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Interactions Between Repetitive Mild Traumatic Brain Injury and Methylphenidate Administration on Catecholamine Transporter Protein Levels Within the Rodent Prefrontal Cortex
Get PDFIt is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within in the prefrontal cortex (PFC) following traumatic brain injury (TBI) leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. Methylphenidate (MPH) is a psychostimulant drug used to treat symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following rmTBI has not.
To investigate this gap, we used the closed head-controlled cortical impact model to induce 3 mild injuries in Long Evans rats of both sexes. Rats received either saline or MPH (2mg/kg) daily for 7 days (4 groups; sham/saline, sham/MPH, rmTBI/saline, rmTBI/MPH). Brain tissue from the medial (mPFC) and orbitofrontal (OFC) regions of the PFC were collected and standard western blotting protocols were used to measure protein levels of NET, tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), catechol-O-methyltransferase (COMT) and monoamine oxidase (MOA). Within the mPFC, female NET and VMAT levels were decreased in the rmTBI/saline group, while the rmTBI/MPH group’s protein levels did not differ from controls. In males, mPFC VMAT levels were decreased in both rmTBI groups. Within the OFC, NET and VMAT levels were decreased in the male rmTBI/MPH group only.
These results suggest that rmTBI reduces transporter levels within regions of the PFC and that sub-chronic MPH treatment may produce restorative benefits on these protein levels in female, but not male rodents following rmTBI. We conclude that interactions between rmTBI and MPH on levels of catecholamine regulatory proteins may begin to elucidate sex differential changes in risk-taking behavior following injury and treatment
Investigation of the Utility of a PTSD Coaching Mobile App to Address Mental Health Services Demand in a Primary Care Clinic: Analysis of CAPS-5 Measures
Get PDFThe COVID-19 pandemic affected countless people globally, resulting in a greater need for mental health professionals and resources1. The demand for mental health care is soaring yet the limitation of resources has strained the healthcare system, making it challenging to help patients in a timely manner2. This poster represents a snapshot of a larger project that is striving to investigate an intervention to help bridge the gap between patient need and prompt referral through a warm handoff approach and use of the PTSD Coach mobile application as well as exploring patients’ satisfaction3,4,5,6,8,9. In this poster, we analyze several measures from the DSM-5 CAPS-5 to assess the efficacy of the PTSD Coach Mobile Application and we also determine the distribution of traumatic life events that patients experienced at intake as per the DSM-5 LEC-57,10. Compared to intake, we observed that patients at follow-up had decreases in the mean values of subjective distress and impairment in occupational functioning, but an increase in the mean value of impairment in social functioning. Furthermore, feedback we received from study participants revealed mixed opinions regarding the application as well as inconsistent usage due to a variety of factors. As this is an ongoing study, the team is continuing to actively recruit participants and upon completion explore further the efficacy of the app as well as the warm handoff approach to facilitating care. Please refer to the QR code on the poster for references
LEP Prevalence in Southern New Jersey and The Use of Interpreting Services in Healthcare Settings
Get PDFLanguage barriers pose a great challenge to populations of Limited English Proficiency (LEP) in understanding their health, diagnosis, and treatments in healthcare settings. Our research aimed to gain a better understanding of the language access needs in Southern New Jersey. We analyzed census data in order to determine the prevalence of LEP populations in Southern New Jersey, as well as the languages most spoken by LEP populations. Additionally, our research looked at the use of interpreting services in healthcare settings. In Camden county, specifically we found that the top 3 languages spoken by LEP populations were Spanish, Vietnamese, and Chinese. Through the Medscape Provider Survey, we also found that only 32% of providers ask patients about their language preferences, only 24% of providers indicated having a formal in-person or telephonic interpreting service, and 40% indicated asking family members of the patient to interpret as the main form of interpreting strategy. These results indicate a large prevalence of LEP populations in Southern New Jersey, especially Atlantic, Cumberland, and Camden county. While our research did not include an analysis of the language access resources made available in Southern New Jersey, one can beg the question of whether the interpreting services and language resources available match the prevalence of LEP populations in these communities. Our research on the use of interpreting services calls attention to the need to increase language accessibility in healthcare settings
“Lupus, Marijuana, and Takotsubo: A Perfect Storm”: An Unusual Presentation of Takotsubo Cardiomyopathy
Get PDFTakotsubo cardiomyopathy is a type of myocardial injury that is marked with left ventricular contraction dysfunction. Various regions of the left ventricular wall may exhibit hypokinetic or hypercontractile activity. There is no exact mechanism elucidated for Takotsubo cardiomyopathy, but it is often associated with a triggering stressful event that leads to a catecholamine surge. We describe a 38-year-old female who presented with typical Takotsubo cardiomyopathy, likely in the setting of worsening systemic lupus erythematosus (SLE) exacerbations and excessive cannabis use. The patient described her pain as a tight burning sensation that started on her right side and traveled to the retrosternal/epigastric region and her head. Notable lab values included UDS positive for amphetamines and cannabis, pro-BNP elevation at 1328 pg/mL, and Troponin T elevation at 29 ng/L. Rheumatologic findings were negative for anti-dsDNA and anti-Smith antibodies, but positive for ANA titers greater than 1:1280. A 2D echocardiogram showed an LVEF of 20-25%, apical akinesis and ballooning, and severe left ventricular systolic dysfunction. Prior to discharge, a loop recorder was placed, and the patient was restarted on ivabradine and put on LifeVest monitoring. She was advised to decrease her alcohol and cannabis use. A subsequent echocardiogram taken three months later showed an LVEF of 55-60%, indicating a return of normal cardiac function. We seek to emphasize the importance of minimizing SLE exacerbations in reducing systemic symptoms, as well as the need for further research on the relationships between SLE, heavy cannabis use, and Takotsubo cardiomyopathy
Review of Missing Data Elements for Client Enrollment in the Minority AIDS Initiative for High-Risk Men of NJ
Get PDFThe Minority AIDS Initiative study funded in NMI seeks to enhance healthcare outcomes for underserved individuals. Implementing outreach programs, the initiative provides healthcare and post-treatment follow-up to this demographic. The proposed project, a component of this study, concentrates on individuals with substance abuse disorder, specifically targeting those who have been onboarded but subsequently lost to follow-up. In the United States, approximately 20 million people are diagnosed with substance abuse disorder, yet in 2016, only 3.8 million received treatment. Within this cohort, between 20% and 70% of individuals undergoing residential substance abuse treatment disengage before completion. Various factors hinder the sustained retention of individuals with substance abuse disorder (SUD), encompassing biopsychosocial requirements like stable housing and employment, alongside strategies for long-term abstinence.1 Additionally, there\u27s a deficiency in incentives for continuous care, both economically and socially, exacerbating challenges for patients lacking robust social support or financial stability.2 A study by the U.S. Veterans Administration revealed a disparity between the perceived necessity for extended treatment and its implementation, with only 62% attempting to adhere to this recommendation.3 Particularly in minority communities, like African Americans and Latinos, higher rates of premature treatment discontinuation underscore the imperative for deeper investigations into contributing factors, including the potential influence of untreated co-occurring mental health conditions such as depression and anxiety.4, 5 Given these complexities, further research is indispensable to comprehensively grasp the reasons behind patient attrition in SUD treatment, necessitating an exploration of various socio-economic elements within this context
Review of Psychogenic Nonepileptic Seizures and Patient-Centered Approaches to Care
Get PDFPsychogenic nonepileptic seizures (PNES) are defined as involuntary experiential and behavioral responses to internal or external stimuli. They are behaviors, not associated with pathological alterations in the physiology of the brain. Although some of them mimic syncope, they have historically been regarded to clinically resemble epileptic episodes.
There is a multiplicity of different names for this condition. PNES is the most widely used term, though the term functional seizures is increasingly used. Alternatives such as psychogenic seizures, dissociative seizures, psychogenic nonepileptic attacks (PNEA), and nonepileptic seizures are also used
Emerin Deficiency Drives MCF7 Cells to an Invasive Phenotype
Get PDFDuring metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer cells showed similar results. Supporting the clinical relevance of emerin reduction in cancer progression, our analysis of 192 breast cancer patient samples showed emerin expression inversely correlates with cancer invasiveness. We conclude emerin loss is an important driver of invasive transformation and has utility as a biomarker for tumor progression
INTEGRATED COMPUTATIONAL APPROACHES: ELUCIDATING MOLECULAR MECHANISMS OF PATHOGENIC PROTEINS AND DESIGNING NOVEL INHIBITORS AGAINST MYCOBACTERIUM TUBERCULOSIS AND SARS-COV-2
No full textChapter 1 introduces computational strategies in computer aided drug design (CADD), focusing on physics-based methodologies to enhance drug discovery. This chapter also discusses the theoretical foundations and practical applications of molecular dynamics (MD) simulations including free energy and stochastic kinetic analysis. In Chapter 2, CADD methods lead to development of inhibitors targeting the RNA Dependent RNA Polymerase (RdRP) of SARS-CoV-2. Inspired by the nucleotide inhibitor Molnupiravir, we aim to design a combinatorial library of 72 novel inhibitors capable of impeding a dual threat inhibition mechanism inducing lethal mutations along with stalling viral replication with specific selectivity to RdRp over Human Polymerase II. In Chapter 3, we concentrate on the characterization of MmpL3, a crucial Resistance Nodulation Division (RND) transporter in MtB. Through molecular dynamics simulations, we gain a comprehensive understanding of MmpL3\u27s structural dynamics and conformational functionality. A significant aspect of this chapter involves investigating the inhibition mechanism of SQ109, an Anti-tuberculosis drug, with a specific focus on understanding it’s the conformational states of MmpL3 and allosteric inhibition effects induced by SQ109
Investigation of Process-Structure-Property Relationships in Additively Manufactured Chopped Fiber-Reinforced Polymer Composites
No full textFiber-reinforced polymer (FRP) composites are widely used in various industries because of their high stiffness-to-weight ratio. However, traditional manufacturing processes restrict the application of FRP composites to the production of parts with simple geometries. With the advent of additive manufacturing (AM), it is possible to produce topologically optimized parts with complex geometries using chopped FRPs. Fully leveraging the advantages of AM in the fabrication of chopped FRP parts requires a thorough understanding of the effect of the process parameters on the microstructure, and subsequently on the mechanical properties of the manufactured part. This research focuses on studying the process-structure-property (P-S-P) relationship in additively manufactured FRPs, particularly carbon fiber-reinforced polyamide composite, using a physics-based model integrated with experiments. The proposed framework consists of two steps: (1) Quantifying the effect of the process parameters on the microstructure using experiments (P-S relationship). (2) Determining the mechanical properties at the macroscale based on the microstructure using a physics-based model (S-P relationship). The macroscale properties predicted by the P-S-P framework at different process parameter settings are compared to observations from experiments to validate this approach. A MATLAB code is developed for the computational efficiency of the P-S and S-P linkage in the proposed framework. This framework will assist in tailoring the microstructure and macroscale properties of additively manufactured chopped FRP parts to meet requirements specific to the intended application
Redefining Culture and Climate in the Alternative Setting: Dumping Grounds or Where Students Are Found?
Get PDFThis autoethnographic study aims to answer the following questions: How can a school leader design a culturally sensitive, inclusive alternative education program? What type of systemic change does an alternative school leader believe to be most effective in supporting students in attaining a high school diploma and a solid postsecondary plan to become productive members of society? What characteristics of culture and climate are most critical in an alternative school setting? The study focused on 4 years and tells how a school leader successfully changed the school culture and climate to best serve students and staff in the alternative school setting. The study viewed these activities through research. Effective school culture can be identified through six factors, namely collaborative leadership, teacher collaboration, professional development, unity of purpose, collegial support, and learning partnership. The study also used Schein (2010) as a framework to gain a deeper understanding of culture. The educational field should find this study helpful as it can be replicated to improve student outcomes for the most vulnerable students