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la Ley de vientre libre de julio de 1821 planteó para la Gran Colombia la manumisión paulatina de los esclavizados y la creación de las Juntas de Manumisión encargadas de llevar a cabo este proceso en cada provincia y cantón del territorio. Desde la promulgación de la norma hasta la abolición defi nitiva de la esclavitud —1851—, la población esclavizada de Medellín se presentó ante las Juntas solicitando ser elegida para gozar del precioso don de la libertad y declarando poseer una serie de cualidades que los hacían hombres y mujeres libres. En este sentido, este artículo indaga sobre el proceso de construcción de esta identidad libre y se plantean los siguientes interrogantes: ¿cómo se configuró la idea de libertad en el imaginario de la población esclavizada?, ¿qué sentido tuvo solicitarla ante la Junta de Manumisión?, ¿qué características hacían que una persona mereciese o no la libertad y de qué manera estas características infl uyeron en la representación que los esclavizados hicieron de sí mismos? Para responder estas preguntas se caracterizaron las solicitudes de libertad de 335 esclavizados y una muestra de estas fue analizada e interpretada a la luz del contexto en que se crearon, con lo que se concluye que a través de las solicitudes los esclavizados hicieron uso de un lenguaje hegemónico y unas estrategias de enunciación que les permitieron construir una identidad de sujetos merecedores de la libertad dada por la Junta de Manumisión de Medellín.

Background & aims: Population-based studies have suggested a protective effect of coffee against development of chronic kidney disease (CKD), possibly through coffee's anti-inflammatory and antioxidant compounds. Studies on coffee and kidney function decline in the general population are scarce. We studied associations of habitual coffee consumption with repeated assessments of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR). Methods: We used data from 7,914 participants of the population-based Rotterdam Study. Baseline coffee consumption data (cups/day) were obtained from home interviews and validated food frequency questionnaires (1997–2008). Repeated assessments of eGFR (ml/min per 1.73 m2, 1997–2014) were calculated according to the creatinine-based CKD Epidemiology Collaboration equation of 2012. Repeated assessments of urinary albumin and creatinine were used to estimate ACR (mg/g, 2006–2014). Data were analyzed by applying linear mixed models, adjusted for sociodemographic, lifestyle and dietary factors, and cardiovascular disease risk factors. Predefined subgroup analyses were performed stratified by CKD risk factors. Results: Participants’ mean (SD) baseline age was 66 (10) years, 57% were women and median [IQR] coffee consumption was 3.0 [2.0, 5.0] cups/day. Those drinking more coffee were more likely to smoke, and to have type 2 diabetes (T2D) and obesity. Mean eGFR was 79 (15) ml/min per 1.73 m2. In the total study population, coffee was not associated with longitudinal eGFR during a median of 5.4 years of follow-up (β = 0.04 ml/min per 1.73 m2 per one cup/day [95% CI: −0.10,0.18]). However, among those aged >70 years, one additional coffee cup/day was associated with on average 0.84 (0.51,1.18) ml/min per 1.73 m2 higher longitudinal eGFR. Among obese participants this estimate was 0.32 (0.01,0.63). A protective trend was also observed among former smokers (0.17 [−0.03,0.39]) and those with T2D (0.42 [−0.05,0.88]). Coffee was not associated with longitudinal ACR (0.01 mg/ml [−0.01,0.02]). Conclusion: While coffee was not associated with eGFR and ACR in the total population, more coffee consumption was associated with higher longitudinal eGFR among those at higher risk for CKD, i.e., among those aged 70+ and obese participants. These findings require confirmation in other prospective cohort studies.

The Colombian agroindustry has high diversity and availability of residual biomass year after year. These wastes are susceptible to being recovered through biological processes to reducing production costs of some raw materials and the pollutant load to the environment. This study identified the value-added by-products during the use of pig manure (PM), coffee mucilage (CM), and cocoa (CoM) through a dark fermentation process in a battery of batch reactors (200 ml bottles). The organic load (2, 5, and 8 gCOD/l), the C/N ratio (25, 35, and 45), and the ratio of the CM: CoM (3:1, 1:1, and 1:3) were evaluated. The highest hydrogen production yield of 271.3 ml H2/gCOD was associated with the experimental conditions of mixture 2 (2 gCOD/l, 35 C/N ratio, and CM: CoM 1: 3). Acetate, propionate, butyrate, and lactate fermentations were associated with the metabolic pathways of the process and participated in the soluble COD with 29, 12, 46, and 13%, respectively. It was identified that the acetate-butyrate pathway was the main metabolic pathway, and the acetate/butyrate ratio was in the range of 1:1–5.9:1. The microbial population found in the co-digestion processes worked on was dominated by the genera Clostridium, Bacillus, and Tisierella. The complex substrates used in this co-digestion process can produce value-added by-products and energy in a range of theoretical stoichiometry.

The residual biomass from agricultural activities has macronutrients and micronutrients, which could be recovered after an anaerobic co-digestion process. In this study, the effluents of the anaerobic co-digestion, which use coffee, cocoa mucilage, and pig manure, were evaluated to produce struvite. The effects of the Ca2+/PO43− ratio on the purity of struvite precipitation from synthetic and anaerobic co-digestion effluents was evaluated. The influence of pH, Ca2+/PO43− ration, and stirring speed on the efficiency of PO43− recovery and the removal of Ca2+ was studied. The phosphorus recovery increased from 85 to 99% with pH change from 8.5 to 10. The lowest removal of Ca2+ was 6.6% in the anaerobic effluent with the a ratio Ca2+/PO43− of 0.3:1 at pH 10. Struvite precipitate with high purity was obtained when the molar ratio was less than 0.3:1, and the pH was fixed to 10. X-ray diffraction analysis and scanning electron microscopy (SEM) confirmed the orthorhombic phases and morphology typical of struvite, respectively. In addition, the presence of K as a macronutrient and Ca and Na as micronutrients increases the viability of the struvite as fertilizer. The high recovery of phosphorus as struvite indicates it could be an alternative for nutrient recovery and utilization of these effluents.

Objetivo Modelar el curso de la pandemia COVID-19 en Chile y proyectar la demanda de recursos hospitalarios y letalidad en escenarios simulados: primero, recurriendo a distintas medidas de mitigación para contener la propagación en un mes —desde el 14 de abril hasta el 14 de mayo del 2020— y, segundo, en el supuesto contagio del 70% de la población, se ún edad, sin límite de tiempo.Métodos Utilizamos como base el número de contagios confirmados con SARS-CoV-2 en Chile hasta el 14 de abril del 2020 (8 273 casos, 94 muertes). Para los distintos escenarios, asumimos un número reproductivo básico que va desde R0=2,5 hasta R0=1,5. La proyección de la demanda hospitalaria y letalidad por edad se fundamentaron en reportes italianos y británicos.Resultados Estimamos que para el 14 de mayo del 2020 habría en Chile 2 019 775 contagiados y 15 068 fallecidos en ausencia de medidas de mitigación (R0=2,5). Al implementar medidas que reduzcan R0 a 1,5 (detección temprana y aislamiento de casos, cuarentena y distanciamiento social de mayores de 70 años), el número de contagios y letalidad disminuirían a 94 235 y 703 respectivamente. Sin embargo, la demanda hospitalaria aún sobrepasaría la capacidad de respuesta. La población de mayor riesgo la componen los mayores de 60 años.Conclusión Encontramos evidencia a favor de las medidas de mitigación implementadas por el Gobierno chileno. Sin embargo, medidas más estrictas son necesarias para no colapsar el sistema sanitario, que cuenta con menos recursos hospitalarios que los proyectados. Es esencial aumentar la capacidad hospitalaria en términos de equipamiento y entrenamiento del personal de salud.

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 10

DNA methylation (DNAm) has been reported to be associated with many diseases and mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction.We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n=15,013). During a mean follow-up of 10 years, there were 4314 deaths from all-causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at P-7, of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk independent of clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed a substantial improvement in prediction of cancer death with 11% and 5% increase in the C-index in internal and external replications, compared with the model trained by clinical risk factors alone. Mendelian randomization identified 15 CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta=1.2, PMR=4.1x10-4), and negatively associated with longevity (Beta=-1.9, PMR=0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune and cancer related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk.

13 páginas, 13 figuras, 4 tablas. Supplementary material associated with this article can be found in the online version at doi:10.1016/j.ultra smedbio.2022.02.016., The analysis of cell motion in an acoustic field is of interest as it can lead to new methods of cell separation, isolation and manipulation for diagnosis and treatment of diseases. Studies of the motion of different species of Leishmania parasites during exposure to ultrasonic standing waves in a microfluidic device allowed identification of acoustic responses of these parasites in their promastigote and amastigote forms. Both forms exhibited a positive acoustic contrast factor and were driven toward the pressure node established in the center of the channel by the acoustically induced radiation force (F). Promastigotes experience calculated F amplitudes one order of magnitude larger than those experienced by amastigotes because of the measured differences in volume. The aggregates formed at the pressure node have distinct shapes and stability conditions, for both promastigotes and amastigotes., This research was supported and funded by the Institute of Physical Technologies and Information ITEFI-CSIC, Spain, through Project COOPA20348, I-COOP+2018, and by the Ministry of Science, Technology, and Innovation of Colombia, Minciencias, through the postdoctoral position in the biophysics laboratory of Centro Internacional de Física (CIF), funded in Conv. 891–2020.

Sex is a major determinant of cardiometabolic risk. DNA methylation (DNAm), an important epigenetic mechanism that differs between sexes, has been associated with cardiometabolic diseases. Therefore, we aimed to systematically review studies in adults investigating sex-specific associations of DNAm with intermediate cardiometabolic traits and incident cardiovascular disease including stroke, myocardial infarction (MI) and coronary heart disease (CHD). Five bibliographic databases were searched from inception to 15 July 2019. We selected 35 articles (based on 30 unique studies) from 17,023 references identified, with a total of 14,020 participants of European, North American or Asian ancestry. Four studies reported sex differences between global DNAm and blood lipid levels and stroke risk. In 25 studies that took a genome wide or candidate gene approach, DNAm at 31 gene sites was associated with sex differences in cardiometabolic diseases. The identified genes were PLA2G7, BCL11A, KDM6A, LIPC, ABCG1, PLTP, CETP, ADD1, CNN1B, HOOK2, GFBP-7,PTPN1, GCK, PTX3, ABCG1, GALNT2, CDKN2B, APOE, CTH, GNASAS, INS, PON1, TCN2, CBS, AMT, KDMA6A, FTO, MAP3K13, CCDC8, MMP-2 and ER-α. Prioritized pathway connectivity analysis associated these genes with biological pathways such as vitamin B12 metabolism, statin pathway, plasma lipoprotein, plasma lipoprotein assembly, remodeling and clearance and cholesterol metabolism. Our findings suggest that DNAm might be a promising molecular strategy for understanding sex differences in the pathophysiology of cardiometabolic diseases and that future studies should investigate the effects of sex on epigenetic mechanisms in cardiometabolic risk. In addition, we emphasize the gap between the translational potential and the clinical utilization of cardiometabolic epigenetics.

OBJECTIVES: Previous studies suggest a positive association between coffee consumption and liver health, yet the evidence available is not unequivocal. Given the burden of liver disease, we studied the relationship of habitual coffee consumption with serum biomarkers of liver health and non-alcoholic fatty liver disease (NAFLD) incidence. METHODS: We included 209,575 participants from the UK Biobank cohort (mean age 56.1 and 68% women, median coffee consumption per day 1.00 cup [0.50, 3.00]), free of disease at baseline. Firstly, we studied cross-sectional associations of coffee consumption with serum concentrations of the liver enzymes alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and total bilirubin using multivariable linear regressions. Secondly, we analyzed associations with elevated enzyme concentrations according to clinical cutoffs to monitor liver damage, using logistic regressions. Lastly, in a longitudinal analysis, we assessed the association of coffee consumption and incident NAFLD in cox proportional hazard models. Models were adjusted for sociodemographic, lifestyle and health-related factors. Results are reported as β log transformed IU/L, odds ratio (OR) or hazard ratio (HR) with their 95% confidence intervals [95% CI] per one cup increase in coffee intake. RESULTS: Over a median follow up of 10.9 years, 2258 cases of incident NAFLD occurred in the population. Higher coffee consumption was associated with lower concentrations of log-transformed ALP (−0.005 [95% CI −0.006, −0.005]), ALT (−0.004 [−0.005, −0.003]), AST (−0.005 [−0.005, −0.004]), GGT (−0.008 [−0.009, −0.007]) and total bilirubin (−0.009 [−0.010, −0.008]). Secondly, higher coffee consumption was associated with lower odds of having elevated levels of all studied liver enzymes (OR from 0.91, [0.89, 0.92] for total bilirubin to 0.98 [0.97, 0.98] for GGT). Finally, higher coffee consumption was associated with lower risk of developing NAFLD (HR 0.98 [0.96, 0.99]). CONCLUSIONS: In this large cohort we observed an inverse association between higher coffee consumption and serum concentrations of baseline liver enzymes and NAFLD risk. These findings suggest that habitual consumption of coffee may be protective of liver health. FUNDING SOURCES: N/A.

OBJECTIVES: Given its popularity, there is an increasing interest in the study of coffee intake and its effect on health. Previous studies linked coffee consumption to lower type 2 diabetes (T2D) risk. However, potential underlying mechanisms remain unclear. We hypothesized that coffee's effects on systemic inflammation may play a role. We studied cross sectional and longitudinal associations of habitual coffee consumption with T2D risk and inflammation. METHODS: Participants from UK Biobank (UKB, n = 145,370) and Rotterdam Study (RS, n = 7172) cohorts were included. Coffee intake data were collected through self-administrated food frequency questionnaire or during home interviews. We studied associations of coffee intake with incident T2D using cox proportional hazard models; with longitudinally measured insulin resistance (HOMA IR) through linear mixed effect models; with serum baseline levels of inflammation markers using linear regressions; and the role of inflammation in coffee-T2D associations using mediation analysis. Models were adjusted for sociodemographic, lifestyle and health factors. Results were respectively expressed as hazard ratio (HR); β log transformed HOMA IR level; β log transformed ug/mL; and percentage mediated; and 95% confidence interval [95% CI]. RESULTS: UKB participants were 58% female and 55.2 years in average; RS were 59.7% female and 65.1 years. The median follow up was 7 (UKB) and 9 (RS) years. The modal coffee consumption was 0.5–2 cups/day (UKB) and 3–4 cups/day (RS). An increase of one coffee cup/day was associated with 4–6% lower T2D risk (RS HR 0.94 [95% CI 0.90; 0.98]; UKB HR 0.96 [0.94; 0.98]); lower HOMA IR (RS β −0.017 [−0.024; −0.010]); lower C reactive protein (CRP, RS β −0.014 [−0.022; −0.005]; UKBB β −0.011 [−0.012; −0.009] and higher adiponectin (RS β 0.025 [0.007; 0.042]. About coffee types, habitual consumers of filtered coffee had the lowest T2D risk (UKB HR 0.88 [0.83; 0.93]), compared to decaffeinated or instantaneous coffee. CRP levels mediated 9.6% (UKB) and 3.4% (RS) of the total effect of coffee on T2D. Adiponectin also showed evidence for mediation. CONCLUSIONS: Coffee's beneficial effects on lower T2D risk may be partially mediated by improvements in systemic inflammation. Among coffee drinkers, filtered coffee may be of preference. FUNDING SOURCES: Partially funded by the Institute for Scientific Information on Coffee.

Background: Coffee intake has been linked to lower type 2 diabetes (T2D) risk. We hypothesized this may be mediated by coffee’s effects on inflammation. Methods: Using participants from the UK Biobank (UKB n=145370) and Rotterdam Study (RS n=7172) cohorts, we studied associations of coffee intake with incident T2D; longitudinally measured insulin resistance (HOMA IR); serum levels of inflammation markers; and the mediating role of inflammation. Statistical regression models were adjusted for sociodemographic, lifestyle and health factors. Results: The median follow up was 7 (UKB) and 9 (RS) years. An increase of one coffee cup/day was associated with 4-6% lower T2D risk (RS HR=0.94 [95% CI 0.90; 0.98]; UKB HR=0.96 [0.94; 0.98]); lower HOMA IR (RS β=-0.017 [-0.024; -0.010]); with lower C reactive protein (CRP) and higher adiponectin (Figure1). Consumers of filtered coffee had the lowest T2D risk (UKB HR=0.88 [0.83; 0.93]). CRP levels mediated 9.6% (UKB) and 3.4% (RS) of the total effect of coffee on T2D (Figure 1). Conclusions: We suggest that coffee’s beneficial effects on lower T2D risk are partially mediated by improvements in systemic inflammation.Figure 1. a CRP and a adiponectin refer to the effect of coffee intake on CRP and adiponectin levels. a CRP RS : β=-0.014 (-0.022; -0.005); UKBB a CRP UKB : β=-0.011 (-0.012; -0.009) and RS a adiponectin : β=0.025 (0.007; 0.042). b CRP and b adiponectin refer to the effect of coffee related levels in CRP and adiponectin on incident T2D, independent of coffee. RS b CRP : HR=1.17 (1.04; 1.31); UKB b CRP : HR=1.45 (1.37; 1.54); and b adiponectin : HR=0.58 (0.32; 0.83). c′ refers to coffee’ effect on T2D going directly or via others mediators. UKB c′ independent of CRP : HR=0.96 (0.94; 0.99); RS c′ independent of CRP : HR=0.94 (0.90; 0.99); and RS c′ independent of CRP+adiponectin : HR=0.90 (0.80; 1.01). Coffee related changes in CRP may partially explain the beneficial link between coffee and T2D, mediating a 3.4% (0.6; 4.8, RS) and 9.6% (5.7; 24.4, UKB). Evidence of mediation was also found for adiponectin.

Resumen Introduccion El ictus isquemico puede ser una complicacion grave en los pacientes con infeccion por SARS-CoV-2. Estudiar y caracterizar los diferentes subtipos etiologicos, las caracteristicas clinicas y el pronostico funcional podra resultar util en la seleccion de pacientes para un manejo y tratamiento optimos. Metodos La recogida de variables se hizo de forma retrospectiva en pacientes consecutivos con infeccion por SARS-CoV-2 que desarrollaron un episodio de isquemia cerebral focal (entre el 1 de marzo del 2020 y el 19 de abril del 2020). Se llevo a cabo en un hospital universitario de tercer nivel en la Comunidad de Madrid (Espana). Resultados Durante el periodo de estudio 1.594 pacientes fueron diagnosticados de infeccion por SARS-CoV-2. Identificamos a 22 pacientes con ictus isquemico (1,38%); de estos, no cumplieron los criterios de inclusion 6. Un total de 16 pacientes con isquemia cerebral focal constituyeron la serie del estudio (15 con ictus isquemico y uno con accidente isquemico transitorio). En la valoracion basal en el National Institutes of Health Stroke Scale la mediana fue de 9 (rango intercuartil: 16), la edad media ± desviacion estandar fue de 73 ± 12,8 anos; 12 pacientes fueron varones (75%). El tiempo desde los sintomas de COVID-19 hasta el ictus fue de 13 dias. Se encontro oclusion de gran vaso en 12 pacientes (75%). El dimero-D estuvo elevado en el 87,5% y la proteina C reactiva en el 81,2% de los casos. La etiologia mas frecuente del ictus isquemico fue la aterotrombosis (9 pacientes, 56,3%) con un subtipo predominante que fue el trombo endoluminal sobre placa de ateroma (5 pacientes, 31,2%), 4 de ellos en la arteria carotida interna y uno de ellos en el arco aortico. La mortalidad en nuestra serie fue del 44% (7 de 16 pacientes). Conclusiones En los pacientes con ictus y COVID-19 la etiologia mas frecuente fue la aterotrombotica, con una elevada frecuencia de trombo endoluminal sobre placa de ateroma (31,2% de los pacientes). Nuestros hallazgos clinicos y de laboratorio apoyan la coagulopatia asociada a COVID-19 como un mecanismo etiopatogenico relevante en el ictus isquemico en este contexto.

Adherence to Enhanced Recovery Protocols (ERPs) is associated with faster functional recovery, better patient satisfaction, lower complication rates and reduced length of hospital stay. Understanding institutional barriers and facilitators is essential for improving adherence to ERPs. The purpose of this study was to identify institutional factors associated with adherence to an ERP for colorectal surgery.A secondary analysis of a nationwide study was conducted including 686 patients who underwent colorectal surgery across twenty-one institutions in Spain. Adherence to ERPs was calculated based upon the components recommended by the Enhanced Recovery After Surgery (ERAS®) Society. Institutional characteristics (i.e., case volume, ERP duration, anesthesia staff size, multidisciplinary meetings, leadership discipline) were captured from each participating program. Multivariable regression was performed to determine characteristics associated with adherence.The median adherence to ERAS was 68.2% (IQR 59.1%-81.8%). Multivariable linear regression revealed that anesthesiologist leadership (+5.49%, 95%CI +2.81% to +8.18%, P 0.01), duration of ERAS implementation (+0.46% per year, 95%CI +0.06% to +0.86%, P 0.01) and the use of regular multidisciplinary meetings (+4.66%, 95%CI +0.06 to +7.74%, P 0.01) were independently associated with greater adherence. Case volume (-2.38% per 4 cases weekly, 95%CI -3.03 to -1.74, P 0.01) and number of anesthesia providers (-1.19% per 10 providers, 95%CI +2.23 to -8.18%, P 0.01) were negatively associated with adherence.Adherence to ERPs is strongly associated with anesthesiology leadership, regular multidisciplinary meetings, and program duration, whereas case volume and the size of the anesthesia staff were potential barriers. These findings highlight the importance of strong leadership, experience and establishing a multidisciplinary team when developing an ERP for colorectal surgery.

Background Type 2 diabetes (T2D) is a heterogeneous disease with well-known genetic and environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones. Results We performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based on the meta-analysis results. We found three novel CpGs associated with prevalent T2D in Europeans at cg00144180 (HDAC4), cg16765088 (near SYNM) and cg24704287 (near MIR23A) and confirmed three CpGs previously identified (mapping to TXNIP, ABCG1 and CPT1A). We also identified 77 T2D associated DMRs, most of them hypomethylated in T2D cases versus controls. In adjusted regressions among diabetic-free participants in ALSPAC, we found that all six CpGs identified in the meta-EWAS were associated with white cell-types. We estimated that these six CpGs captured 11% of the variation in T2D, which was similar to the variation explained by the model including only the common risk factors of BMI, sex, age and smoking (R2 = 10.6%). Conclusions This study identifies novel loci associated with T2D in Europeans. We also demonstrate associations of the same loci with other traits. Future studies should investigate if our findings are generalizable in non-European populations, and potential roles of these epigenetic markers in T2D etiology or in determining long term consequences of T2D.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world since it emerged in Wuhan and coronavirus disease 2019 (COVID-19) has become a pandemic1. There is still little information regarding possible neurologic complications of this spread. Herein, we describe a patient with Guillain-Barré syndrome (GBS) preceded by COVID-19, raising the possibility of a causal relationship.

Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P −3 ). Hypermethylation of cg18181703 ( SOCS3 ) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality ( P =5.7×10 −15 ). Ten additional diet-associated CpGs were nominally associated with all-cause mortality ( P P −4 ). For example, hypermethylation of cg11250194 ( FADS2 ) was associated with lower triglyceride concentrations (MR, P =1.5×10 −14 ).and hypermethylation of cg02079413 ( SNORA54 ; NAP1L4 ) was associated with body mass index (corrected MR, P =1×10 −6 ). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

To date, non-pharmacological interventions (NPI) have been the mainstay for controlling the coronavirus disease-2019 (COVID-19) pandemic. While NPIs are effective in preventing health systems overload, these long-term measures are likely to have significant adverse economic consequences. Therefore, many countries are currently considering to lift the NPIs—increasing the likelihood of disease resurgence. In this regard, dynamic NPIs, with intervals of relaxed social distancing, may provide a more suitable alternative. However, the ideal frequency and duration of intermittent NPIs, and the ideal “break” when interventions can be temporarily relaxed, remain uncertain, especially in resource-poor settings. We employed a multivariate prediction model, based on up-to-date transmission and clinical parameters, to simulate outbreak trajectories in 16 countries, from diverse regions and economic categories. In each country, we then modelled the impacts on intensive care unit (ICU) admissions and deaths over an 18-month period for following scenarios: (1) no intervention, (2) consecutive cycles of mitigation measures followed by a relaxation period, and (3) consecutive cycles of suppression measures followed by a relaxation period. We defined these dynamic interventions based on reduction of the mean reproduction number during each cycle, assuming a basic reproduction number (R0) of 2.2 for no intervention, and subsequent effective reproduction numbers (R) of 0.8 and 0.5 for illustrative dynamic mitigation and suppression interventions, respectively. We found that dynamic cycles of 50-day mitigation followed by a 30-day relaxation reduced transmission, however, were unsuccessful in lowering ICU hospitalizations below manageable limits. By contrast, dynamic cycles of 50-day suppression followed by a 30-day relaxation kept the ICU demands below the national capacities. Additionally, we estimated that a significant number of new infections and deaths, especially in resource-poor countries, would be averted if these dynamic suppression measures were kept in place over an 18-month period. This multi-country analysis demonstrates that intermittent reductions of R below 1 through a potential combination of suppression interventions and relaxation can be an effective strategy for COVID-19 pandemic control. Such a “schedule” of social distancing might be particularly relevant to low-income countries, where a single, prolonged suppression intervention is unsustainable. Efficient implementation of dynamic suppression interventions, therefore, confers a pragmatic option to: (1) prevent critical care overload and deaths, (2) gain time to develop preventive and clinical measures, and (3) reduce economic hardship globally. Electronic supplementary material The online version of this article (10.1007/s10654-020-00649-w) contains supplementary material, which is available to authorized users.

En el presente artículo se plantea la importancia, beneficios y prácticas de gestión ambiental que se pueden implementar en pequeñas y medianas empresas, para el caso del sector turismo, específicamente, hoteles. En la actualidad la gestión del medio ambiente se configura como una variable que genera ventaja competitiva, en la medida que las organizaciones hacen más eficientes sus procesos, reducen costos, evitan sanciones y constituyen una imagen corporativa responsable con el entorno y la sociedad, alcanzando mayor aceptación en el mercado y una mejor relación con clientes y la comunidad. En este sentido, se hace preponderante que estas prácticas se implementen en las pequeñas y medianas empresas, siendo estas las organizaciones con el peor comportamiento en este campo, para el caso en los pequeños y medianos hoteles de la ciudad de Cartagena, dada su representatividad dentro del sector empresarial y la economía local. El trabajo se soporta en una revisión de literatura en bases de datos de libre acceso y privadas utilizando descriptores como: “gestión ambiental” y “Pymes”, a partir de la cual se pudo establecer los beneficios y las prácticas de gestión ambiental que se pueden asociar a este tipo de empresas.

OBJECTIVE To investigate the role of epigenetics in statins’ diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood. RESEARCH DESIGN AND METHODS Five cohort studies’ participants (n = 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise. Associations of DNAm with various outcomes like incident type 2 diabetes, plasma glucose, insulin, and insulin resistance (HOMA of insulin resistance [HOMA-IR]) as well as with gene expression were investigated. RESULTS Discovery (n = 6,820) and replication (n = 1,450) phases associated five DNAm sites with statin use: cg17901584 (1.12 × 10−25 [DHCR24]), cg10177197 (3.94 × 10−08 [DHCR24]), cg06500161 (2.67 × 10−23 [ABCG1]), cg27243685 (6.01 × 10−09 [ABCG1]), and cg05119988 (7.26 × 10−12 [SC4MOL]). Two sites were associated with at least one glycemic trait or type 2 diabetes. Higher cg06500161 methylation was associated with higher fasting glucose, insulin, HOMA-IR, and type 2 diabetes (odds ratio 1.34 [95% CI 1.22, 1.47]). Mediation analyses suggested that ABCG1 methylation partially mediates the effect of statins on high insulin and HOMA-IR. Gene expression analyses showed that statin exposure and ABCG1 methylation were associated with ABCG1 downregulation, suggesting epigenetic regulation of ABCG1 expression. Further, outcomes insulin and HOMA-IR were significantly associated with ABCG1 expression. CONCLUSIONS This study sheds light on potential mechanisms linking statins with type 2 diabetes risk, providing evidence on DNAm partially mediating statins’ effects on insulin traits. Further efforts shall disentangle the molecular mechanisms through which statins may induce DNAm changes, potentially leading to ABCG1 epigenetic regulation.

espanolEn el presente texto se propone una ruptura con los modos convencionales de hacer investigacion en ciencias sociales, esto sera una especie de ensamblaje experimental, una apuesta politica, social, estetica, etica que implica performancias metodologicas que cuestionan las formas normalizadas de produccion de conocimiento, y explora una actitud esquizo como potencia intensiva de un cuerpo que piensa otros modos de investigar. Transgrede fronteras identitarias, traiciona el yo, la conciencia y la ciencia en una transvaloracion de todos los valores. Inicialmente se pretende hacer una cartografia, quiza poetica, de la condicion neoliberal: un abordaje que navega en el fantasma del Edipo endeudado. Posteriormente seguiremos los trazados del territorio rizomatico de Deleuze y Guattari, bosquejando lineas y tareas del esquizoanalisis; finalmente se presenta la formula paradojica de la traicion: la actitud experimental esquizoanalitica situada al margen, devenir menor de la practica investigativa que agrieta lenguajes, metodos y corporalidades codificadas en un regimen de produccion capitalista; actitud metodologica que libera la vida, el deseo, produce realidad. Una metodologia dionisiaca de la esquizofrenia borderline que hace un cuerpo sin organos. EnglishThis paper intends to break up with mainstream approaches to do research in social sciences, a sort of experimental assembly, a political, social, aesthetic, ethic wager involving methodological performances calling into question normalised ways of producing knowledge, and exploring a schizo mindset as an intensive power of a body thinking of different ways to do research. It trespasses identity boundaries, betraying the Self, consciousness, and science in a trans-valuation of all and any value. Initially, it intends to cartography, perhaps poetically, the neoliberal condition: an approach that sails on the ghost of indebted Oedipus. Then, we will trail the courses in Deleuze and Guattari’s rhizomatic landscape, by sketching several lines and tasks in schizoanalysis. Finally, we will introduce the paradoxical formula of betrayal: an experimental schizoanalytic attitude on the margin, a minor becoming of research practice cracking languages, methods and corporalities as coded in a capitalist production regime; a methodological mindset freeing life and desire, producing reality. A Dyonisian methodology of borderline schizofrenia performed by an organless body portuguesPropoe-se, no presente texto, uma ruptura com os modos convencionais de fazer pesquisa nas Ciencias Sociais, isto e, uma especie de montagem experimental, uma aposta politica, social, estetica e etica que envolve performances metodologicas que, por seu turno, questionam as formas naturalizadas da producao do conhecimento. Explora uma atitude esquizo como potencia intensiva de um corpo que pensa em outros jeitos de pesquisar. Uma atitude que transgride fronteiras identitarias, trai o eu, a consciencia e a ciencia numa transvaloracao de todos os valores. Busca-se, no primeiro momento, construir uma cartografia, talvez poetica, da condicao neoliberal: uma abordagem que navega no fantasma do Edipo endividado. No segundo momento, seguiremos as pegadas do territorio rizomatico de Deleuze e Guattari, rascunhando linha e tarefas da esquizoanalise. Por fim, apresenta-se a formula paradoxal da traicao: a atitude experimental esquizoanalitica localizada na margem, como devir menor da pratica de pesquisa que quebra linguagens, metodos e corporalidades codificadas num regime de producao capitalista. Como uma atitude metodologica que liberta a vida, o desejo e produz realidade. Uma metodologia dionisiaca da esquizofrenia borderline que faz um corpo sem orgaos.

El propósito de este análisis es demostrar la manera en la cual el escritor neogranadino Hernando Domínguez Camargo deconstruye, a través de sus octavas, la visión bélica que exalta la Conquista española, por medio de un análisis meticuloso de algunos momentos de su obra magna: el Poema Heroico.

Aims There are several epidemiological studies on the association between statins and incident diabetes, but most of them lack details. In this study, we aimed to investigate the association of statin use with glycaemic traits and incident type 2 diabetes. Methods Using the prospective population‐based Rotterdam Study, we included 9535 individuals free from diabetes at baseline (>45 years) during the study period between 1997 and 2012. Linear regression analysis was applied to examine the cross‐sectional associations between statin use and glycaemic traits including fasting blood serum of glucose and insulin concentrations, and insulin resistance. In a longitudinal follow‐up study, we applied a Cox regression analysis to determine adjusted hazard ratios (HR) for incident type 2 diabetes in new users of statins. Results The mean age at baseline was 64.3 ± 10.1 years and 41.7% were men. In the fully adjusted model, compared to never users of statins, baseline use of statins was associated with higher concentrations of serum fasting insulin (β = 0.07; 95% CI: 0.02–0.13) and insulin resistance (β = 0.09; 95% CI: 0.03–0.14). Ever use of statins was associated with a 38% higher risk of incident type 2 diabetes (HR = 1.38; 95% CI: 1.09–1.74). This risk was more prominent in subjects with impaired glucose homeostasis and in overweight/obese individuals. Conclusions Individuals using statins may be at higher risk for hyperglycaemia, insulin resistance and eventually type 2 diabetes. Rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy might help minimize the risk of diabetes.

Type 2 diabetes and its accompanying complications constitute a major health burden worldwide, which can be partly attributed to the interplay between genetics and environments. Extensive research over the last decades has shown that our genome is not the only determinant of disease risk. Epigenetic marks induced by lifestyle and environmental factors are associated with altered gene expression patterns in important tissues, leading to altered susceptibility to disease later in life. Hence, the identification of epigenetic biomarkers unfolds the possibility for a novel personalized disease prevention strategy and at the same time holds the potential to be a promising prognostic tool for diabetes. So far, evidence on the predictive value of epigenetics in diabetes management is very limited. Unlike in cancer pathology, where examples of important epigenetic tools are now widely used in clinical practice as predictive/diagnostic biomarkers, for complex pathophysiological diseases such as diabetes, this still remains a challenge. These topics are discussed extensively in this chapter.

Current evidence associates statin use with increased risk of type 2 diabetes (T2D). Mechanism are unclear. Statins may impact DNA methylation, a key regulator in gene expression. We conducted an epigenome-wide association study among 8313 Europeans (7163 never users and 1150 current statin users) from 7 cohorts to assess the association of statin use and DNA methylation in blood. After replication we found genome-wide associations of methylation sites annotated to DHCR24 (cg17901584, cg10177197), SC4MOL (cg05119988), and ABCG1 (cg06500161, cg27243685), which are involved in cholesterol, insulin and lipoprotein lipase pathways. Cg06500161 hypermethylation was related to decreased ABCG1 expression in two probes (P = 5 x 10-12 and 9 x 10-13), lower high density lipoprotein cholesterol (HDL, P = 0.002) and higher triglycerides (P = 1 x 10-4). Mendelian Randomization suggested that HDL and triglycerides might be a consequence of cg06500161 rather than a cause. Lower methylation of cg17901584 was associated with higher insulin (P = 0.006). Prevalent T2D was related to all sites except cg27243685 (P from 6 x 10-10 to 9 x 10-4). Only cg06500161 independently predicted incident T2D (P = 6 x 10-7), implicating that ABCG1 may be a causal factor for T2D as suggested by Mendelian Randomization (Figure 1). Our study is the first to provide evidence of DNA methylation as potential mechanism by which statin use can lead to adverse metabolic alterations and subsequently T2D. Disclosure C. Ochoa-Rosales: None. E. Portilla-Fernandez: None. R. Wilson: None. J. Nano: None. M. Ghanbari: None. O.L. Rueda-Ochoa: None. T. Lehtimäki: None. X. Gao: None. B. Lehne: None. T. Voortman: None. O. Franco: None. T. Muka: Employee; Self; Novo Nordisk A/S.

Phytoestrogen-based medications are commonly used by menopausal women, and especially by obese postmenopausal women, to relieve menopausal symptoms. Substitution of animal with soy protein is often used in weight loss regimens, yet the effect of phytoestrogens, the main constituent of soy foods, on body composition is not completely understood. We conducted a systematic review and meta-analysis to investigate the associations between phytoestrogen supplementation and body weight and the main parameters of body composition in postmenopausal women. A literature search was done using 5 electronic databases from inception to April 2018. Randomized controlled trials (RCTs) with postmenopausal women comparing phytoestrogen supplementation followed by usual diet and placebo were included in the present meta-analysis. From 5932 references, we identified 23 RCTs that met our inclusion criteria, with a total of 1880 postmenopausal women. No association was observed between phytoestrogen supplementation and body weight, body mass index, waist and hip circumference, total fat mass or percentage of body fat. However, the use of phytoestrogens supplementation was associated with a slight decrease in waist-hip ratio; the pooled mean difference was -0.01 cm (95%CI: -0.01 to -0.006). In subgroup analysis, we found a modest decrease in body weight with phytoestrogens supplementation compared with placebo in healthy postmenopausal women [pooled mean difference of changes -0.28 kg (95%CI: -0.52 to -0.04)] and in RCTs with a median number of participants of 66 or less [pooled mean difference of changes -0.49 kg (95%CI: -0.87 to -0.11)]. In contrast, phytoestrogen supplementation was associated with increased body weight in postmenopausal women with preexisting metabolic disorders (prediabetes, type 2 diabetes, prehypertension and hyperlipidemia) [pooled mean difference of changes: 0.78 kg (95%CI: 0.53-1.03)]. In addition, there were some indications that some types of phytoestrogens, such as daidzein, but not soy products or isoflavone mix, could lead to modest adverse changes in body composition in menopausal women. Therefore, future studies should investigate the potential adverse effects of phytoestrogen supplementation on body composition among postmenopausal women.

This is a text derivated from the presentation “La fijeza: tiempo y espacio insulares”, in the 38th Conference of the Caribbean Studies Association, on June 4th, 2013 at Grenada Grand Beach Resort, Grand Anse, Grenada.Lezama Lima was a Cuban poet, essayist, and novelist considered as well as Alejo Carpentier, one of the greatest figures of the Caribbean island literature. His detailed knowledge of the baroque literature specially Góngora’s poetry, and also his necessity of fixing a Cuban identity, allowed him to propose a very innovative esthetic which goes beyond the disenchantment proper of the baroque. The verses of “La fijeza” are some examples of this vision. In this order of ideas, the purpose of this work in to present the analysis of some poems of “La fijeza” in order to explain the manner in which Lezama distances himself from the baroque disenchantment conception of the world and how, at the same time, he presents verses of hope, identity and universalism by means of presenting the poetic image of the Caribbean scenery and its spatio-temporal relationships in a way to explain a vision of the poetry as privileged way to re-create the world.