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As treatment of the early, inflammatory phase of sepsis improves, post-sepsis immunosuppression and secondary infection have increased in importance. How early inflammation drives immunosuppression remains unclear. Although IFN-γ typically helps microbial clearance, we found that increased plasma IFN-γ in early clinical sepsis was associated with the later development of secondary Candida infection. Consistent with this observation, we found that exogenous IFN-γ suppressed macrophage phagocytosis of zymosan in vivo, and antibody blockade of IFN-γ after endotoxemia improved survival of secondary candidemia. Transcriptomic analysis of innate lymphocytes during endotoxemia suggested that NKT cells drove IFN-γ production by NK cells via mTORC1. Activation of invariant NKT (iNKT) cells with glycolipid antigen drove immunosuppression. Deletion of iNKT cells in Cd1d(–/–) mice or inhibition of mTOR by rapamycin reduced immunosuppression and susceptibility to secondary Candida infection. Thus, although rapamycin is typically an immunosuppressive medication, in the context of sepsis, rapamycin has the opposite effect. These results implicated an NKT cell/mTOR/IFN-γ axis in immunosuppression following endotoxemia or sepsis. In summary, in vivo iNKT cells activated mTORC1 in NK cells to produce IFN-γ, which worsened macrophage phagocytosis, clearance of secondary Candida infection, and mortality.

Resumen Introducción El síndrome metabólico es una condición muy prevalente en nuestra sociedad, y durante las últimas dos décadas la prevalencia ha aumentado significativamente convirtiéndose en un problema con una carga en salud importante. El cáncer de próstata por su parte es la primera causa de cáncer en hombres en el mundo. Numerosos estudios han sugerido una asociación entre la presencia de síndrome metabólico y el diagnóstico de cáncer de próstata. La información acerca de la asociación Del cáncer de próstata y obesidad es controversial. Nuestro objetivo es determinar si existe una relación entre la presencia de obesidad y el diagnóstico de cáncer de próstata en adultos mayores de la ciudad de Bogotá. Objetivos y Métodos Se analizaron los datos del estudio Salud, Bienestar y Envejecimiento (SABE) Bogotá 2012. Se utilizó como variable dependiente el autorreporte de examen de próstata en los 2 últimos años y se evaluó con respecto a variables antropométricas así como factores sociodemográficos por medio de un análisis multivariado. Resultados La prevalencia de cáncer de próstata fue de 3,15%. El 31.9% de los hombres tienen un IMC mayor de 30. Se encontró una asociación significativa entre el IMC y el diagnóstico de cáncer de próstata (p = 0.005), Enfermedad coronaria y cáncer de próstata (p = 0.03) y nivel de escolaridad y diagnóstico de Cáncer de próstata (p = 0.012). Conclusión Nuestro estudio demuestra que existe una asociación significativa entre estas dos entidades en una población bogotana de adultos mayores. Es necesario realizar más estudios que aporten mayor información acerca de esta asociación.

Objective: To assess the self-reported vaccination in older adults within the city of Bogotá and its distribution by sociodemographic factors. Methods: Data analyzed was taken from the SABE-Bogotá study. A total of 2000 persons aged 60 years and older were selected for this cross-sectional population-based study. Bivariate and multivariate analyses were performed testing the association between vaccination and sociodemographic factors. Results: A total of 73.0% of respondents received the influenza vaccine, 57.8% received pneumococcal vaccine and 47.6% received tetanus vaccine. In multivariate analyses, individuals aged between 65-74 years had higher odds of receiving influenza, pneumococcus and tetanus vaccination, compared to those between 60-64 years. Older adults with higher socioeconomic status (SES) had lower odds of having influenza and pneumococcus vaccines, compared to those with lower SES (OR= 0.16 95% confidence intervals= CI 0.08-0.30; OR 0.20 95% CI 0.10-0.38, respectively). Individuals covered by health insurance (contributive or subsidized) had higher odds (between 3 and 5 times higher) of having influenza, pneumococcus and tetanus vaccination, compared to those with no insurance. Conclusion: Older adults between 65 and 74 years, those with health care coverage and people with low SES are groups that have increased odds for self-reported vaccination. Further studies should identify factors that increase vaccination coverage in these groups and implement interventions targeted at improving coverage among older adults in general.

Introduccion. El envejecimiento de la poblacion es un fenomeno epidemiologico universal que conlleva un acentuado aumento de la expectativa de vida y al cual no somos ajenos. Las enfermedades concomitantes dependientes de la edad, entre ellas los problemas auditivos, son cada dia mas prevalentes e inciden notoriamente en la calidad de vida. Objetivo. Estimar la prevalencia de los problemas de audicion, asi como de los factores asociados y su efecto en la calidad de vida de los adultos mayores en Bogota. Materiales y metodos. Se analizaron los datos del estudio SABE, Bogota, en el curso del cual se entrevisto a 2.000 personas de 60 anos o mas en una muestra transversal probabilistica por conglomerados (cobertura de 81,9 %). Se utilizo la variable “problemas en la audicion” y se relaciono con los factores sociodemograficos, el uso de dispositivos auriculares, la percepcion de la propia salud, las enfermedades concomitantes, la funcionalidad, la cognicion y la calidad de vida, medida esta con la escala visual analogica del grupo EuroQOL ( EuroQoL-Visual Analogue Scale , EQ-VAS). Resultados. Se encontro una prevalencia de problemas de audicion en 267 personas (13,5 %), de las cuales el 15 % utilizaba audifonos; dicha prevalencia fue mayor en aquellas de 75 o mas anos (46,1 %), en el nivel socioeconomico bajo (20,2 %) y entre analfabetas (19,3 %, p

Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m . Pharmacological activation of AMP‐activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF‐1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF‐1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia.

Mechanical ventilation is necessary to support patients with acute lung injury, but also exacerbates injury through mechanical stress-activated signaling pathways. We show that stretch applied to cultured human cells, and to mouse lungs in vivo, induces robust expression of metallothionein, a potent antioxidant and cytoprotective molecule critical for cellular zinc homeostasis. Furthermore, genetic deficiency of murine metallothionein genes exacerbated lung injury caused by high tidal volume mechanical ventilation, identifying an adaptive role for these genes in limiting lung injury. Stretch induction of metallothionein required zinc and the zinc-binding transcription factor MTF1. We further show that mouse dietary zinc deficiency potentiates ventilator-induced lung injury, and that plasma zinc levels are significantly reduced in human patients who go on to develop acute respiratory distress syndrome (ARDS) compared with healthy and non-ARDS intensive care unit (ICU) controls, as well as with other ICU patients without ARDS. Taken together, our findings identify a potentially novel adaptive response of the lung to stretch and a critical role for zinc in defining the lung's tolerance for mechanical ventilation. These results demonstrate that failure of stretch-adaptive responses play an important role in exacerbating mechanical ventilator-induced lung injury, and identify zinc and metallothionein as targets for lung-protective interventions in patients requiring mechanical ventilation.

Objective: To determine the nutritional status and factors associated to malnutrition in older adults. Method: Data come from the SABE Bogotá study (Health, Well-Being, and Aging), a cross-sectional survey conducted in Bogotá, Colombia, in 2012 in community-dwelling adults aged 60 years and older. Using the Mini Nutritional Assessment (MNA), we evaluated the nutritional status and factors associated to malnutrition in this population with regression models. Results: From the 1,573 older adults interviewed, 4.58% were malnourished and 34.27% were at risk of malnourishment. Factors associated to malnourishment were older age (odds ratio [OR] =1.02, 95% confidence interval [CI] = [1.00, 1.04]), perceived poor health (OR = 1.46, 95% CI = [1.13, 1.88]), comorbidities (OR = 1.16, 95% CI = [1.04, 1.30]), and low calf circumference (OR = 2.63, 95% CI = [1.86, 3.72]). Having dentures, perception of being well-nourished, and higher functionality decreased the odds for malnourishment ( p < .05). Conclusion: The MNA is useful to evaluate factors associated with malnutrition among older adults in Bogotá. Malnutrition is associated with perception of poor health, comorbidities, number of medications, and cognitive impairment.

Introducción. La declinación funcional produce un amplio espectro de efectos negativos como dificultad para la movilidad, aislamiento social, deterioro de la calidad de vida, discapacidad e institucionalización, lo que hace de la medición de la funcionalidad un marcador importarte de bienestar.Objetivo. Caracterizar y determinar los factores asociados con el deterioro funcional del anciano en Bogotá, Colombia.Materiales y métodos. Se utilizaron los datos del Estudio SABE-Bogotá. El estado funcional de los participantes se evaluó usando las escalas de Barthel) y Lawton. Se usaron como variables independientes factores sociodemográficos, comorbilidades, medidas antropométricas y tertiles de actividad física, y se obtuvieron análisis bivariados y multivariados con regresiones lineales.Resultados. Se entrevistaron 2.000 personas de 60 o más años, con una edad promedio de 71,2 ± 8 años. Mayor funcionalidad en actividades instrumentales se asoció con una menor edad: (beta estandarizado: -0,15 (p

Doxorubicin is commonly used to treat leukemia, lymphomas, and solid tumors, such as soft tissue sarcomas or breast cancer. A major side effect of doxorubicin therapy is dose-dependent cardiotoxicity. Doxorubicin's effects on cardiac energy metabolism are emerging as key elements mediating its toxicity. We evaluated the effect of doxorubicin on [14C]creatine uptake in rat neonatal cardiac myocytes and HL-1 murine cardiac cells expressing the human creatine transporter protein. A significant and irreversible decrease in creatine transport was detected after an incubation with 50–100 nmol/l doxorubicin. These concentrations are well below peak plasma levels (5 μmol/l) and within the ranges (25–250 nmol/l) for steady-state plasma concentrations reported after the administration of 15–90 mg/m2 doxorubicin for chemotherapy. The decrease in creatine transport was not solely because of increased cell death due to doxorubicin's cytotoxic effects. Kinetic analysis showed that doxorubicin decreased Vmax, Km, and creatine transporter protein content. Cell surface biotinylation experiments confirmed that the amount of creatine transporter protein present at the cell surface was reduced. Cardiomyocytes rely on uptake by a dedicated creatine transporter to meet their intracellular creatine needs. Our findings show that the cardiomyocellular transport capacity for creatine is substantially decreased by doxorubicin administration and suggest that this effect may be an important early event in the pathogenesis of doxorubicin-mediated cardiotoxicity.

Functional impairment produces a wide range of negative effects such as difficulty in mobility, social isolation, decreased quality of life, disability and institutionalization. Thus, functional status measurement is a marker of social wellbeing.To determine and characterize the socio-demographic factors and health conditions related to functional impairment in older adults in Bogotá, Colombia.Data was collected from the SABE Bogotá Study. Functional status was assessed using the Barthel and Lawton scales. Independent variables included socio-demographic factors, comorbidities, anthropometric measurements and physical activity (by tertiles). Bivariate analyzes were performed, and multivariate results were obtained using linear regression models.There were 2,000 participants aged 60 years and older, with a mean age of 71.2 ± 8 years. Younger age (standardized beta = -0.15, p0.01), fewer medications (beta= -0.13, p0.01), higher MMSE score (beta = 0.3, p0.01), higher level of physical activity (middle beta tertile = 0.18, p0.01, and higher beta tertile= 0.18, p0.01vs lower tertile) and better performance in the handgrip test (beta= 0.10, p0.01) were associated with better function in daily life instrumental activities. Similarly, higher MMSE score (beta= 0.3, p0.01) and better performance in the handgrip test (beta= 0.07, p= 0.02) were associated with better function in daily life basic activities.We found several factors related with functional impairment, which are likely to be modified to reduce dependence in this population.

Profound alterations in myocellular creatine and phosphocreatine levels are observed during human heart failure. To maintain its intracellular creatine stores, cardiomyocytes depend upon a cell membrane creatine transporter whose regulation is not clearly understood. Creatine transport capacity in the intact heart is modulated by substrate availability, and it is reduced in the failing myocardium, likely adding to the energy imbalance that characterizes heart failure. AMPK, a key regulator of cellular energy homeostasis, acts by switching off energy-consuming pathways in favor of processes that generate energy. Our objective was to determine the effects of substrate availability and AMPK activation on creatine transport in cardiomyocytes. We studied creatine transport in rat neonatal cardiomyocytes and HL-1 cardiac cells expressing the human creatine transporter cultured in the presence of varying creatine concentrations and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Transport was enhanced in cardiomyocytes following incubation in creatine-depleted medium or AICAR. The changes in transport were due to alterations in Vmax that correlated with changes in total and cell surface creatine transporter protein content. Our results suggest a positive role for AMPK in creatine transport modulation for cardiomyocytes in culture.

The objective of this study was to measure the impact of edentulism and dental prostheses on quality of life (QOL) in older adults in Bogota, Colombia. Edentulism is a frequent condition in older adults and has great impact on their QOL. No epidemiological data are currently available on edentulism among older adults in Colombia. Data were obtained from the SABE-Bogota study, a cross-sectional study conducted in 2012, and used to analyze the EQ-VAS (Visual Analog Scale) from the EuroQol instrument to measure the perception of quality of life (QOL) in relation to edentulism. The study included 2,000 individuals over 60 years old. The Spearman-Rho correlation was used to analyze the correlation between EQ-VAS and edentulism. Chi-Square, ANOVA and t-test were used to study the differences in EQ-VAS scores between edentulous and healthy subjects. Statistical significance was set at p0.05. Of the 2000 respondents, 98.3% were edentulous, 73.0% reported half or more missing teeth, 76.9% used dental prostheses and 23.7% had related eating problems. Older age, lower social class and lower education were related to edentulism. Individuals with fewer teeth and dental prostheses had lower EQ-VAS scores (p0.05) and dental prosthesis did not improve EQ-VAS scores (p=0.22). Edentulism also showed a significant negative correlation with EQ-VAS scores (rho= -0.102, p0.01). In summary, EQ-VAS is a useful tool for measuring the perception of QOL in dental health scenarios. Edentulism significantly affects QOL in older adults and the use of dental prosthesis does not improve the perception of QOL.

Aim: Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies and tissue engineering, but have been limited by their low isolation yield. We increase pBD-EC yield via administration of the chemokine receptor type 4 antagonist AMD3100, as well as via a diluted whole blood incubation (DWBI). Materials & Methods: Porcine pBD-ECs were isolated using AMD3100 and DWBI and tested for EC markers, acetylated LDL uptake, growth kinetics, metabolic activity, flow-mediated nitric oxide production and seeded onto titanium tubes implanted into vessels of pigs. Results: DWBI increased the yield of porcine pBD-ECs 6.6-fold, and AMD3100 increased the yield 4.5-fold. AMD3100-mobilized ECs were phenotypically indistinguishable from nonmobilized ECs. In porcine implants, the cells expressed endothelial nitric oxide synthase, reduced thrombin-antithrombin complex systemically and prevented thrombosis. Conclusion: Administration of AMD3100 and the DWBI method both increase pBD-EC yield.

The aging of the population is a universal epidemiological phenomenon which is not unfamiliar to us and is accompanied by a marked increase of life expectancy. Age-dependent comorbidities, such as hearing disorders, are more prevalent and affect the quality of life in a noticeable manner.To estimate the prevalence of hearing disorders, of the associated factors and their impact on the quality of life of older adults in Bogota.Data was taken from the Bogotá SABE Study, which included 2,000 individuals aged =60 years in a probabilistic cross-sectional study sampled by clusters (with 81.9% coverage). We used the "hearing disorders" variable relating it to socio-demographic variables, as well as to the use of hearing aids, the self-perceived health, the comorbidities, the functionality, the cognition and the quality of life as measured with the Visual Analog Scale of the EuroQol Group (EQ-VAS).We found a prevalence of hearing disorders in 267 individuals (13.5%), of whom 15% used hearing aids. The frequency was higher in individuals aged =75 years (46.1%), in the low socioeconomic level (20.2%) and among illiterate people (19.3%, p0.05). Regarding comorbidities, we found a higher prevalence in individuals suffering from depression (20.2%, p0.001), and high blood pressure (15%, p0.01). The quality of life was worse in individuals with hearing disorders, as measured with the EuroQol EQ-VAS (60.93 ± 1.38 vs. 71.75 ± 0.45, p0.0001), but it improved among those who used hearing aids as compared to those who did not use them (59.59 ± 1.52, p0.01).Hearing disorders are relevant in elderly individuals and they affect their perceived quality of life in a noticeable manner. In addition, they are associated with other clinical, functional and cognitive problems. Nevertheless, the intervention with hearing aids reverses that perception.

Mechanical ventilation is a necessary intervention to support patients with lung injury and the acute respiratory distress syndrome (ARDS), but can also exacerbate injury through mechanical stress-activated signaling pathways. We show that stretch applied to cultured human lung cells, and to mouse lungs in vivo, induces robust expression of metallothionein, a potent anti-oxidant and cyto-protective molecule critical for cellular zinc homeostasis. Furthermore, genetic deficiency of murine metallothionein genes exacerbated lung injury caused by injurious mechanical ventilation, identifying an adaptive role for these genes in limiting lung injury. Stretch induction of metallothionein required zinc and the zinc binding transcription factor MTF-1. We further show that dietary zinc-deficiency in mice potentiates ventilator-induced lung injury, and that plasma zinc levels are significantly reduced in human patients with ARDS compared to healthy and non-ARDS ICU controls, as well as to other critically ill patients without ARDS. Taken together, our findings identify a novel adaptive response of the lung to stretch mediated by metallothionein and zinc. These results demonstrate that failure of stretch-adaptive responses play an important role in exacerbating ventilator-induced lung injury, and identify zinc and metallothionein as targets for developing lung-protective interventions in patients requiring mechanical ventilation.