EFFECT OF INJURY MECHANISM AND SEVERITY ON THE MOLECULAR PATHOPHYSIOLOGY OF TRAUMATIC BRAIN INJURY

Traumatic brain injury (TBI) mechanism and severity are heterogenous clinically, resulting in a multitude of physical, cognitive, and behavioral deficits. However, approximately 80% suffer from milder injuries. Thus, examining pathophysiological changes associated with mild TBI is imperative for improving clinical translation and evaluating the efficacy of potential therapeutic strategies. Through this work, we developed models of TBI, ranging in both injury mechanism and severity, using an electromagnetic controlled cortical impact (CCI) device. First, we characterized and optimized a closed head, mild TBI model (DTBI) to determine the clinical translatability and practicality of producing repeated mild injuries. Interestingly, we determined that impact speed was highly dependent on both input velocity and depth. Indeed, impact conditions differed from input parameters, and we suggest researchers characterize closed head models using CCI devices to ensure data is interpreted based on the true impact conditions. Additionally, we investigated how impact speeds influenced pathophysiology, specifically autophagic flux. Our results show that autophagic flux was impaired acutely in the hippocampus, regardless of impact speed, providing rationale for evaluating autophagic flux following mild, diffuse impacts. Thus, we continued investigating pathophysiological changes associated with a spectrum of TBI, including severe CCI, modified mild TBI (MTBI), and previously characterized DTBI. Following impacts, we observed distinct differences in gross neuropathology, which corresponded with changes in the progression of cell death. Indeed, severe CCI resulted in dramatic increases in oncosis, while mild models differed regarding apoptotic response, suggesting injury mechanism and severity shift the progression of cell death. Interestingly, each of the three impact models resulted in impaired autophagic flux, which coincided with changes in both oncotic and apoptotic cell death. Thus, these results provide evidence that the pathophysiological mechanisms affiliated with TBI heterogeneity may be linked through common upstream events, namely impaired autophagic flux and lysosomal dysfunction. Therefore, therapeutic strategies designed to intervene in the amelioration of these consequences may alleviate molecular dysfunction, in addition to the cognitive and behavioral deficits observed following TBI. Advisor: Forrest M. Kievi

Nanoparticle Treatment to Counter Reactive Oxygen Species after Traumatic Brain Injury

Traumatic brain injury (TBI) is defined as damage to the brain, resulting from an external mechanical force, such as an impact to the head (Kievit et. al, 2016).There are several examples that could result in a potential TBI; such as falling with contact to the head, car accidents and even physical activities including football, wrestling, and boxing. Because of the several different scenarios that an individual could impact their head, TBI’s have become an all too common aspect of everyday life. TBI is currently the leading cause of death and disability in children and adults under the age of 45, with 1.7 million reported cases annually in the United States alone(Bharadwaj et. al, 2016). The major problem that causes TBIs to be so lethal is the combination of both the initial damage and the secondary corrosive damage on the surrounding brain tissue. The initial damage is capable of being prevented by wearing helmets, seat belts and taking other safety precautions. However, there are currently no treatments that protect the brain from secondary deterioration, spread of the injury beyond primary damage (Kievit et. al, 2016). While some individuals are capable of fully recovering from a TBI without secondary brain damage, unfortunately, roughly 35% of TBI survivors face long-term disabilities (McConeghy et. al, 2012). The lethal progression of this secondary injury is in part caused by the release of reactive oxygen species (ROS) into the surroundings of the normal brain (Kievit et. al, 2016). From this information, it seems that the best way to prevent this secondary spread to the brain would be to reduce or eliminate the spread of ROS. In order to control this release of ROS, there must be a chemical, or biological entity, placed into the brain that reacts with these ROS so that they are incapable of reacting with the healthy portions of the brain. Currently, Dr. Kievit’s lab is developing nanoparticles that can react with these ROS and prevent them from spreading into other areas of the brain

Barbara Powers: Witch or Myth? The Last Case of Witchcraft in South Carolina

Was an elderly woman from the upstate of South Carolina the last to be accused of and put on trial for witchcraft in the United States? In this paper, we investigate claims from an old letter sent to the president of South Carolina College to determine whether or not Barbara Powers was truly accused of witchcraft during a criminal trial. After thoroughly investigating census data, court records, marriage records, and other historical data in the named counties and those surrounding them, we were unable to determine conclusively if the trial was real or fabricated. Despite not knowing if the case occurred or not, we explored the historical context of the United States and specifically upstate South Carolina in and around 1813. The purpose of this study was to identify factors that may have prompted a witchcraft trial and to analyze moral panics including the causes and ramifications of historical and contemporary moral panics. Ultimately, we concluded that moral panics, such as those that lead to accusations of witchcraft, continue to shape our perceptions of the world

The fate of manure phosphorus during production and harvest of turfgrass sod

Removal of manure from dairies to sites less prone to point-source nutrient pollution is an option for dealing with dairy confined animal feeding operation wastes. Applications of dairy manure waste to turfgrass sod can be an environmentally sound approach because both plant matter and soil are removed during harvest (Vietor et al., 2002). Field scale research was conducted on a pair of adjacent, 1.42 ha Tifway bermudagrass fields on a fine-textured clay soil to investigate the fate of manure phosphorus (P) from composted dairy manure applications. Both fields received equal rates of supplemental nitrogen fertilizer but one was treated with composted dairy manure. The treated field received 75 kg ha-1 P during the first crop. After harvest, 127 kg ha-1 P was applied to the second crop. Once reestablished, this crop was harvested. Surface layer sod and subsurface soil were frequently sampled on a grid pattern from each field and analyzed to monitor soil P. Both plant extractable and total P analyses were used. It was determined that a sod harvest couldeffectively remove all of the applied manure P. Below the sod layer, there were no increases in soil P as a result of the composted dairy manure treatments, indicating that P leaching did not occur. Phosphorus runoff during rain events or irrigation was monitored by members of the Department of Biological and Agricultural Engineering. It was reported that more P was lost in runoff from the compost treated field than the untreated field. Cumulative water infiltration rate, soil bulk density, and plant available water holding capacity of the soil were tested to determine if the composted dairy manure treatments affected these soil physical properties. The only significant change was an increase in plant available water holding capacity on the surface layer of the treated field. An economic analysis was performed using actual financial data from the project. A scenario was created to investigate the feasibility of a dairy farm profitably adding a small turfgrass sod enterprise to its operation. It was determined that a sod field enterprise could be moderately to highly profitable for a dairy

Effectiveness of extra enforcement in construction and maintenance work zones

As traffic-related work zone crashes continue to increase across the nation, safety of road users and workers has become a top priority for transportation agencies. Since inattention and irresponsible behavior by drivers are surmised to contribute to the frequency of work zone crashes, a program featuring extraordinary presence of and enforcement by law officers has been implemented in many states to address this concern. A literature search of such programs and related research was conducted. While the overall benefits of these activities have been found positive, much of the evidence has been anecdotal. To assess the scope of extra work zone enforcement programs, a survey was developed and distributed to state departments of transportation across the nation. This survey sought information regarding these efforts such as criteria for selection of target work zones, methods of enforcement operations, and beneficial results. A special survey was also designed and distributed to enforcement agencies in Iowa and other selected states. In addition to the surveys, personal contacts and office visits were conducted by the research team staff. The study found that use of extra enforcement in work zones is a common practice in many states and these activities appear to be increasing. Current literature, survey responses, and interviews have all indicated a prevalent opinion for the benefits of increased law enforcement presence and activity in work zones. Very few comments offered conclusions of negative impacts, such as additional congestion, from these efforts. However, the beneficial effects of focused enforcement have not been intensively quantified. In addition, procedures for the use of law officers in work zones are quite inconsistent across the nation, as is the general implementation of specific legislation addressing work zone traffic violations. Similar variation can be found in funding levels and sources for enforcement activities in work zones among the states. Training of law officers prior to work zone duty does not appear to be commonly required, though the value of focused training is being recognized in some states. As crashes and deaths continue to rise annually in our nation\u27s work zones, it is imperative that demonstrated beneficial programs such as the expanded use of law officers in these locations be continued, refined, and expanded. Future study is needed to supplement the knowledge base and provide guidance to agencies when considering the use of law enforcement to calm traffic, ensure compliance with traffic laws, and thus provide for safer work zones

The Nanotheranostic Researcher’s Guide for Use of Animal Models of Traumatic Brain Injury

Traumatic brain injury (TBI) is currently the leading cause of injury-related morbidity and mortality worldwide, with an estimated global cost of USD 400 billion annually. Both clinical and preclinical behavioral outcomes associated with TBI are heterogeneous in nature and influenced by the mechanism and frequency of injury. Previous literature has investigated this relationship through the development of animal models and behavioral tasks. However, recent advancements in these methods may provide insight into the translation of therapeutics into a clinical setting. In this review, we characterize various animal models and behavioral tasks to provide guidelines for evaluating the therapeutic efficacy of treatment options in TBI.We provide a brief review into the systems utilized in TBI classification and provide comparisons to the animal models that have been developed. In addition, we discuss the role of behavioral tasks in evaluating outcomes associated with TBI. Our goal is to provide those in the nanotheranostic field a guide for selecting an adequate TBI animal model and behavioral task for assessment of outcomes to increase research in this field

An evaluation of sexual dimorphism in head size and shape of Red Salamanders (Pseudotriton ruber)

For many secretive species of amphibians and reptiles, observations of reproductive behavior are limited to sparse anecdotes from the field or to animals held in captivity. However, a careful examination of morphological differences between the sexes can help shape hypotheses about behaviors with which they may be correlated. For example, sexual dimorphism in head size and shape are correlated with courtship, territoriality, and mate-defense behaviors in some salamanders. One widespread species with a poorly described reproductive natural history is the Red Salamander (Pseudotriton ruber). Here, we measure head size and employ geometric morphometric methods to evaluate head shape in P. ruber, with the goals of: 1) quantifying and visualizing sexual variation; 2) forming hypotheses about reproductive behavior. We found preliminary evidence for differences in head size and shape that are consistent with mate-guarding behavior, and we remark upon directions for future research

Biodiversity benefits of an ecosystem engineer are negated by an invasive predator

Ecosystem engineers play a vital role in community assembly by modifying the environment to create novel habitat features. Woodrats (Neotoma sp.) build and maintain intricate stick-nests that stockpile organic materials and create habitat for other small species. The Key Largo woodrat (Neotoma floridana smalli) is an endangered subspecies endemic to Key Largo, Florida, USA, that has undergone substantial declines due to habitat loss and predation by invasive predators. We leveraged data from a camera trap monitoring grid at supplemental woodrat nest structures to survey bird communities to evaluate the role of woodrat nest use and stick-nest building related to bird abundance using generalized linear models. We predicted that woodrat occurrence and stick-nest building would positively correlate with bird species richness and abundance due to the creation of habitat structures that support prey for birds. To test this, we analyzed the relationship that bird abundance and species richness have with several indicators of woodrat activity along with other environmental and predator variables. Bird abundance was positively associated with woodrat supplemental nest use and stick-nest building. However, these positive associations were largely negated by the presence of free-roaming cats (Felis catus), an invasive predator, and dampened by proximity to human development. We provide evidence that woodrats may have cascading effects on their local food webs by creating foraging grounds for birds, but this positive relationship is disrupted by the presence of an introduced predator

High Precision Measurements Lend No Supporting Evidence of Previously Reported Large Verdet Constants for Olive Oil

Motivated by a previous report of surprisingly large Verdet constant measurements for olive oil at 633 nm and 650 nm (Shakir, et. al., 2013), and the practical utility of materials possessing such large values, we considered it worthwhile to validate those results. In this work, high precision Faraday rotation measurements were performed utilizing ac magnetic fields, phase sensitive detection, and a collection of diode lasers. Specifically, we measured the dispersion of the Verdet constant for a single brand of olive oil from 410 nm to 675 nm. In addition, we determined the Verdet constant for eight different samples of olive oil at 654 nm, very near the wavelength where the “anomalous” results, i.e. large Verdet constants, were reported. Our measurements of the Faraday rotations, and hence the determination of the respective Verdet constants, call into question those previously reported measurements. Generally, our results suggest that their experimental technique most likely led to inaccurate results for all five of the Verdet constant values they reported

High variability within pet foods prevents the identification of native species in pet cats' diets using isotopic evaluation

Domestic cats preying on wildlife is a frequent conservation concern but typical approaches for assessing impacts rely on owner reports of prey returned home, which can be biased by inaccurate reporting or by cats consuming prey instead of bringing it home. Isotopes offer an alternative way to quantify broad differences in animal diets. By obtaining samples of pet food from cat owners we predicted that we would have high power to identify cats feeding on wild birds or mammals, given that pet food is thought to have higher C isotope values, due to the pervasive use of corn and/or corn by-products as food ingredients, than native prey. We worked with citizen scientists to quantify the isotopes of 202 cat hair samples and 239 pet food samples from the US and UK. We also characterized the isotopes of 11 likely native prey species from the southeastern US and used mixing models to assess the diet of 47 cats from the same region. Variation in C and N isotope values for cat food was very high, even within the same brand/flavor, suggesting that pet food manufacturers use a wide range of ingredients, and that these may change over time. Cat food and cat hair from the UK had lower C values than the US, presumably reflecting differences in the amount of corn used in the food chains of the two countries. This high variation in pet food reduced our ability to classify cats as hunters of native prey, such that only 43% of the animals could be confidently assigned. If feral or free ranging cats were considered, this uncertainty would be even higher as pet food types would be unknown. Our results question the general assumption that anthropogenic foods always have high C isotope values, because of the high variability we documented within one product type (cat food) and between countries (US vs. UK), and emphasize the need to test a variety of standards before making conclusions from isotope ecology studies