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The goal of this project is to advance the understanding of tendon disease and injury through the design and validation of a new model of tendon injury. Controlled, mechanically-induced traction injury was created in rat Achilles’ tendons with a tensioning apparatus through a minimally invasive surgical approach. Tendons were tensioned to subailure loads. Assessments of damage to tendons included gross morphology, evaluation of biomechanical of load strain curves, histopathology under light microscopy (H&E), collagen fibril structure and disruption under scanning electron microscopy, and immunohistochemical study of MMP-13 expression under confocal laser microscopy. Tendon injuries were found to be more severe with respect to loads placed upon them. Differences between treatment groups were identified subjectively in microscopic appearance (H&E), in collagen fibril organization (SEM), and in MMP-13 expression. However, analysis of the numerical data did not provide definitive evidence that this model for acute tendon injury is consistent and repeatable.

Introduction: Anterior cruciate ligament (ACL) injuries are the most common ligamentous injury in the adolescent knee, resulting in long-term health consequences including early onset knee osteoarthritis and a high predominance of re-injury. The current ACL rehabilitation measures need improvement, in particular for adolescents. Information surrounding energy absorption strategies during demanding tasks may provide important insight into functional capacity and movement quality and could be a variable that is considered in ACL rehabilitation programs. The purpose of this thesis was therefore to evaluate energy absorption strategies in adolescent males and females with and without ACL injuries. Specifically, to first identify sex and injury status differences in lower extremity kinematics and kinetics in adolescent males and females with and without an ACL injury, and then secondly, determine if there is a generalizable relationship between strength and energy absorption strategies within these populations during drop-vertical jumps. Methods: Fifty-two ACL injured (17 males) and 68 control adolescent (34 males) males and females between the ages of 10 and 18 performed five trials of a lunge and drop vertical jump (DVJ) task. Ankle plantarflexion, and knee extension and flexion maximum voluntary isometric contractions (MVIC) were collected, along with 3D kinematics and kinetics including joint angles, joint moments, and energy absorption at the hip, knee, and ankle joint. Two-way analyses of variance (ANOVA), statistical non-parametric mapping (SnPM), and multiple linear regressions were used to determine statistically significant differences and relationships in joint kinematics, kinetics, and MVIC's between the male and female ACL injured and control individuals. Results: Males displayed greater knee extension torque compared to females, while controls displayed greater knee extension and ankle plantarflexion torque compared to ACL injured. There were no energy absorption differences found during the DVJ, however, during the lunge male controls display greater energy absorption compared to females. Furthermore, small effect sizes were found in the hip, knee, and ankle joint energy absorption for knee strength (knee extension or knee flexion), sex, and injury status. However, sex, injury status, and knee strength did not significantly add to the prediction of energy absorption. Conclusion: These findings indicate that isometric strength might be an important variable to be considered in ACL injury rehabilitation and injury prevention programs with injured individuals displaying weaker knee extension and ankle plantarflexion torques. However, energy absorption may not be as important of a variable to consider as there were limited statistically significant differences between injury status and sex at the hip, knee, and ankle joints. Additionally, there does not appear to be a generalizable relationship between hip, knee, and ankle energy absorption and knee flexion and extension isometric strength in male and female control and ACL injured individuals. Injured individuals absorb similar energy levels at each joint compared to controls, with isometric strength showing a weak relationship with energy absorption. Therefore, it is possible that there is not a specific energy absorption or muscular strength strategy that can be used to improve adolescent ACL rehabilitation measures.

No description available.

Off-target deposition of herbicides to non-target plant species has been extensively studied and well documented over time. Off-target movement can often be detrimental to plant growth and yield. The geography of Mississippi is favorable for off-target herbicide deposition due to many crops existing in close proximity to differing crops such as soybeans (Glycine max L.) and rice (Oryza sativa L.). Therefore, research was conducted in each of three locations in Mississippi in 2016 and 2017 to determine if enhanced ALS-tolerant soybeans could be used to mitigate off-target deposition of rice herbicides penoxsulam and bispyribac-sodium. Results indicate that this technology (specifically BOLT soybean) can be utilized if herbicide residue is below 1/16X of the full labeled rate and is not deposited at V3 or early reproductive growth stages (R1-R4).

Moral injury is a relatively new psychological syndrome characterized by profound emotional, cognitive, and social pain following perceived moral violations. Though often overlapping, moral violations can involve either the perpetration of a moral transgression (via action or inaction) or the experience of a moral betrayal by a trusted other. In each case, symptoms of moral injury may include guilt, shame, anger, loss of trust and meaning, and social withdrawal. To date, the study of moral injury has remained nearly exclusive to the military arena. In turn, the aim of this thesis is to highlight the relevance of moral injury to other populations vulnerable to its effects. These include: 1) justice-involved individuals found Not Criminally Responsible on Account of Mental Disorder who may experience moral injury after regaining insight into their offending behaviour; and 2) Public Safety Personnel who are often exposed to morally ambiguous situations while under high levels of social responsibility. To appreciate the impact of moral injury for these populations, adequate tools must first be developed to measure and assess it. The three studies included in this dissertation outline the key steps to instrument development using a mixed-method approach: first, a qualitative investigation with justice-involved individuals explores the unique emotional consequences following a criminal offence that will inform subsequent phases of instrument development; second, quantitative inquiries are taken to construct, evaluate, and employ a new moral injury assessment for Public Safety Personnel to uncover important causes and consequences of moral injury in this group. This dissertation serves as a strong indicator that moral injury is a unique and costly health outcome relevant across societal groups. / Dissertation / Doctor of Philosophy (PhD) / Moral injury is a new psychological syndrome developed to understand an individual’s response to a moral trauma. As with other traumatic stress disorders, some people may develop a moral injury after experiencing a situation or event that violates deeply held moral standards. These morally injurious events may be moral violations perpetrated by the individual and result in deep feelings of shame and guilt, or may be moral betrayals by a trusted other and result in feelings of anger and loss of trust. To better understand the causes, symptoms, and consequences of moral injury, we must first develop tools to measure and assess it. This thesis outlines the key steps involved in developing new moral injury assessments in two groups who have an elevated risk of experiencing morally injurious events and so may be more likely to develop a moral injury: justice-involved individuals found Not Criminally Responsible and Public Safety Personnel.

Despite its prevalence, there are currently zero treatments available for traumatic brain injuries (TBI). Neuroinflammation is a key aspect of the secondary injury process, but remains poorly understood. Recent work has shown that Type I Interferons, inflammatory cytokines typically produced in response to viral infection, are present in the post-mortem brains of human TBI patients. The cyclic GMP-AMP Synthase- Stimulator of Interferon Genes (cGAS-STING) pathway is one of the primary methods of producing Type I IFNs; therefore, this work sought to evaluate the role of the cGAS-STING pathway in a murine controlled cortical impact (CCI) model of TBI. Using cGAS knockout (KO) or STING KO mice, we show that global loss of either protein results in substantial neuroprotection. One day after injury, animals have reduced lesion size, cell death, and inflammatory cytokine production, as well as reduced motor deficits several days after injury. We also determined that mitochondrial DNA (mtDNA) is present in the cytosol of injured cortical cells, indicating it is available to bind cGAS, a cytosolic pattern recognition receptor. To determine whether brain-resident or peripheral immune cells are responsible for detrimental cGAS-STING signaling after TBI, we utilized bone marrow chimeric animals lacking STING in either the brain or hematopoietic cells and animals lacking STING specifically in microglia. We found that both microglia and peripheral immune cells contribute to STING signaling after neurotrauma, and that loss of STING in either cell population is beneficial. Taken together, this work demonstrates that canonical, cGAS-dependent STING signaling occurs primarily in microglia and peripheral immune cells, resulting in detrimental neuroinflammatory events after TBI. / Doctor of Philosophy / Traumatic brain injuries (TBI), including concussions and more severe injuries, are a leading cause of death and disability across the globe; yet, there are no Food and Drug Administration (FDA) approved treatments. There are two phases in the injury: primary injury, which is the immediate damage to brain cells upon impact, and secondary injury, which includes a wide range of cellular processes in the minutes to weeks after injury. Because the primary injury is so rapid, we utilize safety measures, such as helmets, to limit the severity of the TBI. The secondary injury, however, occurs over a longer period of time; therefore, this is where most research is focused for developing potential treatments. Inflammation in the brain, termed neuroinflammation, is a key part of this secondary injury. While some inflammation is useful for clearance of damaged cells, too much inflammation can cause additional damage. The goal of this work was to examine how a specific inflammatory pathway, the cGAS-STING (cyclic GMP-AMP synthase- stimulator of interferon genes) pathway, contributes to neuroinflammation after brain injury.

Mild traumatic brain injury (mTBI) accounts for approximately 73-83% of all traumatic brain injuries (TBI) and continues to be a serious clinical challenge [1]. The role of injury mechanism in TBI has been widely debated, and it is believed that although there are differences between diffuse and focal TBI, the resulting injury is not influenced by the way in which it was acquired [1], [2]. It is known that TBIs can cause cognitive impairments that are often due to injury experienced in the hippocampus [2]. In response to insult, quiescent neural stem cell (NSC) populations within the dentate gyrus region of the hippocampus become activated. Stem cell differentiation following injury is hypothesized to be unique for diffuse and impact TBIs, primarily due to the differences in mechanotransduction pathways triggered by each respective injury. By quantifying the lineage of stem cells through immunohistochemistry, this study examined the dentate gyrus following mTBI in a rodent model, and the contribution that injury mechanism plays in mTBI outcomes. Additionally, the behavioral effects of mTBI were assessed through open field testing at 72 hours and four weeks following injury. Overall, these findings indicated that after four weeks following mTBI, there are not significant differences between impact and blast both from an immunohistochemical and behavioral standpoint. Despite there being few differences between injury groups, these findings help clarify the role of injury mechanism not only in the context of neurogenesis, but they also inform future studies addressing preventative and treatment strategies for mTBI. / Master of Science / Mild traumatic brain injury (mTBI) accounts for approximately 73-83% of all traumatic brain injuries (TBI) [1]. There are two main ways in which a mTBI can occur: through diffuse or focal injury. A diffuse injury is due to the brain experiencing a force that does not physically come into contact with the head, such as a shockwave from an explosion. These types of injuries typically affect the entire head. Impact injuries on the other hand, are caused by the head encountering an object at a force that causes injury to the brain. These injuries tend to be focal, as the entire head rarely comes into contact with an object. Both diffuse and focal injuries can cause mTBI, and there is a current debate questioning if the mode of injury has an impact on the damage experienced by the brain [1], [2]. However, it is also known that mTBI can cause cognitive impairments such as changes in behavior, memory, and even mental health, which can occur in the hippocampus of the brain [2]. Within the hippocampus, there is a small subset of cells referred to as neural stem cells (NSC) that become active following injury. The activation of these cells is believed to be in response to injury in the brain. Furthermore, NSCs have the ability to differentiate into various cell types within the brain, including astrocytes, oligodendrocytes, and neurons. Each of these cell types perform an integral role in the function of the brain. It is hypothesized that the response of NSCs in the hippocampus is unique depending on if an injury was acquired through diffuse or impact mechanisms. To investigate this, the lineage of NSCs was quantified within the hippocampus following blast and impact mTBI in a rodent model. Additionally, the behavioral effects of diffuse and impact injury were investigated at 72 hours and four weeks following injury. Despite there being no significant differences in outcomes between injury groups, these findings help clarify the role of injury mechanism not only in the context of NSC response, but they also inform future studies addressing preventative and treatment strategies for mTBI.

Combat-related blast injuries are occurring more frequently with the increased use of improvised explosive devices in current military conflicts. Though much research has focused on how the body responds to the relatively low loading rates associated with blunt trauma, little is known regarding the response of the body to the higher loading rates associated with blast trauma. While soldiers are surviving once-lethal blast events due to enhanced protective equipment, injuries such as those to the eye and face that were once considered inconsequential, can now be detrimental to long-term healthcare costs and quality of life. Although it is suggested primary blast overpressure (i.e., the shock wave) can cause severe eye injuries, there remains few empirical data in the literature that confirms this. Adding to this, there are currently no testing standards to assess the effectiveness of personal protective equipment during blast exposure. Expanding upon traditional research techniques within the field of injury biomechanics, the research in this dissertation focuses specifically on developing experimental and physical models of the eye, face, and orbit for blast overpressure exposure. Foremost, a porcine eye model is used to quantify eye injury risk from blast overpressure exposure. Subsequently, these biomechanical data are used to develop a physical model of the eye that can be used in lieu of cadaver specimens for blunt and blast loading. Lastly, military spectacles and goggles are examined for effectiveness at protecting the eye during blast exposure. Combined with detailed computer-aided design geometries, these data can be used to validate computational models of the eye, orbit, and face to blast loading. Results from these tests support one theory that shock waves may enter the skull through the orbit, alluding to future work that is essential to more fully understanding the physiological response of the brain and ocular motor system to blast exposure. Ultimately, the experimental methods and analysis techniques disseminated herein serve as a framework for future experimental work related to blast and other high-rate loading scenarios. / Ph. D.

Airbags save lives; however, first generation airbags resulted in unintended fatal and injurious consequences for children and small statured adults seated in front of them. An immediate solution allowed for the development of less aggressive airbags (second generation), a subsequent revision to FMVSS 208 required further changes to airbags for the protection of children. These advanced airbags are required to either suppress or with a LRD in the presence of a child. Though car manufacturers have spent a considerable amount of time and money to meet the advanced airbag requirements, the effects of these airbags and characteristics of children seated in front of them have not been extensively studied. This thesis presents the requirements for advanced airbags, characteristics of children in MVCs, an evaluation of crashes involving children involved in crashes in the RFP seat for all airbag types and finally a case study of children seated in front of an advanced airbag during a crash. Overall, vehicles with advanced airbags were found to be safer for children than vehicles equipped with earlier airbag generations including vehicles not equipped with airbags. These findings suggest that vehicles overall are safer since one option for an advanced airbag is suppression which would render the occupant without an airbag. Further, the advanced airbags appear to be working as intended during real-world crashes. However, the back seat remains the safest place for children; this work in no way advocates that children should be seated in the RFP seat. / Master of Science