Epigenetic Factors Impacting Type 2 Diabetes in American Indians

American Indians have been found to be at higher risk of type 2 diabetes (T2D) than any other ethnic or racial groups in the United States, with an estimated prevalence rate of 33%. Given that T2D prevalence rates amongst the American Indian population are so high, studying the complex factors that contribute to T2D is crucial. Of particular importance to this study is identifying heritable effects involved in development of T2D. Epigenetic effects, heritable changes to DNA that affect gene expression such as DNA methylation (DNAm), have been shown to be associated with T2D phenotypes. Studies in other subpopulations have previously identified differential DNAm at the ABCG1 gene as being associated with T2D. ABCG1 plays a significant role in promoting cholesterol efflux, and it has been associated with T2D and related traits. As such, we sought to determine whether those results generalized to American Indians by assaying DNAm at ABCG1 within a sample population of 285 American Indian participants in the Strong Heart Study (SHS). In verifying whether there is a significant association between DNAm levels and T2D, we hypothesize that individuals diagnosed with T2D will have higher rates of DNAm at loci in ABCG1 than individuals who do not have T2D. Ultimately, we hope the results of this experiment can provide more insight on the role that differential DNAm has to play in the risk and development of T2D

Oleic acid induces migration through a FFAR1/4, EGFR and AKT-dependent pathway in breast cancer cells

Free fatty acids (FFAs) are an energy source, and induce activation of signal transduction pathways that mediate several biological processes. In breast cancer cells, oleic acid (OA) induces proliferation, matrix metalloproteinase-9 (MMP-9) secretion, migration and invasion. However, the signal transduction pathways that mediate migration and invasion induced by OA in breast cancer cells have not been studied in detail. We demonstrate here that FFAR1 and FFAR4 mediate migration induced by OA in MDA-MB-231 and MCF-7 breast cancer cells. Moreover, OA induces migration, invasion, AKT1 and AKT2 activation, 12-LOX secretion and an increase of NFκB-DNA binding activity in breast cancer cells. Cell migration requires FFAR1, FFAR4, EGFR, AKT and PI3K activity, whereas invasion is mediated though a PI3K/Akt-dependent pathway. Furthermore, OA promotes relocalization of paxillin to focal contacts and it requires PI3K and EGFR activity, whereas NFκB-DNA binding activity requires PI3K and AKT activity

Metastatic pheochromocytoma to liver without elevation of metanephrines and catecholamines

AbstractIntroductionMalignant pheochromocytoma represents 10% of all patients with pheochromocytoma. Of these cases, only 5–9% presents without elevation of metanephrines and catecholamines.Presentation of caseA 43-year-old female patient presented with an abdominal tumor. An exploratory laparotomy was performed and the final report was a pheochromocytoma. After ten years, multiple liver lesions were detected and surgical treatment was performed. Pathological evaluation revealed a malignant pheochromocytoma with negative margins after 5 years of follow-up without evidence of disease.DiscussionThe recurrence rate of malignant pheochromocytoma is 15–20% at ten years and a 5-year survival rate that ranges from 50% to 80%. The presence of synchronous metastases is rare (10–27%), but have been reported until 20 years later with the most common metastatic sites being the local lymph nodes, bone (50%), liver (50%) and lung (30%). The prognostic factor such as size >6cm, age over 45 years, synchronous metastasis and no tumor excision are related with poor prognosis.ConclusionSurgical treatment offers the best survival rate and the only chance of cure so far and the goal is an R0 resection as in our case. So it should be the treatment of choice

Formulación mixta de bacterias lácticas para el control de Listeria monocytogenes

La combinación de la actividad metabólica de cepas bacterianas potencializa la actividad antimicrobiana contra microorganismos patógenos, en comparación con la actividad que pueden presentar las cepas microbianas en forma individual. La formulación mixta de bacterias acido lácticas ha sido estudiada para la producción de preparados probióticos con actividad antimicrobiana contra patógenos. Listeria monocytogenes es considerado un microorganismo patógeno para el hombre y animales, causando principalmente, la enfermedad conocida como listeriosis. Se evaluó la actividad antimicrobiana de una formulación mixta de Lactobacillus brevis y Weisella cibaria frente a Listeria monocytogenes. L. brevis y W. cibaria se reprodujeron por fermentaciones en discontinuo durante 48 horas. Se midió la cinética de la actividad antimicrobiana contra L. monocytogenes en los siguientes tiempos de fermentación, 0, 1, 2, 6, 12, 24 y 48 horas. En cada tiempo, la actividad antimicrobiana de la mezcla de cepas se comparó con la actividad antimicrobiana de las cepas en forma individual. La actividad antimicrobiana se midió mediante el diámetro de Feret, utilizando un software de evaluación de imágenes. Se encontró que la actividad antimicrobiana de la mezcla de cepas contra L. monocytogenes fue estable desde la segunda hora de fermentación hasta las 48 horas. A partir de 18 horas de fermentación la mezcla de cepas presentó actividad antimicrobiana superior, comparada con las cepas individuales. Los resultados indican que la formulación mixta de L. brevis y W. cibaria podría ser una opción biotecnológica para el desarrollo de antimicrobianos naturales para el control y prevención de L. monocytogenes.The combination of the metabolic activity of bacterial strains potentiates the antimicrobial activity against pathogenic microorganisms, in comparison with the activity that the microbial strains can present individually. The mixed formulation of lactic acid bacteria has been studied to the production of probiotic preparations with antimicrobial activity against pathogens. Listeria monocytogenes is considered a pathogenic microorganism for man and animals, causing the disease known as listeriosis. The antimicrobial activity of a mixed formulation of Lactobacillus brevis and Weisella cibaria was evaluated against Listeria monocytogenes. L. brevis and W. cibaria were reproduced by discontinuous fermentations for 48 hours. The kinetics of antimicrobial activity against L. monocytogenes were measured at the next fermentation times, 0, 1, 2, 6, 12, 24 and 48 hours. At each time, the antimicrobial activity of the mixed formulation was compared with the antimicrobial activity of the strains individually. The antimicrobial activity was measured by Feret's diameter, using image evaluation software. It was found that the antimicrobial activity of the mixed formulation against L. monocytogenes was stable from the second hour of fermentation to 48 hours of fermentation. After 18 hours of fermentation the mixed formulation presented superior antimicrobial activity, compared to the individual strains. The results indicate that the mixed formulation of L. brevis and W. cibaria could be a biotechnological option for the development of natural antimicrobials for the control and prevention of L. monocytogenes

Estado del Arte de la Investigación en Educación, Pedagogía, Didáctica, Aportes teóricos a las discusiones educativas sobre la diversidad, y Diversidad en procesos de aprendizaje y transformación de la escuela en la MEVI – 2018 - 2021.

Elaborar un estado del arte de la investigación en la MEVI en relación con la educación, la pedagogía, la didáctica, los aportes teóricos a las discusiones educativas sobre la diversidad y la diversidad en procesos de aprendizaje y transformación de la escuela entre 2018 y 2021El presente estado del arte evidencia los intereses investigativos y las conceptualizaciones derivadas en el campo de la educación la pedagogía, la didáctica, los aportes teóricos a las discusiones educativas sobre la diversidad y la diversidad en procesos de aprendizaje y transformación de la escuela, en las investigaciones realizadas en el programa de Maestría en Educación Virtual (en adelante MEVI), de la Corporación Universitaria Minuto de Dios ( en adelante UNIMINUTO), entre los años 2018 y 2021. Este proyecto sombrilla, se desarrolla bajo la sub-línea de Procesos educativos para la diversidad y la transformación cultural se realiza bajo un enfoque cualitativo descriptivo a partir de una selección aleatoria de 160 tesis de la MEVI. En el capítulo 1 se presenta una contextualización sobre el proceso investigativo dentro de la MEVI. También, se presentan los estudios nacionales e internacionales relacionados con la investigación; al tiempo que se presenta en detalle el planteamiento de objetivos con la intención de lograr categorías de estudio

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years