Functional evaluation of skeletal muscle regeneration following severe crush trauma and the therapeutic application of specialized tissue engineering in the rat

Introduction: Skeletal muscle trauma is a common condition which may result in long term pain and disability. Despite the pool of muscle-specific stem cells termed satellite cells, which are stimulated to proliferate, grow and differentiate to repair muscle fibers upon injury, return to pre-injury function is often impossible. We hypothesized that the transplantation of Mesenchymal Stromal Cells (MSCs) in a synthetic niche supplemented by stimulatory growth factors may support the regenerative process through paracrine modulation of the post-traumatic microcellular environment Methods: A crushed-muscle injury model was implemented in rats. Upon completion, rats received either intramuscular Injections of the growth factors (GF) Insulin Growth Factor-1 and Vascular Endothelial Growth Factor and/or autologous MSCs which had previously been harvested in a bone marrow aspiration, or a specially engineered porous Alginate enriched with the before mentioned growth factors and/or seeded with MSCs. Animals were sacrificed at 7-, 28- and 56 days following trauma and their fast twitch- and tetanic contraction forces were measured via an electromechanical stimulatory device. Results: All experimental groups showed significant decreases in contraction strength at day 7 following injury, with little difference amongst groups. On the contrary, fast twitch and tetanic contraction forces differed significantly between the Alginate-alone control group and the groups transplanted with with Alginates seeded with MSCs and Alginates enriched with GFs and seeded with MSCs at day 28. The highest relative force was found in the latter group, which differed significantly from the others (p (Alginate) <0.001; p (Alginate + GFs) = 0.003). No significant increases in muscle force could be observed in between the groups evaluated at 28 days following trauma and the groups evaluated at 56 days following trauma. Conclusion: We could confirm that the transplantation of a porous Alginate enriched with growth factors and seeded with autologous Mesenchymal Stromal Cells resulted in significantly improved functional outcomes. Tissue engineering, which relies on the transplantation of cells and growth factors conducive of regeneration seeded on scaffolds which support their survival and release into the microcellular environment, may be a solution in particular to nosocomial damage created by incisions necessary during a surgical procedure.Einleitung: Schwere Skelettmuskeltraumata sind ein häufiges klinisches Problem was zu langfristigen Schmerzen und eingeschränkter Mobilität führen kann. Trotz des Pools an muskelspezifischen Stammzellen, die als Satellitenzellen bezeichnet werden, die zur Proliferation, zum Wachstum und zur Differenzierung stimuliert werden, um Muskelfasern nach einer Verletzung zu reparieren, ist die Rückkehr zur Vorverletzungsfunktion oft unmöglich. Wir stellten die Hypothese auf, dass die Transplantation von mesenchymalen Stromalzellen in einem flexiblen Konstrukt, ergänzt durch stimulierende Wachstumsfaktoren, den regenerativen Prozess durch parakrine Modulation der posttraumatischen Mikrozellularumgebung unterstützen kann. Methodik: Es wurde Ratten ein Quetschtrauma des Skelettmuskels zugefügt. Posttraumatisch erhielten die Ratten entweder intramuskuläre Injektionen der Wachstumsfaktoren Insulin- Wachstumsfaktor-1 und des vaskulär-endothelialem Wachstumsfaktors und / oder autologe mesenchymale Stromalzellen, die zuvor in einer Knochenmarkaspiration gewonnen worden waren, oder ein speziell konstruiertes poröses Alginat, angereichert mit den eben genannten Wachstumsfaktoren und / oder mit mesenchymalen Stromalzellen. Die fast twitch sowie die tetanische Kontraktionskraft der Tiere wurden an den Tagen 7, 28 und 56 nach dem Trauma mittels einer elektromechanischen Stimulationsvorrichtung gemessen. Ergebnisse: Alle Versuchsgruppen zeigten am Tag 7 nach der Verletzung eine signifikante Abnahme der Kontraktionskraft, mit geringen Unterschieden zwischen den einzelnen Gruppen. Im Gegensatz dazu unterschieden sich die Kontraktionskräfte zwischen der Kontrollgruppe, der leere Alginate transplantiert wurden, und der mit Wachstumsfaktoren und/oder Stromalzellen bereichterten Alginaten transplantierten Gruppen am Tag 28 nach der Verletzung signifikant. Die höchste Kraft wurde in der Versuchsgruppe gefunden, in der Alginate mit Wachtumsfaktoren und mesenchymalen Stammzellen transplantiert wurden, gefunden. Sie hob sich signifikant von den anderen ab (p (Alginat) <0,001; p (Alginat + GF) = 0,003). Zwischen den Versuchsgruppen, die 28 Tage nach dem Trauma ausgewertet wurden, und den Gruppen, die 56 Tage nach dem Trauma ausgewertet wurden, konnte keine signifikante Zunahme der Muskelkraft beobachtet werden. Schlussfolgerung: Wir konnten bestätigen, dass die Transplantation eines mit Wachstumsfaktoren angereicherten und mit autologen mesenchymalen Stammzellen besetzten porösen Alginats zu signifikant verbesserten funktionellen Ergebnissen führt. Spezialisiertes Tissue Engineering, das auf der Transplantation von Zellen und wachstumsfördernden Faktoren beruht die mittels eines flexiblen Biomaterials transplantiert werden können, dürfte eventuell eine Lösung für nosokomiale Muskelschäden sein, die während eines chirurgischen Eingriffs entstehen können

Cognition and Motor Function: A Novel Outcome Measure for Studies on Pre-Dementia Syndromes

Advances in dementia research have shifted attention towards earlier stages in the natural history, such as Mild Cognitive Impairment. The current gold standard outcome measure, the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, is not optimally responsive to changes in pre-dementia populations. Modifications to scoring methodology and content have improved the measurement performance of the ADAS-Cog. However, no published modifications have addressed a second key shift in the field towards understanding motor function as an important component of dementia and pre-dementia syndromes. This thesis used a Pooled Index approach to combine an ADAS-Cog-Proxy measure with assessments of gait velocity and dual-task cost. The responsiveness of the PI to baseline discrimination between older adults with normal cognition, Subjective Cognitive Impairment, and MCI was similar to the ADAS-Cog-Proxy. The PI demonstrated greater responsiveness than the ADAS-Cog-Proxy to change over 6mo. and 48mo., but not 36mo. of follow-up. Overall, motor function assessments improve ADAS-Cog responsiveness

Developing artificial intelligence and machine learning to support primary care research and practice

This thesis was motivated by the potential to use everyday data , especially that collected in electronic health records (EHRs) as part of healthcare delivery, to improve primary care for clients facing complex clinical and/or social situations. Artificial intelligence (AI) techniques can identify patterns or make predictions with these data, producing information to learn about and inform care delivery. Our first objective was to understand and critique the body of literature on AI and primary care. This was achieved through a scoping review wherein we found the field was at an early stage of maturity, primarily focused on clinical decision support for chronic conditions in high-income countries, with low levels of primary care involvement and model evaluation in real-world settings. Our second objective was to demonstrate how AI methods can be applied to problems in descriptive epidemiology. To achieve this, we collaborated with the Alliance for Healthier Communities, which provides team-based primary health care through Community Health Centres (CHCs) across Ontario to clients who experience barriers to regular care. We described sociodemographic, clinical, and healthcare use characteristics of their adult primary care population using EHR data from 2009-2019. We used both simple statistical and unsupervised learning techniques, applied with an epidemiological lens. In addition to substantive findings, we identified potential avenues for future learning initiatives, including the development of decision support tools, and methodological considerations therein. Our third objective was to advance interpretable AI methodology that is well-suited for heterogeneous data, and is applicable in clinical epidemiology as well as other settings. To achieve this, we developed a new hybrid feature- and similarity-based model for supervised learning. There are two versions, fit by convex optimization with a sparsity-inducing penalty on the kernel (similarity) portion of the model. We compared our hybrid models with solely feature- and similarity-based approaches using synthetic data and using CHC data to predict future loneliness or social isolation. We also proposed a new strategy for kernel construction with indicator-coded data. Altogether, this thesis progressed AI for primary care in general and for a particular health care organization, while making research contributions to epidemiology and to computer science

Comparison of measurements of canine plasma glucose, creatinine, urea, total proteins, alanine aminotransferase, and alkaline phosphatase obtained with the APOLOWAKO and Vitros 250 analyzers

The APOLOWAKO is an entirely automatic benchtop biochemistry analyzer that uses stabilized liquid reagents. It was tested for canine blood and plasma glucose, creatinine, urea, total proteins, alanine aminotransferase, and alkaline phosphatase. The APOLOWAKO gave very similar results for whole blood and the corresponding plasma (n = 32). Within-laboratory imprecision was below 2.2% and 5.8% for substrates and enzymes, respectively. Comparison of results with whole blood by APOLOWAKO and with the corresponding plasma by Vitros 250 (n = 139) showed very good correlations. Passing–Bablok’s regression slopes ranged from 0.83 to 1.12 and intercepts were close to zero, except for ALP where the results obtained by APOLOWAKO were approximately 1.5 times higher than by Vitros. The APOLOWAKO system can be a reliable instrument in veterinary practices where larger systems are not available but it should be further validated and reference intervals should be determined

Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

Malnutrition and starvation’s possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality

Influence of hydraulic property correlation on predicted dense nonaqueous phase liquid source zone architecture, mass recovery and contaminant flux

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94685/1/wrcr9972.pd

A mobile app to identify lifestyle indicators related to undergraduate mental health (smart healthy campus): Observational app-based ecological momentary assessment

Background: Undergraduate studies are challenging, and mental health issues can frequently occur in undergraduate students,straining campus resources that are already in demand for somatic problems. Cost-effective measures with ubiquitous devices,such as smartphones, offer the potential to deliver targeted interventions to monitor and affect lifestyle, which may result inimprovements to student mental health. However, the avenues by which this can be done are not particularly well understood,especially in the Canadian context.Objective: The aim of this study is to deploy an initial version of the Smart Healthy Campus app at Western University, Canada,and to analyze corresponding data for associations between psychosocial factors (measured by a questionnaire) and behaviorsassociated with lifestyle (measured by smartphone sensors).Methods: This preliminary study was conducted as an observational app-based ecological momentary assessment. Undergraduatestudents were recruited over email, and sampling using a custom 7-item questionnaire occurred on a weekly basis.Results: First, the 7-item Smart Healthy Campus questionnaire, derived from fully validated questionnaires-such as the BriefResilience Scale; General Anxiety Disorder-7; and Depression, Anxiety, and Stress Scale-21-was shown to significantly correlatewith the mental health domains of these validated questionnaires, illustrating that it is a viable tool for a momentary assessmentof an overview of undergraduate mental health. Second, data collected through the app were analyzed. There were 312 weeklyresponses and 813 sensor samples from 139 participants from March 2019 to March 2020; data collection concluded whenCOVID-19 was declared a pandemic. Demographic information was not collected in this preliminary study because of technicallimitations. Approximately 69.8% (97/139) of participants only completed one survey, possibly because of the absence of anyincentive. Given the limited amount of data, analysis was not conducted with respect to time, so all data were analyzed as a singlecollection. On the basis of mean rank, students showing more positive mental health through higher questionnaire scores tendedto spend more time completing questionnaires, showed more signs of physical activity based on pedometers, and had their devicesrunning less and plugged in charging less when sampled. In addition, based on mean rank, students on campus tended to reportmore positive mental health through higher questionnaire scores compared with those who were sampled off campus. Some datafrom students found in or near residences were also briefly examined.Conclusions: Given these limited data, participants tended to report a more positive overview of mental health when on campusand when showing signs of higher levels of physical activity. These early findings suggest that device sensors related to physical activity and location are useful for monitoring undergraduate students and designing interventions. However, much more sensordata are needed going forward, especially given the sweeping changes in undergraduate studies due to COVID-19

Organic matter in termite mounds of an Amazonian rain forest.

This study investigates how termites alter the organic matter in rain forests near Manaus, Brazil. Samples were collected from the outer and inner parts of typical termite nests of Nasutitermes, Termes, Embiratermes, Cornitermes, Anoplotermes, and Constrictotermes genera, as well as from the surrounding topsoil (0cm-10cm) and potential wooden food. The termite nests were signficant sinks for organic matter and its associated nutrients. The organic C contents ranged between 100g kg-1 and 500g kg-1 in the nests, compared to 17g kg-1 to 42g kg-1 in the surrounding topsoils. As lignin contents of the mounds were higher than in wood, lignin may be accumulated in preference to other organic compounds. This findings also sugests that the interior part of the nests is a region of higher organic matter turnover and lignin degradation

Comparison of two‐dimensional and three‐dimensional simulations of dense nonaqueous phase liquids (DNAPLs): Migration and entrapment in a nonuniform permeability field

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95015/1/wrcr10030.pd

Sealant materials for solid oxide fuels and other high-temperature ceramics

Glass-ceramic sealing materials have been developed with mechanical and chemical properties suitable for a variety of high-temperature applications. We have demonstrated the ability to tailor the thermal expansion coefficient between 8 and 12 x 10{sup -6}/{degrees}C, and the softening temperature can be adjusted such that the materials have suitable viscosities for a soft, compliant seal at temperatures ranging from 650 to 1000{degrees}C. These materials form excellent bonds to a variety of ceramics and metals during heating to the target operation temperature. They have limited reactivity with the fuel cell materials tested and are stable in both air and reducing environments