Identification of HCV protease inhibitor resistance mutations by selection pressure-based method

A major challenge to successful antiviral therapy is the emergence of drug-resistant viruses. Recent studies have developed several automated analyses of HIV sequence polymorphism based on calculations of selection pressure (Ka/Ks) to predict drug resistance mutations. Similar resistance analysis programs for HCV inhibitors are not currently available. Taking advantage of the recently available sequence data of patient HCV samples from a Phase II clinical study of protease inhibitor boceprevir, we calculated the selection pressure for all codons in the HCV protease region (amino acid 1–181) to identify potential resistance mutations. The correlation between mutations was also calculated to evaluate linkage between any two mutations. Using this approach, we identified previously known major resistant mutations, including a recently reported mutation V55A. In addition, a novel mutation V158I was identified, and we further confirmed its resistance to boceprevir in protease enzyme and replicon assay. We also extended the approach to analyze potential interactions between individual mutations and identified three pairs of correlated changes. Our data suggests that selection pressure-based analysis and correlation mapping could provide useful tools to analyze large amount of sequencing data from clinical samples and to identify new drug resistance mutations as well as their linkage and correlations

Endovascular Abdominal Aortic Aneurysm Repair With Ovation Alto Stent Graft: Protocol for the ALTAIR (ALTo endogrAft Italian Registry) Study

Background: Since 2010, the Ovation Abdominal Stent Graft System has offered an innovative sealing option for abdominal aortic aneurysm (AAA) by including a sealing ring filled with polymer 13 mm from the renal arteries. In August 2020, the redesigned Ovation Alto, with a sealing ring 6 mm closer to the top of the fabric, received CE Mark approval. Objective: This registry study aims to evaluate intraoperative, perioperative, and postoperative results in patients treated by the Alto stent graft (Endologix Inc.) for elective AAA repair in a multicentric consecutive experience. Methods: All consecutive eligible patients submitted to endovascular aneurysm repair (EVAR) by Alto Endovascular AAA implantation will be included in this analysis. Patients will be submitted to EVAR procedures based on their own preferences, anatomical features, and operators experience. An estimated number of 300 patients submitted to EVAR with Alto stent graft should be enrolled. It is estimated that the inclusion period will be 24 months. The follow-up period is set to be 5 years. Full data sets and cross-sectional images of contrast-enhanced computed tomography scan performed before EVAR, at the first postoperative month, at 24 or 36 months, and at 5-year follow-up interval will be reported in the central database for a centralized core laboratory review of morphological changes. The primary endpoint of the study is to evaluate the technical and clinical success of EVAR with the Alto stent graft in short- (90-day), mid- (1-year), and long-term (5-year) follow-up periods. The following secondary endpoints will be also addressed: operative time; intraoperative radiation exposure; contrast medium usage; AAA sac shrinkage at 12-month and 5-year follow-up; any potential role of patients' baseline characteristics, valuated on preoperative computed tomography angiographic study, and of device configuration (number of component) in the primary endpoint. Results: The study is currently in the recruitment phase and the final patient is expected to be treated by the end of 2023 and then followed up for 5 years. A total of 300 patients will be recruited. Analyses will focus on primary and secondary endpoints. Updated results will be shared at 1- and 3-5-year follow-ups. Conclusions: The results from this registry study could validate the safety and effectiveness of the new design of the Ovation Alto Stent Graft. The technical modifications to the endograft could allow for accommodation of a more comprehensive range of anatomies on-label

El Camí : setmanari valencianista.: Número 61 - 6 mayo 1933

International audienc

Challenges for Rural Livelihoods, Participatory Agroforestry, and Biodiversity Conservation in a Neotropical Biosphere Reserve in Mexico

We report on 10 years of participatory research processes linking livelihoods, agroforestry, and conservation in the La Sepultura Man and the Biosphere (MAB) Reserve in Chiapas, Mexico. These processes entail both cooperation and conflict between farmers and external actors who try to create and/or prevent the collapse of “nature-friendly” land uses. We developed a multidimensional research agenda with the participation of 12 communities and many graduate students. This agenda began with the promotion and monitoring of experimental fodder-tree plantations to counter dry season livestock starvation and forest degradation. Poor adoption of fodder trees motivated us to explore the history, conditions, needs, and motivations of farmers in this territory, and how these play out in their interaction with other actors when implementing agroforestry projects linked explicitly with biodiversity conservation. We report an analysis of three processes: (1) efforts to promote fodder-tree plantations as a means to intensify and move livestock production away from forest browsing; (2) “conservation” shade-coffee production in which benefits for farmers and forests are dubious, which also might collapse due to recent rust epidemics; (3) Pinus oocarpa resin extraction in pine-grass rangelands, where cattle exclusion, fire use prohibition, and unfavorable market deals could render this activity unsustainable. We reflect on how silvopastoral and agroforestry projects constitute an unstable balancing act among actors in this MAB reserve (and probably in similar ones). We discuss what participatory processes seem promising and need to be developed for the sake of long-term decent rural livelihoods and high-quality conservation landscapes