Introduction:We investigated frameshift suppressor tRNAs previously reported to use five-base anticodon-codon interactions in order to provide a collection of frameshift suppressor tRNAs to the synthetic biology community and to develop modular frameshift suppressor logic devices for use in synthetic biology applications.Results and Discussion: We adapted eleven previously described frameshift suppressor tRNAs to the BioBrick cloning format, and built three genetic logic circuits to detect frameshift suppression. The three circuits employed three different mechanisms: direct frameshift suppression of reporter gene mutations, frameshift suppression leading to positive feedback via quorum sensing, and enzymatic amplification of frameshift suppression signals. In the course of testing frameshift suppressor logic, we uncovered unexpected behavior in the frameshift suppressor tRNAs. The results led us to posit a fourbase binding hypothesis for the frameshift suppressor tRNA interactions with mRNA as an alternative to the published five-base binding model. Conclusion and Prospects:The published five-base anticodon/codon rule explained only 17 of the 58 frameshift suppression experiments we conducted. Our deduced fourbase binding rule successfully explained 56 out of our 58 frameshift suppression results. In the process of applying biological knowledge about frameshift suppressor tRNAs to the engineering application of frameshift suppressor logic, we discovered new biological knowledge. This knowledge leads to a redesign of the original engineering application and encourages new ones. Our study reinforces the concept that synthetic biology is often a winding path from science to engineering and back again; scientific investigations spark engineering applications, the implementation of which suggests new scientific investigations.
Background: The association between obesity and a reduction in life expectancy is well established, and cardiovascular disease is a leading cause of mortality. Bariatric surgery has long been established as the most effective and durable intervention for obesity, and is the only intervention for obesity that consistently improves multiple comorbidities, reduces cardiovascular disease and long-term mortality. The purpose of this review article is to describe the impact of metabolic/bariatric surgery on type 2 diabetes mellitus and cardiometabolic parameters, including cardiovascular mortality. Methods: A systematic literature search of Pubmed, MEDLINE, and Cochrane Central Register was performed. We included randomized controlled trials, metanalysis, case-control trials, and cohort studies that contain data on reductions in cardiovascular risk factors and cardiovascular mortality in subjects who underwent metabolic/bariatric surgery from January 1, 2005, to June 1, 2020. Conclusion: There is sufficient evidence of randomized controlled trials that metabolic/bariatric surgery is associated with a significant improvement of all cardiovascular risk factors. Although studies are showing a reduction of macrovascular events and cardiovascular mortality, these findings come from observational studies and should be confirmed in randomized clinical trials.
Introducción: la diabetes constituye una entidad que aumenta significativamente la morbimortalidad cardiovascular. De acuerdo con los datos de la Cuarta Encuesta Nacional de Factores de Riesgo (ENFR), la prevalencia de glucemia elevada o diabetes aumentó de 9,8% en 2013 a 12,7% en 2018, siendo la obesidad uno de los principales factores de riesgo asociados, cuya prevalencia incrementó más del 70% en los últimos 15 años. Se pronostica acorde a la Federación Internacional de Diabetes (IDF) que al menos 578 millones de personas tendrán diabetes en el año 2030.Objetivos: describir los datos hallados en una encuesta de detección de factores de riesgo cardiovascular y alteraciones en el metabolismo de los hidratos de carbono en el marco del Día Internacional de la Diabetes realizada el día 14 de noviembre de 2019.Materiales y métodos: estudio descriptivo de corte transversal de los datos obtenidos durante la campaña realizada el 14 de noviembre de 2019 en una institución de Buenos Aires, la cual se desarrolló de manera interdisciplinaria entre personal médico del servicio de diabetes, personal de enfermería y estudiantes del servicio de nutrición.La misma que consistió en invitar a participar voluntariamente a sujetos ambulatorios que se encontraban en la cercanía del centro médico y brindaron su consentimiento verbal, a quienes: 1)se realizó una encuesta (sobre hábitos, antecedentes de diabetes, hipertensión arterial (HTA), enfermedad cardiovascular (ECV), enfermedad renal (ER); 2)se tomaron medidas antropométricas (peso, talla, circunferencia de cintura [CC]); 3) se realizó medición capilar de glucemia mediante un refractómetros para glucosa. Para este reporte se incluyeron los sujetos que cumplieron con la realización de los procedimientos 1 y 2 enlistados previamente. Las variables categóricas se describen como porcentaje, las variables cuantitativas como mediana/RIQ acorde la distribución de los datos.
Hypoglycemia may exert proarrhythmogenic effects on the heart and insulin induced hypoglycemia has been considered responsible for nocturnal death in diabetic patients. Even so hypoglycemia associated fatal cardiac arrhythmia is difficult to document. Objective: examined the effect of hypoglycemia on episodes of arrhythmias and cardiac repolarization disorders in diabetic mellitus (DM) patients. Design and Methods: prospective study in which we included 30 subjects with DM who underwent of simultaneous ambulatory 24 hours electrocardiographic holter and continuous interstitial glucose monitoring (FREE STYLE system). Inclusion criteria: men and women > or = 50 years old with a type 2 insulin-treated DM and 2 or more major cardiovascular risk factors (hypertension, dyslipidemia, active smoking, overweight or obesity) or subjects older than 18 years old with a history of type 1 DM of more than 10 years who sign an informed consent. Exclusion criteria: pacemakers, treatment with drugs that prolong QT, chronic atrial fibrillation or branch blocks, previous stroke, heart failure stage III-IV, Wolf Parkinson White Syndrome. Results: A total of 30 patients with DM participated in this study; 14 patients with type 1 DM (46.67%) and 16 patients with type 2 DM (53.33%). Within the group of type 1 DM, 61.54% presented hypoglycemic events vs. 56.25% of the patients in type 2 DM group, (p= 0.774) which correlates with the increased risk of hypoglycemic events in type 1 DM group. A total of 60% of the patients presented hypoglycemic events (n= 18) independently of glucose levels, and 40% of the patients (n=12) did not present it. Most of the hypoglycemic events (72.22% p=0.035) did not correlate with an arrhythmia event or cardiac repolarization disorder. Conclusions: In our group of patients, high cardiovascular risks and long-term duration of type 1 or type 2 DM were strong enough factors to develop arrhythmia, independently of glucose levels. Maybe it would be necessary to study patients with a 48-hour holter in order to find out this association. Disclosure C. Musso: None. N.S. Sforza: None. Y.J. Morosan Allo: None. R.G. Clemente: None. A. Pavesi: None. C.C. Folino: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc.
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