Visual object similarity, action similarity and semantic information are believed to influence both object naming and action production. The Naming and Action Model (NAM) developed by Yoon, Heinke, and Humphreys (2002) suggests that naming objects requires access to semantics, but that there are two routes to action production; an indirect route via semantics, and a direct route that bypasses semantics. For example, when presented with a known object like a hammer, one may retrieve action information from the representational knowledge of its function or directly from its visual characteristics. Past research suggests that producing actions with known objects relies mostly on using the direct route and producing actions with novel objects relies mostly on using the indirect route via semantics. However, this has not been clearly shown. Therefore, the current study examines the role of semantics on object naming and producing actions when training on novel object-action associations. Participants were asked to learn novel object-action associations that were labeled with either the names of semantically similar items or semantically dissimilar items. After an initial learning session, participants named the objects, produced novel actions with the objects and produced novel actions with a cylinder in response to the previously learned labels. Participants then practiced the actions with the objects over three sessions. During the final session, participants were given a reminder of the object-action associations and then they were tested on them again. Results showed that before and after practice, participants made more naming errors and action errors with the cylinder for objects associated with semantically similar labels than objects associated with semantically dissimilar labels. This suggests that when naming objects and producing actions with the cylinder before and after practice, participants were likely relying on the semantic route. However, when participants produced actions with the objects, the pattern of results was different. Before practice, participants made more action errors with objects associated with semantically similar labels than objects associated with semantically dissimilar labels. After practice, participants made equivalent numbers of action errors for objects associated with semantically similar and dissimilar labels. This suggests that participants were likely using the semantic route before practice and the direct route after practice.

Manual muscle tests (MMTs) are frequently used in clinical settings to evaluate a specific muscle’s function and strength in a position at which this muscle is believed to be most isolated from other synergists and antagonists. It is necessary for a muscle to be tested in a state of isolation (as much as is physiologically possible), as interpretation of strength and function can be compromised by the contributions of other active muscles. In the present study, electromyographic activation of 14 shoulder muscles was assessed in 12 males during 29 shoulder exertions. Maximal isolation ratios defined which of these exertions most isolated the rotator cuff muscles. Results confirmed the appropriateness of nine clinical MMTs in isolating the rotator cuff muscles, but suggested that several other exertions were equally appropriate in isolating these muscles. Forces produced during isolation exertions can be compared to patient exertions to promote more objective MMT grading.

The purpose of this study was to examine the effects of exogenous peroxynitrite (ONOO-) on the cardiac isoform of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and to determine if overexpression of heat shock protein 70 (Hsp70) could protect SERCA2a function. To characterize the interaction between SERCA2a and Hsp70, cDNAs encoding each protein were co-transfected in human embryonic kidney cells (HEK-293) using the calcium-phosphate technique. Western blotting confirmed the expression of SERCA2a and a ~1.9-fold overexpression of Hsp70 in HEK-293 cells. ONOO- was added chronically (250 μM bolus each minute for 10 minutes) to co-transfected HEK-293 cells in culture. Maximal Ca2+-ATPase activity (Vmax) was assessed on microsomal fractions isolated following exposure to ONOO-. Vmax was reduced by ~20% in HEK-293 cells transfected with SERCA2a alone (S2a-pMT2). When Hsp70 was co-transfected with SERCA2a (S2a-Hsp70), Vmax was fully protected following incubation with ONOO-. Western blot analysis showed that there were no changes in FITC binding capacity and 3-nitrotyrosine content in any of the groups. However, overexpression of Hsp70 prevented oxidation of SERCA2a, as assessed by reactive carbonyl content, following exposure to ONOO- when compared to S2a-pMT2. In addition, SERCA2a aggregation was lower compared to S2a-pMT2 groups under both control and ONOO- conditions. Co-immunoprecipitation of SERCA2a and Hsp70 confirmed that Hsp70 physically interacts with SERCA2a under all conditions. These results suggest that Hsp70 physically binds to SERCA2a and prevents oxidation and aggregation of SERCA2a, thus preserving enzyme activity.

Background: Osteoarthritis (OA), the most common form of arthritis, is a disorder that affects bi-articular synovial joints and is characterized as the focal loss of articular cartilage with changes to the subchondral and marginal bone, synovium and para-articular structures. Biomechanical factors such as obesity, joint loading, joint injury, joint deformity, level of sports participation, occupational factors, and muscle weakness specifically affect joint loading which influences local OA development. One way to assess the effect of altered loading patterns on a joint is to examine changes following joint injury. An appropriate model for this purpose is the anterior cruciate ligament (ACL) rupture in the knee joint. Recent evidence has shown that some ACL-D subjects are able to perform activities at levels similar to those of normal subjects. Termed ‘Copers’, these individuals demonstrate greater knee stability than other ACL-D subjects who are considered ‘Non-Copers’. Therefore, the purpose of this study was to evaluate the dynamic control strategies used by ACL-D Copers and Non-Copers during a stair climbing task, and compare them to a healthy population as a means to identify possible susceptabilities to OA. Methods: A total of 20 participants were collected including 10 (5 male and 5 female) Healthy controls, 5 (2 male and 3 female) ACL-D Copers, and 5 (1 male and 4 females) ACL-D Non-Copers. The Healthy group had an average mass of 75.9 kg ±16.1 kg and an average height of 174.3 cm ±12.1cm, while the Copers group had an average mass of 71.7 kg ±6.2 kg and an average height of 170.8 cm ±5.6 cm, and the Non-Copers group had an average mass of 71.3 kg ±13.1 kg and an average height of 168.7 cm ±4.8 cm. ACL-D subjects were classified as either a Coper and Non-Coper based on a screening examination prior to the evaluation.The stair climbing task involved each subject completing 20 stair-climbing trials (10 ascent and 10 descent). Kinematic and kinetic outcomes were collected on the lower limbs, as well as,electromyography (EMG) of the tibilais anterior, medial and lateral gastrocnemius, vastus lateralis, vastus medialis, semitendinosus, and biceps femoris muscle group were collected bi-laterally. A one-way analysis of variance (ANOVA) was used to test each outcome’s statistical significance (α= 0.05). Results and Discussion: During ascent the Non-Copers and Copers group completed the task with greater knee flexion than the healthy group (although not significant), while during descent the Non-Copers maintained approximately 5 degrees greater flexion than the other groups. A significant difference was observed with the moment about the knee (flex-ext) between the Healthy group and the Non-Copers group during the late stages of stair ascent with the healthy group maintaining a flexor moment and the Non-Copers group using an extensor moment. This extensor moment correlated with the increase of quadriceps activity among the Non-Copers which may lead to instances of knee joint instability. The Non-Copers group had increased activity of the hamstring muscle group without any attenuation in the quadriceps muscles. This will most likely increase the forces acting on the knee joint. Since, the knee is at greater flexion with an increased amount of forces, the Non-Copers may be at a greater risk articular cartilage breakdown. Throughout the majority of descent we saw an elevated amount of hamstring activity in the Non-Copers group at greater knee flexion angles as a potential means of controlling displacement of the tibia. This increase in hamstring muscle activity by the Non-Copers, without any significant decrease in quadriceps activity, places greater forces on the knee at different knee angle, when compared to the healthy group and may promote the onset of osteoarthritis. The Non-Copers also had increased moments about the knee joint for the majority of stance in both the flexion-extension plane and the abduction-adduction plane, when compared to the healthy group.

Visual object similarity, action similarity and semantic information are believed to influence both object naming and action production. The Naming and Action Model (NAM) developed by Yoon, Heinke, and Humphreys (2002) suggests that naming objects requires access to semantics, but that there are two routes to action production; an indirect route via semantics, and a direct route that bypasses semantics. For example, when presented with a known object like a hammer, one may retrieve action information from the representational knowledge of its function or directly from its visual characteristics. Past research suggests that producing actions with known objects relies mostly on using the direct route and producing actions with novel objects relies mostly on using the indirect route via semantics. However, this has not been clearly shown. Therefore, the current study examines the role of semantics on object naming and producing actions when training on novel object-action associations. Participants were asked to learn novel object-action associations that were labeled with either the names of semantically similar items or semantically dissimilar items. After an initial learning session, participants named the objects, produced novel actions with the objects and produced novel actions with a cylinder in response to the previously learned labels. Participants then practiced the actions with the objects over three sessions. During the final session, participants were given a reminder of the object-action associations and then they were tested on them again. Results showed that before and after practice, participants made more naming errors and action errors with the cylinder for objects associated with semantically similar labels than objects associated with semantically dissimilar labels. This suggests that when naming objects and producing actions with the cylinder before and after practice, participants were likely relying on the semantic route. However, when participants produced actions with the objects, the pattern of results was different. Before practice, participants made more action errors with objects associated with semantically similar labels than objects associated with semantically dissimilar labels. After practice, participants made equivalent numbers of action errors for objects associated with semantically similar and dissimilar labels. This suggests that participants were likely using the semantic route before practice and the direct route after practice.

Background: Following spinal cord injury (SCI) declines in sub-lesional bone mineral density (BMD) occur, and are associated with a high prevalence of fractures. Conventional risk factors for osteoporosis diagnosis in the non-SCI population put all individuals with SCI at a high risk of fracturing, however not all experience fractures. Vitamin D and parathyroid hormone (PTH) levels have been linked to skeletal health in the non-SCI population, and therefore may be a fracture risk factor worth targeting post-SCI. Objectives: To evaluate: 1) the prevalence of suboptimal vitamin D (Serum 25(OH)D <75nmol/L) status and identify the relationships between 25(OH)D and bone quality; and 2) the prevalence of secondary hyperparathyroidism (Serum intact PTH ≥ 7.0 pmol/L) and identify the relationships between serum PTH and bone quality, in males and females with chronic SCI. Methods: Individuals were assessed via cross-sectional study design. Serum 25(OH)D was measured using a chemiluminescent immunoassay and serum intact PTH was measured using an electrochemiluminescent immunoassay. Bone quality parameters evaluated include: 1) DXA assessed distal femur and proximal tibia aBMD; and 2) pQCT assessed vBMD at the 4% tibia trabecular and 66% tibia cortical sites, and 66% tibia cortical thickness. Correlates of suboptimal vitamin D status were identified through univariate logistic regression analaysis. Pearson correlations were run to assess the relationships between the serum measures and the bone quality outcomes. Significance was p<0.05. Results: Thirty-eight percent of the included 45 adult males and females with chronic SCI had suboptimal serum 25(OH)D levels. Those with vitamin D assessed in the winter months (OR=6.3, p=0.022), not taking calcium supplements (OR=7.1, p=0.038), not taking vitamin D supplements (OR=10.5, p=0.049), and of younger age (OR=0.92, p=0.038) were associated with suboptimal vitamin D levels. A weak, non-significant association was observed between PTH and serum 25(OH)D (r=-0.327, p=0.068) and there was a trend towards an inverse association between PTH and 66% tibia cortical thickness (r=-0.353, p=0.071). Conclusions: Disruption of the vitamin D-PTH axis may contribute to the bone loss seen in the chronic SCI population, particularly in cortical bone. Optimal serum 25(OH)D levels in the chronic SCI population may be higher than in the non-SCI population.

Subcortical and cortical loci interact with the primary motor cortex (M1) and influence the neural circuitry mediating hand movement. Area 5 located within the superior parietal lobule has direct connectivity with M1, is largely dedicated to the representation of the hand, and is considered important for thumb opposition movements. The present study examined the modulation of inhibitory and excitatory neural circuits within bilateral M1 before and after continuous (cTBS), intermittent (iTBS), and sham theta-burst stimulation (TBS) over left-hemisphere area 5. Two experiments were performed to address the influence of area 5 on neural circuitry within M1. Specifically, inhibitory circuitry (short interval intracortical inhibition (SICI)) and excitatory circuitry (motor evoked potentials (MEPs), intracortical facilitation (ICF)), were examined for the representation of the first dorsal interosseous (FDI) muscle within bilateral M1. MEPs, SICI, and ICF were measured bilaterally before and at 5-20 minutes, 25-40 minutes, and 45-60 minutes after TBS cessation. The order for right versus left M1 recordings for MEPs, SICI, and ICF recordings were kept constant within subjects across each time block and this order of cortex stimulated (right, left) was randomized across subjects. The results of Experiment 1 and 2 demonstrate that area 5 selectively influences M1 circuitry such that MEPs are increased bilaterally following area 5 cTBS and increased in the right FDI following area 5 iTBS. Area 5 TBS does not modulate ICF or SICI. The novel findings from the Master’s thesis suggest area 5 is a cortical loci that influences M1 excitatory circuitry and possibly motor control of the hand.

Background/Objectives: Low areal bone mineral density (aBMD) of the hip and knee region has been associated with fracture risk in individuals with SCI; however the contribution of bone micro-architecture to fracture risk has not been evaluated. The primary objective of this study was to determine whether a relationship exists between indices of bone strength (aBMD at the distal femur and proximal tibia; trabecular vBMD; average hole size, HA; cortical thickness, CTh; buckling ratio, BR; cross-sectional moment of inertia, CSMI; and polar moment of inertia, PMI) and potential fracture risk factors (gender, age, bisphosphonate use, time post-injury, fractures, and completeness of injury). The secondary objectives were to 1) determine whether indices of bone strength can discriminate between SCI patients with and without fragility fractures; 2) determine if these indices of bone strength correlate with the number of fractures sustained; and 3) determine the proportion of individuals with SCI who have a trabecular vBMD at the ultra-distal tibia that is below 72mg/cm3. Materials and Methods: A nested case-control study was performed. Forty seven men (n=33) and women (n=14) with chronic SCI (C2-T12 AIS A-D) with a duration of paralysis of at least two years were included in this study. Subjects with SCI were questioned about the cause, location, and time of the lower extremity fragility fractures. Fracture presence was verified by x-rays. aBMD of the distal femur and proximal tibia were determined using dual energy x-ray absorptiometry (DXA). Trabecular volumetric bone mineral density (vBMD) and HA were measured at 4% of the tibia length, and CTh, BR, CSMI, and PMI were measured at 66% of the tibia length of individuals with chronic SCI using peripheral quantitative computed tomography (pQCT). Linear and multiple regression models were used to determine significant correlates (age, gender, completeness of injury, duration of injury, bisphosphonate use, and fractures) of indices of bone strength, while logistic regression was used to assess the relationship between indices of bone strength and fragility fractures. To assess the relationship between multiple fragility fractures and indices of bone strength, a poisson regression analysis was performed. Results: Risk factors found to be related to the indices of bone strength include gender, completeness of injury, duration of injury, bisphosponate use, and prior fractures. An increase in HA (OR=1.081, 95% CI=1.001-1.166, p=0.0470), a decrease in aBMD in the distal femur (OR=0.988, 95% CI=0.978-0.998, p=0.0226), and a decrease in CSMI (OR=0.098, 95% CI=0.012-0.838), p=0.0338) were associated with fractures. Fractures were not associated with aBMD at the proximal tibia, trabecular vBMD, CTh, or BR. The poisson regression model predicting the number of fragility fractures sustained among individuals with chronic SCI from aBMD, vBMD, HA, CTh, CSMI, PMI, and BR were each statistically significant. Finally, only 7.7% of our population had a trabecular vBMD fracture threshold of less than or equal to 72mg/cm3. We found a trabecular vBMD fracture breaking point of approximately 126mg/cm3 and 115mg/cm3 at the ultra distal tibia in individuals with complete and incomplete SCI, respectively. Conclusion: Specific bone strength measures, specifically aBMD at the distal femur, HA, and CSMI are associated with fracture risk and may improve our ability to identify individuals with SCI at high risk of fracture. Larger population based studies are needed to determine the most appropriate risk factors that contribute to bone loss and understand the role and importance of these and other indices of bone strength on skeletal fragility in individuals with SCI.

Essential hypertension is a disease involving impaired endothelium-dependant vasomotor function which is partially mediated through an increase in reactive oxygen species. Recent evidence has demonstrated that resveratrol (RSV), a polyphenol with antioxidant capabilities, alleviates this impaired endothelium-dependant vasomotor function and can provide cardiovascular health benefits. The aim of this study was to examine the effects of chronic resveratrol treatment for 28 days on the endothelium-dependant vasomotor function and hemodynamic measures of the common carotid artery (CCA) of Spontaneously Hypertensive rat (SHR) aged 20-22 weeks at a high (2.7 mg per day, equivalent to a 500mg dose in humans) and a low (0.027mg per day, equivalent to moderate red wine consumption in humans) dose. The 20-22 week old SHR (n=9) demonstrated an elevated mean arterial blood pressure compared to the normotensive control, Wistar Kyoto rats (WKY) (n=9) (p<0.001). The SHR also demonstrated decreased endothelium-dependant vasorelaxation and increased endothelium-dependant contraction, indicating impaired endothelium-dependant vasomotor function. Following chronic treatment with resveratrol for 28 days at a high dose maximal relaxation to acetylcholine (ACh) of phenylephrine (PE) pre-contracted CCA vessels was increased when compared to SHR CON (High 100.4 + 5.2%, CON 53.6 + 6%) (p<0.001). This difference is possibly mediated by improved nitric oxide (NO) bioavailability. This study also confirmed that SHR demonstrate increased endothelium-dependant contractions in quiescent, non pre-contracted rings of the CCA (P<0.001). High dose resveratrol treatment reduced SHR endothelium-dependant contraction in the CCA compared to SHR CON (High 55 + 5.4%, CON 68 + 5%) (p<0.05). This effect was likely mediated by an observed reduction in prostacyclin (PGI2) production, when compared to the SHR CON (p<0.05). This result is likely to be cause by inhibition of cycloxygenase 1 (COX 1) since reversal of SHR endothelium-dependant contraction is demonstrated following inhibition of COX 1, an interpretation supported by the observation that resveratrol treatment had no effect on the sensitivity of the thromboxane-prostaglandin receptor, and no effect on the protein expression of COX 1. This study indicates that chronic treatment with resveratrol at a high dose improves CCA endothelium- dependent vasomotor function in SHR via improved NO bioavailability and a reduction in endothelium-dependant PGI2-mediated contraction. These improvements in vasomotor function produced an alteration in vascular tone to a less contracted state. If these observations extend to the resistance vasculature they could contribute to the explanation for resveratrol-dependant reduction in mean arterial blood pressure.

Background: Exercise interventions reduce falls in older adults. Methods for enhancing uptake and adherence to exercise programs in at-risk individuals are needed. Objectives: This pilot study evaluated feasibility of recruitment, short-term retention and adherence to PEPTEAM (Prescribe Exercise for Prevention of Falls and Fractures), an exercise plus behaviour change intervention. Methods: Patients > 65 years old plus ≥ 1 additional risk factor for falls/fractures (≥2 falls in 6 months, age 75+, high CAROC fracture risk, difficulty walking/balance, acute fall, fragility fracture) were identified by nursing staff at the Center for Family Medicine. The intervention was delivered in two visits, with two follow-up calls, and included: a) physician telling the patient they are at risk; b) exercise prescription provided by a physical therapist; c) motivational interviewing, action and coping planning delivered by a kinesiologist. The primary outcome was change in minutes per day of moderate to vigorous physical activity (MVPA) from baseline to six-week follow-up, measured using X2 mini accelerometers. Secondary outcomes included: feasibility of recruitment and retention, an action planning questionnaire, EQ-5D-5L, Short Physical Performance Battery, and the Timed Up and Go. Adherence to exercise was determined using activity logs. Results: 92 patients were screened, 22 were eligible and 11 were recruited (mean [SD] age 72.64 [6.47] years). All participants returned at 6 weeks. Adherence to exercise was 52%. Mean [SD] minutes of MVPA were 24.7 [22.8] at baseline and 21.6 [15.8] at six weeks (p=0.722). Participant action planning and coping planning abilities were significantly improved (P=0.008), (P=0.012) respectively. Patient-rated health at 6 weeks also significantly improved (P=0.010). Conclusion: Many but not all patients demonstrated positive changes in intensity-specific MVPA. The feasibility information collected from this study in addition to practical recommendations identified for future work could be used to inform a future multicenter randomized controlled trial.