Anxiety in children with Williams syndrome : association with negative reactivity, self-regulation, and sensory modulation.

Williams syndrome (WS) is a neurodevelopmental disorder caused by a submicroscopic deletion of approximately 25 genes on chromosome 7q11.23 (Hillier et al., 2003). This genotype is associated with a characteristic set of phenotypic features including mild to moderate intellectual disability, a distinctive cognitive profile, facial dysmorphology, common personality traits, cardiovascular problems, and connective tissue disorders (Morris, 2010). In addition, behavioral difficulties such as anxiety symptoms (e.g., Leyfer, Woodruff-Borden, & Mervis, 2009), negative reactivity (e.g., Davies, Udwin, & Howlin, 1998), problems with self-regulation (e.g., Woodruff-Borden, Kistler, Henderson, Crawford, & Mervis, 2010), and sensory modulation difficulties (e.g., John & Mervis, 2010) are common. While anxiety as a behavioral concern for individuals with WS is well-documented, little is known about why these individuals are at an increased risk for this type of problem. Several features of the WS behavioral phenotype have been associated with child anxiety in the general population, specifically negative reactivity (e.g., Lonigan, Phillips, & Hooe, 2003), self-regulation problems (e.g., Eisenberg et al., 2001), and sensory modulation difficulties (e.g., Ben-Sasson, Cermak, Orsmond, Tager-Flusberg, Kadlec, & Carter, 2008). The purpose of this dissertation was to explore the relations of negative reactivity (NR), difficulties with self-regulation (SR), and sensory modulation difficulties (SM) to the increased prevalence of anxiety symptoms in children with WS. Study hypotheses are: (1) The shared variance between NR, SR, and SM will be adequately represented by a single underlying ‘behavioral phenotype’ factor. (2) This factor will share a significant relation with anxiety symptoms in children with WS. Participants were 115 children with WS aged 6 – 10 years. Primary caregivers completed four measures: (1) Children’s Behavior Questionnaire (Rothbart, Ahadi, Hershey, & Fisher, 2001). NR was measured using the Negative Affectivity factor score. (2) Short Sensory Profile (McIntosh, Miller, Shyu, & Dunn, 1999). SM was measured using the Total Sensory Modulation score. (3) Behavior Rating Inventory of Executive Functioning (Gioia, Isquith, Guy, & Kenworthy, 2000). SR was measured using the Behavioral Regulation Index T-score. (4) Child Behavior Checklist 6 – 18 (Achenbach & Rescorla, 2001). Anxiety symptoms were measured using the DSM-IV Anxiety Problems T-score. Exploratory factor analysis and regression analysis were conducted to test the study hypotheses. The results supported both hypotheses: The WS behavioral phenotype features of negative reactivity, difficulties with sensory modulation, and difficulties with self-regulation were adequately represented by one underlying factor; and this factor explained a substantial portion of the variance in anxiety symptoms for children with WS aged 6 – 10 years. Implications for future research and treatment of anxiety in children with WS are discussed

Clinical Efficacy of the GnRH Agonist (Deslorelin) in Dogs Affected by Benign Prostatic Hyperplasia and Evaluation of Prostatic Blood Flow by Doppler Ultrasound.

In six German Shepherds dogs, GnRH agonist implants (Deslorelin) were inserted subcutaneously one month after histological confirmation of benign prostatic hyperplasia (BPH). Prostatic volume (PV), characteristics of ejaculate, serum testosterone concentrations and Doppler parameters of prostatic and subcapsular arteries were detected at different time intervals, for 6 month. The prostatic volume showed a significantly reduction starting at day 37. The decrease in sperm concentration, motility and increase in morphological abnormal sperm were observed from day 22 to day 37, when it was no longer possible to obtain the ejaculate. The values of peak systolic velocity and end-diastolic velocity in prostatic and subcapsular arteries showed from day 11 a gradual decrease, significant at day 22 until day 37 and reaching the lowest values at day 52 until the end of observation. The power Doppler pixel intensity of both arteries showed a gradual decrease from day 5 until day 52. In particular, a significant decrease was observed for both arteries from day 11. Testosterone serum concentration decreased to undetectable levels by day 11 until the end of the observations. All these Doppler parameters and testosterone values were positively correlated with the prostatic volume. Furthermore, testosterone values were positively correlated with peak systolic velocity, end diastolic velocity and pixel numbers. The use of implants containing GnRH analogues, even in asymptomatic subjects, is effective for the control of BPH and the application of Doppler exam of prostatic blood flow represent an non-invasive tool for monitoring the response of medical treatment

The implementation and evaluation of a media literacy intervention about PAES use in sport science students

With respect to both competitive and amateur/fitness sports, media may strongly influence young people’s opinions and behaviors concerning the use of PAES (Performance and Appearance Enhancing Substances). The present investigation addressed this topic by focusing on sport sciences students’ beliefs concerning the possible role of media related to the implementation and evaluation of a PAES-focus media literacy intervention conducted with sport science students. This study relied on a sample of 521 students (attrition rate 10.3%) (45.1% female, mean age = 22.6, SD = 2.20), which provided baseline data on students’ levels of media literacy concerning the use of PAES (i.e. “descriptive sample”), and a sample of 248 students, who participated in and provided data on the media literacy intervention. This latter sample included a group of 128 students (44.5% female, mean age = 23.03, SD = 3.76) who actively participated in the intervention (i.e. “intervention group”), and a group of 120 students who did not (i.e. “control group”, 53.3% female, mean age = 22.25, SD = 2.47). All students filled out media literacy questionnaires targeting students’ awareness of media influence, their views about the realism of media content, their sense of confidence in dealing with media messages, and their positive attitudes toward PAES use. Analyses of questionnaire data showed that students are relatively aware of media influence on people’s views and behaviors with respect to PAES use. At the same time, students also believed that young people do not consider media as “realistic sources” of information; nonetheless, they also did not consider themselves entirely capable of dealing effectively with media messages. With respect to the intervention, students overall appreciated and greatly welcomed the educational program on media literacy, and the analyses of intervention data across intervention and control groups showed that key media literacy variables changed over time, attesting to the overall effectiveness of the intervention

Transcriptome of male breast cancer matched with germline profiling reveals novel molecular subtypes with possible clinical relevance

SIMPLE SUMMARY: Breast cancer in men is a rare disease; however, morbidity and mortality in male breast cancer (MBC) patients is a serious concern. The identification of specific molecular features in MBC is essential for developing more appropriate and targeted therapeutic strategies for MBC patients. In this study, by transcriptome analysis of 63 MBCs characterized for germline mutations in the most relevant BC susceptibility genes, mainly BRCA1/2, we highlighted possible differences in the molecular pathways underlying MBC pathogenesis in relation to germline mutation status. Furthermore, we identified two distinct subgroups of MBCs of clinical relevance, which are characterized by different biological features and prognosis. Overall, our results showed that transcriptome profiling by RNA sequencing is a valuable approach to dissect the molecular heterogeneity of MBC and suggest that the transcriptome matched with germline profiling may lead to the identification of MBC subtypes with possible relevance in the clinical setting, which is a primary step to improve the clinical management of MBC patients. ABSTRACT: Male breast cancer (MBC) is a rare and understudied disease compared with female BC. About 15% of MBCs are associated with germline mutation in BC susceptibility genes, mainly BRCA1/2 and PALB2. Hereditary MBCs are likely to represent a subgroup of tumors with a peculiar phenotype. Here, we performed a whole transcriptome analysis of MBCs characterized for germline mutations in the most relevant BC susceptibility genes in order to identify molecular subtypes with clinical relevance. A series of 63 MBCs, including 16 BRCA2, 6 BRCA1, 2 PALB2, 1 RAD50, and 1 RAD51D germline-mutated cases, was analyzed by RNA-sequencing. Differential expression and hierarchical clustering analyses were performed. Module signatures associated with central biological processes involved in breast cancer pathogenesis were also examined. Different transcriptome profiles for genes mainly involved in the cell cycle, DNA damage, and DNA repair pathways emerged between MBCs with and without germline mutations. Unsupervised clustering analysis revealed two distinct subgroups, one of which was characterized by a higher expression of immune response genes, high scores of gene-expression signatures suggestive of aggressive behavior, and worse overall survival. Our results suggest that transcriptome matched with germline profiling may be a valuable approach for the identification and characterization of MBC subtypes with possible relevance in the clinical setting

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well-characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non-BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer-associated genes. The main clinical-pathologic characteristics of MBC in pathogenic variant carriers and non-carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 non-BRCA1/2 MBC patients were examined in our study. Twenty-seven of the non-BRCA1/2 MBC patients were carriers of germline pathogenic variants in other genes, including two APC p.Ile1307Lys variant carriers and one MUTYH biallelic variant carrier. PALB2 was the most frequently altered gene (1.2%) and PALB2 pathogenic variants were significantly associated with high risk of MBC. Non-BRCA1/2 pathogenic variant carriers were more likely to have personal (p = 0.0005) and family (p = 0.007) history of cancer. Results of our study support a central role of PALB2 in MBC susceptibility and show a low impact of CHEK2 on MBC predisposition in the Italian population. Overall, our data indicate that a multigene testing approach may benefit from appropriately selected patients with implications for clinical management and counseling of MBC patients and their family members