Cardiac Harms of Sofosbuvir: Systematic Review and Meta-Analysis

INTRODUCTION: Sofosbuvir is a new direct-acting pyrimidine nucleotide analogue antiviral drug that has shown remarkable efficacy in the treatment of hepatitis C in clinical trials. However, observational anecdotal data have recently suggested an increased risk of serious bradycardia among patients treated with sofosbuvir and amiodarone. OBJECTIVE: We aimed to estimate and characterize the cardiac safety of sofosbuvir by performing a systematic review of randomized controlled trials (RCTs). METHODS: We conducted a systematic review of RCTs (PROSPERO 2016: CRD42016033109) comparing sofosbuvir and non-sofosbuvir regimens in patients with chronic hepatitis C by searching the MEDLINE, Embase, and Cochrane Library databases up to January 2017. Non-published data were obtained from the sofosbuvir marketing authorization holder. Random-effects meta-analysis was performed to derive pooled estimates of relative risks (RRs) and corresponding 95% confidence intervals (CIs). RESULTS: Six trials, enrolling 2346 patients (1625 treated with sofosbuvir), were included. The overall risk of bias across studies was moderate. The risk of reported cardiac events (RR 0.87; 95% CI 0.41-1.85), arrhythmias (RR 0.93; 95% CI 0.34-2.51), bradycardia (RR 0.47; 95% CI 0.04-5.20), and tachycardia (RR 0.91; 95% CI 0.20-4.20) were not significantly different between sofosbuvir and non-sofosbuvir regimens. The risks of reported syncope, presyncope, loss of consciousness, or palpitations were similar among those receiving sofosbuvir regimens and controls. CONCLUSIONS: The pooled data from RCTs did not show an increased risk of cardiac outcomes, including arrhythmias (and bradycardia), among sofosbuvir-treated patients, although the overall quality of the evidence supporting this conclusion was very low

Imprisonment and internment: Comparing penal facilities North and South

Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

First Evidence of Immunomodulation in Bivalves under Seawater Acidification and Increased Temperature

Water acidification, temperature increases and changes in seawater salinity are predicted to occur in the near future. In such a global climate change (GCC) scenario, there is growing concern for the health status of both wild and farmed organisms. Bivalve molluscs, an important component of coastal marine ecosystems, are at risk. At the immunological level, the ability of an organism to maintain its immunosurveillance unaltered under adverse environmental conditions may enhance its survival capability. To our knowledge, only a few studies have investigated the effects of changing environmental parameters (as predicted in a GCC scenario) on the immune responses of bivalves. In the present study, the effects of both decreased pH values and increased temperature on the important immune parameters of two bivalve species were evaluated for the first time. The clam Chamelea gallina and the mussel Mytilus galloprovincialis, widespread along the coast of the Northwestern Adriatic Sea, were chosen as model organisms. Bivalves were exposed for 7 days to three pH values (8.1, 7.7 and 7.4) at two temperatures (22 and 28°C). Three independent experiments were carried out at salinities of 28, 34 and 40 PSU. The total haemocyte count, Neutral Red uptake, haemolymph lysozyme activity and total protein levels were measured. The results obtained demonstrated that tested experimental conditions affected significantly most of the immune parameters measured in bivalves, even if the variation pattern of haemocyte responses was not always linear. Between the two species, C. gallina appeared more vulnerable to changing pH and temperature than M. galloprovincialis. Overall, this study demonstrated that climate changes can strongly affect haemocyte functionality in bivalves. However, further studies are needed to clarify better the mechanisms of action of changing environmental parameters, both individually and in combination, on bivalve haemocytes

Innovating home visiting to mothers and infants by community health workers: an action-oriented guide

Abstract Objectives: to describe the process of development and the structure of an action-oriented guide for home visits (HVs) to mothers and infants by Community Health Workers (CHWs). The guide was adopted in a controlled trial aimed at assessing its efficacy in improving CHWs' performance. Methods: steps to develop the guide included: 1) Review of international and national standards and recommendations for community interventions for maternal and child care; 2) Assessment of perceived needs of CHWs and other Family Health professionals regarding prenatal and postnatal HVs; 3) Identification of elements to construct the guide. Results: the Guide provides action-oriented instructions for 10 HVs during prenatal and postnatal period up to 9 months instead of the 18 HVs currently recommended by Ministry of Health. Specific tasks for each visit including assessment and promotion of early child development (ECD) and an action-oriented risk classification are introduced as standardized operational practice. Conclusions: the described approach to guide construction allows adapting the guide contents to the health system context in Brazil and other countries interested in improving quality of HVs by CHWs. The guide, by identifying tasks to be carried out and actions to be taken at each HV, provides an innovative approach and represents a requisite for a more efficient and effective use of their time

Degradation of metalaxyl and folpet by filamentous fungi isolated from Portuguese (Alentejo) vineyard soils

Degradation of xenobiotics by microbial populations is a potential method to enhance the effectiveness of ex situ or in situ bioremediation. The purpose of this study was to evaluate the impact of repeated metalaxyl and folpet treatments on soil microbial communities and to select soil fungal strains able to degrade these fungicides. Results showed enhanced degradation of metalaxyl and folpet in vineyards soils submitted to repeated treatments with these fungicides. Indeed, the greatest degradation ability was observed in vineyard soil samples submitted to greater numbers of treatments. Respiration activities, as determined in the presence of selective antibiotics in soil suspensions amended with metalaxyl and folpet, showed that the fungal population was the microbiota community most active in the degradation process. Batch cultures performed with a progressive increase of fungicide concentrations allowed the selection of five tolerant fungal strains: Penicillium sp. 1 and Penicillium sp. 2, mycelia sterila 1 and 3, and Rhizopus stolonifer. Among these strains, mycelium sterila 3 and R. stolonifer presented only in vineyard soils treated with repeated application of these fungicides and showed tolerance >1,000 mg l−1 against commercial formulations of metalaxyl (10 %) plus folpet (40 %). Using specific methods for inducing sporulation, mycelium sterila 3 was identified as Gongronella sp. Because this fungus is rare, it was compared using csM13-polymerase chain reaction (PCR) with the two known species, Gongronella butleri and G. lacrispora. The high tolerance to metalaxyl and folpet shown by Gongronella sp. and R. stolonifer might be correlated with their degradation ability. Our results point out that selected strains have potential for the bioremediation of metalaxyl and folpet in polluted soil sites

Human Angiostrongyliasis Outbreak in Dali, China

Angiostrongyliasis, caused by the rat lungworm Angiostrongylus cantonensis, is a potentially fatal food-borne disease. It is endemic in parts of Southeast Asia, the Pacific Islands, Australia, and the Caribbean. Outbreaks have become increasingly common in China due to the spread of efficient intermediate host snails, most notably Pomacea canaliculata. However, infections are difficult to detect since the disease has a rather long incubation period and few diagnostic clinical symptoms. Reliable diagnostic tests are not widely available. The described angiostrongyliasis epidemic in Dali, China lasted for eight months. Only 11 of a total of 33 suspected patients were clinically confirmed based on a set of diagnostic criteria. Our results demonstrate that the rapid and correct diagnosis of the index patient is crucial to adequately respond to an epidemic, and a set of standardized diagnostic procedures is needed to guide clinicians. Integrated control and management measures including health education, clinical guidelines and a hospital-based surveillance system, should be implemented in areas where snails are a popular food item

Phenolic and furanic compounds of Portuguese chestnut and French, American and Portuguese oak wood chips

Botanical species used on aging process must be wisely and judiciously chosen, and for this selection, a basic knowledge of the chemical composition of woods is warranted. Aiming to contribute to extend the knowledge of the chemical composition of several wood species useful for enological purposes, we have focused our studies on Portuguese chestnut and French, American and Portuguese oak chips. The profile of low molecular weight phenolic composition of these chips was achieved, using an optimized extraction method based on pressurized liquid extraction, followed by the quantification of phenolic acids, phenolic aldehydes and furanic derivatives by high-performance liquid chromatography (HPLC-DAD). The identification of those compounds was also confirmed by LC-DAD/ESI-MS. This study allowed the determination of the low molecular phenolic composition of Portuguese chestnut and French, American and Portuguese oak wood. According to our results, the influence of the botanical species seems to be more relevant than the geographic origin of the wood species

Differential Responses of Calcifying and Non-Calcifying Epibionts of a Brown Macroalga to Present-Day and Future Upwelling pCO2

Seaweeds are key species of the Baltic Sea benthic ecosystems. They are the substratum of numerous fouling epibionts like bryozoans and tubeworms. Several of these epibionts bear calcified structures and could be impacted by the high pCO2 events of the late summer upwellings in the Baltic nearshores. Those events are expected to increase in strength and duration with global change and ocean acidification. If calcifying epibionts are impacted by transient acidification as driven by upwelling events, their increasing prevalence could cause a shift of the fouling communities toward fleshy species. The aim of the present study was to test the sensitivity of selected seaweed macrofoulers to transient elevation of pCO2 in their natural microenvironment, i.e. the boundary layer covering the thallus surface of brown seaweeds. Fragments of the macroalga Fucus serratus bearing an epibiotic community composed of the calcifiers Spirorbis spirorbis (Annelida) and Electra pilosa (Bryozoa) and the non-calcifier Alcyonidium hirsutum (Bryozoa) were maintained for 30 days under three pCO2 conditions: natural 460±59 µatm, present-day upwelling1193±166 µatm and future upwelling 3150±446 µatm. Only the highest pCO2 caused a significant reduction of growth rates and settlement of S. spirorbis individuals. Additionally, S. spirorbis settled juveniles exhibited enhanced calcification of 40% during daylight hours compared to dark hours, possibly reflecting a day-night alternation of an acidification-modulating effect by algal photosynthesis as opposed to an acidification-enhancing effect of algal respiration. E. pilosa colonies showed significantly increased growth rates at intermediate pCO2 (1193 µatm) but no response to higher pCO2. No effect of acidification on A. hirsutum colonies growth rates was observed. The results suggest a remarkable resistance of the algal macro-epibionts to levels of acidification occurring at present day upwellings in the Baltic. Only extreme future upwelling conditions impacted the tubeworm S. spirorbis, but not the bryozoans