Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women

AIM: To investigate the safety/efficacy of Boceprevirbased triple therapy in hepatitis C virus (HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure (7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEGIFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNA-positive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response (SVR) (HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4 (RVR), 8 (RVR BOC), 12 (EVR), or at the end-of-treatment (ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used. RESULTS: After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤ 1 logio decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56 (57.1%) and at week 12 in 41/56 (73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56 (44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders (Ρ = 0.250), in 44% F0-F2 vs 54% F3-F4 (Ρ = 0.488), and in 11/19 (57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy (OR = 2.662, 95%CI: 0.957-6.881, Ρ= 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4 (3.733, 95%CI: 1.676-12.658, Ρ= 0.034) and achievement of RVR BOC (7.347, 95%CI: 2.156-25.035, Ρ= 0.001) were significantly related with the SVR, al-though RVR BOC only (6.794, 95%CI: 1.596-21.644, Ρ = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR

When and where did India and Asia collide?

Timing of the collision between India and Asia is the key boundary condition in all models for the evolution of the Himalaya-Tibetan orogenic system. Thus it profoundly affects the interpretation of the rates of a multitude of associated geological processes ranging from Tibetan Plateau uplift through continental extrusion across eastern Asia, as well as our understanding of global climate change during the Cenozoic. Although an abrupt slowdown in the rate of convergence between India and Asia around 55 Ma is widely regarded as indicating the beginning of the collision, most of the effects attributed to this major tectonic episode do not occur until more than 20 Ma later. Refined estimates of the relative positions of India and Asia indicate that they were not close enough to one another to have collided at 55 Ma. On the basis of new field evidence from Tibet and a reassessment of published data we suggest that continent-continent collision began around the Eocene/Oligocene boundary (∼34 Ma) and propose an alternative explanation for events at 55 Ma. Copyright 2007 by the American Geophysical Union.published_or_final_versio

Association Between Total Number of Deaths, Diabetes Mellitus, Incident Cancers, and Haplotypes in Chromosomal Region 8q24 in a Prospective Study

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Increase of circulating cell free mitochondrial DNA in amateur boxers after sparring matches

Objectives: To determine if circulating mitochondrial deoxyribonucleic acid levels increase after sport activity involving blows to the head, such as boxing, and if it could play a role in inflammatory cascade regulation in response to trauma. Design: Observational, longitudinal. Methods: We measured mitochondrial deoxyribonucleic acid levels and integrity in ten non-professional male boxers before and after three weekly sparring matches. We set up a protocol to separate three different plasma fractions enriched in mitochondria-containing vesicles, mitochondrial deoxyribonucleic acid bound to proteins and naked mitochondrial deoxyribonucleic acid. We quantified the levels of the main cytokines involved in inflammatory response and the levels of neurofilament light, a well-known marker of brain damage. Results: Circulating mitochondrial deoxyribonucleic acid levels increased after each match. In the second fraction, we also observed an increase over the weeks. Mitochondrial deoxyribonucleic acid is less intact after each match if compared with pre-match integrity, especially the naked form which is not protected within vesicles or mitochondria. Circulating levels of interleukin-6, interleukin-1beta and interleukin-10 increased after each match linking traumatic brain injuries to inflammatory state. Neurofilament light chain showed a similar trend to mitochondrial deoxyribonucleic acid. Conclusions: As mitochondrial deoxyribonucleic acid displays an inflammatory effect and neurofilament light chain is more specific for brain injury, we concluded that the simultaneous analysis of these two parameters could be helpful to monitor the effects of traumatic brain injury in contact sports, and that mitochondrial deoxyribonucleic acid is a promising candidate biomarker to study the inflammatory state of patients who suffered repeated traumatic brain injuries

GALAD outperforms aMAP and ALBI for predicting HCC in patients with compensated advanced chronic liver disease: A 12-year prospective study

Background and aims: Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most reliable and commonly used technique, especially when associated with serum determination of α-fetoprotein, but different score systems have been proposed to overcome the unsatisfactory diagnostic accuracy of α-fetoprotein. The aim of this 12-year prospective study is to compare the gender, age, AFP-L3, AFP, des-gamma-carboxy prothrombin (GALAD) versus age, gender, bilirubin, albumin, and platelets and albumin-bilirubin scores in predicting HCC onset. Approach and results: A cohort of 545 consecutive patients with compensated advanced chronic liver disease without suspected focal lesions was followed up every 6 months by liver imaging and α-fetoprotein to detect HCC occurrence. Harrell's C-index for censored data was employed to evaluate the performance of any parameters or scores helping to predict HCC development. ROC curve analysis showed that the GALAD score was more accurate in evaluating HCC development than albumin-bilirubin and age, gender, bilirubin, albumin, and platelets. The AUC ranged from 0.7268 to 0.6851 at 5 and 10 years, both in the total cohort and in the sub-cohorts (viral hepatitis, NASH, and alcohol). The HCC Risk model was constructed using univariate and multivariate Cox proportional hazard regression analysis, showing a strong association of GALAD with HR > 1, p < 0.05, in the total and sub-cohorts, and a better risk prediction in the alcohol cohort, both alone and standardized with other blood parameters. Conclusions: GALAD is the most reliable and accurate score system to detect HCC risk of development in patients with compensated advanced chronic liver disease

Early menopause is associated with lack of response to antiviral therapy in women with chronic hepatitis C.

BACKGROUND AND AIMS: Chronic hepatitis C (CHC) and liver fibrosis progress more rapidly in men and menopausal women than in women of reproductive age. We investigated the associations among menopause, sustained virologic response (SVR), and liver damage in patients with CHC. METHODS: We performed a prospective study of 1000 consecutive, treatment-naïve patients 18 years of age and older with compensated liver disease from CHC. Liver biopsy samples were analyzed (for fibrosis, inflammation, and steatosis) before patients received standard antiviral therapy. From women (n = 442), we collected data on the presence, type, and timing of menopause; associated hormone and metabolic features; serum levels of interleukin-6; and hepatic tumor necrosis factor (TNF)-α. RESULTS: Postmenopausal women achieved SVRs less frequently than women of reproductive age (46.0% vs 67.5%; P < .0001) but as frequently as men (51.1%; P = .283). By multivariate regression analysis, independent significant predictors for women to not achieve an SVR were early menopause (odds ratio [OR], 8.055; 95% confidence interval [CI], 1.834-25.350), levels of γ-glutamyl transpeptidase (OR, 2.165; 95% CI, 1.364-3.436), infection with hepatitis C virus genotype 1 or 4 (OR, 3.861; 95% CI, 2.433-6.134), and cholesterol levels (OR, 0.985; 95% CI, 0.971-0.998). Early menopause was the only independent factor that predicted lack of an SVR among women with genotype 1 hepatitis C virus infection (OR, 3.933; 95% CI, 1.274-12.142). Baseline levels of liver inflammation, fibrosis, steatosis, serum interleukin-6 (P = .04), and hepatic TNF-α (P = .007) were significantly higher among postmenopausal women than women of reproductive age. CONCLUSIONS: Among women with CHC, early menopause was associated with a low likelihood of SVR, probably because of inflammatory factors that change at menopause

Benefits and pitfalls of multimedia and interactive features in technology-enhanced storybooks:A meta-analysis

A meta-analysis was conducted on the effects of technology-enhanced stories for young children’s literacy development when compared to listening to stories in more traditional settings like storybook reading. A small but significant additional benefit of technology was found for story comprehension (g+ = 0.17) and expressive vocabulary (g+ = 0.20), based on data from 2,147 children in 43 studies. When investigating the different characteristics of technology-enhanced stories, multimedia features like animated pictures, music, and sound effects were found beneficial. In contrast, interactive elements like hotspots, games, and dictionaries were found to be distracting. Especially for children disadvantaged because of less stimulating family environments, multimedia features were helpful and interactive features were detrimental. Findings are discussed from the perspective of cognitive processing theories

Gestores escolares da rede pública em Minas Gerais: fatores de satisfação no trabalho

O objetivo deste trabalho foi investigar a presença ou ausência de satisfação no trabalho dos diretores/gestores da educação básica pública, bem como sua interferência na gestão escolar. Tomou-se como referencial as categorias de Qualidade de Vida no Trabalho sugeridas por Walton. A pesquisa é descritiva, numa abordagem qual-iquantitativa, usando um questionário semiestruturado. A amostra consistiu de 124 casos distribuídos em 52 cidades de Minas Gerais. Os resultados indicam que há sentimento de satisfação por parte dos diretores/gestores com relação aos fatores relevância do trabalho, integração social na organização, uso e desenvolvimento de capacidades, constitucionalismo e oportunidade de crescimento profissional, o que propicia interferência considerada positiva na gestão escolar. Todavia, existe um sentimento de ausência de satisfação com relação aos fatores associados à remuneração; e um sentimento de indiferença, considerando os fatores associados às condições de trabalho e ao equilíbrio trabalho e vida.The objective of this study was to investigate the presence or absence of satisfaction at work of the directors/managers of basic state/public education, as well as its influence on school management. The category suggestions made by Walton in his "Quality of Work life", were referred to. This research is descriptive, with a qualitative and quantitative approach, using a semi-structured questionnaire. The sample consisted of 124 cases distributed across 52 municipalities of MG. The results indicate that there is a sense of satisfaction on the part of directors / managers with regard to the relevance of their work. Social integration in the organization, use of (and development of) employees’ capacities, constitutionalism and opportunities for professional growth, all provide proof of their positive influence on school management. However, there is a feeling of dissatisfaction with respect to factors associated with remuneration (salary), and a feeling of indifference regarding working conditions (and their associated factors) and concerning the work-life/home-life balance