Biomedical Physiology and Kinesiology, Department of

Receive updates for this collection

Mobility-Related Gaze Training in Individuals With Glaucoma: A Proof-of-Concept Study

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-10-09
Abstract: 

Purpose: Older adults with glaucoma show inappropriate gaze strategies during routine mobility tasks. Furthermore, glaucoma is a risk factor for falling and colliding with objects when walking. However, effective interventions to rectify these strategies and prevent these adverse events are scarce. We designed a gaze training program with the goal of providing proof-of-concept that we could modify mobility-related gaze behavior in this population.

Methods: A total of 13 individuals with moderate glaucoma participated in this study. We taught participants general and task-specific gaze strategies over two 1-hour sessions. To determine the efficacy of this gaze training program, participants performed walking tasks that required accurate foot placement onto targets and circumventing obstacles before and after training. We used a mobile eye tracker to quantify gaze and a motion-capture system to quantify body movement.

Results: After training, we found changes in the timing between gaze shifts away from targets relative to stepping on them (P < 0.05). In the obstacle negotiation task, we found a greater range of gaze shifts early in walking trials and changes in the timing between gaze shifts away from obstacles after training (P < 0.05), each suggesting better route planning. A posttraining reduction in foot-placement error and obstacle collisions accompanied these changes (P < 0.05).

Conclusions: Our results demonstrated that it is possible to modify mobility-related gaze behavior and mobility performance in older adults with glaucoma.

Translational Relevance: This study provides proof-of-concept for a gaze training program for glaucoma. A larger, randomized controlled trial is warranted.

Document type: 
Article
File(s): 

Dynamic Wheelchair Seating Positions Impact Cardiovascular Function after Spinal Cord Injury

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2107-06-30
Abstract: 

Background

Innovative wheelchairs allow individuals to change position easily for comfort and social situations. While these wheelchairs are beneficial in multiple ways, the effects of position changes on blood pressure might exacerbate hypotension and cerebral hypoperfusion, particularly in those with spinal cord injury (SCI) who can have injury to autonomic nerves that regulate cardiovascular control. Conversely, cardiovascular benefits may be obtained with lowered seating. Here we investigate the effect of moderate changes in wheelchair position on orthostatic cardiovascular and cerebrovascular reflex control.

Methods

Nineteen individuals with SCI and ten neurologically-intact controls were tested in supine and seated positions (neutral, lowered, and elevated) in the Elevation™ wheelchair. Participants with SCI were stratified into two groups by the severity of injury to cardiovascular autonomic pathways. Beat-to-beat blood pressure, heart rate and middle cerebral artery blood flow velocity (MCAv) were recorded non-invasively.

Results

Supine blood pressure and MCAv were reduced in individuals with lesions to autonomic pathways, and declined further with standard seating compared to those with preserved autonomic control. Movement to the elevated position triggered pronounced blood pressure and MCAv falls in those with autonomic lesions, with minimum values significantly reduced compared to the seated and lowered positions. The cumulative duration spent below supine blood pressure was greatest in this group. Lowered seating bolstered blood pressure in those with lesions to autonomic pathways.

Conclusions

Integrity of the autonomic nervous system is an important variable that affects cardiovascular responses to orthostatic stress and should be considered when individuals with SCI or autonomic dysfunction are selecting wheelchairs.

Document type: 
Article
File(s): 

Pubertal Hormonal Changes and the Autonomic Nervous System: Potential Role in Pediatric Orthostatic Intolerance

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-11-12
Abstract: 

Puberty is initiated by hormonal changes in the adolescent body that trigger physical and behavioral changes to reach adult maturation. As these changes occur, some adolescents experience concerning pubertal symptoms that are associated with dysfunction of the autonomic nervous system (ANS). Vasovagal syncope (VVS) and Postural Orthostatic Tachycardia Syndrome (POTS) are common disorders of the ANS associated with puberty that are related to orthostatic intolerance and share similar symptoms. Compared to young males, young females have decreased orthostatic tolerance and a higher incidence of VVS and POTS. As puberty is linked to changes in specific sex and non-sex hormones, and hormonal therapy sometimes improves orthostatic symptoms in female VVS patients, it is possible that pubertal hormones play a role in the increased susceptibility of young females to autonomic dysfunction. The purpose of this paper is to review the key hormonal changes associated with female puberty, their effects on the ANS, and their potential role in predisposing some adolescent females to cardiovascular autonomic dysfunctions such as VVS and POTS. Increases in pubertal hormones such as estrogen, thyroid hormones, growth hormone, insulin, and insulin-like growth factor-1 promote vasodilatation and decrease blood volume. This may be exacerbated by higher levels of progesterone, which suppresses catecholamine secretion and sympathetic outflow. Abnormal heart rate increases in POTS patients may be exacerbated by pubertal increases in leptin, insulin, and thyroid hormones acting to increase sympathetic nervous system activity and/or catecholamine levels. Given the coincidental timing of female pubertal hormone surges and adolescent onset of VVS and POTS in young women, coupled with the known roles of these hormones in modulating cardiovascular homeostasis, it is likely that female pubertal hormones play a role in predisposing females to VVS and POTS during puberty. Further research is necessary to confirm the effects of female pubertal hormones on autonomic function, and their role in pubertal autonomic disorders such as VVS and POTS, in order to inform the treatment and management of these debilitating disorders.

Document type: 
Article
File(s): 

Investigating the Utility of Adult Zebrafish Ex Vivo Whole Hearts to Pharmacologically Screen hERG Channel Activator Compounds

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-10-30
Abstract: 

There is significant interest in the potential utility of small molecule activator compounds to mitigate cardiac arrhythmia caused by loss-of-function of hERG1a voltage-gated potassium channels. Zebrafish (Danio rerio) have been proposed as a cost effective, high throughput drug-screening model to identify compounds that cause hERG1a dysfunction. However, there are no reports on the effects of hERG1a activator compounds in zebrafish, and consequently on the utility of the model to screen for potential gain-of-function therapeutics. Here, we examined the effects of hERG1a blocker, and type 1 and type 2 activator, compounds on isolated zkcnh6a (zERG3) channels in the Xenopus laevis oocyte heterologous expression system, as well as action potentials recorded from ex vivo adult zebrafish whole hearts using optical mapping. Our functional data from isolated zkcnh6a channels show that these channels respond to hERG1a channel blockers (dofetilide and terfenadine), and type 1 (RPR260243) and type 2 (NS1643, PD-118057) hERG1a activator compounds, in a similar manner to hKCNH2a channels, with minor differences largely accounted for by subtly different biophysical properties in the two channels. In ex vivo zebrafish whole hearts, two of the three hERG1a activators examined caused abbreviation of the APD, while hERG1a blockers caused APD prolongation. These data represent, to our knowledge, the first pharmacological characterization of isolated zkcnh6a channels and the first assessment of hERG enhancing therapeutics in zebrafish. Our findings suggest that the zebrafish ex vivo whole heart model serves as a valuable tool in the screening of hKCNH2a blocker and activator compounds.

Document type: 
Article

The Super-Seniors Study: Phenotypic Characterization of a Healthy 85+ Population

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2018-05-24
Abstract: 

Background

To understand why some people live to advanced age in good health and others do not, it is important to study not only disease, but also long-term good health. The Super-Seniors Study aims to identify factors associated with healthy aging.

Methods

480 healthy oldest-old ‘Super-Seniors’ aged 85 to 105 years and never diagnosed with cancer, cardiovascular disease, diabetes, dementia, or major pulmonary disease, were compared to 545 mid-life controls aged 41–54, who represent a group that is unselected for survival from late-life diseases. Health and lifestyle information, personal and family medical history, and blood samples were collected from all participants. Super-Seniors also underwent four geriatric tests.

Results

Super-Seniors showed high cognitive (Mini-Mental State Exam mean = 28.3) and functional capacity (Instrumental Activities of Daily Living Scale mean = 21.4), as well as high physical function (Timed Up and Go mean = 12.3 seconds) and low levels of depression (Geriatric Depression Scale mean = 1.5). Super-Seniors were less likely to be current smokers than controls, but the frequency of drinking alcohol was the same in both groups. Super-Seniors were more likely to have 4 or more offspring; controls were more likely to have no children. Female Super-Seniors had a mean age of last fertility 1.9 years older than controls, and were 2.3 times more likely to have had a child at ≥ 40 years. The parents of Super-Seniors had mean ages of deaths of 79.3 years for mothers, and 74.5 years for fathers, each exceeding the life expectancy for their era by a decade.

Conclusions

Super-Seniors are cognitively and physically high functioning individuals who have evaded major age-related chronic diseases into old age, representing the approximately top 1% for healthspan. The familiality of long lifespan of the parents of Super-Seniors supports the hypothesis that heritable factors contribute to this desirable phenotype.

Document type: 
Article
File(s): 

A Modelling Approach for Exploring Muscle Dynamics during Cyclic Contractions

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2018-04-16
Abstract: 

Hill-type muscle models are widely used within the field of biomechanics to predict and understand muscle behaviour, and are often essential where muscle forces cannot be directly measured. However, these models have limited accuracy, particularly during cyclic contractions at the submaximal levels of activation that typically occur during locomotion. To address this issue, recent studies have incorporated effects into Hill-type models that are oftentimes neglected, such as size-dependent, history-dependent, and activation-dependent effects. However, the contribution of these effects on muscle performance has yet to be evaluated under common contractile conditions that reflect the range of activations, strains, and strain rates that occur in vivo. The purpose of this study was to develop a modelling framework to evaluate modifications to Hill-type muscle models when they contract in cyclic loops that are typical of locomotor muscle function. Here we present a modelling framework composed of a damped harmonic oscillator in series with a Hill-type muscle actuator that consists of a contractile element and parallel elastic element. The intrinsic force-length and force-velocity properties are described using Bézier curves where we present a system to relate physiological parameters to the control points for these curves. The muscle-oscillator system can be geometrically scaled while preserving dynamic and kinematic similarity to investigate the muscle size effects while controlling for the dynamics of the harmonic oscillator. The model is driven by time-varying muscle activations that cause the muscle to cyclically contract and drive the dynamics of the harmonic oscillator. Thus, this framework provides a platform to test current and future Hill-type model formulations and explore factors affecting muscle performance in muscles of different sizes under a range of cyclic contractile conditions.

Document type: 
Article
File(s): 

Effect of Aging on Muscle-Pump Baroreflex of Individual Leg Muscles During Standing

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2109-07-16
Abstract: 

Activation of leg muscles is an important component in the regulation of blood pressure during standing, failure of which could result in syncope and falls. Our previous work demonstrated baroreflex mediated activation of leg muscles (muscle-pump baroreflex) as an important factor in the regulation of blood pressure during standing; however, the effect of aging on the muscle-pump baroreflex of individual leg muscles during standing remains to be understood. Here, the interaction between systolic blood pressure (SBP) and the activation of lateral gastrocnemius (LG), medial gastrocnemius (MG), tibialis anterior (TA), and soleus (SOL) muscles during standing was quantified. Beat-to-beat heart period (RR interval), SBP, electromyography impulse (EMGimp) were derived from continuously acquired electrocardiography, finger blood pressure, and calf-electromyography, respectively. The cardiac baroreflex (SBP→RR) causality (0.88 ± 0.08 vs. 0.94 ± 0.03, p = 0.01), percent time with significant coherence (%SC: 50.95 ± 23.31 vs. 76.75 ± 16.91, p = 0.001), and gain (4.39 ± 4.38 vs. 13.05 ± 8.11, p < 0.001) was lower in older (69 ± 4 years) compared to young (26 ± 2 years) persons. Muscle-pump baroreflex (SBP→EMGimp) causality of LG (0.81 ± 0.08 vs. 0.88 ± 0.05, p = 0.01) and SOL (0.79 ± 0.11 vs. 0.88 ± 0.04, p = 0.01) muscles was lower in older compared to young persons. %SC was lower for all muscles in the older group (LG, p < 0.001; MG, p = 0.01; TA, p = 0.01; and SOL, p < 0.001) compared to young. The study outcomes highlighted impairment in muscle-pump baroreflex with age in addition to cardiac baroreflex. The findings of the study can assist in the development of an effective system for monitoring orthostatic tolerance via cardiac and muscle-pump baroreflexes to mitigate syncope and falls.

Document type: 
Article
File(s): 

Adiposity Measures and Their Validity in Estimating Risk of Hypertension in South Asian Children: A Cross-Sectional Study

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-02-20
Abstract: 

Objective Given the South Asian phenotype of higher body fat at similar body mass index (BMI) relative to Caucasians, we sought to explore the association between prominent adiposity indicators with blood pressure (BP) and hypertension, to compare the accuracy of these indicators in estimating hypertension, and to provide cut-off values associated with adverse hypertension risk in South Asian children.

Design Cross-sectional study.

Setting Community-based recruitment in two Canadian cities (Hamilton and Surrey).

Participants South Asian children (n=762) were recruited from two Canadian cities. Waist circumference, waist to height ratio and BMI were determined. Body fat percentage was assessed by bioelectrical impedance analysis and BP was assessed using an automated device. All variables (except body fat percentage) were transformed to z-scores using published standards.

Outcome measures Linear and Poisson regression was used to explore associations between the adiposity indicators with BP z-score and hypertension. Receiver operating curve (ROC) analysis was used to explore the strength of the adiposity indicators in estimating hypertension risk and sex-stratified optimal adiposity cut-off values associated with hypertension risk.

Results Significant associations were detected in adjusted and unadjusted models between the adiposity indicators with BP z-score and hypertension (p<0.01 for all). The area under the curve (AUC) values for the adiposity indicators for boys and girls ranged from 0.74 to 0.80, suggesting that the adiposity indicators are fair measures of estimating hypertension risk. Sex-stratified cut-off associated with adverse risk of hypertension for girls and boys, respectively, were at the 92nd and 82nd percentile for BMI z-scores, 65th and 80th percentile for WC z-score, 63rd and 67th percentile for WHtR z-score and at 29.8% and 23.5% for body fat.

Conclusion Our results show associations between adiposity indicators with BP and hypertension and suggests that South Asian children might be at adverse risk of hypertension at levels of adiposity considered normal.

Document type: 
Article
File(s): 

Direct Brain Excision: An Easier Method to Harvest the Pig's Brain

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2018-05-29
Document type: 
Article
File(s): 

10-Year Follow-Up of the Super-Seniors Study: Compression of Morbidity and Genetic Factors

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-02-28
Abstract: 

Background: Super-Seniors are healthy, long-lived individuals who were recruited at age 85 years or older with no history of cancer, cardiovascular disease, diabetes, dementia, or major pulmonary disease. In a 10-year follow-up, we aimed to determine whether surviving Super-Seniors showed compression of morbidity, and to test whether the allele frequencies of longevity-associated variants in APOE and FOXO3 were more extreme in such long-term survivors.

Methods: Super-Seniors who survived and were contactable were re-interviewed 10 years after initial characterization. Health and lifestyle were characterized via questionnaire. Geriatric tests including the Timed Up and Go (TUG), Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL) and the Mini-Mental State Exam (MMSE) were administered, and data were compared to results from on average 10 years earlier. As well, genotype and allele frequencies for SNPs rs7412 and rs429358 in APOE, and rs2802292 in FOXO3 were compared to the frequencies in the original collection of Super-Seniors and mid-life controls.

Results: Of the 480 Super-Seniors recruited from 2004 to 2007, 13 were alive, contactable, and consented to re-interview (mean age = 100.1 ± 3.3). Eight of these 13 participants (62%) still met Super-Senior health criteria. Diseases that occurred in late life were cardiovascular (5 of 13; 38%) and lung disease (1 of 13; 8%). MMSE and IADL scores declined in the decade between interviews, and GDS and TUG scores increased. The surviving group of centenarians had a higher frequency of APOE and FOXO3 longevity-associated variants even when compared to the original long-lived Super-Senior cohort.

Conclusions: Although physical and mental decline occurred in the decade between interviews, the majority of Super-Seniors re-interviewed still met the original health criteria. These observations are consistent with reports of compression of morbidity at extreme ages, particularly in centenarians. The increased frequency of longevity- associated variants in this small group of survivors is consistent with studies that reported genetics as a larger contributor to longevity in older age groups.

Document type: 
Article
File(s):