Peripheral Quantitative Computed Tomography: Review of Evidence and Recommendations for Image Acquisition, Analysis, and Reporting, Among Individuals With Neurological Impairment

The final publication is available at Elsevier via https://doi.org/10.1016/j.jocd.2018.07.003. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/In 2015, the International Society for Clinical Densitometry (ISCD) position statement regarding peripheral quantitative computed tomography (pQCT) did not recommend routine use of pQCT, in clinical settings until consistency in image acquisition and analysis protocols are reached, normative studies conducted, and treatment thresholds identified. To date, the lack of consensus-derived recommendations regarding pQCT implementation remains a barrier to implementation of pQCT technology. Thus, based on description of available evidence and literature synthesis, this review recommends the most appropriate pQCT acquisition and analysis protocols for clinical care and research purposes, and recommends specific measures for diagnosis of osteoporosis, assigning fracture risk, and monitoring osteoporosis treatment effectiveness, among patients with neurological impairment. A systematic literature search of MEDLINE, EMBASE©, CINAHL, and PubMed for available pQCT studies assessing bone health was carried out from inception to August 8th, 2017. The search was limited to individuals with neurological impairment (spinal cord injury, stroke, and multiple sclerosis) as these groups have rapid and severe regional declines in bone mass. Of 923 references, we identified 69 that met review inclusion criteria. The majority of studies (n = 60) used the Stratec XCT 2000/3000 pQCT scanners as reflected in our evaluation of acquisition and analysis protocols. Overall congruence with the ISCD Official Positions was poor. Only 11% (n = 6) studies met quality reporting criteria for image acquisition and 32% (n = 19) reported their data analysis in a format suitable for reproduction. Therefore, based on current literature synthesis, ISCD position statement standards and the authors’ expertise, we propose acquisition and analysis protocols at the radius, tibia, and femur sites using Stratec XCT 2000/3000 pQCT scanners among patients with neurological impairment for clinical and research purposes in order to drive practice change, develop normative datasets and complete future meta-analysis to inform fracture risk and treatment efficacy evaluation.Spinal Cord Injury - OntarioCanada Research Chair in Musculoskeletal and Postmenopausal HealthOntario Ministry of Research and InnovationCanadian Foundation for InnovationCanadian Institutes of Health Research [grant 86251]ONF-REPAR [2011-ONF-REPAR2-885]Rick Hansen Foundation [2011-15S-RES3-tri-100812]Craig H. Neilsen Foundation [350642

Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.

Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNAAla mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin

Effects of exercise interventions on cardiovascular health in individuals with chronic, motor complete spinal cord injury: protocol for a randomised controlled trial [Cardiovascular Health/Outcomes: Improvements Created by Exercise and education in SCI (CHOICES) Study]

INTRODUCTION Recent studies demonstrate that cardiovascular diseases and associated complications are the leading cause of morbidity and mortality in individuals with spinal cord injury (SCI). Abnormal arterial stiffness, defined by a carotid-to-femoral pulse wave velocity (cfPWV) ≥10 m/s, is a recognised risk factor for heart disease in individuals with SCI. There is a paucity of studies assessing the efficacy of conventional training modalities on arterial stiffness and other cardiovascular outcomes in this population. Therefore, this study aims to compare the efficacy of arm cycle ergometry training (ACET) and body weight-supported treadmill training (BWSTT) on reducing arterial stiffness in individuals with chronic motor complete, high-level (above the sixth thoracic segment) SCI. METHODS AND ANALYSIS This is a multicentre, randomised, controlled, clinical trial. Eligible participants will be randomly assigned (1:1) into either ACET or BWSTT groups. Sixty participants with chronic (>1 year) SCI will be recruited from three sites in Canada (Vancouver, Toronto and Hamilton). Participants in each group will exercise three times per week up to 30 min and 60 min for ACET and BWSTT, respectively, over the period of 6 months. The primary outcome measure will be change in arterial stiffness (cfPWV) from baseline. Secondary outcome measures will include comprehensive assessments of: (1) cardiovascular parameters, (2) autonomic function, (3) body composition, (4) blood haematological and metabolic profiles, (5) cardiorespiratory fitness and (6) quality of life (QOL) and physical activity outcomes. Outcome measures will be assessed at baseline, 3 months, 6 months and 12 months (only QOL and physical activity outcomes). Statistical analyses will apply linear-mixed modelling to determine the training (time), group (ACET vs BWSTT) and interaction (time × group) effects on all outcomes. ETHICS AND DISSEMINATION Ethical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated. TRIAL REGISTRATION NUMBER NCT01718977; Pre-results. TRIAL STATUS Recruitment for this study began on January 2013 and the first participant was randomized on April 2013. Recruitment stopped on October 2018