Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Metodología para el análisis de problemas y limitaciones en emprendimientos universitarios

Los emprendimientos universitarios se caracterizan por ser una actividad de alto riesgo, debido al elevado número de factores que influyen en su desarrollo, ya sean sociales, económicos o tecnológicos. A estos factores, se suma la inexperiencia de los emprendedores universitarios en la utilización de métodos, técnicas y herramientas, que les permitan alcanzar el éxito. Por ello, la definición adecuada de una estrategia es relevante, con miras a aumentar las posibilidades de éxito de un emprendimiento, además de ayudar a atenuar y disminuir el riesgo de este. Sin embargo, los emprendedores universitarios no siempre cuentan con las capacidades y el conocimiento necesario que les permita crear un análisis apropiado, lo que trae como consecuencia una mayor dificultad en el proceso de obtención de información relevante, así como en la planificación de sus actividades y de los recursos que posee. Frente a esta problemática, el proceso de enseñanza de los emprendedores requiere de nuevas herramientas, técnicas y métodos que les permitan evaluar y anticipar problemas, con el fin de disminuir el riesgo futuro de su emprendimiento. Teniendo en cuenta esta premisa, este artículo presenta una metodología estructurada, que tiene como objetivo contextualizar y analizar un emprendimiento universitario, pero teniendo en cuenta para ello los recursos reales que este posee, junto a la priorización de soluciones que los emprendedores puedan aplicar, con base en la teoría de resolución de problemas de inventiva

Metodología para el análisis de problemas y limitaciones en emprendimientos universitarios

Los emprendimientos universitarios se caracterizan por ser una actividad de alto riesgo, debido al elevado número de factores que influyen en su desarrollo, ya sean sociales, económicos o tecnológicos. A estos factores, se suma la inexperiencia de los emprendedores universitarios en la utilización de métodos, técnicas y herramientas, que les permitan alcanzar el éxito. Por ello, la definición adecuada de una estrategia es relevante, con miras a aumentar las posibilidades de éxito de un emprendimiento, además de ayudar a atenuar y disminuir el riesgo de este. Sin embargo, los emprendedores universitarios no siempre cuentan con las capacidades y el conocimiento necesario que les permita crear un análisis apropiado, lo que trae como consecuencia una mayor dificultad en el proceso de obtención de información relevante, así como en la planificación de sus actividades y de los recursos que posee. Frente a esta problemática, el proceso de enseñanza de los emprendedores requiere de nuevas herramientas, técnicas y métodos que les permitan evaluar y anticipar problemas, con el fin de disminuir el riesgo futuro de su emprendimiento. Teniendo en cuenta esta premisa, este artículo presenta una metodología estructurada, que tiene como objetivo contextualizar y analizar un emprendimiento universitario, pero teniendo en cuenta para ello los recursos reales que este posee, junto a la priorización de soluciones que los emprendedores puedan aplicar, con base en la teoría de resolución de problemas de inventiva

Increased C-reactive protein plasma levels are not involved in the onset of post-operative atrial fibrillation

Background: Increased inflammation biomarkers plasma levels, including C-reactive protein (CRP), have been associated with the initiation and perpetuation of atrial fibrillation (AF). However, it is not known whether an increased CRP plasma level, without concomitant inflammation, is sufficient to induce AF. We investigated whether higher CRP plasma levels, determined by the presence of +219G>A CRP gene polymorphism, is associated with an increased risk of post-operative AF. Methods: One hundred and fifteen adult patients submitted to elective coronary surgery were genotyped for the CRP +219G>A polymorphism. CRP plasma levels were determined by enzyme-linked immunosorbent assay. Results: CRP plasma levels before surgery were higher in GG than in GA + AA patients (3.4 +/- 3.1 vs. 1.7 +/- 1.8, p < 0.015). Thirteen percent of the patients presented post-operative AF. Despite the positive correlation between the polymorphism and CRP levels, there was no significant difference in the occurrence of post-operative AF between the different genotypes. Conclusions: These results suggest that increased CRP plasma levels that are not associated with an inflammatory process are not sufficient to trigger AF after cardiac surgery

Herpud1 negatively regulates pathological cardiac hypertrophy by inducing IP3 receptor degradation

Cardiac hypertrophy is an adaptive response triggered by pathological stimuli. Regulation of the synthesis and the degradation of the Ca2+ channel inositol 1,4,5-trisphosphate receptor (IP3R) affects progression to cardiac hypertrophy. Herpud1, a component of the endoplasmic reticulum-associated degradation (ERAD) complex, participates in IP3R1 degradation and Ca2+ signaling, but the cardiac function of Herpud1 remains unknown. We hypothesize that Herpud1 acts as a negative regulator of cardiac hypertrophy by regulating IP3R protein levels. Our results show that Herpud1-knockout mice exhibit cardiac hypertrophy and dysfunction and that decreased Herpud1 protein levels lead to elevated levels of hypertrophic markers in cultured rat cardiomyocytes. In addition, IP3R levels were elevated both in Herpud1-knockout mice and Herpud1 siRNA-treated rat cardiomyocytes. The latter treatment also led to elevated cytosolic and nuclear Ca2+ levels. In summary, the absence of Herpud1 generates a pathological hypertrophic phenotype by regulating IP3R protein levels. Herpud1 is a novel negative regulator of pathological cardiac hypertrophy.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT, Chile) Fondo de Financiamiento de Centros de Investigacion en Areas Prioritarias (FONDAP) 15130011 Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) 1161156 Japan Society for the Promotion of Scienc

Herpudl impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis

Skeletal muscle plays a central role in insulin-controlled glucose homeostasis. The molecular mechanisms related to insulin resistance in this tissue are incompletely understood. Herpud1 is an endoplasmic reticulum membrane protein that maintains intracellular Cat homeostasis under stress conditions. It has recently been reported that Herpudl-knockout mice display intolerance to a glucose load without showing altered insulin secretion. The functions of Herpud1 in skeletal muscle also remain unknown. Based on these findings, we propose that Herpud1 is necessary for insulin-dependent glucose disposal in skeletal muscle. Here we show that Herpudl silencing decreased insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane, and Akt Ser(473) phosphorylation in cultured L6 myotubes. A decrease in insulin-induced Akt Ser(473) phosphorylation was observed in soleus but not in extensor digitorum longus muscle samples from Herpudl-knockout mice. Herpudl knockdown increased the IP3R-dependent cytosolic Cat response and the activity of Ca2+-dependent serine/threonine phosphatase calcineurin in L6 cells. Calcineurin decreased insulin-dependent Akt phosphorylation and glucose uptake. Moreover, calcineurin inhibition restored the insulin response in Herpudl-depleted L6 cells. Based on these findings, we conclude that Herpudl is necessary for adequate insulin-induced glucose uptake due to its role in Ca2+/calcineurin regulation in L6 myotubes.Fondo Nacional de Investigacion Cientifica y Tecnologica (FONDECYT) 1161156 11130285 170032 Fondo de Financiamiento de Centros de Investigacion en Areas Prioritarias (FONDAP) 15130011 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT), Chil

Prevalence of hearing loss and clinical otologic manifestations in patients with 22q11.2 deletion syndrome : A literature review

Background: Hearing loss and otitis media are frequently reported in patients with 22q11.2 deletion syndrome. Objective of review: Our objective was to review the current literature on the prevalence of hearing loss and otologic manifestations in patients with 22q11.2 deletion syndrome. Type of review: Systematic review. Search strategy: We conducted a systematic search in PubMed and Embase combining the term “22q11.2 deletion syndrome” and synonyms with “hearing loss” and “otologic manifestations” and synonyms. Evaluation method: We screened title/abstract and full text of all retrieved articles on pre-defined in- and exclusion criteria. The remaining articles were assessed on risk of bias. Outcome measures included the prevalence of hearing loss and otologic manifestations such as otitis media. Results: Our search yielded 558 unique studies of which a total of 25 articles were included for critical appraisal and data extraction. Twenty-one studies reported on hearing loss, and 21 studies on otologic manifestations. The prevalence of hearing loss varied from 6.0% to 60.3%, where in most studies conductive hearing loss was most prevalent. Rates of recurrent or chronic otitis media varied from 2.2% to 89.8%. Conclusion: Although a very broad range in prevalences is reported in different studies, hearing loss and recurrent or chronic otitis media are frequently present in patients with 22q11.2 deletion syndrome. Regular check-ups and audiometric testing are advised in these patients