Internal Medicine Commons^™

Prioritization Of Kidney Cell Types Highlights Myofibroblast Cells In Regulating Human Blood Pressure, Mahboube Ganji-Arjenaki, Zoha Kamali, International Consortium Of Blood Pressure; Soroush Sardari, Soroush Sardari, Martin De Borst, Harold Snieder, Ahmad Vaez

Faculty, Staff and Student Publications

INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.

METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.

RESULTS: …

Persistent ∆Fosb Expression Limits Recurrent Seizure Activity And Provides Neuroprotection In The Dentate Gyrus Of App Mice, Gabriel S Stephens, Jin Park, Andrew Eagle, Jason You, Manuel Silva-Pérez, Chia-Hsuan Fu, Sumin Choi, Corey P St Romain, Chiho Sugimoto, Shelly A Buffington, Yi Zheng, Mauro Costa-Mattioli, Yin Liu, A J Robison, Jeannie Chin

Faculty, Staff and Student Publications

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection …

The Association Of Self-Reported Sleep And Circadian Measures With Glycemic Control And Diabetes Complications Among Young Adults With Type 2 Diabetes, Dorit Koren, Kristen L Knutson, Brian K Burke, Kimberly L Drews, Fida Bacha, Lorraine Katz, Marsha D Marcus, Siripoom Mckay, Kristen Nadeau, Babak Mokhlesi, Today Study Group

Children’s Nutrition Research Center Staff Publications

We aim to examine the association of sleep duration, sleep quality, late chronotype, and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ). We examined diabetes complications including loss of glycemic control (defined as hemoglobin A1c ≥8%), hypertension, dyslipidemia, albuminuria, and diabetic peripheral neuropathy. Multivariable logistic regression models were …

Unveiling The Influence Of Hyponatremia On Morbidity, Mortality, And Resource Utilization In Colorectal Carcinoma: Insights From A 5-Year Nationwide Study., Priya Hotwani Md, Vikash Kumar, Bhavyakumar Vachhani, Mrunanjali Gaddam, Jayalekshmi Jayakumar, Manasa Ginjupalli, Ankushi Sanghvi, Jincy Clement, Dhairya Nanavaty

Internal Medicine Residency

Meeting Abstract: 2024 ASCO Annual Meeting

Background: Historically, Hyponatremia has been associated with higher mortality rates and longer hospital stays in patients with solid tumors. The existing literature contains limited information on the connection between hyponatremia and Colorectal cancer (CRC). Thus, our study aimed to assess the impact of hyponatremia on mortality, morbidity, and resource usage in patients with CRC.

Methods: A retrospective analysis using the National Inpatient Sample database and International Classification of Diseases, Tenth Revision codes was conducted to examine the impact of hyponatremia on mortality, morbidity, and resource utilization in patients with CRC. Categorical variables were compared …

Loss Of Lpar6 And Cab39l Dysregulates The Basal-To-Luminal Urothelial Differentiation Program, Contributing To Bladder Carcinogenesis, Sangkyou Lee, Jolanta Bondaruk, Yishan Wang, Huiqin Chen, June Goo Lee, Tadeusz Majewski, Rachel D Mullen, David Cogdell, Jiansong Chen, Ziqiao Wang, Hui Yao, Pawel Kus, Joon Jeong, Ilkyun Lee, Woonyoung Choi, Neema Navai, Charles Guo, Colin Dinney, Keith Baggerly, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Marek Kimmel, Peng Wei, Bogdan Czerniak

Faculty, Staff and Student Publications

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two …

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Aba-Mediated Regulation Of Rice Grain Quality And Seed Dormancy Via The Nf-Yb1-Slrl2-Bhlh144 Module, Jin-Dong Wang, Jing Wang, Li-Chun Huang, Li-Jun Kan, Chu-Xin Wang, Min Xiong, Peng Zhou, Li-Hui Zhou, Chen Chen, Dong-Sheng Zhao, Xiao-Lei Fan, Chang-Quan Zhang, Yong Zhou, Lin Zhang, Qiao-Quan Liu, Qian-Feng Li

Faculty, Staff and Student Publications

Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation …

Not Your Typical Recurrent Pericarditis Patient!, Tarek Alsibai, Naomi Cret, Shaiva G. Meka

Conference Presentation Abstracts

No abstract provided.

From Immune Checkpoint Inhibition To Intubation, Sabena Toor, Samridhi Gulati, Shaiva G. Meka

Conference Presentation Abstracts

No abstract provided.

Reaction Mechanisms Of H2s Oxidation By Naphthoquinones, Kenneth R Olson, Kasey J Clear, Tsuyoshi Takata, Yan Gao, Zhilin Ma, Ella Pfaff, Anthony Travlos, Jennifer Luu, Katherine Wilson, Zachary Joseph, Ian Kyle, Stephen M Kasko, Prentiss Jones, Jon Fukuto, Ming Xian, Gang Wu, Karl D Straub

Faculty, Staff and Student Publications

1,4-naphthoquinones (NQs) catalytically oxidize H2S to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine H2S oxidation by NQs with various substituent groups. In general, the order of H2S oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions. DMNQ does not form adducts with GSH or cysteine (Cys), yet it readily oxidizes H2S to polysulfides and sulfoxides. …

The Long-Term Effects Of Blood Urea Nitrogen Levels On Cardiovascular Disease And All-Cause Mortality In Diabetes: A Prospective Cohort Study, Hongfang Liu, Xiaoqin Xin, Jinghui Gan, Jungao Huang

Faculty, Staff and Student Publications

BACKGROUND: The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes.

METHODS: In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were …

Life-Space Mobility And Cognitive Function: The Reasons For Geographic And Racial Differences In Stroke (Regards) Study, Emiri Matsuda, Michael Crowe, Virginia J. Howard, Cynthia J. Brown, Madeline R. Sterling, Emily B. Levitan

School of Medicine Faculty Publications

No abstract provided.

Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker

Faculty, Staff and Student Publications

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes …

Improving Quality Of Life In Menopausal Women Through A Best Practice Protocol: The Use Of Hormone Therapy, Mindfulness-Based Module And Exercise, Claire Czerwonka

Evidence-Based Practice Project Reports

Menopause is a normal process of aging, but many of the symptoms negatively impact women’s day-to-day quality of life (QOL), as well as activities of daily living, physical and mental health (ACOG, 2014). Generally, systemic estrogen hormone therapy is indicated for menopause-related vasomotor symptoms, but there is no research further addressing QOL issues or lifestyle management in addition to hormone therapy. The purpose of this evidence-base practice (EBP) project was to implement a menopause protocol to address QOL issues in menopausal women with the use of hormone replacement therapy, education through an online mindfulness module, and the use of exercise. …

The Unusual Suspect: Citrobacter Infection As A Rare Cause Of Renal Abscess, Nismat Javed, Nishant Allena, Sai Allu, Paul Kelly

Journal of Community Hospital Internal Medicine Perspectives

Citrobacter infections have emerged as now a common nosocomial pathogen. Most of the infections manifest in patients with underlying medical conditions. The features of infection can range from infections in the lower urinary tract, respiratory tract, gastrointestinal disease, or bacteremia, however renal abscesses remain uncommon. Here we present the case of a 48-year-old female with medical history of diabetes that presented with a right renal abscess secondary to Citrobacter koseri infection managed with drainage and antimicrobial treatment.

The Not-So-Benign Sickle Cell Trait: A Case Of Renal Medullary Carcinoma, Fatima Halilu, Siddartha Guru, Fuscaldo Joseph

Journal of Community Hospital Internal Medicine Perspectives

Sickle cell trait (SCT) has long been considered a benign carrier state with malarial protection, but carriers can be affected by increased venous thromboembolism, exercise-related injury, renal complications and very rarely a fatal renal malignancy. Renal medullary carcinoma is a very rare and aggressive renal tumor described almost exclusively in sickle cell trait. A review of the current literature provides clues to this link and describes trends expected in these cases. We report a case of renal medullary carcinoma in a 32-year-old female with known sickle trait who presented with cough, hemoptysis, left flank pain and gross hematuria. Initial presentation …

Role Of Artificial Intelligence In Endoscopic Intervention: A Clinical Review, Nismat Javed, Haider Ghazanfar, Bhavna Balar, Harish Patel

Journal of Community Hospital Internal Medicine Perspectives

Gastrointestinal diseases are increasing in global prevalence. As a result, the contribution to both mortality and healthcare costs is increasing. While interventions utilizing scoping techniques or ultrasound are crucial to both the timely diagnosis and management of illness, a few limitations are associated with these techniques. Artificial intelligence, using computerized diagnoses, deep learning systems, or neural networks, is increasingly being employed in multiple aspects of medicine to improve the characteristics and outcomes of these tools. Therefore, this review aims to discuss applications of artificial intelligence in endoscopy, colonoscopy, and endoscopic ultrasound.

A Multi-Modal Intervention To Decrease Hpv Vaccine Hesitancy And Increase Uptake In Young Adult Women, Rylee Cartales

Evidence-Based Practice Project Reports

Human Papillomavirus (HPV) is the leading cause of cervical cancer worldwide and the most common sexually transmitted disease, yet hesitancy towards the HPV vaccine remains high and uptake of the HPV vaccine remains remarkably low (CDC, 2021b). The purpose of this evidence-based practice (EBP) project was to determine if the implementation of a multimodal intervention including a motivational interview, strong provider recommendation, and educational materials will decrease HPV vaccine hesitancy and consequentially increase uptake of the vaccine. Eleven young adult women ages 18-26 from a rural outpatient Obstetrics and Gynecology (OBGYN) clinic in Indiana participated in this project. After agreeing …

Assessing Quality Of Health-Related Social Needs Screening Across Jefferson Hospital’S Clinical Sites, Aparna Sarin, Md, Mph, Olivia Quinn, Mph, Nolan Chiles, Bs

Health Equity and Quality Improvement (HEQI) Summit

Objectives

• Assess the rate of completed health-related social needs (HRSNs) screenings at different TJUH sites
• Compare screening outcomes across TJUH clinical sites

Background

- Centers for Medicare and Medicaid (CMS) is mandating Health Related Social Needs (HRSNs) screening for all admitted patients

- First-year Sidney Kimmel Medical College (SKMC) students screen patients at four different Jefferson clinical sites alongside Community Health Workers (CHWs) as part of their ‘Clinical Experience’ curriculum

- SKMC screens 7 domains

• Food*
• Housing*
• Utilities*
• Transportation*
• Medication expenses
• Primary care
• Insurance
  
  *Screened by CMS, as well as interpersonal safety

- The data is gathered from:

• inpatient floors …

Effect Of Education Level On Adequacy Of Bowel Preparation Prior To Colonoscopy, Anna Chen, Md, Michael Dimarino, Md, Akash Patel, Do, Katherine Duffey, Md, Gregory Habig, Md, Aaron Martin, Md, Cuckoo Choudhary, Md, Stephanie Moleski, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Adequate bowel preparation is crucial for obtaining a high-quality colonoscopy.
• Inadequate preparation leads to impaired visualization, which can lower adenoma detection rate, increase the risk of complications and potentially necessitate repeating the procedure.¹
• Patients with higher health literacy and a higher level of education have been associated with better bowel preparation quality.^2,3,4,5