Medicine (Austin & Northern Health) - Research Publications
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ItemProlonged Eyelid Closure Episodes during Sleep Deprivation in Professional Drivers(AMER ACAD SLEEP MEDICINE, 2016)STUDY OBJECTIVES: Real life ocular measures of drowsiness use average blink duration, amplitude and velocity of eyelid movements to reflect drowsiness in drivers. However, averaged data may conceal the variability in duration of eyelid closure episodes, and more prolonged episodes that indicate higher levels of drowsiness. The current study aimed to describe the frequency and duration of prolonged eyelid closure episodes during acute sleep deprivation. METHODS: Twenty male professional drivers (mean age ± standard deviation = 41.9 ± 8.3 years) were recruited from the Transport Workers Union newsletter and newspaper advertisements in Melbourne, Australia. Each participant underwent 24 hours of sleep deprivation and completed a simulated driving task (AusEd), the Psychomotor Vigilance Task, and the Karolinska Sleepiness Scale. Eyelid closure episodes during the driving task were recorded and analyzed manually from digital video recordings. RESULTS: Eyelid closure episodes increased in frequency and duration with a median of zero s/h of eyelid closure after 3 h increasing to 34 s/h after 23 h awake. Eyelid closure episodes were short and infrequent from 3 to 14 h of wakefulness. After 17 h of sleep deprivation, longer and more frequent eyelid closure episodes began to occur. Episodes lasting from 7 seconds up to 18 seconds developed after 20 h of wakefulness. Length of eyelid closure episodes was moderately to highly correlated with the standard deviation of lateral lane position, braking reaction time, crashes, impaired vigilance, and subjective sleepiness. CONCLUSIONS: The frequency and duration of episodes of prolonged eyelid closure increases during acute sleep deprivation, with very prolonged episodes after 17 hours awake. Automated devices that assess drowsiness using averaged measures of eyelid closure episodes need to be able to detect prolonged eyelid closure episodes that occur during more severe sleep deprivation.
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ItemRelationship between autonomic cardiovascular control and obstructive sleep apnoea in persons with spinal cord injury: a retrospective study.(Springer Science and Business Media LLC, 2018)STUDY DESIGN: Retrospective study. OBJECTIVE: To determine if there is an association between obstructive sleep apnoea (OSA) and blood pressure (BP) pattern or heart rate variability (HRV) in people with spinal cord injury (SCI). SETTING: A state-based spinal cord service in Victoria, Australia. METHODS: We identified 42 subjects who had ambulatory BP monitoring (ABPM) within 6 months of a diagnostic sleep study at Austin Hospital between 2009 and 2014. Markers for autonomic function, including circadian BP pattern and HRV were extracted from the ABPM study database. Apnoea/hypopnoea index (AHI), arousals/hour and oxygen desaturation index were extracted from the sleep study database. Subjects with a nocturnal systolic BP dipping more than 10% of daytime value were defined as dippers, between 10 and 0% were non-dippers and those with a higher night than day systolic BP were reverse dippers. Severity of OSA is classified as non-OSA (AHI < 5), mild (AHI 5-15), moderate (AHI 15-30) and severe (AHI > 30). RESULTS: Subjects (n = 42) were predominantly male (85.7%), aged 44 ± 15.4 (mean ± SD), with a BMI of 24.4 ± 5.7 (mean ± SD) and mainly tetraplegic (92.9%). There was no difference in AHI, oxygen desaturation index or arousals/hour between dippers, non-dippers and reverse dippers. None of the HRV parameters differed between dippers, non-dippers and reverse dippers. No differences were found in 24 h, night-time, daytime or nocturnal dip in BP between subjects with non-OSA, mild, moderate and severe OSA. CONCLUSION: We found no relationship between BP pattern or HRV and the severity of OSA in persons with SCI.
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ItemQuantifying sex, race, and age specific differences in bone microstructure requires measurement of anatomically equivalent regions(Elsevier, 2017-08-01)INTRODUCTION: Individuals differ in forearm length. As microstructure differs along the radius, we hypothesized that errors may occur when sexual and racial dimorphisms are quantified at a fixed distance from the radio-carpal joint. METHODS: Microstructure was quantified ex vivo in 18 cadaveric radii using high resolution peripheral quantitative computed tomography and in vivo in 158 Asian and Caucasian women and men at a fixed region of interest (ROI), a corrected ROI positioned at 4.5-6% of forearm length and using the fixed ROI adjusted for cross sectional area (CSA), forearm length or height. Secular effects of age were assessed by comparing 38 younger and 33 older women. RESULTS: Ex vivo, similar amounts of bone mass fashioned adjacent cross sections. Larger distal cross sections had thinner porous cortices of lower matrix mineral density (MMD), a larger medullary CSA and higher trabecular density. Smaller proximal cross-sections had thicker less porous cortices of higher MMD, a small medullary canal with little trabecular bone. Taller persons had more distally positioned fixed ROIs which moved proximally when corrected. Shorter persons had more proximally positioned fixed ROIs which moved distally when corrected, so dimorphisms lessened. In the corrected ROIs, in Caucasians, women had 0.6 SD higher porosity and 0.6 SD lower trabecular density than men (p<0.01). In Asians, women had 0.25 SD higher porosity (NS) and 0.5 SD lower trabecular density than men (p<0.05). In women, Asians had 0.8 SD lower porosity and 0.3 SD higher trabecular density than Caucasians (p<0.01). In men, Asians and Caucasians had similar porosity and trabecular density. Results were similar using an adjusted fixed ROI. Adjusting for secular effects of age on forearm length resulted in the age-related increment in porosity increasing from 2.08 SD to 2.48 SD (p<0.05). CONCLUSION: Assessment of sex, race and age related differences in microstructure requires measurement of anatomically equivalent regions.
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ItemA genome-wide association study of corneal astigmatism: The CREAM Consortium(MOLECULAR VISION, 2018-02-05)PURPOSE: To identify genes and genetic markers associated with corneal astigmatism. METHODS: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. RESULTS: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). CONCLUSIONS: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.
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ItemNo Preview AvailableIntensive exercise program after spinal cord injury (SCIPA full-on): A randomized controlled trial(Elsevier, 2018-01-01)Introduction/Background: While upper body training is effective for improving aerobic fitness and muscle strength after spinal cord injury (SCI), activity-based therapies (ABT) intended to activate the paralysed extremities have been reported to promote neurological improvement. We investigated the effectiveness of intensive ABT compared with upper body training for people with SCI. Material and method: One hundred and sixteen participants (C2-T12, AIS A-D) were recruited from six SCI units in Australia and New Zealand, and randomised to experimental or control groups. Experimental participants received a 12-week ABT program including locomotor training, functional electrical stimulation-assisted leg cycling, and trunk and lower extremity exercises, while control group participants undertook upper body strength and aerobic fitness training. The primary outcome measure was the ASIA motor scores for upper and lower extremities. Results: One hundred and three participants completed the interventions and were included in the primary analysis. Mean (SD) upper extremity motor scores for experimental (n = 49) and control (n = 54) groups were 41.45 (12.11) and 39.39 (11.94), respectively, with an adjusted mean between-group difference of −0.039 (95% CI: −1.12 to 1.04). Mean (SD) lower extremity motor scores were 12.51 (17) and 10.24 (17.19) for experimental and control groups, with an adjusted mean between-group difference of 0.895 (95% CI: −0.48 to 2.27). There were 15 serious adverse events within each group, but only one of these was related to the experimental intervention (bilateral femoral condyle and tibial plateau subchondral fractures). Conclusion: Activity-based therapy did not lead to greater improvements in ASIA motor scores compared to upper body training
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ItemVery Low Calorie Diets for Weight Loss in Obese Older Adults-A Randomized Trial(OXFORD UNIV PRESS INC, 2018-01)BACKGROUND: Obesity contributes to disability in older adults, and this is offset by weight loss and exercise. Very Low Calorie Diets (VLCDs) achieve rapid weight loss; however, these have not been rigorously evaluated in older people. METHODS: A randomized trial was conducted from August 2012 through December 2015. The intervention was 12 weeks of thrice weekly exercise combined with either healthy eating advice (Ex/HE), hypocaloric diet (Ex/Diet), or VLCD (Ex/VLCD). Outcomes were physical function, measured by 6-minute walk test (6MWT) and De Morton Mobility Index (DEMMI). Other measures were body composition measured by Dual Energy X-Ray Absorptiometry, and nutritional parameters (albumin, vitamins B12 and D, ferritin and folate). RESULTS: 36, 40, and 41 participants were randomized to Ex/HE, Ex/Diet, and Ex/VLCD, respectively. At 12 weeks, weight was reduced by 3.7, 5.1, and 11.1% (p < .01), respectively. Ex/VLCD had significant reduction in fat (16.8%), lean mass (4.8%), and bone mineral density (1.2%), but increased relative lean mass (3.8%). DEMMI improved by 14.25, 14.25, and 13.75 points in Ex/HE, Ex/Diet, and Ex/VLCD, respectively; however, there was no between-group difference (p = .30). 6MWT improved by 53.1, 64.7, and 84.4 meters in Ex/HE, Ex/Diet, and Ex/VLCD (p = .18). Post hoc stratification for gender and adjustment for initial physical function and type 2 diabetes only revealed significant between-group differences for men in the 6MWT, with improvement by 57.8, 77.8, and 140.3 meters in Ex/HE, Ex/Diet, and Ex/VLCD, respectively (p = .01). Improvements in nutritional parameters were seen in Ex/VLCD, but not in Ex/HE and Ex/Diet. The VLCD was well tolerated. CONCLUSIONS: VLCDs have potential in the treatment of obesity in older persons; of particular benefit is improvement in nutritional status. The gait speed improvement observed in men warrants further investigation.
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ItemSCIPA Full-On: A Randomized Controlled Trial Comparing Intensive Whole-Body Exercise and Upper Body Exercise After Spinal Cord Injury(SAGE PUBLICATIONS INC, 2018-06)Background. While upper body training has been effective for improving aerobic fitness and muscle strength after spinal cord injury (SCI), activity-based therapies intended to activate the paralyzed extremities have been reported to promote neurological improvement. Objective. To compare the effectiveness of intensive whole-body exercise compared with upper body exercise for people with chronic SCI. Methods. A parallel-group randomized controlled trial was conducted. Participants with a range of SCI levels and severity were randomized to either full-body exercise (FBE) or upper body exercise (UBE) groups (3 sessions per week over 12 weeks). FBE participants underwent locomotor training, functional electrical stimulation-assisted leg cycling, and trunk and lower extremity exercises, while UBE participants undertook upper body strength and aerobic fitness training only. The primary outcome measure was the American Spinal Injury Association (ASIA) motor score for upper and lower extremities. Adverse events were systematically recorded. Results. A total of 116 participants were enrolled and included in the primary analysis. The adjusted mean between-group difference was -0.04 (95% CI -1.12 to 1.04) for upper extremity motor scores, and 0.90 (95% CI -0.48 to 2.27) for lower extremity motor scores. There were 15 serious adverse events in UBE and 16 in FBE, but only one of these was definitely related to the experimental intervention (bilateral femoral condyle and tibial plateau subchondral fractures). No significant between-group difference was found for adverse events, or functional or behavioral variables. Conclusions. Full-body training did not lead to improved ASIA motor scores compared with upper body training in people with chronic SCI.
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ItemAccuracy and reproducibility of mouse cortical bone microporosity as quantified by desktop microcomputed tomography(PUBLIC LIBRARY SCIENCE, 2017-08-10)Bone's microporosity plays important roles in bone biology and bone mechanical quality. In this study, we explored the accuracy and reproducibility of nondestructive desktop μCT for 3D visualization and subsequent morphometric analysis of mouse cortical bone microporosity including the vascular canal network and osteocyte lacunae. The accuracy of measurements was evaluated in five murine fibula using confocal laser scanning microscopy (CLSM) in conjunction with Fluorescein isothiocyanate (FITC) staining as the reference method. The reproducibility of μCT-derived cortical bone microstructural indices was examined in 10 fibulae of C57Bl/6J male mice at a nominal resolution of 700 nanometer. Three repeated measurements were made on different days. An excellent correlation between μCT and CLSM was observed for both mean lacuna volume (r = 0.98, p = 0.002) and for mean lacuna orientation (r = 0.93, p = 0.02). Whereas the two techniques showed no significant differences for these parameters, the mean lacuna sphericity acquired from μCT was significantly higher than CLSM (p = 0.01). Reproducibility was high, with precision errors (PE) of 1.57-4.69% for lacuna parameters, and of 1.01-9.45% for vascular canal parameters. Intraclass correlation coefficient (ICC) showed a high reliability of the measurements, ranging from 0.998-1.000 for cortical parameters, 0.973-0.999 for vascular canal parameters and 0.755-0.991 for lacuna parameters. In conclusion, desktop μCT is a valuable tool to quantify the 3D characteristics of bone vascular canals as well as lacunae which can be applied to intact murine bones with high accuracy and reproducibility. Thus, μCT might be an important tool to improve our understanding of the physiological and biomechanical significance of these cannular and lacunar structure in cortical bone.
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ItemMechanical Loading Differentially Affects Osteocytes in Fibulae from Lactating Mice Compared to Osteocytes in Virgin Mice: Possible Role for Lacuna Size(SPRINGER, 2018-12)Hormonal changes during lactation are associated with profound changes in bone cell biology, such as osteocytic osteolysis, resulting in larger lacunae. Larger lacuna shape theoretically enhances the transmission of mechanical signals to osteocytes. We aimed to provide experimental evidence supporting this theory by comparing the mechanoresponse of osteocytes in the bone of lactating mice, which have enlarged lacunae due to osteocytic osteolysis, with the response of osteocytes in bone from age-matched virgin mice. The osteocyte mechanoresponse was measured in excised fibulae that were cultured in hormone-free medium for 24 h and cyclically loaded for 10 min (sinusoidal compressive load, 3000 µε, 5 Hz) by quantifying loading-related changes in Sost mRNA expression (qPCR) and sclerostin and β-catenin protein expression (immunohistochemistry). Loading decreased Sost expression by ~ threefold in fibulae of lactating mice. The loading-induced decrease in sclerostin protein expression by osteocytes was larger in lactating mice (55% decrease ± 14 (± SD), n = 8) than virgin mice (33% decrease ± 15, n = 7). Mechanical loading upregulated β-catenin expression in osteocytes in lactating mice by 3.5-fold (± 0.2, n = 6) which is significantly (p < 0.01) higher than the 1.6-fold increase in β-catenin expression by osteocytes in fibulae from virgin mice (± 0.12, n = 4). These results suggest that osteocytes in fibulae from lactating mice with large lacunae may respond stronger to mechanical loading than those from virgin mice. This could indicate that osteocytes residing in larger lacuna show a stronger response to mechanical loading.
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ItemAging, Osteocytes, and Mechanotransduction(SPRINGER, 2017-10)PURPOSE OF REVIEW: The bone is able to adapt its structure to mechanical signals via the bone remodeling process governed by mechanosensitive osteocytes. With aging, an imbalance in bone remodeling results in osteoporosis. In this review, we hypothesized that changes in lacunar morphology underlie the decreased bone mechanoresponsiveness to mechanical loading with aging. RECENT FINDINGS: Several studies have reported considerable variations in the shape of osteocytes and their lacunae with aging. Since osteocytes can sense matrix strain directly via their cell bodies, the variations in osteocyte morphology may cause changes in osteocyte mechanosensitivity. As a consequence, the load-adaptive response of osteocytes may change with aging, even when mechanical loading would remain unchanged. Though extensive quantitative data is lacking, evidence exists that the osteocyte lacunae are becoming smaller and more spherical with aging. Future dedicated studies might reveal whether these changes would affect osteocyte mechanosensation and the subsequent biological response, and whether this is (one of) the pathways involved in age-related bone loss.