Medical Specialties Commons^™

The Cx3cl1-Cx3cr1 Chemokine Axis Can Contribute To Tumor Immune Evasion And Blockade With A Novel Cx3cr1 Monoclonal Antibody Enhances Response To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri, Xia Bu, Yunfei Wang, Michael Gomez, James A Torchia, Ping Hua, Shao-Hsi Hung, Michael A Davies, Gregory A Lizee, Ulrich Von Andrian, Patrick Hwu, Gordon J Freeman

Faculty, Staff and Student Publications

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration. We generated a novel monoclonal antibody against mouse CX3CR1 that binds to CX3CR1 and blocks the CX3CL1-CX3CR1 interaction. We next explored the immune evasion strategies implemented by the CX3CL1-CX3CR1 axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of soluble …

Stephen Massey: A Career In Visual Neuroscience, Stephen L Mills, David W Marshak

Faculty, Staff and Student Publications

This review is a memoir by Dr. Stephen C. Massey's longtime collaborator, Dr. Stephen L. Mills, and written, for the most part, in the first person. It also serves as an introduction to the virtual festschrift to celebrate Dr. Massey's retirement. and. The references cited here are only a few of the highlights of Dr. Massey's distinguished career. A complete list is found here: https://pubmed.ncbi.nlm.nih.gov/?term=massey+sc+%28retina+or+photoreceptors%29&sort=date.

Nano-Embedded Medical Devices And Delivery Systems In Interventional Radiology, Erin Marie D San Valentin, Allan John R Barcena, Carleigh Klusman, Benjamin Martin, Marites P Melancon

Faculty, Staff and Student Publications

Nanomaterials research has significantly accelerated the development of the field of vascular and interventional radiology. The incorporation of nanoparticles with unique and functional properties in medical devices and delivery systems has paved the way for the creation of novel diagnostic and therapeutic procedures for various clinical disorders. In this review, we discuss the advancements in the field of interventional radiology and the role of nanotechnology in maximizing the benefits and mitigating the disadvantages of interventional radiology theranostic procedures. Several nanomaterials have been studied to improve the efficacy of interventional radiology interventions, reduce the complications associated with medical devices, improve the …

Associative Learning Contributes To The Persistence Of Fatigue-Like Behavior In Male Mice In A Model Of Cancer Survivorship, Elisabeth G Vichaya, Josephine K Darpolor, Phillip S Gross, Jessica M Molkentine, Daniel W Vermeer, Paola D Vermeer, John H Lee, Cullen M Taniguchi, Robert Dantzer

Faculty, Staff and Student Publications

Persistent fatigue is a debilitating side effect that impacts a significant proportion of cancer survivors for which there is not yet an FDA-approved treatment. While certainly a multi-factorial problem, persistent fatigue could be due, in part, to associations learned during treatment. Therefore, we sought to investigate the role of associative learning in the persistence of fatigue using a preclinical model of cancer survivorship. For this purpose, we used a murine model of human papilloma virus-related head and neck cancer paired with a curative regimen of cisplatin-based chemoradiation in male C57BL/6J mice. Fatigue-like behavior was assessed by measuring variations in voluntary …

Small Molecule Inhibitor Of Tau Self-Association In A Mouse Model Of Tauopathy: A Preventive Study In P301l Tau Jnpl3 Mice, Eliot J Davidowitz, Patricia Lopez, Heidy Jimenez, Leslie Adrien, Peter Davies, James G Moe

Faculty, Staff and Student Publications

Advances in tau biology and the difficulties of amyloid-directed immunotherapeutics have heightened interest in tau as a target for small molecule drug discovery for neurodegenerative diseases. Here, we evaluated OLX-07010, a small molecule inhibitor of tau self-association, for the prevention of tau aggregation. The primary endpoint of the study was statistically significant reduction of insoluble tau aggregates in treated JNPL3 mice compared with Vehicle-control mice. Secondary endpoints were dose-dependent reduction of insoluble tau aggregates, reduction of phosphorylated tau, and reduction of soluble tau. This study was performed in JNPL3 mice, which are representative of inherited forms of 4-repeat tauopathies with …

Artificial Intelligence-Driven Meta-Analysis Of Brain Gene Expression Identifies Novel Gene Candidates And A Role For Mitochondria In Alzheimer’S Disease, Caitlin A Finney, Fabien Delerue, Wendy A Gold, David A Brown, Artur Shvetcov

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the most common form of dementia. There is no treatment and AD models have focused on a small subset of genes identified in familial AD. Microarray studies have identified thousands of dysregulated genes in the brains of patients with AD yet identifying the best gene candidates to both model and treat AD remains a challenge. We performed a meta-analysis of microarray data from the frontal cortex (n = 697) and cerebellum (n = 230) of AD patients and healthy controls. A two-stage artificial intelligence approach, with both unsupervised and supervised machine learning, combined with a functional …

A Unified Mediation Analysis Framework For Integrative Cancer Proteogenomics With Clinical Outcomes, Licai Huang, James P Long, Ehsan Irajizad, James D Doecke, Kim-Anh Do, Min Jin Ha

Faculty, Staff and Student Publications

MOTIVATION: Multilevel molecular profiling of tumors and the integrative analysis with clinical outcomes have enabled a deeper characterization of cancer treatment. Mediation analysis has emerged as a promising statistical tool to identify and quantify the intermediate mechanisms by which a gene affects an outcome. However, existing methods lack a unified approach to handle various types of outcome variables, making them unsuitable for high-throughput molecular profiling data with highly interconnected variables.

RESULTS: We develop a general mediation analysis framework for proteogenomic data that include multiple exposures, multivariate mediators on various scales of effects as appropriate for continuous, binary and survival outcomes. …

Sparse Tree-Based Clustering Of Microbiome Data To Characterize Microbiome Heterogeneity In Pancreatic Cancer, Yushu Shi, Liangliang Zhang, Kim-Anh Do, Robert Jenq, Christine B Peterson

Faculty, Staff and Student Publications

There is a keen interest in characterizing variation in the microbiome across cancer patients, given increasing evidence of its important role in determining treatment outcomes. Here our goal is to discover subgroups of patients with similar microbiome profiles. We propose a novel unsupervised clustering approach in the Bayesian framework that innovates over existing model-based clustering approaches, such as the Dirichlet multinomial mixture model, in three key respects: we incorporate feature selection, learn the appropriate number of clusters from the data, and integrate information on the tree structure relating the observed features. We compare the performance of our proposed method to …

Late Effects Of Craniospinal Irradiation Using Electron Spinal Fields For Pediatric Patients With Cancer, Brian De, Marcus A Florez, Ethan B Ludmir, Moshe H Maor, Susan L Mcgovern, Mary Frances Mcaleer, David R Grosshans, Eric L Chang, Anita Mahajan, Arnold C Paulino

Faculty, Staff and Student Publications

Purpose: For children, craniospinal irradiation (CSI) with photons is associated with significant toxic effects. The use of electrons for spinal fields is hypothesized to spare anterior structures but the long-term effects remain uncertain. We studied late effects of CSI using electrons for spinal radiation therapy (RT).

Methods and materials: Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution between 1983 and 2014 were reviewed. Median age at RT was 5 (range, 1-14) years. The most common histologies were medulloblastoma/primitive neuroectodermal tumor (59%) and ependymoma (8%). The median prescribed dose to the entire …

Protective Role Of Colitis In Inflammatory Arthritis Via Propionate-Producing Bacteroides In The Gut, Hoh-Jeong Shon, Yu-Mi Kim, Kyeong Seog Kim, Jin-Ouk Choi, Sang-Hyun Cho, Sujin An, Se-Hyeon Park, Yong-Joon Cho, Joo-Hong Park, Sang-Uk Seo, Joo-Youn Cho, Wan-Uk Kim, Donghyun Kim

Faculty, Staff and Student Publications

OBJECTIVES: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events.

METHODS: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated …

Predictive Modeling Using Shape Statistics For Interpretable And Robust Quality Assurance Of Automated Contours In Radiation Treatment Planning, Zachary T Wooten, Cenji Yu, Laurence E Court, Christine B Peterson

Faculty, Staff and Student Publications

Deep learning methods for image segmentation and contouring are gaining prominence as an automated approach for delineating anatomical structures in medical images during radiation treatment planning. These contours are used to guide radiotherapy treatment planning, so it is important that contouring errors are flagged before they are used for planning. This creates a need for effective quality assurance methods to enable the clinical use of automated contours in radiotherapy. We propose a novel method for contour quality assurance that requires only shape features, making it independent of the platform used to obtain the images. Our method uses a random forest …

Grid Cells, Border Cells, And Discrete Complex Analysis, Yuri Dabaghian

Faculty, Staff and Student Publications

We propose a mechanism enabling the appearance of border cells-neurons firing at the boundaries of the navigated enclosures. The approach is based on the recent discovery of discrete complex analysis on a triangular lattice, which allows constructing discrete epitomes of complex-analytic functions and making use of their inherent ability to attain maximal values at the boundaries of generic lattice domains. As it turns out, certain elements of the discrete-complex framework readily appear in the oscillatory models of grid cells. We demonstrate that these models can extend further, producing cells that increase their activity toward the frontiers of the navigated environments. …

Pediatric Diarrhea Patients Living In Urban Areas Have A Higher Incidence Of Clostridioides Difficile Infection, Ayodele T Adesoji, Osaro Mgbere, Charles Darkoh

Faculty, Staff and Student Publications

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and an unappreciated contributor to child mortality in low- and middle-income countries where the diagnosis may be difficult. There is little information about the prevalence of CDI among infants, children, and adolescents in Africa. Using a cross-sectional design, seventy-six samples were collected from pediatric patients presenting with diarrhea, including infants (≤ 2 years old), children (2-12 years), and adolescents (13 ≤17 years) from three hospitals between January and December 2019. Demographic data, medical history, and prior antibiotic use were recorded. Toxigenic culture and PCR were used to detect and …

Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Charles Darkoh, Ekere James Essien

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic constitutes a global health threat and poses a major burden on the African continent. We assessed the real-world burden of COVID-19 infection in African Union (AU) member states to determine the distributional patterns of epidemiological measures during the first 1 year of the pandemic.

METHODS: This retrospective cross-sectional study utilized COVID-19 data from publicly available data repositories of the African Center for Disease Control and Prevention and

RESULTS: A total of 3.21 million cases were reported during the 1-year period, with 2.6 million recoveries, 536,784 cases remaining active, and 77,486 deaths. Most countries (49.1%,

CONCLUSION: Understanding …

Evolutionary Aspects Of Infections: Inflammation And Sickness Behaviors, Robert Dantzer

Faculty, Staff and Student Publications

Sickness behavior was conceptualized initially as the behavioral counterpart of the fever response to infectious pathogens. It helps to raise body temperature to its higher setpoint and to maintain it at this new level and it has the additional benefit of enabling a weakened organism to protect itself from other dangers. The discovery of the behavioral effects of proinflammatory cytokines produced by activated immune cells provided a cellular and molecular basis to this phenomenon. The administration of cytokines or cytokine inducers like lipopolysaccharide to healthy rodents allowed to reveal the similarities and differences between inflammation-induced sickness behavior and the fever …

Inhibition Of Nox2 Or Nlrp3 Inflammasome Prevents Cardiac Remote Ischemic Preconditioning, Sandra Benavides, Rodrigo Palavecino, Jaime A Riquelme, Luis Montecinos, José Pablo Finkelstein, Paulina Donoso, Gina Sánchez

Faculty, Staff and Student Publications

Introduction: Short episodes of ischemia-reperfusion (IR) in the heart (classical ischemic preconditioning, IPC) or in a limb (remote ischemic preconditioning, RIPC) before a prolonged ischemic episode, reduce the size of the infarct. It is unknown whether IPC and RIPC share common mechanisms of protection. Animals KO for NOX2, a superoxide-producing enzyme, or KO for NLRP3, a protein component of inflammasome, are not protected by IPC. The aim of this study was to investigate if NOX2 or NLRP3 inflammasome are involved in the protection induced by RIPC. Methods: We preconditioned rats using 4 × 5 min periods of IR in the …

Endothelial Activation Impairs The Function Of Small Extracellular Vesicles, Nicolas Herrera-Zelada, Úrsula Zúñiga-Cuevas, Andrés Ramírez-Reyes, Ignacio Norambuena-Soto, Leslye Venegas-Zamora, Mayarling F Troncoso, Alejandra Hernández, Gina Sánchez, Zully Pedrozo, Sergio Lavandero, Jaime A Riquelme

Faculty, Staff and Student Publications

Small extracellular vesicles are nanosized vesicles (30-200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were …

Targeting Mcl-1 Protein To Treat Cancer: Opportunities And Challenges, Shady I Tantawy, Natalia Timofeeva, Aloke Sarkar, Varsha Gandhi

Faculty, Staff and Student Publications

Evading apoptosis has been linked to tumor development and chemoresistance. One mechanism for this evasion is the overexpression of prosurvival B-cell lymphoma-2 (BCL-2) family proteins, which gives cancer cells a survival advantage. Mcl-1, a member of the BCL-2 family, is among the most frequently amplified genes in cancer. Targeting myeloid cell leukemia-1 (MCL-1) protein is a successful strategy to induce apoptosis and overcome tumor resistance to chemotherapy and targeted therapy. Various strategies to inhibit the antiapoptotic activity of MCL-1 protein, including transcription, translation, and the degradation of MCL-1 protein, have been tested. Neutralizing MCL-1's function by targeting its interactions …

การศึกษาลักษณะกลายพันธุ์ของยีนที่ถอดรหัสเป็นโปรตีนในเยื่อหุ้มเซลล์เม็ดเลือดแดงในผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติ, จารุวรรณ ปานาราช

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติเป็นโรคโลหิตจางตั้งแต่กำเนิดเกิดจากการกลายพันธุ์ของยีนที่กำหนดการสร้างโปรตีนไซโทสเกเลตอนซึ่งเป็นโครงสร้างของเยื่อหุ้มเซลล์เม็ดเลือดแดงเพื่อให้เซลล์เม็ดเลือดแดงมีความยืดหยุ่นและรักษารูปร่างได้โดยยีนที่เกี่ยวข้องได้แก่ ANK1, SPTA1, SPTB, EPB42 และ SLC4A1 งานวิจัยนี้ทำการศึกษาการกลายพันธุ์โดยใช้ Whole exome sequence (WES) และตรวจยืนยันผลด้วยเทคนิค Sanger sequencing ซึ่งงานวิจัยนี้พบการกลายพันธุ์ตำแหน่งใหม่ที่เป็นสาเหตุทำให้เกิดโรคเม็ดเลือดแดงป่องพันธุกรรมจำนวน 3 ตำแหน่งและพบการกลายพันธุ์ในผู้ป่วย hereditary pyropoikilocytosis (HPP) 1 ตำแหน่ง การกลายพันธุ์ตำแหน่งใหม่ประกอบด้วยการกลายพันธุ์ในยีน SPTB ตำแหน่ง c.5692C>T และ c.3823delG และในยีน ANK1 c.1994C>A ผลการศึกษาผลของการกลายพันธุ์ในระดับอาร์เอ็นเอพบว่าการกลายพันธุ์ตำแหน่ง c.5692C>T และ c.3823delG ในยีน SPTB และ c.1994C>A ในยีน ANK1 ส่งผลให้เกิด premature stop codon และพบว่าการกลายพันธุ์ตำแหน่ง c.5692C>T และ c.3823delG ในยีน SPTB ส่งผลให้ระดับการแสดงออกของยีนลดลงเมื่อเทียบกับคนปกติซึ่งอาจเกิดจากกระบวนการ nonsense-mediated mRNA degradation ทำให้ mRNA ที่ผิดปกติถูกทำลาย ผลจากการเพาะเลี้ยงเซลล์เม็ดเลือดตัวอ่อนพบว่าผู้ป่วยเม็ดเลือดแดงป่องพันธุกรรมมีอัตราการเพิ่มจำนวนเซลล์เม็ดเลือดแดงตัวอ่อนมากกว่าคนปกติ แต่มีการเจริญเติบโตและพัฒนาช้ากว่าคนปกติ จากการวัดปริมาณไมโครพาติเคิลด้วยเทคนิคโฟลไซโทเมทรีพบว่าในผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติมีปริมาณไมโครพาติเคิลที่สูงกว่าคนปกติ องค์ความรู้ที่ได้จากงานวิจัยนี้ทำให้ทราบกลไกการเกิดความผิดที่เกิดจากการกลายพันธุ์ของยีน SPTB และ ANK1 ในเซลล์เม็ดเลือดแดงผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติเพิ่มขึ้น

The Effect Of Water Temperature And Carbohydrate Drink On Intestinal Epithelial Injury, Endotoxemia, Splanchnic Perfusion, And Core Temperature, During Running In The Heat, Warot Rangsimahariwong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Prolonged exercise can result in splanchnic hypoperfusion and elevated core body temperature (Tcore), which can contribute to gastrointestinal injury and endotoxemia. The effects of fluid temperature and carbohydrate consumption during exercise on these variables are less clear. Objectives: The study aimed to determine the effects of the temperature of water and carbohydrate drinks on intestinal epithelial injury, endotoxemia, splanchnic perfusion, and Tcore during 60-minute of moderate-intensity running. Methods: Ten participants completed four 60-minute running trials at 70% VO2max with different types of hydration: no water (NW), ambient temperature water (ATW), cold water (CW), and cold carbohydrate water (CW+CHO). Doppler …

การเปรียบเทียบผลการฟื้นฟูผ่านระบบกายภาพบำบัดทางไกล กับที่สถานพยาบาล จากรายงานผู้ป่วยหลังผ่าตัดกระดูกสันหลังแบบแผลเล็ก, พงศ์ธนา โรจนรัตนางกูร

Chulalongkorn University Theses and Dissertations (Chula ETD)

การออกกำลังกายกล้ามเนื้อแกนกลางลำตัวเพื่อฟื้นฟูหลังผ่าตัดกระดูกสันหลังแบบแผลเล็กเป็นหนึ่งในวิธีที่ได้รับความนิยมสำหรับการลดอาการไม่พึงประสงค์ แต่จำเป็นต้องทำหลายครั้งและต่อเนื่อง ปัจจัยอื่น ๆ รบกวนจนไม่สามารถทำได้ครบจำนวน จึงมีการใช้ระบบการภาพบำบัดทางไกลเข้ามาทดแทน แต่ยังขาดการศึกษาวิจัยเกี่ยวกับรูปแบบการให้บริการ การศึกษาวิจัยนี้จึงมีวัตถุประสงค์ เพื่อศึกษาผลด้านระดับคุณภาพชีวิต ระดับความปวด ระดับความเชื่อในการหลีกเลี่ยงความกลัว ความสามารถในการปฏิบัติกิจวัตรประจำวัน และความแข็งแรงของกล้ามเนื้อแกนกลางลำตัว จากการออกกำลังกายฟื้นฟูกล้ามเนื้อแกนกลางลำตัวของผู้ป่วยหลังผ่าตัดกระดูกสันหลังแบบแผลเล็กผ่านระบบกายภาพบำบัดทางไกล เปรียบเทียบกับการฟื้นฟูที่สถานพยาบาล ศึกษาวิจัยในผู้ป่วยหลังผ่าตัดกระดูกสันหลังแบบแผลเล็กที่พักฟื้นมาแล้วอย่างน้อยสี่สัปดาห์ อายุสี่สิบถึงเจ็ดสิบปี จำนวนสามสิบแปดคน โดยแบ่งออกเป็นสองกลุ่มจำนวนเท่ากัน กลุ่มละสิบเก้าคน ได้แก่กลุ่มที่ออกกำลังกายฟื้นฟูผ่านระบบกายภาพบำบัดทางไกลหรือกลุ่มทดลอง และกลุ่มออกกำลังฟื้นฟูที่สถานพยาบาลหรือกลุ่มควบคุม ทั้งสองกลุ่มการศึกษาวิจัย จะได้รับการสอนออกกำลังกายเพื่อฟื้นฟูกล้ามเนื้อแกนกลางลำตัว สองครั้งต่อสัปดาห์ เป็นเวลาหกสัปดาห์ ผลการศึกษาวิจัยพบว่า ผู้เข้าร่วมวิจัยออกกำลังกายฟื้นฟูกล้ามเนื้อแกนกลางลำตัวครบสิบสองครั้ง ทั้งกลุ่มใช้ระบบกายภาพบำบัดทางไกลและกลุ่มออกกำลังกายฟื้นฟูที่สถานพยาบาล ผลจากรายงานผู้เข้าร่วมวิจัยพบว่า ทั้งสองกลุ่มการศึกษาไม่แตกต่างกัน ในด้านระดับคุณภาพชีวิต ระดับความปวด ความสามารถในการปฏิบัติกิจวัตรประจำวัน และความแข็งแรงของกล้ามเนื้อแกนกลางลำตัว สรุปผลการศึกษาวิจัยคือ การออกกำลังกายฟื้นฟูกล้ามเนื้อแกนกลางผ่านระบบกายภาพบำบัดทางไกล มีผลไม่ด้อยไปกว่าการออกกำลังกายฟื้นฟูที่สถานพยาบาล ในผู้ป่วยหลังผ่าตัดกระดูกสันหลังแบบแผลเล็ก

The Rising Tide Of Revisional Surgery: Tracking Changes In Index Cases Among Bariatric-Accredited Fellowships, Lincoln N Strickland, Erika Y Faraoni, Wei Ruan, Xiaoyi Yuan, Holger K Eltzschig, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of …

Retinal Alpha-Synuclein Accumulation Correlates With Retinal Dysfunction And Structural Thinning In The A53t Mouse Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson's disease's (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14  months of age (male and female,

Exaptation And Evolutionary Adaptation In Nociceptor Mechanisms Driving Persistent Pain, Edgar T Walters

Faculty, Staff and Student Publications

Background: Several evolutionary explanations have been proposed for why chronic pain is a major clinical problem. One is that some mechanisms important for driving chronic pain, while maladaptive for modern humans, were adaptive because they enhanced survival. Evidence is reviewed for persistent nociceptor hyperactivity (PNH), known to promote chronic pain in rodents and humans, being an evolutionarily adaptive response to significant bodily injury, and primitive molecular mechanisms related to cellular injury and stress being exapted (co-opted or repurposed) to drive PNH and consequent pain.

Summary: PNH in a snail (Aplysia californica), squid (Doryteuthis pealeii), fruit fly (Drosophila melanogaster), mice, rats, …

Oral Small Molecule Agents In Management Of Ulcerative Colitis: Fact Or Fancy?, Benan Kasapoğlu, Atilla Ertan

Faculty, Staff and Student Publications

Ulcerative colitis is a chronic, immune-mediated disease characterized by recurring episodes of mucosal inflammation in the colon and rectum. The primary pathogenic mechanism of ulcerative colitis is the dysregulation of the mucosal immune response. The disease follows a relapsing-remitting course, and the goal of management is to successfully induce and then maintain remission. Effectively managing this chronic disease requires addressing all aspects of it. Currently, we have various antitumor necrosis factor agents and novel biologics available for treating ulcerative colitis patients with moderate-to-severe disease. However, none of the existing treatments are considered entirely satisfactory or ideal in these cases. After …

Antimicrobial Activity Of Plasma Rich In Platelets (Prp) On The Ocular Microbiota Of Healthy Horses From Minas Gerais, Luis E C Torres, Camilo O Florez, Jéssica G Oliveira, Giovanna D Vieira, Ilza S Ribeiro, Kelly M Keller, Fabíola O P Leme, Priscila Fantini, Renata P A Maranhão

Faculty, Staff and Student Publications

In equine ophthalmology, ulcerative keratitis is among the most common conditions and, in general, arises as a consequence of some trauma suffered. Secondarily, subsequent contamination by pathogenic or resident bacteria of the horse's ocular microbiota may have undesirable consequences. Under physiological conditions, the normal microbiota coexists with the immune status of the host, serving as a barrier, ensuring the health of the ocular surface, and inhibiting the proliferation of pathogens. However, in the imbalance of immune barriers, the normal microbiota can become pathogenic and lead to infection, acting as an opportunistic agent. The present study aims to demonstrate the antimicrobial …

Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz

Theses and Dissertations

The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-b) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the Kras^G12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation …

Adolescent Loneliness During The Covid-19 Pandemic: The Role Of Pre-Pandemic Risk Factors, Hena Thakur, Morgan Stutts, Jae Wan Choi, Jeff R Temple, Joseph R Cohen

Faculty, Staff and Student Publications

The COVID-19 pandemic is a global mental health crisis that disproportionately impacts adolescents. Loneliness is a particularly salient pandemic psychosocial outcome to understand; however, research to date on this outcome is sparse and largely cross-sectional. In response, we examined pre-pandemic risk factors for pandemic loneliness. Further, we examined how risk may differ based on key demographics, and whether mediation or moderation models best explained potential disparities in experiencing loneliness. Self-reported, pre-pandemic mental health, trauma exposure, and family conflict survey data were collected at Wave 1 in a diverse sample of 369 adolescents (54.5% female, 45.5% male; 30.1% White; 30.9% Black; …

Are Trauma Surgeons Prepared? A Survey Of Trauma Surgeons’ Disaster Preparedness Before And During The Covid-19 Pandemic, Jay Doucet, David V Shatz, Lewis J Kaplan, Eileen M Bulger, Jeannette Capella, Deborah A Kuhls, Mary Fallat, Kyle N Remick, Christopher Newton, Adam Fox, Randeep Jawa, John A Harvin, David P Blake, Marko Bukur, Jonathan Gates, James Ficke, Mark L Gestring, The American Association For Surgery Of Trauma Disaster Committee

Faculty, Staff and Student Publications

OBJECTIVE: US trauma centers (TCs) must remain prepared for mass casualty incidents (MCIs). However, trauma surgeons may lack formal MCI training. The recent COVID-19 pandemic drove multiple patient surges, overloaded Emergency Medical Services (EMS) agencies, and stressed TCs. This survey assessed trauma surgeons' MCI training, experience, and system and personal preparedness before the pandemic compared with the pandemic's third year.

METHODS: Survey invitations were emailed to all 1544 members of the American Association for the Surgery of Trauma in 2019, and then resent in 2022 to 1575 members with additional questions regarding the pandemic. Questions assessed practice type, TC characteristics, …

Research On Cloud Manufacturing Service Recommendation Based On Graph Neural Network, Minghui Li, Xiaoqiu Shi, Yuqiang Shi, Yong Cai, Xuewen Dong

Faculty, Staff and Student Publications

There are an increasing number of manufacturing service resources appeared on the cloud manufacturing (CMfg) service platform recently, which leads to a serious information overloading problem to the enterprises that need these resources. To tackle this problem, a graph neural network-based recommendation method for CMfg service resources is proposed, which effectively overcomes some limitations of the traditional recommendation methods. Specifically, we first use different similarity calculation methods (e.g., Cosine similarity, Pearson correlation coefficient, etc.) to calculate the similarities between different resources based on the feature information of CMfg service resources. A resource graph dataset is accordingly established. A graph neural …