Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

Explaining unexplained pain to fibromyalgia patients: finding a narrative that is acceptable to patients and provides a rationale for evidence based interventions

As the cause of fibromyalgia is controversial, communicating with patients can be challenging, particularly if the patient adopts the narrative ‘I am damaged and so I need a more powerful pain killer’. Research shows that providing patients with alternative narratives can be helpful, but it remains unclear what particular narratives are most acceptable to patients and at the same time provide a rationale for evidence based psychological and exercise interventions. This article described the development of a new narrative and the written comments made about the narrative by fibromyalgia patients. The narrative derives from a complexity theory model and provides an alternative to biogenic and psychogenic models. The model was presented to 15 patients whose comments about comprehensibility led to the final format of the narrative. In the final form, the body is presented as ‘a very, very clever computer’ where fibromyalgia is caused by a software rather than a hardware problem. The software problem is caused by the body adapting when people have to ‘keep going’ despite ‘stop signals’, such as pain and fatigue. The narrative provides a rationale for engaging in psychological and exercise interventions as a way of correcting the body’s software. This way of explaining fibromyalgia was evaluated by a further 25 patients attending a 7-week ‘body reprogramming’ intervention, where the therapy was presented as correcting the body’s software, and included both exercise and psychological components. Attendance at the course was 85%. Thematic analysis of written patient feedback collected after each session showed that patients found the model believable and informative, it provided hope and was empowering. Patients also indicated that they had started to implement lifestyle change with perceived benefit. Fibromyalgia patients appear to respond positively to a technology-derived narrative based on the analogy of the body as a computer

An Assessment of the Hydration Status of Recreational Endurance Athletes during Mountain Marathon Events.

Changes in hydration status have been shown to have deleterious effects on physiological functioning, physical performance, mental decision making, and subjective sensation of effort. This exploratory study assessed the hydration status of athletes taking part in mountain marathon events and the implications on performance, cognition and well-being markers. Twenty-nine male recreational athletes from the Original Mountain Marathon (OMM) and nineteen from the Longmynd Hike (LH) provided urine samples before, at mid-point (in the OMM) and after the events. Body mass; reaction time tests; and subjective ratings of well-being and effort were also collected/performed at these time points. Post-urine specific gravity (Usg) values [(OMM: 1.023 (range: 1.008 – 1.038) g/ml; LH: 1.024 (range: 1.014 – 1.035) g/ml] were significantly higher than pre-values [(OMM: 1.013 (range: 1.002 – 1.026) g/ml; LH: 1.013 (range: 1.002 – 1.026) g/ml] in both events (p 0.05). There was no association between hydration status and overall performance in the LH, whilst change in Usg from pre- to mid-event was positively associated with performance in the OMM (r = .561, p = 0.004). Whilst no associations were observed between hydration status and reaction time, rate of perceived exertion and subjective ratings of nausea showed positive associations with Usg. These findings suggest that although changes in hydration status of this level may not significantly affect performance, they can impact on participant sensations of effort and well-being

Macronutrient Consumption Prior to, and During, Mountain Marathon Events

Participation in ultra-endurance events such as mountain marathons is increasing, yet analysis of the nutritional intake and requirements of this group of athletes have received relatively little attention. This field study examined athletes’ food intake prior to, and during a mountain marathon event to assess compliance with recommendations and to identify associations with performance. Nineteen male athletes competing in the Longmynd Hike (LH) completed a 7-day food diary in the week prior to the event and a weighed food inventory of all items consumed during the event. Despite reported intentions to increase carbohydrate (CHO) consumption in the week prior to the event, there was no significant change in consumption across the week. The mean daily CHO intake of 4.5 g/kg/d was below that recommended to effectively enhance glycogen stores. CHO and energy consumption prior to the event were positively associated with performance [energy (kJ/kg/d): r = .56, p = 0.03; CHO (g/kg/d): r = .54, p = 0.04]. Energy and CHO consumption during the event were also positively correlated with performance [energy (kJ/kg/h): r = .80, p < 0.001; CHO (g/kg/h): r = .75, p = 0.001)], despite most participants again failing to meet recommendations for intake. Further research is needed to determine reasons for non-compliance with nutritional guidelines and to investigate to what extent type and timing of macronutrient intake during such events impacts on performance

Promoting healthy weight in primary school children through physical activity and nutrition education: a pragmatic evaluation of the CHANGE! randomised intervention study

Background: This pragmatic evaluation investigated the effectiveness of the Children’s Health, Activity and Nutrition: Get Educated! (CHANGE!) Project, a cluster randomised intervention to promote healthy weight using an educational focus on physical activity and healthy eating. Methods: Participants (n = 318, aged 10–11 years) from 6 Intervention and 6 Comparison schools took part in the 20 weeks intervention between November 2010 and March/April 2011. This consisted of a teacher-led curriculum, learning resources, and homework tasks. Primary outcome measures were waist circumference, body mass index (BMI), and BMI z-scores. Secondary outcomes were objectively-assessed physical activity and sedentary time, and food intake. Outcomes were assessed at baseline, at post-intervention (20 weeks), and at follow-up (30 weeks). Data were analysed using 2-level multi-level modelling (levels: school, student) and adjusted for baseline values of the outcomes and potential confounders. Differences in intervention effect by subgroup (sex, weight status, socio-economic status) were explored using statistical interaction. Results: Significant between-group effects were observed for waist circumference at post-intervention (β for intervention effect =−1.63 (95% CI = −2.20, -1.07) cm, p<0.001) and for BMI z-score at follow-up (β=−0.24 (95% CI = −0.48, -0.003), p=0.04). At follow-up there was also a significant intervention effect for light intensity physical activity (β=25.97 (95% CI = 8.04, 43.89) min, p=0.01). Interaction analyses revealed that the intervention was most effective for overweight/obese participants (waist circumference: β=−2.82 (95% CI = −4.06, -1.58) cm, p<0.001), girls (BMI: β=−0.39 (95% CI = −0.81, 0.03) kg/m2, p=0.07), and participants with higher family socioeconomic status (breakfast consumption: β=8.82 (95% CI = 6.47, 11.16), p=0.07). Conclusions: The CHANGE! intervention positively influenced body size outcomes and light physical activity, and most effectively influenced body size outcomes among overweight and obese children and girls. The findings add support for the effectiveness of combined school-based physical activity and nutrition interventions. Additional work is required to test intervention fidelity and the sustained effectiveness of this intervention in the medium and long term

Non-invasive assessment of peripheral arterial disease: Automated ankle brachial index measurement and pulse volume analysis compared to duplex scan

Objectives: This cross-sectional study aimed to individually and cumulatively compare sensitivity and specificity of the (1) ankle brachial index and (2) pulse volume waveform analysis recorded by the same automated device, with the presence or absence of peripheral arterial disease being verified by ultrasound duplex scan. Methods: Patients (n=205) referred for lower limb arterial assessment underwent ankle brachial index measurement and pulse volume waveform recording using volume plethysmography, followed by ultrasound duplex scan. The presence of peripheral arterial disease was recorded if ankle brachial index 50% was evident with ultrasound duplex scan. Outcome measure was agreement between the measured ankle brachial index and interpretation of pulse volume waveform for peripheral arterial disease diagnosis, using ultrasound duplex scan as the reference standard. Results: Sensitivity of ankle brachial index was 79%, specificity 91% and overall accuracy 88%. Pulse volume waveform sensitivity was 97%, specificity 81% and overall accuracy 85%. The combined sensitivity of ankle brachial index and pulse volume waveform was 100%, specificity 76% and overall accuracy 85%. Conclusion: Combining these two diagnostic modalities within one device provided a highly accurate method of ruling out peripheral arterial disease, which could be utilised in primary care to safely reduce unnecessary secondary care referrals

Improving mental health literacy in year 9 high school children across Wales: a protocol for a randomised control treatment trial (RCT) of a mental health literacy programme across an entire country

Background: Adolescence is a crucial period for developing and maintaining good habits for mental health and well-being. This is important for future mental health, as most mental health problems manifest during adolescence. Mental health literacy is the foundation for mental health prevention, stigma reduction, and increased help-seeking efficacy particularly among adolescents. The mental health literacy programme “The Guide”, which was developed in Canada, has shown success in increasing mental health literacy in North American 16-17 year olds. “The Guide Cymru” is an adaptation of The Guide designed for a younger age group (13-14 year olds) and for the Welsh culture and context and is being offered to all state schools in Wales. Methods: This two-armed cluster randomised control trial (RCT) will evaluate the effectiveness of The Guide Cymru. All 205 secondary schools in Wales will be invited to take part, involving up to 30,000 year 9 pupils. Schools will be randomised to either the immediate implementation of The Guide Cymru or to a wait-list control. The wait-list control will receive The Guide Cymru around 12 weeks later. Measures of mental health literacy (assessed via the Knowledge and Attitudes to Mental Health scale) and mental health problems (via the PedsQL and Strengths and Difficulties Questionnaire) will be taken at baseline (pre-intervention), 12 weeks later (after the active group has received The Guide Cymru), and 24 weeks later (after the wait-list control has received The Guide Cymru).Discussion: The trial aims to evaluate if The Guide Cymru increases mental health literacy, including reduced stigma to others and to the self, and increased levels of good mental health behaviours and help-seeking for mental health problems. Trial Registration: ISRCTN15462041. Registered 03/10/2019. https://doi.org/10.1186/ISRCTN15462041Keywords: Mental health literacy, Randomised Control Trial, Early intervention, Self-stigma, Stigma, Education, Adolescence, Help-seeking efficacy, School-based intervention