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    Nasal Resistance Is Elevated in People with Tetraplegia and Is Reduced by Topical Sympathomimetic Administration
    Gainche, L ; Berlowitz, DJ ; LeGuen, M ; Ruehland, WR ; O'Donoghue, FJ ; Trinder, J ; Graco, M ; Schembri, R ; Eckert, DJ ; Rochford, PD ; Jordan, AS (AMER ACAD SLEEP MEDICINE, 2016)
    STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in individuals with tetraplegia and associated with adverse health outcomes. The causes of the high prevalence of OSA in this population are unknown, but it is important to understand as standard treatments are poorly tolerated in tetraplegia. Nasal congestion is common in tetraplegia, possibly because of unopposed parasympathetic activity. Further, nasal obstruction can induce OSA in healthy individuals. We therefore aimed to compare nasal resistance before and after topical administration of a sympathomimetic between 10 individuals with tetraplegia (T) and 9 able-bodied (AB) controls matched for OSA severity, gender, and age. METHODS: Nasal, pharyngeal, and total upper airway resistance were calculated before and every 2 minutes following delivery of ≈0.05 mL of 0.5% atomized phenylephrine to the nostrils and pharyngeal airway. The surface tension of the upper airway lining liquid was also assessed. RESULTS: At baseline, individuals with tetraplegia had elevated nasal resistance (T = 7.0 ± 1.9, AB = 3.0 ± 0.6 cm H2O/L/s), that rapidly fell after phenylephrine (T = 2.3 ± 0.4, p = 0.03 at 2 min) whereas the able-bodied did not change (AB = 2.5 ± 0.5 cm H2O/L/s, p = 0.06 at 2 min). Pharyngeal resistance was non-significantly higher in individuals with tetraplegia than controls at baseline (T = 2.6 ± 0.9, AB = 1.2 ± 0.4 cm H2O/L/s) and was not altered by phenylephrine in either group. The surface tension of the upper airway lining liquid did not differ between groups (T = 64.3 ± 1.0, AB = 62.7 ± 0.6 mN/m). CONCLUSIONS: These data suggest that the unopposed parasympathetic activity in tetraplegia increases nasal resistance, potentially contributing to the high occurrence of OSA in this population.
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    Relationship between autonomic cardiovascular control and obstructive sleep apnoea in persons with spinal cord injury: a retrospective study.
    Fang, X ; Goh, MY ; O'Callaghan, C ; Berlowitz, D (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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    Diacetylbis(N(4)-methylthiosemicarbazonato) Copper(II) (CuII(atsm)) Protects against Peroxynitrite-induced Nitrosative Damage and Prolongs Survival in Amyotrophic Lateral Sclerosis Mouse Model
    Soon, CPW ; Donnelly, PS ; Turner, BJ ; Hung, LW ; Crouch, PJ ; Sherratt, NA ; Tan, J-L ; Lim, NK-H ; Lam, L ; Bica, L ; Lim, S ; Hickey, JL ; Morizzi, J ; Powell, A ; Finkelstein, DI ; Culvenor, JG ; Masters, CL ; Duce, J ; White, AR ; Barnham, KJ ; Li, Q-X (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2011-12-23)
    Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical changes to key disease markers. Systemic treatment of SOD1G93A mice significantly delayed onset of paralysis and prolonged lifespan, even when administered to symptomatic animals. Consistent with the properties of this compound, treated mice had reduced protein nitration and carbonylation, as well as increased antioxidant activity in spinal cord. Treatment also significantly preserved motor neurons and attenuated astrocyte and microglial activation in mice. Furthermore, CuII(atsm) prevented the accumulation of abnormally phosphorylated and fragmented TAR DNA-binding protein-43 (TDP-43) in spinal cord, a protein pivotal to the development of ALS. CuII(atsm) therefore represents a potential new class of neuroprotective agents targeting multiple major disease pathways of motor neurons with therapeutic potential for ALS.
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    Rehabilitation Outcomes In Persons With Spina Bifida: A Randomized Controlled Trial
    Khan, F ; Amatya, B ; Ng, L ; Galea, M (Medical Journals Sweden, 2015-09-01)
    Objective: To assess the effectiveness of an interdisciplinary ambulatory rehabilitation programme for persons with spina bifida in an Australian community cohort. Methods: Fifty-four participants randomized to a treatment group (n = 27) for a high-intensity rehabilitation programme (with cognitive behavioural therapy) or a control group (n = 27) comprising usual care. Outcome measures include: Disability: Urogenital Distress Inventory (UDI6), Incontinence Impact Questionnaire-7 (IIQ7), American Urological Association Symptom Index (AUA), Wexner-Faecal Incontinence Score (WFIS), Neurological Disability Scale (NDS); Participation: Depression, Anxiety Stress Scale (DASS), McGill Quality of Life (MQOL), Brief COPE Scale, Genera-lized Self-efficacy Scale (GSE). Assessments were made at baseline and 3-months post-intervention. Results: Adjusted for baseline disease and demographic covariates, the intervention group improved significantly at 3-month follow-up for primary and secondary outcomes, with moderate to large effect sizes (r): urinary/bowel dysfunction (AUA, UDI6, IIQ7, WFIS) (p < 0. 001 for all, r = 0. 4–0. 7); and cognitive function: NDS “cognitive” and “mood” (p < 0. 01, r = 0. 6 for both); DASS “depression”, “anxiety” and “stress” (p < 0. 001 for all, r = 0. 5–0. 7); MQOL total (p = 0. 013, r = 0. 5), “psychological symptoms” (p < 0. 001, r = 0. 8); “active coping” (p = 0. 035) and “self-efficacy” scores (GSE p < 0. 001). No difference between groups was noted in other subscales. Conclusion: Targeted rehabilitation can improve clinical outcomes in persons with spina bifida. Further research is needed for longer-term outcomes related to “ageing” and participation restriction.
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    Supportive Care Needs following Cancer Treatment: A Comparison of Breast and Brain Cancer in an Australian Cohort
    Bhasker, A ; Khan, F ; Ng, L ; Galea, M (Hindawi Publishing Corporation, 2014)
    Objective. To assess and identify patient-reported supportive care needs following definitive treatment in persons with breast cancer (BC) and primary brain tumours (gliomas) (BT) in an Australian community cohort and to assess the commonalities and/or discrepancies of the reported needs in these oncological populations. Methods. A prospective cross-sectional survey of persons with BC () and BT () using questionnaires for supportive care needs, psychological morbidity, and quality of life. Results. BT participants were younger than BC patients (mean ages 51 and 57 years). The median time since diagnosis for both groups was over 2 years. The level of psychological morbidity, mainly depression, was high in both groups: BC (22%) and BT (20%). Participants in both groups reported at least one need (“met” or “unmet”). The BC patients reported higher numbers of “needs” and “unmet” needs compared with BT patients (mean 13.7 versus 11.6 needs; “unmet” needs mean 6.0 versus 4.1). The common “met” and “unmet” needs highlighted by both groups were comparable; the domain for most “met” needs included comprehensive cancer care, while “unmet” needs related to existential survivorship issues. Conclusion. Despite successful treatment many cancer survivors experience unmet supportive care needs in longer term. Understanding the impact of these beyond the acute phase is important as care shifts to community settings. More research in existential survivorship issues is needed.
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    An enriched environmental programme during inpatient neuro-rehabilitation: A randomized controlled trial
    Khan, F ; Amatya, B ; Elmalik, A ; Lowe, M ; Ng, L ; Reid, I ; Galea, MP (Medical Journals Sweden, 2016-05-01)
    Objective: To assess the effectiveness of an enriched environmental activities programme in an inpatient tertiary neuro-rehabilitation unit. Methods: A total of 103 participants were randomized to an intervention group (n = 52) undertaking an enriched environmental activities programme or a control group (n = 51) receiving usual ward activity. Primary outcome measure: Depression, Anxiety Stress Scale (DASS). Other measures included: Neurological Impairment Scale; Multidimensional Health Locus of Control, Rosenberg Self-Esteem Scale, Montreal Cognitive Assessment (MoCA); Functional Independence Measure (FIM), and Euro-Quality of Life-5D. Questionnaire assessments were performed at admission, discharge and 3-months post-discharge. Results: Mean age of subjects was 62. 5 years (standard deviation 18. 5), 63% were male; 53 had stroke and the remainder had other neurological conditions. Compared with controls, the intervention group showed significant improvement at discharge in: DASS: “total”, “depression”, and “stress” subscales (p < 0. 05 for all, with small effect sizes (η2) = 0. 04–0. 05); MoCA (p = 0. 048, η2 = 0. 04) and FIM motor (total and “self-care”, “mobility” subscales (p < 0. 05 for all, with moderate effect sizes, η2 = 0. 0–0. 08). At 3-month follow-up, significant differences were maintained in most secondary outcomes in the intervention group. Cognitive function and activities improved most in participants with stroke. Conclusion: An enriched environmental programme can produce significant improvements in functional and cognitive ability in inpatient neurological cohorts compared with routine ward activity programmes.
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    Peripheral neuropathy in the hands of people with diabetes mellitus
    Ennis, SL ; Galea, MP ; O'Neal, DN ; Dodson, MJ (ELSEVIER IRELAND LTD, 2016-09)
    AIMS: Peripheral sensorimotor neuropathy is a recognised complication of diabetes mellitus however little attention has been given to its development in the hands. The aim of this study was to determine the prevalence of sensory impairment in the hands of participants with diabetes, the agreement between two measurement tools for assessing sensation and the association between hand sensibility, age, glycaemic control and end-organ damage. METHODS: A total of 162 participants were recruited and divided into two cohorts based on a diagnosis of diabetes. Participants were tested for the presence of hand neuropathy using Semmes-Weinstein monofilaments and the AsTex™. Medical records of participants with diabetes were accessed retrospectively to determine glycaemic control and diabetes complications. RESULTS: A highly statistically significant association was found between neuropathy and diabetes status (P<0.001) on monofilament testing. The prevalence of neuropathy was 64% compared to ∼10% amongst participants without diabetes. Age, male gender and diabetic retinopathy were associated with neuropathy. The AsTex™ identified participants with diminished protective sensation on monofilament testing. CONCLUSIONS: This study demonstrates a relationship between diabetes and upper limb neuropathy. Age, male gender and retinopathy were associated with diminished hand sensation. The AsTex™ may have a role as a screening tool for identifying clinically significant hand neuropathy.
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    Rehabilitation for people with multiple sclerosis: An overview of Cochrane systematic reviews
    Amatya, B ; Khan, F ; Ng, L ; Galea, M (Wiley, 2017-07-25)
    This is a protocol for a Cochrane Review (Overview). The objectives are as follows: This review will systematically evaluate evidence from published Cochrane Reviews/meta analyses of clinical trials to determine the effectiveness and safety of rehabilitation interventions for the management of people with MS, in order to improve patient outcomes and will highlight current gaps in knowledge. Specific questions to be addressed by this review include the following. • Are rehabilitation interventions (unidisciplinary, or multidisciplinary, or both) effective in minimising impairment, activity limitation, and participation restriction in people with MS? • Are rehabilitation interventions (unidisciplinary, or multidisciplinary, or both) effective in minimising the burden of care and improving quality of life in people with MS? • What types of rehabilitation interventions (unidisciplinary, or multidisciplinary,or both) are effective in people with MS, and in which setting? The specific aim of the review is to compile evidence from published multiple Cochrane Reviews of interventions for people with MS into one accessible and coherent document to be used by clinicians, researchers, funding bodies, policy makers, and consumers to aid decision making and evidence implementation.
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    Elucidating the mechanism of the Ley-Griffith (TPAP) alcohol oxidation
    Zerk, TJ ; Moore, PW ; Harbort, JS ; Chow, S ; Byrne, L ; Koutsantonis, GA ; Harmer, JR ; Martinez, M ; Williams, CM ; Bernhardt, PV (ROYAL SOC CHEMISTRY, 2017-12-01)
    The Ley-Griffith reaction is utilized extensively in the selective oxidation of alcohols to aldehydes or ketones. The central catalyst is commercially available tetra-n-propylammonium perruthenate (TPAP, n-Pr4N[RuO4]) which is used in combination with the co-oxidant N-methylmorpholine N-oxide (NMO). Although this reaction has been employed for more than 30 years, the mechanism remains unknown. Herein we report a comprehensive study of the oxidation of diphenylmethanol using the Ley-Griffith reagents to show that the rate determining step involves a single alcohol molecule, which is oxidised by a single perruthenate anion; NMO does not appear in rate law. A key finding of this study is that when pure n-Pr4N[RuO4] is employed in anhydrous solvent, alcohol oxidation initially proceeds very slowly. After this induction period, water produced by alcohol oxidation leads to partial formation of insoluble RuO2, which dramatically accelerates catalysis via a heterogeneous process. This is particularly relevant in a synthetic context where catalyst degradation is usually problematic. In this case a small amount of n-Pr4N[RuO4] must decompose to RuO2 to facilitate catalysis.
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    Induction monotherapy with sirolimus has selected beneficial effects on glomerular and tubulointersititial injury in nephrotoxic serum nephritis
    Succar, L ; Lai-Kwon, J ; Nikolic-Paterson, DJ ; Rangan, GK (DOVE MEDICAL PRESS LTD, 2014)
    BACKGROUND: The study aimed to test the hypothesis that therapeutic treatment with a mammalian target of rapamycin complex 1 inhibitor reduces renal cell proliferation and attenuates glomerular and tubulointerstitial injury in the early phase of nephrotoxic serum nephritis (NSN) in rats. METHODS: Male Wistar-Kyoto rats received a single tail-vein injection of sheep anti-rat glomerular basement membrane serum (day 0) and were treated with vehicle or sirolimus (0.25 mg/kg/day by subcutaneous injection) from day 1 until day 14. RESULTS: Treatment with sirolimus attenuated kidney enlargement by 41% (P<0.05), improved endogenous creatinine clearance by 50% (P<0.05), and reduced glomerular and tubulointerstitial cell proliferation by 53% and 70%, respectively, (P<0.05 compared to vehicle) in rats with NSN. In glomeruli, sirolimus reduced segmental fibrinoid necrosis by 69%, autologous rat immunoglobulin G deposition, glomerular capillary tuft enlargement, and periglomerular myofibroblast (α-smooth muscle actin-positive cells) accumulation (all P<0.05) but did not significantly affect glomerular crescent formation (P=0.15), macrophage accumulation (P=0.25), or the progression of proteinuria. In contrast, sirolimus preserved tubulointerstitial structure and attenuated all markers of injury (interstitial ED-1- and α-smooth muscle actin-positive cells and tubular vimentin expression; all P<0.05). By immunohistochemistry and Western blot analysis, sirolimus reduced the glomerular and tubulointerstitial expression of phosphorylated (Ser 235/236) S6-ribosomal protein (P<0.05). CONCLUSION: Induction monotherapy with sirolimus suppressed target of rapamycin complex 1 activation, renal cell proliferation, and injury during the early stages of rodent NSN, but the degree of histological protection was more consistent in the tubulointerstitium than the glomerular compartment.