Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.

Current approaches and future perspectives on strategies for the development of personalized tissue engineering therapies

Personalized tissue engineering and regenerative medicine (TERM) therapies propose patient-oriented effective solutions, considering individual needs. Cell-based therapies, for example, may benefit from cell sources that enable easier autologous set-ups or from recent developments on IPS cells technologies towards effective personalized therapeutics. Furthermore, the customization of scaffold materials to perfectly fit a patientâ s tissue defect through rapid prototyping technologies, also known as 3D printing, is now a reality. Nevertheless, the timing to expand cells or to obtain functional in vitrotissue substitutes prior to implantation prevents advancements towards routine use upon patient´s needs. Thus, personalized therapies also anticipate the importance of creating off-the-shelf solutions to enable immediately available tissue engineered products. This paper reviews the main recent developments and future challenges to enable personalized TERM approaches and to bring these technologies closer to clinical applications.

Impact of Delftia tsuruhatensis and Achromobacter xylosoxidans on Escherichia coli dual-species biofilms treated with antibiotic agents

Recently it was demonstrated that for urinary tract infections species with a lower or unproven pathogenic potential, such as Delftia tsuruhatensis and Achromobacter xylosoxidans, might interact with conventional pathogenic agents such as Escherichia coli. Here, single- and dual-species biofilms of these microorganisms were characterized in terms of microbial composition over time, the average fitness of E. coli, the spatial organization and the biofilm antimicrobial profile. The results revealed a positive impact of these species on the fitness of E. coli and a greater tolerance to the antibiotic agents. In dual-species biofilms exposed to antibiotics, E. coli was able to dominate the microbial consortia in spite of being the most sensitive strain. This is the first study demonstrating the protective effect of less common species over E. coli under adverse conditions imposed by the use of antibiotic agents.

Protective effect of left ventricular hypertrophy in right coronary artery occlusions

OBJECTIVE: To test the hypothesis that left ventricular hypertrophy (LVH) reduces the electrocardiographic and functional effects of right coronary artery occlusion. METHODS: We analysed 215 patients (166 males and 49 women,age of 58.9±10.6 years), with occlusion of the right coronary artery without other associated lesions. There was no significant difference (p>0.05) in age and gender distribution between the 78 patients with LVH (left ventricular mass >100g/m²) (Group A) when compared with the 137 patients without LVH (left ventricular mass <100g/m²) (Group B). RESULTS: The electrocardiographic finding of transmural necrosis was more often found in group B patients than in group A patients (56.9% and 30.8%, respectively; p<0.05). The left ventricular function parameters of group A were better than those of group B: the ratio end-diastolic pressure/systolic pressure (EDP/SP) (A: 0.108±0.036; B: 0.121±0.050; p<0.05); the end-diastolic volume index (A: 75.9±31.3ml/m²; B: 88.0±31.0ml/m²; p<0.01); the end-systolic volume index (A: 16.0±10.0ml/m²; B: 27.0 ±20.0ml/m²; p<0.001); the ejection fraction (A 78.6±10.8%; B 67.7±17.9%; p<0.001); the anteroinferior shortening (A: 43.9±10.3%; B: 35.1±12.8%; p<0.001). A higher degree of coronary tortuosity was observed in group A than in group B (78.2% and 24.1%; p<0.001) and also a more frequent absent or minimal diaphragmatic hypokinetic area (A: 80.8%; B: 54.0%; p<0.05). CONCLUSION: LVH reduces the effects of myocardial sequela and protects LV function when right coronary occlusion develops.

Listening to the public: enacting power : citizen access, Standing and influence in public participation discourses

Public participation in environmental governance is typically associated with citizen access to power despite many closures and limitations having been identified in participatory processes. This article proposes an analytical framework to analyse discursive practices involved in public consultation processes. Critical Discourse Analysis is used to examine and appraise citizens’ access, standing and influence. We apply that framework to a ‘notice and comment’ process on a hydroelectric power plan in Portugal and show that it was discursively managed to justify the decision of constructing 10 large dams and to reject critical or alternative views. Citizens’ access, standing and influence were constrained through diverse discursive practices which (re)produced very unequal power relationsbetween policy proponents and participating individuals. More generally, the article illustrates the potential of Critical Discourse Analysis to assess voice(s) in policy processes. Focusing on argumentative, interactional and rhetorical levels, and how they are interwoven in public consultation discourses, the proposed framework is conceivably applicable in other studies.

Media(ted) discourse and society: rethinking the framework of critical discourse analysis

The analysis of journalistic discourse and its social embeddedness has known significant advances in the last two decades, especially due to the emergence and development of Critical Discourse Analysis. However, three important aspects remain under-researched: the time plane in discourse analysis, the discursive strategies of social actors, and the extra- and supra-textual effects of mediated discourse. Firstly, understanding the biography of public matters requires a longitudinal examination of mediated texts and their social contexts but most forms of analysis of journalistic discourse do not account for the time sequence of texts and its implications. Secondly, as the media representation of social issues is, to a large extent, a function of the discursive construction of events, problems and positions by social actors, the discursive strategies that they employ in a variety of arenas and channels ‘‘before’’ and ‘‘after’’ journalistic texts need to be examined. Thirdly, the fact that many of the modes of operation of discourse are extra- or supra-textual calls for a consideration of various social processes ‘‘outside’’ the text. This paper aims to produce a theoretical and methodological contribution to the integration of these issues in discourse analysis by proposing a framework that combines a textual dimension with a contextual one

Sefficiency (sustainable efficiency) of water–energy–food entangled systems

Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/07900627.2015.1070091. It includes an easy-to-use spreadsheet that calculates the efficiencies used in this paper, that is Sefficiency with energy considerations.

First- and second-time parents’ couple relationship: from pregnancy to second year postpartum

First- and second-time parents’ couple relationships were studied from early pregnancy to the second year postpartum. The Relationship Questionnaire (RQ) was administered to Portuguese couples (N = 82), first- or second-time parents, at the first, second and third pregnancy trimester, childbirth, 3 and 18 months postpartum. Adverse changes in positive and negative partner relationship dimensions were reported from early pregnancy to the second year postpartum by all participants; in the same way by mothers and fathers and by first- and second-time parents. Second-time parents reported a worse couple relationship (lower RQ-positive scores) than first-time parents, but only during pregnancy. Results from the present study suggest a decline in partner relationship quality during the transition to parenthood both in mothers and fathers, as well as in first- and second-time parents.

Sleep during the third trimester of pregnancy: the role of depression and anxiety

Depression has been associated with sleep disturbances in pregnancy; however, no previous research has controlled the possible confounding effect of anxiety on this association. This study aims to analyze the effect of depression on sleep during the third trimester of pregnancy controlling for anxiety. The sample was composed by 143 depressed (n = 77) and non-depressed (n = 66) pregnant women who completed measures of depression, anxiety, and sleep. Differences between groups in sleep controlling for anxiety were found. Depressed pregnant women present higher number of nocturnal awakenings and spent more hours trying falling asleep during the night and the entire 24 h period. Present findings point out the effect of depression on sleep in late pregnancy, after controlling for anxiety.

Self-reported psychosocial factors among In Vitro Fertilization patients interviewed alone or with the partner

"Published online: 07 Nov 2015"

Post-divorce representations of marital negotiation during marriage predict parenting alliance in newly divorced parents

Literature demonstrates that marital and co-parenting subsystems are intercorrelated and have autonomous functions in the family system. This study explored representations of marital negotiation strategies for conflict resolution during marriage and parenting alliance relationship after divorce, using data from Portuguese newly divorced parents. In multiple regression analysis, representations of marital negotiation strategies for conflict resolution during marriage used by ex-spouses predict positive parenting alliance relationship after divorce. These results suggest that representations of pre-divorce marital relationship influence positively current interparental relationship regarding child rearing after marital dissolution. Implications for clinical interventions are also discussed.

Chronic prenatal depression and neonatal outcome

Four hundred and thirty pregnant women were recruited at approximately 22 weeks gestation at prenatal clinics. Of these, 86 (20%) were diagnosed as depressed. The women were seen again at approximately 32 weeks gestation and after delivery. Chronicity of depression was evidenced by continuing high depression scores in those women diagnosed as depressed. Comorbid problems were chronically high anxiety, anger, sleep disturbance, and pain scores. Less optimal outcomes for the depressed women included lower gestational age and lower birthweight of their newborns.

Transnational identities in the fiction of Monica Ali: In the Kitchen and Alentejo Blue

Monica Ali’s In the Kitchen shows London as a cosmopolitan and postmodern city, a locus of transnational identities. Although this is not a new theme in contemporary English writing, in this novel the topic of migration is detached from the usual postcolonial loci that feature in “immigrant” or “diasporic” literature. In the novel Alentejo Blue, set in the South of Portugal, Monica Ali had already approached the question of migration from the point of view of the exiled citizen, whose situation is part of globalization processes outside of the normal push/pull (centre/periphery, east/west, north/south) conceptions of migration. The focus in the article is, thus, on the ways the new world order of economic globalization relates to the processes of immigration and the dispersal of a stable sense of individual and national identity.

Separation by thermal diffusion in a rotary column

A rotary thermal diffusion column with the inner cylinder rotating and the outer cylinder static was used to separate n-heptane-benzene mixtures at different speeds of rotation. The results show that the column efficiency depends on the speed of rotation. For the optimum speed the increase in efficiency relative to the static column was of the order of 8%. The role of the geometric irregularities in the annulus width on performance of the rotary column is also discussed.