Establishing a mouse model of post-traumatic epilepsy using video-EEG-ECG Monitoring

Traumatic brain injury (TBI) is a major cause of death and permanent disability. Patients with TBI are at an increased risk of developing post-traumatic epilepsy (PTE), and it has been estimated that PTE may account for up to 20% of symptomatic epilepsy cases in the general population. The process of epileptogenesis is defined as the mechanism by which a brain insult starts a cascade that culminates in the development of spontaneous seizures. Following TBI, the occurrence of seizures has been categorized as immediate (\u3c 24 h), early (days), or latent (weeks). These immediate and early seizures are considered to reflect the severity of the injury itself, whereas the latent seizures are thought to result from maturation of epileptogenic pathology. The specific objective of this pilot study was to establish a protocol for video-EEG-ECG of mice following TBI to determine latent PTE development. Mice underwent surgery and EEG-ECG electrodes were placed immediately prior to TBI via controlled cortical impact. We initially chose 2 depth levels of injury (1mm and 1.5mm). We determined that 1.5 mm led to a high mortality rate, leading us to proceed with 1 mm. Currently, we have detected (and verified) seizures in two of four mice at 4 weeks post injury. An additional 8 mice have been EEG analyzed, with potential seizures detected via EEG in five out of eight (awaiting verification). We found that there was post-ictal Atrial-Ventricular block in one mouse. We also observed large fluctuations in heart rate during seizure free periods. Further analysis of ECG recordings is ongoing. Overall, our goal is to establish a 50-60% PTE development rate in our model for future applications. Our findings on ECG abnormalities mimic those observed in other models of epilepsy, suggesting that neuro-cardiac interactions in TBI warrant deeper investigation

Effects of Adolescent Nicotine Exposure on Acute and Chronic Ethanol Consumption in a Heritable Model of Psychosis

Schizophrenia (SZ) is characterized by sensorimotor gating deficits, disordered thought processes, and hallucinations. Individuals diagnosed with SZ often exhibit comorbid substance abuse, particularly nicotine and alcohol (EtOH) use disorder. Our laboratory has established a novel heritable model of schizophrenia administering neonatal quinpirole (NQ), a dopamine (DA) D2-like receptor agonist (1 mg/kg), which results in permanent increases of DAD2 receptor sensitivity throughout the animal\u27s lifetime. We have shown offspring of male-female pairs of NQ-treated rats (QQ) demonstrate heritability of increased DAD2 sensitivity, consistent with clinical data. In the current study, male and female Sprague-Dawley rats that were postnatal day (PND) 28-48 days of age were given a two-bottle choice (2BC) test with water or water with 10% ethanol for 24 hours daily. On each day, animals were administered intraperitoneal (IP) injections of nicotine (0.6 mg/kg base). We assessed drinking of EtOH at the 3- and 6-h post-injection time points. Chronic drinking was assessed based on 24-h drinking measurements. Following 21-days of EtOH/nicotine exposure, nicotine injections and EtOH ceased from PND 49-62. During this period, locomotor activity was recorded as a measurement of withdrawal over 4 days of testing. In adulthood, a 2BC test was also conducted from PND 63-76. Results revealed adolescent nicotine exposure enhanced EtOH drinking in QQ animals. During withdrawal, QQ females given nicotine demonstrated enhanced locomotor activity and showed lack of habituation compared to other groups. Significant enhancement of acute EtOH following nicotine administration was also observed at the 3- and 6-h marks for the quinpirole (QQ) rats in adolescence compared to control (SS) rats at PND 63. Prefrontal cortex oxidative stress is being assessed using a TBARS assay (data will be presented). Findings suggest that adolescent exposure to nicotine and ethanol can have long-lasting effects on EtOH consumption in a heritable model of psychosis

Unleashing a Swarm: Characterizing the Mechanisms by which Neutrophil Swarming Restricts Fungal Hyphae

Neutrophils, a critical effector cell of innate immunity, utilize many mechanisms to combat infection. These cells employ a strong arsenal of tools, such as phagocytosis, NET production, and reactive oxygen species production, to eliminate pathogens within the body. Neutrophil swarming, a collective process of many neutrophils synchronizing their activities to target a single pathogen, has also been recently characterized. Although the molecular events triggering swarming have been characterized against artificial clusters of Canida albicans yeast, the biological relevance to this function remains unclear. We hypothesized that C. albicans hyphae, a larger morphology that is highly relevant to human disease and virulence during infection, would be a potent swarm inducing target and therefore a better system to elucidate the molecular mechanisms engaged during swarming. Unfortunately, swarming events against fungal hyphae are poorly characterized. To address this knowledge gap, we leveraged a microscale printing assay to target fungal hyphae and elucidate molecular pathways that neutrophils might use to induce swarming. To do this, 8x8 grids of Poly-l-lysine spots were printed using a Picospotter (PolyPico, Galway, Ireland) onto glass slides and C. albicans hyphae were attached to each spot. Confocal timelapse microscopy was used to monitor human neutrophil responses against these targets. Isolated human neutrophils were treated with inhibitors to target specific signaling pathways that are important for swarming function. We found that hyphae were indeed able to induce potent swarming responses. We found that by inhibiting spleen tyrosine kinase (SYK), Bruton’s tyrosine kinase (BTK), or cellular receptor CD18, neutrophils were unable to either induce or maintain swarming responses, which compromised the restriction of hyphal growth. Lastly, we observed interesting insights into pioneer neutrophil interactions with hyphal cells. This assay allowed us to further understand the biology behind neutrophil swarming and contribute to understanding the role swarming plays against infectious fungal pathogen

Bridging (Setubandha Sarvangasana-ing) the gap between yoga and digestion

Exploration of the gut-brain-axis has been at the forefront of nutrition research, and the various connections between stress and digestion have been established through many studies. Yoga is a multifaceted form of holistic therapy known for its stretching techniques, breathing (pranayama) practices, and focus on the mind-body connection; it is a common practice amongst those looking to improve flexibility, build strength, and reduce stress. This research aims to explore the connection between yoga and digestion by surveying yogis in the tri-cities area of East Tennessee. The participants must be at least 18 years of age and have at least 2 months of previous experience in yoga. We will be surveying their perceived bowel movement quality, quantity, and frequency changes through the Qualtrics surveying platform, providing the Bristol Stool Chart to aid in participants’ ability to give adequate feedback. As a result of this research, we expect to see improvements in the frequency and quality of bowel movements associated with the implementation of yoga into a regular routine

Cyclic-di-GMP phosphodiesterase STM3615 regulates Salmonella physiology

Foodborne-related diseases pose a global health threat, with Salmonella being a leading cause worldwide. To develop better prevention strategies against Salmonella-related food poisoning, we need a deeper understanding of how Salmonella senses its environment to adjust its behavior and enhance its chances of survival. One way bacteria achieve this is through second messengers, molecular signals that help relay this type of information. A key second messenger of interest is cyclic-di-GMP that bacteria use to regulate genes that enhance survival and infectious potential by influencing processes such as biofilm formation, flagellar motility, and virulence. Previous studies identified the cyclic-di-GMP phosphodiesterase STM3615 as important for Salmonella survival inside macrophages and virulence in a mouse model. Here, we investigated STM3615’s role in Salmonella physiology. Using a dye-based agar assay, we found that deleting STM3615 reduced survival in the stationary phase. Microscopy revealed that the mutant also exhibited a shorter bacterial morphology. Given that both phenotypes relate to bacterial division, we tested its susceptibility to A22, an antimicrobial that disrupts bacterial replication machinery, and observed significantly reduced survival. STM3615 contains multiple domains, including transmembrane, periplasmic, HAMP, and phosphodiesterase (PDE) domains. Surprisingly, the periplasmic domain, rather than the PDE domain responsible for breaking down cyclic-di-GMP, emerged as the key regulator of bacterial morphology and division. A protein fold prediction algorithm suggested STM3615 interacts with a periplasmic protein partner to mediate this response. Using random transposon mutagenesis, we identified mutations in the Rcs pathway—linked to envelope stress and morphology regulation—that restored wild-type phenotypes. Future research will investigate STM3615’s interactions with a periplasmic binding partner to further define its role in cell division. Understanding this mechanism could provide new insights into bacterial growth regulation, with implications for therapeutic strategies and infection control

An ecological study of campylobacteriosis risk factors in Tennessee

Background: Data from the Center for Disease Control and Prevention (CDC) estimates that about 1.5 million cases of campylobacteriosis occurs annually in the U.S. In Tennessee, campylobacteriosis incidence increased gradually from about 9 per 100,000 people in 2020 to about 13 per 100,000 people in 2022. Ecological studies are useful when exposure data are available at the aggregate level rather than individual-case level. Therefore, this study examined the relationships between campylobacteriosis cases and ecological risk factors in Tennessee. Methods: The study was based on CDC FoodNet data in Tennessee with 7876 sporadic cases. Frequency distribution of the sociodemographic characteristics and yearly incidence of the disease were determined. The data were then aggregated at the zip code level for the ecological analysis. Bivariate and multivariate negative binomial regressions were used to determine factors associated with number of cases. Results: The majority of cases were male (52.85%). The median age was 44 years and 83% of the cases were racially white. About 62% of the persons infected with campylobacteriosis were hospitalized. The disease incidence in 2022 was the highest (18.44/100,000) and lowest in 2014 (13.35/100,000). The risk factors for campylobacteriosis include increasing percentage of whites in a zip code (IRR=1.0146; 95% CI: 1.0081–1.0211), increasing population density (IRR=1.0006; 95% CI: 1.0002–1.0009), the presence of chicken operation (IRR=1.2895; 95% CI: 1.0232–1.6150) and number of well water in a zip code area (IRR=1.0002; 95% CI: 1.0001–1.0004). Conclusion: The increase in the disease incidence from the least incidence in 2014 to the highest in 2022 suggest that intensified public health interventions will be required to lower the incidence trend. Furthermore, measures must be implemented to mitigate the risk associated with private well water safety and contaminated of water sources by chicken operation run-off. Hence, mitigation strategies aiming at reducing the pathogen transmission routes are needed

The Ethics of Child Advocacy: Balancing Autonomy and Protection in our Legal Systems

Children hold a special place in our society; as adults, we assume a responsibility to protect our children, yet we are also taught to grant children the opportunities to practice independence. The question of how much autonomy children should be allowed is longstanding, and its answer is critical to how our youth are viewed and utilized in our legal systems. How do we balance a child\u27s autonomy and independence with our duty to protect them, and how does this apply to our utilization of children in our legal systems? There are times in which a child’s life is at risk of being upended due to legal circumstances, such as cases of abuse and neglect. In these cases, hearing the voice and opinions of the child can provide us with critical insight into a situation as well as a valuable perspective on how to approach the decision making process. However, it is clear that this also presents the risk of adding to a child’s trauma; additionally, there are times in which the wants of the child are vastly different than the child’s needs. This raises the following question: How can legal systems ensure that children’s voices are heard while also protecting their safety and well-being? This thesis will explore the ideas of autonomy, protection, and children’s rights through philosophical study and interviews with those directly involved with children in our legal system. I believe the findings will show that legal systems can balance a child’s autonomy and their protection by adopting a reformed and more nuanced version of the “best interests of the child” standard, which would incorporate both the child’s expressed wishes and the results of well-being assessments. Additionally, integrating child participation into our legal systems as a fundamental human rights obligation, rather than as a conditional privilege, can help to ensure a more ethical approach to balancing the concerns at hand

A Comparative Study of Quantum Computing Performance in Information Systems Analysis

The thesis will involve a comparison between quantum and classical computers to determine how quantum technology can be used to solve problems faced by modern information systems. Research on quantum technology as a solution to modern information processing challenges will help to provide solutions for some unanswered questions – whether in the field of quantum computing, information systems design, or both. Given that a real quantum computer is expensive, a bare-metal hardware approach is simply not possible for this project’s limited timeframe. Therefore, the researcher will gather the relevant data using a virtual machine designed to emulate a modern quantum system. Quantum computing research is still a developing field, but its future prospects are exciting – especially in enterprise information systems. Quantum computers, at their core, are fundamentally different from classical computers in how computational logic is handled. The differences, while not yet fully understood, allow a quantum system to achieve results in calculations that are considered impossible to solve by a classical system. Some calculations that quantum systems might face will be solvable with classical technology, but in an impractical amount of time. Quantum computers have the potential to speed up some calculations that would otherwise be considered infeasible with certain time constraints, depending on the problem’s context. Quantum research is no longer purely theoretical, with many well-known companies worldwide establishing implementation of quantum principles into their own workflows. The choice to explore quantum computer science for the thesis is an ideal opportunity to provide new insight into the effects that quantum can have on information management. Quantum systems can potentially be applied in many different contexts, and modern enterprises are eager to take advantage of their capabilities