Across intra-mammalian stages of the liver fluke Fasciola hepatica: a proteomic study

Fasciola hepatica is the agent of fasciolosis, a foodborne zoonosis that affects livestock production and human health. Although flukicidal drugs are available, re-infection and expanding resistance to triclabendazole demand new control strategies. Understanding the molecular mechanisms underlying the complex interaction with the mammalian host could provide relevant clues, aiding the search for novel targets in diagnosis and control of fasciolosis. Parasite survival in the mammalian host is mediated by parasite compounds released during infection, known as excretory/secretory (E/S) products. E/S products are thought to protect parasites from host responses, allowing them to survive for a long period in the vertebrate host. This work provides in-depth proteomic analysis of F. hepatica intra-mammalian stages, and represents the largest number of proteins identified to date for this species. Functional classification revealed the presence of proteins involved in different biological processes, many of which represent original findings for this organism and are important for parasite survival within the host. These results could lead to a better comprehension of host-parasite relationships, and contribute to the development of drugs or vaccines against this parasite

Molecular fragmentation of wheat-germ agglutinin induced by food irradiation reduces its allergenicity in sensitised mice

WGA, an agglutinin from wheat germ which is largely responsible for many of wheat's allergies, was used as a model to investigate the action of ionising radiation on WGA's anti-nutritive effects in sensitised mice. Based on the molecular structure, the present study also examined the structural modification of WGA in relation to the range of dose. Structural integrity was monitored using HPLC, fluorescence spectrometry and circular dichroism. Results showed a loss of intrinsic activity and the formation of insoluble amorphous aggregates with a lack of native conformational structures after irradiation. Current findings suggest that the allergenic epitopes of WGA became less active and antigenic after high-dose radiation. the reduction of cytokines typical of allergic reactions, with decreased lymphocytic infiltrate, was observed in the gut of mice given irradiated versus native WGA. Food irradiation proved effective and safe in combating immunological and allergic effects of WGA. (C) 2011 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ministerio da Ciencia e Tecnologia (Brazilian)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE)Univ Fed Pernambuco, Dept Bioquim, Recife, PE, BrazilUniv Fed Pernambuco, Dept Histol & Embriol, Recife, PE, BrazilUniv Fed Pernambuco, Dept Biofis & Radiobiol, Recife, PE, BrazilUniv Fed Pernambuco, Dept Antibiot, Recife, PE, BrazilUniv Estadual Oeste Parana, Ctr Engn & Ciencias Exatas, Toledo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilWeb of Scienc

Computer-assisted tomography for studies of an Albaqualf

Na busca de técnicas mais apuradas para a determinação e avaliação de parâmetros físicos do solo com aplicabilidade em várzeas, vem se destacando a tomografia computadorizada, por medir a densidade e a umidade com boa sensibilidade e alta resolução espacial. O presente trabalho teve como objetivo descrever aspectos e procedimentos da calibração de um minitomógrafo de raios-X e gama para estudo da densidade e umidade de um Planossolo no Rio Grande do Sul, bem como estabelecer parâmetros estatísticos para sua adequada utilização. A calibração do minitomógrafo foi obtida pela regressão linear entre as unidades tomográficas (UT), apresentadas pelo programa de reconstrução de imagem, e os coeficientes de atenuação linear (µl, cm-1), medidos por transmissão direta de raios gama, em amostras dos horizontes A e B do Planossolo, água destilada, benzina e alumínio. Para as medidas de transmissão direta de radiação utilizaram-se recipientes com água destilada, benzina, solo e Al, obtendo-se as seguintes fórmulas para o cálculo da densidade do solo no horizonte A: Ds = [(UT/986,16)-(0,200xq)]/0,267; e no horizonte B: Ds = [(UT/986,16)-(0,200xq)]/0,297, em que UT é o valor médio de UT em cada linha e q é a umidade volumétrica da amostra de solo, em m3 m-3. Com as configurações obtidas, verificou-se variabilidade média de 2,74% e 0,73%, respectivamente, em termos de homogeneidade e repetibilidade. Os erros atribuídos ao equipamento são de 0,051 e 0,046 Mg m-3, respectivamente, nos horizontes A e B, revelando precisão e adaptabilidade no emprego da técnica em estudos do Planossolo._________________________________________________________________________________ ABSTRACT: In order to find better techniques to evaluate the soil physical parameters applied to lowland soils, the computerized tomography has been used to measure soil density and water content with accuracy and high spatial resolution. This work was carried out in order to describe features and calibration procedures of a computerized minitomographer using X-ray and gama-rays as sources of radiation and to establish suitable statistical parameters on the study of soil bulk density and water content in a Planosol (Albaqualf) from Rio Grande do Sul State, Brazil. The minitomographer calibration was obtained from the linear regression equation among the tomography's unities (TU) presented by the image reconstruction program and the linear attenuation coefficient (µl, cm-1), by the measurement of direct transmission of g-rays as source of radiation in soil samples from A and B horizons, distilled water, benzin and aluminum. In order to get measures of the direct radiation transmission, containers with distilled water, benzin, soil and aluminum were used to obtain the following equations to calculate soil bulk density in the A horizon: Ds = [(TU/986.16)-(0.200xq)]/0.267 and in the B horizon: Ds = [(TU/986.16)-(0.200xq)]/0.297, where TU is the mean value in the line and q is the soil volumetric water content (m3 m-3). The obtained configurations allowed to attain average variabilities of 2.74% and 0.73% for homogeneity and repeatability, respectively. The expected errors related to the equipment are 0.051 and 0.046 Mg m-3, to the A and B horizons, respectively. The results showed the technique accuracy and adaptability in the studies of the physical characteristics of a Planosol

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes : Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.Peer reviewe

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease