Digital Commons Network^™

Discordance Interpretation Of Left Ventricular Size Between Echocardiography And Cardiac Magnetic Resonance In Pediatric Patients With Aortic/Mitral Regurgitation, Anastasia Barros, Michelle Udine, Chris Spurney, Laura Olivieri, Yue-Hin Loke

Jefferson Hospital Staff Papers and Presentations

PURPOSE: This study investigated discordance between echocardiography (echo) and cardiac magnetic resonance (CMR) measurements of the left ventricle (LV) in pediatric patients with aortic and/or mitral regurgitation (AR/MR).

METHODS: Retrospective cohort study of pediatric patients. The cohorts were comprised of patients with AR/MR vs. non-AR/MR. Left ventricular end diastolic volume (LVEDV) by CMR and left ventricular internal diameter diastolic (LVIDd) by echo were obtained from clinical reports then echo images were reviewed to remeasure LVEDV by bullet method. Left ventricular internal diameter systolic (LVIDs) and left ventricular ejection fraction (LVEF) measurements by echo and LVEF by CMR were obtained from …

Edge-Wise Analysis Reveals White Matter Connectivity Associated With Focal To Bilateral Tonic-Clonic Seizures, Sam S. Javidi, Xiaosong He, Ankeeta Ankeeta, Qirui Zhang, Salvatore Citro, Michael R. Sperling, Joseph I. Tracy

Farber Institute for Neuroscience Faculty Papers

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS.

METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs …

Temporal Considerations In Brain Metastases Radiation Therapy: The Intersection Of Chronobiology And Patient Profiles, Nicolas Nelson, Sara Burke, Louis Cappelli, Lauren Matlack, Alexandria Smith, Noelle Francois, Joseph Lombardo, Yash Shah, Kuang-Yi Wen, Ayesha A Shafi, Nicole Simone

Department of Radiation Oncology Faculty Papers

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing’s impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival …

The Binding And Mechanism Of A Positive Allosteric Modulator Of Kv3 Channels, Qiansheng Liang, Gamma Chi, Leonardo Cirqueira, Lianteng Zhi, Agostino Marasco, Nadia Pilati, Martin Gunthorpe, Giuseppe Alvaro, Charles Large, David Sauer, Werner Treptow, Manuel Covarrubias

Farber Institute for Neuroscience Faculty Papers

Small-molecule modulators of diverse voltage-gated K⁺ (Kv) channels may help treat a wide range of neurological disorders. However, developing effective modulators requires understanding of their mechanism of action. We apply an orthogonal approach to elucidate the mechanism of action of an imidazolidinedione derivative (AUT5), a highly selective positive allosteric modulator of Kv3.1 and Kv3.2 channels. AUT5 modulation involves positive cooperativity and preferential stabilization of the open state. The cryo-EM structure of the Kv3.1/AUT5 complex at a resolution of 2.5 Å reveals four equivalent AUT5 binding sites at the extracellular inter-subunit interface between the voltage-sensing and pore domains of the …

Mental Health Screening In Pediatric Lower Limb Deficiency Population, Emily Marshall, Eileen Shieh, Jeanne M. Franzone, Paul T. Enlow

Department of Pediatrics Faculty Papers

BACKGROUND: Youth with lower limb deficiency (LLD) may be at increased risk for mental health difficulties. However, guidelines around psychosocial screening are not well established.

OBJECTIVE: To describe the implementation and results of a mental health screening process in a multidisciplinary prosthetics clinic.

DESIGN: Survey.

SETTING: Outpatient specialty care clinic located within a children's hospital.

PATIENTS: All patients ages 0-18 years with LLD seen at a monthly multidisciplinary prosthetics clinic between September 2019 and January 2023 (n = 75).

INTERVENTIONS: Not applicable.

MAIN OUTCOMES MEASURES: Quality of life was measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric proxy …

Racial Disparities In The Utilization Of Invasive Neuromodulation Devices For The Treatment Of Drug-Resistant Focal Epilepsy, Juan Luis Alcala-Zermeno, Brandy Fureman, Caitlin L. Grzeskowiak, Ojas Potnis, Maria Taveras, Margaret W. Logan, Delanie Rybacki, Daniel Friedman, Daniel Lowenstein, Ruben Kuzniecky, Jacqueline French, Hep2 Investigators

Student Papers, Posters & Projects

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for …

Nurse-Led Brief Intervention For Enhancing Safe Sex Practice Among Emerging Adults In Hong Kong Using Instant Messaging: Feasibility Study, Sharon Hoi Lam Pak, Man Ping Wang, Anne M. Teitelman, Janet Yuen Ha Wong, Daniel Yee Tak Fong, Edmond Pui Hang Choi

College of Nursing Faculty Papers & Presentations

BACKGROUND: The incidence of sexually transmitted infections has been increasing throughout the world. Additionally, substantial changes in emerging adults' attitudes toward sex and the popularization of premarital sex could further affect the diagnosis and treatment of sexually transmitted infections. With the high acceptability and effectiveness of instant messaging (IM) interventions for health promotion, there is potential for such interventions to improve condom use knowledge and promote safer sex practice.

OBJECTIVE: The study evaluates the feasibility of a nurse-led IM intervention to promote safer sex practices in emerging adults.

METHODS: A 30-minute adaptive IM intervention and a 5-day booster dose of …

Design Of The Strive-Ipf Trial-Study Of Therapeutic Plasma Exchange, Rituximab, And Intravenous Immunoglobulin For Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Tejaswini Kulkarni, Gerard Criner, Daniel Kass, Ivan Rosas, Mary Beth Scholand, Daniel Dilling, Ross Summer, Steven Duncan

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

METHODS: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population …

The Association Between Robotic Lung Cancer Resection And Esophagectomy Outcomes: A Facility-Level Analysis, Micaela L. Collins, Gregory L. Whitehorn, Shale J. Mack, Brian M. Till, Hamza Rshaidat, Tyler Grenda, Nathaniel R. Evans Iii, Karen A. Chojnacki, Olugbenga T. Okusanya

Department of Neurosurgery Faculty Papers

Background: Within the field of robotic thoracic surgery, the association between facility surgical volume, conversion rates, and patient outcomes across multiple procedures has not been explored. This study aims to examine the potential association between robotic lung cancer resection surgical volume and conversion rates for robotic-assisted minimally invasive esophagectomy (RAMIE). Methods: A retrospective analysis of the National Cancer Database, between the years 2010–2018 was conducted. Facility-years were categorized into one of four groups based on a combination of robotic lung cancer resection surgical volume and RAMIE volumes. Cutoffs were based on previously identified surgical volume thresholds. Results: A total of …

Antithrombotic Therapy In Cerebral Cavernous Malformations: A Systematic Review, Meta-Analysis, And Network Meta-Analysis, Basel Musmar, Hamza Salim, Jihad Abdelgadir, Samantha Spellicy, Nimer Adeeb, Ali Zomorodi, Allan Friedman, Issam Awad, Pascal Jabbour, David Hasan

Department of Neurosurgery Faculty Papers

BACKGROUND: Cerebral cavernous malformations are complex vascular anomalies in the central nervous system associated with a risk of intracranial hemorrhage. Traditional guidelines have been cautious about the use of antithrombotic therapy in this patient group, citing concerns about potential bleeding risk. However, recent research posits that antithrombotic therapy may actually be beneficial. This study aims to clarify the association between antithrombotic therapy, including antiplatelet and anticoagulant medications, and the risk of intracranial hemorrhage in patients with cerebral cavernous malformations.

METHODS AND RESULTS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases, following Preferred Reporting Items …

Point Of View On Outcome Prediction Models In Post-Stroke Motor Recovery, Onno Van Der Groen, Manonita Ghosh, Richard Norman, Amy Kuceyeski, Ceren Tozlu, Teresa J. Kimberley, David J. Lin, Laurel J. Buxbaum, Gert Kwakkel, Steven C. Cramer, Dylan J. Edwards

Moss-Magee Rehabilitation Papers

Stroke is a leading cause of disability worldwide which can cause significant and persistent upper limb (UL) impairment. It is difficult to predict UL motor recovery after stroke and to forecast the expected outcomes of rehabilitation interventions during the acute and subacute phases when using clinical data alone. Accurate prediction of response to treatment could allow for more timely and targeted interventions, thereby improving recovery, resource allocation, and reducing the economic impact of post-stroke disability. Initial motor impairment is currently the strongest predictor of post-stroke motor recovery. Despite significant progress, current prediction models could be refined with additional predictors, and …

Delayed Diagnosis Of Mycobacterium Bovis Bacillus Calmette-Guérin Periprosthetic Joint Infection Following Total Knee Arthroplasty, Christopher E. Pelt, Salika Shakir, Michael J. Cahill, Jakrapun Pupaibool, Barbara C. Cahill

SKMC Student Presentations and Publications

Periprosthetic joint infection (PJI) can present challenges in diagnosis and treatment, particularly in the setting of atypical causative organisms such as fungi and mycobacteria. Herein, we present a case and provide a review of the diagnosis and treatment of an unusual PJI caused by bacillus Calmette-Guérin, administered during the treatment of bladder cancer 3 years prior to total knee arthroplasty and subsequent PJI. Although the patient's history of bladder cancer was known, neither his Bacillus Calmette-Guérin treatment nor its potential for distant site spread that could lead to PJI were appreciated, leading to a prolonged diagnostic evaluation and treatment course.

Reaching The Unheard: Overcoming Challenges In Health Research With Hard-To-Reach Populations, Venera Bekteshi, Munjireen Sifat, Darla Kendzor

Kimmel Cancer Center Faculty Papers

PURPOSE: Addressing obstacles such as logistical complexities, social stigma, and the impact of historical traumas is essential for the successful inclusion of underrepresented groups in health research.

METHODS: This article reviews engagement and interview techniques used to ethically engage recently settled Afghan refugees in Oklahoma and rural Mexican-born women in Illinois in research. The paper concludes with a reflective discussion on the challenges and lessons learned.

RESULTS: Creative strategies to engage hard-to-reach populations in research included considering the participants' socioeconomic and cultural contexts in their interactions and developing community partnerships to establish trust and obtain reliable data. Other engagement strategies …

Most Recent Advances And Applications Of Extracellular Vesicles In Tackling Neurological Challenges, Mandeep Kaur, Salvatore Fusco, Bram Van Den Broek, Jaya Aseervatham, Abdolmohamad Rostami, Lorraine Iacovitti, Claudio Grassi, Barbara Lukomska, Amit K. Srivastava

Cardeza Foundation for Hematologic Research

Over the past few decades, there has been a notable increase in the global burden of central nervous system (CNS) diseases. Despite advances in technology and therapeutic options, neurological and neurodegenerative disorders persist as significant challenges in treatment and cure. Recently, there has been a remarkable surge of interest in extracellular vesicles (EVs) as pivotal mediators of intercellular communication. As carriers of molecular cargo, EVs demonstrate the ability to traverse the blood-brain barrier, enabling bidirectional communication. As a result, they have garnered attention as potential biomarkers and therapeutic agents, whether in their natural form or after being engineered for use …

What Do Cervical Cancer Patients Know, How Do They Learn, And Who Do They Tell? A Pilot Study, Sharon Larson, Brian Mcanany, Ilene Ladd, Radhika Gogoi

College of Population Health Faculty Papers

BACKGROUND: This study explored what patients identified with cervical cancer know about the link between human papillomavirus (HPV) and cervical cancer and where they learned this information. Patients share a great deal of information with family, friends and colleagues and we were interested in the accuracy and sources of information they are sharing.

METHODS: Patients identified through the EHR of a health system who had a history of cervical cancer were invited to participate in a brief survey of their experience. The sample represents an opportunity sample of patients who responded.

RESULTS: Generally, these patients, drawn from the Geisinger Health …

A Representative Clinical Course Of Progression, With Molecular Insights, Of Hormone Receptor-Positive, Her2-Negative Bone Metastatic Breast Cancer, Elizabeth Magno, Karen M. Bussard

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite treatment advances, breast cancer remains a leading cause of death of women in the United States, mostly due to metastatic disease. Bone is a preferential site for breast cancer metastasis, and most metastatic breast cancer patients experience bone involvement at the time of death. The majority of patients with bone metastatic breast cancer are first diagnosed with and treated for early-stage disease, and from development of early-stage breast cancer to the recurrence of cancer in the bones, up to 30 years may elapse. Throughout this timeframe, a typical patient undergoes many treatments that have effects on the bone microenvironment. …

Automated Seizure Detection Based On State-Space Model Identification, Zhuo Wang, Michael Sperling, Dale Wyeth, Allon Guez

Department of Neuroscience Faculty Papers

In this study, we developed a machine learning model for automated seizure detection using system identification techniques on EEG recordings. System identification builds mathematical models from a time series signal and uses a small number of parameters to represent the entirety of time domain signal epochs. Such parameters were used as features for the classifiers in our study. We analyzed 69 seizure and 55 non-seizure recordings and an additional 10 continuous recordings from Thomas Jefferson University Hospital, alongside a larger dataset from the CHB-MIT database. By dividing EEGs into epochs (1 s, 2 s, 5 s, and 10 s) and …

Dendritic Cells Overcome Cre/Lox Induced Gene Deficiency By Siphoning Cytosolic Material From Surrounding Cells, Christopher H. Herbst, Aurélie Bouteau, Evelin J. Menykő, Zhen Qin, Ervin Gyenge, Qingtai Su, Vincent Cooper, Neil A. Mabbott, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

In a previous report, keratinocytes were shown to share their gene expression profile with surrounding Langerhans cells (LCs), influencing LC biology. Here, we investigated whether transferred material could substitute for lost gene products in cells subjected to Cre/Lox conditional gene deletion. We found that in human Langerin-Cre mice, epidermal LCs and CD11b+CD103+ mesenteric DCs overcome gene deletion if the deleted gene was expressed by neighboring cells. The mechanism of material transfer differed from traditional antigen uptake routes, relying on calcium and PI3K, being susceptible to polyguanylic acid inhibition, and remaining unaffected by inflammation. Termed intracellular monitoring, this process was specific …

Quality Improvement Protocol: Improving The Use Of Nonpharmacological Pain Management Strategies Within The Inpatient Hospital Setting, Katherine Salamon, Christina Russell, Dara Devinney, Catherine M Soprano

Department of Medicine Faculty Papers

Background: There are many nonpharmacological pain management services available to hospitalized youth; however, not all youth are offered these services. Lack of knowledge about resources, difficulty with the referral process, and lack of understanding about nonpharmacological pain management services and when to refer patients are among the main reasons for lack of utilization. Quality improvement (QI) initiatives have grown within hospital settings and can serve to create change in fast-paced environments. Methods: The current QI project aimed to pilot an educational program to increase the use of nonpharmacological pain management interventions. Staff located on one floor of a pediatric hospital …

Microcurrent-Mediated Modulation Of Myofibroblasts For Cardiac Repair And Regeneration, Dipthi Bachamanda Somesh, Karsten Jürchott, Thomas Giesel, Thomas Töllner, Alexander Prehn, Jan-Peter Richters, Dragana Kosevic, J. Eduardo Rame, Peter Göttel, Johannes Müller

Division of Cardiology Faculty Papers

Cardiovascular diseases are a significant cause of illness and death worldwide, often resulting in myofibroblast differentiation, pathological remodeling, and fibrosis, characterized by excessive extracellular matrix protein deposition. Treatment options for cardiac fibrosis that can effectively target myofibroblast activation and ECM deposition are limited, necessitating an unmet need for new therapeutic approaches. In recent years, microcurrent therapy has demonstrated promising therapeutic effects, showcasing its translational potential in cardiac care. This study therefore sought to investigate the effects of microcurrent therapy on cardiac myofibroblasts, aiming to unravel its potential as a treatment for cardiac fibrosis and heart failure. The experimental design involved …

A Novel Staging System To Consolidate Silent Sinus Syndrome And Chronic Maxillary Atelectasis: A Systematic Review And Case Series, Dev Amin, Shreya Mandloi, Kathryn Nunes, Neha Garg, Chase Kahn, Alexander Duffy, Elina Toskala, Mindy Rabinowitz, Marc Rosen, Gurston Nyquist

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Key points:

• Silent sinus syndrome (SSS) and chronic maxillary atelectasis (CMA) represent an overlapping clinical entity, both likely lying on the spectrum of one disease process.
• There is widespread inconsistency of diagnosis in the literature of reported cases of SSS and CMA.
• We propose a novel, comprehensive staging system to simplify diagnosis and inform management.

The Impact Of Robotic Assistance For Lumbar Fusion Surgery On 90-Day Surgical Outcomes And 1-Year Revisions, Jeremy Heard, Yunsoo Lee, Nicholas D D'Antonio, Rajkishen Narayanan, Mark Lambrechts, John Bodnar, Caroline Purtill, Joshua Pezzulo, Dominic Farronato, Pat Fitzgerald, Jose Canseco, Ian Kaye, Alan Hilibrand, Alex Vaccaro, Christopher Kepler, Gregory Schroeder

Department of Orthopaedic Surgery Faculty Papers

Objectives: To evaluate the (1) 90-day surgical outcomes and (2) 1-year revision rate of robotic versus nonrobotic lumbar fusion surgery. Methods: Patients >18 years of age who underwent primary lumbar fusion surgery at our institution were identified and propensity-matched in a 1:1 fashion based on robotic assistance during surgery. Patient demographics, surgical characteristics, and surgical outcomes, including 90-day surgical complications and 1-year revisions, were collected. Multivariable regression analysis was performed. Significance was set to P < 0.05. Results: Four hundred and fifteen patients were identified as having robotic lumbar fusion and were matched to a control group. Bivariant analysis revealed no significant difference in total 90-day surgical complications (P = 0.193) or 1-year revisions (P = 0.178). The operative duration was longer in robotic surgery (287 + 123 vs. 205 + 88.3, P ≤ 0.001). Multivariable analysis revealed that robotic fusion was not a significant predictor of 90-day surgical complications (odds ratio [OR] = 0.76 [0.32-1.67], P = 0.499) or 1-year revisions (OR = 0.58 [0.28-1.18], P = 0.142). Other variables identified as the positive predictors of 1-year revisions included levels fused (OR = 1.26 [1.08-1.48], P = 0.004) and current smokers (OR = 3.51 [1.46-8.15], P = 0.004). Conclusion: Our study suggests that robotic-assisted and nonrobotic-assisted lumbar fusions are associated with a similar risk of 90-day surgical complications and 1-year revision rates; however, robotic surgery does increase time under anesthesia.

Strabismus Management In Retinoblastoma Survivors, Babak Masoomian, Carol L. Shields, Hamid Riazi Esfahani, Atefeh Khalili, Fariba Ghassemi, Pukhraj Rishi, Mohammad Reza Akbari, Masoud Khorrami-Nejad

Wills Eye Hospital Papers

PURPOSE: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients.

METHODS: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist.

RESULTS: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor's group was D …

Quality Improvement In Public-Private Partnerships In Low- And Middle-Income Countries: A Systematic Review, Cassandra Iroz, Rohit Ramaswamy, Zulfiqar Bhutta, Paul Barach

College of Population Health Faculty Papers

BACKGROUND: Public-private partnerships (PPP) are often how health improvement programs are implemented in low-and-middle-income countries (LMICs). We therefore aimed to systematically review the literature about the aim and impacts of quality improvement (QI) approaches in PPP in LMICs.

METHODS: We searched SCOPUS and grey literature for studies published before March 2022. One reviewer screened abstracts and full-text studies for inclusion. The study characteristics, setting, design, outcomes, and lessons learned were abstracted using a standard tool and reviewed in detail by a second author.

RESULTS: We identified 9,457 citations, of which 144 met the inclusion criteria and underwent full-text abstraction. We …

Health Care Costs Among Patients With Hematologic Malignancies Receiving Allogeneic Transplants: A Us Payer Perspective, Richard Maziarz, Usama Gergis, Marie Louise Edwards, Yan Song, Qing Liu, Annika Anderson, James Signorovitch, Rocio Manghani, Ronit Simantov, Heayoung Shin, Smitha Sivaraman

Department of Medical Oncology Faculty Papers

Patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) require extensive care. Using the Merative MarketScan Commercial Claims and Encounters database (2016 Q1-2020 Q2), we quantified the costs of care and assessed real-world complication rates among commercially insured US patients diagnosed with a hematologic malignancy and aged between 12 and 64 years undergoing inpatient allo-HCT. Health care resource use and costs were assessed from 100 days before HCT to 100 days after HCT. Primary hospitalization was defined as the time from HCT until first discharge date. Incidence of complications was assessed using medical billing codes from HCT date to …

Safety And Tolerability Of Atogepant For The Preventive Treatment Of Migraine: A Post Hoc Analysis Of Pooled Data From Four Clinical Trials, Paul Rizzoli, Michael Marmura, Jennifer Robblee, Jennifer Mcvige, Sara Sacco, Stephanie Nahas, Jessica Ailani, Rosa De Abreu Ferreira, Julia Ma, Jonathan Smith, Brett Dabruzzo, Messoud Ashina

Department of Jefferson Headache Center Papers and Presentations

BACKGROUND: Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene-related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders.

METHODS: This post hoc analysis was performed using data pooled …

Nf-Κb As An Inducible Regulator Of Inflammation In The Central Nervous System, Sudha Anilkumar, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. The proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor in the upregulation of proinflammatory genes. Stimuli that initiate NF-κB activation are diverse but are canonically attributed to proinflammatory cytokines and chemokines. Downstream effects of NF-κB are cell type-specific and, in the majority of cases, result in the activation of pro-inflammatory cascades. Acting as …

Mir-200c Reprograms Fibroblasts To Recapitulate The Phenotype Of Cafs In Breast Cancer Progression, Zhao Lin, Megan Roche, Víctor Díaz-Barros, Marina Domingo-Vidal, Diana Menezes, Madalina Tuluc, Guldeep Uppal, Jaime Caro, Joseph Curry, Ubaldo Martinez-Outshoorn

Kimmel Cancer Center Faculty Papers

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma …

Characterizing Multimorbidity Prevalence And Adverse Outcomes In Ethnically And Culturally Diverse Sub-Populations In India: Gaps, Opportunities, And Future Directions, Preeti Zanwar, Robyn Taylor, Tanisha Hill-Jarrett, Elena Tsoy, Jason Flatt, Zunera Mirza, Carl Hill, Arokiasamy Perianayagam

College of Population Health Faculty Papers

India is a large middle-income country and has surpassed China in overall population, comprising 20% of the global population (over 1.43 billion people). India is experiencing a major demographic shift in its aging population. Chronic diseases are common among older adults and can be persistent over the life course, lead to the onset of disability, and be costly. Among older adults in India, the existence of multiple comorbid chronic conditions (i.e., multimorbidity) is rapidly growing and represents a burgeoning public health burden. Prior research identified greater rates of multimorbidity (e.g., overweight/obesity diabetes, hypertension, cardiovascular disease, stroke, and malignancies) in minority …

Microvascular Vasoregulatory Dysfunction In African Americans - An Enhanced Opportunity For Early Prevention And Treatment Of Atherosclerotic Cardiovascular Disease, Renee Bullock-Palmer, Panithaya Chareonthaitawee, Ervin Fox, Garth Beache

Division of Cardiology Faculty Papers

Atherosclerotic cardiovascular disease and its risk factors and precursors are a major driver of disparities in cardiovascular health. This review examines reported evidence that vascular endothelial dysfunction, and its manifestation as coronary microvascular dysfunction, underlies observed excess morbidity and mortality in African Americans. Advanced imaging insights that reveal patho-mechanisms, along with population evidence from the Jackson Heart Study, and the growing evidence emanating from national and international clinical trials and registries are presented. We examine a physiological framework that recognizes insulin-resistant cardiometabolic underpinnings of the conditions of the American Heart Associations' Life's Essential Eight construct of cardiovascular health as a …