Prostate cancer biomarkers: a practical review based on different clinical scenarios

Traditionally, diagnosis and staging of prostate cancer (PCa) have been based on prostate-specific antigen (PSA) level, digital rectal examination (DRE), and transrectal ultrasound (TRUS) guided prostate biopsy. Biomarkers have been introduced into clinical practice to reduce the overdiagnosis and overtreatment of low-grade PCa and increase the success of personalized therapies for high-grade and high-stage PCa. The purpose of this review was to describe available PCa biomarkers and examine their use in clinical practice. A nonsystematic literature review was performed using PubMed and Scopus to retrieve papers related to PCa biomarkers. In addition, we manually searched websites of major urological associations for PCa guidelines to evaluate available evidence and recommendations on the role of biomarkers and their potential contribution to PCa decision-making. In addition to PSA and its derivates, thirteen blood, urine, and tissue biomarkers are mentioned in various PCa guidelines. Retrospective studies have shown their utility in three main clinical scenarios: (1) deciding whether to perform a biopsy, (2) distinguishing patients who require active treatment from those who can benefit from active surveillance, and (3) defining a subset of high-risk PCa patients who can benefit from additional therapies after RP. Several validated PCa biomarkers have become commercially available in recent years. Guidelines now recommend offering these tests in situations in which the assay result, when considered in combination with routine clinical factors, is likely to affect management. However, the lack of direct comparisons and the unproven benefits, in terms of long-term survival and cost-effectiveness, prevent these biomarkers from being integrated into routine clinical use

A pervasive approach to a real-time intelligent decision support system in intensive medicine

The decision on the most appropriate procedure to provide to the patients the best healthcare possible is a critical and complex task in Intensive Care Units (ICU). Clinical Decision Support Systems (CDSS) should deal with huge amounts of data and online monitoring, analyzing numerous parameters and providing outputs in a short real-time. Although the advances attained in this area of knowledge new challenges should be taken into account in future CDSS developments, principally in ICUs environments. The next generation of CDSS will be pervasive and ubiquitous providing the doctors with the appropriate services and information in order to support decisions regardless the time or the local where they are. Consequently new requirements arise namely the privacy of data and the security in data access. This paper will present a pervasive perspective of the decision making process in the context of INTCare system, an intelligent decision support system for intensive medicine. Three scenarios are explored using data mining models continuously assessed and optimized. Some preliminary results are depicted and discussed.Fundação para a Ciência e a Tecnologia (FCT

Talking alone : Reality TV, emotions and authenticity

This article examines reality TV as an illustration of contemporary confessional culture in which the key attraction is the disclosure of true emotions. This article hopes to contribute to the understanding of the production of self-disclosure through a formal analysis of international and domestic dating, adventure and lifestyle-oriented reality shows broadcast on Finnish television between 2002 and 2004. The diverse programmes verify that reality TV shows capitalize on a variety of talk situations within one programme, but it is the monologue that is used as a truth-sign of direct access to the authentic. We also suggest that the power of monologue in the reality genre promotes the transformation of television from a mass medium to first-person medium addressing masses of individuals.Peer reviewe

Child and parent predictors of picky eating from preschool to school age

Background: Picky eating is prevalent in childhood. Because pickiness concerns parents and is associated with nutrient deficiency and psychological problems, the antecedents of pickiness need to be identified. We propose an etiological model of picky eating involving child temperament, sensory sensitivity and parent-child interaction. Methods: Two cohorts of 4-year olds (born 2003 or 2004) in Trondheim, Norway were invited to participate (97.2% attendance; 82.0% consent rate, n = 2475) and a screen-stratified subsample of 1250 children was recruited. We interviewed 997 parents about their child’s pickiness and sensory sensitivity using the Preschool Age Psychiatric Assessment (PAPA). Two years later, 795 of the parents completed the interview. The Children’s Behavior Questionnaire (CBQ) was used to assess children’s temperament. Parent- child interactions were videotaped and parental sensitivity (i.e., parental awareness and appropriate responsiveness to children’s verbal and nonverbal cues) and structuring were rated using the Emotional Availability Scales (EAS). Results: At both measurement times, 26% of the children were categorized as picky eaters. Pickiness was moderately stable from preschool to school age (OR = 5.92, CI = 3.95, 8.86), and about half of those who displayed pickiness at age 4 were also picky eaters two years later. While accounting for pickiness at age 4, sensory sensitivity at age 4 predicted pickiness at age 6 (OR = 1.25, CI = 1.08, 2.23), whereas temperamental surgency (OR = 0.88, CI = 0.64, 1.22) and negative affectivity (OR = 1.17, CI = 0.75, 1.84) did not. Parental structuring was found to reduce the risk of children’s picky eating two years later (OR = 0.90, CI = 0.82, 0.99), whereas parental sensitivity increased the odds for pickiness (OR = 1.10, CI = 1.00, 1.21). Conclusions: Although pickiness is stable from preschool to school age, children who are more sensory sensitive are at higher risk for pickiness two years later, as are children whose parents display relatively higher levels of sensitivity and lower levels of structuring. Our findings suggest that interventions targeting children’s sensory sensitivity, as well as parental sensitivity and structuring, might reduce the risk of childhood pickiness. Health care providers should support parents of picky eaters in repeatedly offering unfamiliar and rejected foods to their children without pressure and acknowledging child autonomy

The Side Population in Human Lung Cancer Cell Line NCI-H460 Is Enriched in Stem-Like Cancer Cells

Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate. Recent studies indicate that tumors contain a subset of stem-like cancer cells that possess certain stem cell properties. Herein, we used Hoechst 33342 dye efflux assay and flow cytometry to isolate and characterize the side population (SP) cells from human lung cancer cell line NCI-H460 (H460). We show that the H460 SP cells harbor stem-like cells as they can readily form anchorage-independent floating spheres, possess great proliferative potential, and exhibit enhanced tumorigenicity. Importantly, the H460 SP cells were able to self-renew both in vitro and in vivo. Finally, we show that the H460 SP cells preferentially express ABCG2 as well as SMO, a critical mediator of the Hedgehog (HH) signaling, which seems to play an important role in H460 lung cancer cells as its blockage using Cyclopamine greatly inhibits cell-cycle progression. Collectively, our results lend further support to the existence of lung cancer stem cells and also implicate HH signaling in regulating large-cell lung cancer (stem) cells

Genetic Modulation of Rpd3 Expression Impairs Long-Term Courtship Memory in Drosophila

There is increasing evidence that regulation of local chromatin structure is a critical mechanism underlying the consolidation of long-term memory (LTM), however considerably less is understood about the specific mechanisms by which these epigenetic effects are mediated. Furthermore, the importance of histone acetylation in Drosophila memory has not been reported. The histone deacetylase (HDAC) Rpd3 is abundant in the adult fly brain, suggesting a post-mitotic function. Here, we investigated the role of Rpd3 in long-term courtship memory in Drosophila. We found that while modulation of Rpd3 levels predominantly in the adult mushroom body had no observed impact on immediate recall or one-hour memory, 24-hour LTM was severely impaired. Surprisingly, both overexpression as well as RNAi-mediated knockdown of Rpd3 resulted in impairment of long-term courtship memory, suggesting that the dose of Rpd3 is critical for normal LTM

An iconic language for the graphical representation of medical concepts

<p>Abstract</p> <p>Background</p> <p>Many medication errors are encountered in drug prescriptions, which would not occur if practitioners could remember the drug properties. They can refer to drug monographs to find these properties, however drug monographs are long and tedious to read during consultation. We propose a two-step approach for facilitating access to drug monographs. The first step, presented here, is the design of a graphical language, called VCM.</p> <p>Methods</p> <p>The VCM graphical language was designed using a small number of graphical primitives and combinatory rules. VCM was evaluated over 11 volunteer general practitioners to assess if the language is easy to learn, to understand and to use. Evaluators were asked to register their VCM training time, to indicate the meaning of VCM icons and sentences, and to answer clinical questions related to randomly generated drug monograph-like documents, supplied in text or VCM format.</p> <p>Results</p> <p>VCM can represent the various signs, diseases, physiological states, life habits, drugs and tests described in drug monographs. Grammatical rules make it possible to generate many icons by combining a small number of primitives and reusing simple icons to build more complex ones. Icons can be organized into simple sentences to express drug recommendations. Evaluation showed that VCM was learnt in 2 to 7 hours, that physicians understood 89% of the tested VCM icons, and that they answered correctly to 94% of questions using VCM (versus 88% using text, <it>p </it>= 0.003) and 1.8 times faster (<it>p </it>< 0.001).</p> <p>Conclusion</p> <p>VCM can be learnt in a few hours and appears to be easy to read. It can now be used in a second step: the design of graphical interfaces facilitating access to drug monographs. It could also be used for broader applications, including the design of interfaces for consulting other types of medical document or medical data, or, very simply, to enrich medical texts.</p

Ectopic hbox12 Expression Evoked by Histone Deacetylase Inhibition Disrupts Axial Specification of the Sea Urchin Embryo

Dorsal/ventral patterning of the sea urchin embryo depends upon the establishment of a Nodal-expressing ventral organizer. Recently, we showed that spatial positioning of this organizer relies on the dorsal-specific transcription of the Hbox12 repressor. Building on these findings, we determined the influence of the epigenetic milieu on the expression of hbox12 and nodal genes. We find that Trichostatin-A, a potent and selective histone-deacetylases inhibitor, induces histone hyperacetylation in hbox12 chromatin, evoking broad ectopic expression of the gene. Transcription of nodal concomitantly drops, prejudicing dorsal/ventral polarity of the resulting larvae. Remarkably, impairing hbox12 function, either in a spatially-restricted sector or in the whole embryo, specifically rescues nodal transcription in Trichostatin-A-treated larvae. Beyond strengthen the notion that nodal expression is not allowed in the presence of functional Hbox12 in the same cells, these results highlight a critical role of histone deacetylases in regulating the spatial expression of hbox12

Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice