A pilot investigation using global positioning systems into the outdoor activity of people with severe traumatic brain injury

Background: Little is known about the post-discharge outdoor activities of people who have incurred severe traumatic brain injury (TBI). This study used a body-worn global positioning system (GPS) device to determine the outdoor activity per day performed by this population. Additionally, this study examined the association that mobility, time since injury and injury severity had with levels of outdoor physical activity. Findings. Seventeen people with TBI and 15 control subjects wore a GPS device for between 3-7 days to monitor their outdoor activity. Based on the individual's location and speed of movement the outdoor physical activity in minutes per day was derived. Assessments of duration of outdoor activity between groups, and the relationship that duration of outdoor activity had with results on the high-level mobility assessment tool, length of post-traumatic amnesia, and time since injury were performed. No significant (p = 0.153, effect size = 0.26) difference in time spent in outdoor physical activity was observed between the TBI (median[IQR] = 19[3-43]mins) and control (median[IQR] = 50[18-65]mins) group. Interestingly, 35% of TBI subjects performed <10 mins of outdoor activity per day compared to 13% of the control group. The TBI group also recorded three of the four highest values for outdoor physical activity. Higher levels of mobility were associated with more outdoor activity (Spearman's rho = 0.443, p = 0.038). No other significant associations were observed. Conclusions: While preliminary, our results indicate that a sub-group of people with TBI exists who restrict their outdoor activities. GPS has potential as an activity tracking tool, with implications for rehabilitation and exercise prescription. © 2014 Clark et al.; licensee BioMed Central Ltd

Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics

Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics

Cross-education does not accelerate the rehabilitation of neuromuscular functions after ACL reconstruction: a randomized controlled clinical trial

Purpose: Cross-education reduces quadriceps weakness 8 weeks after anterior cruciate ligament (ACL) surgery, but the long-term effects are unknown. We investigated whether cross-education, as an adjuvant to the standard rehabilitation, would accelerate recovery of quadriceps strength and neuromuscular function up to 26 weeks post-surgery. Methods: Group allocation was randomized. The experimental (n = 22) and control (n = 21) group received standard rehabilitation. In addition, the experimental group strength trained the quadriceps of the non-injured leg in weeks 1–12 post-surgery (i.e., cross-education). Primary and secondary outcomes were measured in both legs 29 ± 23 days prior to surgery and at 5, 12, and 26 weeks post-surgery. Results: The primary outcome showed time and cross-education effects. Maximal quadriceps strength in the reconstructed leg decreased 35% and 12% at, respectively, 5 and 12 weeks post-surgery and improved 11% at 26 weeks post-surgery, where strength of the non-injured leg showed a gradual increase post-surgery up to 14% (all p ≤ 0.015). Limb symmetry deteriorated 9–10% more for the experimental than control group at 5 and 12 weeks post-surgery (both p ≤ 0.030). One of 34 secondary outcomes revealed a cross-education effect: Voluntary quadriceps activation of the reconstructed leg was 6% reduced for the experimental vs. control group at 12 weeks post-surgery (p = 0.023). Both legs improved force control (22–34%) and dynamic balance (6–7%) at 26 weeks post-surgery (all p ≤ 0.043). Knee joint proprioception and static balance remained unchanged. Conclusion: Standard rehabilitation improved maximal quadriceps strength, force control, and dynamic balance in both legs relative to pre-surgery but adding cross-education did not accelerate recovery following ACL reconstruction

Inhibition of Insulin-Regulated Aminopeptidase: A Novel Therapeutic Strategy for Stroke

This thesis characterises and validates a preclinical model of stroke that closely mimics human stroke. In this preclinical model, novel drug therapies that target the insulin-regulated aminopeptidase (IRAP), an enzyme found in the brain, were tested. This thesis identified that following stroke, targeting IRAP reduces tissue damage in the brain and improves physical mobility

A 10-year experience in managing thoraco-abdominal mycotic aortic aneurysms

Purpose: Mycotic aneurysms hold a high risk of rupture with a peri-operative mortality rate of up to 44%. The aim is to describe the outcomes and management of mycotic aortic, iliac or lower limb arterial aneurysms over 10 years in an Australian quaternary hospital. Methodology: Patients who underwent operative management of mycotic aneurysms between 2012 – 2022 at an Australian quaternary hospital were identified. Aneurysm characteristics and infective micro-organisms were noted. The primary outcome is mortality (in-hospital and 30-day). Secondary outcomes include complications (stroke, delirium, bowel, lower limb and spinal cord ischaemia), return to theatre and length of hospital stay (LOS). Results: Preliminary results identified twelve patients. Average age of presentation was 71.2 years with majority of patients being male (n = 9, 75%). Half of patients underwent open repair (n = 6, 50%) while five patients underwent endovascular repair (41.2%) and one underwent hybrid repair. Salmonella species were the organism responsible in three cases, other organisms included serratia, streptococcus, methicillin resistant staphylococcal species and pseudomonas. Patients who underwent open repair had a longer LOS with average of 16.5 days (range 5-33 days) compared to those who underwent endovascular repair (average 14.80 days, range 4-29 days). Complication encountered included spinal cord ischaemia (n=1), hospital acquired pneumonia (n=3), stroke (n=1), pleural effusion requiring intervention (n=1), delirium (n=2) and retroperitoneal haematoma (n=2) with one requiring return to theatre for washout. Most of the complications occurred in those undergoing endovascular repair. There was one re-admission within 30-days and all patients survived 30-days post intervention. Conclusion: In our institution, mycotic aneurysms most commonly presented in the supra-renal aorta and the iliac arteries. Despite endovascular repair being thought to be less co-morbid than open procedures, our centre has shown a higher complication rate in those undergoing endovascular repair

Supplemental Material - The prevalent causes of death in patients with peripheral artery disease undergoing revascularisation or amputation

Supplemental Material for The prevalent causes of death in patients with peripheral artery disease undergoing revascularisation or amputation by Stacey Telianidis and Sarah Joy Aitken in Vascular</p

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration