Translational Medical Research Commons^™

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 …

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 …

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 …

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 …