RESUMEN

A 25-year-old man with no medical history presented with a seizure one month after taking a self-administered dose of albendazole. Magnetic resonance imaging (MRI) of the brain revealed multiple ring-enhancing lesions, and the workup confirmed neurocysticercosis (NCC). Treatment with antiparasitics was delayed due to concern for worsening symptoms from the presence of cysts in the midbrain and hippocampus. The balance between treating NCC and limiting cerebral inflammation is delicate and relies on judgment from a multispecialty clinical team. In this case, corticosteroids and antiepileptics alone prevented additional seizures but failed to reduce the overall inflammation of cysts and the progression of the disease. Evidence of new cysts on MRI at week 13 from the onset of symptoms was evidence of an acute, evolving infectious process. Treatment with albendazole and praziquantel was initiated at 13 weeks from the onset of symptoms, and by 31 weeks, nearly all cysts had resolved with minimal residual inflammation.

RESUMEN

FlyBase (flybase.org) is an essential online database for researchers using Drosophila melanogaster as a model organism, facilitating access to a diverse array of information that includes genetic, molecular, genomic and reagent resources. Here, we describe the introduction of several new features at FlyBase, including Pathway Reports, paralog information, disease models based on orthology, customizable tables within reports and overview displays ('ribbons') of expression and disease data. We also describe a variety of recent important updates, including incorporation of a developmental proteome, upgrades to the GAL4 search tab, additional Experimental Tool Reports, migration to JBrowse for genome browsing and improvements to batch queries/downloads and the Fast-Track Your Paper tool.

Asunto(s)

RESUMEN

The catalytic activities of enzymes can be described using Gene Ontology (GO) terms and Enzyme Commission (EC) numbers. These annotations are available from numerous biological databases and are routinely accessed by researchers and bioinformaticians to direct their work. However, enzyme data may not be congruent between different resources, while the origin, quality and genomic coverage of these data within any one resource are often unclear. GO/EC annotations are assigned either manually by expert curators or inferred computationally, and there is potential for errors in both types of annotation. If such errors remain unchecked, false positive annotations may be propagated across multiple resources, significantly degrading the quality and usefulness of these data. Similarly, the absence of annotations (false negatives) from any one resource can lead to incorrect inferences or conclusions. We are systematically reviewing and enhancing the functional annotation of the enzymes of Drosophila melanogaster, focusing on improvements within the FlyBase (www.flybase.org) database. We have reviewed four major enzyme groups to date: oxidoreductases, lyases, isomerases and ligases. Herein, we describe our review workflow, the improvement in the quality and coverage of enzyme annotations within FlyBase and the wider impact of our work on other related databases.

Asunto(s)

RESUMEN

BACKGROUND: Despite modern advances in surgical care, triple-valve surgery (TVS) remains a challenge and carries a mortality of 10% to 20%. No validated risk score is available for TVS, and the effect of advanced age is unknown. This study examined our results in the modern era with the aim of identifying perioperative predictors of adverse outcomes. METHODS: Between 1997 and 2013, 131 patients (mean age, 67.2±13.4 years) underwent TVS at our institution. Sixty-eight patients (51.9%) were aged 70 years and older. The most common etiology for aortic and mitral disease was degenerative (77.1%), rheumatic (10%), and endocarditis or prosthetic-related, or both, in the rest. Tricuspid valve disease was functional in 96%. New York Heart Association functional class III/IV was present in 69.4%, and 24% had had previous cardiac operations. One or more concomitant cardiac procedures were performed in 77 patients (58.8%), including coronary revascularization in 54. All aortic procedures were replacements, 14 patients required a prosthetic root conduit and 7 thoracic aorta replacement. Mitral replacements were used in 55%, repairs in 45%, and 96.2% of tricuspid procedures were repairs. Univariate and multivariate analyses were used to determine predictors of adverse outcomes. RESULTS: The 30-day and hospital mortality was 10.6% (n=14). Major complications occurred in 70 (53.4%). Univariate analysis identified New York Heart Association functional class III/IV (p=0.04), preoperative renal failure requiring dialysis (p=0.04), urgent operation (p=0.04), intraaortic balloon pump placement (p=0.02), and postoperative low cardiac output (p<0.0001) as predictors for early death. Proximal aortic operations, urgent operation, and New York Heart Association class IV correlated with increased early mortality (p<0.04) in patients aged 70 and older in addition to their decreased overall survival and decreased likelihood of discharge to home. Overall actuarial survival at 1, 5, and 10 years was 84.5%, 75%, and 45%, respectively. CONCLUSIONS: TVS remains a surgical challenge in the modern era. Despite a trend of increasing age and surgical risk, the early mortality rate and long-term survival remain respectable. Advanced age is associated with increased perioperative risk, but age per se should not be a contraindication for TVS.

Asunto(s)

RESUMEN

Se prepararon comprimidos matriciales de liberación prolongada de clorhidrato de ambroxol con diversas proporciones de fármaco: polímero tales como F-1(1:1), F-2(1:1,5) y F-3 (1:2). Se utilizó goma xántica para la formación de la matriz y celulosa microcristalina como diluyente. Se prepararon y evaluaron gránulos para determinar la densidad aparente sin compactar, la densidad compactada, el índice de compresibilidad, el índice de Hausner y el ángulo de reposo. Todos los gránulos se lubricaron y comprimieron con punzones planos de 9 mm. Los comprimidos se evaluaron para determinar la uniformidad de peso, el contenido de principios activos, la friabilidad, la dureza y la disolución in vitro. Todas las formulaciones se ajustaron a los estándares farmacopeicos. F-3 mostró una liberación prolongada de fármaco durante 12 horas con una liberación del 97,3% y el perfi l de liberación fue similar al de la muestra de clorhidrato de ambroxol comercial (A-MS). Además, se realizaron estudios de estabilidad según la guía ICH. La liberación de fármaco sigue cinéticas de orden cero (0,9661) y se determinó que el mecanismo era difusión combinada con erosión (AU)

Sustained release matrix tablets of ambroxol hydrochloride of different drug: polymer ratios, such as F-1(1:1), F- 2(1:1.5) and F-3 (1:2). Xanthan gum was used as matrix former and microcrystalline cellulose was used as diluent. Granules were prepared and evaluated for loose bulk density, tapped density, compressibility index, hausners ratio and angle of repose. All the granules were lubricated and compressed using 9mm fl at-faced punches. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness and In-vitro dissolution. All the formulations showed compliance with Pharmacopoeial standards. F-3 showed the sustained release of drug for 12 hours with 97.3% release and the release profi le was close to the marketed sample of ambroxol hydrochloride (A-MS) and Stability studies were performed as per ICH guide. The drug release follows zero order kinetics (0.9661) and the mechanism was found to be diffusion coupled with erosion (AU)

Asunto(s)