Congenital diaphragmatic hernia and retinoids: searching for an etiology

Congenital diaphragmatic hernia (CDH) is a major life-threatening cause of respiratory failure in the newborn. Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the epidemiology and pathophysiology of human CDH, the metabolism of retinoids and the implications of retinoids in the development of the diaphragm and lung. Finally, we describe the existing evidence of a disruption of the retinoid-signaling pathway in CDH

Recruiting to a large-scale physical activity randomised controlled trial – experiences with the gift of hindsight

Background: Recruitment issues continue to impact a large number of trials. Sharing recruitment information is vital to support researchers to accurately predict recruitment and to manage the risk of poor recruitment during study design and implementation. The purpose of this paper is to build on the knowledge available to researchers on recruiting to community based trials. Methods: A critical commentary of the recruitment challenges encountered during the ‘Booster’ Study, a randomised controlled trial which investigated the effectiveness of a Motivational Interviewing style intervention on the maintenance of physical activity. An overview of recruitment is provided, as well as strategies employed to recruit prospective participants and possible barriers to recruitment. Results: Two hundred and eighty two people, 47% of the original target, were recruited through mail-outs with secondary recruitment pathways yielding no additional participants. The research team encountered problems re-contacting interested participants and providing study materials in non-English languages. A lower response rate to the mail-out and a greater number of non-contactable participants in the full study compared to the pilot study resulted in a smaller pool of eligible participants from the brief intervention eligible for recruitment into the RCT. Conclusion: Despite utilising widely accepted recruitment strategies and incorporating new recruitment tactics in response to challenges, the ‘Booster’ study failed to randomise a sufficient number of participants. Recruitment to community based, behavioural interventions may face different challenges than trials based in clinical or primary care pathways. Specific challenges posed by the complexity of the study design and problems with staffing and resources were exacerbated by the need to revise upwards the number of mailed invitations as a result of the pilot study. Researchers should ensure study design is facilitative to recruitment and consider the implications of changing recruitment on the operational aspects of the trial. Where possible the impact of new strategies should be measured, and recruitment successes and challenges shared with those planning similar studies. The study was a registered controlled trial (ISRCTN56495859 12 Feb 2009; NCT00836459 03 Feb 2009) KEYWORDS: Recruitment, Physical Activity, mail-outs, BOOSTER, behaviour maintenance

Heritability of non-speech auditory processing skills

Recent insight into the genetic bases for autism spectrum disorder, dyslexia, stuttering, and language disorders suggest that neurogenetic approaches may also reveal at least one etiology of auditory processing disorder (APD). A person with an APD typically has difficulty understanding speech in background noise despite having normal pure-tone hearing sensitivity. The estimated prevalence of APD may be as high as 10% in the pediatric population, yet the causes are unknown and have not been explored by molecular or genetic approaches. The aim of our study was to determine the heritability of frequency and temporal resolution for auditory signals and speech recognition in noise in 96 identical or fraternal twin pairs, aged 6–11 years. Measures of auditory processing (AP) of non-speech sounds included backward masking (temporal resolution), notched noise masking (spectral resolution), pure-tone frequency discrimination (temporal fine structure sensitivity), and nonsense syllable recognition in noise. We provide evidence of significant heritability, ranging from 0.32 to 0.74, for individual measures of these non-speech-based AP skills that are crucial for understanding spoken language. Identification of specific heritable AP traits such as these serve as a basis to pursue the genetic underpinnings of APD by identifying genetic variants associated with common AP disorders in children and adults

Learning health professionalism at Makerere University: an exploratory study amongst undergraduate students

<p>Abstract</p> <p>Background</p> <p>Anecdotal evidence shows that unprofessional conduct is becoming a common occurrence amongst health workers in Uganda. The development of appropriate professional values, attitudes and behaviors is a continuum that starts when a student joins a health professional training institution and as such health professionals in training need to be exposed to the essence of professionalism. We sought to explore undergraduate health professions students' perceptions and experiences of learning professionalism as a preliminary step in addressing the problem of unprofessional conduct amongst health workers in Uganda.</p> <p>Methods</p> <p>Eight focus group discussions were conducted with 49 first to fifth year health professions undergraduate students of the 2008/2009 academic year at Makerere University College of Health Sciences. The focus group discussions were recorded and transcribed, and were analyzed using content analysis with emergent coding.</p> <p>Results</p> <p>The difference in the way first and fifth year students of Makerere University College of Health Sciences conceptualized professionalism was suggestive of the decline in attitude that occurs during medical education. The formal curriculum was described as being inadequate while the hidden and informal curricula were found to play a critical role in learning professionalism. Students identified role models as being essential to the development of professionalism and emphasized the need for appropriate role modeling. In our setting, resource constraints present an important, additional challenge to learning universal standards of health professionalism. Furthermore, students described practices that reflect the cultural concept of communalism, which conflicts with the universally accepted standard of individual medical confidentiality. The students questioned the universal applicability of internationally accepted standards of professionalism.</p> <p>Conclusions</p> <p>The findings call for a review of the formal professionalism curriculum at Makerere University College of Health Sciences to make it more comprehensive and to meet the needs expressed by the students. Role models need capacity building in professionalism as health professionals and as educators. In our setting, resource constraints present an additional challenge to learning universal standards of health professionalism. There is need for further research and discourse on education in health professionalism in the Sub-Saharan context of resource constraints and cultural challenges.</p

A systematic review of the effectiveness of self-management interventions in people with multiple sclerosis at improving depression, anxiety and quality of life.

BACKGROUND: Self-management interventions have become increasingly popular in the management of long-term health conditions; however, little is known about their impact on psychological well-being in people with Multiple Sclerosis (MS). PURPOSE: To examine the effectiveness of self-management interventions on improving depression, anxiety and health related quality of life in people with MS. METHOD: A structured literature search was conducted for the years 2000 to 2016. The review process followed the PRISMA guidelines, and is registered with PROSPERO (no. CRD42016033925). RESULTS: The review identified 10 RCT trials that fulfilled selection criteria and quality appraisal. Self-management interventions improved health-related quality of life in 6 out of 7 studies, with some evidence of improvement in depression and anxiety symptoms. CONCLUSION: Although the results are promising more robust evaluation is required in order to determine the effectiveness of self-management interventions on depression, anxiety and quality of life in people with MS. Evaluation of the data was impeded by a number of methodological issues including incomplete content and delivery information for the intervention and the exclusion of participants representing the disease spectrum. Recommendations are made for service development and research quality improvement

Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

BACKGROUND: To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH). METHODS: Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test. RESULTS: We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase. CONCLUSION: Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively

Projection of participant recruitment to primary care research: a qualitative study.

BACKGROUND: Recruitment to clinical trials remains a challenge, particularly in primary care settings. Initial projections of participant recruitment need to be as accurate as possible in order to avoid the financial, clinical and ethical costs of trial extensions or failures. However, estimation of recruitment rates is challenging and often poorly executed, if attempted at all. We used qualitative methods to explore the experiences and views of researchers on the planning of recruitment in this setting. METHODS: Participants had registered accrual to a UK-based primary care research study between April 2009 and March 2012. We conducted nine interviews with chief investigators or study managers, using a semi-structured topic guide. Analysis was conducted using the framework approach. RESULTS: Three themes are presented: 1) the factors affecting recruitment rates, 2) the use of planning techniques, and 3) influences on poor estimation. 1) A large number of factors affecting recruitment rates were discussed, including those relating to the study protocol, the clinical setting and the research setting. Use of targeted mail-outs to invite apparently eligible individuals to participate was preferred in order to eliminate some of the uncertainty in the recruitment rate associated with opportunistic clinician referrals. 2) The importance of pilot work was stressed. We identified significant uncertainty as to how best to schedule trial timelines to maximise efficiency. 3) Several potential sources of bias involved in the estimation of recruitment rates were explored and framed as technological, psychological or political factors. CONCLUSIONS: We found a large number of factors that interviewees felt impact recruitment rates to primary care research and highlighted the complexity of realistic estimation. Suitable early planning of the recruitment process is essential, and there may be potential to improve the projection of trial timelines by reducing biases involved in the process. Further research is needed to develop formal approaches that would be suitable for use in this setting