacitación mediante reuniones en donde un profesional de la salud mental dirija sesiones sobre las emociones para afrontar situaciones relacionadas con la muerte y manejar la angustia.

Summary: One of the priority elements in medical ethics is the physician-patient relationship. Communication is essential so patients and their families can make decisions at the end of life. The main aim of this article is to be aware, from the experience of patients with terminal cancer relatives, the timely information provided by the physician about the prognosis and conditions of the patient to make decisions that alleviate discomfort or suffering. A qualitative study was carried out starting from the phenomenological hermeneutic paradigm, which allows us to know the perception people have of the world in which they live and the meaning they give it. Eleven family members and primary caregivers were interviewed using the van Manen's thematic analysis and method. The experience of family members shows that some patients did not receive information about their condition and prognosis. It can be concluded that some of the physicians need training through meetings where a mental health professional leads sessions on emotions to cope with situations related to death and manage distress.

Resumo: Um dos elementos prioritários da ética médica é a relação médico-paciente. A comunicação é essencial para que os pacientes e suas famílias tomem decisões no final da vida. O objetivo deste artigo é conhecer, a partir da experiência de familiares de pacientes com câncer em estágio terminal, as informações oportunas fornecidas pelo médico sobre o prognóstico e as condições do paciente para que decisões que aliviem o desconforto ou o sofrimento possam ser tomadas. Foi reali -zado um estudo qualitativo baseado no paradigma hermenêutico fenomenológico, que nos permite conhecer a percepção que as pessoas têm do mundo em que vivem e o significado que elas dão a ele. Onze familiares e cuidadores primários foram entrevistados e a análise temática e o método de van Manen foram utilizados. A experiência dos familiares mostra que alguns pacientes não receberam informações sobre sua condição e prognóstico. Pode-se concluir que alguns médicos precisam de treinamento por meio de reuniões em que um profissional de saúde mental realize sessões sobre emoções para lidar com situações relacionadas à morte e a como lidar com a angústia.

Role of KLHL3 and dietary K+ in regulating KS-WNK1 expression.

The physiological role of the shorter isoform of with no lysine kinase (WNK)1 that is exclusively expressed in the kidney (KS-WNK1), with particular abundance in the distal convoluted tubule, remains elusive. KS-WNK1, despite lacking the kinase domain, is nevertheless capable of stimulating the NaCl cotransporter, apparently through activation of WNK4. It has recently been shown that a less severe form of familial hyperkalemic hypertension featuring only hyperkalemia is caused by missense mutations in the WNK1 acidic domain that preferentially affect cullin 3 (CUL3)-Kelch-like protein 3 (KLHL3) E3-induced degradation of KS-WNK1 rather than that of full-length WNK1. Here, we show that full-length WNK1 is indeed less impacted by the CUL3-KLHL3 E3 ligase complex compared with KS-WNK1. We demonstrated that the unique 30-amino acid NH2-terminal fragment of KS-WNK1 is essential for its activating effect on the NaCl cotransporter and recognition by KLHL3. We identified specific amino acid residues in this region critical for the functional effect of KS-WNK1 and KLHL3 sensitivity. To further explore this, we generated KLHL3-R528H knockin mice that mimic human mutations causing familial hyperkalemic hypertension. These mice revealed that the KLHL3 mutation specifically increased expression of KS-WNK1 in the kidney. We also observed that in wild-type mice, the expression of KS-WNK1 was only detectable after exposure to a low-K+ diet. These findings provide new insights into the regulation and function of KS-WNK1 by the CUL3-KLHL3 complex in the distal convoluted tubule and indicate that this pathway is regulated by dietary K+ levels.NEW & NOTEWORTHY In this work, we demonstrated that the kidney-specific isoform of with no lysine kinase 1 (KS-WNK1) in the kidney is modulated by dietary K+ and activity of the ubiquitin ligase protein Kelch-like protein 3. We analyzed the role of different amino acid residues of KS-WNK1 in its activity against the NaCl cotransporter and sensitivity to Kelch-like protein 3.

Experimental and theoretical study of dyes adsorption process on chitosan-based cryogel.

In this research, the adsorption of three synthetic dyes dissolved in an aqueous solution on chitosan cryogel beads (Q-C-EGDE) was compared. The effect of the pH of the solution on the adsorption capacity of each dyes was analyzed. Furthermore, the kinetics and adsorption isotherms were compared, at temperatures of 283.15 K, 303.15 K and 323.15 K, and the kinetic and adsorption equilibrium data were fitted to three mathematical models, respectively. The biosorbent was characterized by scanning electron microscopy (SEM), the nitrogen physisorption BET method and Fourier transform infrared spectroscopy (FTIR). The characterization results show that the cryogel is composed of low-surface, macroporous, porous grooved walls. The functional groups that took part in the adsorption were mainly amino groups (NH3+). When comparing the adsorption capacities, it was found that the dyes adsorb in the following order Blue 1 > Red 2 > Yellow 5 reaching capacities from 1600 mg/L to 850 mg/L. The results of the adsorption and mathematical modelling suggest that the process is regulated mainly by physisorption and is largely limited by mass transfer mechanisms within the cryogel, where the electrostatic charges present affect adsorption. The latter was corroborated by the Monte Carlo simulation.

Determination of structural properties in the adsorption of drugs on chitosan-hydrogels for type 2 diabetes by means of the PM6 method / Determinación de propiedades estructurales en la adsorción de fármacos en hidrogeles de quitosano para diabetes tipo 2 mediante el método PM6 / Determinação das propriedades estruturais en adsorção de drogas em hidrogelos de quitosan para diabetes do tipo 2 pelo método PM6

Abstract Computational chemistry performs the modeling and calculation of physicochemical properties that allow understanding of the different molecular interactions at the nanometric scale in medical applications such as the design of controlled release systems. The PM6 model was used to analyze metformin and glibenclamide. First, the energy properties as the Gibbs free energy and enthalpies were obtained. The results showed the affinity of both drugs with water (glibenclamide: -7.96 and metformin: -11.49) due to the formation of hydrogen bonds, which were verified by the electronegativities corresponding to the dipole moment and to the partition coefficient (Log P). Subsequently, the main properties for the design of a release system using the metformin/glibenclamide complex in the chitosan hydrogel were determined. In this process it was appreciated that the Gibbs free energy (-2157.60 kcal/ mol) determined the thermodynamic stability of the adsorption. In addition, the Log P (-25.82) indicated an instantaneous solubility through the formation of hydrogen bonds and were verified by the electronic distribution and the change in dipole moment.

Resumen La química computacional realiza el modelado y el cálculo de propiedades fisicoquímicas que permiten comprender las diferentes interacciones moleculares a escala nanométrica en aplicaciones médicas como el diseño de sistemas de liberación controlada, por ejemplo. El modelo PM6 se utilizó para analizar metformina y glibenclamida. Primero se obtuvieron las propiedades energéticas como la energía libre de Gibbs y las entalpias. Los resultados mostraron la afinidad de ambos fármacos con el agua (glibenclamide: -7,96 y metformina: -11,49) debido a la formación de enlaces de hidrógeno que fueron verificados por las electronegatividades correspondientes al momento dipolar y al coeficiente de partición (Log P). Posteriormente, se determinaron las principales propiedades para el diseño de un sistema de liberación que usa el complejo metformina/glibenclamida en el hidrogel de quitosano. En este proceso se apreció que la energía libre de Gibbs (-2157,60 kcal/mol) determinó la estabilidad termodinámica de la adsorción. Además, el Log P (-25,82) indicó una solubilidad instantánea a través de la formación de enlaces de hidrógeno y se verificó mediante la distribución electrónica y el cambio en el momento dipolar.

Resumo A química computacional realiza a modelagem e o cálculo das propriedades físico-químicas que permitem compreender as diferentes interações moleculares em escala nanométrica em aplicações médicas, como o projeto de sistemas de liberação controlada. O modelo PM6 é usado para analisar metformina e glibenclamida. Primeiro, obtenha as propriedades energéticas como a energia livre de Gibbs e as entalpias. Os resultados mostram a afinidade de ambos os componentes com água (glibenclamida: -7.96 e forma: -11.49) debitados na forma de ligações de hidrogénio, que verificam por eletronegatividades correspondentes no momento dipolar e coeficiente de participação (Log P). Posteriormente, selecione as principais propriedades para o projeto de um sistema de liberação que usa o método completo/glibenclamida no hidrogel de quitosano. Neste processo, aprecie a energia livre de Gibbs (-2157.60 kcal/mol) que determina a estabilidade termodinâmica da adsorção. Além disso, o Log P (-25.82) indica uma solução instantânea para a passagem de forma de hidrogénio e é verificada usando a distribuição eletrônica e o câmbio no momento dipolar.

WNK3 and WNK4 exhibit opposite sensitivity with respect to cell volume and intracellular chloride concentration.

Cation-coupled chloride cotransporters (CCC) play a role in modulating intracellular chloride concentration ([Cl-]i) and cell volume. Cell shrinkage and cell swelling are accompanied by an increase or decrease in [Cl-]i, respectively. Cell shrinkage and a decrease in [Cl-]i increase the activity of NKCCs (Na-K-Cl cotransporters: NKCC1, NKCC2, and Na-Cl) and inhibit the activity of KCCs (K-Cl cotransporters: KCC1 to KCC4), wheras cell swelling and an increase in [Cl-]i activate KCCs and inhibit NKCCs; thus, it is unlikely that the same kinase is responsible for both effects. WNK1 and WNK4 are chloride-sensitive kinases that modulate the activity of CCC in response to changes in [Cl-]i. Here, we showed that WNK3, another member of the serine-threonine kinase WNK family with known effects on CCC, is not sensitive to [Cl-]i but can be regulated by changes in extracellular tonicity. In contrast, WNK4 is highly sensitive to [Cl-]i but is not regulated by changes in cell volume. The activity of WNK3 toward NaCl cotransporter is not affected by eliminating the chloride-binding site of WNK3, further confirming that the kinase is not sensitive to chloride. Chimeric WNK3/WNK4 proteins were produced, and analysis of the chimeras suggests that sequences within the WNK's carboxy-terminal end may modulate the chloride affinity. We propose that WNK3 is a cell volume-sensitive kinase that translates changes in cell volume into phosphorylation of CCC.