The study of the mechanism of traumatic brain injury (TBI) processes at the cellular level is vital to obtain characterization of nerve cell damage after mechanical deformation. This understanding is needed to find feasible therapeutic targets for mechanically damaged neurons. To study the cellular level of TBI damage, development of a new in vitro cellular model of TBI might be done to simulate in vivo cellular TBI. In this research, two studies were performed: (1) the design and construction of an in vitro cell stretching device to mechanically injure cells and (2) the characterization of the molecular and cellular level of the TBI mechanism. The cell stretching device design allows for the precise control of cell strain and duration of stretching cells such that TBI can be mimicked. Analysis of the cellular and molecular level mechanisms of TBI in the proposed in vitro model might help in the design of therapeutic strategies for the treatment of TBI. Our proposed mechanism of injury due to TBI is as follows: after the cell is stretched, a cellular signaling molecule is released to activate the cellular signaling pathway. The activated cell signal may activate kinases which phosphorylate proteins and initiate new protein synthesis. Newly phosphorylated and synthesized proteins may activate the apoptotic process. Using a variety of pharmacological agents, one could block steps in the hypothesized mechanism and examine the effect of those agents on downstream cellular processes and cell apoptosis. For example, the inhibitions of calcium transport, protein synthesis, and caspases were performed to examine the initial activation of the signaling pathway and the role of both in the apoptosis process. Proteomics of TBI may help the understanding of the mechanism of TBI related protein expression. This work will contribute to the discovery of new therapeutic targets and better treatments for TBI.

Every year, several thousand individuals suffer spinal cord injury (SCI) in North America, while 1.5 million suffer traumatic brain injury in the U.S.A. alone. Primary mechanical trauma to the CNS is followed by a complex pathology, including vascular dysregulation, ischemia, edema and traumatic hemorrhage. Secondary damage is to a large extent caused by oxidative stress and inflammatory processes, resulting in necrosis and apoptosis of neural cells. If secondary tissue injury could be limited by interference with any of the pathomechanisms involved, preservation of structure and function would increase the potential for functional recovery. Experiments performed in other laboratories have shown that the polyphenolic flavonoid quercetin acts as an anti-oxidant and anti-inflammatory, reduces edema formation and apoptotic cell death. Quercetin is also an excellent iron chelator. This action profile suggested a high therapeutic potential for acute CNS trauma. Therefore, I used models of both spinal cord injury and head trauma in adult male rats to test the hypothesis that administration of quercetin is beneficial for the therapy of acute traumatic CNS injury. While the primary focus of my work was on therapy of acute traumatic spinal cord injury, quercetin was also evaluated in the settings of chronic SCI and acute head trauma. I found that, in a rat model of mid-thoracic spinal cord compression injury, 1) administration of quercetin, starting 1 hr after injury and continued every 12 hr, improved recovery of motor function in the hind limbs in more than half of the injured animals to a degree that allowed previously paraplegic animals to step or walk. The minimum quercetin dose that was efficacious was 5 µmol/kg. The minimum treatment duration for optimal outcome was determined to be 3 days. In control animals, some spontaneous recovery of motor function did occur, but never to an extent that allowed animals to step or walk. Quercetin administration was associated with more efficient iron clearance from the site of injury, decreased inflammatory response as reflected in decrease of myeloperoxidase activity and decreased apoptosis of neural cells at the site of injury. 2) Quercetin administered in the same injury model as late as 2 weeks after injury, given in a higher dose than that used for treatment in the acute phase, still resulted in significant recovery of motor function in 40% of the injured animals, although at a lower level of performance, when compared to early onset of treatment. 3) Quercetin administered after moderate fluid percussion brain injury resulted in decreased oxidative stress, as reflected in higher tissue glutathione levels at the site of injury. In animals receiving quercetin, the amplitude of compound action potentials was significantly better maintained at 24 hr and 72 hr after injury than in saline-treated control animals. My experiments have shown that the flavonoid quercetin is neuroprotective in a rat model of brain trauma and in a rat model of spinal cord injury. My data show that administration of quercetin after CNS trauma promotes iron clearance, decreases oxidative stress and inflammation. Quercetin also decreases apoptotic cell death following neurotrauma. These results suggest that quercetin may be a valuable adjunct in the therapy of acute CNS trauma. There is a possibility that administration of quercetin may be beneficial even in certain settings of chronic CNS trauma. These conclusions are based solely on the results from animal experiments. However, the fact that few adverse reactions have been noted to date in either animal experiments or human trials targeting other diseases is encouraging for the progression to human clinical trials for patients with spinal cord injury.

Every year, several thousand individuals suffer spinal cord injury (SCI) in North America, while 1.5 million suffer traumatic brain injury in the U.S.A. alone. Primary mechanical trauma to the CNS is followed by a complex pathology, including vascular dysregulation, ischemia, edema and traumatic hemorrhage. Secondary damage is to a large extent caused by oxidative stress and inflammatory processes, resulting in necrosis and apoptosis of neural cells. If secondary tissue injury could be limited by interference with any of the pathomechanisms involved, preservation of structure and function would increase the potential for functional recovery. Experiments performed in other laboratories have shown that the polyphenolic flavonoid quercetin acts as an anti-oxidant and anti-inflammatory, reduces edema formation and apoptotic cell death. Quercetin is also an excellent iron chelator. This action profile suggested a high therapeutic potential for acute CNS trauma. Therefore, I used models of both spinal cord injury and head trauma in adult male rats to test the hypothesis that administration of quercetin is beneficial for the therapy of acute traumatic CNS injury. While the primary focus of my work was on therapy of acute traumatic spinal cord injury, quercetin was also evaluated in the settings of chronic SCI and acute head trauma. I found that, in a rat model of mid-thoracic spinal cord compression injury, 1) administration of quercetin, starting 1 hr after injury and continued every 12 hr, improved recovery of motor function in the hind limbs in more than half of the injured animals to a degree that allowed previously paraplegic animals to step or walk. The minimum quercetin dose that was efficacious was 5 µmol/kg. The minimum treatment duration for optimal outcome was determined to be 3 days. In control animals, some spontaneous recovery of motor function did occur, but never to an extent that allowed animals to step or walk. Quercetin administration was associated with more efficient iron clearance from the site of injury, decreased inflammatory response as reflected in decrease of myeloperoxidase activity and decreased apoptosis of neural cells at the site of injury. 2) Quercetin administered in the same injury model as late as 2 weeks after injury, given in a higher dose than that used for treatment in the acute phase, still resulted in significant recovery of motor function in 40% of the injured animals, although at a lower level of performance, when compared to early onset of treatment. 3) Quercetin administered after moderate fluid percussion brain injury resulted in decreased oxidative stress, as reflected in higher tissue glutathione levels at the site of injury. In animals receiving quercetin, the amplitude of compound action potentials was significantly better maintained at 24 hr and 72 hr after injury than in saline-treated control animals. My experiments have shown that the flavonoid quercetin is neuroprotective in a rat model of brain trauma and in a rat model of spinal cord injury. My data show that administration of quercetin after CNS trauma promotes iron clearance, decreases oxidative stress and inflammation. Quercetin also decreases apoptotic cell death following neurotrauma. These results suggest that quercetin may be a valuable adjunct in the therapy of acute CNS trauma. There is a possibility that administration of quercetin may be beneficial even in certain settings of chronic CNS trauma. These conclusions are based solely on the results from animal experiments. However, the fact that few adverse reactions have been noted to date in either animal experiments or human trials targeting other diseases is encouraging for the progression to human clinical trials for patients with spinal cord injury.

This study evaluated the impact of delivery of the Period of PURPLE Crying (PURPLE), in a group of first-time mothers. Frustration with crying is reported as a trigger for abusive head trauma (AHT).The primary objective was to determine whether there was a change in knowledge about crying and shaking after exposure to PURPLE. Factors associated with behavioral responses to crying were studied as was the utility of PURPLE. There was a significant increase in knowledge about infant crying (P = 0.001) after program delivery that was predicted by low baseline knowledge (P < 0.01). There was a non-significant negative change in shaking knowledge (P = 0.5), which may have been the consequence of high baseline knowledge of shaking. The PURPLE program was characterized as informative and useful by participants. Additional to evaluate the impact of program delivery on other caregivers and on the rates of AHT is recommended.

Background: Chronic traumatic encephalopathy (CTE) is an enigma that has become synonymous with combat sports over the past few decades. Mixed martial arts (MMA) is a combat sport that is growing in popularity world-wide. The objective of this study is to determine the factors associated with head trauma among MMA athletes. Methods: Logistic regression analyses using SPSS 20 was employed to model putative covariates against the dichotomous outcomes of unconsciousness (for the full dataset) and diagnosed concussion (for the enriched subset of fighters who were rendered unconscious). Results: Increasing age, black or African-American ethnicity, shorter rest periods between fights, increasing numbers of significant clinch strikes landed, significant distance body strikes landed and power strikes landed to the body at distance are all factors associated with being diagnosed with a concussion among the fighters rendered unconscious. Conclusion: If bolstered by confirming laboratory and clinical evidence, policies should be developed for implementation by MMA governing bodies to help reduce incidences of head trauma and concussion, built around fighters’ demographic and behavioural characteristics. In particular, enforcing a mandatory rest period between fights and placing an upper limit on fighters’ age are ideas worth exploring.

No description available.

This study employed a new model of mild-to-moderate head trauma to specifically identify the role of dural mast cell (MC) histamine in trauma-induced increased permeability in the blood-brain barrier (BBB). A single line was scored partially through the left dorsal parietal skull. Immediately following the trauma, degranulation was seen in 39% of the MCs on the left and in 2% on the right. After a 20 min survival period, left duras showed 55% with MC degranulation (fewer with complete degranulation) compared to 34% on the right. In the other experiments two parallel lines were scored following the injection of Evan's blue. Histamine assay showed histamine increased in the left cortex to 154% at 5 min, 174% at 10 min, and 151% at 20 min. Fluorescent quantitation of extravasated Evan's blue at 20 min following the trauma gave an increase of 1385% over the value measured for the right cortex. Zolantidine, a selective histamine H2 receptor antagonist, administered at 10- and 20- mg/kg 30 min before the trauma blocked 65% of the Evan's blue extravasation compared with the control and 2.5 mg group.

Background: Child maltreatment is a serious health concern in the United States (U.S.) affecting as many as one in four children throughout their lifetime (Finkelhor, Turner, Ormond, & Hamby, 2013). In 2013, a reported 678, 932 victims of child maltreatment were reported to Child Protective Services (CPS), and of those cases 1,520 were fatal (CDC, 2015a). Out of all the various types of child maltreatment, Shaken Baby Syndrome (SBS) is the leading cause of child abuse deaths in the U.S. (CDC, n.d.). While current research has focused on validating the effectiveness of educational interventions, very few studies have analyzed the efficacy of individualized, patient-centered action plans. Such data would be beneficial to assess the usefulness of action plans in preparing caregivers for coping with an inconsolable infant at home. Purpose: To enhance caregiver knowledge about SBS and to provide parents with the skills and resources necessary to cope effectively and efficiently at home when unable to console their infant. Methods: This study utilized a quasi-experimental pre-test/post-test design. Participants were recruited from the Franciscan Women’s Health Associates located at St. Joseph Medical Center in Tacoma, Washington and were members of the Centering prenatal groups. The entirety of the study was completed during these groups including the pre-test, intervention, action plan, and post-test. Data was analyzed through the utilization of descriptive statistics as well as a paired t test. Results: Overall, results revealed that participant (n=26) knowledge significantly improved after the educational intervention (p=0.000) with a mean score of 87.56% on the pre-test and a mean score of 95.38% on the post-test. In addition, a majority of participants (57.5%) found both the action plan and the education to be extremely useful. Discussion: The results of this study were consistent with current evidence indicating that education on SBS, the dangers of shaking, and healthy coping mechanisms significantly impacts caregiver knowledge. In addition, a majority of participants viewed the action plans favorably identifying that they would be beneficial if they felt frustrated. Future research is warranted to gather more information on the long-term outcomes of educational interventions as well as individualized action plans.

No description available.

abstract: Traumatic injuries are the leading cause of death in children under 18, with head trauma being the leading cause of death in children below 5. A large but unknown number of traumatic injuries are non-accidental, i.e. inflicted. The lack of sensitivity and specificity required to diagnose Abusive Head Trauma (AHT) from radiological studies results in putting the children at risk of re-injury and death. Modern Deep Learning techniques can be utilized to detect Abusive Head Trauma using Computer Tomography (CT) scans. Training models using these techniques are only a part of building AI-driven Computer-Aided Diagnostic systems. There are challenges in deploying the models to make them highly available and scalable. The thesis models the domain of Abusive Head Trauma using Deep Learning techniques and builds an AI-driven System at scale using best Software Engineering Practices. It has been done in collaboration with Phoenix Children Hospital (PCH). The thesis breaks down AHT into sub-domains of Medical Knowledge, Data Collection, Data Pre-processing, Image Generation, Image Classification, Building APIs, Containers and Kubernetes. Data Collection and Pre-processing were done at PCH with the help of trauma researchers and radiologists. Experiments are run using Deep Learning models such as DCGAN (for Image Generation), Pretrained 2D and custom 3D CNN classifiers for the classification tasks. The trained models are exposed as APIs using the Flask web framework, contained using Docker and deployed on a Kubernetes cluster. The results are analyzed based on the accuracy of the models, the feasibility of their implementation as APIs and load testing the Kubernetes cluster. They suggest the need for Data Annotation at the Slice level for CT scans and an increase in the Data Collection process. Load Testing reveals the auto-scalability feature of the cluster to serve a high number of requests. / Dissertation/Thesis / Masters Thesis Software Engineering 2020