Perspectives of the Friedreich ataxia community on gene therapy clinical trials.

Gene therapy is a potential treatment for Friedreich ataxia, with multiple programs on the horizon. The purpose of this study was to collect opinions about gene therapy from individuals 14 years or older with Friedreich ataxia or parents/caregivers of Friedreich ataxia patients who were diagnosed as children 17 or younger. Participants were asked to complete a survey after reading brief educational materials regarding gene therapy. Most of the patients captured in this survey have an early-onset (classical) presentation of the disease. Participants expressed urgency in participating in gene therapy clinical trials despite the associated risks. About half of the respondents believed that gene therapy would cease progression or minimize symptoms, whereas nearly one-fourth expected to be cured. The survey also revealed how participants perceive their symptom burden, because a substantial majority reported that balance/walking issues most interfere with their quality of life and would be the symptom they would prioritize treating. Although not statistically significant, more caregivers prioritized treating cardiomyopathy than patients. This study provides valuable information on priorities, beliefs, and expectations regarding gene therapy and serves to guide future gene therapy opinion studies and gene therapy trial design.

Examining the Importance of Family History in Pediatric Behavioural Referrals.

In recent years, there has been a substantial increase in the diagnosis of attention deficit hyperactivity disorder (ADHD) in children. Without appropriate management of symptoms and care, ADHD has been associated with a variety of negative child and adult outcomes. Environmental and familial factors that may contribute to three different pediatric referral types (academic, behavioural, and attentional) associated with ADHD were examined in the current study. In total, data from 477 families who were interviewed as a part of the intake process to a pediatric clinic were included in this study. Data for the current study was extracted from the intake questionnaires and included information on family history of mental health issues, socioeconomic status, and family relationships. The sample included children between the ages of three and 17 and mostly comprised males (n = 340). A frequency analysis of the data demonstrated relatively high rates of mental health issues within families (61.4%); almost half of the mothers reported some post-secondary education (46.1%) and most reported having normal relationships with their children (mothers, 78%; fathers, 62.9%). Finally, three stepwise regression analyses were conducted to predict referral type. All three regressions yielded significant models. Fifteen percent of the variability of the academic referral type was predicted by being male, age at the time of referral, mother's education level, and mother's learning. The behavioural referral types were predicted by a family history of depression, being male, mother-child relationship, and age at the time of referral; these accounted for 23% of the variance. Attentional referral type was predicted only by mother-child relationship that captured 6% of the variance. Overall, this study describes a population of parents of children with academic, behavioural, and attention-related referrals to pediatrics. Results indicate that mothers have a profound influence on their child's referral types, something that may transfer into later diagnosis and perhaps prognosis. Clinicians and researchers alike should focus their efforts toward developing integrative service assessment and treatment approaches that include important people in the child's life. The implementation of Community Social Pediatrics (a streamlined, inclusive approach to care) should be considered in urban centres like this one, where referrals like this are prevalent.

Service user involvement in preregistration general nurse education: a systematic review.

AIMS AND OBJECTIVES: A systematic review of published studies on service user involvement in undergraduate, preregistration general nursing education (excluding mental health-specific programmes). The objective is to examine how students are exposed to engagement with service users. BACKGROUND: The requirement of service user involvement in all nurse education is policy expectation of health professional education providers, in response to the increased public and political expectations. Previous literature reviews have focused solely on mental health. DESIGN: Systematic review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines; timeframe 1997-2014; published in English. METHODS: Search of CINAHL, Cochrane Review, Education Research Complete, Internurse, MEDLINE, PsychINFO, Scopus, SocINDEX and Web of Science yielded 229 citations; 11 studies met the review eligibility criteria. RESULTS: Seven studies used qualitative methodology, two quantitative and two mixed methods. Studies from the United Kingdom dominated (n = 9), the remainder from South Africa and Turkey. The results are described using four themes: benefits and limitations of service user involvement; nursing student selection; education delivery; practice-based learning and assessment. Most studies were small scale; nine had less than 30 participants. Overall the evidence suggests that student, lecturers and service users valued service user involvement in nurse education, to provide an authentic insight into the illness experience. Logistical considerations around support and student cohort size emerged. CONCLUSIONS: This is the first systematic review to focus on service user involvement in general nurse education. It reveals that service user involvement commenced later and is more limited in general programmes as compared to equivalent mental health education provision. Most of the evidence focuses on perceptions of the value of involvement. Further research is required to more clearly establish impact on learning and clinical practice. RELEVANCE TO CLINICAL PRACTICE: Service user involvement in nurse education is valued by stakeholders but preparation and support for those involved, including mentors is underestimated.

Developmental profiles and expression of the DNA methyltransferase genes in the fathead minnow (Pimephales promelas) following exposure to di-2-ethylhexyl phthalate.

DNA methylation is an epigenetic regulator of gene expression, and this process has been shown to be disrupted by environmental contaminants. Di-2-(ethylhexyl) phthalate (DEHP) and related phthalate esters have been shown to affect development in early life stages of fish and can alter genomic methylation patterns in vertebrates. The objectives of this study were the following: (1) Describe the expression patterns of the DNA methyltransferase (dnmt) genes during early fathead minnow (FHM) development. These genes are critical for methylation and imprinting during development. (2) Determine the effects of DEHP on the development of FHM larvae [1 and 14 days post-hatch (dph)]. (3) Determine the effect of DEHP on dnmt expression and global methylation status in larval FHM. FHMs were first collected over a developmental time course [1, 3, 5, 6, and 14 days post-fertilization (dpf)] to investigate the expression patterns of five dnmt isoforms. The expression of dnmt1 and dnmt7 was relatively high in embryos at 1 dpf but was variable in expression, and these transcripts were later expressed at a lower level (>3 dpf); dnmt3 was significantly higher in embryos at 1 dpf compared to those at 3 dpf. Dnmt6 showed more of a constitutive pattern of expression during the first 2 weeks of development, and the mRNA levels of dnmt8 were higher in embryos at 5 and 6 dpf compared to those at 1 and 3 dpf, corresponding to the hatching period of the embryos. A waterborne exposure to three concentrations of DEHP (1, 10 and 100 µg/L) was conducted on 1-day FHM embryos for 24 h and on larval fish for 2 weeks, ending at 14 dpf. DEHP did not negatively affect survival, hatch rate, or the expression of dnmt isoforms in FHMs. There were no differences in global cytosine methylation following DEHP treatments in 14 dpf larvae, suggesting that environmentally relevant levels of DEHP may not affect global methylation at this stage of FHM development. However, additional targeted methylome studies are required to determine whether specific gene promoters are differently methylated following exposure to DEHP. This study offers new insight into the roles of the dnmt enzymes during FHM development.