Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder.

Background: Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5 mC), have been associated with AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) have identified differentially methylated genes associated with AUD in human peripheral and brain tissue. More recently, epigenetic studies of AUD have also evaluated DNA hydroxymethylation (5 hmC) in the human brain. However, most of the epigenetic work in postmortem brain tissue has examined bulk tissue. In this study, we investigated neuronal-specific 5 mC and 5 hmC alterations at CpG sites associated with AUD in the human orbitofrontal cortex (OFC). Methods: Neuronal nuclei from the OFC were evaluated in 34 human postmortem brain samples (10 AUD, 24 non-AUD). Reduced representation oxidative bisulfite sequencing was used to assess 5 mC and 5 hmC at the genome-wide level. Differential 5 mC and 5 hmC were evaluated using the methylKit R package and significance was set at false discovery rate < 0.05 and differential methylation > 2. Functional enrichment analyses were performed, and gene-level convergence was evaluated in an independent dataset that assessed 5 mC and 5 hmC of AUD in bulk cortical tissue. Results: We identified 417 5 mC and 363 5hmC significant differential CpG sites associated with AUD, with 59% in gene promoters. Some of the identified genes have been previously implicated in alcohol consumption, including SYK, DNMT3A for 5 mC, GAD1, DLX1, DLX2, for 5 hmC and GATA4 in both. Convergence with a previous AUD 5 mC and 5 hmC study was observed for 28 genes. We also identified 5 and 35 differential regions for 5 mC and 5 hmC, respectively. Lastly, GWAS enrichment analysis showed an association with AUD for differential 5 mC genes. Discussion: This study reveals neuronal-specific methylome and hydroxymethylome dysregulation associated with AUD, identifying both previously reported and potentially novel gene associations with AUD. Our findings provide new insights into the epigenomic dysregulation of AUD in the human brain.

Neuronal-specific methylome and hydroxymethylome analysis reveal replicated and novel loci associated with alcohol use disorder.

Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5mC), have been associated with AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) have identified differentially methylated genes associated with AUD in human peripheral and brain tissue. More recently, epigenetic studies of AUD have also evaluated DNA hydroxymethylation (5hmC) in the human brain. However, most of the epigenetic work in postmortem brain tissue has examined bulk tissue. In this study, we investigated neuronal-specific 5mC and 5hmC alterations at CpG sites associated with AUD in the human orbitofrontal cortex (OFC). Neuronal nuclei from the OFC were evaluated in 34 human postmortem brain samples (10 AUD, 24 non-AUD). Reduced representation oxidative bisulfite sequencing was used to assess 5mC and 5hmC at the genome-wide level. Differential 5mC and 5hmC were evaluated using the methylKit R package and significance was set at false discovery rate <0.05 and differential methylation >2. Functional enrichment analyses were performed and replication was evaluated replication in an independent dataset that assessed 5mC and 5hmC of AUD in bulk cortical tissue. We identified 417 5mC and 363 5hmC genome-wide significant differential CpG sites associated with AUD, with 59% in gene promoters. We also identified genes previously implicated in alcohol consumption, such as SYK, CHRM2, DNMT3A, and GATA4, for 5mC and GATA4, and GAD1, GATA4, DLX1 for 5hmC. Replication was observed for 28 CpG sites from a previous AUD 5mC and 5hmC study, including FOXP1. Lastly, GWAS enrichment analysis showed an association with AUD for differential 5mC genes. This study reveals neuronal-specific methylome and hydroxymethylome dysregulation associated with AUD. We replicated previous findings and identified novel associations with AUD for both 5mC and 5hmC marks within the OFC. Our findings provide new insights into the epigenomic dysregulation of AUD in the human brain.

Comparative effectiveness and duration of protection of ChAdOx1, CoronaVac, BNT162b2, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines for symptomatic and hospitalized Mu, Delta, and Omicron: A test-negative case-control study.

OBJECTIVE: We carried out a study to estimate the vaccine effectiveness (VE) of homologous vaccination schedules against COVID-19, using data from mandatory information systems from Bogota, Colombia. METHODS: A test-negative case-control study in adults from Bogota (Colombia), between March 1st of 2021 and February 25th of 2022. We assess VE among symptomatic COVID-19 cases during the Mul, Delta, and Omicron predominance periods in Bogota, with controls matched by sex, age (±5 years), and date of testing (±7 days), using a case:control ratio of 1:1. We selected homologous vaccination schedules with ChAdOx1, CoronaVac, BNT162b2, mRNA-1273, and Ad26.COV2.S. VE was reported as one minus the odds ratio in adjusted conditional logistic regressions, with their 95% confidence intervals (CI). A p-value < 0.05 was considered statistically significant. RESULTS: 52,913 cases were matched to controls, 16,722 for Mu, 14,094 for Delta, and 22,097 for Omicron. VE was high against COVID-19 during Mu weeks with full vaccination using the monovalent BNT162b2 (VE: 69; 95% CI, 65 to 72) vaccine and ChAdOx1 (VE: 64; 95% CI, 31 to 81) and significantly lower with CoronaVac (P < 0.001) and Ad26.COV2.S (P = 0.005). During Delta, VE against COVID-19 was higher with BNT162b2 (VE: 55; 95% CI, 51 to 58). The VE for COVID-19 cases during Omicron was higher with a booster dose of monovalent BNT162b2 (VE: 45; 95% CI, 34 to 54). The VE of primary series and booster for ChAdOx1, Ad26.COV2.S, and CoronaVac did not show protection for Omicron. CONCLUSION: Our study provides further evidence on the protective effect of mRNA vaccines for Omicron, and warrant that the duration of protection against symptomatic infection may last for only a few months.

Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review.

Introduction: Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals. Methods: A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms. Results: Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species. Discussion: Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.

Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex.

Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD = 26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.

Decoding the role of transcriptomic clocks in the human prefrontal cortex.

Aging is a complex process with interindividual variability, which can be measured by aging biological clocks. Aging clocks are machine-learning algorithms guided by biological information and associated with mortality risk and a wide range of health outcomes. One of these aging clocks are transcriptomic clocks, which uses gene expression data to predict biological age; however, their functional role is unknown. Here, we profiled two transcriptomic clocks (RNAAgeCalc and knowledge-based deep neural network clock) in a large dataset of human postmortem prefrontal cortex (PFC) samples. We identified that deep-learning transcriptomic clock outperforms RNAAgeCalc to predict transcriptomic age in the human PFC. We identified associations of transcriptomic clocks with psychiatric-related traits. Further, we applied system biology algorithms to identify common gene networks among both clocks and performed pathways enrichment analyses to assess its functionality and prioritize genes involved in the aging processes. Identified gene networks showed enrichment for diseases of signal transduction by growth factor receptors and second messenger pathways. We also observed enrichment of genome-wide signals of mental and physical health outcomes and identified genes previously associated with human brain aging. Our findings suggest a link between transcriptomic aging and health disorders, including psychiatric traits. Further, it reveals functional genes within the human PFC that may play an important role in aging and health risk.

Maternal outcomes according to the type of placenta previa in a high complexity hospital in Cali, Colombia. Retrospective cohort study / Desenlaces maternos según el tipo de placenta previa en un hospital de alta complejidad en Cali, Colombia. Estudio de cohorte retrospectivo

Objectives: To describe the frequency of maternal complications in pregnant women with major or minor placenta previa (PP), and to assess a potential association between PP type and the presence of severe maternal bleeding and other associated outcomes. Materials and methods: Retrospective descriptive cohort. The study included pregnant women with 20 weeks of gestation or more and a confirmed diagnosis of placenta previa who were seen in a high complexity hospital in Cali (Colombia), between January 2011 and December 2020. Women with a diagnosis of placenta previa and concomitant placenta accreta were excluded. The collected variables were maternal age, body mass index, smoking, obesity, parity, presence of bleeding, postpartum hemorrhage, management of postpartum hemorrhage, transfusion, and maternal ICU admission. A descriptive analysis was performed. The protocol was approved by the ethics committee of Fundaciónn Valle de Lili. Results: A total of 146 patients met the inclusion criteria. The population consisted of women with a mean age of 32 years, with no history of prior surgery, with a prenatal diagnosis of placente previa at week 22; 70 % were major placenta previa cases. The most frequent complications were postpartum hemorrhage (37.9 % vs. 16.3 % for patients with major and minor placenta previa, respectively), transfusion requirement (23.3 and 9.3 %, respectively), and maternal ICU admission (40.8 % vs. 18.6 %, respectively). There were no cases of maternal death. Conclusions: There is a high frequency of complications in women with placenta previa, and it is probably higher in cases of major placenta previa. Further studies are needed to compare the frequency of maternal complications according to the type of placenta previa.

Objetivos: describir la frecuencia de complicaciones maternas en mujeres gestantes con placenta previa (PP) mayor o menor y evaluar una posible asociación entre tipo de PP y la presencia de hemorragia materna severa y otros resultados maternos asociados. Materiales y métodos: cohorte retrospectiva, descriptiva. Se incluyeron gestantes con 20 semanas o más de embarazo, con diagnóstico confirmado de placenta previa, quienes fueron atendidas en un hospital de alto nivel de complejidad localizado en Cali (Colombia), entre enero de 2011 y diciembre de 2020. Se excluyeron las gestantes con diagnóstico de placenta previa y acretismo placentario concomitante. Las variables recolectadas fueron: edad materna, índice de masa corporal, tabaquismo, obesidad, paridad, presencia de sangrado, hemorragia posparto, manejo de la hemorragia posparto, transfusión y admisión a UCI de la gestante. Se realizó análisis descriptivo. El protocolo fue aprobado por el comité de ética de la Fundación Valle de Lili. Resultados: 146 pacientes cumplieron con los criterios de inclusión. La población estuvo constituida por mujeres con una mediana de edad de 32 años, sin antecedente quirúrgico, con diagnóstico prenatal de placenta previa a la semana 22. En el 70,5 % de los casos se trató de pacientes con placenta previa mayor. Las complicaciones más frecuentes fueron hemorragia posparto (37,9 % vs. 16,3 % para pacientes con placenta previa mayor y menor, respectivamente), requerimiento de transfusión (23,3 y 9,3 %, respectivamente) y el ingreso materno a la UCI (40,8 % vs. 18,6 %, respectivamente). No se registraron muertes maternas. Conclusiones: las mujeres con placenta previa experimentan una frecuencia elevada de complicaciones; probablemente, dicha frecuencia es más alta cuando se documenta placenta previa mayor. Se requieren más estudios que comparen la frecuencia de complicaciones maternas según el tipo de placenta previa.

Desenlaces maternos según el tipo de placenta previa en un hospital de alta complejidad en Cali, Colombia. Estudio de cohorte retrospectivo / Maternal outcomes according to the type of placenta previa in a high complexity hospital in Cali, Colombia. Retrospective cohort study

Objetivos: Describir la frecuencia de complicaciones maternas en mujeres gestantes con placenta previa (PP) mayor o menor y evaluar una posible asociación entre tipo de PP y la presencia de hemorragia materna severa y otros resultados maternos asociados. Materiales y métodos: Cohorte retrospectiva, descriptiva. Se incluyeron gestantes con 20 semanas o más de embarazo, con diagnóstico confirmado de placenta previa, quienes fueron atendidas en un hospital de alto nivel de complejidad localizado en Cali (Colombia), entre enero de 2011 y diciembre de 2020. Se excluyeron las gestantes con diagnóstico de placenta previa y acretismo placentario concomitante. Las variables recolectadas fueron: edad materna, índice de masa corporal, tabaquismo, obesidad, paridad, presencia de sangrado, hemorragia posparto, manejo de la hemorragia posparto, transfusión y admisión a UCI de la gestante. Se realizó análisis descriptivo. El protocolo fue aprobado por el comité de ética de la Fundación Valle de Lili. Resultados: 146 pacientes cumplieron con los criterios de inclusión. La población estuvo constituida por mujeres con una mediana de edad de 32 años, sin antecedente quirúrgico, con diagnóstico prenatal de placenta previa a la semana 22. En el 70,5 % de los casos se trató de pacientes con placenta previa mayor. Las complicaciones más frecuentes fueron hemorragia posparto (37,9 % vs. 16,3 % para pacientes con placenta previa mayor y menor, respectivamente), requerimiento de transfusión (23,3 y 9,3 %, respectivamente) y el ingreso materno a la UCI (40,8 % vs. 18,6 %, respectivamente). No se registraron muertes maternas. Conclusiones: Las mujeres con placenta previa experimentan una frecuencia elevada de complicaciones; probablemente, dicha frecuencia es más alta cuando se documenta placenta previa mayor. Se requieren más estudios que comparen la frecuencia de complicaciones maternas según el tipo de placenta previa.

Objectives: To describe the frequency of maternal complications in pregnant women with major or minor placenta previa (PP), and to assess a potential association between PP type and the presence of severe maternal bleeding and other associated outcomes. Material and methods: Retrospective descriptive cohort. The study included pregnant women with 20 weeks of gestation or more and a confirmed diagnosis of placenta previa who were seen in a high complexity hospital in Cali (Colombia), between January 2011 and December 2020. Women with a diagnosis of placenta previa and concomitant placenta accreta were excluded. The collected variables were maternal age, body mass index, smoking, obesity, parity, presence of bleeding, postpartum hemorrhage, management of postpartum hemorrhage, transfusion, and maternal ICU admission. A descriptive analysis was performed. The protocol was approved by the ethics committee of Fundaciónn Valle de Lili. Results: A total of 146 patients met the inclusion criteria. The population consisted of women with a mean age of 32 years, with no history of prior surgery, with a prenatal diagnosis of placente previa at week 22; 70% were major placenta previa cases. The most frequent complications were postpartum hemorrhage (37.9 % vs. 16.3 % for patients with major and minor placenta previa, respectively), transfusion requirement (23.3 and 9.3 %, respectively), and maternal ICU admission (40.8 % vs. 18.6 %, respectively). There were no cases of maternal death. Conclusions: There is a high frequency of complications in women with placenta previa, and it is probably higher in cases of major placenta previa. Further studies are needed to compare the frequency of maternal complications according to the type of placenta previa.

Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

Central and Peripheral Immune Dysregulation in Posttraumatic Stress Disorder: Convergent Multi-Omics Evidence.

Posttraumatic stress disorder (PTSD) is a chronic and multifactorial disorder with a prevalence ranging between 6-10% in the general population and ~35% in individuals with high lifetime trauma exposure. Growing evidence indicates that the immune system may contribute to the etiology of PTSD, suggesting the inflammatory dysregulation as a hallmark feature of PTSD. However, the potential interplay between the central and peripheral immune system, as well as the biological mechanisms underlying this dysregulation remain poorly understood. The activation of the HPA axis after trauma exposure and the subsequent activation of the inflammatory system mediated by glucocorticoids is the most common mechanism that orchestrates an exacerbated immunological response in PTSD. Recent high-throughput analyses in peripheral and brain tissue from both humans with and animal models of PTSD have found that changes in gene regulation via epigenetic alterations may participate in the impaired inflammatory signaling in PTSD. The goal of this review is to assess the role of the inflammatory system in PTSD across tissue and species, with a particular focus on the genomics, transcriptomics, epigenomics, and proteomics domains. We conducted an integrative multi-omics approach identifying TNF (Tumor Necrosis Factor) signaling, interleukins, chemokines, Toll-like receptors and glucocorticoids among the common dysregulated pathways in both central and peripheral immune systems in PTSD and propose potential novel drug targets for PTSD treatment.

Mucopolysaccharidosis type IV: report of 5 cases of Morquio Syndrome.

Mucopolysaccharidosis type IV or Morquio Syndrome, is a lysosomal deposit disease, of autosomal recessive inheritance with a similar incidence in men and women. The clinical picture is of variable expressiveness, its phenotype is characterized by skeletal dysplasia that includes neck and short trunk, short stature, keel thorax, kyphosis, scoliosis, genus valgus, flat foot, coxa valga, gait disorders, instability of the cervical spine and wedge or ovoid vertebrae. The treatment is symptomatic, with enzyme replacement. We present a series of 5 cases, the product of 2 couples, with a confirmed diagnosis of Mucopolysaccharidosis type IV, and different clinical presentation.

CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder.

Introduction: DNA methylation (DNAm), an epigenetic mechanism, has been associated with opioid use disorder (OUD) in preclinical and human studies. However, most of the studies have focused on DNAm at CpG sites. DNAm at non-CpG sites (mCpHs, where H indicates A, T, or C) has been recently shown to have a role in gene regulation and to be highly abundant in neurons. However, its role in OUD is unknown. This work aims to evaluate mCpHs in the human postmortem orbital frontal cortex (OFC) in the context of OUD. Methods: A total of 38 Postmortem OFC samples were obtained from the VA Brain Bank (OUD = 12; Control = 26). mCpHs were assessed using reduced representation oxidative bisulfite sequencing in neuronal nuclei. Differential analysis was performed using the "methylkit" R package. Age, ancestry, postmortem interval, PTSD, and smoking status were included as covariates. Significant mCpHs were set at q-value < 0.05. Gene Ontology (GO) and KEGG enrichment analyses were performed for the annotated genes of all differential mCpH loci using String, ShinyGO, and amiGO software. Further, all annotated genes were analyzed using the Drug gene interaction database (DGIdb). Results: A total of 2,352 differentially methylated genome-wide significant mCpHs were identified in OUD, mapping to 2,081 genes. GO analysis of genes with differential mCpH loci showed enrichment for nervous system development (p-value = 2.32E-19). KEGG enrichment analysis identified axon guidance and glutamatergic synapse (FDR 9E-4-2.1E-2). Drug interaction analysis found 3,420 interactions between the annotated genes and drugs, identifying interactions with 15 opioid-related drugs, including lofexidine and tizanidine, both previously used for the treatment of OUD-related symptoms. Conclusion: Our findings suggest a role of mCpHs for OUD in cortical neurons and reveal important biological pathways and drug targets associated with the disorder.

Administración crónica de cafeína evita la alteración de la glucosa postprandial en ratas / Chronic caffeine administration prevents postprandial glucose disturbance in rats

La administración crónica de cafeína evita la alteración de la glucosa postprandial en ratas. El aumento en el consumo de la cafeína alrededor del mundo no es discutible, es así como su investigación se ha vuelto extensa en sus diferentes campos. Objetivo. Analizar los efectos de la administración crónica de cafeína en ratas alimentadas con dieta de cafetería, a través de evaluar índices de consumo, antropométricos y bioquímicos. Materiales y métodos. La dieta de cafetería es un modelo dietético equivalente a las características de la dieta occidental típica que origina síndrome metabólico en humanos. En esta investigación se realizó la administración crónica vía intraperitoneal de cafeína por ocho semanas a ratas adultas macho Wistar alimentadas con dieta de cafetería. Dada la poca evidencia acerca de los efectos biológicos y comportamentales de la administración crónica de dicha sustancia frente a un modelo de dieta de cafetería se evaluaron parámetros de consumo, antropométricos y bioquímicos. Resultados. La dieta de cafetería ocasionó anomalías asociadas al síndrome metabólico; no obstante, la administración de cafeína en las ratas alimentadas con esa dieta resultó ser un factor protector en la glucosa postprandial, más no en la alteración de la tolerancia a la glucosa o perfil lipídico. Conclusiones. La cafeína permitió proteger los niveles de glucosa postprandial al término del experimento y un descenso en el peso corporal y consumo de alimento solo en la primera semana. Sin embargo, no se observaron mejoras significativas en el perfil de lípidos, adiposidad, tolerancia a la glucosa y glucosa plasmática(AU)

Chronic caffeine administration prevents postprandial glucose disturbance in rats. The increase in caffeine consumption is not debatable, this is how his research has become extensive in his different fields. Objective. To analyze the effects of chronic administration of caffeine in rats fed a cafeteria diet, by evaluating consumption, anthropometric and biochemical indices. Previous studies refer to administering caffeine in diets high in carbohydrates and / or in fat that induce obesity or symptoms of metabolic syndrome. Material and methods. The cafeteria diet is a dietary model equivalent to the characteristics of the typical western diet that causes metabolic syndrome in humans. In this research, chronic intraperitoneal administration of caffeine was performed for 8 weeks to adult male Wistar rats fed a cafeteria diet. Given the little evidence about the biological and behavioral effects of the chronic administration of this substance against a cafeteria diet model, consumption, anthropometric and biochemical parameters were evaluated. Results. After eight weeks it was found that the cafeteria diet given to the controls caused abnormalities associated with the metabolic syndrome; regarding the administration of caffeine in the rats fed this diet, the treatment turned out to be a protective factor in postprandial glucose, but not in the alteration of glucose tolerance or lipid profile. Conclusions. Caffeine allowed to protect postprandial glucose levels at the end of the experiment and a decrease in body weight and food consumption only in the first week. However, no significant improvements were seen in lipid profile, adiposity, glucose tolerance, and plasma glucose(AU)

Association of Kidney Disease, Potassium, and Cardiovascular Risk Factor Prevalence with Coronary Arteriosclerotic Burden, by Sex.

The present study aimed to determine the relationship between the prevalence of cardiovascular risk factors and the number and severity of coronary artery atherosclerotic lesions obtained by coronary angiography. We reviewed and analyzed 1642 records from consecutive patients at the Catheter Laboratory of Talca Regional Hospital in Chile between March 2018 and May 2019. Patients were stratified according to the presence and severity of atherosclerotic lesions: 632 (38.5%) had no lesions or <30% stenosis and 1010 (61.5%) had at least one coronary atherosclerotic lesion with ≥30% stenosis (CALS-30). CALS-30 was more frequent in males, smokers, and patients with diabetes and/or hypertension (all p-values < 0.02). Serum potassium, glycaemia, creatinine and glomerular filtration rates were also associated with CALS-30 (all p-values < 0.01) in males. The age and the proportion of males with CALS-30 increased with the number of risk factors (p-values for trends < 0.001). Our results showed a stronger association between the accumulation of risk factors and CALS-30 in women than in men. Serum potassium levels were inversely associated with CALS-30 in men but not in women.

Diagnostic Criteria for Metabolic Syndrome in Diet-Induced Rodent Models: A Systematic Review.

BACKGROUND: Thousands of publications in recent years have addressed the induction of metabolic syndrome (MetS) in rodents. However, the criteria and the reference values for diagnosing this disease have not been defined. OBJECTIVE: Our main objective was to carry out a systematic review to gather evidence about the criteria for biochemical and anthropometric parameters in which scientific studies have relied on to report that rats developed MetS from a previous dietary manipulation. METHODS: We compiled characteristics and findings of diet-induced MetS with high-fat, high-carbohydrate, high-fat/high-carbohydrates, and cafeteria diet from PubMed and Science Direct databases published in the last 5 years. RESULTS: The results on the principal determinants for the syndrome, published in the reviewed articles, were chosen to propose reference values in the rat models of food induction. CONCLUSION: The values obtained will serve as reference cut-of points in the development of the disease; in addition, the compilation of data will be useful in planning and executing research protocols in animal models.

Melatonin Decreases Circulating Levels of Galectin-3 and Cytokines, Motor Activity, and Anxiety Following Acute Global Cerebral Ischemia in Male Rats.

BACKGROUND: Global cerebral ischemia (GCI) elicits damages to cerebral structures, learning dysfunction, memory impairments, hyperactivity, and anxiety. Circulating levels of galectin-3 (Gal-3) are associated with patient severity and outcome. AIM: To report circulating levels of Gal-3, and cytokines (TNF-α, IL-6, IL-10) in the initial hours (acute) following GCI in a four-vessel occlusion (4-VO) rat model and the effect of melatonin treatment. METHODS: 4-VO model was used to produce GCI using male Sprague-Dawley rats. Groups were: Sham-Veh, Sham-Mel, Isch-Veh and Isch-Mel. Melatonin was administered 30 min after carotid clamp removal. Gal-3 and cytokines levels were measured at 0, 30 min, 6 h and 24 h after the end of cerebral flow interruption using ELISA kits. Motor activity and anxiety were measured using open-field test. RESULTS: Acute GCI (AGCI) followed by reperfusion decreased serum concentrations of TNF-α and increased IL-6 levels 24 h after ischemia, whereas melatonin reduced significantly the concentrations of these cytokines. In all groups IL-10 was higher 30 min and negligible at other times. Circulating levels of Gal-3 were reduced 30 min after ischemia/reperfusion. In the Isch-Mel group the neuroprotective effect generated a reduction in circulating Gal-3 at 6 and 24 h after AGCI, compared with all the groups. Motor activity was increased due to ischemic reperfusion, but acute melatonin treatment reduced locomotion, similar to the control group. Anxiety was reduced in the melatonin group. CONCLUSIONS: Melatonin treatment following AGCI reduces pro-inflammatory factors, Gal-3, motility, and anxiety, therefore it should be considered as supplementary treatment following ischemic stroke.

Lactate: a biological marker of physical activity in colombian weightlifting athletes / Lactato: um marcador biológico da atividade física em atletas colombianos de halterofilismo / Lactato: un marcador biológico de la actividad física en atletas colombianos de halterofilia

ABSTRACT Introduction Blood biomarkers are measurable metabolic products that allow objective monitoring of the training process, and their analysis provides an opportunity to improve athletic performance. Objective To evaluate blood lactate concentrations in a group of the Valle League weightlifting athletes as a tool to determine the effects of training and its direct relationship to performance during competition. Methods This is an observational cross-sectional study. Lactate levels of 32 weightlifting athletes belonging to the Valle Weightlifting League were evaluated. Blood samples were taken from the ear lobe to quantify the lactate concentration, using a Scout Lactate analyzer. Samples were taken before and after a high intensity training section consisting of four maximum repetition (MR) sports gestures, in which 5 series and 15 repetitions were performed for each sports gesture, with a rest period of 40 seconds between each exercise. The software program SPSS, version 25, was used to determine the lactate concentrations. Results An average lactate concentration 22.46 mg/dL was obtained for the athletes at rest, and an average of 98.30 mg/dL in the final lactate concentration, after high intensity exercise. Significant differences were found between the initial and final lactate concentrations. Conclusion Lactate concentration increases with physical activity; it varies from one individual to another; and it can be used as a biomarker of intensity of physical activity in the field of sports. Level of evidence; II type of study: Prognostic Studies Investigating the Effect of a Patient Characteristic on a disease outcome.

RESUMO Introdução Os biomarcadores sanguíneos são produtos metabólicos mensuráveis que permitem a monitorização objetiva do processo de treino, e sua análise é uma oportunidade para melhorar o desempenho atlético. Objetivos Avaliar as concentrações de lactato no sangue de um grupo de atletas de halterofilismo da Liga Valle como ferramenta para determinar os efeitos do treino e sua relação direta com o desempenho durante a competição. Métodos Este é um estudo transversal e observacional. Foram avaliados os níveis de lactato em 32 atletas da Liga de Halterofilismo Valle. A amostra de sangue foi retirada do lóbulo da orelha com o intuito de quantificar a concentração de lactato com o analisador Scout Lactate. As amostras foram colhidas antes e depois de uma seção de treino de alta intensidade, que consistiu em quatro gestos esportivos de repetição máxima (RM), nos quais foram realizadas 5 séries e 15 repetições para cada gesto esportivo, com um período de repouso de 40 segundos entre cada exercício. O software SPSS, versão 25 foi usado para determinar as concentrações de lactato. Resultados A concentração média de lactato nos atletas em repouso foi 22,46 mg/dl e a concentração média final foi de 98,30 mg/dl depois de exercício de alta intensidade. Foram encontradas diferenças significativas ao comparar a concentração inicial com a concentração final de lactato. Conclusões A concentração de lactato aumenta com a realização da atividade física, é variável de um indivíduo para outro e pode ser usada como biomarcador de intensidade da atividade física na área dos esportes. Nível de Evidência II; Estudos prognósticos - Investigação do efeito de característica de um paciente sobre o desfecho da doença.

RESUMEN Introducción Los biomarcadores sanguíneos son productos metabólicos mensurables que permiten la monitorización objetiva del proceso de entrenamiento, y su análisis es una oportunidad para mejorar el desempeño atlético. Objetivos Evaluar las concentraciones de lactato en la sangre de un grupo de atletas de halterofilia de la Liga Valle como herramienta para determinar los efectos del entrenamiento y su relación directa con el desempeño durante la competición. Métodos Este es un estudio transversal y observacional. Fueron evaluados los niveles de lactato en 32 atletas de la Liga de Halterofilia Valle. La muestra de sangre fue retirada del lóbulo de la oreja con el objetivo de cuantificar la concentración de lactato con el analizador Scout Lactate. Las muestras fueron tomadas antes y después de una sección de entrenamiento de alta intensidad, que consistió en cuatro gestos deportivos de repetición máxima (RM), en los que se realizaron 5 series y 15 repeticiones para cada gesto deportivo, con un período de descanso de 40 segundos entre cada ejercicio. El software SPSS versión 25 fue usado para determinar las concentraciones de lactato. Resultados La concentración promedio de lactato en los atletas en reposo fue 22,46 mg/dl y la concentración promedio final fue de 98,30 mg/dl después del ejercicio de alta intensidad. Fueron encontradas diferencias significativas al comparar la concentración inicial con la concentración final de lactato. Conclusiones La concentración de lactato aumenta con la realización de actividad física, es variable de un individuo para otro, y puede ser usada como biomarcador de intensidad de la actividad física en el área de los deportes. Nivel de evidencia II; Estudios pronósticos - Investigación del efecto de característica de un paciente sobre el resultado de la enfermedad

Anticancer Effects of Extracts from Three Different Chokeberry Species.

Colon cancer risk appears to be lowered by consumption of a diet rich in fruits and vegetables. Chokeberries are rich in phytochemicals that may act as potent anticancer agents. Phytochemicals that are particularly abundant in chokeberries include anthocyanins and phenolic acids. In this study, we compared the growth inhibitory activity of three chokeberry extracts in HT-29 human colon cancer cells. The three extracts tested were derived from Aronia arbutifolia (red), Aronia prunifolia (purple), and Aronia melanocarpa (black). Cells were incubated with either red, purple, or black chokeberry extracts and cell viability was quantified using the thiazolyl blue tetrazolium bromide (MTT) assay. The black chokeberry extract had the greatest effect in reducing cell proliferation. The extracts were also characterized for total phenols (Folin-Ciocalteu assay), total antioxidant activity (oxygen radical absorbance capacity assay), and levels of bioactive phenolic acids (high-performance liquid chromatography). The growth inhibitory activities of the extracts correlated well with total phenolic content, antioxidant activity, and levels of caffeic and chlorogenic acids. The black chokeberry extract had the greatest level of total phenols, antioxidant activity, and individual phenolic acids. This research suggests that the phenolic profile of foods such as chokeberries can help determine their cancer cell growth inhibitory activity.

[Nutritional strategies in the management of patients with diabetes mellitus]. / Estrategias nutricionales en el tratamiento del paciente con diabetes mellitus.

Diabetes mellitus is a highly prevalent disease in the world and in Mexico. Due to its chronic evolution it causes multiple sequelae, disability and mortality. An adequate control of diabetic patients based on reaching glycemic targets, maintenance of healthy weight, as well as lipid and blood pressure control is essential to reduce the risk of progression of its complications. Lifestyle changes are also key for preventing and treating the disease. Knowledge of the relationship and mechanism involved between diabetes and alterations in nutrient metabolism should be considered to provide an adequate nutritional program. This article aims to bring healthcare professionals the concepts and strategies, proposed by several scientific societies, about nutritional management of adult patients with diabetes mellitus.

La diabetes mellitus es una enfermedad altamente prevalente en el mundo y en México. Debido a su evolución crónica, es también causa de múltiples secuelas, discapacidad y mortalidad. Un adecuado control del paciente diabético que se logre a partir de metas de glucemia, mantenimiento de peso sano, así como control de lípidos y presión arterial es indispensable a fin de disminuir el riesgo de progresión de las complicaciones de la diabetes mellitus. Los cambios en el estilo de vida son clave en la prevención y el tratamiento de la enfermedad. El conocimiento de la relación y el mecanismo involucrados entre la diabetes y las alteraciones en el metabolismo de los nutrientes debe ser considerado para brindar un programa nutricional adecuado. Este artículo pretende aproximar a los profesionales de la salud los conceptos y las estrategias nutricionales actuales, propuestos por diversas sociedades científicas, para el manejo nutricional de pacientes adultos con diabetes mellitus.