Review Article p16 INK4A and p14 ARF Gene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review

Head and neck squamous cell carcinoma is a heterogeneous group of tumors with each subtype having a distinct histopathological and molecular profile. Most tumors share, to some extent, the same multistep carcinogenic pathways, which include a wide variety of genetic and epigenetic changes. Epigenetic alterations represent all changes in gene expression patterns that do not alter the actual DNA sequence. Recently, it has become clear that silencing of cancer related genes is not exclusively a result of genetic changes such as mutations or deletions, but it can also be regulated on epigenetic level, mostly by means of gene promoter hypermethylation. Results from recent studies have demonstrated that DNA methylation patterns contain tumor-type-specific signatures, which could serve as biomarkers for clinical outcome in the near future. The topic of this review discusses gene promoter hypermethylation in oral and oropharyngeal squamous cell carcinoma (OSCC). The main objective is to analyse the available data on gene promoter hypermethylation of the cell cycle regulatory proteins p16 INK4A and p14 ARF and to investigate their clinical significance as novel biomarkers in OSCC. Hypermethylation of both genes seems to possess predictive properties for several clinicopathological outcomes. We conclude that the methylation status of p16 INK4A is definitely a promising candidate biomarker for predicting clinical outcome of OSCC, especially for recurrence-free survival

Splanchnic Artery Stenosis and Abdominal Complaints: Clinical History Is of Limited Value in Detection of Gastrointestinal Ischemia

BACKGROUND: Splanchnic artery stenosis is common and mostly asymptomatic and may lead to gastrointestinal ischemia (chronic splanchnic syndrome, CSS). This study was designed to assess risk factors for CSS in the medical history of patients with splanchnic artery stenosis and whether these risk factors can be used to identify patients with high and low risk of CSS. METHODS: All patients referred for suspected CSS underwent a standardized workup, including a medical history with questionnaire, duplex ultrasound, gastrointestinal tonometry, and angiography. Definitive diagnosis and treatment advice was made in a multidisciplinary team. Patients with confirmed CSS were compared with no-CSS patients. RESULTS: A total of 270 patients (102 M, 168 F; mean age, 53 years) with splanchnic artery stenosis were analyzed, of whom 109 (40%) had CSS and 161 no CSS. CSS-patients more often reported postprandial pain (87% vs. 72%, p = 0.007), weight loss (85% vs. 70%, p = 0.006), adapted eating pattern (90% vs. 79%, p = 0.005) and diarrhea (35% vs. 22%, p = 0.023). If none of these risk factors were present, the probability of CSS was 13%; if all were present, the probability was 60%. Adapted eating pattern (odds ratio (OR) 3.1; 95% confidence interval (CI) 1.08-8.88) and diarrhea (OR 2.6; 95% CI 1.31-5.3) were statistically significant in multivariate analysis. CONCLUSIONS: In patients with splanchnic artery stenosis, the clinical history is of limited value for detection of CSS. A diagnostic test to detect ischemia is indispensable for proper selection of patients with splanchnic artery stenosis who might benefit from treatment

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

Educação integral, institucionalização do tempo livre: outras lógicas educacionais no contexto Luso-Brasileiro

A finalidade principal do presente artigo é refletir sobre os debates que circundam a educação integral. Baseado em revisão bibliográfica de estudos específicos sobre essa temática, propõe um breve diálogo entre concepções de educação integral no Brasil e em Portugal, articulando-as com propostas no campo da educação não formal. São apresentadas observações sobre as peculiaridades da educação integral em ambos os países, atentos para outros jeitos de organizar o processo educacional, escapando de uma única lógica e do risco de institucionalização cada vez maior do tempo livre.The main purpose of the article is to reflect on the debates surrounding full-time education, and based on a bibliographical review of specific studies on the subject, to propose a brief dialogue between the conceptions of full-time education in Brazil and Portugal, articulating them with proposals in the field of non-formal education. Observations on the peculiarities of full-time education in both countries are presented here, attentive to other ways of organizing the educational process, escaping from a single logic and the risk of institutionalization of free time. Keywords: Full-time education; Non-formal and informal education; Community interventio

Histoire inachevée de la régulation du marché du riz pour un développement durable à Madagascar : [Filières et marchés].

L'envolée récente des prix du riz à Madagascar, fortement impulsée de l'extérieur, a mis en évidence la nécessité de rénover le mode de régulation de la filière. La sortie de crise vers une trajectoire d'accumulation du capital repose sur l'émergence de compromis institutionnalisés entre agents de la filière. Le nouveau cadre de régulation à construire limite l'intervention de l'Etat à la création des conditions favorables au fonctionnement d'un marché libre et en voie d'organisation. (Résumé d'auteur