The genome of the blood fluke Schistosoma mansoni

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

Matching prescription claims with medication data for nursing home residents: Implications for prescriber feedback, drug utilisation studies and selection of prescription claims database

Medication data retrieved from Australian Repatriation Pharmaceutical Benefits Scheme (RPBS) claims for 44 veterans residing in nursing homes and Pharmaceutical Benefits Scheme (PBS) claims for 898 nursing home residents were compared with medication data from nursing home records to determine the optimal time interval for retrieving claims data and its validity. Optimal matching was achieved using 12 weeks of RPBS claims data, with 60% of medications in the RPBS claims located in nursing home administration records, and 78% of medications administered to nursing home residents identified in RPBS claims. In comparison, 48% of medications administered to nursing home residents could be found in 12 weeks of PBS data, and 56% of medications present in PBS claims could be matched with nursing home administration records. RPBS claims data was superior to PBS, due to the larger number of scheduled items available to veterans and the veteran's file number, which acts as a unique identifier. These findings should be taken into account when using prescription claims data for medication histories, prescriber feedback, drug utilisation, intervention or epidemiological studies. (C) 2001 Elsevier Science Inc. All rights reserved.

Research commentary: Information systems and conceptual modeling - A research agenda

Within the information systems field, the task of conceptual modeling involves building a representation of selected phenomena in some domain. High-quality conceptual-modeling work is important because it facilitates early detection and correction of system development errors. It also plays an increasingly important role in activities like business process reengineering and documentation of best-practice data and process models in enterprise resource planning systems. Yet little research has been undertaken on many aspects of conceptual modeling. In this paper, we propose a framework to motivate research that addresses the following fundamental question: How can we model the world to better facilitate our developing, implementing, using, and maintaining more valuable information systems? The framework comprises four elements: conceptual-modeling grammars, conceptual-modeling methods, conceptual-modeling scripts, and conceptual-modeling contexts. We provide examples of the types of research that have already been undertaken on each element and illustrate research opportunities that exist.

Contributo das tecnologias de informação na gestão do regime terapêutico no diabético

A diabetes é a doença do seculo XXI, atinge mais de um milhão de portugueses cada vez mais jovens em idades trabalhadoras, e já custa mais de 1% do PIB, além dos enormes danos que pode causar às pessoas e à sociedade. Segundo o Relatório Anual do Observatório Nacional da Diabetes, em 2011, cerca de um quarto da população portuguesa integrada no escalão etário dos 60 aos 79 tem Diabetes. Um estudo realizado pelo Lisbon Internet and Networks Institute (LINI), em 2010, diz-nos que “a internet é um recurso para a informação e educação para a saúde”. Em 2010 49% dos lares portugueses possuem acesso à internet e 44% da população é utilizadora (acréscimo significativo relativamente aos 29% em 2003). Destes, dois terços têm entre os 15 e os 24 anos. Os idosos representam 1,6%, dos quais os reformados e pensionistas representam 5%, as domésticas representam 11% e os trabalhadores manuais 22%, sendo estes os menos utilizadores. Um terço da restante população procura informação sobre saúde semanalmente, cerca de 16%. Face à atual conjuntura económica, com restrições orçamentais, nomeadamente na área da saúde, devem-se encontrar meios para prevenir e lidar com a Diabetes numa perspetiva de custo-benefício, isto porque a Diabetes pode reduzir as oportunidades de emprego e de aprendizagem. O atual diretor da Organização para a Cooperação e Desenvolvimento Económico (OCDE) Yyes Leterme diz que “Prevenir e tratar a Diabetes e as suas complicações custa cerca de 90 mil milhões de euros anualmente na Europa”. Atualmente, não é muito utilizado nem explorado o potencial das tecnologias de informação e as ferramentas web ao serviço da saúde, quer por profissionais de saúde, quer por utentes na gestão ao regime terapêutico na doença crónica, mais precisamente na gestão adequada da Diabetes. Potenciar uma visão integrada dos diferentes recursos de comunicação e a sua utilização conjugada com a promoção da saúde e prevenção da doença poderá enfatizar em termos de eficácia e eficiência a minimização de recursos das organizações de saúde e promover a gestão adequada da Diabetes. Tendo por base esta problemática, este estudo pretende abordar e refletir o possível contributo das tecnologias de informação e das ferramentas web na gestão adequada ao regime terapêutico da Diabetes.

Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome

Background Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer. Methods SOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62). Results SOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients’ outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression. Conclusions We showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.

Promoción de la salud bucodental en el ámbito escolar : "programa aprende a sonreír" : propuesta didáctica

En port.: Secretaría General de Salud Pública y Participación. Consejería de Salud. Dirección General de Innovación Educativa. Consejería de Educación. Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Ciudadanía / Nuestra Salud / Vida sana / Salud bucodental / Materiales para la Salud Bucodental Infantil)

Tabla de equivalencias entre la Organización Diagnóstica de Atención Temprana (ODAT) y la Clasificación Internacional de Enfermedades (CIE) [Recurso electrónico]

Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Salud Pública /Prevención / Atención Temprana /)

Frecuencia de la cesárea en Andalucía: relación con factores sociales, clínicos y de los servicios sanitarios (2007-2009).

BACKGROUND Increasing trend and geographical variations in the use of caesarean section suggest the influence of non-clinical factors. The objective was to describe the use of caesarean section in the Andalusian region in Spain by exploring the role of social, clinical, and health services variables. METHODS A cross-sectional study was carried out using vital statistics. It involves all births occurred in Andalusia during the period of 2007-2009. The dependent variable was the use of caesarean section and the set of covariates were classified into three groups: those with a clinical meaning, those related to the health services organization, and those with a social significance. Multivariate logistic regressions were used. RESULTS In the data set of 293,558 births, the prevalence of caesarean delivery was 24.8%. The multivariate analysis highlights the labour complications as the clinical variable with the highest odds ratio (OR=19.36). Regarding the health services variables, the odds of experiencing a caesarean delivery were 55% higher on weekdays than on weekends. Cádiz was the province with the highest OR for caesarean section (comparison between Cádiz and Almería: OR=1,21) where the ratio between births in public and private hospitals was 3.7. The frequency of caesarean section was 34% higher in women with third level education than those with no education. CONCLUSIONS Labour complication is the most influential variable for caesarean section. Caesarean birth rate is above the accepted standards for all social classes and increases with educational level. Inter-provincial differences reflect different patterns with regard to the use of private medicine.

Human Exposure to Endocrine-Disrupting Chemicals and Prenatal Risk Factors for Cryptorchidism and Hypospadias: A Nested Case-Control Study

BACKGROUND. Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs. OBJECTIVE. In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations. METHODS. In a case-control study, nested in a mother-child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS. TEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus non-detectable TEXB of 2.82 (95% CI, 1.10-7.24). More pesticides were detected in cases than in controls (9.34 +/- 3.19 vs. 6.97 +/- 3.93). ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p'-DDT (OR = 2.25; 95% CI, 1.03-4.89), p,p'-DDT (OR = 2.63; 95% CI, 1.21-5.72), lindane (OR = 3.38; 95% CI, 1.36-8.38), mirex (OR = 2.85; 95% CI, 1.22-6.66), and endosulfan alpha (OR = 2.19; 95% CI, 0.99-4.82). Engagement of mothers in agriculture (OR = 3.47; 95% CI, 1.33-9.03), fathers' occupational exposure to xenoestrogens (OR = 2.98; 95% CI, 1.11-8.01), and history of previous stillbirths (OR = 4.20; 95% CI, 1.11-16.66) were also associated with risk of malformations. CONCLUSIONS We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta.

NUTRISOL: un programa informático para la evaluación nutricional comunitaria y hospitalaria de acceso libre.

We have developed the computer programme NUTRISOL, a nutritional programme destined to analysis of dietary intake by means of the food transformation to nutrient. It has been performed under Windows operative system, using Visual Basic 6.0. It is presented in a CD-Rom. We have used the Spanish CSIC Food Composition Table and domestic food measures commonly used in Spain which could be modified and updated. Diverse kind of diets and reference anthropometric data are also presented. The results may be treated using various statistical programmes. The programme contains three modules: 1) Nutritional epidemiology, which allows to create or open a data base, sample management, analyse food intake, consultation of nutrient content and exportation of data to statistical programmes. 2) Analyses of diets and recipes, creation or modification of new ones. 3) To ask different diets for prevalent pathologies. Independent tools for modifying the original tables, calculate energetic needs, recommend nutrient intake and anthropometric indexes are also offered. In conclusion, NUTRISOL Programme is an application which runs in PC computers with minimal equipment in a friendly interface, of easy use, freeware, which may be adapted to each country, and has demonstrated its usefulness and reliability in different epidemiologic studies. Furthermore, it may become an efficient instrument for clinical nutrition and health promotion.

Web 2.0 y redes sociales, experiencias innovadoras en el SSPA

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

Telemedicine influence on the follow-up of type 2 diabetes patients.

OBJECTIVE This study was designed to evaluate the impact of a teleassistance system on the metabolic control of type 2 diabetes patients. RESEARCH DESIGN AND METHODS We conducted a 1-year controlled parallel-group trial comparing patients randomized (1) to an intervention group, assigned to a teleassistance system using real-time transmission of blood glucose results, with immediate reply when necessary, and telephone consultations, or (2) to a control group, being regularly followed-up at their healthcare center. Study subjects were type 2 diabetes patients >30 years of age followed in the primary care setting. RESULTS A total of 328 type 2 diabetes patients were recruited from 35 family practices in the province of Málaga, Spain. There was a reduction in hemoglobin A1c after 12 months from 7.62 +/- 1.60% to 7.40 +/- 1.43% (P = 0.027) in the intervention group and from 7.44 +/- 1.31% to 7.35 +/- 1.38% (P = 0.303) in the control group. The difference in the change between groups was not statistically significant. There was also a significant decrease in systolic and diastolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and body mass index in the intervention group. In the control group, the only significant decline was in low-density lipoprotein cholesterol. CONCLUSIONS A teleassistance system using real-time transmission of blood glucose results with an option to make telephone consultations is feasible in the primary care setting as a support tool for family physicians in their follow-up of type 2 diabetes patients.

The Andalusian Public Health System Virtual Library. Four years on

The Andalusian Public Health System Virtual Library (Biblioteca Virtual del Sistema Sanitario Público de Andalucía, BV-SSPA) set up in June 2006 was determined by the II Quality Plan 2005-2008. It consists of a regional government action with the aim of democratizing the health professional access to quality scientific information, regardless of the professional workplace. Andalusia is a region with more than 8 million inhabitants, with 92,000 health professionals for 41 hospitals, 1,500 primary healthcare centres, and 10 centres for non-medical attention purposes. • To obtain documentary resources for health professionals. • To help citizens to find health information. • To coordinate the Andalusian Health Documentary centres. • To establish strategic agreements with organizations. • To contribute to the Knowledge Management Development • The BV-SSPA acquires in a centralised way, all of the information resources for the whole system. • It offers services for all professionals: o Document Supply Service o Online Learning o User service • Remote access to these resources and services. • Communication and marketing plan to promote the knowledge and use of the BV-SSPA. Presently the BV-SSPA has reached: • The subscription of 2,431 electronic reviews, 8 data bases and other scientific information resources. • The establishment of the Document Supply Service, which focuses all the article orders from and for the Andalusian Public Health System. • The starting up for the online learning platform. • The introduction of the user service and virtual reference service in beta mode. • The use of appropriate tools, as the meta-researcher and the link resolver, which allow the presentation of resources and services in a tidy, easily findable way, through a Web 2.0 page where the user can take part with his contributions and where his offers and suggestion are gathered. • Access to the resources, for the Andalusian Health Professionals worldwide requiring only an internet connection. Andalusian Health Professionals have access to the greatest Health Science Electronic Resources Collection in Spain. The BV-SSPA has become the undisputed medium for the Health Research and Clinical Healthcare in our region, being consolidated as the Knowledge Manager into the Andalusian Public Health System. In 2010, it faces new projects such as the institutional repository creation, HypatiaSalud; the analysis of our research activity; and the drafting of a normalised licence model for the contracting of electronic resources.

Telehealth system (e-CUIDATE) to improve quality of life in breast cancer survivors: rationale and study protocol for a randomized clinical trial.

BACKGROUND Breast cancer survivors suffer physical impairment after oncology treatment. This impairment reduces quality of life (QoL) and increase the prevalence of handicaps associated to unhealthy lifestyle (for example, decreased aerobic capacity and strength, weight gain, and fatigue). Recent work has shown that exercise adapted to individual characteristics of patients is related to improved overall and disease-free survival. Nowadays, technological support using telerehabilitation systems is a promising strategy with great advantage of a quick and efficient contact with the health professional. It is not known the role of telerehabilitation through therapeutic exercise as a support tool to implement an active lifestyle which has been shown as an effective resource to improve fitness and reduce musculoskeletal disorders of these women. METHODS / DESIGN This study will use a two-arm, assessor blinded, parallel randomized controlled trial design. People will be eligible if: their diagnosis is of stages I, II, or IIIA breast cancer; they are without chronic disease or orthopedic issues that would interfere with ability to participate in a physical activity program; they had access to the Internet and basic knowledge of computer use or living with a relative who has this knowledge; they had completed adjuvant therapy except for hormone therapy and not have a history of cancer recurrence; and they have an interest in improving lifestyle. Participants will be randomized into e-CUIDATE or usual care groups. E-CUIDATE give participants access to a range of contents: planning exercise arranged in series with breathing exercises, mobility, strength, and stretching. All of these exercises will be assigned to women in the telerehabilitation group according to perceived needs. The control group will be asked to maintain their usual routine. Study endpoints will be assessed after 8 weeks (immediate effects) and after 6 months. The primary outcome will be QoL measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0 and breast module called The European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire. The secondary outcomes: pain (algometry, Visual Analogue Scale, Brief Pain Inventory short form); body composition; physical measurement (abdominal test, handgrip strength, back muscle strength, and multiple sit-to-stand test); cardiorespiratory fitness (International Fitness Scale, 6-minute walk test, International Physical Activity Questionnaire-Short Form); fatigue (Piper Fatigue Scale and Borg Fatigue Scale); anxiety and depression (Hospital Anxiety and Depression Scale); cognitive function (Trail Making Test and Auditory Consonant Trigram); accelerometry; lymphedema; and anthropometric perimeters. DISCUSSION This study investigates the feasibility and effectiveness of a telerehabilitation system during adjuvant treatment of patients with breast cancer. If this treatment option is effective, telehealth systems could offer a choice of supportive care to cancer patients during the survivorship phase. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01801527.