Medicine and Health Sciences Commons^™

Injury-Induced Foxm1 Expression In The Mouse Kidney Drives Epithelial Proliferation By A Cyclin F-Dependent Mechanism, Megan L. Noonan, Yoshiharu Muto, Yasuhiro Yoshimura, Aidan Leckie-Harre, Haojia Wu, Vladimir V. Kalinichenko, Benjamin D. Humphreys, Monica Chang-Panesso

2020-Current year OA Pubs

Acute kidney injury (AKI) strongly upregulates the transcription factor Foxm1 in the proximal tubule in vivo, and Foxm1 drives epithelial proliferation in vitro. Here, we report that deletion of Foxm1 either with a nephron-specific Cre driver or by inducible global deletion reduced proximal tubule proliferation after ischemic injury in vivo. Foxm1 deletion led to increased AKI to chronic kidney disease transition, with enhanced fibrosis and ongoing tubule injury 6 weeks after injury. We report ERK mediated FOXM1 induction downstream of the EGFR in primary proximal tubule cells. We defined FOXM1 genomic binding sites by cleavage under targets and release using …

Role Of The Afferent Lymph As An Immunological Conduit To Analyze Tissue Antigenic And Inflammatory Load, Padma P Nanaware, Cheryl F Lichti, Xiaoxiao Wan, Emil R Unanue, Et Al.

2020-Current year OA Pubs

The lymphatic fluid is the conduit by which part of the tissue "omics" is transported to the draining lymph node for immunosurveillance. Following cannulation of the pre-nodal cervical and mesenteric afferent lymphatics, herein we investigate the lymph proteomic composition, uncovering that its composition varies according to the tissue of origin. Tissue specificity is also reflected in the dendritic cell-major histocompatibility complex class II-eluted immunopeptidome harvested from the cervical and mesenteric nodes. Following inflammatory disruption of the gut barrier, the lymph antigenic and inflammatory loads are analyzed in both mice and subjects with inflammatory bowel diseases. Gastrointestinal tissue damage reflects the …

The Attainment Of A Patient Acceptable Symptom State In Patients Undergoing Revision Spine Fusion, Tariq Z. Issa, Omar H. Tarawneh, Teeto Ezeonu, Ameer A. Haider, Rajkishen Narayanan, Jose A. Canseco, Alan S. Hilibrand, Alexander R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Rothman Institute Papers

INTRODUCTION: Revision lumbar fusion is most commonly due to nonunion, adjacent segment disease (ASD), or recurrent stenosis, but it is unclear if diagnosis affects patient outcomes. The primary aim of this study was to assess whether patients achieved the patient acceptable symptom state (PASS) or minimal clinically important difference (MCID) after revision lumbar fusion and assess whether this was influenced by the indication for revision.

METHODS: We retrospectively identified all 1-3 level revision lumbar fusions at a single institution. Oswestry Disability Index (ODI) was collected at preoperative, three-month postoperative, and one-year postoperative time points. The MCID was calculated using a …

Tumor Biomechanical Stiffness By Magnetic Resonance Elastography Predicts Surgical Outcomes And Identifies Biomarkers In Vestibular Schwannoma And Meningioma, Bailey H Duhon, Kristin Thompson, Melanie Fisher, Vivian F Kaul, Han Tn Nguyen, Michael S Harris, Varun Varadarajan, Oliver F Adunka, Daniel M Prevedello, Arunark Kolipaka, Yin Ren

Faculty, Staff and Student Publications

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial …

An Improved Method For Diagnosis Of Parkinson’S Disease Using Deep Learning Models Enhanced With Metaheuristic Algorithm, Babita Majhi, Aarti Kashyap, Siddhartha Suprasad Mohanty, Sujata Dash, Saurav Mallik, Aimin Li, Zhongming Zhao

Faculty, Staff and Student Publications

Parkinson's disease (PD) is challenging for clinicians to accurately diagnose in the early stages. Quantitative measures of brain health can be obtained safely and non-invasively using medical imaging techniques like magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). For accurate diagnosis of PD, powerful machine learning and deep learning models as well as the effectiveness of medical imaging tools for assessing neurological health are required. This study proposes four deep learning models with a hybrid model for the early detection of PD. For the simulation study, two standard datasets are chosen. Further to improve the performance of …

Paralumbar Compartment Syndrome, A Rare Sequela Of Deadlifting: A Case Report And Review Of Current Literature., Mark Lagreca, Thomas Falconiero, Anthony Viola, Aakash Patel, Arash Bagragheh, Brian Danshaw, Scott Rushton

Orthopedic Surgery Resident Research

BACKGROUND: Compartment syndrome is a well-known phenomenon that is most commonly reported in the extremities. However, paralumbar compartment syndrome is rarely described in available literature. The authors present a case of paralumbar compartment syndrome after high intensity deadlifting.

CASE PRESENTATION: 53-year-old male who presented with progressively worsening low back pain and paresthesias one day after high-intensity deadlifting. Laboratory testing found the patient to be in rhabdomyolysis; he was admitted for intravenous fluid resuscitation and pain control. Orthopedics was consulted, and Magnetic Resonance Imaging revealed significant paravertebral edema and loss of muscle striation. Given the patient's lack of improvement with intravenous …

A Comparison Of Icare And Goldmann Applanation Tonometry Measurements During The Covid-19 Pandemic: A Retrospective Study, Shreya Swaminathan, Amber M. Kisielewski, M. Hossein Nowroozzadeh, Shahin Hallaj, Daniel Lee, Natasha N. Kolomeyer, Jonathan S. Myers, Reza Razeghinejad

Wills Eye Hospital Papers

PURPOSE: To evaluate factors associated with differences in intraocular pressure (IOP) readings between iCare and Goldmann applanation tonometry (GAT) in established glaucoma patients.

METHODS: This retrospective comparative study included clinical data of 350 eyes from 350 established glaucoma patients who had iCare and GAT IOP measured by an ophthalmic technician and a glaucoma specialist, respectively. The main outcome measure was the difference in IOP measurements of the right eyes with iCare and GAT.

RESULTS: The intraclass correlation coefficient (ICC) between GAT and iCare was 0.90. The mean IOP difference between tonometers was - 0.18 ± 2.89 mmHg. Bland-Altman plots indicated …

A Case Of Severe Anaphylactic Reaction After Administration Of Diagnostic-Dose Ferumoxytol In A Pediatric Patient, Fam Ekladious, David Saul

Jefferson Hospital Staff Papers and Presentations

We describe a case of anaphylaxis during administration of intravenous (IV) ferumoxytol as a magnetic resonance imaging (MRI) contrast agent in a 4-year-old patient with complicated past medical history including YARS genetic mutation with resultant liver failure and deceased donor liver transplantation, stage IV chronic kidney disease (CKD), and hypertension. The patient was noted to have labored breathing 4 min after initiation of ferumoxytol infusion and was subsequently rapidly intubated and returned to the intensive care unit (ICU) for monitoring. Anaphylactic reactions to therapeutic doses of ferumoxytol led to issuance of a black box warning by the FDA in 2015. …

Noninvasive Assessment Of The Lung Inflammation-Fibrosis Axis By Targeted Imaging Of Cmklr1, Philip Z Mannes, Taylor S Adams, Samaneh Farsijani, Clayton E Barnes, Joseph D Latoche, Kathryn E Day, Jessie R Nedrow, Farida Ahangari, Naftali Kaminski, Janet S Lee, Sina Tavakoli

2020-Current year OA Pubs

Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and therapeutic monitoring. Here, we validated the accuracy of CMKLR1 as an imaging biomarker of the lung inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, we demonstrated

The Relationship Between Medication Beliefs, Patient Activation, And Self-Rated Health In Patients Taking Oral Anticancer Agents, Misun Hwang, Youmin Cho, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH.

Methods: A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, …

Association Between Obstructive Sleep Apnea And Risk Of Benign Vocal Fold Lesions: A Nationwide 9-Year Follow-Up Cohort Study, Yong Tae Hong, Min Gu Kang, Min Gyu Lee, Sang Woo Yeom, Jong Seung Kim

Faculty, Staff and Student Publications

Since obstructive sleep apnea (OSA) affects various parts of the body, there has been little interest about the effect of OSA on voice. The objective of this study was to evaluate the risk of benign vocal fold lesions (BVFL) in OSA patients. This study used data from the National Health Insurance Service (NHIS) database. The study group was defined as the group diagnosed with OSA between 2008 and 2011. Non-OSA groups were selected based on propensity score (PS) matching. Incidence of BVFL among participants during the follow-up was analyzed. Cox proportional hazard regression analyses were performed to evaluate the association …

Changes In Plasma Concentrations Of Per- And Polyfluoroalkyl Substances After Bariatric Surgery In Adolescents From The Teen-Longitudinal Assessment Of Bariatric Surgery (Teen-Labs) Study, Brittney O Baumert, Sandrah P Eckel, Jesse A Goodrich, Zhenjiang Li, Nikos Stratakis, Douglas I Walker, Yinqi Zhao, Fabian Christoph Fischer, Scott Bartell, Damaskini Valvi, Xiangping Lin, Zoe Coates Fuentes, Thomas Inge, Justin Ryder, Todd Jenkins, Rohit Kohli, Stephanie Sisley, Stavra Xanthakos, Sarah Rock, Michele A La Merrill, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate …

Cognitive Enhancing Effect Of Rtms Combined With Tdcs In Patients With Major Depressive Disorder: A Double-Blind, Randomized, Sham-Controlled Study, Xingxing Li, Junyao Liu, Shuochi Wei, Chang Yu, Dongmei Wang, Yuchen Li, Jiaxin Li, Wenhao Zhuang, Rui-Chen-Xi Luo, Yanli Li, Zhiwang Liu, Yuqiu Su, Jimeng Liu, Yongming Xu, Jialin Fan, Guidong Zhu, Weiqian Xu, Yiping Tang, Hui Yan, Raymond Y Cho, Thomas R Kosten, Dongsheng Zhou, Xiangyang Zhang

Staff and Researcher Publications

BACKGROUND: Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients.

METHODS: In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, …

Improving Emergency Medicine Resident Pediatric Lumbar Puncture Procedural Performance Through A Brief Just-In-Time Video Intervention, Sarayna S Mcguire, Alexander S Finch, Jenna M Thomas, Octavio Lazaro, Sara A Hevesi, Aidan F Mullan, Jim L Homme

2020-Current year OA Pubs

BACKGROUND: Emergency medicine (EM) trainee comfort level with lumbar puncture (LP) has decreased over time due to changing practice guidelines, particularly amongst pediatric patients. We implemented a "just in time" (JIT) brief educational video based on a previously published LP Performance Scoring Checklist to improve trainee efficiency and competence in LP performance.

METHODS: Our pilot quasi-experimental study took place January-June 2022 within a large, academic Midwestern emergency department (ED) with an established 3-year EM residency program. All 9 interns performed a timed diagnostic LP on an infant LP model in January, scored according to the LP Performance Scoring Checklist. In …

Elderly Mice With History Of Acetaminophen Intoxication Display Worsened Cognitive Impairment And Persistent Elevation Of Astrocyte And Microglia Burden, Celso S G Catumbela, Rodrigo Morales

Faculty, Staff and Student Publications

Acetaminophen (APAP) is a leading cause of acute liver failure. The effect of APAP metabolite's effects in the periphery are well characterized; however, associated consequences in the brain remain poorly understood. Animal studies on this subject are few and reveal that frequent APAP intake can trigger cerebral abnormalities that vary depending on the subject's age. Alarmingly, experimental efforts have yet to examine associated consequences in elderly hosts, who correspond to the highest risk of medication overload, impaired drug clearance, and cognitive deficits. Here, we interrogated the cerebral and peripheral pathology of elderly mice submitted to monthly episodes of APAP intoxication …

Successful Management Of Chromoblastomycosis Utilizing Conventional Antifungal Agents And Imiquimod Therapy, Jinjin Zheng, Shougang Liu, Zhenmou Xie, Yangxia Chen, Liyan Xi, Hongfang Liu, Yinghui Liu

Faculty, Staff and Student Publications

Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal …

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results Of A Multicenter, Randomized, Controlled Trial, Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where …

Enabling Tobacco Treatment For Gastroenterology Patients Via A Novel Low-Burden Point-Of-Care Model, Suha Abushamma, Li-Shiun Chen, Jingling Chen, Nina Smock, Giang Pham, Chien-Huan Chen

2020-Current year OA Pubs

BACKGROUND & AIM: Smoking is a major risk factor for multiple gastrointestinal cancers, and adversely affects peptic ulcer disease, gastroesophageal reflux, pancreatitis and Crohn's disease. Despite key recommendations for diagnosing and treating tobacco use disorder in healthcare settings, the degree to which this is implemented in Gastroenterology (GI) clinics is unknown. We aimed to assess our providers' practices, identify barriers for implementing evidence-based smoking cessation treatments, and address these barriers by implementing a novel low-burden point of care Electronic health record-enabled evidence-based tobacco treatment (ELEVATE), in GI clinics.

METHODS: An online survey was distributed to clinic gastroenterologists. ELEVATE module training …

Advanced Hiv Disease And Associated Factors Among Young People Aged 15-24 Years At A Tertiary Hospital In Sierra Leone: A Cross-Sectional Study, Mamadu Baldeh, Samuel Kizito, Sulaiman Lakoh, Daniel Sesay, Samuel Adeyemi Williams, Umu Barrie, Frida Dennis, Dimbintsoa Rakotomalala Robinson, Franck Lamontagne, Franck Amahowe, Patrick Turay, Ozge Sensoy Bahar, Elvin Geng, Fred M Ssewamala

2020-Current year OA Pubs

BACKGROUND: Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 - 24 years seeking medical services at a major public hospital in Sierra Leone.

METHODS: We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone …

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo UDP fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through Calcium Extruder (“CalEx”) …

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

Faculty, Staff and Student Publications

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …

Impact Of Cognitive Impairment On Driving Behaviour And Route Choices Of Older Drivers: A Real-World Driving Study, Reihaneh Derafshi, Ganesh M Babulal, Sayeh Bayat

2020-Current year OA Pubs

Maintaining driving independence is important for older adults. However, cognitive decline, a common issue in older populations, can impair older adults' driving abilities and overall safety on the roads. This study explores how cognitive impairment influences driving patterns and driving choices among older adults. We analyzed real-world driving patterns of 246 older adults using GPS dataloggers. Our sample included 230 cognitively normal older adults (CN; Clinical Dementia Rating

Real World Predictors Of Response And 24-Month Survival In High-Grade Tp53-Mutated Myeloid Neoplasms, Amandeep Kaur, Alexandra E Rojek, Emily Symes, Mariam T Nawas, Anand A Patel, Jay L Patel, Payal Sojitra, Barina Aqil, Madina Sukhanova, Megan E Mcnerney, Leo P Wu, Aibek Akmatbekov, Jeremy Segal, Melissa Y Tjota, Sandeep Gurbuxani, Jason X Cheng, Su-Yeon Yeon, Harini V Ravisankar, Carrie Fitzpatrick, Angela Lager, Michael W Drazer, Caner Saygin, Pankhuri Wanjari, Panagiotis Katsonis, Olivier Lichtarge, Jane E Churpek, Sharmila B Ghosh, Ami B Patel, Madhu P Menon, Daniel A Arber, Peng Wang, Girish Venkataraman

Faculty, Staff and Students Publications

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 …

Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke

Faculty, Staff and Student Publications

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody …

Protein Restriction Slows The Development And Progression Of Pathology In A Mouse Model Of Alzheimer's Disease, Reji Babygirija, Natalie M Niemi, Et Al.

2020-Current year OA Pubs

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also …

Incidence And Risk Factors For New And Recurrent Infarcts In Adults With Sickle Cell Disease, Lori C Jordan, Allison A King, Andria L Ford, Taniya E Varughese, Lisa Garrett, Et Al.

2020-Current year OA Pubs

BACKGROUND: Most adults with sickle cell disease will experience a silent cerebral infarction (SCI) or overt stroke. Identifying patient subgroups with increased stroke incidence is important for future clinical trials focused on stroke prevention. Our 3-center prospective cohort study tested the primary hypothesis that adults with sickle cell disease and SCIs have a greater incidence of new stroke or SCI compared with those without SCI. A secondary aim focused on identifying additional risk factors for progressive infarcts, particularly traditional risk factors for stroke in adults.

METHODS AND RESULTS: This observational study included adults with sickle cell disease and no history …

Efficacy And Safety Of Esmethadone (Rel-1017) In Patients With Major Depressive Disorder And Inadequate Response To Standard Antidepressants: A Phase 3 Randomized Controlled Trial, Maurizio Fava, Stephen M Stahl, Luca Pani, Sara De Martin, Andrew J Cutler, Vladimir Maletic, Charles W Gorodetzky, Frank J Vocci, Frank L Sapienza, Thomas R Kosten, Cornelia Kröger, Paggard Champasa, Cedric O'Gorman, Clotilde Guidetti, Andrea Alimonti, Stefano Comai, Andrea Mattarei, Franco Folli, David Bushnell, Sergio Traversa, Charles E Inturrisi, Paolo L Manfredi, Marco Pappagallo

Faculty, Staff and Students Publications

No abstract provided.

The Ifitm5 Mutation In Osteogenesis Imperfecta Type V Is Associated With An Erk/Sox9-Dependent Osteoprogenitor Differentiation Defect, Ronit Marom, I-Wen Song, Emily C Busse, Megan E Washington, Ava S Berrier, Vittoria C Rossi, Laura Ortinau, Youngjae Jeong, Ming-Ming Jiang, Brian C Dawson, Mary Adeyeye, Carolina Leynes, Caressa D Lietman, Bridget M Stroup, Dominyka Batkovskyte, Mahim Jain, Yuqing Chen, Racel Cela, Alexis Castellon, Alyssa A Tran, Isabel Lorenzo, D Nicole Meyers, Shixia Huang, Alicia Turner, Vinitha Shenava, Maegen Wallace, Eric Orwoll, Dongsu Park, Catherine G Ambrose, Sandesh Cs Nagamani, Jason D Heaney, Brendan H Lee

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with …

Diverse Mentoring Connections Across Institutional Boundaries In The Biomedical Sciences: Innovative Graph Database Analysis, Toufeeq Ahmed Syed, Erika L Thompson, Zainab Latif, Jay Johnson, Damaris Javier, Katie Stinson, Gabrielle Saleh, Jamboor K Vishwanatha

Faculty, Staff and Student Publications

BACKGROUND: With an overarching goal of increasing diversity and inclusion in biomedical sciences, the National Research Mentoring Network (NRMN) developed a web-based national mentoring platform (MyNRMN) that seeks to connect mentors and mentees to support the persistence of underrepresented minorities in the biomedical sciences. As of May 15, 2024, the MyNRMN platform, which provides mentoring, networking, and professional development tools, has facilitated more than 12,100 unique mentoring connections between faculty, students, and researchers in the biomedical domain.

OBJECTIVE: This study aimed to examine the large-scale mentoring connections facilitated by our web-based platform between students (mentees) and faculty (mentors) across institutional …

Maldi Imaging Mass Spectrometry Visualizes The Distribution Of Antidepressant Duloxetine And Its Major Metabolites In Mouse Brain, Liver, Kidney, And Spleen Tissues, Saleh M Khalil, Xuan Qin, John M Hakenjos, Jian Wang, Zhaoyong Hu, Xinli Liu, Jin Wang, Mirjana Maletic-Savatic, Kevin R Mackenzie, Martin M Matzuk, Feng Li

Faculty, Staff and Student Publications

Imaging mass spectrometry (IMS) is a powerful tool for mapping the spatial distribution of unlabeled drugs and metabolites that may find application in assessing drug delivery, explaining drug efficacy, and identifying potential toxicity. This study focuses on determining the spatial distribution of the antidepressant duloxetine, which is widely prescribed despite common adverse effects (liver injury, constant headaches) whose mechanisms are not fully understood. We used high-resolution IMS with matrix-assisted laser desorption/ionization to examine the distribution of duloxetine and its major metabolites in four mouse organs where it may contribute to efficacy or toxicity: brain, liver, kidney, and spleen. In none …