What is the best way to keep walking and moving around for individuals with Machado-Joseph disease? A scoping review through the lens of Aboriginal families with Machado-Joseph disease in the Top End of Australia

Objectives: Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide. Prevalence is highest in affected remote Aboriginal communities of the Top End of Australia. Aboriginal families with MJD from Groote Eylandt believe 'staying strong on the inside and outside' works best to keep them walking and moving around, in accordance with six key domains that form the 'Staying Strong' Framework. The aim of this current study was to review the literature to: (1) map the range of interventions/strategies that have been explored to promote walking and moving around (functional mobility) for individuals with MJD and; (2) align these interventions to the 'Staying Strong' Framework described by Aboriginal families with MJD. Design: Scoping review. Data sources: Searches were conducted in July 2018 in MEDLINE, EMBASE, CINAHL, PsychINFO and Cochrane Databases. Eligibility criteria for selecting studies: Peer-reviewed studies that (1) included adolescents/adults with MJD, (2) explored the effects of any intervention on mobility and (3) included a measure of mobility, function and/or ataxia were included in the review. Results: Thirty studies were included. Few studies involved participants with MJD alone (12/30). Most studies explored interventions that aligned with two 'Staying Strong' Framework domains, 'exercising your body' (n=13) and 'searching for good medicine' (n=17). Few studies aligned with the domains having 'something important to do' (n=2) or 'keeping yourself happy' (n=2). No studies aligned with the domains 'going country' or 'families helping each other'. Conclusions: Evidence for interventions to promote mobility that align with the 'Staying Strong' Framework were focused on staying strong on the outside (physically) with little reflection on staying strong on the inside (emotionally, mentally and spiritually). Findings suggest future research is required to investigate the benefits of lifestyle activity programmes that address both physical and psychosocial well-being for families with MJD

Staying Strong Toolbox: co-design of a physical activity and lifestyle program for Aboriginal families with Machado-Joseph disease in the Top End of Australia

Physical activity has positive health implications for individuals living with neurodegenerative diseases. The success of physical activity programs, particularly in culturally and linguistically diverse populations, is typically dependent on their alignment with the culture, lifestyle and environmental context of those involved. Aboriginal families living in remote communities in the Top End of Australia invited researchers to collaborate with them to co-design a physical activity and lifestyle program to keep individuals with Machado-Joseph disease (MJD) walking and moving around. The knowledge of Aboriginal families living with MJD, combined with findings from worldwide MJD research, formed the foundation for the co-design. An experience-based co-design (EBCD) approach, drawing from Indigenous and Participatory methodologies, was used. An expert panel of individuals with lived experience of MJD participated in a series of co-design phases. Prearranged and spontaneous co-design meetings were led by local community researchers within each phase. Data was collected using a culturally responsive ethnographic approach and analysed thematically. Sixteen panel members worked to develop the 'Staying Strong Toolbox' to cater for individuals with MJD who are 'walking strong'; or 'wobbly'; or 'in a wheelchair'. Based on the 'Staying Strong Framework', the Toolbox was developed as a spiral bound A3 book designed to guide the user to select from a range of activities to keep them walking and moving around and to identify those activities most important to them to work on. The 'Staying Strong Toolbox' is a community driven, evidence based resource for a physical activity and lifestyle program for Aboriginal families with MJD. The Toolbox provides a guide for health professionals and support workers to deliver person-centred support to Aboriginal families with MJD, and that can be modified for use by other families with MJD or people with other forms of ataxia around the world

Exercise intensity and postprandial health outcomes in adolescents

© 2014, Springer-Verlag Berlin Heidelberg. Method: Twenty adolescents (10 male, 14.3 ± 0.3 years) completed three 1-day trials: (1) rest (CON); (2) 8 × 1 min cycling at 90 % peak power with 75 s recovery (HIIE); (3) cycling at 90 % of the gas exchange threshold (MIE), 1 h before consuming a high-fat milkshake (1.50 g fat and 80 kJ kg−1). Postprandial TAG, SBP and fat oxidation were assessed over 4 h Results : Compared to CON, the incremental area under the curve for TAG (IAUC-TAG) was not significantly lowered in HIIE [P = 0.22, effect size (ES) = 0.24] or MIE (P = 0.65, ES = 0.04) for boys. For girls, HIIE and MIE lowered IAUC-TAG by 34 % (P = 0.02, ES = 0.58) and 38 % (P = 0.09, ES = 0.73), respectively, with no difference between HIIE and MIE (P = 0.74, ES = 0.14). Changes in TAG were not related to energy expenditure during exercise or postprandial fat oxidation. Postprandial SBP (total-AUC pooled for both sexes) was lower in HIIE compared to CON (P = 0.01, ES = 0.68) and MIE (P = 0.02, ES = 0.60), with no difference between MIE and CON (P = 0.45, ES = 0.14). Purpose: The effect of exercise intensity and sex on postprandial risk factors for cardiovascular disease in adolescents is unknown. We examined the effect of a single bout of work-matched high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on postprandial triacylglycerol (TAG) and systolic blood pressure (SBP) in adolescents. Conclusion: A single bout of HIIE and MIE, performed 1 h before an HFM, can meaningfully attenuate IAUC-TAG in girls but not boys. Additionally, HIIE, but not MIE, may lower postprandial SBP in normotensive adolescents

Perceptual and prefrontal cortex haemodynamic responses to high-intensity interval exercise with decreasing and increasing work-intensity in adolescents

ObjectivesAffect experienced during high-intensity interval exercise (HIIE) is dependent on work-intensity, but the influence of increasing (low-to-high (L-H)) or decreasing (high-to-low (H-L)) work-intensity during HIIE remains unclear in adolescents. The role of prefrontal cortex haemodynamics in mediating changes in affect during HIIE also remains unexplored in adolescents. We examined affect, enjoyment and cerebral haemodynamic responses to HIIE with increasing or decreasing work intensities in adolescents.MethodsParticipants (N = 16; 8 boys; age 12.5 ± 0.8 years) performed, on separate days, HIIE cycling consisting of 8 × 1-min work-intervals at 100%-to-70% (HIIEH-L), 70%-to-100% (HIIEL-H) or 85% (HIIECON) peak power separated by 75 s recovery. Affect, enjoyment and cerebral haemodynamics (oxygenation (∆O2Hb), deoxygenation (∆HHb) and tissue oxygenation index (TOI)) were recorded before, during, and after all conditions. Results: Affect and enjoyment were lower during HIIEH-L compared to HIIEL-H and HIIECON at work-intervals 1 to 3 (all P  0.83) but were greater during HIIEH-L than HIIEL-H and HIIECON at work-interval 8 (all P  0.83). ∆O2Hb was similar across conditions (P = 0.87) but TOI and ∆HHb were significantly greater and lower, respectively during HIIEH-L compared to HIIEL-H and HIIECON at work-interval 8 (all P  0.40). Affect was correlated with TOI (all r > 0.92) and ∆HHb (all r > −0.73) across conditions.ConclusionsHIIEH-L offers advancement to the HIIECON and HIIEL-H which bring significant greater affect and enjoyment towards the end HIIE work-interval, implicating the feasibility and adoption of this protocol for health promotion in youth. Also, changes in prefrontal cortex haemodynamics are associated with the affect during HIIE

Perceptual and Cardiorespiratory Responses to High-Intensity Interval Exercise in Adolescents: Does Work Intensity Matter?

High-intensity interval exercise (HIIE) may not elicit prominent unpleasant feelings even with elevated perceived exertion and physiological stress in adolescents. However, the influence of different HIIE work intensities on the affective experience and cardiorespiratory responses is unknown. This study examined the acute affective, enjoyment, perceived exertion and cardiorespira-tory responses to HIIE with different work intensities in adolescents. Participants (n = 16; 8 boys; age 12.0 ± 0.3 years) performed, on separate days, HIIE conditions consisting of 8 x 1-minute work-intervals at 70%, 85%, or 100% peak power separated by 75 seconds recovery at 20 W. Affect, enjoyment and rating of perceived exertion (RPE) were recorded before, during, and after HIIE. Heart rate (HR) and oxygen uptake were collected during HIIE. Affect declined in all conditions (p 1.74; 70%HIIE = 2.5 ± 0.8; 85%HIIE = 1.1 ± 1.5; 100%HIIE =-1.5 ± 1.4 on feeling scale). Similar enjoyment was evident during and after all conditions (all p > 0.44). RPE was significantly higher during 100%HIIE than 70%HIIE and 85%HIIE across all work-intervals (all p 1.56). The majority of the participants attained ≥90%HRmax during 85%HIIE (87%) and 100%HIIE (100%), but not during 70%HIIE (6%). Affect responses during HIIE are dependent on the intensity of the work-interval and are not entirely negative (unpleasant feelings). Despite similar enjoyment, positive affect experienced during 70%HIIE and 85%HIIE could serve as a strategy to encourage exercise adoption and adherence in adolescents, but only 85%HIIE elicits sufficient HR stimulus to facilitate potential health benefits

Perceptual and Cardiorespiratory Responses to High-Intensity Interval Exercise in Adolescents: Does Work Intensity Matter?

High-intensity interval exercise (HIIE) may not elicit prominent unpleasant feelings even with elevated perceived exertion and physiological stress in adolescents. However, the influence of different HIIE work intensities on the affective experience and cardiorespiratory responses is unknown. This study examined the acute affective, enjoyment, perceived exertion and cardiorespira-tory responses to HIIE with different work intensities in adolescents. Participants (n = 16; 8 boys; age 12.0 ± 0.3 years) performed, on separate days, HIIE conditions consisting of 8 x 1-minute work-intervals at 70%, 85%, or 100% peak power separated by 75 seconds recovery at 20 W. Affect, enjoyment and rating of perceived exertion (RPE) were recorded before, during, and after HIIE. Heart rate (HR) and oxygen uptake were collected during HIIE. Affect declined in all conditions (p 1.74; 70%HIIE = 2.5 ± 0.8; 85%HIIE = 1.1 ± 1.5; 100%HIIE =-1.5 ± 1.4 on feeling scale). Similar enjoyment was evident during and after all conditions (all p > 0.44). RPE was significantly higher during 100%HIIE than 70%HIIE and 85%HIIE across all work-intervals (all p 1.56). The majority of the participants attained ≥90%HRmax during 85%HIIE (87%) and 100%HIIE (100%), but not during 70%HIIE (6%). Affect responses during HIIE are dependent on the intensity of the work-interval and are not entirely negative (unpleasant feelings). Despite similar enjoyment, positive affect experienced during 70%HIIE and 85%HIIE could serve as a strategy to encourage exercise adoption and adherence in adolescents, but only 85%HIIE elicits sufficient HR stimulus to facilitate potential health benefits

'Staying strong on the inside and outside' to keep walking and moving around: perspectives from Aboriginal people with Machado Joseph Disease and their families from the Groote Eylandt Archipelago, Australia

Machado Joseph Disease (MJD) (spinocerebellar ataxia 3) is a hereditary neurodegenerative disease causing progressive ataxia and loss of mobility. It is the most common spinocerebellar ataxia worldwide. Among Aboriginal families of Groote Eylandt and related communities across Australia's Top End, MJD is estimated to be more prevalent than anywhere else in the world. This study explored lived experiences of individuals and families with MJD to determine what is important and what works best to keep walking and moving around. A collaborative qualitative exploratory study, drawing from constructivist grounded theory methods, was undertaken for data collection and analysis. Semi-structured in-depth interviews were conducted with individuals with MJD (n = 8) and their family members (n = 4) from the Groote Eylandt Archipelago where similar to 1500 Aboriginal people (Warnumamalya) live. Interviews were led by Warnumamalya community research partners in participants' preferred language(s). Participants described their experience of living with MJD, from 'knowing about MJD', 'protecting yourself from MJD' and 'adjusting to life with MJD'. While the specific importance of walking and moving around differed widely between participants, all perceived that walking and moving around enabled them to do what mattered most to them in life. 'Staying strong on the inside and outside' (physically, mentally, emotionally, spiritually) was perceived to work best to keep walking and moving around as long as possible. A framework that included personal and environmental strategies for staying strong emerged: 'Exercising your body', 'having something important to do', 'keeping yourself happy', 'searching for good medicine', 'families helping each other' and 'going country'. This study, the first to explore lived experiences of MJD in Australia, highlights the importance of maintaining mobility as long as possible. Strategies perceived to work best address physical and psychosocial needs in an integrated manner. Services supporting families with MJD need flexibility to provide individualised, responsive and holistic care

Aerobic Function and Muscle Deoxygenation Dynamics during Ramp Exercise in Children

PURPOSE:To characterise changes in deoxyhemoglobin ([HHb]) response dynamics in boys and girls during ramp incremental exercise to investigate whether the reduced peak oxygen uptake (peakV˙O2) in girls is associated with a poorer matching of muscle O2 delivery to muscle O2 utilisation, as evidenced by a more rapid increase in [HHb].METHODS:52 children (31 boys, 9.9 ± 0.6 years, 1.38 ± 0.07 m, 31.70 ± 5.78 kg) completed ramp incremental exercise on a cycle ergometer during which pulmonary gas exchange and muscle oxygenation parameters were measured.RESULTS:When muscle [HHb] was expressed against absolute work rate and V˙O2, girls had an earlier change in [HHb] as evidenced by the lower c/d parameter (Girls: 54 ± 20 W vs Boys: 67 ± 19 W, P=0.023; Girls: 0.82 ± 0.28 L·min vs. Boys: 0.95 ± 0.19 L·min, P=0.055) and plateau (Girls: 85 ± 12 W vs. Boys: 99 ± 18 W, P=0.031; Girls: 1.02 ± 0.25 L·min vs. Boys: 1.22 ± 0.28 L·min, P=0.014). However, when expressed against relative work-rate or V˙O2, there were no sex differences in [HHb] response dynamics (all P>0.20). Significant correlations were observed between absolute and fat-free mass normalised peak V˙O2 and the HHb c/d and plateau parameters when expressed against absolute work-rate or V˙O2. Furthermore, when entered into a multiple regression model, the [HHb] plateau against absolute V˙O2 contributed 12% of the variance in peak V˙O2 after adjusting for fat-free mass, gas exchange threshold, and body fatness (model R =0.81, P<0.001).CONCLUSION:The sex-difference in peak V˙O2 in 9-10 year old children is, in part, related to sex-specific changes in muscle O2 extraction dynamics during incremental exercise

E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Diverse outcomes of CO2 fixation using alkali metal amides including formation of a heterobimetallic lithium-sodium carbamato-anhydride via lithium-sodium bis-hexamethyldisilazide

Fixation of CO2 by lithium amides derived from pyrrole and diisopropylamine generates a lithium carbamate polymer and dodecamer respectively. Moving to lithium-sodium hexamethyldisilazide produces a more complicated, intriguing reaction, where unusually the bimetallic composition is maintained in the product but its composition contains both carbamato and anhydride functionalities