Medicine and Health Sciences Commons^™

Hiv-1 Transcription Elongation By Tat-Mediated Recruitment Of P-Tefb, Elizabeth Griggs

Honors Program: Senior Projects (Public)

Over 38.0 million people live with the human immunodeficiency virus (HIV) as of 462019. HIV hijacks the host's cellular machinery to replicate its viral DNA and transcribe the corresponding RNA. HIV-1 transcription relies on both cellular and viral transcription factors for proper regulation. The viral transcriptional activator Tat is a primary regulator. Transcription activation and elongation is controlled through the interaction of Tat with Positive Transcription Elongation Factor b (P-TEFb), a cellular transcriptional activator. The focus of this paper is 1) an in-depth understanding of the interaction between P-TEFb and Tat in HIV transcription, and 2) a review of recent …

Social Determinants Of Health Correlating With Mechanical Ventilation Of Covid-19 Patients; A Multi-Center Observational Study, Alexa Giovanatti, Heba Elassar, Patrick Karabon, Tracy Wunderlich-Barillas, Alexandra Halalau

Conference Presentation Abstracts

Importance: Several studies have relayed the disproportionate impact of COVID-19 on marginalized communities, however few have specifically examined the association between social determinants of health and mechanical ventilation (MV). Objective: To determine which demographics impact MV rates among COVID-19 patients. Design: This observational study included COVID-19 patient data from eight hospitals’ EMR between February 25, 2020 to December 31, 2020. Associations between demographic data and MV rates were evaluated using uni- and multivariate analyses. Setting: Multicenter (8 hospitals), largest health system in Southeast Michigan Participants: Inpatients with a positive RT-PCR for SARS-CoV-2 on nasopharyngeal swab. Exclusion criteria were missing demographic …

Intracardiac Leiomyomatosis Presenting As Syncope, Ujjwal Karki, Bijaya Thapa, Shailesh Niroula, Bipin Ghimire, Tucker Billups, Shrinjaya Thapa

Conference Presentation Abstracts

Primary cardiac tumors are rare, with incidence less than 0.1 percent. Secondary tumors are 20 times more common. Tumor thrombus extending to the right heart is commonly seen with renal cell carcinoma. Less common etiologies include intravenous leiomyoma, gynecological malignancies, Wilms tumor, hepatoma, and adrenocortical carcinoma. 46-year-old female with history of uterine fibroid presented with two episodes of syncope, lasting 30 seconds each. Echocardiogram revealed a mobile echogenic mass in right atrium extending from the inferior vena cava (IVC) and moving across the tricuspid valve, causing dynamic obstruction. Cardiac MRI showed the mass originated from the renal vein with similar …

Gallstone Ileus Complicating Rectal Cancer: A Red Herring Cause Of Abdominal Pain, Nicholas Lazar, Ovidiu Niculescu, Carol Lima, Neiberg Lima

Conference Presentation Abstracts

A 68-year-old male with a history of alcohol abuse presented with a one-week history of fatigue and weakness, and a one-year history of fecal incontinence. On admission, vital signs were stable. Physical exam revealed cachexia, skin pallor, and mild abdominal distention. Fecal occult blood testing was positive. Laboratory analysis was significant for hemoglobin of 6.8g/dL. Of note, computed tomography (CT) scans of his chest, abdomen, and pelvis done months prior for evaluation of anemia and incontinence had shown rectal wall thickening, lung nodules concerning for metastasis, and gallstones. He declined further diagnostic evaluation and was lost to follow up. During …

Bleeding From The Holes In The Theory: How Flawed Deterrence In Federal Tort Claims Enables Police Brutality, Andrew Reisman

Cardozo Journal of Equal Rights & Social Justice

The note argues that federal tort laws, particularly the Federal Tort Claims Act (FTCA) and Bivens actions, are ineffective in deterring police brutality due to structural flaws that prevent individual accountability. It proposes reforms to strengthen these legal mechanisms and promote transparency and accountability within federal law enforcement agencies.

What Factors Predict An Anesthesiologist’S Willingness To Proceed With An Anesthetic?, Nadine K. Ragbir

Doctoral Dissertations and Master's Theses

Anesthesiologists are exposed to higher stress levels than many other physician specialties. They are also at an increased risk for developing mental disorders, alcohol and drug dependencies, sleep disturbances, and suicidal ideations. Therefore, the purpose of this dissertation was to explore the factors that predict an anesthesiologist’s willingness to proceed with an anesthetic. The current study consisted of two stages. The first stage was developing a regression equation that was used to predict anesthesiologists’ willingness to proceed with an anesthetic. During the second stage, additional data was collected to test the model that was developed in the first stage. Six …

Development And Validation Of A Framework To Improve Neglected Tropical Diseases Surveillance And Response At Sub-National Levels In Kenya, Arthur K.S. Ng’Etich, Kuku Voyi, Clifford M. Mutero

All Peer-Reviewed Publications

Background Assessment of surveillance and response system functions focusing on notifiable diseases has widely been documented in literature. However, there is limited focus on diseases targeted for elimination or eradication, particularly preventive chemotherapy neglected tropical diseases (PC-NTDs). There are limited strategies to guide strengthening of surveillance and response system functions concerning PC-NTDs. The aim of this study was to develop and validate a framework to improve surveillance and response to PC-NTDs at the sub-national level in Kenya. Methods A multi-phased approach using descriptive cross-sectional mixed-method designs was adopted. Phase one involved a systematic literature review of surveillance assessment studies to …

A Global-Scale Expert Assessment Of Drivers And Risks Associated With Pollinator Decline, Lynn V. Dicks, Tom D. Breeze, Hien T. Ngo, Deepa Senapathi, Jiandong An, Marcelo A. Aizen, Parthiba Basu, Damayanti Buchori, Leonardo Galetto, Lucas A. Garibaldi, Barbara Gemmill-Herren, Brad G. Howlett, Vera L. Imperatriz-Fonseca, Steven D. Johnson, Anikó Kovács-Hostyánszki, Yong Jung Kwon, H. Michael G. Lattorff, Thingreipi Lungharwo, Colleen L. Seymour, Adam J. Vanbergen, Simon G. Potts

All Peer-Reviewed Publications

Pollinator decline has attracted global attention and substantial efforts are underway to respond through national pollinator strategies and action plans. These policy responses require clarity on what is driving pollinator decline and what risks it generates for society in different parts of the world. Using a formal expert elicitation process, we evaluated the relative regional and global importance of eight drivers of pollinator decline and ten consequent risks to human well-being. Our results indicate that global policy responses should focus on reducing pressure from changes in land cover and configuration, land management and pesticides, as these were considered very important …

Bioactive Nanotherapeutic Trends To Combat Triple Negative Breast Cancer, Pallabita Chowdhury, Upasana Ghosh, Kamalika Samanta, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical …

Interferon Gamma Release Assays For Detection Of Latent Mycobacterium Tuberculosis In Older Hispanic People, Julia M. Scordo, Genesis P. Aguillón-Durán, Doris Ayala, Ana Paulina Quirino-Cerrillo, Eminé Rodriguez-Reyna, Mateo Joya-Ayala, Francisco Mora-Guzmán, Eder Ledezma-Campos, Alejandro Villafañez, Larry S. Schlesinger, Blanca I. Restrepo

School of Medicine Publications

Background: Interferon gamma release assays (IGRAs) are used to detect latent Mycobacterium tuberculosis (M.tb) infection (LTBI) in adults, but their performance in older people is not well-established. We evaluated IGRAs for LTBI detection in older Hispanic recent TB contacts (ReC) or community controls (CoC).

Methods: Cross-sectional assessment of LTBI with T-SPOT.TB and/or QuantiFERON-Gold in-tube or -Plus assay in older (≥60 years) and adult (18-50 years) Hispanic people.

Results: We enrolled 193 CoC (119 adults, 74 older persons) and 459 ReC (361 adults, 98 older persons). LTBI positivity increased with age in CoC (19%-59%, P<0.001), but was similar in ReC (59%-69%, P=0.329). Older people had lower concordance between IGRAs (kappa 0.465 vs 0.688 in adults) and more inconclusive results (indeterminate/borderline 11.6% vs 5.8% in adults, P=0.012). With simultaneous IGRAs, inconclusive results were resolved as positive or negative with the other IGRA. The magnitude of response to M.tb peptides in IGRAs was similar among age groups, but responsiveness to mitogens was lower in older people.

Conclusions: IGRAs are suitable for LTBI …

Friends And Foes: Extracellular Vesicles In Aging And Rejuvenation, Brian V Lananna, Shin-Ichiro Imai

2020-Current year OA Pubs

Extracellular vesicles (EVs) are released by many different cell types throughout the body and play a role in a diverse range of biological processes. EVs circulating in blood as well as in other body fluids undergo dramatic alterations over an organism's lifespan that are only beginning to be elucidated. The exact nature of these changes is an area of active and intense investigation, but lacks clear consensus due to the substantial heterogeneity in EV subpopulations and insufficiencies in current technologies. Nonetheless, emerging evidence suggests that EVs regulate systemic aging as well as the pathophysiology of age-related diseases. Here, we review …

Neutralisation Of Sars-Cov-2 Lineage P.1 By Antibodies Elicited Through Natural Sars-Cov-2 Infection Or Vaccination With An Inactivated Sars-Cov-2 Vaccine: An Immunological Study, William M Souza, Michael S Diamond, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response.

METHODS: We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) …

White Matter Plasticity In Healthy Older Adults: The Effects Of Aerobic Exercise, Andrea Mendez Colmenares, Michelle W Voss, Jason Fanning, Elizabeth A Salerno, Neha P Gothe, Michael L Thomas, Edward Mcauley, Arthur F Kramer, Agnieszka Z Burzynska

2020-Current year OA Pubs

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60-79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions …

Intra- And Inter-Tumoral Heterogeneity Of Liver Metastases In A Patient With Uveal Melanoma Revealed By Single-Cell Rna Sequencing, Weitao Lin, Aaron Beasley, Nima Mesbah Ardakani, Elena Denisenko, Leslie Calapre, Matthew Jones, Benjamin Woods, Lydia Warburton, Alistair R.R. Forrest, Elin S. Gray

Research outputs 2014 to 2021

Tumour heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition of tumour heterogeneity is critical in the clinical management of cancer patients. Here, we utilised single-cell RNA sequencing (scRNA-seq) to uncover the intra- and inter-tumoural heterogeneity of liver metastases from a patient with metastatic uveal melanoma. The two metastases analysed were largely infiltrated by non-cancerous cells with significant variability in the proportion of different cell types. Analysis of copy number variations (CNVs) showed gain of 8q and loss of 6q in both tumours, but loss of chromosome 3 was only detected in one …

Challenges In Treating Cancer Patients With Unstable Psychiatric Disorder, Val Bellman, Nina Russell, Kartik Depala, Alexandra Dellenbaugh, Saral Desai, Ramu Vadukapuram, Shweta Patel, Sushma Srinivas

School of Medicine Publications

In this review, we first present a case of chronic myeloid leukemia with acute psychosis, and then we will discuss the incidence of cancer in patients with psychotic disorders, the manifestations of new-onset psychosis, and the prevalence of preexisting psychosis in cancer patients, coupled with their impact on the treatment, diagnosis, and prognosis of cancer. This was a case that presented with acute psychosis and was found to have an elevated white blood cell count upon admission to an inpatient psychiatric unit. He was diagnosed with chronic myeloid leukemia and successfully managed with imatinib/dasatinib therapy. Psychiatrically, he was stabilized on …

Impact Of Home Garden Interventions In East Africa: Results Of Three Randomized Controlled Trials, Lutz Depenbusch, Pepijn Schreinemachers, Ralph Roothaert, Sylvia Namazzi, Charles Onyango, Sophia Bongole, James Mutebi

All Peer-Reviewed Publications

Sub-Saharan Africa has the lowest per capita consumption of vegetables of all regions in the world. As low vegetable consumption is associated with poor human health, there is need for effective policies and interventions to increase it. Home garden interventions have proven effective in several countries in Asia, but evidence from large trials is scant in Africa. Using data from a home garden promotion project in Kenya, Tanzania and Uganda, this study tests the hypothesis that home garden interventions, offered to rural households with women 14–35 years of age and/or with children under five years of age, increase household production …

Contribution Of The Ledgf/P75 Protein Interactome To Prostate Cancer Chemoresistance, Greisha Lee Ortiz Hernández

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate Cancer (PCa) progression leads to an advanced stage called metastatic castration resistant PCa (mCRPC), for which currently there is no cure in spite of advances in treatment with new generation anti-androgen drugs and chemotherapy with taxanes such as docetaxel (DTX). Our laboratory demonstrated previously that the stress oncoprotein Lens Epithelium Derived Growth Factor of 75 kD (LEDGF/p75) is upregulated in clinical prostate tumors and contributes to DTX-resistance in mCRPC cells. However, little is known about the molecular mechanisms by which LEDGF/p75 promotes taxane resistance. The C-terminus of LEDGF/p75 contains a domain called the Integrase Binding Domain (IBD), which in …

Telework Intensity, Work-Family Conflict, And Work-Family Balance, During The Covid-19 Pandemic, Timir Jayesh Bharucha

Dissertations

The COVID-19 pandemic has led to increased popularity, application, and utilization of telework. To vastly reduce the spread of COVID-19, governmental agencies worldwide have implemented lockdowns and emphasized businesses and corporations should implement telework wherever possible (Anderson & Kelliher, 2020; Belzunegui- Eraso & Erro-Garces, 2020; Buomprisco et al., 2021; Chong et al., 2020; Contreras et al., 2020; Mouratidis & Papagiannakis, 2021; Nguyen, 2021; Oz & Crooks, 2020; Raišienė et al., 2020; Tavares et al., 2020). States of emergency can disturb employees’ workflow and lead to financial difficulties; thus, telework presents an option to reduce that disruption. In such unprecedented times, …

Impact Of Counselor Wellness On Positive And Negative Consequences Of Covid-19 Shared Trauma, Monique Rahman

Dissertations

This study sought to explore how the shared trauma of the COVID-19 pandemic has impacted Texan counselors both positively and negatively, as well as the mediating or moderating effect of counselor wellness. Negative consequences of stress such as secondary traumatic stress, burnout and compassion fatigue were explored, but also positive consequences such as compassion satisfaction and post-traumatic growth. Measures such as the Five Factor Wellness Inventory (FFWEL), the Shared traumatic and Professional Posttraumatic Growth Inventory (STPPGI), and the Professional Quality of Life Measure (ProQOL) will be utilized in addition to demographic questions and COVID-19 stress related questions mirroring Park et …

Preliminary Findings Of A Study On The Practice Of Self-Medication Of Antibiotics Among The Practicing Nurses Of A Tertiary Care Hospital, Akbar Shoukat Ali, Rahim Jandani, Arwa A. Al-Qahtani, Abdulkarem A S. Alenzi

Department of Medicine

Objectives: Antibiotic resistance is indeed a global concern. It is of significant concern especially in the low-middle income countries because of the ease of accessibility, affordability, and absence of regulations pertaining to the dispensing of non-prescription antibiotics. This study aims to estimate the frequency and factors associated with the self-medication of antibiotics found among the practicing nurses.
Methods: We conducted a descriptive cross-sectional study at a tertiary care hospital in Karachi, Pakistan from July 2016 to August 2016.
Results: Of the 48 recruited nurses, 60.4% (29/48) were practicing self-medication of antibiotics. There were slightly more male nurses (17/29) than their …

Impact Of Acetylcholine On Amygdala Network Oscillations, Joshua Xavier Bratsch-Prince

Theses and Dissertations

The ability to appropriately respond to and store memories of emotionally salient events is a critical feature of survival. The basolateral amygdala (BLA) is a temporal lobe structure that is essential in mediating emotional behaviors, learning, and memory. Important to circuit function are synchronized neuronal oscillations. Different oscillatory signatures are implicated in mediating different aspects of behavior and learning and memory processes: theta frequency (3-12 Hz) oscillations represent “online” states and are important for information encoding and learning, and sharp wave ripples (SWRs) represent more “offline” states that are important for the consolidation of memory. In the BLA, both of …

Advancing Knowledge Of Exercise As A Therapeutic Management Strategy For Women With Polycystic Ovary Syndrome, Pamela J. Wright

Theses and Dissertations

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among premenopausal women with a prevalence that ranges 15-21%. The estimated financial burden in the United States for evaluating and treating premenopausal women with PCOS was over $8 billion in 2020. PCOS etiology is complex and poorly understood, as is the optimal treatment and management. Endocrine Society Clinical Practice Guidelines recommend exercise as first-line treatment. Yet, the optimal exercise type and “dosing” are not defined. As last reported for women with PCOS, less than 60% are regularly physically active and more than 25% are sedentary. Additionally, little to no published data …

Real Time Neurochemical Analysis Of The Brain For Pharmacological Treatments In Mood Disorders And Neurodegeneration, Anna Marie Buchanan

Theses and Dissertations

The monoamine, serotonin, is an important modulator in the central nervous system. It is believed to participate in a variety of functions ranging from moderating stress, promoting brain plasticity, and regulating sleep and appetite. Dysfunction of the serotonergic system has also been implicated in mood disorders and neurodegenerative diseases. While serotonin is of great interest to the research community, real-time in vivo serotonin dynamics remain understudied. This is because direct measurement of fast serotonergic transmission is analytically challenging. In 2009, the Hashemi lab pioneered the direct measurement of endogenously evoked serotonin using a method called fast scan cyclic voltammetry (FSCV). …

Evaluating The Health Impact Of Centeringpregnancy Program Versus Traditional Prenatal Care In Midland Obstetric Clinics And Validating Selected Item On Birth Certificate, Oluwatosin A. Momodu

Theses and Dissertations

The primary focus of this dissertation is to evaluate the health impact of the CenteringPregnancy (CP) program versus traditional prenatal care (TPNC) on important maternal outcomes of pregnancy. This is looked at in two outcomes-gestational weight gain (GWG) and pregnancy induced hypertension (PIH). The specific aims are to examine the: (1) effects of CenteringPregnancy program versus traditional prenatal care on gestational weight gain (GWG); (2) effects of CenteringPregnancy program versus traditional prenatal care on pregnancy induced hypertension (PIH).

Birth certificate (BC) data were linked to hospital discharge records of women who delivered in midland’s obstetric clinics of South Carolina between …

Food Choice Decision-Making Among School-Going Adolescents Amidst The Nutrition Transition In Urban Accra, Ghana, Krystal Krsna Rampalli

Theses and Dissertations

Like many countries of the world, Ghana is experiencing a nutrition transition and rising non-communicable diseases. Adolescents are susceptible to diet-related health risks as they experience significant physical and psychological changes, which are happening in tandem with food environment changes, including widespread proliferation of large portion and package sizes of energy-dense, nutrient-poor foods. Both local and multinational food and beverage companies have encouraged consumption of their products through various marketing tactics targeted directly to adolescents. Some of these tactics include the use of characters or celebrity endorsement, promotional discounts, and appeal to sociocultural values, including messages about body size preferences. …

Pre-Exposure Prophylaxis (Prep) Knowledge, Willingness To Use & Uptake Among Black Heterosexual Men, Akeen Lowell Hamilton

Theses and Dissertations

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is a pill, taken orally, that has been shown to be effective at reducing the chance that someone who is HIV-negative and at-risk for HIV will contract the disease during sexual intercourse with someone who is living with HIV. One demographic group that has been under-researched is Black heterosexual men. This dissertation presents research on evaluating the heterosexual Black men’s awareness of, prior use, and network of friends/family’s perceived interest in learning more about PrEP.

METHODS: Two-hundred and six Black heterosexual men living in Brooklyn, New York City, were surveyed about their sexual behaviors and PrEP …

Utilization Of Remote Sensing To Analyze Aedes Mosquito Egg Abundance With Combined Weather Variables In Two Southeastern Coastal Cities, Danielle M. Johnson

Theses and Dissertations

Several vector-borne diseases have recently resurfaced, and many have suddenly spread to new areas in the United States (U.S.) due to climate change and tropicalization. Two vectors of public health importance are Aedes aegyptiand Aedes albopictus. The Southeastern region of the U.S. appears to be a preferential ecological niche for both Aedes species. Aedes aegyptiand Aedes albopictus are highly susceptible to environmental conditions, such as humidity, precipitation, temperature. Remote sensing technology has proven to be useful for estimating vector populations. Miami-Dade County is an established hotspot for disease transmission. Charleston County is newly vulnerable due to similar …

Variations In Er Stress And Unfolded Protein Response Predict Disease Susceptibility, Youwen Zhang

Theses and Dissertations

Numerous studies linked endoplasmic reticulum (ER) stress and unfolded protein response (UPR) to physiological responses to stress and various human pathologies, including metabolic disorders. Although variability in stress responses among individuals has been widely recognized, how such variations in the UPR affect susceptibility to diseases remains unknown. Using outbred deer mice as a model, we explored the consequences of the differential propensity to UPR at the transcriptomic, cellular, and organismic level.

Initially, we analyzed the correlation between several UPR-related genes in primary fibroblasts, at the whole transcriptome level, after ER stress induction. The analysis of correlated transcripts revealed that their …

The Development Of Novel Cdk8 And Cdk19 Inhibitors And Degraders As Potential Anti-Cancer Agents, Li Zhang

Theses and Dissertations

CDK8 and its homolog CDK19 are essential for transcription regulation and their dysregulation has been identified in numerous diseases, especially in cancers. CDK8 and CDK19 have been implicated in cancer development through their kinase activity and kinase independent functions. Despite the existing CDK8/19 inhibitors, there is still a need to develop novel CDK8/19 inhibitors with improved potency and PK profile. It is also necessary to develop CDK8/19 degraders that are able to eliminate the kinase-independent functions. Although two CDK8-degrading PROteolysis Activating Chimeras (PROTACs) have been reported, they have limited CDK8 degradation efficacy and no effect on CDK19. PROTACs with improved …

The Association Of Antidepressants Use With Healthcare Utilization, Patient-Reported Outcomes, And Alzheimer's Disease And Related Dementias (Adrd) Among Medicare Beneficiaries With Depression, Abdulrahman Abdullah A Alnijadi

Theses and Dissertations

Background: Depression and Alzheimer's Disease and Related Dementias (ADRD) are common among older adults. Currently, depression is recognized as one of the risk factors for ADRD. There is conflicting evidence on the association between depression and ADRD. Inadequate detection, diagnosis, and management of depression appear to pose a significant risk to the quality of life and healthcare utilization among older adults. To date, there are few studies on the impact of depression on self-reported healthcare utilization and self-reported health outcomes among Medicare beneficiaries.

Objectives: The aims of this study were to (1) quantify the association between depression and ADRD, quality …