Translational Medical Research Commons^™

Augmented Immunomodulation Of Endogenous Marrow-Derived Stem Cells In The Setting Of Acl Rupture, Mackenzie Fleischer, Michael Newton, Samantha Hartner, John A. Driscoll, Anthony Arveschoug, Chritopher C. Vasileff, Kevin Baker

Conference Presentation Abstracts

PURPOSE: Augmentation of MSC immunomodulation is an unexplored, potentially useful therapeutic to combat PTOA following ACLR. Lower kynurenine-to-tryptophan ratios observed in synovial fluid of ACL rupture (ACLR) rats suggests decreased activity of tryptophan metabolizing enzyme, Ido, known to be secreted by MSCs to promote T-reg expansion and Th17 suppression. This study aims to characterize the immunomodulatory capacity of pharmacologically mobilized MSCs in conjunction with exogenously delivered Ido. METHODS: Rats (N = 48) underwent ACLR to evaluate the effects of mobilized MCSs on Ido1 and inflammatory cytokine expression profiles in the synovial fluid. Additionally, rats (N = 160) underwent ACLR to …

Evaluating Simulation-Based Tobacco Treatment Scenarios For Providers Delivering Treatment For People Living With Mental Illnesses, Chizimuzo T. C. Okoli, Janet Otachi, Sarret Seng, Bassema Abufarsakh, Lovoria B. Williams

Clinical and Translational Science Faculty Publications

Background: People living with mental illnesses (PMI) experience elevated tobacco use and related morbidity and mortality. Despite the availability of effective and safe tobacco treatments along with evidence that PMI are motivated and able to quit successfully, few Mental and behavioral healthcare providers (MHPs) engage PMI in such treatment. MHPs may lack the confidence or skills to engage their clients in tobacco treatment. Currently, there are limited training modalities to prepare MHPs in delivering tobacco treatment for PMI. However, animated scenario-based simulated encounters can bridge this gap to effectively provide tailored MHP training to enhance treatment delivery. Hence, the purpose …

Tumor Suppressor Par-4 Regulates Complement Factor C3 And Obesity, Nathália Araujo, James Sledziona, Sunil K. Noothi, Ravshan Burikhanov, Nikhil Hebbar, Saptadwipa Ganguly, Tripti Shrestha-Bhattarai, Beibei Zhu, Wendy S. Katz, Yi Zhang, Barry S. Taylor, Jinze Liu, Li Chen, Heidi L. Weiss, Daheng He, Chi Wang, Andrew J. Morris, Lisa A. Cassis, Mariana N. Nikolova‑Karakashian, Prabhakara R. Nagareddy, Olle Melander, B. Mark Evers, Phillip A. Kern, Vivek M. Rangnekar

Clinical and Translational Science Faculty Publications

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4^-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4^-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed …

Aorta In Pathologies May Function As An Immune Organ By Upregulating Secretomes For Immune And Vascular Cell Activation, Differentiation And Trans-Differentiation-Early Secretomes May Serve As Drivers For Trained Immunity, Yifan Lu, Yu Sun, Keman Xu, Fatma Saaoud, Ying Shao, Charles Drummer, Sheng Wu, Wenhui Hu, Jun Yu, Satya P Kunapuli, John R Bethea, Roberto I Vazquez-Padron, Jianxin Sun, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

To determine whether aorta becomes immune organ in pathologies, we performed transcriptomic analyses of six types of secretomic genes (SGs) in aorta and vascular cells and made the following findings: 1) 53.7% out of 21,306 human protein genes are classified into six secretomes, namely, canonical, caspase 1, caspase 4, exosome, Weibel-Palade body, and autophagy; 2) Atherosclerosis (AS), chronic kidney disease (CKD) and abdominal aortic aneurysm (AAA) modulate six secretomes in aortas; and Middle East Respiratory Syndrome Coronavirus (MERS-CoV, COVID-19 homologous) infected endothelial cells (ECs) and angiotensin-II (Ang-II) treated vascular smooth muscle cells (VSMCs) modulate six secretomes; 3) AS aortas upregulate …

Pkcε Activation Restores Loss Of Pkcε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, And Microvessels In Aged And Alzheimer's Disease Hippocampus, Guetchyn Millien, Huaixing Wang, Zongxiu Zhang, Dan L Alkon, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

Vascular endothelial dysfunction and capillary loss are currently considered to be a primary phenotype of normal human aging and Alzheimer's disease (AD). Activation of protein kinase C (PKCε) improves several molecular, cellular, physiological, and behavioral endpoints, yet it is not known whether a loss of PKCε activity occurs in the microvascular endothelium in aged and AD hippocampi, whether this loss contributes to microvascular change, or whether activation of PKCε protects against microvascular damage, an early change that induces age-associated memory defect and AD. We investigated the effect of the PKCε activation on microvascular loss in the hippocampus, important for memory …

Pulmonary Post-Acute Sequelae Of Covid-19, Usman Akbar, Shivam Gulati, Johnny Zakhour Md, Alex Glynn, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Introduction: Persistent symptoms have been observed in a substantial proportion of survivors of COVID-19 since relatively early in the pandemic. Among these post-acute sequelae of COVID-19 (PASC), respiratory symptoms appear to be the most prevalent.

Methods: We conducted a literature review of peer-reviewed publications in English on the clinical and epidemiological features of respiratory PASC in cohorts of 100 or more patients with a follow-up of four weeks or more after acute infection. Included studies reported the prevalence of persistent respiratory symptoms and/or the results of follow-up pulmonary function tests.

Results: On our review included 14 studies across eight countries …

Abi1 Mediates Airway Smooth Muscle Cell Proliferation And Airway Remodeling Via Jak2/Stat3 Signaling, Ruping Wang, Yinna Wang, Guoning Liao, Bohao Chen, Reynold A. Panettieri, Jr., Raymond B. Penn, Albany Medical College

Center for Translational Medicine Faculty Papers

Asthma is a complex pulmonary disorder with multiple pathological mechanisms. A key pathological feature of chronic asthma is airway remodeling, which is largely attributed to airway smooth muscle (ASM) hyperplasia that contributes to thickening of the airway wall and further drives asthma pathology. The cellular processes that mediate ASM cell proliferation are not completely elucidated. Using multiple approaches, we demonstrate that the adapter protein Abi1 (Abelson interactor 1) is upregulated in ∼50% of ASM cell cultures derived from patients with asthma. Loss-of-function studies demonstrate that Abi1 regulates the activation of Jak2 (Janus kinase 2) and STAT3 (signal transducers and activators …

Compliance With Guidelines For Treatment Of Staphylococcus Aureus Bacteremia Is Associated With Decreased Mortality In Patients Hospitalized For Community-Acquired Pneumonia With Staphylococcus Aureus Bacteremia, Leslie Beavin, Vidyulata Salunkhe, Shashvin Singh, Ahmed Gana, Balaji Sekaran, Mahder A. Tella, Stephen P. Furmanek, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Introduction: Staphylococcus aureus bacteremia has a minimum treatment duration of two weeks, while S. aureus community-acquired pneumonia (CAP) treatment is at least five days. Treatment failure, persistent bacteremia, and recurrence are common among patients with community-acquired S. aureus bacteremia. There is conflicting information in the current Infectious Diseases Society of America (IDSA) guidelines for the treatment of S.aureus bacteremia patients with CAP. Therefore, the appropriate treatment duration and modality for S. aureus CAP with bacteremia is unclear. The objective of this study was to compare outcomes among patients with S. aureus CAP and bacteremia treated in compliance versus non-compliance with …

Spatial Transcriptomics Of Dorsal Root Ganglia Identifies Molecular Signatures Of Human Nociceptors, Diana Tavares-Ferreira, Stephanie Shiers, Pradipta R Ray, Andi Wangzhou, Vivekanand Jeevakumar, Ishwarya Sankaranarayanan, Anna M Cervantes, Jeffrey C Reese, Alexander Chamessian, Bryan A Copits, Patrick M Dougherty, Robert W Gereau, Michael D Burton, Gregory Dussor, Theodore J Price

Faculty, Staff and Student Publications

Nociceptors are specialized sensory neurons that detect damaging or potentially damaging stimuli and are found in the dorsal root ganglia (DRG) and trigeminal ganglia. These neurons are critical for the generation of neuronal signals that ultimately create the perception of pain. Nociceptors are also primary targets for treating acute and chronic pain. Single-cell transcriptomics on mouse nociceptors has transformed our understanding of pain mechanisms. We sought to generate equivalent information for human nociceptors with the goal of identifying transcriptomic signatures of nociceptors, identifying species differences and potential drug targets. We used spatial transcriptomics to molecularly characterize transcriptomes of single DRG …

29 M 6 A-Rna Methylation (Epitranscriptomic) Regulators Are Regulated In 41 Diseases Including Atherosclerosis And Tumors Potentially Via Ros Regulation - 102 Transcriptomic Dataset Analyses, Ming Liu, Keman Xu, Fatma Saaoud, Ying Shao, Ruijing Zhang, Yifan Lu, Yu Sun, Charles Drummer Iv, Li Li, Sheng Wu, Satya P Kunapuli, Gerard J Criner, Jianxin Sun, Huimin Shan, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; …

Clinical Outcomes For Patients With Community-Acquired Pneumonia Are Worse In Those With A History Of Stroke, Pradeepthi Badugu, Dilip Kc, Bibodh Jung Karki, Mahder A. Tella, Vidyulata Salunkhe

The University of Louisville Journal of Respiratory Infections

Background: Stroke is one of the most prevalent neurological diseases in the United States. Community-acquired pneumonia (CAP) is the leading cause of infections in survivors of stroke. There is limited research evaluating the clinical outcomes of CAP in patients with stroke. The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients with CAP and a history of stroke.

Methods: This was a secondary analysis of the University of Louisville Pneumonia Study database. Patients were divided into two groups based on the presence or absence of a history of stroke. Clinical outcomes were length of …

Ovarian Cancer G Protein-Coupled Receptor 1 Inhibits A549 Cells Migration Through Casein Kinase 2Α Intronless Gene And Neutral Endopeptidase, Adhikarimayum Lakhikumar Sharma, Puyam Milan Meitei, Takhellambam Chanu Machathoibi, Naorem Tarundas Singh, Thiyam Ramsing Singh, Lisam Shanjukumar Singh

Center for Translational Medicine Faculty Papers

Background: We have previously reported that a new intronless gene for casein kinase 2α (CK2α), CSNK2A3, is expressed in human cells. The promoter of the well-known CK2α, CSNK2A1, displays characteristics of a housekeeping gene, whereas CSNK2A3 has a characteristic of a regulated promoter with two TATA boxes and a CAAT box. GPR68, a family of the G protein-coupled receptors, is also known as ovarian cancer G protein-coupled receptor 1 (OGR1). In the current study, we analyzed the roles of CK2α genes and neutral endopeptidase (NEP), a key enzyme that influences a variety of malignancies, in the OGR1-induced inhibition of A549 …

Retraction Note: Obesity-Induced Adipokine Imbalance Impairs Mouse Pulmonary Vascular Endothelial Function And Primes The Lung For Injury, Dilip Shah, Freddy Romero, Michelle Duong, Nadan Wang, Bishnuhari Paudyal, Benjamin T Suratt, Caleb B Kallen, Jianxin Sun, Ying Zhu, Kenneth Walsh, Ross Summer

Center for Translational Medicine Faculty Papers

The Authors have retracted this Article. Afer publication of this Article, concerns have been raised about irregularities in the western blot data. In particular, the following bands appear to be duplicated: – Fig. 1e HFD/p-Src lane 1 and 3; – Fig. 4c NCD/Ve-cadherin lane 1 and 3 – Fig. 5e HFD+APN/ICAM-1 lane 1 and 2 – Fig. 5f HFD/beta-catenin lane 2 and HFD+APN/beta-catenin lane 1 – Fig. S1d HFD/beta-catenin all lanes – Fig. S4c NCD/beta-catenin lane 1 and 3. Additionally, the beta-catenin subpanel in Fig. 5f was subsequently reused in another study [1] and described as showing GRP87. Te Authors …

Regulatory T Cells Control Effector T Cell Inflammation In Human Prediabetes, Rui Liu, Gabriella H. Pugh, Erin Tevonian, Katherine Thompson, Douglas A. Lauffenburger, Philip A. Kern, Barbara S. Nikolajczyk

Clinical and Translational Science Faculty Publications

A disparate array of plasma/serum markers provides evidence for chronic inflammation in human prediabetes, a condition that is most closely replicated by standard mouse models of obesity and metaflammation. These remain largely nonactionable and contrast with our rich understanding of inflammation in human type 2 diabetes. New data show that inflammatory profiles produced by CD4+ T cells define human prediabetes as a unique inflammatory state. Regulatory T cells (Treg) control mitochondrial function and cytokine production by CD4+ effector T cells (Teff) in prediabetes and type 2 diabetes by supporting T helper (Th)17 or Th1 cytokine production, respectively. These data suggest …

Path To Publication: A Peer Mentorship Model For Student-Lead Surgical Research, Usama Waqar, Hareem Rauf, Muskaan Abdul Qadir, Hina Inam

Medical College Documents

Early and sustained involvement in research is imperative for medical students to ensure better career prospects in addition to provision of high-quality, evidence-based care to patients. However, involvement of students in surgical research still remains limited, owing to inadequate research training. The current paper was planned to describe the structure of the "Path to Publication" series, incorporating peer mentorship with capacity-building research workshops for medical students. A total of 25 students were grouped into 8 surgical subspecialty groups to conduct research, supervised by experienced student research and faculty mentors. In addition, a series of research workshops were organized in synchronization …

Medical Management Of Infants With Supraventricular Tachycardia: Results From A Registry And Review Of The Literature, Nathan Wei, Avani Lamba, Sonia Franciosi, Ian H Law, Luis A Ochoa, Christopher L Johnsrude, Sit Yee Kwok, Teng Hong Tan, Santokh S Dhillon, Anne Fournier, Stephen P Seslar, Elizabeth A Stephenson, Andrew D Blaufox, Michel Cabrera Ortega, Jeffrey N Bone, Ash Sandhu, Carolina A Escudero, Shubhayan Sanatani

Faculty, Staff and Student Publications

BACKGROUND: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT.

METHODS: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected. …

Crossroads Of Drug Abuse And Hiv Infection: Neurotoxicity And Cns Reservoir, Shilpa Sonti, Kratika Tyagi, Amit Pande, René Daniel, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Drug abuse is a common comorbidity in people infected with HIV. HIV-infected individuals who abuse drugs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care. A modest proportion of HIV-infected individuals develop HIV-associated neurocognitive issues, the severity of which further increases with drug abuse. Moreover, the tendency of the virus to go into latency in certain cellular reservoirs again complicates the elimination of HIV and HIV-associated illnesses. Antiretroviral therapy (ART) successfully decreased the overall viral load in infected people, yet it does not effectively eliminate the virus from all latent reservoirs. Although ART increased …

Monitoring And Evaluation Of Patient Engagement In Health Product Research And Development: Co-Creating A Framework For Community Advisory Boards, Sevgi E. Fruytier, Lidewij Eva Vat, Rob Camp, François Houÿez, Hilde De Keyser, Denise Dunne, Davide Marchi, Laura Mckeaveney, Richard H. Pitt, Carina A.C.M. Pittens, Meagan F. Vaughn, Elena Zhuravleva, Tjerk Jan Schuitmaker-Warnaar

Journal of Patient-Centered Research and Reviews

Purpose: While patient engagement is becoming more customary in developing health products, its monitoring and evaluation to understand processes and enhance impact are challenging. This article describes a patient engagement monitoring and evaluation (PEME) framework, co-created and tailored to the context of community advisory boards (CABs) for rare diseases in Europe. It can be used to stimulate learning and evaluate impacts of engagement activities.

Methods: A participatory approach was used in which data collection and analysis were iterative. The process was based on the principles of interactive learning and action and guided by the PEME framework. Data were collected via …

Impact Of Pooling Samples On Analytic Sensitivity Of A Real-Time Reverse Transcriptase Pcr Assay For Sars Cov-2, Subathra Marimuthu, Stephen P. Furmanek, Holly Aliesky, Leslie A. Wolf

The University of Louisville Journal of Respiratory Infections

During the COVID-19 pandemic, laboratories experienced periods of shortages for certain critical materials required to meet the high demand for SARS-CoV-2 testing. The U.S. Food & Drug Administration provided a template for molecular diagnostic testing, including guidance for a specimen pooling process in order to evaluate performance of the SARS-CoV-2 nucleic acid amplification assay. This study aimed to evaluate the testing of pooled specimens consisting of four nasopharyngeal swab specimens using the Luminex ARIES^® nucleic acid amplification platform. Results indicated that there was a loss of analytic sensitivity with pooled nasopharyngeal swab samples, demonstrating that this approach should be …

Optimizing Biomedical Discoveries As An Engine Of Culture Change In An Academic Medical Center, Anne K. Dechant, Stephen Fening, Michael Haag, William Harte, Mark R. Chance

Faculty Scholarship

Academic discovery in biomedicine is a growing enterprise with tens of billions of dollars in research funding available to universities and hospitals. Protecting and optimizing the resultant intellectual property is required in order for the discoveries to have an impact on society. To achieve that, institutions must create a multidisciplinary, collaborative system of review and support, and utilize connections to industry partners. In this study, we outline the efforts of Case Western Reserve University, coordinated through its Clinical and Translational Science Collaborative (CTSC), to promote entrepreneurial culture, and achieve goals of product development and startup formation for biomedical and population …

Research Annual Report Fy2022, Children's Mercy Kansas City

Research Annual Reports

Annual report of the research at Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Improving Antibiotic Administration Timing In Neonatal Early-Onset Sepsis, Donia B. Bass

Regis University Student Publications (comprehensive collection)

Abstract

Neonatal early onset sepsis (EOS) remains one of the most common causes of neonatal morbidity and mortality. Neonates requiring evaluation and treatment for suspected EOS inconsistently receive antibiotics within one hour of decision to treat as recommended in the 2012 neonatal sepsis guidelines by the National Institutes for Health and Care Excellence (NICE). A mixed method quality improvement initiative was employed in a level three NICU, applying a standardized admission process to mitigate systems flaws impacting delay of first dose antibiotic. A nursing sepsis education module was provided, and the novel SAM admission prioritization tool was developed to guide …

Regulation Of Skeletal Muscle Plasticity By The Gut Microbiome, Taylor R. Valentino

Theses and Dissertations--Physiology

Recent evidence suggests that the gut microbiome could play a role in skeletal muscle plasticity, providing novel treatments for muscle wasting diseases and/or performance enhancements. I first sought to determine if the gut microbiome is necessary for skeletal muscle adaptation to exercise. Forty-two, four-month old, female C57Bl/6J underwent nine weeks of weighted wheel running or remained in cage with a locked wheel, without or without the administration of antibiotics (treated). In response to wheel running, I found that antibiotic depletion of the microbiome led to a blunted hypertrophic response in the soleus muscle as measured by normalized muscle wet weight …

Improving Pharmacovigilance Signal Detection From Clinical Notes With Locality Sensitive Neural Concept Embeddings, Justin Mower, Elmer Bernstam, Hua Xu, Sahiti Myneni, Devika Subramanian, Trevor Cohen

Faculty, Staff and Student Publications

Although pharmaceutical products undergo clinical trials to profile efficacy and safety, some adverse drug reactions (ADRs) are only discovered after release to market. Post-market drug safety surveillance - pharmacovigilance - leverages information from various sources to proactively identify such ADRs. Clinical notes are one source of observational data that could assist this process, but their inherent complexity can obfuscate possible ADR signals. In previous research, embeddings trained on observational reports have improved detection of such signals over commonly used statistical measures. Moreover, neural embedding methods which further encode juxtapositional information have shown promise on analogical retrieval tasks, suggesting proximity-based alternatives …

Recolonization Of Microbiomes’ Influence On Autism Spectrum Disorder, Hattie Cole

Capstone Showcase

In recent years, there has been an increase in the number of studies conducted on the complications of gastrointestinal (GI) comorbidities associated with autism spectrum disorder (ASD) in children. Some of these GI issues include irritable bowel syndrome (IBS), diarrhea and constipation. The causes of these disorders are poorly understood. The dominant gut phyla are Firmicutes and Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia. Research conducted on children with ASD compared with typical developing (TD) children showed higher ratios of Firmicutes/Bacteroidetes in the ASD group. Biflobacterium, Actinobacteria phyla, has been shown to be a good intestinal bacterium that may help with …

Temporal Cohort Logic, Guo-Qiang Zhang, Xiaojin Li, Yan Huang, Licong Cui

Faculty, Staff and Student Publications

We introduce a new logic, called Temporal Cohort Logic (TCL), for cohort specification and discovery in clinical and population health research. TCL is created to fill a conceptual gap in formalizing temporal reasoning in biomedicine, in a similar role that temporal logics play for computer science and its applications. We provide formal syntax and semantics for TCL and illustrate the various logical constructs using examples related to human health. Relationships and distinctions with existing temporal logical frameworks are discussed. Applications in electronic health record (EHR) and in neurophysiological data resource are provided. Our approach differs from existing temporal logics, in …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Overcoming Resistance To Sg-Aris In Castration-Resistant Prostate Cancer, Chaohao Li

Theses and Dissertations--Toxicology and Cancer Biology

Prostate cancer (PCa) ranks as the most diagnosed type of cancer and the second leading cause of death in men. Androgen receptor (AR) signaling plays a pivotal function in promoting the survival and progression of PCa. Therefore, medication for PCa mainly focuses on the inhibition of AR pathway, which is termed androgen deprivation therapy (ADT). However, the disease eventually progresses and develops to a lethal stage called castration-resistant prostate cancer (CRPC) that is characterized by resistance to canonical ADT. To deal with this situation, several second-generation AR inhibitors (SG-ARIs) have been created that have better efficacy against AR, including Enzalutamide …

Vaping During Pregnancy: Effects On Vascular And Behavioral Outcomes In Offspring, Eiman A. Aboaziza

Graduate Theses, Dissertations, and Problem Reports (ETD)

Electronic cigarette (e-cig) use is increasing due to aggressive marketing, tempting flavors, and seemingly higher acceptability in the community (lesser perceived social stigma) despite unproven claims of safety. In an alarming trend, pregnant women smokers have turned to novel “modified risk” products, such as e-cigs, in response to heavy marketing of e-cigs as safer alternatives to cigarettes and a tool to help quit smoking. This is despite proven detrimental effects of nicotine on a growing fetus, and scarcity of information regarding toxicity of e-liquid (with and without nicotine) on child development. Moreover, rampant e-cig use among youth (nearly 4 million …

The Three-Way Interplay Among Early Life Exposures, The Gut Microbiome, And Outcomes In Infancy, Yuka Moroishi

Dartmouth College Ph.D Dissertations

The bidirectional relationship between the gut microbiome and immune system plays an important role in host immune status: the immune system provides the gut microbiome the optimal environment to thrive in, and the gut microbiome helps regulate the immune system. This relationship is especially important in infants, whose immune system is still premature and rely on innate immunity.

We investigated the three-way interplay among early-life exposures, the developing gut microbiome, and outcomes in infancy from the general population in New Hampshire, US. We used prospective cohort data from the New Hampshire Birth Cohort study to 1) determine whether timing of …