MicroRNA Predictors of Longevity in Caenorhabditis elegans

Neither genetic nor environmental factors fully account for variability in individual longevity: genetically identical invertebrates in homogenous environments often experience no less variability in lifespan than outbred human populations. Such variability is often assumed to result from stochasticity in damage accumulation over time; however, the identification of early-life gene expression states that predict future longevity would suggest that lifespan is least in part epigenetically determined. Such “biomarkers of aging,” genetic or otherwise, nevertheless remain rare. In this work, we sought early-life differences in organismal robustness in unperturbed individuals and examined the utility of microRNAs, known regulators of lifespan, development, and robustness, as aging biomarkers. We quantitatively examined Caenorhabditis elegans reared individually in a novel apparatus and observed throughout their lives. Early-to-mid–adulthood measures of homeostatic ability jointly predict 62% of longevity variability. Though correlated, markers of growth/muscle maintenance and of metabolic by-products (“age pigments”) report independently on lifespan, suggesting that graceful aging is not a single process. We further identified three microRNAs in which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti-correlates. Two of these three microRNA “biomarkers of aging” act upstream in insulin/IGF-1–like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan

Binary Classification Using Pairs of Minimum Spanning Trees or N-Ary Trees

One-class classifiers are trained only with target class samples. Intuitively, their conservative modeling of the class description may benefit classical classification tasks where classes are difficult to separate due to overlapping and data imbalance. In this work, three methods leveraging on the combination of one-class classifiers based on non-parametric models, Trees and Minimum Spanning Trees class descriptors (MST_CD) are proposed. These methods deal with inconsistencies arising from combining multiple classifiers and with spurious connections that MST-CD creates in multi-modal class distributions. Experiments on several datasets show that the proposed approach obtains comparable and, in some cases, state-of-the-art results

Efficacy of absolute alcohol injection compared with band ligation in the eradication of esophageal varices Eficácia da injeção de álcool absoluto comparada com ligadura elástica na erradicação de varizes de esôfago

BACKGROUND: Endoscopic sclerotherapy is an absolute indication for treating esophageal varices. Re-bleeding is common during the treatment period, before all varices become eradicated. AIM: To compare two techniques of endoscopic esophageal varices eradication: sclerotherapy with absolute alcohol and banding ligation. PATIENTS AND METHOD: Forty-six patients with liver cirrhosis and esophageal varices were prospectively randomized into two treatment groups: endoscopic sclerotherapy with absolute alcohol and banding ligation. Patients were included if they had large varices with signs of high bleeding risk. Informed writing consent was obtained from every patient and the Ethics Committee of Federal University of São Paulo, SP, Brazil, approved the study. After eradication, all patients were followed up to 1 year to look for re-bleeding episodes and variceal recurrence. RESULTS: Both groups were similar except that male gender was more common in the sclerotherapy group. There was no statistical difference regarding variceal eradication (78.3% in sclerotherapy group vs 73.9% in the ligation group), recurrence (26.7% vs 42.9%, respectively) and death related to any cause (21.7% vs 13.9%). In the sclerotherapy group more sessions were need to obtain complete variceal eradication. In this group we did observe a high re-bleeding rate (34.8%) and more ulcers associated with retrosternal pain right after the procedure. There was no difference regarding overall morbidity and mortality. CONCLUSIONS: Banding ligation requires fewer sessions than sclerotherapy with absolute alcohol to eradicate esophageal varices. Both methods are equally efficient regarding variceal eradication and recurrence during a short follow-up period.<br>RACIONAL: Escleroterapia endoscópica tem indicação absoluta no tratamento das varizes de esôfago. Ressangramento é comum durante o período de tratamento, antes que as varizes sejam erradicadas. OBJETIVO: Comparar duas técnicas de erradicação endoscópica de varizes de esôfago: escleroterapia com álcool absoluto e ligadura elástica. PACIENTES E MÉTODOS: Quarenta e seis pacientes com cirrose hepática e varizes de esôfago foram prospectivamente randomizados em dois grupos de tratamento: escleroterapia endoscópica com álcool absoluto e ligadura elástica. Os pacientes foram incluídos no estudo se tivessem varizes de grosso calibre com sinais de alto risco de sangramento. Consentimento informado por escrito foi obtido de cada paciente e o estudo foi aprovado pelo Comitê de Ética da instituição onde o estudo foi realizado. Após a erradicação, todos os pacientes foram seguidos durante 1 ano para avaliar a taxa de ressangramento e a recidiva das varizes. RESULTADOS: Ambos os grupos foram parecidos exceto no que se refere ao sexo masculino, mais comum no grupo da escleroterapia. Não houve diferença estatisticamente significante em relação a erradicação das varizes (78,3% no grupo da escleroterapia vs. 73,9% no grupo da ligadura), recidiva (26,7% vs. 42,9%, respectivamente) e mortalidade relacionada a qualquer causa (21,7% vs. 13,9%). No grupo da escleroterapia houve necessidade de maior número de sessões para obtenção da erradicação completa das varizes. Neste mesmo grupo observou-se alta taxa de ressangramento (34,8%) e presença de mais úlceras associadas com dor retroesternal logo após o procedimento. Não houve diferença na morbimortalidade global. CONCLUSÕES: O tratamento com ligadura elástica requer menos sessões do que a escleroterapia com álcool absoluto para erradicar as varizes de esôfago. Ambos os métodos são igualmente eficazes, a curto prazo, no que diz respeito à taxa de erradicação e recidiva das varizes