Human macrophages differentiated in the presence of vitamin D3 restrict dengue virus infection and innate responses by downregulating mannose receptor expression

ABSTARCT: Severe dengue disease is associated with high viral loads and overproduction of pro-inflammatory cytokines, suggesting impairment in the control of dengue virus (DENV) and the mechanisms that regulate cytokine production. Vitamin D3 has been described as an important modulator of immune responses to several pathogens. Interestingly, increasing evidence has associated vitamin D with decreased DENV infection and early disease recovery, yet the molecular mechanisms whereby vitamin D reduces DENV infection are not well understood. METHODS AND PRINCIPAL FINDINGS: Macrophages represent important cell targets for DENV replication and consequently, they are key drivers of dengue disease. In this study we evaluated the effect of vitamin D3 on the differentiation of monocyte-derived macrophages (MDM) and their susceptibility and cytokine response to DENV. Our data demonstrate that MDM differentiated in the presence of vitamin D3 (D3-MDM) restrict DENV infection and moderate the classical inflammatory cytokine response. Mechanistically, vitamin D3-driven differentiation led to reduced surface expression of C-type lectins including the mannose receptor (MR, CD206) that is known to act as primary receptor for DENV attachment on macrophages and to trigger of immune signaling. Consequently, DENV bound less efficiently to vitamin D3-differentiated macrophages, leading to lower infection. Interestingly, IL-4 enhanced infection was reduced in D3-MDM by restriction of MR expression. Moreover, we detected moderate secretion of TNF-α, IL-1β, and IL-10 in D3-MDM, likely due to less MR engagement during DENV infection. CONCLUSIONS/SIGNIFICANCE: Our findings reveal a molecular mechanism by which vitamin D counteracts DENV infection and progression of severe disease, and indicates its potential relevance as a preventive or therapeutic candidate

Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: paciente obeso

Guideline; Journal Article; Review;As a response to metabolic stress, obese critically-ill patients have the same risk of nutritional deficiency as the non-obese and can develop protein-energy malnutrition with accelerated loss of muscle mass. The primary aim of nutritional support in these patients should be to minimize loss of lean mass and accurately evaluate energy expenditure. However, routinely used formulae can overestimate calorie requirements if the patient's actual weight is used. Consequently, the use of adjusted or ideal weight is recommended with these formulae, although indirect calorimetry is the method of choice. Controversy surrounds the question of whether a strict nutritional support criterion, adjusted to the patient's requirements, should be applied or whether a certain degree of hyponutrition should be allowed. Current evidence suggested that hypocaloric nutrition can improve results, partly due to a lower rate of infectious complications and better control of hyperglycemia. Therefore, hypocaloric and hyperproteic nutrition, whether enteral or parenteral, should be standard practice in the nutritional support of critically-ill obese patients when not contraindicated. Widely accepted recommendations consist of no more than 60-70% of requirements or administration of 11-14 kcal/kg current body weight/day or 22-25 kcal/kg ideal weight/day, with 2-2.5 g/kg ideal weight/day of proteins. In a broad sense, hypocaloric-hyperprotein regimens can be considered specific to obese critically-ill patients, although the complications related to comorbidities in these patients may require other therapeutic possibilities to be considered, with specific nutrients for hyperglycemia, acute respiratory distress syndrome (ARDS) and sepsis. However, there are no prospective randomized trials with this type of nutrition in this specific population subgroup and the available data are drawn from the general population of critically-ill patients. Consequently, caution should be exercised when interpreting these data.YesEl paciente obeso crítico, como respuesta al estrés metabólico, tiene igual riesgo de depleción nutricional que el paciente no obeso, pudiendo desarrollar una malnutrición energeticoproteica,con una acelerada degradación de masa muscular. El primer objetivo del soporte nutricional en estos pacientes debe ser minimizar la pérdida de masa magra y realizar una evaluación adecuada del gasto energético. Sin embargo, la aplicación de las fórmulas habituales para el cálculo de las necesidades calóricas puede sobrestimarlas si se utiliza el peso real, por lo que sería más correcto su aplicación con el peso ajustado o el peso ideal, aunque la calorimetría indirecta es el método de elección. La controversia se centra en si hay que aplicar un criterio estricto de soporte nutricional ajustado a los requerimientos o se aplica un cierto grado de hiponutrición permisiva. La evidencia actual sugiere que la nutrición hipocalórica puede mejorar los resultados, en parte debido a una menor tasa de complicaciones infecciosas y a un mejor control de la hiperglucemia, por lo que la nutrición hipocalórica e hiperproteica, tanto enteral como parenteral, debe ser la práctica estándar en el soporte nutricional del paciente obeso crítico si no hay contraindicaciones para ello. Las recomendaciones generalmente admitidas se centran en no exceder el 60-70% de los requerimientos o administrar 11-14 o 22-25 kcal/kg peso ideal/día, con 2-2,5 g/kg peso ideal/día de proteínas. En sentido amplio puede considerarse la nutrición hipocalórica-hiperproteica como específica del paciente obeso crítico, aunque las complicaciones ligadas a su comorbilidad hace que se planteen otras posibilidades terapéuticas, con nutrientes específicos para hiperglucemia, síndrome del distrés respiratorio agudo (SDRA) y sepsis. Sin embargo, no existe ningún estudio prospectivo y aleatorio con este tipo de nutrientes en este subgrupo concreto de población y los datos de que disponemos se extraen de una población general de pacientes críticos, por lo que deben tomarse con mucha precaución

Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Paciente obeso

Guideline; Journal Article; Review;As a response to metabolic stress, obese critically-ill patients have the same risk of nutritional deficiency as the non-obese and can develop protein-energy malnutrition with accelerated loss of muscle mass. The primary aim of nutritional support in these patients should be to minimize loss of lean mass and accurately evaluate energy expenditure. However, routinely used formulae can overestimate calorie requirements if the patient's actual weight is used. Consequently, the use of adjusted or ideal weight is recommended with these formulae, although indirect calorimetry is the method of choice. Controversy surrounds the question of whether a strict nutritional support criterion, adjusted to the patient's requirements, should be applied or whether a certain degree of hyponutrition should be allowed. Current evidence suggested that hypocaloric nutrition can improve results, partly due to a lower rate of infectious complications and better control of hyperglycemia. Therefore, hypocaloric and hyperproteic nutrition, whether enteral or parenteral, should be standard practice in the nutritional support of critically-ill obese patients when not contraindicated. Widely accepted recommendations consist of no more than 60-70% of requirements or administration of 11-14 kcal/kg current body weight/day or 22-25 kcal/kg ideal weight/day, with 2-2.5 g/kg ideal weight/day of proteins. In a broad sense, hypocaloric-hyperprotein regimens can be considered specific to obese critically-ill patients, although the complications related to comorbidities in these patients may require other therapeutic possibilities to be considered, with specific nutrients for hyperglycemia, acute respiratory distress syndrome (ARDS) and sepsis. However, there are no prospective randomized trials with this type of nutrition in this specific population subgroup and the available data are drawn from the general population of critically-ill patients. Consequently, caution should be exercised when interpreting these data.YesEl paciente obeso crítico, como respuesta al estrés metabólico, tiene igual riesgo de depleción nutricional que el paciente no obeso, pudiendo desarrollar una malnutrición energeticoproteica,con una acelerada degradación de masa muscular. El primer objetivo del soporte nutricional en estos pacientes debe ser minimizar la pérdida de masa magra y realizar una evaluación adecuada del gasto energético. Sin embargo, la aplicación de las fórmulas habituales para el cálculo de las necesidades calóricas puede sobrestimarlas si se utiliza el peso real, por lo que sería más correcto su aplicación con el peso ajustado o el peso ideal, aunque la calorimetría indirecta es el método de elección. La controversia se centra en si hay que aplicar un criterio estricto de soporte nutricional ajustado a los requerimientos o se aplica un cierto grado de hiponutrición permisiva. La evidencia actual sugiere que la nutrición hipocalórica puede mejorar los resultados, en parte debido a una menor tasa de complicaciones infecciosas y a un mejor control de la hiperglucemia, por lo que la nutrición hipocalórica e hiperproteica, tanto enteral como parenteral, debe ser la práctica estándar en el soporte nutricional del paciente obeso crítico si no hay contraindicaciones para ello. Las recomendaciones generalmente admitidas se centran en no exceder el 60-70% de los requerimientos o administrar 11-14 o 22-25 kcal/kg peso ideal/día, con 2-2,5 g/kg peso ideal/día de proteínas. En sentido amplio puede considerarse la nutrición hipocalórica-hiperproteica como específica del paciente obeso crítico, aunque las complicaciones ligadas a su comorbilidad hace que se planteen otras posibilidades terapéuticas, con nutrientes específicos para hiperglucemia, síndrome del distrés respiratorio agudo (SDRA) y sepsis. Sin embargo, no existe ningún estudio prospectivo y aleatorio con este tipo de nutrientes en este subgrupo concreto de población y los datos de que disponemos se extraen de una población general de pacientes críticos, por lo que deben tomarse con mucha precaución

Curr Diabetes Rev

BACKGROUND: Type 2 diabetes represents an increasing health burden world-wide and its prevalence in particularly higher in elderly population. Consistent epidemiological evidence suggests an increased risk of dementia associated to type 2 diabetes; the mechanisms underlying these associations, however, remain unclear. OBJECTIVE: The study aims to review epidemiological, clinical and pre-clinical data that weigh on pathophysiological links, mechanisms of disease and associations between type 2 diabetes and dementia to identify areas of opportunity for future research. METHODS: We searched the following electronic bibliographic databases: PUBMED, EMBASE, SCIELO, MEDLINE and OVID for clinical, translational and epidemiological research literature that summarize diabetes-related risk factors for dementia, metabolic and neurological changes associated to T2D, evidence of therapeutic approaches in type 2 diabetes and its pathophysiological implications for dementia. RESULTS: Type 2 diabetes mellitus increases risk for all-cause dementia, vascular dementia and Alzheimer's disease. The most evaluated mechanisms linking both disorders in pre-clinical studies include an increase in neuronal insulin resistance, impaired insulin signaling, pro-inflammatory state, mitochondrial dysfunction and vascular damage which increase deposition of beta-amyloid, tau proteins and GSK3beta, leading to an earlier onset of dementia in individuals with impairment in the glucose metabolism. Neuroimaging and neuropathology evidence linking cerebrovascular lesions, neurodegeneration and particularly small-vessel disease in the onset of dementia is consistent with the increased risk of incident dementia in type 2 diabetes, but consistent evidence of AD-related pathology is scarce. Epidemiological data shows increased risk of dementia related to hypoglycemic episodes, glycemic control, metabolic syndrome, insulin resistance and genetic predisposition, but the evidence is not consistent and statistical analysis might be affected by inconsistent covariate controlling. Therapeutic approaches for T2D have shown inconsistent result in relation to dementia prevention and delay of cognitive decline; lifestyle intervention, particularly physical activity, is a promising alternative to ameliorate the impact of disability and frailty on T2D-related dementia. CONCLUSION: Vascular disease, inflammation and impaired brain insulin signaling might occur in T2D and contribute to dementia risk. Evidence from epidemiological studies has not consistently reported associations that could integrate a unified mechanism of disease in humans. Evaluation of the effect of antidiabetic medications and non-pharmacological interventions in dementia prevention in type 2 diabetes is promising but has thus far offered inconsistent results