Motor vehicles collisions and falls have gradually increase the risk for spinal cord injuries. An increased knowledge of the spinal behavior and its injury mechanisms can be used as preventive strategies. Total Human Model for Safety (THUMS) SAFER is used as a tool for injury prevention, however, there is a lack of studies that evaluate the spinal cord injuries. The aim of this thesis is to implement a cervical spinal cord into the THUMS model. The mesh element quality was modified and the spinal cord was further adjusted for a correct insertion into the THUMS. The strain of the posterior and anterior surface of the cervical spinal cord during a head flexion were analyzed against experiments. Subsequently, a comparison of the head kinematics in frontal collision of the THUMS with and without the cervical spinal cord was performed. A refinement of the mesh element quality for a suitable computational time was achieved. The strain evaluation of the the spinal cord showed the same behavior as in the experiment for the posterior surface but the results were contradictory for the anterior surface. The results of the head kinematics with and without spinal cord showed no good correlation with the experimental data. Moreover, the models exhibited a bigger difference between them during the extension of the head than flexion. A further improvement of the mesh element quality required smaller element size. Nonetheless, it is important to consider that computational time increases with a decrease of element size. Several factors were critical for the strain comparison, such as the lack of information for the calculation of the strain. The difference in head kinematics from the experiment may be due to the material properties of the neck skin and the lack of the active muscles. Moreover, the contact constraints in the model may result in the differences between the THUMS models. In general, the spinal cord has been refined to obtain a favorable computational time. The evaluations have indicated that further modifications in the neck skin and contact constraints are needed for a better resemblance with the human body. Likewise, further validations against experimental studies are suggested.

Idiopathic tracheal stenosis (ITS) is a rare condition, and diagnosis of exclusion should be suspected in patients with exercise intolerance, wheezing, and dyspnea on exertion with a flow-volume loop suggestive of fixed airway obstruction. We report a case of a 32-year-old asthmatic woman with an existing diagnosis of vocal cord dysfunction and previous normal CT scan of the neck. She continued to have fixed upper airway obstruction on repeated flow-volume loops with persistent wheezing and cough along with occasional stridor and hoarseness of voice despite appropriate management of her asthma. She was finally diagnosed with ITS on a repeat CT scan of the neck for which she underwent laser surgery, steroid injection, and controlled radial expansion balloon dilation with a successful reduction of stenosis. This case illustrates the importance of clinical suspicion for early diagnosis of ITS in poorly controlled asthmatic patients and the relevance of non-surgical management of this condition.

Although there are thousands of new spinal cord injury cases each year, length of stay in rehabilitation has significantly decreased, leaving individuals with SCI returning to the community unprepared. Empower SCI is a non-profit organization that aims to fix this gap by providing rehabilitation services to community-dwelling adolescents and adults with SCI. The outcome measures currently used at Empower SCI were assessed to determine if they were a good fit for the program based on their items, scoring system, psychometric properties, and effectiveness at capturing change. In addition, a new assessment measure, the SCI-QOL Resilience SF, was piloted with two participants in a case study format to capture an additional important change, resilience, at Empower SCI. The SCI-QOL Resilience Short Form captured significant change in resilience for one out of two participants. However, both participants shared that Empower SCI provided them with new resources to overcome obstacles to occupational participation and a more positive outlook on life after SCI. Recommendations for the continuation, discontinuation, or altered use of all assessment measures were made based on if they fit the needs of Empower SCI participants and the environment. With an improved data collection system, Empower SCI can demonstrate its positive outcomes to key stakeholders and continue expanding its program to new states and countries. / 2022-10-09T00:00:00Z

The purpose of this dissertation was to explore methods for generating neuroplastic changes in healthy individuals using transcutaneous spinal cord stimulation (TSCS) and perturbation-based training in order to improve balance performance. This was done to gain an understanding of their effects on healthy individuals, which could then be used in designing treatments for both healthy and motor-impaired subjects. Three studies were undertaken. First, we set out to show that the Robotic Upright Stand Trainer (RobUST) could generate improvements in balance after perturbation balance training (PBT). In this same study, we showed that the assist-as-needed support of RobUST generates postural control improvements. Balance performance metrics including (i) margin of stability (MOS), (ii) metrics based on the center of pressure (COP) and center of mass (COM) excursions, (iii) postural muscle activations, (iv) balance strategy selection (between ankle and hip strategies) were used in this study. Electromyographic data were also collected from 11 subjects who participated in this study. Subjects were split into a RobUST assisted group (FF) and a non-assisted group (NF). An analysis of variance (ANOVA) was carried out to identify the main effects of the two factors, i.e., training and grouping. We also studied the interaction effects between the two factors in the performance variables. After training, the threshold of the forces that destabilize balance increased for all participants. In addition, the area within which they could withstand perturbations without falling also increased. Muscle activation decreased in most muscles for subjects in both groups indicating that subjects improved balance while demonstrating more energetically efficient strategies. The post-training behavior of the two groups differed in the following way: the NF group adapted towards faster reactions to perturbations, greater use of the hip strategy, and more use of the erector spinae muscle, while the FF group adapted towards slower responses and less MOS. These results show that although balance adaptations with RobUST-assisted PBT are not the same as without RobUST, it is still a platform capable of improving balance performance. Second, the effect of TSCS as a means of boosting neuroplasticity and a replacement for epidural stimulation were tested. Eight subjects were given TSCS for 30 mins while lying supine, and their neurophysiological and balance performance measures were tested before and after the intervention. T-tests were used to assess the difference in performance, and it was found that TSCS caused hypopolarisation of the sensory neurons, which increased the synaptic efficacy of sensory afferent–motoneuron synapses. This change was evidenced by increased H-reflex recovery and a leftward shift of the H-reflex recruitment curve. No improvement in fall frequency was observed, although balance adjustments were made that reduced muscle activity. This experiment showed that TSCS could be used to modulate the excitability of the spinal cord in healthy subjects. Third, TSCS was combined with a training intervention in order to study how these two sources of plasticity interact. TSCS was applied to eleven subjects while they underwent a training intervention in which they played a game in virtual reality (VR) while their balance was perturbed by forces applied by RobUST. Balance characteristics were measured both with and without TSCS, before and after the intervention. It was found that TSCS initially caused an increase in muscle activity and an increase in fall frequency for perturbations in the forward direction. With more practice, though, muscle activity decreased. It was postulated that the CNS adjusted to the initial elevated levels of muscle activity caused by TSCS by suppressing muscle activity in order to ensure successful motor control. These results suggest that TSCS can be used to elevate the resting potential of neurons in the dorsal (close to the back of the body) root, making them more easily excited by cortical signals. These changes induced by TSCS can be beneficial to spinal cord injury patients.

Cryopreservation is currently the only method allowing for the long-term preservation of hematopoietic stem and progenitor cell (HSPC) grafts until their use. However, cryoinjuries reduce cell viability and potency of HSPC. New cryoprotectant (CPA) solutions have recently emerged that have not yet been investigated that may improve the cryopreservation of HSPCs. The overarching hypothesis of the work described in this thesis, is that different CPAs have diverse impact on the key biochemical processes essential for HSPC homeostasis which influences post thaw cell viability and potency. To test this hypothesis, 4 CPAs were extensively characterized for their cryoprotective properties on cord blood (CB) HSPCs in comparison to DMSO control. CryoProtectPure (CPP) supported similar post thaw cell viability and engraftment as DMSO control, whereas pentaisomaltose (PIM) and cryonovo (CN) failed as CPAs for HSPCs. Subsequently, the impact of CPAs on key biological pathways was explored to identify potential biochemical pathways implicated in HSPC cryopreservation. The impact of CPAs on cell membrane integrity, oxidative phosphorylation, glycolysis, and autophagy was examined. CPP and DMSO had varying impact on glycolytic and mitochondrial respiratory activities of HSPCs post-thaw, whereas both CPAs as well as PIM and CN had negligible impact on cell membrane parameters prefreeze. Cryopreservation and thawing strongly induced autophagy in HSPCs. Importantly, early inhibition of autophagy with 3-Methyladenine (3-MA) reduced the recovery of functional CB HSPCs post thaw. Together, my findings provide new insights regarding the biological processes impacted by CPAs and cryopreservation of HSPCs and identify potential targets to improve cryopreservation of HSC grafts.

Spinal Cord Injury (SCI) is a physically debilitative impairment with a poor prognosis that disrupts the connection between the brain and body. Reduced somatic and autonomic nervous system control over motor and sensory function of muscles and organs causes paralysis and dysregulation of physiological systems. Complications, such as deep vein thromboses, urinary tract infections, and chronic pain, often cause high, life-long economic burdens. Seniors with SCI also have an increased risk of developing cognitive decline. Development of Major Neurocognitive Disorder (Dementia) is characterized by a reduced ability to perform daily activities. In addition to the physical impairments due to SCI, older adults would experience further decreased quality of life. There are various postulations about what contributes to an increased risk of cognitive decline in SCI patients, although the specific mechanism is uncertain. This research project is focused on examining whether blood pressure dysregulation may play a key role in inducing cognitive decline in older adults with SCI. To fulfill this goal, published reviews and clinical and laboratory data from 1997 to 2023 have been analytically reviewed following the presentation of background physiological and pathophysiological information. The outcomes demonstrated that SCI above T6 leads to an increased risk of blood pressure dysregulation and other conditions associated with an increased risk of cognitive decline, including orthostatic hypotension, vascular dementia, and deficient dynamic cerebral autoregulation. Overall, the findings suggest that blood pressure dysregulation that causes cerebral hypoperfusion may be a major contributor to cognitive decline in older adults with SCI.

This work proposes minimally invasive solutions for spinal cord regeneration after trauma. In particular, injectable biomaterials can be precisely positioned in the lesion site, and eventually repetitively injected until the complete regeneration of the tissue. For this application, a silk fibroin functionalized with collagen type IV and laminin-derived peptides, called bio-inspired multifunctionalized silk fibroin (BMS), possessing piezoelectric properties, has been synthesized. Another approach that avoids damages to the spinal cord is proposed in the thesis as a multilayer hydrogel with piezoelectric properties that acts as a bridge between the healthy parts surrounding the injury. The multilayer hydrogel consists of i) a thin-layer of gelatin and fish collagen functionalized with VEGF for blood vessels formation, which helps the survival of the cells integrating with the pia mater of the spinal cord; ii) a BMS layer, which helps the adhesion, migration of neural stem cells and induces the sprouting of the axons thanks to the presence of Netrin (a chemoattractive protein); and iii) an adhesive layer of polydopamine (PDA) to fix the patch on the injured site. The adhesive patch exhibits a potential larger than an injectable hydrogel that could guarantee a long-term cell survival and help the axons to move towards a direction. The adhesive patch will be located on the surface of the spinal cord and the chemoattractive protein will induce the sprouting of the ascendant or descendant axons in the spinal cord to reach the axons present in the patch, restoring a signal connection. Even if not final, the results indicate that the above strategy could be explored further for the regeneration of the spinal cord.

Perceived exertion is how hard or heavy an individual feels they are working. Perceived exertion is often quantified using the ratings of perceived exertion (RPE) scale and can be used to measure exercise intensity based on the experience of an individual. While objective methods of assessing exercise intensity, such as measurement of heart rate and percent of peak oxygen uptake, are useful, RPE is commonly implemented for the ease of use and feasibility. For example, RPE is commonly implemented in rehabilitation settings for people with a spinal cord injury and individuals with coronary artery disease because of their non-linear heart rate response to increases in exercise workload. The overarching purpose of this dissertation was to investigate a range of research questions designed to advance the knowledge and use of RPE guided exercise. Through a systematic review and meta-analysis, we examined evidence for the impact on cardiorespiratory fitness and peak power output using RPE-guided interventions in individuals with a spinal cord injury (SCI) and found that RPE-guided interventions improved both after a variety of exercise intervention types and lengths. In a separate retrospective cross-sectional analysis, we then demonstrated that perceived exertion, measured by leg cycling effort during a cardiopulmonary exercise test on a leg cycle ergometer in non-disabled individuals, was predicted by power and maximum power output. After further investigation we found that quadriceps strength predicted maximum power output and therefore is related to leg cycling effort. In the third study of the thesis, we conducted semi-structured interviews in individuals with an SCI and their healthcare practitioners and found that individuals commonly described their sensations associated with the 0-10 RPE scale using muscle sensations when both recalling exercise and after the completion of an acute exercise trial on an arm cycle ergometer. Lastly, we investigated the relationship between psychological and physiological measures and RPE during an arm cycling exercise during a maximal graded exercise test, high intensity interval training, and moderate intensity continuous training using a crossover experimental design in both non-disabled individuals and individuals who were mobility impaired due to SCI. While there were no relationships between any variable and RPE in non-disabled individuals, age and triceps strength predicted central RPE and peak feeling scale predicted peripheral RPE in individuals with an SCI. These mixed methods results collectively suggest that muscle strength, not heart rate, is the strongest predictor of perceived exertion especially in clinical populations completing high intensity exercise. Our novel findings suggest that RPE is regulated through a system of psychological and physiological phenomena, strongly related to muscle sensations arising from the working muscle groups and may have utility and relevance in complementing measures of exercise intensity for a broad range of individuals across the spectrum of health and disease. Future studies should examine the use of muscle sensation descriptions as descriptors of exercise intensity prior to the development of high intensity exercise guidelines in clinical populations, such as individuals with SCI. / Thesis / Candidate in Philosophy / It has been well established that heart rate and ratings of perceived exertion are related in young, healthy individuals, however the nuances of the relationships between other contributors and how clinical populations feel during exercise remain unclear. Using mixed methods, this research sought to determine what sensations help people determine how they feel during exercise, with a focus on high intensity interval training exercise. Our results show that muscle strength may be a key determinant in the perception of effort in individuals with a spinal cord injury and in clinical populations during arm and leg maximal graded exercise tests, but the relationships between physiological variables and perceptions of arm effort in non-impaired individuals remains to be determined. Sensations of effort are regulated through a variety of different mechanisms that vary with population, and the relationships depend on the parameters (e.g., exercise modality and intensity) of the exercise. Future studies should be conducted to determine the individual contributions of different body systems to perceived exertion during exercise in a wide range of populations.

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