Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Fish composition and species richness in eastern South American coastal lagoons: additional support for the freshwater ecoregions of the world

The relationships between fish composition, connectivity and morphometry of 103 lagoons in nine freshwater ecoregions (FEOW) between 2·83° S and 37·64° S were evaluated in order to detect possible congruence between the gradient of species richness and similarities of assemblage composition. Most lagoons included in the study were <2 km(2) , with a maximum of 3975 km(2) in surface area. Combined surface area of all lagoons included in the study was 5411 km(2) . Number of species varied locally from one to 76. A multiple regression revealed that latitude, attributes of morphometry and connectivity, and sampling effort explained a large amount of variability in species richness. Lagoon area was a good predictor of species richness except in low latitude ecoregions, where lagoons are typically small-sized and not affected by marine immigrants, and where non-native fish species accounted for a significant portion of species richness. Relationships between species and area in small-sized lagoons (<2 km(2) ) is highly similar to the expected number in each ecoregion, with systems located between 18·27° S and 30·15° S attaining higher levels of species richness. Similarities in species composition within the primary, secondary and peripheral or marine divisions revealed strong continental biogeographic patterns only for species less tolerant or intolerant to salinity. Further support for the FEOW scheme in the eastern border of South America is therefore provided, and now includes ecotonal systems inhabited simultaneously by freshwater and marine species of fishes.Fil: Petry, A. C.. Universidade Federal do Rio de Janeiro; BrasilFil: Guimarães, T. F. R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Vasconcelos, F. M. Universidade Federal do Rio de Janeiro; BrasilFil: Hartz, S. M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Becker, F. G.. Universidade Federal do Rio Grande do Sul; BrasilFil: Rosa, R. S.. Universidade Federal da Paraíba; BrasilFil: Goyenola, G.. Universidad de la República; UruguayFil: Caramaschi, E. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Díaz de Astarloa, Juan Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Sarmento Soares, L. M.. Instituto Nacional da Mata Atlântica; BrasilFil: Vieira, J. P.. Universidade Federal do Rio Grande; BrasilFil: García, A. M.. Universidade Federal do Rio Grande; BrasilFil: Teixeira de Mello, Franco. Universidad de la República; UruguayFil: de Mello, F. T.. Universidade Federal Do Piaui.; BrasilFil: Meerhoff, M.. Universidad de la República; UruguayFil: Attayde, J. L.. Universidade Federal do Rio Grande do Norte; BrasilFil: Menezes, R. Fernandes de. Universidade Federal do Rio Grande do Norte; BrasilFil: Mazzeo, N.. Universidad de la República; UruguayFil: Di Dario F.. Universidade Federal do Rio de Janeiro; Brasi

Influência do cultivar, do tipo de folha e do tempo de cultivo na medida indireta da clorofila (spad) em mudas de goiabeira Influence of cultivars, type of leaf, and cultivation time in the indirect measurement of chlorophyll (SPAD) in guava (psidium guajava l.) seedlings

A análise foliar de nitrogênio, comumente empregada em laboratórios de rotina, é destrutiva e nem sempre rápida, obstante para a tomada de decisão. Objetivou-se com a pesquisa estudar as medidas SPAD, em mudas de goiabeira (Psidium guajava L.) cultivada em solução nutritiva completa, observando-se as diferenças entre cultivares, épocas de amostragem e tipos de folhas avaliadas. O delineamento foi inteiramente casualizado, com quatro repetições, em parcelas sub-subdivididas. Assim, foi utilizada como parcela as duas cultivares de goiabeira (Paluma e Século XXI), como subparcelas os tipos de folhas (+1, +2 e +3) e, cinco épocas de amostragem ao longo do período experimental (60, 75, 90, 105 e 120 dias, após o transplantio de mudas) Concluiu-se que a leitura SPAD em mudas de goiabeira é influenciada pela cultivar, tipo de folha e época de amostragem. O terceiro par de folhas mostrou-se mais adequado para avaliar o estado nutricional do nitrogênio nas mudas de goiabeira a partir da leitura SPAD. As cultivares de goiabeira apresentaram diferença na leitura SPAD apenas aos 60 e 90 dias após o transplantio, independentemente do tipo de folha.<br>Foliar nitrogen analysis, also used in routine laboratories, is destructive and not always fast enough for decision making. The objective of this research was to study SPAD measurements, in guava seedlings (Psidium guajava L.) cultivated in a complete nutritive solution, observing the differences between cultivation, times of sampling, and types of evaluated leaves. The experimental design was a completely randomized scheme, with four repetitions, in split lots. The lots consisted of two guava cultivars (Paluma and Século XXI), as sub-lots, the types of leaves (+1, +2 ,and +3), and five sampling times throughout the experimental period (60, 75, 90, 105, and 120 days). It was concluded that the SPAD measurements in guava seedlings are influenced by cultivation, type of leaf, and time of sampling. The third pair of leaves was shown to be more adequate for evaluating the nutritional status of nitrogen in the guava seedlings from the SPAD reading. The guava cultivars presented differences in SPAD readings only at 60 and 90 days, regardless of the type of leaf

Fatal outcome of chikungunya virus infection in Brazil.

BACKGROUND: Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused ~2.1 million cases and over 600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological and virus genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. METHODS: Sera, cerebrospinal fluid (CSF) and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue (DENV) and Zika virus (ZIKV). Clinical, epidemiological and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. RESULTS: 68 fatal cases had CHIKV infection confirmed by RT-qPCR (52.9%), viral antigen (41.1%), and/or specific-IgM (63.2%). Co-detection of CHIKV with DENV were found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV-deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the sub-acute phase. Genetic analysis showed circulation of two CHIKV-East Central South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. CONCLUSION: The investigation of the largest cross-sectional cohort of CHIKV-deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and non-risk groups, including young adults