The Key Role of Patient Involvement in the Development of Core Outcome Sets in Prostate Cancer

Funding/Support and role of the sponsor: This research was supported by funding under the PIONERR Consortium. The Consortium played a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript.Peer reviewedPublisher PD

Aggressions, social cognitions, anger and sadness in bullies and victims

Background: The present study aimed to investigate children's social information processing (SIP) and emotions in the bullying situation, taking into account reactive and proactive aggression. More specifically, we investigated the way in which children interpret social information, which goals they select, how they evaluate their responses and which emotions they express in hypothetical situations. Method: The participants comprised 242 Dutch children (120 girls and 122 boys; mean age: 117.2 months), who were assigned by means of peer nominations (Salmivalli, Lagerspetz, et al., 1996) to one of the following roles: bully (n = 21), follower of the bully (n = 38), victim (n = 35), defender of the victim (n = 48), outsider (n = 52) and not involved (n = 32). Sixteen children (including 3 bully/victims) were not given any role. The reactive and proactive aggression scale (Dodge, & Coie, 1987) was filled out by teachers in order to test the association between these types of aggression and involvement in bullying. Children were presented with ambiguous scenarios and responded to questions about attribution of intent, goal selection and emotions (anger and sadness). In addition, two questionnaires were administered to children: one assessed perceived self-efficacy in performing aggression, inhibiting aggression and using verbal persuasion skills, and the other assessed expected outcomes from behaving aggressively or prosocially. Results: Results showed that while reactive aggression was common in bullies and victims, proactive aggression was only characteristic of bullies. Both bullies and victims, compared to the other children, scored higher on hostile interpretation, anger, retaliation and ease of aggression. Bullies and followers claimed that it was easy for them to use verbal persuasion, while victims turned out to be the saddest group. All children, irrespective of their role in the peer group, thought that aggressive as well as prosocial behavior was more likely to produce desired results from a friendly peer than from an aggressive one. Conclusions: Bullies and victims seem to be similar in reactive aggression, SIP, and in the expression of anger, but the motivations which lead to their behavior may be different, as well as the final outcomes of their acts. © Association for Child Psychology and Psychiatry, 2004

Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells

Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ω-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli

Diferencias intra e inter individuales en inteligencia social de estudiantes portugueses

Social intelligence is a favorable condition for career decision-making and development. The social intelligence indices of Portuguese students in school years prior to a career transition are characterized and intra and interindividual differences are analyzed. Participants were 1095 students (552, 50.4% women) with a mean age of 14.78 years (SD = 1.86), in the 8th (542, 49.5%), 10th (295, 26.9%) and 11th (258, 23.6%) grades. The Cognitive Test of Social Intelligence (PCIS) was administered at two moments, six months apart. Results indicate that the 8th grade obtained higher average scores in Problem Solving, Motivation and Self-confidence (time 1), while the 10th grade obtained better results in Problem Solving, Motivation and Familiarity (time 2). Between the assessment moments, all school years register an increase in Problem Solving and Self-confidence in social situations. These results constitute favorable psychological conditions for the promotion of ethical questioning in career guidance interventions.A inteligência social constitui uma condição favorável à tomada de decisão e ao desenvolvimento vocacional. Este trabalho visa caracterizar os níveis de inteligência social, e analisar as diferenças intra e interindividuais, em alunos portugueses em anos de pré-transição vocacional. Participaram 1095 alunos (552, 50% mulheres), com uma média de idades de 14,78 anos (DP = 1,86), do 8º, 10º, e 11º níveis escolares. Administrou-se a Prova Cognitiva de Inteligência Social (PCIS), em dois momentos (T1 e T2), com seis meses de intervalo. Os resultados indicam que o 8º ano obteve resultados médios superiores, nos índices de Resolução de Problemas, Motivação e Autoconfiança (T1), enquanto o 10º ano obteve resultados superiores, em Resolução de Problemas, Motivação e Familiaridade (T2). Entre momentos de avaliação, registra-se, para todos os níveis escolares, um aumento em Resolução de Problemas e Autoconfiança em situações sociais. Estes resultados constituem condições psicológicas favoráveis à promoção do questionamento ético nas intervenções de orientação vocacional.La inteligencia social es una condición favorable para la toma de decisiones y el desarrollo de la carrera. Se caracterizan los niveles de inteligencia social y sus diferencias intra e interindividuales en estudiantes portugueses en transición pre-profesional. Participaron 1095 estudiantes (552, 50.4% mujeres) con una edad media de 14.78 (DE = 1.86), del 8º (542, 49,5%), 10º (295, 26.9%) y 11º (258, 23.6%) años escolares. Se administró la Prueba Cognitiva de Inteligencia Social (PCIS) en dos ocasiones, con seis meses de diferencia. Los resultados indican que los estudiantes del 8º grado obtuvieron puntajes medios más altos en la Resolución de Problemas, Motivación y Confianza (T1), mientras que los del 10º grado obtuvieron mejores resultados en la Resolución de Problemas, Motivación y Familiaridad (T2). Entre momentos de evaluación se registra, para todos los años, un aumento en la Resolución de Problemas y Confianza en situaciones sociales. Estos resultados constituyen condiciones psicológicas favorables a la promoción del cuestionamiento ético en las intervenciones de orientación profesional.Project coordinated by the fourth author and co-funded by the Foundation for Science and Technology and the Compete Program - PTDC/CPE-CED/098896/200

Using next-generation sequencing for high resolution multiplex analysis of copy number variation from nanogram quantities of DNA from formalin-fixed paraffin-embedded specimens

The use of next-generation sequencing technologies to produce genomic copy number data has recently been described. Most approaches, however, reply on optimal starting DNA, and are therefore unsuitable for the analysis of formalin-fixed paraffin-embedded (FFPE) samples, which largely precludes the analysis of many tumour series. We have sought to challenge the limits of this technique with regards to quality and quantity of starting material and the depth of sequencing required. We confirm that the technique can be used to interrogate DNA from cell lines, fresh frozen material and FFPE samples to assess copy number variation. We show that as little as 5 ng of DNA is needed to generate a copy number karyogram, and follow this up with data from a series of FFPE biopsies and surgical samples. We have used various levels of sample multiplexing to demonstrate the adjustable resolution of the methodology, depending on the number of samples and available resources. We also demonstrate reproducibility by use of replicate samples and comparison with microarray-based comparative genomic hybridization (aCGH) and digital PCR. This technique can be valuable in both the analysis of routine diagnostic samples and in examining large repositories of fixed archival material

Findings from the Peutz-Jeghers Syndrome Registry of Uruguay

Background: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. Methods: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. Results and discussion: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000. Conclusion: The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation

Integrated mutation, copy number and expression profiling in resectable non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to identify critical genes involved in non-small cell lung cancer (NSCLC) pathogenesis that may lead to a more complete understanding of this disease and identify novel molecular targets for use in the development of more effective therapies.</p> <p>Methods</p> <p>Both transcriptional and genomic profiling were performed on 69 resected NSCLC specimens and results correlated with mutational analyses and clinical data to identify genetic alterations associated with groups of interest.</p> <p>Results</p> <p>Combined analyses identified specific patterns of genetic alteration associated with adenocarcinoma vs. squamous differentiation; <it>KRAS </it>mutation; <it>TP53 </it>mutation, metastatic potential and disease recurrence and survival. Amplification of 3q was associated with mutations in <it>TP53 </it>in adenocarcinoma. A prognostic signature for disease recurrence, reflecting <it>KRAS </it>pathway activation, was validated in an independent test set.</p> <p>Conclusions</p> <p>These results may provide the first steps in identifying new predictive biomarkers and targets for novel therapies, thus improving outcomes for patients with this deadly disease.</p

Alzheimer's disease biomarker discovery using SOMAscan multiplexed protein technology

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Sexually Dimorphic Serotonergic Dysfunction in a Mouse Model of Huntington's Disease and Depression

Depression is the most common psychiatric disorder in Huntington's disease (HD) patients. In the general population, women are more prone to develop depression and such susceptibility might be related to serotonergic dysregulation. There is yet to be a study of sexual dimorphism in the development and presentation of depression in HD patients. We investigated whether 8-week-old male and female R6/1 transgenic HD mice display depressive-like endophenotypes associated with serotonergic impairments. We also studied the behavioral effects of acute treatment with sertraline. We found that only female HD mice exhibited a decreased preference for saccharin as well as impaired emotionality-related behaviors when assessed on the novelty-suppressed feeding test (NSFT) and the forced-swimming test (FST). The exaggerated immobility time displayed by female HD in the FST was reduced by acute administration of sertraline. We also report an increased response to the 5-HT1A receptor agonist 8-OH-DPAT in inducing hypothermia and a decreased 5-HT2A receptor function in HD animals. While tissue levels of serotonin were reduced in both male and female HD mice, we found that serotonin concentration and hydroxylase-2 (TPH2) mRNA levels were higher in the hippocampus of males compared to female animals. Finally, the antidepressant-like effects of sertraline in the FST were blunted in male HD animals. This study reveals sex-specific depressive-related behaviors during an early stage of HD prior to any cognitive and motor deficits. Our data suggest a crucial role for disrupted serotonin signaling in mediating the sexually dimorphic depression-like phenotype in HD mice