Personalised nutrition: status and perspectives

Personalised, genotype-based nutrition is a concept that links genotyping with specific nutritional advice in order to improve the prevention of nutrition-associated, chronic diseases. This review describes the current scientific basis of the concept and discusses its problems. There is convincing evidence that variant genes may indeed determine the biological response to nutrients. The effects of single-gene variants on risk or risk factor levels of a complex disease are, however, usually small and sometimes inconsistent. Thus, information on the effects of combinations of relevant gene variants appears to be required in order to improve the predictive precision of the genetic information. Furthermore, very few associations between genotype and response have been tested for causality in human intervention studies, and little is known about potential adverse effects of a genotype-derived intervention. These issues need to be addressed before genotyping can become an acceptable method to guide nutritional recommendations.

Human Stem Cell Cultures from Cleft Lip/Palate Patients Show Enrichment of Transcripts Involved in Extracellular Matrix Modeling By Comparison to Controls

Nonsyndromic cleft lip and palate (NSCL/P) is a complex disease resulting from failure of fusion of facial primordia, a complex developmental process that includes the epithelial-mesenchymal transition (EMT). Detection of differential gene transcription between NSCL/P patients and control individuals offers an interesting alternative for investigating pathways involved in disease manifestation. Here we compared the transcriptome of 6 dental pulp stem cell (DPSC) cultures from NSCL/P patients and 6 controls. Eighty-seven differentially expressed genes (DEGs) were identified. The most significant putative gene network comprised 13 out of 87 DEGs of which 8 encode extracellular proteins: ACAN, COL4A1, COL4A2, GDF15, IGF2, MMP1, MMP3 and PDGFa. Through clustering analyses we also observed that MMP3, ACAN, COL4A1 and COL4A2 exhibit co-regulated expression. Interestingly, it is known that MMP3 cleavages a wide range of extracellular proteins, including the collagens IV, V, IX, X, proteoglycans, fibronectin and laminin. It is also capable of activating other MMPs. Moreover, MMP3 had previously been associated with NSCL/P. The same general pattern was observed in a further sample, confirming involvement of synchronized gene expression patterns which differed between NSCL/P patients and controls. These results show the robustness of our methodology for the detection of differentially expressed genes using the RankProd method. In conclusion, DPSCs from NSCL/P patients exhibit gene expression signatures involving genes associated with mechanisms of extracellular matrix modeling and palate EMT processes which differ from those observed in controls. This comparative approach should lead to a more rapid identification of gene networks predisposing to this complex malformation syndrome than conventional gene mapping technologies.

Mixed-initiative decision support for care planning based on clinical practice guidelines

Care Plan On-Line (CPOL) is an intranet based system that supports a “Coordinated Care” model for chronic/complex disease management. CPOL combines provision of solicited and unsolicited advice features based on integration of the electronic medical record (EMR) with its decision support logic. The objective is to support General Practitioners (GPs) in formulating a 12-month care plan of services such that: (a) the plan is proactive and patient-centered; (b) the GP is kept in awareness of project- and diseasespecific clinical practice guidelines; and (c) the support integrates with GP workflow in a natural fashion. A key feature of our approach is to blur the distinction of EMR and decision support by presenting guidelines in layers with the top-most being a problem-oriented presentation of patient status, progressing on through to patient-independent supporting evidence. In conjunction with a degree of automated inclusion of care planning services, the system demonstrates mixed user and software initiative. We describe the CPOL deployment setting, the challenges of guideline-based clinical decision support, our approach to guideline delivery, and the CPOL architecture.

New approaches to gene discovery with animal models of obesity and diabetes

DNA-based approaches to the discovery of genes contributing to the development of type 2 diabetes have not been very successful despite substantial investments of time and money. The multiple gene-gene and gene-environment interactions that influence the development of type 2 diabetes mean that DNA approaches are not the ideal tool for defining the etiology of this complex disease. Gene expression-based technologies may prove to be a more rewarding strategy to identify diabetes candidate genes. There are a number of RNA-based technologies available to identify genes that are differentially expressed in various tissues in type 2 diabetes. These include differential display polymerase chain reaction (ddPCR), suppression subtractive hybridization (SSH), and cDNA microarrays. The power of new technologies to detect differential gene expression is ideally suited to studies utilizing appropriate animal models of human disease. We have shown that the gene expression approach, in combination with an excellent animal model such as the Israeli sand rat (Psammomys obesus), can provide novel genes and pathways that may be important in the disease process and provide novel therapeutic approaches. This paper will describe a new gene discovery, beacon, a novel gene linked with energy intake. As the functional characterization of novel genes discovered in our laboratory using this approach continues, it is anticipated that we will soon be able to compile a definitive list of genes that are important in the development of obesity and type 2 diabetes.

Applications of aptamers in nanodelivery systems in cancer, eye and inflammatory diseases

Aptamers are an interesting class of molecules that have potential in many facets of human health. They are characterized by high affinity and specificity to their targets, are small in size, have similar properties to antibodies, but are made synthetically. All of these properties, among others, give aptamers the potential to diagnose, image and treat like no other molecules. By combining the unique properties of aptamers with the ever expanding field of nanotechnology and all it has to offer, we are entering a very promising new area of targeted nanodelivery treatments. These treatments have found success in the complex disease processes of cancer, eye and inflammatory diseases.

Prevention of childhood obesity

Childhood obesity is a complex disease with different genetic, metabolic, environmental and behavioural components that are interrelated and potentially confounding, thus making causal pathways difficult to define. Given the tracking of obesity and the associated risk factors, childhood is an important period for prevention. To date, evidence would support preventative interventions that encourage physical activity and a healthy diet, restrict sedentary activities and offer behavioural support. However, these interventions should involve not only the child but the whole family, school and community. If the current global obesity epidemic is to be halted, further large-scale, well-designed prevention studies are required, particularly within settings outside of the USA, in order to expand the currently limited evidence base upon which clinical recommendations and public health approaches can be formulated. This must be accompanied by enhanced monitoring of paediatric obesity prevalence and continued support from all stakeholders at global, national, regional and local levels.

Genes candidatos de suscetibilidade a pré-eclampsia: estudo de associação

Preeclampsia is a multifactorial disease of unknown etiology that features with wide clinical symptoms, ranging from mild preeclampsia to severe forms, as eclampsia and HELLP syndrome. As a complex disease, preeclampsia is also influenced by genetic and environmental factors. Aiming to identify preeclampsia susceptibility genes, we genotyped a total of 22 genetic markers (single nucleotides polymorphisms SNPs) distributed in six candidates genes (ACVR2A, FLT1, ERAP1, ERAP2, LNPEP e CRHBP). By a case-control approach, the genotypic frequencies were compared between normotensive (control group) and preeclamptic women. The case s group was classified according to the disease clinical form in: preeclampsia, eclampsia and HELLP syndrome. As results we found the following genetic association: 1) ACVR2A and preeclampsia; 2) FLT1 and severe preeclampsia; 3) ERAP1 and eclampsia; 4) FLT1 and HELLP syndrome. When stratifying preeclampsia group according to symptoms severity (mild and severe preeclampsia) or according to the time of onset (early and late preeclampsia), it was detected that early preeclampsia is strongly associated to risk preeclampsia, eclampsia and HELLP syndrome have different genetic bases, although FLT1 gene seems to be involved in preeclampsia and HELLP syndrome pathophisiology

TRAIL-R3-related apoptosis: Epigenetic and expression analyses in women with ovarian neoplasia

Objective. To assess the expression of TRAIL-R3 and the methylation of a CpG island within the TRAIL-R3 promoter both in cystadenoma tumors and primary and metastatic epithelial ovarian carcinoma (EOC).Methods. RNA was obtained from women with normal ovarian (NO) tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and EOC (n = 16) using Trizol (R). Quantitative PCR (gRT-PCR) was performed to quantify the relative levels of TRAIL-R3. The methylation frequency of the CpG island in the TRAIL-R3 promoter was assessed using the methylation-specific PCR (MSP) assay after DNA bisulfite conversion. The differences between the groups were evaluated using the chi-square, Student's t, ANOVA, Mann-Whitney U, Wilcoxon or Kruskal-Wallis tests as indicated. The survival rates were calculated using the Kaplan-Meier method.Results. Cystadenoma and metastatic EOC tumors expressed significantly more TRAIL-R3 mRNA than primary EOC tumors. Methylation of the TRAIL-R3 promoter was absent in NO tissues, while hemimethylation of the TRAIL-R3 promoter was frequently found in the neoplasia samples with 45.4% of the cystadenoma tumors, 8.3% of the primary EOC samples and 11.1% of the metastatic EOC samples showing at least partial methylation (p = 0.018). Neither the expression of TRAIL-R3 nor alterations in the methylation profile were associated to cumulative progression-free survival or the overall survival in EOC patients.Conclusions. Primary EOC is associated to a lower TRAIL-R3 expression, which leads to a better understanding of the complex disease and highlighting potential therapeutic targets. Promoter DNA methylation was not related to this finding, suggesting the presence of other mechanisms to transcriptional control. (C) 2012 Elsevier B.V. All rights reserved.

Transcriptional changes associated with recurrent airway obstruction in affected and unaffected horses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Microscopical Evaluation of Extracellular Matrix and Its Relation to the Palatopharyngeal Muscle in Obstructive Sleep Apnea

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Detecção do Grapevine leafroll-associated virus 5 no Estado de São Paulo

O enrolamento da folha da videira (grapevine leafroll) é uma doença atribuída a pelo menos nove vírus sorologicamente distintos, Grapevine leafroll-associated viruses 1 a 9 e designados GLRaV-1 a GLRaV-9. No Brasil, já é conhecida a existência do GLRaV-1, GLRaV-2, GLRaV-3 e GLRaV-6. Neste trabalho, foi demonstrada a ocorrência do GLRaV-5 em amostras de videiras cultivadas no Estado de São Paulo, mediante teste de Biotina-ELISA. O vírus foi detectado com baixa incidência nas cultivares avaliadas, exceto na 'Cardinal', que apresentou 100% de infecção. Este é o primeiro relato da ocorrência do GLRaV-5 no Brasil.

Alterações ultrassonográficas abdominais, hematológicas e de perfil bioquímico em cães com linfoma

Pós-graduação em Medicina Veterinária - FMVZ

Alterações cardiovasculares e desenvolvimento de obesidade em animais submetidos à dieta hipercalórica e estresse crônico

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Contribuição das moléculas de antígeno de histocompatibilidade leucocitária (HLA) para a contratura de Dupuytren em uma população do Sudeste do Brasil

Objetivo:O objetivo deste estudo foi investigar o fenótipo do HLA em pacientes com contratura de Dupuytren (CD) para verificar a correlação desses alelos com os fatores de risco para o desenvolvimento da CD na população brasileira.Métodos:Este foi um estudo de caso-controle de 25 pacientes com CD e 443 indivíduos saudáveis sem histórico de doenças associadas ao HLA. As tipagens classe I e classe II do HLA foram feitas utilizando o método iniciador de sequências específicas da reação em cadeia da polimerase.Resultados:O fenótipo HLA-B*18 foi observado em 32% dos pacientes e 10,5% do grupo controle. Contudo, os valores de p não permaneceram significativos após correção.Discussão:Apesar de termos observado um aumento na tendência de os pacientes com CD terem o alelo HLA-B*18, os resultados não foram estatisticamente significativos após correção. Esse alelo foi maior em pacientes de etnia italiana e/ou espanhola, locais com frequências superiores a 18% e 14%, respectivamente. São necessárias investigações adicionais com uma coorte maior de pacientes com CD para confirmar o possível papel do HLA nessa doença.

Experiência discente com o cuidado a paciente portador de Epidermodisplasia Verruciforme

Report of an experience of nursing students in providing care to a patient with epidermodysplasia verruciformis, during the internship in the discipline Nursing in Transmittable Diseases, at the dermatology ward of a teaching hospital, located in the state of São Paulo, Brazil, in 2009. This is a rare genodermatosis, susceptible to infection with different types of human papilloma viruses, that cause exacerbated physical changes that impact the psyche of the affected individual. Care delivery was based on the assistance complexity indicated by the application of the Patient Classification System proposed by Perroca. The experience allowed students to learn how to cope with a patient affected by a rare and complex disease, of difficult resolution, and to provide integral care to this individual, perceiving him beyond the lesions. One conclude that the experience has greatly contributed to the growth of the students as future professionals.