Medicine and Health Sciences Commons^™

Comprehensive Characterization Of The Transcriptional Landscape In Alzheimer’S Disease (Ad) Brains, Chengxuan Chen, Zhao Zhang, Yuan Liu, Wei Hong, Hande Karahan, Jun Wang, Wenbo Li, Lixia Diao, Meichen Yu, Andrew J Saykin, Kwangsik Nho, Jungsu Kim, Leng Han

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events. We additionally identified 25,351 aberrantly expressed ncRNAs and altered PTM events associated with AD …

Meta-Ea: A Gene-Specific Combination Of Available Computational Tools For Predicting Missense Variant Effects, Panagiotis Katsonis, Olivier Lichtarge

Faculty, Staff and Students Publications

Computational methods for estimating missense variant impact suffer from inconsistent performance across genes, which poses a major challenge for their reliable use in clinical practice. While ensemble scores leverage multiple prediction methods to enhance consistency, the overrepresentation of certain genes in the training data can bias their outcomes. To address this critical limitation, we propose a gene-specific ensemble framework trained on reference computational annotations rather than on clinical or experimental data. Accordingly, we generate Meta-EA ensemble scores that achieve comparable performance to the top individual predicting method for each gene set. Incorporating the effects of splicing and the allele frequency …

N-Linked Fucosylated Glycans Are Biomarkers For Prostate Cancer With A Neuroendocrine And Metastatic Phenotype, Joseph E Ippolito, Hani Nakhoul, Cody Weimholt, Elena Nunez, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at the time of prostatectomy that eventually developed recurrent metastatic disease. Analysis of …

T Helper 2 Cell-Directed Immunotherapy Eliminates Precancerous Skin Lesions, Tomonori Oka, Neel S. Raval, Mary Tabacchi, Lynn A. Cornelius, Et Al.

2020-Current year OA Pubs

The continuous rise in skin cancer incidence highlights an imperative for improved skin cancer prevention. Topical calcipotriol-plus-5-fluorouracil (calcipotriol-plus-5-FU) immunotherapy effectively eliminates precancerous skin lesions and prevents squamous cell carcinoma (SCC) in patients. However, its mechanism of action remains unclear. Herein, we demonstrate that calcipotriol-plus-5-FU immunotherapy induces T helper type 2 (Th2) immunity, eliminating premalignant keratinocytes in humans. CD4+ Th2 cells were required and were sufficient downstream of thymic stromal lymphopoietin cytokine induction by calcipotriol to suppress skin cancer development. Th2-associated cytokines induced IL-24 expression in cancer cells, resulting in toxic autophagy and anoikis followed by apoptosis. Calcipotriol-plus-5-FU immunotherapy was dependent …

Immunologic Investigations Into Transgene Directed Immune-Mediated Myositis Following Delandistrogene Moxeparvovec Gene Therapy, Rachael A Potter, Ida H Moeller, Sohrab Khan, Hélène Haegel, Andreas Hollenstein, Guido Steiner, Christoph Wandel, Alexander P Murphy, Damon R Asher, Emanuel Palatinsky, Danielle A Griffin, Stefanie Mason, Susan T Iannaccone, Craig M Zaidman, Louise R Rodino-Klapac

2020-Current year OA Pubs

Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It is approved in the US and in other select countries. Two serious adverse event cases of immune-mediated myositis (IMM) were reported in the phase Ib ENDEAVOR trial (NCT04626674). We hypothesized that immune responses to the micro-dystrophin transgene product may have mediated these IMM events. An interferon-gamma ELISpot assay was used to detect T cell responses to delandistrogene moxeparvovec micro-dystrophin peptide pools. ELISpot analysis suggested that IMM resulted …

Covid-19 Pandemic And Racial And Ethnic Disparities In Long-Term Nursing Home Stay Or Death Following Hospital Discharge, Laurent G Glance, Karen E Joynt Maddox, Patricia W Stone, Jingjing Shang, E Yoko Furuya, Ashley M Chastain, Ji Won Lee, Bridget Morse-Karzen, Andrew W Dick

2020-Current year OA Pubs

IMPORTANCE: Long-term nursing home stay or death (long-term NH stay or death), defined as new long-term residence in a nursing home or death following hospital discharge, is an important patient-centered outcome.

OBJECTIVE: To examine whether the COVID-19 pandemic was associated with changes in long-term NH stay or death among older adults with sepsis, and whether these changes were greater in individuals from racial and ethnic minoritized groups.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used patient-level data from the Medicare Provider Analysis and Review File, the Master Beneficiary Summary File, and the Minimum Data Set. Community-dwelling individuals aged at least …

Delivering Guideline-Concordant Care For Patients With High-Risk Hpv And Normal Cytologic Findings, Jasmin A Tiro, Jacquelyn M Lykken, Patricia M Chen, Cheryl R Clark, Sarah Kobrin, Jessica Chubak, Sarah Feldman, Claudia Werner, Steven J Atlas, Michelle I Silver, Jennifer S Haas

2020-Current year OA Pubs

IMPORTANCE: As US health care systems shift to human papillomavirus (HPV)-based cervical cancer screening, more patients are receiving positive high-risk non-16/18 genotype HPV results and negative for intraepithelial lesion or malignancy (NILM) cytological findings. Risk-based management guidelines recommend 2 consecutive negative annual results to return to routine screening.

OBJECTIVE: To quantify patterns of surveillance testing and associated outcomes for patients after an HPV-positive results and NILM cytologic findings.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed patients in the METRICS (Multi-level Optimization of the Cervical Cancer Screening Process in Diverse Settings and Populations) cohort of the PROSPR II (Population-Based Research …

Brain Age Modeling And Cognitive Outcomes In Young Adults With And Without Sickle Cell Anemia, Andria L Ford, Slim Fellah, Yan Wang, Kira Unger-Levinson, Maria Hagan, Martin N Reis, Amy Mirro, Josiah B Lewis, Chunwei Ying, Kristin P Guilliams, Melanie E Fields, Hongyu An, Allison A King, Yasheng Chen

2020-Current year OA Pubs

IMPORTANCE: Both sickle cell anemia (SCA) and socioeconomic status have been associated with altered brain structure and cognitive disability, yet precise mechanisms underlying these associations are unclear.

OBJECTIVE: To determine whether brains of individuals with and without SCA appear older than chronological age and if brain age modeling using brain age gap (BAG) can estimate cognitive outcomes and mediate the association of socioeconomic status and disease with these outcomes.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study of 230 adults with and without SCA, individuals underwent brain magnetic resonance imaging (MRI) and cognitive assessment. Brain age was estimated using DeepBrainNet, …

Multiparametric Mri Along With Machine Learning Predicts Prognosis And Treatment Response In Pediatric Low-Grade Glioma, Anahita Fathi Kazerooni, Adam Kraya, Komal Rathi, Meen Chul Kim, Arastoo Vossough, Nastaran Khalili, Ariana Familiar, Deep Gandhi, Neda Khalili, Varun Kesherwani, Debanjan Haldar, Hannah Anderson, Run Jin, Aria Mahtabfar, Sina Bagheri, Yiran Guo, Qi Li, Xiaoyan Huang, Yuankun Zhu, Alex Sickler, Matthew R Lueder, Saksham Phul, Mateusz Koptyra, Phillip Storm, Jeffrey Ware, Yuanquan Song, Christos Davatzikos, Jessica Foster, Sabine Mueller, Michael J Fisher, Adam Resnick, Ali Nabavizadeh

Department of Neurosurgery Faculty Papers

Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free …

Covid-19 Vaccine Hesitancy Among Black Women In The Us, Brittany C Slatton, Farrah G Cambrice, Serwaa S Omowale

Faculty, Staff and Student Publications

IMPORTANCE: COVID-19 vaccine hesitancy among Black women is a critical public health concern, potentially exacerbating existing health disparities and impacting community-wide vaccination efforts.

OBJECTIVE: To explore the factors associated with COVID-19 vaccine hesitancy among Black women in the US and identify the specific concerns and experiences shaping hesitant attitudes toward vaccination.

DESIGN, SETTING, AND PARTICIPANTS: Qualitative study using in-depth, semistructured interviews conducted virtually between June and November 2021. Thematic analysis was used to identify key themes from the interview data. Participants were recruited through social media platforms and word-of-mouth referrals from various regions of the US. Interviews were conducted remotely …

Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …

Enhanced Motivated Behavior Mediated By Pharmacological Targeting Of The Fgf14/Nav16 Complex In Nucleus Accumbens Neurons, Nolan M Dvorak, Paul A Wadsworth, Guillermo Aquino-Miranda, Pingyuan Wang, Douglas S Engelke, Jingheng Zhou, Nghi Nguyen, Aditya K Singh, Giuseppe Aceto, Zahra Haghighijoo, Isabella I Smith, Nana Goode, Mingxiang Zhou, Yosef Avchalumov, Evan P Troendle, Cynthia M Tapia, Haiying Chen, Reid T Powell, Timothy J Baumgartner, Jully Singh, Leandra Koff, Jessica Di Re, Ann E Wadsworth, Mate Marosi, Marc R Azar, Kristina Elias, Paul Lehmann, Yorkiris M Mármol Contreras, Poonam Shah, Hector Gutierrez, Thomas A Green, Martin B Ulmschneider, Marcello D'Ascenzo, Clifford Stephan, Guohong Cui, Fabricio H Do Monte, Jia Zhou, Fernanda Laezza

Faculty, Staff and Student Publications

Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na+ channel 1.6 (Nav1.6) complex regulates excitability of medium spiny neurons (MSN) of the nucleus accumbens (NAc), a central hub of reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl 3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate), a brain-permeable small molecule that targets FGF14R117, a critical residue located within a druggable pocket at the FGF14/Nav1.6 PPI interface. We found that 1028 modulates FGF14/Nav1.6 complex assembly and depolarizes the voltage-dependence of Nav1.6 channel inactivation with …

Dexamethasone Dose Intensity Does Not Impact Outcomes In Newly Diagnosed Multiple Myeloma: A Secondary Swog Analysis, Rahul Banerjee, Rachael Sexton, Andrew J Cowan, Aaron S Rosenberg, Sikander Ailawadhi, S Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Sagar Lonial, Brian G M Durie, Paul G Richardson, Saad Z Usmani, Antje Hoering, Robert Z Orlowski

Faculty, Staff and Student Publications

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM), despite common toxicities, including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 mg once weekly was associated with lower mortality than higher doses. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM has not been fully characterized. We conducted a secondary pooled analysis of the SWOG 0777 and SWOG 1211 studies of NDMM, which used lenalidomide and dexamethasone (Rd) alone, with or without bortezomib, and with or without elotuzumab. The planned …

Adverse Prehospital Events And Outcomes After Traumatic Brain Injury, Amelia W Maiga, Hsing-Hua Sylvia Lin, Stephen R Wisniewski, Joshua B Brown, Ernest E Moore, Martin A Schreiber, Bellal Joseph, Chad T Wilson, Bryan A Cotton, Daniel G Ostermayer, Brian G Harbrecht, Mayur B Patel, Jason L Sperry, Francis X Guyette, Henry E Wang

Faculty, Staff and Student Publications

Importance: While national guidelines recommend avoidance of hypoxia, hypotension, and hypocarbia in the prehospital care of traumatic brain injury (TBI), limited data validate the association of these adverse physiologic events with TBI outcomes.

Objective: To validate the associations of prehospital hypoxia, hypotension, and hypocarbia with TBI outcomes in a US national trauma network.

Design, setting, and participants: This cohort study examined data from 8 level I trauma centers and their affiliated ground and air emergency medical services (EMS) agencies in the Linking Investigations in Trauma and Emergency Services (LITES) Network from January 1, 2017, to June 30, 2021. Adult patients …

The Role Of Iowa Gambling Task Performance In Response To Citalopram Treatment For Cocaine Use Disorder, Constanza De Dios, Robert Suchting, Charles E Green, Heather E Webber, F Gerard Moeller, Scott D Lane, Joy Schmitz

Faculty, Staff and Student Publications

Background:

Cocaine use disorder (CUD) is associated with executive functioning impairments linked to serotonergic function. Previous studies reported efficacy with the selective serotonin reuptake inhibitor citalopram in reducing cocaine use.

Objectives:

The current study explored moderation and mediation of citalopram effects on cocaine use by performance across executive function domains.

Methods:

We conducted a secondary analysis of a double-blind, placebo-controlled, randomized Bayesian adaptive trial investigating citalopram efficacy in CUD treatment-seeking adults. At baseline and mid-treatment, participants completed assessments of decision-making (Iowa Gambling Task; IGT), attention, response inhibition, and cognitive flexibility. Outcomes were longest duration of abstinence (LDA; count of consecutive …

Nucleus-Translocated Gclm Promotes Chemoresistance In Colorectal Cancer Through A Moonlighting Function, Jin-Fei Lin, Ze-Xian Liu, Dong-Liang Chen, Ren-Ze Huang, Fen Cao, Kai Yu, Ting Li, Hai-Yu Mo, Hui Sheng, Zhi-Bing Liang, Kun Liao, Yi Han, Shan-Shan Li, Zhao-Lei Zeng, Song Gao, Huai-Qiang Ju, Rui-Hua Xu

Faculty, Staff and Student Publications

Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, GCLM is phosphorylated by P38 …

Cardiovascular Disease And Breast Cancer Stage At Diagnosi\S, Ivan Angelov, Allen M Haas, Elizabeth Brock, Lingfeng Luo, Jing Zhao, Benjamin D Smith, Sharon H Giordano, Nicholas J Leeper, Kevin T Nead

Faculty, Staff and Student Publications

Importance: Cardiovascular disease (CVD) and cancer are the leading causes of mortality in the US. Large-scale population-based and mechanistic studies support a direct effect of CVD on accelerated tumor growth and spread, specifically in breast cancer.

Objective: To assess whether individuals presenting with advanced breast cancers are more likely to have prevalent CVD compared with those with early-stage breast cancers at the time of diagnosis.

Design, setting, and participants: This population-based case-control study used data from the Surveillance, Epidemiology, and End Results-Medicare linked databases from 2009 to 2020. The analysis was completed from May 2023 to August 2024. Participants were …

Optimizing Electrode Configurations For Eeg Mild Cognitive Impairment Detection, Yi Jiang, Xin Zhang, Zhiwei Guo, Xiaobo Zhou, Jiayuan He, Ning Jiang

Faculty, Staff and Student Publications

The Optimal electrode configuration of Electroencephalograms (EEG) systems for mild cognitive impairment (MCI) detection and monitoring in non-clinical settings, i.e. number of electrodes and the positions of the electrodes, remains to be explored. In the current study, we explored the optimization of electrode configuration for MCI detection. We used a 32-channel EEG device to record the data of 21 MCI patients and 20 cognitively normal elderly (NC) undergoing working memory (WM) tasks. Based on the differential value (MCI group vs. NC group) from the Power Spectral Density (PSD) value of each electrode in θ and α frequency band during WM …

Utility Of Candidate Genes From An Algorithm Designed To Predict Genetic Risk For Opioid Use Disorder, Christal N Davis, Alexander S Hatoum, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

OBJECTIVE: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study examined the association of 15 candidate genetic variants with risk of OUD using electronic health record data from December 20, 1992, to September 30, 2022. Electronic health record …

A Single-Cell Compendium Of Human Cerebrospinal Fluid Identifies Disease-Associated Immune Cell Populations, Claudia Cantoni, Roman A. Smirnov, Maria Firulyova, Prabhakar S. Andhey, Tara R. Bradstreet, Ekaterina Esaulova, Marina Terekhova, Elizabeth A. Schwarzkopf, Nada M. Abdalla, Maksim Kleverov, Anne H. Cross, Maxim N. Artyomov, Brian T. Edelson, Gregory F. Wu, Et Al.

2020-Current year OA Pubs

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, …

Beyond The Numbers: A Qualitative Exploration Of Patient Perspectives On Postpartum Care And Maternal Mortality, Kristen A. Waters

Master of Public Health Program Student Publications

Introduction

Montgomery County faces one of Ohio's highest maternal mortality rates, with notable disparities by race. Despite their importance in reducing maternal deaths, up to 40% of women nationwide do not attend a postpartum care (PPC) visit. While well researched guidelines exist regarding the content and timing of PPC visits, there is a lack of patient perspective on this topic, specifically in the Black-identifying population in an area with a significant burden of maternal mortality.

Methods

Semi-structured interviews and focus group sessions were conducted with 31 participants of maternal health community events in Dayton, OH. Participants were asked their opinions …

Investigating The Relationship Between Adult Obesity And Various Socio-Economic Factors In Ohio, Medhavi Anand, Nicholas Gural

Scholarship in Medicine - All Papers

Background: Obesity continues to be a significant concern in the United States for decades. While several advancements in the field of medicine have been established over the years, obesity has been a serious issue in the adult population in terms of its resources and cost. Objective: The aim is to direct and explore how obesity is linked to various factors such as median household income, access to exercise opportunities, excessive drinking and diabetes prevalence in the state of Ohio.
Methods: Data was collected from the County Health Rankings website from the years 2016 and 2023. Data analytics were done using …

The Cdk8 Kinase Module: A Novel Player In The Transcription Of Translation Initiation And Ribosomal Genes, Brittany Friedson, Stephen D Willis, Natalia Shcherbik, Alicia N Campbell, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Survival following stress is dependent upon reprogramming transcription and translation. Communication between these programs following stress is critical for adaptation but is not clearly understood. The Cdk8 kinase module (CKM) of the Mediator complex modulates the transcriptional response to various stresses. Its involvement in regulating translational machinery has yet to be elucidated, highlighting an existing gap in knowledge. Here, we report that the CKM positively regulates a subset of ribosomal protein (RP) and translation initiation factor (TIF)-encoding genes under physiological conditions in Saccharomyces cerevisiae. In mouse embryonic fibroblasts and HCT116 cells, the CKM regulates unique sets of RP and TIF …

Cd4+ T Cell-Innate Immune Crosstalk Is Critical During Staphylococcus Aureus Craniotomy Infection, Gunjan Kak, Zachary A. Van Roy, Rachel W. Fallet, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. Staphylococcus aureus accounts for half of craniotomy infections, increasing morbidity in a medically fragile patient population. T cells preferentially traffic to the brain during craniotomy infection; however, their functional importance is unknown. Using a mouse model of S. aureus craniotomy infection, CD4+ T cells were critical for bacterial containment, as treatment of WT animals with anti-CD4 exacerbated infection that was similar to phenotypes in Rag1-/- mice. Single-cell RNA-Seq (scRNA-Seq) revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent that displayed …

Electronic And Regular Cigarettes Induce Transcriptional And Physiological Changes In Cardiomyocytes, Hesham Basma, Kajari Dhar, Jason Payne, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cigarette smoking is an important etiology for cardiac diseases and electronic cigarettes are increasing in popularity. In the current study, we assessed physiological and transcriptional changes in human induced pluripotent stem cell derived cardiomyocytes (iPS-CMs) after exposure to electronic cigarette extract (ECE) and conventional cigarette extract (CSE).

METHODS: iPS-CMS were plated on multi-electrode array plates (MEA), electrical and contractile properties were determined by Maestro Edge and computer assisted video analysis (MuscleMotion). Transcriptional profiles were accessed by direct digital mRNA detection of heart failure targeted genes.

RESULTS: Both ECE and CSE extracts significantly prolong beat period from baseline compared to …

Pgc-1Α Activation To Enhance Macrophage Immune Function In Mycobacterial Infections, Joel R. Frandsen, Zhihong Yuan, Brahmchetna Bedi, Zohra Prasla, Seoung-Ryoung Choi, Prabagaran Narayanasamy, Ruxana Sadikot

Journal Articles: Pathology and Microbiology

Nontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence are rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment and potential successful outcomes. Although information exists on the clinical significance of NTMs, little is known about host immune response to infection. NTM infections alter macrophage mitochondrial capacity and decrease ATP production, efficient immune response, and bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis, influencing metabolism, mitochondrial pathways, and antioxidant response. Mitochondrial transcription factor A (TFAM) is a …

Effect Of Praziquantel Treatment On The Nutritional Status Of Children Infected With Schistosoma Haematobium, Louis Fok, Hongying Dai, David Brett-Major, Abebe Animut, Berhanu Erko, John Linville, Yohannes Negash, Abraham Degarege

Journal Articles: Epidemiology

This quasi-experimental trial examined the relationship between Schistosoma haematobium infection and nutritional status, and the impact of single dose praziquantel (PZQ) therapy on undernutrition. A total of 353 children were examined, 112 of which were infected with S. haematobium and treated with PZQ. Children's heights, weights, and mid-upper arm circumferences (MUAC) were measured at baseline and one month post-treatment. Infected children had significantly smaller mean BMI-for-age z-scores (BAZ) (-1.16 vs. 0.11, p < 0.01) and weight-for-age z-scores (WAZ) (-0.61 vs. -0.31, p = 0.03) than the uninfected ones at baseline. S. haematobium infection was associated with underweight (adjusted OR: 1.76, 95% CI: 1.63-1.90). One month after treatment, BAZ, WAZ, …

Is There An Association Between Living In A Rural Area And The Incidence Of Postoperative Complications Or Hospital Readmissions Following Left Ventricular Assist Device (Lvad) Implantation, Compared To Urban Lvad Recipients? A Systematic Review., Samrat Gollapudi, Abhiram Gollapudi, Sri Banala, Sheraj Singh, Kiran Tadi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Left ventricular assist devices (LVADs) are utilized as a therapeutic option for patients with end-stage heart failure. While LVAD implantation can enhance survival rates and quality of life, the procedure has its risks, and postoperative complications are common. This review aims to investigate whether there is an association between living in a rural area and the incidence of postoperative complications or hospital readmissions following LVAD implantation, compared to urban LVAD recipients.

METHODS: A comprehensive literature review examined studies that compared postoperative outcomes between rural and urban LVAD recipients. Data on adverse events, hospitalizations, and mortality rates were extracted, focusing …

Zinc Promotes Mitochondrial Health Through Pgc-1alpha Enhancing Bacterial Clearance In Macrophages Infected With Mycobacterium Avium Complex, Ruxana Sadikot, Prabagaran Narayanasamy, Zhihong Yuan, Deandra R. Smith, Daren L. Knoell

Journal Articles: Pulmonary & Critical Care Med

Mitochondria are increasingly recognized as important contributors to immune function, in addition to energy production. They exert this influence through modulation of various signaling pathways that regulate cellular metabolism and immune function in response to pathogens. Peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha (PGC-1α) is the primary transcription factor and regulator involved in mitochondrial biogenesis. Long known to be involved in immune function, zinc (Zn) is also required for proper mitochondrial function. It is increasingly recognized that many cellular immunometabolic activities are also Zn-dependent. Taken together, we investigated the role of Zn deficiency, both dietary and genetically induced, and Zn …

Catalytic Effect Of Amyloid-Β On Native Tau Aggregation At Physiologically Relevant Concentrations, Rakhi Chowdhury, Apu Chandra Das, Ruan Van Deventer, Luda S. Shlyakhtenko, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Alzheimer's disease (AD) is characterized by the accumulation and aggregation of tau and amyloid-β (Aβ). The pathophysiology and progression of AD are facilitated by the neurotoxic effects of these aggregated proteins, resulting in neurodegeneration and memory loss. In this context, the interaction between tau and Aβ42 is considered, but the mechanism underlying their pathogenic interplay remains unclear. Here, we addressed this question by studying the aggregation of full-length, unmodified tau and Aβ42 at physiologically low concentrations using atomic force microscopy (AFM). AFM imaging and data analyses demonstrate an increase in tau aggregation in the presence of Aβ42, characterized by increased …