A network approach for managing and processing big cancer data in clouds

Translational cancer research requires integrative analysis of multiple levels of big cancer data to identify and treat cancer. In order to address the issues that data is decentralised, growing and continually being updated, and the content living or archiving on different information sources partially overlaps creating redundancies as well as contradictions and inconsistencies, we develop a data network model and technology for constructing and managing big cancer data. To support our data network approach for data process and analysis, we employ a semantic content network approach and adopt the CELAR cloud platform. The prototype implementation shows that the CELAR cloud can satisfy the on-demanding needs of various data resources for management and process of big cancer data

GPC3 gene expression and allelic discrimination of FZD7 gene in Egyptian patients with hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, and especially in Egypt. Early diagnosis of HCC greatly improves the survival and prognosis of patients. Low sensitivity and specificity of alpha-fetoprotein (AFP) has led to the demand for novel biomarkers of HCC. The aim of the present study was to evaluate the validity of frizzled-7 (FZD7) and glypican-3 (GPC3) gene expression as potential biomarkers for HCC early diagnosis, and to investigate the association between FZD7 rs2280509 polymorphism and HCC risk. Materials and methods: Quantification of FZD7 and GPC3 gene expression by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay, and genotyping FZD 7 (rs2280509 SNP) gene polymorphism using RT-PCR. Results: The current results revealed that FZD7 gene expression had a greater area under the curve (AUC) for identifying HCC than GPC3 gene expression and AFP levels. The combination of the three markers as a panel showed a better diagnostic performance with a greater AUC than any of the single markers alone (p < 0.05). The FZD7 rs2280509 polymorphism (CT) was found to be significantly associated with an increased risk of HCC. The CT genotype and T allele were significantly more prevalent in the HCC group compared to either the cirrhosis (p = 0.03) or control groups (p = 0.0009 and 0.002; respectively). Conclusion: FZD7 and GPC3 gene expressions have a complementary role in early HCC detection, with a greater diagnostic sensitivity and accuracy than AFP. In addition, FZD7 rs2280509 polymorphism is significantly associated with an increased risk of HCC in the Egyptian population

AVALIAÇÃO DE SITUAÇÃO VACINAL DE CRIANÇAS ADSCRITAS NA UBS DO BAIRRO DE FÁTIMA NO MUNICÍPIO DE VALENÇA- RJ

Introdução: A vacinação de rotina consiste no estabelecimento de um calendário vacinal que deve ser aplicado ao indivíduo desde o nascimento, visando garantir prevenção específica das doenças imunopreveníveis e indução da imunidade de massa. Objetivo: Caracterizar a cobertura vacinal da população infantil adscrita na UBS Bairro de Fátima - Valença – RJ. Materiais e Métodos: Trata-se de um estudo quantitativo, do tipo coorte transversal, que produz resultados “instantâneos” da situação de saúde de um local. O método utilizado foi coleta de dados a partir da caderneta vacinal. O estudo fora realizado com base em dados vacinais de 100 crianças, de 0 a 5 anos de idade, incluindo ambos os sexos. A partir dos dados obtidos, foram separados em grupos com vacinação completa e incompleta, bem como as vacinas com maior índice de inadimplência. Resultados: De 100 crianças, 52% eram do sexo masculino e 48% do sexo feminino e a taxa de vacinação incompleta, foi respectivamente, 23% e 27%. A maior taxa de falta de cobertura está entre as vacinas contra Difteria, Tétano, Coqueluche e Varicela. Conclusão: A taxa de falta da cobertura vacinal condiz com a média dos estudos nacionais. Contudo, nos estudos base as principais vacinas não realizadas foram Hepatite A e Poliomielite, diferente do nosso estudo em que as de menor cobertura foram tríplice e tetra virais. Apesar de estar dentro da meta esperada pelo Ministério da Saúde, a cobertura vacinal local deve ser estimulada para redução de ocorrência de doenças

PREVALÊNCIA DE SINDROME METABÓLICA EM CRIANÇAS E ADOLESCENTES OBESOS DO MUNICÍPIO DE RIO DAS FLORES – RJ

Introdução: A obesidade é um problema pediátrico de saúde pública, com prevalência em fase de crescimento, tornando sua prevenção e tratamento essenciais para diminuir futuras complicações. Destaca-se a Síndrome Metabólica como reconhecido fator de risco para o desenvolvimento de doença cardiovascular e fortemente associada ao excesso de peso. Objetivo: Caracterizar os pacientes obesos, pelo IMC e medida da circunferência abdominal e realizar exames físico-laboratoriais que confirmem o diagnóstico de Síndrome Metabólica. Materiais e Métodos: Foi realizado um estudo quantitativo, do tipo coorte transversal, no município de Rio das Flores - RJ, envolvendo 34 crianças entre 10 e 16 anos. Utilizou-se o método de medida de peso e altura de todas as crianças, a fim de obter o valor do índice de massa corporal (IMC), além das medidas dos níveis pressóricos arteriais, medida de cintura abdominal e coleta de material para exames laboratoriais. Resultados: Foram classificadas 8,8% das crianças como apresentando SM, dessas, 66,7% eram meninos. A grande maioria das alterações encontradas foi no critério de PA, o equivalente a 92,3%. Conclusão: A obesidade na infância e adolescência é um importante fator de risco para o desenvolvimento de síndrome metabólica, tornando-se necessária a implementação de medidas intervencionistas e de prevenção no combate a este distúrbio nutricional, tais como a promoção do aumento da atividade física e o incentivo à aquisição de hábitos alimentares saudáveis

RELAÇÃO DAS MEDIDAS ANTROPOMÉTRICAS E VALORES DE PRESSÃO ARTERIAL DE CRIANÇAS E ADOLESCENTES DO MUNICÍPIO DE RIO DAS FLORES – RJ

Introdução: A obesidade é problema de saúde pública, associado ao risco de complicações na infância e aumento da morbimortalidade na vida adulta. Objetivo: Fornecer base que comprove associação entre obesidade e alteração dos níveis pressóricos. Metodologia: Trata-se de um estudo transversal, descritivo e correlacional, com abordagem quantitativa dos dados. Realizado em doze instituições de ensino em Rio das Flores – RJ. A população alvo foi 780 estudantes, com idade entre 3-18 anos. O método foi aferição da pressão arterial e coleta de dados para cálculo do IMC. A partir da amostra realizou-se correlação dos dados e comparação das alterações dos níveis pressóricos em expostos e não expostos. Em um segundo momento foram realizadas novas medidas pressóricas para confirmação diagnóstica. Resultados: Foram avaliados 780 alunos, desses 64,8% com IMC adequado, 18,7% sobrepeso e 15% obeso. Quanto aos níveis pressóricos 90,6% eram normotensos, 3,4% pré-hipertensos e 6% hipertensos. 91% dos eutróficos eram normotensos; 3,3% pré hipertensos e 5,7% hipertensos. Com sobrepeso, 82,3% eram normotensos, 6,1% pré-hipertensos e 11,6%, hipertensos. Dos obesos 68,7% eram normotensos, 8,2% pré-hipertensos e 23,1% hipertensos. A prevalência de alteração nos níveis pressóricos, nos expostos foi 34,7% e não expostos 6,0%. Conclusão: Em relação aos estudos base, nota-se aumento do percentual de crianças com sobrepeso e obesas no nosso estudo. Contudo, a prevalência de HAS da população estudada está dentro dos achados nacionais e internacionais. Quanto maior IMC, maiores serão os níveis pressóricos. Logo, IMC alterado é importante fator de risco para hipertensão precoce

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

Alpha-melanocyte stimulating hormone (alpha-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of alpha-, beta- and gamma-MSH correlated clinically with malignant melanoma development, but other studies suggest alpha-MSH acts to retard invasion. In the present study, we investigated the action of alpha-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. alpha-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-kappaB transcription factor. However, A375-SM and C8161 cells did not respond to alpha-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for alpha-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to alpha-MSH, although all three lines responded to acute alpha-MSH addition (+(-)-N(6)-(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by alpha-MSH. From this data, we conclude that alpha-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Identification of new FK866 analogues with potent anticancer activity against pancreatic cancer

11 p.- 2 fig.-4 tab.-8 schem.-1 graph. abst.Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases for which chemotherapy has not been very successful yet. FK866 ((E)-N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) is a well-known NAMPT (nicotinamide phosphoribosyltransferase) inhibitor with anti-cancer activities, but it failed in phase II clinical trials. We found that FK866 shows anti-proliferative activity in three PDAC cell lines, as well as in Jurkat T-cell leukemia cells. More than 50 FK866 analogues were synthesized that introduce substituents on the phenyl ring of the piperidine benzamide group of FK866 and exchange its buta-1,4-diyl tether for 1-oxyprop-3-yl, (E)-but-2-en-1,4-diyl and 2- and 3-carbon tethers. The pyridin-3-yl moiety of FK866 was exchanged for chlorinated and fluorinated analogues and for pyrazin-2-yl and pyridazin-4-yl groups. Several compounds showed low nanomolar or sub-nanomolar cell growth inhibitory activity. Our best cell anti-proliferative compounds were the 2,4,6-trimethoxybenzamide analogue of FK866 ((E)-N-(4-(1-(2,4,6-trimethoxybenzoyl)piperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) (9), the 2,6-dimethoxybenzamide (8) and 2-methoxybenzamide (4), which exhibited an IC50 of 0.16 nM, 0.004 nM and 0.08 nM toward PDAC cells, respectively.The research leading to these results has received funding from the European Community's Seventh Framework Programme [FP7-2007-2013] under grant agreement no. 256986 (PANACREAS), from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 813284 (INTEGRATA), by the Spanish Ministry of Science, Innovation, and Universities (SAF2017-89672-R) and by the Associazione Italiana per la Ricerca sul Cancro (AIRC), IG#22098.Peer reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication