MASTer cell: chief immune modulator and inductor of antimicrobial immune response.

Mast cells have long been recognized for their involvement in allergic pathology through the immunoglobulin E (IgE)-mediated degranulation mechanism. However, there is growing evidence of other "non-canonical" degranulation mechanisms activated by certain pathogen recognition receptors. Mast cells release several mediators, including histamine, cytokines, chemokines, prostaglandins, and leukotrienes, to initiate and enhance inflammation. The chemical nature of activating stimuli influences receptors, triggering mechanisms for the secretion of formed and new synthesized mediators. Mast cells have more than 30 known surface receptors that activate different pathways for direct and indirect activation by microbes. Different bacterial strains stimulate mast cells through various ligands, initiating the innate immune response, which aids in clearing the bacterial burden. Mast cell interactions with adaptative immune cells also play a crucial role in infections. Recent publications revealed another "non-canonical" degranulation mechanism present in tryptase and chymase mast cells in humans and connective tissue mast cells in mice, occurring through the activation of the Mas-related G protein-coupled receptor (MRGPRX2/b2). This receptor represents a new therapeutic target alongside antibiotic therapy. There is an urgent need to reconsider and redefine the biological role of these MASTer cells of innate immunity, extending beyond their involvement in allergic pathology.

A Polyherbal Mixture with Nutraceutical Properties for Ruminants: A Meta-Analysis and Review of BioCholine Powder.

BioCholine Powder is a polyherbal feed additive composed of Achyrantes aspera, Trachyspermum ammi, Azadirachta indica, and Citrullus colocynthis. The objective of this study was to analyze published results that support the hypothesis that the polyherbal product BioCholine Powder has rumen bypass choline metabolites through a meta-analysis and effect size analysis (ES). Using Scopus, Web of Science, ScienceDirect, PubMed, and university dissertation databases, a systematic search was conducted for experiments published in scientific documents that evaluated the effects of BioCholine supplementation on the variables of interest. The analyzed data were extracted from twenty-one publications (fifteen scientific articles, three abstracts, and three graduate dissertations available in institutional libraries). The studies included lamb growing-finishing, lactating ewes and goats, calves, and dairy cows. The effects of BioCholine were analyzed using random effects statistical models to compare the weighted mean difference (WMD) between BioCholine-supplemented ruminants and controls (no BioCholine). Heterogeneity was explored, and three subgroup analyses were performed for doses [(4 (or 5 g/d), 8 (10 g/d)], supplementation in gestating and lactating ewes (pre- and postpartum supplementation), and blood metabolites by species and physiological state (lactating goats, calves, lambs, ewes). Supplementation with BioCholine in sheep increased the average daily lamb gain (p < 0.05), final body weight (p < 0.01), and daily milk yield (p < 0.05) without effects on intake or feed conversion. Milk yield was improved in small ruminants with BioCholine prepartum supplementation (p < 0.10). BioCholine supplementation decreased blood urea (p < 0.01) and increased levels of the liver enzymes alanine transaminase (ALT; p < 0.10) and albumin (p < 0.001). BioCholine doses over 8 g/d increased blood glucose, albumin (p < 0.10), cholesterol, total protein, and globulin (p < 0.05). The ES values of BioCholine in retained energy over the control in growing lambs were +7.15% NEm (p < 0.10) and +9.25% NEg (p < 0.10). In conclusion, adding BioCholine Powder to domestic ruminants' diets improves productive performance, blood metabolite indicators of protein metabolism, and liver health, showing its nutraceutical properties where phosphatidylcholine prevails as an alternative that can meet the choline requirements in ruminants.

Diferencias en la atención sostenida en jóvenes universitarios con distintos niveles de uso de smartphone / Differences in sustained attention in young university students with different levels of smartphone use

Resumen El uso constante de los dispositivos móviles está generando nuevos fenómenos de comportamiento. En años recientes, se ha puesto énfasis en los cambios cognitivos que se podrían generar en los jóvenes que hacen uso excesivo de estos dispositivos. El objetivo del trabajo fue conocer las diferencias en la atención sostenida en jóvenes universitarios asociadas a distintos niveles de uso del teléfono inteligente. Se obtuvo una muestra de 94 adultos, 34 hombres y 60 mujeres de 18 a 23 años (M = 19.34, DE = 1.09) alumnos de la escuela superior de Actopan, Hidalgo-México. Se aplicó la Escala de Dependencia y Adicción al Smartphone EDAS (Aranda-López et al., 2017) y una prueba computarizada de ejecución continua (CPT) Test of Atenttional Vigilance (TOAV; Mueller y Pipper, 2014). Se realizó un ANOVA de una vía, en el que la variable independiente fue el nivel de uso del teléfono inteligente (sin dependencia, dependencia y adicción) y la variable dependiente fueron las puntuaciones obtenidas en el TOAV. Se observó que existen diferencias significativas a nivel estadístico en lo relativo a errores de omisión de la segunda mitad de la prueba (p = .005); las diferencias fueron entre los grupos de sin dependencia-dependencia (p = .010) y sin dependencia-adicción (p = .024). Acorde a los hallazgos del presente estudio, existen diferencias en el proceso de atención sostenida entre usuarios con diferentes niveles de uso del teléfono inteligente; los estudiantes con niveles de dependencia y adicción enfrentan dificultades en la atención sostenida cuando la tarea se prolonga y aumenta la demanda cognitiva.

Abstract The constant use of mobile devices changed our lives dramatically during the past years and its usage increased over the years. Smartphone use is associated with isolation and interpersonal problems; its overuse can cause cognitive problems too (Matar Boumosleh & Jaalouk, 2017). Cognitive problems associated with smartphones in young people are reduction of sustained attention and working memory. Findings have been reported in which younger populations show deterioration in different components of care, highlighting the difficulty of walking and using the smartphone at the same time (Prupetkaew et al., 2019). It has been reported that the impulsivity associated with use of smartphone in silent mode interferes in memory tests unlike when it is in off mode in young populations (Canale et al., 2019). It is necessary to evaluate the effects of using a smartphone on young people because it is a population that uses it constantly to develop in work, academic, sports, and even socializing activities. The aim of this paper was to find out the differences in sustained attention in young university students with different levels of smartphone use. A sample of 94 adults, 34 men and 60 women between the ages of 18 and 23 (M = 19.34, SD = 1.09), who were students of the higher school of Actopan, Hidalgo-Mexico. The EDAS -Smartphone Dependency and Addiction Scale- was applied (Aranda-López et al., 2017). For the evaluation of attention, a Computerized Continuous Running Test (CPT), Test of Attentional Vigilance (TOAV) was applied using the Psychology Experimental Building Language PEBL-2 platform (Mueller & Pipper, 2014). The inclusion criteria were that the participants were between 18-23 years old, right-handed, with normal and/or corrected vision. They were excluded from the investigation if they had a history of psychiatric and/or neurological diseases, learning difficulties, chronic alcohol and/or drug use. A one-way ANOVA was performed, where the independent variable was the level of smartphone use (no dependence, dependence and addiction) and the dependent variable was the scores obtained in the TOAV. It was observed that there are statistically significant differences in the errors of omission of the second half of the test (p = .05), the differences were found between the groups of no dependence-dependence (p =.10) and without dependence-addiction (p = .24). The results showed that there are differences in the execution of a neuropsychological task, regarding the omission errors of the second part of the test. These differences could suggest that the level of sustained attention is diminished in the participants of the dependency and addiction group at the end of the task. On the other hand, it is also concluded that students with levels of dependence and smartphone addiction face attention difficulties when the task is longer and cognitive demand increases. This type of data must be analyzed taking into consideration variables such as sex, socioeconomic level, age, profile of use, quality of sleep, level of physical activity, among others.

[Detecting non-alcoholic fatty liver in children with owerweight and obesity.] / Detección de hígado graso no alcohólico en niños con sobrepeso y obesidad.

Background: Non-alcoholic fatty liver disease (NAFLD) has serious health implications and upward trends of the disease, accompanied by the obesity epidemic worldwide. Objective: To screen for fatty liver in overweight and obese children and evaluate the factors associated with an increased likelihood of presenting a positive-screen result. Material and methods: In a cross-sectional study, 102 children were recruited at a secondary care medical unit. Serum alanine aminotransferase (ALT) levels were quantified and hepatic ultrasounds were performed; multiple logistic regression models were used to evaluate factors associated with the increased odds of presenting with NAFLD (fatty infiltration on ultrasound and ALT > 52 U/L for boys and > 44 U/L for girls). Results: The overall prevalence of NAFLD was 10.8%. In multivariate analysis, a waist-to-hip ratio ≥ 1 was associated with increased odds of screening positive for NAFLD (odds ratio (OR) = 4.96, 95% CI 1.17-20.90). Conclusions: Our findings indicate that one out of ten children with overweight or obesity has data suggestive of NAFLD and is at risk of presenting its consequences on health.

Introducción: la enfermedad del hígado graso no alcohólico (EHGNA) tiene graves implicaciones para la salud y, asociada a la epidemia de obesidad, es una tendencia creciente. Objetivo: detectar la presencia de hígado graso en niños con sobrepeso y obesidad, así como evaluar los factores asociados con una mayor posibilidad de presentar un resultado positivo en la detección. Material y metódos: se realizó un estudio de tipo transversal en una unidad médica del segundo nivel de atención médica en el que fueron reclutados 102 niños. Los niveles séricos de alanina aminotransferasa (ALT) fueron cuantificados y se realizaron ecografías hepáticas. Modelos de regresión logística múltiple fueron utilizados para evaluar los factores asociados con la presencia de EHGNA (infiltración grasa en la ecografía y ALT > 52U/L para niños y > 44 U/L para niñas). Resultados: la prevalencia de EHGNA fue del 10.8%. En el análisis multivariante, una relación entre cintura y cadera ≥ 1 se asoció con una mayor posibilidad de EHNGA (razón de momios (RM) = 4.96, IC del 95%: 1.17 - 20.90). Conclusiones: nuestros hallazgos indican que uno de cada diez niños sobrepeso y obesidad tiene datos sugestivos de EHGNA y está en riesgo de presentar sus consecuencias para la salud.

Detección de hígado graso no alcohólico en niños con sobrepeso y obesidad / Detecting non-alcoholic fatty liver in children with owerweight and obesity

Introducción: la enfermedad del hígado graso no alcohólico (EHGNA) tiene graves implicaciones para la salud y, asociada a la epidemia de obesidad, es una tendencia creciente. Objetivo: detectar la presencia de hígado graso en niños con sobrepeso y obesidad, así como evaluar los factores asociados con una mayor posibilidad de presentar un resultado positivo en la detección. Metódos: se realizó un estudio de tipo transversal en una unidad médica del segundo nivel de atención médica en el que fueron reclutados 102 niños. Los niveles séricos de alanina aminotransferasa (ALT) fueron cuantificados y se realizaron ecografías hepáticas. Modelos de regresión logística múltiple fueron utilizados para evaluar los factores asociados con la presencia de EHGNA (infiltración grasa en la ecografía y ALT > 52U/L para niños y > 44 U/L para niñas). Resultados: la prevalencia de EHGNA fue del 10,8%. En el análisis multivariante, una relación entre cintura y cadera ≥ 1 se asoció con una mayor posibilidad de EHNGA (razón de momios (RM) = 4.96, IC del 95%: 1.17 - 20.90). Conclusiones: nuestros hallazgos indican que uno de cada diez niños sobrepeso y obesidad tiene datos sugestivos de EHGNA y está en riesgo de presentar sus consecuencias para la salud.

Background: Non-alcoholic fatty liver disease (NAFLD) has serious health implications and upward trends of the disease, accompanied by the obesity epidemic worldwide. Objective: To screen for fatty liver in overweight and obese children and evaluate the factors associated with an increased likelihood of presenting a positive-screen result. Methods: In a cross-sectional study, 102 children were recruited at a secondary care medical unit. Serum alanine aminotransferase (ALT) levels were quantified and hepatic ultrasounds were performed; multiple logistic regression models were used to evaluate factors associated with the increased odds of presenting with NAFLD (fatty infiltration on ultrasound and ALT > 52 U/L for boys and > 44 U/L for girls). Results: The overall prevalence of NAFLD was 10.8%. In multivariate analysis, a waist-to-hip ratio ≥ 1 was associated with increased odds of screening positive for NAFLD (odds ratio (OR) = 4.96, 95% CI 1.17-20.90). Conclusions: Our findings indicate that one out of ten children with overweight or obesity has data suggestive of NAFLD and is at risk of presenting its consequences on health.

Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication.

Human coronavirus (HCoV) similar to other viruses rely on host cell machinery for both replication and to spread. The p97/VCP ATPase is associated with diverse pathways that may favor HCoV replication. In this study, we assessed the role of p97 and associated host responses in human lung cell line H1299 after HCoV-229E or HCoV-OC43 infection. Inhibition of p97 function by small molecule inhibitors shows antiviral activity, particularly at early stages of the virus life cycle, during virus uncoating and viral RNA replication. Importantly, p97 activity inhibition protects human cells against HCoV-induced cytopathic effects. The p97 knockdown also inhibits viral production in infected cells. Unbiased quantitative proteomics analyses reveal that HCoV-OC43 infection resulted in proteome changes enriched in cellular senescence and DNA repair during virus replication. Further analysis of protein changes between infected cells with control and p97 shRNA identifies cell cycle pathways for both HCoV-229E and HCoV-OC43 infection. Together, our data indicate a role for the essential host protein p97 in supporting HCoV replication, suggesting that p97 is a therapeutic target to treat HCoV infection.

Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice.

Mycetoma is a chronic human infectious disease that produces severe deformation frequently in the lower extremities. Etiological agents include fungi (eumycetoma) and bacteria (actinomycetoma) that produce similar clinical and microscopic changes. The clinical appearance includes swelling, abscesses, ulcers, scars and sinuses that drain purulent material with microbe microcolonies. The pathogenesis of actinomycetoma has been studied mainly in rodents. Using this approach, it was found that Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A. Nitric oxide (NO) is a molecule with biological activities depending on its local concentration. Its effect on killing intracellular bacteria such as Mycobacterium tuberculosis has been known for decades. NO plays an important role in innate and adaptive immunity. It can promote or suppress some biological activities despite its short half-ife. NO is produced by three different nitric oxide synthases (NOS). We used the genetic blockade of eNOS in C57BL/6 mice to demonstrate the role of NO in actinomycetoma development. Inflammation and actinomycetoma were prevented in genetically modified mice infected with N. brasiliensis. T cell proliferation was increased in these rodents, and antibody production, IL-6 and IL-10 expression were similar and TNF-α was lower.

Chemoresistance in Breast Cancer Patients Associated With Changes in P2X7 and A2A Purinergic Receptors in CD8+ T Lymphocytes.

Breast cancer (BRCA) is the most frequent cancer type that afflicts women. Unfortunately, despite all the current therapeutic strategies, many patients develop chemoresistance hampering the efficacy of treatment. Hence, an early indicator of therapy efficacy might aid in the search for better treatment and patient survival. Although emerging evidence indicates a key role of the purinergic receptors P2X7 and A2A in cancer, less is known about their involvement in BRCA chemoresistance. In this sense, as the chemotherapeutic treatment stimulates immune system response, we evaluated the expression and function of P2X7 and A2A receptors in CD8+ T cells before and four months after BRCA patients received neoadjuvant chemotherapy. The results showed an increase in the levels of expression of P2X7 and a decrease in the expression of A2A in CD8+ T cells in non-chemoresistant (N-CHR) patients, compared to chemoresistant (CHR) patients. Interestingly, in CHR patients, reduced expression of P2X7 occurs along with a decrease in the CD62L shedding and the production of IFN-γ. In the case of the A2A function, the inhibition of IFN-γ production was not observed after chemotherapy in CHR patients. A possible relationship between the modulation of the expression and function of the P2X7 and A2A receptors was found, according to the molecular subtypes, where the patients that were triple-negative and human epidermal growth factor receptor 2 (HER2)-enriched presented more alterations. Comorbidities such as overweight/obesity and type 2 diabetes mellitus (T2DM) participate in the abnormalities detected. Our results demonstrate the importance of purinergic signaling in CD8+ T cells during chemoresistance, and it could be considered to implement personalized therapeutic strategies.

Characterisation of palliative sedation use in inpatients at a medium-stay palliative care unit.

BACKGROUND: Palliative sedation has been used to refer to the practice of providing symptom control through the administration of sedative drugs. The objective of this article was to characterise palliative sedation use in inpatients at a medium-stay palliative care unit. MATERIAL AND METHODS: A cross-sectional study was conducted on 125 randomly selected patients (aged 15 or older) who had died in 2014. The Palliative Performance Scale was used to evaluate the functional status. RESULTS: Palliative sedation was documented in 34.4% of the patients and midazolam was the most commonly used sedative agent (86.0%). More than half (53.5%) of those who recieved sedation presented with delirium. Liver dysfunction was more frequent in the sedated patients (p=0.033) and patients with heart disease were less likely (p=0.026) to be sedated. CONCLUSION: Palliative sedation is an ethically accepted practice. It was commonly midazolam-induced, and differences were documented, among sedated and non-sedated patients, in terms of liver dysfunction and heart disease.

Decreased levels and activity of Sirt1 are modulated by increased miR-34a expression in adipose tissue mononuclear cells from subjects with overweight and obesity: A pilot study.

BACKGROUND AND AIMS: Overweight and obesity are important risk factors for chronic disorders. Fat accumulation is one of the central manifestations; it occurs via a complex mechanism where multiple metabolic signals converge. Sirtuins are an enzyme family with deacetylase functions that are implicated in the regulation of several genes. Sirt1 and its upstream regulator (miR-34a) are elements of a converging mechanism that integrates the dynamic metabolic state. In this work, we hypothesized that elevated levels of miR-34a in overweight/obese group inhibits Sirt1 activity. Therefore, we studied the miR-34a/Sirt1 axis in mononuclear cells obtained from adipose tissue. METHODS: Adipose tissue samples were collected from 36 subjects, and they were categorized according to body mass index (BMI) as overweight/obesity and normoweight. Subcutaneous adipose tissue samples were enzymatically dissociated, and mononuclear cells from adipose tissue were isolated by Ficoll Hypaque. Sirt1-positive cells and relative Sirt1 expression were determined by flow cytometry and real-time polymerase chain reaction (qPCR), respectively. Finally, Sirt1 activity was measured with a luminescence assay. RESULTS: The percentage of Sirt1-positive mononuclear cells from adipose tissue decreased along with Sirt1 enzymatic activity in overweight/obese participants. miR-34a expression increased in the overweight/obese group compared to normoweight individuals. There was a negative association between the relative miR-34a expression and Sirt1-positive cells and a synergistic effect on Sirt1-positive cells mediated by the miR-34a inhibitor and Sirt1 agonist. CONCLUSIONS: Our results describe for the first time the presence of miR-34a and Sirt1 in mononuclear cells isolated from subcutaneous adipose tissue. Additionally, these results suggest altered sirtuin function in overweight/obese patients and open the possibility for new therapies that involve these metabolic targets.

Trends in Teen Births in Mexico Spanning 25 Years: A Need for Regionally-directed Preventive Strategies.

AIM OF THE STUDY: We aimed to explore national and regional trends in teen births in Mexico from 1992-2016, ranking the states with the highest rates in 2016. METHODS: A cross-sectional analysis was conducted and the data on the total number of live births to teenage mothers were analyzed. The age-standardized rates (ASRs) per 1,000 adolescent girls were obtained and the annual percent changes (APCs) with 95% confidence intervals (CIs) were calculated using the Poisson regression models. RESULTS: The national ASRs during the study period dropped from 2.11-1.74 in girls aged 10-14 years and from 86.04-70.82 in adolescents aged 15-19 years. Higher APC rates were documented for teenage girls under 15 years of age (‒0.6, 95% CI:-1.0, -0.3), when compared with older girls (-0.3, 95% CI:-0.6, -0.04). Heterogeneous APCs were observed in the stratified analysis and the overall declines were higher from 2011-2016. States with significantly increasing trends in teen births were also documented. The highest ASRs (per 1,000 girls aged 10-19 years) in 2016 were registered in the states of Coahuila de Zaragoza (49.45), Chiapas (46.24), and Guerrero (44.94). CONCLUSIONS: Teen birth rates decreased over the period of time analyzed. However, that decline has not been monotonic or homogeneous across Mexico, and recent (2011-2016) increasing rates were observed in some states in girls aged 14 years and younger. Teenage parenthood can negatively affect multiple dimensions of health, and therefore, regionally directed efforts focusing on its reduction must be strengthened.

Altered levels of sirtuin genes (SIRT1, SIRT2, SIRT3 and SIRT6) and their target genes in adipose tissue from individual with obesity.

INTRODUCTION: Sirtuins regulate energy metabolism and insulin sensitivity through their ability to act as energy sensors and regulators in several metabolic tissues. AIM: To evaluate the expression levels of sirtuin genes SIRT1, SIRT2, SIRT3 and SIRT6 and their target genes (PPAR-α, PGC1-α, NRF1, DGAT1, PPAR-γ and FOXO3a) in subcutaneous adipose tissue collected from individuals with normoweight, overweight and obesity. METHODS: Adipose tissue samples, obtained by lipoaspiration during liposuction surgery, were processed to obtain RNA, which was reverse-transcribed to cDNA. Then, we measured the expression levels of each gene by qPCR. RESULTS: We found differences in the mRNA expression of SIRT1, SIRT2, SIRT3 and SIRT6 and their target genes (PPAR-α, PGC1-α, NRF1, DGAT1, PPAR-γ and FOXO3a) in adipose tissue from overweight or obese subjects when compared to normoweight subjects. All genes analyzed, except SIRT2, showed correlation with BMI. CONCLUSIONS: Our findings in human subcutaneous adipose tissue show that increased body mass index modifies the expression of genes encoding sirtuins and their target genes, which are metabolic regulators of adipose tissue. Therefore, these could be used as biomarkers to predict the ability of adipose tissue to gain mass of adipose tissue.

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis.

BACKGROUND: Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known. OBJECTIVES: To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection. METHODS: We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence. The levels of cell surface markers for activation secreted cytokines and chemokines, bacterial association, and intracellular bacterial growth were evaluated. FINDINGS: The expression levels of HLA-DR, CD80, and CD86 were low while those of of PD-L1 were high in uninfected MDMs derived from patients with diabetes; as a result of Mtb infection, changes were only observed in the expression levels of PD-L1. The levels of cytokines (e.g., IL-6, IL-1ß, IL-10, and IL-12) and chemokines (e.g., MCP-1, MIG, and RANTES) are perturbed in MDMs derived from patients with diabetes, both before infection and in response to Mtb infection. In response to the more virulent Mtb strains, the levels of association and bacterial clearance were diminished in MDMs derived from patients with diabetes. CONCLUSIONS: T2D affects the basal activation state of the macrophages and its capacity to respond and control Mtb infection.

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

BACKGROUND Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known. OBJECTIVES To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection. METHODS We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence. The levels of cell surface markers for activation secreted cytokines and chemokines, bacterial association, and intracellular bacterial growth were evaluated. FINDINGS The expression levels of HLA-DR, CD80, and CD86 were low while those of of PD-L1 were high in uninfected MDMs derived from patients with diabetes; as a result of Mtb infection, changes were only observed in the expression levels of PD-L1. The levels of cytokines (e.g., IL-6, IL-1β, IL-10, and IL-12) and chemokines (e.g., MCP-1, MIG, and RANTES) are perturbed in MDMs derived from patients with diabetes, both before infection and in response to Mtb infection. In response to the more virulent Mtb strains, the levels of association and bacterial clearance were diminished in MDMs derived from patients with diabetes. CONCLUSIONS T2D affects the basal activation state of the macrophages and its capacity to respond and control Mtb infection.

Expression and vitamin D-mediated regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy skin and in diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are chronic wounds with high matrix metalloproteinase (MMP) activity, and are a frequent complication on diabetics. This work studied the expression of selected MMP and tissue inhibitor of metalloproteinases (TIMP) gene family members in DFU and normal skin biopsies, and in vitamin D-treated keratinocytes cultured from those biopsies. We report for the first time the expression of some of these genes in healthy skin. Our results suggest that vitamin D may modulate the expression of some MMP gene family members in keratinocytes. Gene expression in DFU and in non-diabetic healthy skin (control) biopsies was evaluated by RT-qPCR for MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-19, TIMP-1 and TIMP-2, and also by immunohistochemistry for MMP-1 and MMP-9. Primary keratinocytes cultured from DFU and healthy skin biopsies were used for gene expression analyses of selected MMPs and TIMPs by RT-qPCR, both in the presence and absence of calcitriol. The expression of MMP-1, MMP-8, MMP-9, MMP-10, and TIMP-2 in healthy skin is reported here for the first time. DFUs showed increased MMP-1, MMP-9 and TIMP-1 expression, compared to healthy skin. Calcitriol down-regulated MMP-1 and MMP-10 expression in DFU-derived keratinocytes but not in those derived from healthy skin. Our data demonstrate the expression of certain MMPs that had not been previously described in healthy skin, and further support previous reports of MMP and TIMP up-regulation in DFUs. Our results point to calcitriol as a potential modulator for the expression of certain MMP members in DFUs.

Vitamin D supplementation promotes macrophages' anti-mycobacterial activity in type 2 diabetes mellitus patients with low vitamin D receptor expression.

The increasing number of people with type 2 diabetes (DM2) is alarming and if it is taken into account that the relative odds of developing tuberculosis in diabetic patients ranges from 2.44 to 8.33 compared with non-diabetic patients, thus in developing countries where these two diseases are encountering face to face, there is a need for prophylaxis strategies. The role of vitamin D has been widely implicated in growth control of Mycobacterium tuberculosis (Mtb) during primary infection mainly through the induction of certain antimicrobial peptides (AMPs). In this study we evaluated the vitamin D serum levels, CYP27B1-hydroxylase enzyme, vitamin D receptor (VDR) and AMPs gene expression in Healthy donors, DM2 and TB patients. Results showed that DM2 group has lower VDR and AMPs expression levels. When Monocytes Derived Macrophages (MDM) from DM2 patients with low VDR expression were supplemented with vitamin D, MDMs eliminate efficiently M. tuberculosis. This preliminary study suggests the use of vitamin D as prophylaxis for tuberculosis in high DM2 endemic countries.

Dieta cetogénica / Ketogenic diet

Históricamente se describió al ayuno como tratamiento de la epilepsia. La dieta cetogénica (DC), es alta enlípidos, baja en proteínas y en hidratos de carbono, es decir, se invierte el cociente normal con la finalidad deproducir y mantener un estado de cetosis. La DC debe producir cuerpos cetónicos debido a la oxidación incompleta de los lípidos. Casi todos los estudios han logrado establecer una asociación entre cetonemia yeficacia anticonvulsiva. Mientras muchos estudios han sugerido que la cetosis persistente es esencial para laprotección anticonvulsiva de la DC, otros han propuesto que la restricción de glucosa es la clave. Los PUFAs, se cree que actúan a nivel cardíaco sobre los canales de sodio y calcio, encuentros similares se han descrito en tejido neuronal.

Historically described fasting as a treatment for epilepsy. The ketogenic diet (KD), is high in fat, low inprotein and carbohydrates, that is, the normal ratio is reversed in order to produce and maintain a state ofHistorically described fasting as a treatment forepilepsy. The ketogenic diet (KD), is high in fat, low inprotein and carbohydrates, that is, the normal ratio isreversed in order to produce and maintain a state ofketosis. The KD should produce ketone bodies due tothe incomplete oxidation of lipids. Almost all studieshave established an association between ketonemia andanticonvulsant efficacy. While many studies havesuggested that persistent ketosis is essential for theprotection of the KD anticonvulsant, others haveproposed that glucose restriction is the key. ThePUFAs, are thought to act at the heart of the sodium andcalcium channels, similar events have been describedin neuronal tissue.

Differential expression of antimicrobial peptides in active and latent tuberculosis and its relationship with diabetes mellitus.

Tuberculosis (TB) is one of the most important infectious diseases, causing 1.8 million deaths annually worldwide. This problem has increased because of the association with human immmunodeficiency virus and diabetes mellitus type 2, mainly in developing countries. In the past few years it has been highlighted the significance of antimicrobial peptides in the immunopathogenesis of TB ex vivo and in experimental models studies. In this study we analyzed the expression of CAMP, DEFA1, DEFB4, and DEFB103A in patients with latent TB and progressive TB with and without comorbidity with diabetes mellitus type 2. Antimicrobial peptide gene expression increased during progressive TB, which could be used as a biomarker for reactivation. By contrast, patients with diabetes mellitus type 2 have lower antimicrobial peptides gene expression, suggesting that the lack of its proper production in these patients contribute to enhance the risk for TB reactivation.

Nutrición enteral: primera parte / Enteral nutrition: first part

La nutrición enteral comprende todas las formas de soporte nutricional que implican el empleo de alimentación para propósitos médicos especiales, independientemente de la vía de alimentación, por vía oral o por sonda de alimentación. Debe ser considerada en pacientes con tracto gastrointestinal funcional que requieren apoyo nutricio. Las contraindicaciones son isquemia gastrointestinal, enterocolitis necrosante, íleo paralítico, megacolon tóxico, vómito o diarrea intratable, íleo paralítico, peritonitis difusa, sangrado de tubo digestivo grave y obstrucción intestinal. Las ventajas incluyen, aún cuando sea estimulación, la preservación de la función gastrointestinal, riesgo disminuido de infección y anormalidades metabólicas, atenuación de la respuesta catabólica, aumento de los sistemas antioxidantes, imita la nutrición humana estándar, reducción del tiempo de estancia hospitalaria, limitada traslocación bacteriana, disminuye la frecuencia de sepsis y falla orgánica múltiple, menor costo, fácil manejo y seguridad. Entre las fórmulas de alimentación se encuentran estándar, poliméricas o con proteínas intactas, hidrolizadas o basadas en péptidos, con aminoácidos libres o elementales, poliméricas artesanales, específicas para enfermedades, y modulares.

Enteral nutrition encompasses all forms of nutritional support involving the use of food for special medical purposes, regardless of route of feeding, orally or by feeding tube. It should be considered in patients with functional gastrointestinal tract who require nutritional support. The benefits include stimulation even when the preservation of gastrointestinal function, decreased risk of infection and metabolic abnormalities, catabolic response attenuation, increased antioxidant systems, mimics the standard human nutrition, reduced hospital stay, limited bacterial translocation, decreases the frequency of sepsis and multiple organ failure, lower cost, easy handling and safety. Among the feeding formulas are standard, polymeric or intact proteins, hydrolyzed or based on peptides, free amino acid or elemental, polymeric craft specific diseases, and modular.