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Objective: The objective is to expose the cardiovascular alterations in patients diagnosed with pediatric inflammatory multisystem syndrome (PIMS) associated with COVID-19 during the SARS-CoV-2 pandemic, in order to understand the disease, its evolution, and optimal management upon diagnosis. Method: Retrospective, observational, cross-sectional analytical study of patients diagnosed with PIMS according to the criteria of the World Health Organization at the National Institute of Pediatrics, from March 2020 to December 2021. Results: During the study period, 77 patients with PIMS were diagnosed. The results showed correlation between the shock state and alteration of laboratory markers (platelets 144217.29 ± 139321.6 µL [p < 0.001], procalcitonin 27.37 ± 38.37 ng/ml [p = 0.05] and ferritin 1937.87 ± 2562.63 [p < 0.001]). The ventricular function in patients with shock was significantly lower compared to those without shock (49.6 ± 9.1% vs. 58.1 ± 8.4 %; t-Student p < 0.001), as well as injury to the left coronary artery (p = 0.02). There is a correlation between NT-proBNP and ventricular dysfunction (Kruskal-Wallis p = 0.007). Statistical significance was found in the association between death, elevation of inflammatory markers and ventricular dysfunction (p < 0.001). Conclusions: The cardiovascular alterations observed, in order of frequency, were pericardial effusion (25.7%), myocarditis (15%), mild ventricular dysfunction (13.5%) and small coronary aneurysm with predominance of the left coronary artery and the anterior descending one.
Objetivo: Exponer las alteraciones cardiovasculares en los pacientes diagnosticados con síndrome inflamatorio multisistémico pediátrico (PIMS) asociado a COVID-19 durante la pandemia por SARS-CoV-2 con el fin de comprender la enfermedad, su evolución y el manejo óptimo al diagnóstico. Método: Estudio retrospectivo, observacional, transversal y analítico de pacientes con diagnóstico de PIMS de acuerdo con los criterios de la Organización Mundial de la Salud en el Instituto Nacional de Pediatría, de marzo de 2020 a diciembre de 2021. Resultados: Durante el periodo de estudio se diagnosticaron 77 pacientes con PIMS. Los resultados demostraron una correlación entre el estado de choque y la alteración de los marcadores de laboratorio (plaquetas 144217.29 ± 139321.6 µl [p < 0.001], procalcitonina 27.37 ± 38.37 ng/ml [p = 0.05] y ferritina 1937.87 ± 2562.63 [p < 0.001]). La función ventricular en los pacientes con choque se registró significativamente menor en comparación con aquellos sin choque (49.6 ± 9.1 % vs. 58.1 ± 8.4 %; t de Student p < 0.001), así como lesión en la arteria coronaria izquierda (p = 0.02). Existe una correlación entre el NT-proBNP y la disfunción ventricular (Kruskal-Wallis p = 0.007). Se encontró significancia estadística en la asociación entre fallecimiento, elevación de los marcadores inflamatorios y disfunción ventricular (p < 0.001). Conclusiones: Las alteraciones cardiovasculares observadas fueron, en orden de frecuencia, derrame pericárdico (25.7%), miocarditis (15%), disfunción ventricular leve (13.5%) y aneurisma pequeño coronario con predominio de la arteria coronaria izquierda y la descendente anterior.
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Advancements in digital technology have brought modelling to the forefront in many disciplines from healthcare to architecture. Mathematical models, often represented using parametrised sets of ordinary differential equations, can be used to characterise different processes. To infer possible estimates for the unknown parameters, these models are usually calibrated using associated experimental data. Structural and practical identifiability analyses are a key component that should be assessed prior to parameter estimation. This is because identifiability analyses can provide insights as to whether or not a parameter can take on single, multiple, or even infinitely or countably many values which will ultimately have an impact on the reliability of the parameter estimates. Also, identifiability analyses can help to determine whether the data collected are sufficient or of good enough quality to truly estimate the parameters or if more data or even reparameterization of the model is necessary to proceed with the parameter estimation process. Thus, such analyses also provide an important role in terms of model design (structural identifiability analysis) and the collection of experimental data (practical identifiability analysis). Despite the popularity of using data to estimate the values of unknown parameters, structural and practical identifiability analyses of these models are often overlooked. Possible reasons for non-consideration of application of such analyses may be lack of awareness, accessibility, and usability issues, especially for more complicated models and methods of analysis. The aim of this study is to introduce and perform both structural and practical identifiability analyses in an accessible and informative manner via application to well established and commonly accepted bioengineering models. This will help to improve awareness of the importance of this stage of the modelling process and provide bioengineering researchers with an understanding of how to utilise the insights gained from such analyses in future model development.
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The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.
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Conducto Arterioso Permeable , Conducto Arterial , Cardiopatías Congénitas , Recién Nacido , Humanos , Alprostadil/uso terapéutico , Conducto Arterioso Permeable/tratamiento farmacológico , EspasmoRESUMEN
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases in the elderly. The key histopathological features of these diseases are the presence of abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain unknown, but there is extensive evidence indicating that excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with a depleted antioxidant system, mitochondrial dysfunction, and intracellular Ca2+ dyshomeostasis, plays a vital role in the pathophysiology of these neurological disorders. Due to an improvement in life expectancy, the incidence of age-related neurodegenerative diseases has significantly increased. However, there is no effective protective treatment or therapy available but rather only very limited palliative treatment. Therefore, there is an urgent need for the development of preventive strategies and disease-modifying therapies to treat AD/PD. Because dysregulated Ca2+ metabolism drives oxidative damage and neuropathology in these diseases, the identification or development of compounds capable of restoring Ca2+ homeostasis and signaling may provide a neuroprotective avenue for the treatment of neurodegenerative diseases. In addition, a set of strategies to control mitochondrial Ca2+ homeostasis and signaling has been reported, including decreased Ca2+ uptake through voltage-operated Ca2+ channels (VOCCs). In this article, we review the modulatory effects of several heterocyclic compounds on Ca2+ homeostasis and trafficking, as well as their ability to regulate compromised mitochondrial function and associated free-radical production during the onset and progression of AD or PD. This comprehensive review also describes the chemical synthesis of the heterocycles and summarizes the clinical trial outcomes.
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Introducción: actualmente, se han diseñado diversas herramientas para detectar oportunamente el riesgo de desnutrición en niños hospitalizados. En aquellos con diagnóstico de cardiopatías congénitas (CC), solo existe una herramienta desarrollada en Canadá, llamada Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), la cual fue diseñada en idioma inglés. Objetivo: evaluar la validez y confiabilidad de la adaptación en español de la herramienta IMFC:CHD en lactantes con CC. Métodos: estudio transversal de validación realizado en dos etapas: la primera, de traducción y adaptación transcultural de la herramienta; y la segunda, de validación de la nueva herramienta traducida, donde se obtuvieron las evidencias de confiabilidad y validez. Resultados: en la primera etapa se obtuvo la herramienta traducida y adaptada al idioma español; para la segunda etapa se incluyeron 24 lactantes con diagnóstico de CC. Se evaluó la validez de criterio concurrente entre la herramienta de tamizaje y la evaluación antropométrica, obteniéndose un acuerdo sustancial (κ = 0,660, IC 95 %: 0,36-0,95). Para la validez de criterio predictiva, la cual fue comparada con los días de estancia hospitalaria, se obtuvo un acuerdo moderado (κ = 0,489, IC 95 %: 0,1-0,8). La confiabilidad de la herramienta se evaluó mediante consistencia externa, midiendo la concordancia interobservador, y se obtuvo un acuerdo sustancial (κ = 0,789, IC 95 %: 0,5-0,9); la reproducibilidad de la herramienta mostró un acuerdo casi perfecto (κ = 1, IC 95 %: 0,9-1,0). Conclusiones: la herramienta IMFC:CHD mostró una adecuada validez y confiabilidad, por lo que podría considerarse un recurso útil para la identificación de desnutrición grave. (AU)
Introduction: currently, various tools have been designed to timely detect the risk of malnutrition in hospitalized children. In those with a diagnosis of congenital heart disease (CHD), there is only one tool developed in Canada: Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), which was designed in English. Objective: to evaluate the validity and reliability of the Spanish adaptation of the IMFC:CHD tool in infants with CHD. Methods: cross-sectional validation study carried out in two stages. The first, of translation and cross-cultural adaptation of the tool, and the second, of validation of the new translated tool, where evidence of reliability and validity were obtained. Results: in the first stage, the tool was translated and adapted to the Spanish language; for the second stage, 24 infants diagnosed with CHD were included. The concurrent criterion validity between the screening tool and the anthropometric evaluation was evaluated, obtaining a substantial agreement (κ = 0.660, 95 % CI: 0.36-0.95) and for the predictive criterion validity, which was compared with the days of hospital stay, moderate agreement was obtained (κ = 0.489, 95 % CI: 0.1-0.8). The reliability of the tool was evaluated through external consistency, measuring theinter-observer agreement, obtaining a substantial agreement (κ = 0.789, 95 % CI: 0.5-0.9), and the reproducibility of the tool showed an almost perfect agreement (κ = 1, CI 95 %: 0.9-1.0). Conclusions: the IMFC:CHD tool showed adequate validity and reliability, and could be considered as a useful resource for the identification of severe malnutrition. (AU)
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Humanos , Masculino , Femenino , Lactante , Trastornos de la Nutrición del Lactante , Cardiopatías Congénitas , Estudios Transversales , Epidemiología Descriptiva , México , Evaluación NutricionalRESUMEN
Introduction: Introduction: currently, various tools have been designed to timely detect the risk of malnutrition in hospitalized children. In those with a diagnosis of congenital heart disease (CHD), there is only one tool developed in Canada: Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), which was designed in English. Objective: to evaluate the validity and reliability of the Spanish adaptation of the IMFC:CHD tool in infants with CHD. Methods: cross-sectional validation study carried out in two stages. The first, of translation and cross-cultural adaptation of the tool, and the second, of validation of the new translated tool, where evidence of reliability and validity were obtained. Results: in the first stage, the tool was translated and adapted to the Spanish language; for the second stage, 24 infants diagnosed with CHD were included. The concurrent criterion validity between the screening tool and the anthropometric evaluation was evaluated, obtaining a substantial agreement (κ = 0.660, 95 % CI: 0.36-0.95) and for the predictive criterion validity, which was compared with the days of hospital stay, moderate agreement was obtained (κ = 0.489, 95 % CI: 0.1-0.8). The reliability of the tool was evaluated through external consistency, measuring the inter-observer agreement, obtaining a substantial agreement (κ = 0.789, 95 % CI: 0.5-0.9), and the reproducibility of the tool showed an almost perfect agreement (κ = 1, CI 95 %: 0.9-1.0). Conclusions: the IMFC:CHD tool showed adequate validity and reliability, and could be considered as a useful resource for the identification of severe malnutrition.
Introducción: Introducción: actualmente, se han diseñado diversas herramientas para detectar oportunamente el riesgo de desnutrición en niños hospitalizados. En aquellos con diagnóstico de cardiopatías congénitas (CC), solo existe una herramienta desarrollada en Canadá, llamada Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), la cual fue diseñada en idioma inglés. Objetivo: evaluar la validez y confiabilidad de la adaptación en español de la herramienta IMFC:CHD en lactantes con CC. Métodos: estudio transversal de validación realizado en dos etapas: la primera, de traducción y adaptación transcultural de la herramienta; y la segunda, de validación de la nueva herramienta traducida, donde se obtuvieron las evidencias de confiabilidad y validez. Resultados: en la primera etapa se obtuvo la herramienta traducida y adaptada al idioma español; para la segunda etapa se incluyeron 24 lactantes con diagnóstico de CC. Se evaluó la validez de criterio concurrente entre la herramienta de tamizaje y la evaluación antropométrica, obteniéndose un acuerdo sustancial (κ = 0,660, IC 95 %: 0,36-0,95). Para la validez de criterio predictiva, la cual fue comparada con los días de estancia hospitalaria, se obtuvo un acuerdo moderado (κ = 0,489, IC 95 %: 0,1-0,8). La confiabilidad de la herramienta se evaluó mediante consistencia externa, midiendo la concordancia interobservador, y se obtuvo un acuerdo sustancial (κ = 0,789, IC 95 %: 0,5-0,9); la reproducibilidad de la herramienta mostró un acuerdo casi perfecto (κ = 1, IC 95 %: 0,9-1,0). Conclusiones: la herramienta IMFC:CHD mostró una adecuada validez y confiabilidad, por lo que podría considerarse un recurso útil para la identificación de desnutrición grave.
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Cardiopatías Congénitas , Trastornos de la Nutrición del Lactante , Desnutrición , Niño , Humanos , Lactante , Reproducibilidad de los Resultados , Lista de Verificación , Estudios Transversales , Evaluación Nutricional , Desnutrición/diagnóstico , Desnutrición/etiología , Trastornos de la Nutrición del Lactante/diagnóstico , Cardiopatías Congénitas/complicacionesRESUMEN
Colorectal cancer (CRC) is associated with mutations in APC/Wnt leading to c-myc activation and the overexpression of ODC1, the limiting step in polyamine synthesis. CRC cells also display a remodeling of intracellular Ca2+ homeostasis that contributes to cancer hallmarks. As polyamines may modulate Ca2+ homeostasis during epithelial tissue repair, we investigated whether polyamine synthesis inhibition may reverse Ca2+ remodeling in CRC cells and, if so, the molecular basis for this reversal. To this end, we used calcium imaging and transcriptomic analysis in normal and CRC cells treated with DFMO, an ODC1 suicide inhibitor. We found that polyamine synthesis inhibition partially reversed changes in Ca2+ homeostasis associated with CRC, including a decrease in resting Ca2+ and SOCE along with an increased Ca2+ store content. We also found that polyamine synthesis inhibition reversed transcriptomic changes in CRC cells without affecting normal cells. Specifically, DFMO treatment enhanced the transcription of SOCE modulators CRACR2A; ORMDL3; and SEPTINS 6, 7, 8, 9, and 11, whereas it decreased SPCA2, involved in store-independent Orai1 activation. Therefore, DFMO treatment probably decreased store-independent Ca2+ entry and enhanced SOCE control. Conversely, DFMO treatment decreased the transcription of the TRP channels TRPC1 and 5, TRPV6, and TRPP1 while increasing TRPP2, thus probably decreasing Ca2+ entry through TRP channels. Finally, DFMO treatment enhanced the transcription of the PMCA4 Ca2+ pump and mitochondrial channels MCU and VDAC3 for enhanced Ca2+ extrusion through the plasma membrane and mitochondria. Collectively, these findings suggested the critical role of polyamines in Ca2+ remodeling in colorectal cancer.
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We study the q-state Potts model for q and the space dimension d arbitrary real numbers using the derivative expansion of the nonperturbative renormalization group at its leading order, the local potential approximation (LPA and LPA^{'}). We determine the curve q_{c}(d) separating the first [q>q_{c}(d)] and second [q
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The molecular basis of amyloid toxicity in Alzheimer's disease (AD) remains controversial. Amyloid ß (Aß) oligomers promote Ca2+ influx, mitochondrial Ca2+ overload and apoptosis in hippocampal neurons in vivo and in vitro, but the primary Ca2+ entry pathways are unclear. We studied Ca2+ entry pathways induced by Aß oligomers in rat hippocampal and cerebellar neurons. Aß oligomers induce Ca2+ entry in neurons. Ca2+ responses to Aß oligomers are large after synaptic networking and prevented by blockers of synaptic transmission. In contrast, in neurons devoid of synaptic connections, Ca2+ responses to Aß oligomers are small and prevented only by blockers of amyloid channels (NA7) and NMDA receptors (MK801). A combination of NA7 and MK801 nearly abolished Ca2+ responses. Non-neuronal cells bearing NMDA receptors showed Ca2+ responses to oligomers, whereas cells without NMDA receptors did not exhibit Ca2+ responses. The expression of subunits of the NMDA receptor NR1/ NR2A and NR1/NR2B in HEK293 cells lacking endogenous NMDA receptors restored Ca2+ responses to NMDA but not to Aß oligomers. We conclude that Aß oligomers promote Ca2+ entry via amyloid channels and NMDA receptors. This may recruit distant neurons intertwisted by synaptic connections, spreading excitation and recruiting further NMDA receptors and voltage-gated Ca2+ channels, leading to excitotoxicity and neuron degeneration in AD.
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We employ the second order of the derivative expansion of the nonperturbative renormalization group to study cubic (Z_{4}-symmetric) perturbations to the classical XY model in dimensionality d∈[2,4]. In d=3 we provide accurate estimates of the eigenvalue y_{4} corresponding to the leading irrelevant perturbation and follow the evolution of the physical picture upon reducing spatial dimensionality from d=3 towards d=2, where we approximately recover the onset of the Kosterlitz-Thouless physics. We analyze the interplay between the leading irrelevant eigenvalues related to O(2)-symmetric and Z_{4}-symmetric perturbations and their approximate collapse for dâ2. We compare and discuss different implementations of the derivative expansion in cases involving one and two invariants of the corresponding symmetry group.
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BACKGROUND: More than half of the worlds's population is deprived of essential healthcare services. In consideration of this, the World Health Organization introduced the concept of Social Determinants of Health to improve the awareness of this problem. AIM: To investigate and compare the pertinence of monetary and multidimensional measures of poverty as indirect measures of health status. MATERIAL AND METHODS: Three indices were used: the Historic Multidimensional Poverty Index (HMPI), calculated using Alkire-Foster method; health deprivations associated with the HMPI; and households in conditions of monetary poverty. The poverty identification outcomes for the three indices mentioned were all estimated using data from the Chilean national socioeconomic survey CASEN for the period 1992-2017. RESULTS: First, independently of how poverty is measured (monetarily or multidimensionally), the degree to which households living in poverty conditions are simultaneously suffering health deprivations steadily decreased during the period 1992-2017. Second, the association between multidimensional poverty and health deprivations is stronger than the association between health deprivations and monetary poverty. CONCLUSIONS: Poverty calculated on the basis of income alone is an inadequate predictor of health deprivations; multidimensional poverty performs better. However, poverty and health indicators have become progressively less associated. Therefore, it becomes necessary either to adapt the health indicators included in Multidimensional Poverty Index to the current health challenges or to implement a Multidimensional Health Deprivation Index, with a view to improving the integration of health within the current social policy framework.
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Composición Familiar , Pobreza , Chile , Atención a la Salud , Humanos , Renta , Factores SocioeconómicosRESUMEN
Pro-apoptotic multi-domain proteins of the BCL2 family such as BAX and BAK are well known for their important role in the induction of mitochondrial outer membrane permeabilization (MOMP), which is the rate-limiting step of the intrinsic pathway of apoptosis. Human or mouse cells lacking both BAX and BAK (due to a double knockout, DKO) are notoriously resistant to MOMP and cell death induction. Here we report the surprising finding that BAX/BAK DKO cells proliferate less than control cells expressing both BAX and BAK (or either BAX or BAK) when they are driven into tetraploidy by transient exposure to the microtubule inhibitor nocodazole. Mechanistically, in contrast to their BAX/BAK-sufficient controls, tetraploid DKO cells activate a senescent program, as indicated by the overexpression of several cyclin-dependent kinase inhibitors and the activation of ß-galactosidase. Moreover, DKO cells manifest alterations in ionomycin-mobilizable endoplasmic reticulum (ER) Ca2+ stores and store-operated Ca2+ entry that are affected by tetraploidization. DKO cells manifested reduced expression of endogenous sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (Serca2a) and transfection-enforced reintroduction of Serca2a, or reintroduction of an ER-targeted variant of BAK into DKO cells reestablished the same pattern of Ca2+ fluxes as observed in BAX/BAK-sufficient control cells. Serca2a reexpression and ER-targeted BAK also abolished the tetraploidy-induced senescence of DKO cells, placing ER Ca2+ fluxes downstream of the regulation of senescence by BAX/BAK. In conclusion, it appears that BAX/BAK prevent the induction of a tetraploidization-associated senescence program. Speculatively, this may contribute to the low incidence of cancers in BAX/BAK DKO mice and explain why human cancers rarely lose the expression of both BAX and BAK.
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Tetraploidía , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Animales , Calcio/metabolismo , Señalización del Calcio , Línea Celular , Senescencia Celular , Células Clonales , Retículo Endoplásmico/metabolismo , Fibroblastos/metabolismo , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Microtúbulos/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Proteína Destructora del Antagonista Homólogo bcl-2/deficiencia , Proteína X Asociada a bcl-2/deficienciaRESUMEN
Resumen Las cardiopatías congénitas (CC) se definen como una anomalía estructural del corazón o de los grandes vasos intratorácicos. Constituyen la malformación congénita más frecuente al nacimiento. Al menos un tercio de los pacientes requieren algún tipo de intervención antes del año de edad. Las manifestaciones clínicas de las cardiopatías en la etapa neonatal se presentan con un amplio contexto clínico y se pueden confundir con problemas a nivel pulmonar o infeccioso, lo que dificulta su diagnóstico y con ello contribuyendo de forma importante a la mortalidad y morbilidad de estos pacientes, ya que se retrasa el diagnóstico y manejo oportuno. El monitoreo por oximetría de pulso en el periodo neonatal se utiliza actualmente como método diagnóstico para la detección de cardiopatías congénitas críticas; a pesar de que las detecta en forma temprana, en muchos países aún no se lleva a cabo. El objetivo de este artículo es ofrecer un panorama general de la presentación clínica, aspectos diagnósticos y manejo inicial de las CC en el primer año de edad que pueda ser de utilidad a los médicos de primer contacto para mejorar la atención en este grupo de pacientes.
Abstract Congenital heart disease (CHD) is defined as a structural abnormality of the heart or large intrathoracic vessels. They constitute the most frequent congenital malformation at birth. At least one third of patients require some type of intervention before the year of age. The clinical manifestations of heart disease in the neonatal stage are presented with a wide clinical context and can be confused with problems at the pulmonary or infectious level making difficult to diagnose them and thereby contributing significantly to the mortality and morbility of these patients since the diagnosis is delayed and timely handling. Pulse oximetry monitoring in the neonatal period is currently used as a diagnostic method for the detection of critical congenital heart disease. Although it detects them early, in many countries it is not yet carried out. The objective of this article is to offer an overview of the clinical presentation, diagnostic aspect and initial management of CHD in the first year of age that may be useful to first contact physicians to improve the management of this group of patients.
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Toll-like receptors (TLRs) or pattern recognition receptors respond to pathogen-associated molecular patterns (PAMPs) or internal damage-associated molecular patterns (DAMPs). TLRs are integral membrane proteins with both extracellular leucine-rich and cytoplasmic domains that initiate downstream signaling through kinases by activating transcription factors like AP-1 and NF-κB, which lead to the release of various inflammatory cytokines and immune modulators. In the central nervous system, different TLRs are expressed mainly in microglia and astroglial cells, although some TLRs are also expressed in oligodendroglia and neurons. Activation of TLRs triggers signaling cascades by the host as a defense mechanism against invaders to repair damaged tissue. However, overactivation of TLRs disrupts the sustained immune homeostasis-induced production of pro-inflammatory molecules, such as cytokines, miRNAs, and inflammatory components of extracellular vesicles. These inflammatory mediators can, in turn, induce neuroinflammation, and neural tissue damage associated with many neurodegenerative diseases. This review discusses the critical role of TLRs response in Alzheimer's disease, Parkinson's disease, ischemic stroke, amyotrophic lateral sclerosis, and alcohol-induced brain damage and neurodegeneration.
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Alcoholismo/fisiopatología , Encéfalo/efectos de los fármacos , Enfermedades Neurodegenerativas/etiología , Enfermedades Neuroinflamatorias/etiología , Receptores Toll-Like/fisiología , Alcoholismo/etiología , Animales , Encéfalo/fisiopatología , Exosomas/patología , Exosomas/fisiología , Expresión Génica , Humanos , Inmunidad Innata , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades Neurodegenerativas/terapia , Enfermedades Neuroinflamatorias/terapiaRESUMEN
Brain tumors comprise a large series of tumor cancer from benign to highly malignant gliomas and metastases from primary tumors outside the brain. Intracellular Ca2+ homeostasis is involved in a large series of cell functions including cell proliferation, migration, and cell death. Store-operated Ca2+ entry (SOCE), the most important Ca2+ entry pathway in non-excitable cells, is involved in cell proliferation and migration and enhanced in tumor cells from breast cancer, colon cancer and cell lines derived from glioblastoma but there are almost no studies in human primary glioblastoma cells or other brain tumors. We have developed a single procedure to obtain primary cells from a large series (n = 49) of human brain tumors including schwannomas, meningiomas, oligodendrogliomas, astrocytomas, glioblastomas and brain metastases from ovary, breast and lung. Cells were characterized by immunofluorescence and subjected to Ca2+ imaging to investigate resting intracellular Ca2+ levels, Ca2+ responses to physiological agonists as well as voltage-operated Ca2+ entry and SOCE. We found significant differences in resting intracellular Ca2+ and Ca2+ responses to plasma membrane depolarization and ATP among the different tumor cells. Only malignant tumor cells, displayed Ca2+ responses to ATP. SOCE is significantly increased in malignant gliomas whereas voltage-gated Ca2+ entry is decreased. In addition, SOCE is significantly larger in high grade gliomas than in low grade gliomas suggesting that SOCE increases with glioma progression. These data may provide new insights on the role of intracellular Ca2+ and purinergic signalling in brain tumors.
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Neoplasias Encefálicas/metabolismo , Calcio/metabolismo , Neoplasias Encefálicas/patología , Señalización del Calcio , Línea Celular Tumoral , HumanosRESUMEN
Background: More than half of the worlds's population is deprived of essential healthcare services. In consideration of this, the World Health Organization introduced the concept of Social Determinants of Health to improve the awareness of this problem. Aim: To investigate and compare the pertinence of monetary and multidimensional measures of poverty as indirect measures of health status. Material and Methods: Three indices were used: the Historic Multidimensional Poverty Index (HMPI), calculated using Alkire-Foster method; health deprivations associated with the HMPI; and households in conditions of monetary poverty. The poverty identification outcomes for the three indices mentioned were all estimated using data from the Chilean national socioeconomic survey CASEN for the period 1992-2017. Results: First, independently of how poverty is measured (monetarily or multidimensionally), the degree to which households living in poverty conditions are simultaneously suffering health deprivations steadily decreased during the period 1992-2017. Second, the association between multidimensional poverty and health deprivations is stronger than the association between health deprivations and monetary poverty. Conclusions: Poverty calculated on the basis of income alone is an inadequate predictor of health deprivations; multidimensional poverty performs better. However, poverty and health indicators have become progressively less associated. Therefore, it becomes necessary either to adapt the health indicators included in Multidimensional Poverty Index to the current health challenges or to implement a Multidimensional Health Deprivation Index, with a view to improving the integration of health within the current social policy framework.
