Medical Sciences Commons^™

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

The Differential Effects Of Acoustic Discriminations On Operant Learning Performance And Neurogenesis In Male And Female Zebra Finches, Kristena L. Newman

Dissertations, Theses, and Capstone Projects

Adult neurogenesis, the creation of new neurons, occurs throughout the lifespan in most organisms. However, though neuronal proliferation occurs daily, most of these neurons do not survive to become incorporated into preexisting neural circuitry and become fully functioning neurons. In the mammalian brain, adult neurogenesis occurs within the hippocampus, a brain region known to be important in learning and memory. In rats, successful acquisition of certain learning tasks increased new neuron numbers when the learning was sufficiently challenging (Curlik and Shors, 2011). It has also been demonstrated that a spatial discrimination task requires new neurons when the discrimination is more …

A Novel Approach Toward Concussion Testing, Jorge K. Mercado, Ari Schacter, Danielle Euzent

Student Theses

A concussion is a violent jarring or shaking of the head caused by whiplash or direct impact that results in a disturbance of brain function. Concussions can be mild and brief, as a person may be dazed momentarily or can be more serious, resulting in a loss of consciousness. Underreporting of concussions is prevalent because they are a symptom-based diagnosis, lacking a clinical test. In this study, we investigated the use of VNG testing as a clinical diagnosis of concussions. Looking at the VNG test battery, the previous research cohort found that saccades, gaze, and positional testing are the most …

Apathy And Brain Atrophy During The First Year Of Moderate-Severe Traumatic Brain Injury: A Longitudinal Study, Gulnaz Kudoiarova

Dissertations, Theses, and Capstone Projects

Apathy, defined as disinterest and loss of motivation, is a common complication after moderate-severe traumatic brain injury (msTBI). The existing body of research in various neurological and neurodegenerative disorders suggests that apathetic symptoms may be associated with variation in the volume of the brain regions such as dorsal anterior cingulate cortex and ventral striatum. However, the longitudinal pattern of TBI-induced atrophy in these key regions and its relationship with apathy symptoms remain to be demonstrated. The current study aimed to describe the atrophy pattern in the anterior cingulate gyrus (ACG) and the nucleus accumbens (NAc; part of ventral striatum) after …

Investigation Of Postmortem Methamphetamine Cases Submitted To The New York City Office Of Chief Medical Examiner, Isaiah Jewell

Student Theses

Methamphetamine (N-methylamphetamine) is a central nervous system stimulant (CNS) and sympathomimetic drug with a high addiction potential. In the United States, there has been a significant increase in the presence of methamphetamine in recent years, specifically in the Northeastern region of the country. The New York City Office of Chief Medical Examiner (NYC-OCME) postmortem methamphetamine casework from 2018 and 2019 was analyzed and revealed that the presence of the drug increased drastically within a span of one year, jumping from 65 cases in 2018 to 99 cases in 2019. Males were overwhelmingly responsible for much of the casework, taking up …

Delayed Modulation Of Glutamate Receptors By Anti-Epileptic Drugs After Traumatic Brain Injury In Rats, Edgar Rodriguez

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is a significant health concern. Around 74 million people sustain a traumatic brain injury worldwide. The damage caused by TBI produces two types of injury; primary and secondary injuries. Primary injury is caused within milliseconds and is irreversible. Secondary brain injury is delayed and produced by molecular, cellular, and structural disruption after the initial injury. One of the most devastating dysfunction after TBI is glutamate neurotransmitter overactivation that could lead to neurotoxic levels of glutamate in the brain (i.e., excitotoxicity). Excitotoxicity has been linked with the development of epilepsy after TBI, also known as post-traumatic epilepsy …

Machine Learning Classification Of Traumatic Brain Injury Patients Versus Healthy Controls Using Arterial Spin Labeled Perfusion Mri, Vanessa I. Grass

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide, yet accurate in vivo detection of TBI neuropathology remains challenging due to complexities in the structural and functional changes observed post-injury as well as limitations in conventional neuroimaging modalities. Although advanced neuroimaging techniques such as arterial spin labeling (ASL) can noninvasively assess cerebral blood flow (CBF) changes observed post-injury, this technique is underutilized in TBI research partly due to the low signal-to-noise-ratio (SNR) inherent in ASL imaging. The aim of the current study is to examine the use of machine learning, specifically a Support …

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses and Dissertations

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …

Osteocyte Activity And Skeletal Muscle Relative Gene Expression Profiling After Short-Term Muscle Paralysis, Michelle Gelbs

Dissertations and Theses

Mechanical loading is essential for maintaining bone tissue. Reduced mechanical loading has been shown to have a negative effect on bone, and can result in the development of disuse osteoporosis. Disuse models of muscle inactivity and immobilization, like the Botox model used in this study, result in changes in the bone microarchitecture, the mechanisms behind which are not fully understood. In a previous four-week Botox disuse study, skeletally mature 20- week-old rats experienced degradation of intracortical bone, increased vascular porosity, and decreased osteocyte lacunar density in the tibiae. The focus of this study was to explicate a potential source of …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Mechanisms Of Value-Biased Prioritization In Fast Sensorimotor Decision Making, Kivilcim Afacan-Seref

Dissertations and Theses

In dynamic environments, split-second sensorimotor decisions must be prioritized according to potential payoffs to maximize overall rewards. The impact of relative value on deliberative perceptual judgments has been examined extensively, but relatively little is known about value-biasing mechanisms in the common situation where physical evidence is strong but the time to act is severely limited. This research examines the behavioral and electrophysiological indices of how value biases split-second perceptual decisions and the possible mechanisms underlying the process. In prominent decision models, a noisy but statistically stationary representation of sensory evidence is integrated over time to an action-triggering bound, and value-biases …

Electroencephalographic Asymmetry, Emotion Regulation, And Their Relationships With Depression Risk, Aliza Jacob

Dissertations, Theses, and Capstone Projects

Background: Research investigating patterns of electroencephalographic (EEG) brain asymmetry aids our understanding of neural systems involved in the processing of emotion, motivation, and psychopathology. Withdrawal-motivated negative emotions characteristic of depression are associated with relative right prefrontal cortex (PFC) activity, whereas approach- motivated positive emotions are associated with relative left PFC activity. Styles of emotion regulation (ER), or modulation of the intensity and duration of emotional responses, are also associated with presence (e.g., suppression, or maladaptive ER) versus absence (e.g., cognitive reappraisal, or adaptive ER) of depression vulnerability. Most PFC asymmetry studies of emotion, depression, and/or ER rely upon EEG recorded …

Inference Of Language Functional Network In Healthy, Cancerous And Bilingual Brains By Fmri And Network Modeling, Qiongge Li

Dissertations, Theses, and Capstone Projects

We study the underlying mechanism by which language processing occurs in the human brain using inference methods on functional magnetic resonance imaging data. The data analyzed stems from several cohorts of subjects; a monolingual group, a bilingual group, a healthy control group and one diseased case. We applied a complex statistical inference pipeline to determine the network structure of brain components involved with language. This healthy network reveals a fully connected triangular relationship between the pre-Supplementary Motor Area (pre-SMA), the Broca's Area (BA), and the ventral Pre-Motor Area (PreMA) in the left hemisphere. This "triangle'' shows consistently in all the …

Eugenics In The 21st Century, Jessica Linn Chin

Dissertations, Theses, and Capstone Projects

Eugenics is the science of enhancing the human population through the management of breeding and hereditary traits. This thesis explores the history of eugenics and shows how eugenic practices continue in the 21^st century with advancements in technology and positive eugenic goals that can result in adverse effects on the human body and society. When Sir Francis Galton coined the term eugenics in 1883, he intended to improve British society with the use of positive eugenics. Galton used positive eugenics to encourage people with good mental and physical qualities to produce more children. He avoided negative eugenics, which involved …

The Morphology And Evolution Of The Primate Brachial Plexus, Brian M. Shearer

Dissertations, Theses, and Capstone Projects

Primate evolutionary history is inexorably linked to the evolution of a broad array of locomotor adaptations that have facilitated the clade’s invasion of new niches. Researchers studying the evolution of primates and of their individual locomotor adaptations have traditionally relied on bony morphology – a practical choice given the virtual non-existence of any other type of tissue in the fossil record. However, this focus downplays the potential importance of the many other structures involved in locomotion, such as muscle, cartilage, and neural tissue, which may each be influenced by separate selective forces because of their different roles in facilitating movement. …

Using Fundamental Properties Of Light To Investigate Photonic Effects In Condensed Matter And Biological Tissues, Laura A. Sordillo

Dissertations and Theses

Light possesses characteristics such as polarization, wavelength and coherence. The interaction of light and matter, whether in a semiconductor or in a biological sample, can reveal important information about the internal properties of a system. My thesis focuses on two areas: photocarriers in gallium arsenide and biomedical optics. Varying the excitation wavelength can be used to study both biological tissue and condensed matter. I altered the excitation wavelengths to be in the longer near-infrared (NIR) optical windows, in the shortwave infrared (SWIR) range, a wavelength region previously thought to be unusable for medical imaging. With this method, I acquired high …

Translational Modeling Of Non-Invasive Electrical Stimulation, Dennis Quangvinh Truong

Dissertations and Theses

Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.

In this dissertation, Finite Element Method (FEM) models of …

A Modern-Day Affliction: Did Wifi Make Joel Dean Sick?, Dominic Mckenzie

Capstones

Electromagnetic Hypersensitivity is one of many disorders that exist in a strange border zone between recognized syndromes and discredited ones. One young man, a computer engineer by trade, had his life turned upside down by the disorder that has doctors and scientists across the world confused on how to treat it. Here's his story:

https://medium.com/@dominic.mckenzie/capstone-1dd7ff866a29

Resting-State Functional Connectivity In Youth With Gender Dysphoria, Felix L. Garcia

Dissertations, Theses, and Capstone Projects

Current developmental models of gender identity and gender dysphoria (GD) lack sex-specific profiles of brain function that differentiate between typically-developing and cross-gender identified youth, as postulated by models like the unified theory of the origins of sex differences (Arnold, 2009) and the neurobiological theory of the origins of transsexuality (Swaab & Garcia-Falgueras, 2009). Previously, investigators have used brain imaging modalities such as Resting-State functional Magnetic Resonance Imaging (R-fMRI) to demonstrate differences in resting-state functional connectivity (RSFC) between typically-developing male and female youth, and between typically-developing and GID-diagnosed youth. In the present pilot study, I used R-fMRI to investigate differences in …

Demystifying The Placebo Effect, Phoebe Friesen

Dissertations, Theses, and Capstone Projects

This dissertation offers a philosophical analysis of the placebo effect. After offering an overview of recent evidence concerning the phenomenon, I consider several prominent accounts of the placebo effect that have been put forward and argue that none of them are able to adequately account for the diverse instantiations of the phenomenon. I then offer a novel account, which suggests that we ought to think of the placebo effect as encompassing three distinct responses: conditioned placebo responses, cognitive placebo responses, and network placebo responses. Next, I consider implications of the placebo effect’s role in complementary and alternative medicine for discussions …

Otologic Blast Injuries, Michelle Singer

Dissertations, Theses, and Capstone Projects

The otologic system functions as a highly sensitive pressure transducer. Because of this, the ear is the most commonly affected organ in primary blast injury. Frequently encountered symptoms include hearing loss, tinnitus, and tympanic membrane perforations. The ear is repeatedly overlooked during triage and easily forgotten in subjects with multiple injuries after major catastrophic events such as explosions. This systematic review provides an overview of the most common otologic injuries observed after blast exposure in a variety of settings and populations. An analysis of 35 studies and an additional 23 reviews was performed in attempt to uncover patterns of otologic …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …

Paired Associative Transspinal And Transcortical Stimulation Produces Bidirectional Plasticity Of Human Cortical And Spinal Motor Pathways, Luke Dixon, Mohamed Ibrahim, Danielle Santora

Dissertations, Theses, and Capstone Projects

Anatomical, physiological, and functional connectivity exists between primary motor cortex (M1) and spinal cord neurons. Paired associative stimulation (PAS) produces enduring changes in M1 based on the Hebbian principle of associative plasticity. The present study aims to discover immediate neurophysiological changes on human corticomotor pathways by pairing noninvasive transspinal and transcortical stimulation via transcranial magnetic stimulation (TMS). We delivered paired transspinal and transcortical stimulation for 40-min at precise interstimulus intervals with TMS being delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Transspinal-transcortical PAS markedly decreased intracortical inhibition, increased intracortical facilitation and M1 excitability with concomitant decreases of motor …

The Relationship Between Lexical Performance And Regional Gray Matter Volumes: A Longitudinal Study Of Cognitively Healthy Elderly, Jungmoon Hyun

Dissertations, Theses, and Capstone Projects

This study investigated the longitudinal relationship among aging, performance on lexical tasks, and regional gray matter volumes over 2-7 years. A total of 137 older participants who remained cognitively normal were administered four lexical tasks at each time point: the Boston Naming Test (BNT), Vocabulary Test, Semantic- and Phonemic-Fluency task. In addition, they underwent repeated magnetic resonance imaging (MRI) scanning acquired within two months of the lexical tasks. The average interval between time points was 2.36 years (range 1.50-7.64) and the average number of time points was 2.65 times (range 2-5).

Results indicated that age differentially affects lexical task performance …

Tcr Alpha Lcr And Non-Lcr Cis-Elements Contributing To Tissue Specific Expression Of The Tcr Alpha Gene In Thymic And Peripheral T Cells, Martina Kucerova-Levisohn

Dissertations, Theses, and Capstone Projects

Orchestrated expression of multiple genes residing in the complex TCRα/δ/Dad1 locus requires tight control from multiple cis-acting elements. The TCRα locus control region (LCR), is positioned between TCRα and Dad1 gene, and has been implicated in the differential expression of both genes. In this study, we focus our work on the hypersensitive site (HS)1 prime (HS1'), located 3' of the classical Eα enhancer, within the TCRα LCR. We investigated its non- redundant role in TCRα expression in thymic and peripheral T cells as assayed by in vivo and in vitro studies. Furthermore, formation of HS1' in both lymphoid and …

An Ethnobotanical, Ecological And Lc-Ms-Based Chemometric Investigation Of Phaleria Nisidai, A Traditional Adaptogen Containing Diterpene Esters From Palau, Micronesia, Daniel Kulakowski

Dissertations, Theses, and Capstone Projects

An ethnobotanical, ecological and LC-MS-based chemometric investigation of Phaleria nisidai, a traditional adaptogen containing diterpene esters from Palau, Micronesia

Palau is a country with a rich heritage of traditional medicine still being practiced. One of the most popular and respected remedies in Palau is a tea made from fresh leaves of Phaleria nisidai Kaneh. (Thymelaeaceae). Interviews conducted to determine the use of this plant revealed that it is employed non-specifically to treat a variety of general health concerns. Its use as a prophylactic to keep away sickness, as a 'system cleaner', as well as for strength and energy indicate …

Quantitative Evaluation Of Microglial Activation And Vascularization In Suicide, Tatiana Pavlovna Schnieder

Dissertations, Theses, and Capstone Projects

Accumulated evidence points to immunological factors in psychiatric disorders. In a variety of chronic neurological disorders, exacerbation is associated with inflammation and a loss of integrity of the blood-brain barrier. Microglia, the principal brain immunological cells in the healthy state, respond to changes in the internal environment of the brain through a sequence of activated states. This study compared microglial phenotypes in the white matter of autopsy brains from 11 suicide victims and 25 subjects who died involuntarily. Both groups included cases with and without major psychiatric disorders, which were determined by PA interviews. Cases were matched for sex, age, …

Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois

Dissertations, Theses, and Capstone Projects

Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates, and is upregulated during commensal interactions, but is downregulated during active C. albicans infections[1]. An amyloid forming core sequence at residues 325-331 has been shown to be important for Als5p function, because a single amino acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence[2]. We evaluated the role of Als5p in host-microbe interactions, using Caenorhabditis elegans as a host model and feeding them Saccharomyces cerevisiae expressing …