Digital Commons Network^™

5-Htp Inhibits Eosinophilia Via Intracellular Endothelial 5-Htrs; Snps In 5-Htrs Associate With Asthmatic Lung Function, Matthew T Walker, Jeffrey C Bloodworth, Timothy S Kountz, Samantha L Mccarty, Jeremy E Green, Ryan P Ferrie, Jackson A Campbell, Samantha H Averill, Kenneth B Beckman, Leslie C Grammer, Celeste Eng, Pedro C Avila, Harold J Farber, William Rodriguez-Cintron, Jose R Rodriguez-Santana, Denise Serebrisky, Shannon M Thyne, Max A Seibold, Esteban G Burchard, Rajesh Kumar, Joan M Cook-Mills

Faculty, Staff and Students Publications

BACKGROUND: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers.

OBJECTIVE: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans.

METHODS: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts.

RESULTS: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil …

Using A Collaborative Learning Health System Approach To Improve Disease Activity Outcomes In Children With Juvenile Idiopathic Arthritis In The Pediatric Rheumatology Care And Outcomes Improvement Network, Julia G Harris, Catherine A Bingham, Sheetal S Vora, Cagri Yildirim-Toruner, Michelle Batthish, Danielle R Bullock, Jon M Burnham, Danielle C Fair, Kerry Ferraro, Suhas Ganguli, Mileka Gilbert, Beth S Gottlieb, Olha Halyabar, Melissa M Hazen, Ronald M Laxer, Tzielan C Lee, Alice Liu, Daniel J Lovell, Melissa L Mannion, Edward J Oberle, Nancy Pan, Michael Shishov, Jennifer E Weiss, Esi M Morgan

Faculty, Staff and Students Publications

INTRODUCTION: The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to …

Improving Lupus Care Index Documentation In Patients With Childhood-Onset Systemic Lupus Erythematosus, Fatima A Barbar-Smiley, Cagri Yildirim-Toruner, Shoghik Akoghlanian, Ohoud Alahmed, Stacy P Ardoin, Ashlee Leone, Edward Oberle, Vidya Sivaraman

Faculty, Staff and Students Publications

INTRODUCTION: Childhood-onset systemic lupus erythematosus (c-SLE) presents unique challenges due to increased risk for severe morbidity and mortality compared to adult-onset SLE. Effective disease management relies on accurate disease assessment and documentation. Our project aimed to improve the documentation of the Lupus Care Index (LCI), a disease assessment bundle, by implementing a quality improvement (QI) initiative.

METHODS: A QI project was conducted at Nationwide Children's Hospital (NCH), targeting patients with c-SLE. The LCI, comprising the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) Physician Global Assessment (PGA) and patient-reported pain score, was introduced to capture comprehensive disease assessment. Interventions included provider …

Optimizing Immunogenicity And Product Presentation Of A Sars-Cov-2 Subunit Vaccine Composition: Effects Of Delivery Route, Heterologous Regimens With Self-Amplifying Rna Vaccines, And Lyophilization, William R Lykins, Jeroen Pollet, Jessica A White, Brian Keegan, Leroy Versteeg, Ulrich Strych, Wen-Hsiang Chen, Raodoh Mohamath, Gabi Ramer-Denisoff, Sierra Reed, Christina Renshaw, Samuel Beaver, Alana Gerhardt, Emily A Voigt, Mark A Tomai, Robert Sitrin, Robert K M Choy, Frederick J Cassels, Peter J Hotez, Maria Elena Bottazzi, Christopher B Fox

Faculty, Staff and Students Publications

INTRODUCTION: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.) route has been shown to improve protective mucosal responses in comparison to intramuscular (i.m.) delivery. As we gain knowledge of the limitations of existing vaccines, it is of interest to understand if changes in product presentation or combinations of multiple vaccine modalities can further improve immunological outcomes.

METHODS: We investigated a commercial-stage SARS-CoV-2 receptor binding domain (RBD) antigen adjuvanted with a clinical-stage TLR-7/8 agonist …

Self-Rectifying Magnetoelectric Metamaterials For Remote Neural Stimulation And Motor Function Restoration, Joshua C Chen, Gauri Bhave, Fatima Alrashdan, Abdeali Dhuliyawalla, Katie J Hogan, Antonios G Mikos, Jacob T Robinson

Faculty, Staff and Students Publications

Magnetoelectric materials convert magnetic fields into electric fields. These materials are often used in wireless electronic and biomedical applications. For example, magnetoelectrics could enable the remote stimulation of neural tissue, but the optimal resonance frequencies are typically too high to stimulate neural activity. Here we describe a self-rectifying magnetoelectric metamaterial for a precisely timed neural stimulation. This metamaterial relies on nonlinear charge transport across semiconductor layers that allow the material to generate a steady bias voltage in the presence of an alternating magnetic field. We generate arbitrary pulse sequences with time-averaged voltage biases in excess of 2 V. As a …

Monoclonal Antibodies In Neuro-Ophthalmology, Caroline C Keehn, Arman Yazdian, Patrick J Hunt, Pamela Davila-Siliezar, Noor A Laylani, Andrew G Lee

Faculty, Staff and Students Publications

Neuro-ophthalmologic diseases include a broad range of disorders affecting the afferent and efferent visual pathways. Recently, monoclonal antibody (mAb) therapies have emerged as a promising targeted approach in the management of several of these complex conditions. Here, we describe the mechanism-specific applications and advancements in neuro-ophthalmologic mAb therapies. The application of mAbs in neuro-ophthalmologic diseases highlights our increasing understanding of disease-specific mechanisms in autoimmune conditions such as neuromyelitis optica, thyroid eye disease, and myasthenia gravis. Due to the specificity of mAb therapies, applications in neuro-ophthalmologic diseases have yielded exceptional clinical outcomes, including both reduced rate of relapse and progression to …

The Maternal Gut Microbiome In Pregnancy: Implications For The Developing Immune System, Omry Koren, Liza Konnikova, Petter Brodin, Indira U Mysorekar, Maria Carmen Collado

Faculty, Staff and Students Publications

The gut microbiome has important roles in host metabolism and immunity, and microbial dysbiosis affects human physiology and health. Maternal immunity and microbial metabolites during pregnancy, microbial transfer during birth, and transfer of immune factors, microorganisms and metabolites via breastfeeding provide critical sources of early-life microbial and immune training, with important consequences for human health. Only a few studies have directly examined the interactions between the gut microbiome and the immune system during pregnancy, and the subsequent effect on offspring development. In this Review, we aim to describe how the maternal microbiome shapes overall pregnancy-associated maternal, fetal and early neonatal …

Outcomes For Patients With Head And Neck Sarcoma Treated Curatively With Radiation Therapy And Surgery, Alison K Yoder, Ahsan Farooqi, Devarati Mitra, J Andrew Livingston, Dejka M Araujo, Erich M Sturgis, Ryan Goepfert, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Students Publications

Purpose: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS.

Methods and materials: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model.

Results: One hundred ninety-two patients had a median follow-up of 82 …

Fluoxetine And Sertraline Inhibit Height Growth And Growth Hormone Signaling During Puberty, Chadi Calarge, Chima Amushie, Stephanie Dinh, James A Mills, Sridevi Devaraj, Griselda Barba-Villalobos, Jacqueline Nguyen, Jose M Garcia, Stephanie Sisley, Fida Bacha, Babette Zemel

Faculty, Staff and Students Publications

Purpose: The aim of this study was to examine the effect of fluoxetine and sertraline on height growth and insulin-like growth factor-1 (IGF-1) during puberty.

Methods: In this 6-month cohort study, electronic medical records were used to identify 8- to 15-year-old participants, within 1 month of starting fluoxetine (n = 39) or sertraline (n = 27), and sexual maturation stages 2 to 4 were confirmed. Conditions that interfere with height growth led to exclusion. Participants underwent anthropometric assessments and phlebotomy. Healthy, unmedicated children (n = 36) also provided anthropometric data.

Results: After the baseline height Z-score, sex, Tanner stage, daily …

Molecular Profiling Of A Hepatocellular Neoplasm Not Otherwise Specified (Hcn-Nos) Demonstrates Distinct Molecular Features In Hepatoblastoma And Hcc-Like Components, Yan Chen Wongworawat, Stephen F Sarabia, Martin Urbicain, Paola Francalanci, Pavel Sumazin, Rita Alaggio, Dolores H López-Terrada

Faculty, Staff and Students Publications

Hepatoblastomas (HB) are embryonal tumors with quiet genomes diagnosed mostly in children under 3 years of age and often cured by surgical resection and chemotherapy. However, a subset of HBs behave aggressively, displaying characteristic histologic features and higher genomic instability. Hepatocellular neoplasm-not otherwise specified (HCN-NOS) is a provisional diagnostic category for tumors exhibiting either intermediate or a combination of both HB and hepatocellular carcinoma (HCC) histological features. In this study, we characterized an HCN-NOS diagnosed in a 3-year-old patient presenting with a liver mass, in which both HB and HCC histological components were amendable to macro-dissection and molecular profiling. The …

Bivalirudin Stability In Citrated Plasma And Citrated Whole Blood, Karen Bruzdoski, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

No abstract provided.

The Mars Complex: A Critical Mediator Of Immune Regulation And Homeostasis, Sharon Bright Amanya, Damilola Oyewole-Said, Keenan J Ernste, Nalini Bisht, Arnav Murthy, Jonathan Vazquez-Perez, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular …

High-Fat Diets Promote Peritoneal Inflammation And Augment Endometriosis-Associated Abdominal Hyperalgesia, Tristin Herup-Wheeler, Mingxin Shi, Madeleine E Harvey, Chandni Talwar, Ramakrishna Kommagani, James A Maclean, Kanako Hayashi

Faculty, Staff and Students Publications

Immune dysfunction is one of the central components in the development and progression of endometriosis by establishing a chronic inflammatory environment. Western-style high-fat diets (HFD) have been linked to greater systemic inflammation to cause metabolic and chronic inflammatory diseases, and are also considered an environmental risk factor for gynecologic diseases. Here, we aimed to examine how HFD cause an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal hyperalgesia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure …

Rapid Gene Fusion Testing Using The Nanostring Ncounter Platform To Improve Pediatric Leukemia Diagnoses In Sub-Saharan Africa, Julie M Gastier-Foster, Fredrick Lutwama, Olive Mbabazi, Steven Mlenga, Kennedy Ulaya, Ruth Namazzi, E Faith Hollingsworth, Dolores Lopez-Terrada, Kevin E Fisher, Angshumoy Roy, Carl E Allen, David G Poplack, Rizine Mzikamanda, Nmazuo Ozuah, Peter Wasswa

Faculty, Staff and Students Publications

Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity. This study aimed to assess the feasibility of implementing molecular assays to improve leukemia diagnoses in SSA. Custom NanoString nCounter gene fusion assays, previously validated in the US, were used to test samples from suspected leukemia patients. The NanoString platform was chosen due to relatively low …

Genetic Variation Between Small Bowel And Colon-Predominant Crohn's Disease, Halee Patel, R Alan Harris, Justin H Qian, Numan Oezguen, Ashleigh Watson, Reka G Szigeti, Stanley Cho, Wenly Ruan, Savini Britto, Antone Opekun, Geoffrey Preidis, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Twenty Years Of Epithelial-Mesenchymal Transition: A State Of The Field From Temtia X, Pierre Savagner, Thomas Brabletz, Chonghui Cheng, Christine Gilles, Tian Hong, Myriam Polette, Guojun Sheng, Marc P Stemmler, Erik W Thompson

Faculty, Staff and Students Publications

This report summarizes the 10th biennial meeting of The Epithelial Mesenchymal Transition International Association (TEMTIA), that took place in Paris on November 7-10, 2022. It provides a short but comprehensive introduction to the presentations and discussions that took place during the 3-day meeting. Similarly to previous TEMTIA meetings, TEMTIA X reviewed the most recent aspects of the epithelial-mesenchymal transition (EMT), a cellular process involved during distinct stages of development but also during wound healing and fibrosis to some degree. EMT has also been associated at various levels during tumor cell progression and metastasis. The meeting emphasized the intermediate stages of …

Pretreatment Characteristics Associated With Symptom Reduction During Group Cognitive Processing Therapy Versus Exposure Therapy For Ptsd: An Exploratory Study Of Veterans, Christopher Hunt, Brooks Casas, Pearl H Chiu, Lia J Smith, Laura Priorello, Kelly Lee, Matthew Estey, Mary R Newsome, M Wright Williams

Faculty, Staff and Students Publications

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT;

Continuing Education And Professional Development: Unifying Opportunities For Genetic Counselors Globally, Kathleen D Valverde, Tiffiney R Hartman, Sara L Reichert, Robin L Bennett, Martha Dudek, Debra Duquette, Daniel Riconda, Nancy J Cox, Gail P Jarvik, Sarah H Elsea, Elizabeth M Mcnally, Kim C Worley, Daniel J Rader

Faculty, Staff and Students Publications

No abstract provided.

Cutting Edge Of Genetically Modified Pigs Targeting Complement Activation For Xenotransplantation, Qin Sun, Si-Yuan Song, Jiabao Ma, Danni Li, Yiping Wang, Zhengteng Yang, Yi Wang

Faculty, Staff and Students Publications

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of …

Fam20a: A Potential Diagnostic Biomarker For Lung Squamous Cell Carcinoma, Yalin Zhang, Qin Sun, Yangbo Liang, Xian Yang, Hailian Wang, Siyuan Song, Yi Wang, Yong Feng

Faculty, Staff and Students Publications

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC.

Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, …

Research Considerations For Prospective Studies Of Patients With Coma And Disorders Of Consciousness, Lorenzo Tinti, Thomas Lawson, Erika Molteni, Daniel Kondziella, Verena Rass, Tarek Sharshar, Yelena G Bodien, Joseph T Giacino, Stephan A Mayer, Moshgan Amiri, Susanne Muehlschlegel, Chethan P Venkatasubba Rao, Paul M Vespa, David K Menon, Giuseppe Citerio, Raimund Helbok, Molly Mcnett

Faculty, Staff and Students Publications

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to …

Activation Of Mechanoreceptor Piezo1 Inhibits Enteric Neuronal Growth And Migration, Chioma Moneme, Oluyinka O Olutoye, Michał F Sobstel, Yuwen Zhang, Xinyu Zhou, Jacob L Kaminer, Britney A Hsu, Chengli Shen, Arabinda Mandal, Hui Li, Ling Yu, Swathi Balaji, Sundeep G Keswani, Lily S Cheng

Faculty, Staff and Students Publications

INTRODUCTION: Dysfunction of the enteric nervous system (ENS) is linked to a myriad of gastrointestinal (GI) disorders. Piezo1 is a mechanosensitive ion channel found throughout the GI tract, but its role in the ENS is largely unknown. We hypothesize that Piezo1 plays an important role in the growth and development of the ENS.

METHODS: Enteric neural crest-derived progenitor cells (ENPC) were isolated from adult mouse intestine and propagated in culture as neurospheres. ENPC-derived neurons were then subject to

RESULTS: Though stretch did not cause upregulation of Piezo1 expression in enteric neurons, both stretch and Piezo1 activation produced similar alterations in …

Green Synthesis Of Zinc Oxide Nanoparticles From Althaea Officinalis Flower Extract Coated With Chitosan For Potential Healing Effects On Diabetic Wounds By Inhibiting Tnf-Α And Il-6/Il-1Β Signaling Pathways, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed Abdul Kareem Saeed Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Ahmed Mohsen Elsaid Hamdan, Mohamed Mansour Khalifa, Sandra Hababeh, Mohammad Ahmad Khasawneh, Gehad M Khamis, Jakline Nelson, Passant M Mohie, Rania A Gad, Amira Rizk, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Tayseer Elnawawy, Fatma E Hassan, Mohamed A El-Nabarawi

Faculty, Staff and Students Publications

BACKGROUND: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia.

METHOD AND RESULTS: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean …

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery Of Cyclosporine And Dithranol: In-Vitro, Ex-Vivo, And In-Vivo Studies, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed A S Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Mohamed Mansour Khalifa, Mohammad Ahmad Khasawneh, Ahmed Mohsen Elsaid Hamdan, Passant M Mohie, Rania A Gad, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Nehal Elfar, Tayseer Elnawawy, Fatma E Hassan, Mohamed Ahmed El-Nabarawi

Faculty, Staff and Students Publications

PURPOSE: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. …

Ketogenic Diet In Treating Sepsis-Related Acquired Weakness: Is It Friend Or Foe?, Yanmei Miao, Leiyu Xie, Shaolin Chen, Xiaoming Zhang, Wenjie Liu, Peng Xie

Faculty, Staff and Students Publications

Background: Sepsis is the body's extreme response to an infection leading to organ dysfunction. Sepsis-related acquired weakness (SAW), a critical illness closely related to metabolic disorders, is characterized by generalized sepsis-induced skeletal muscle weakness, mainly manifesting as symmetrical atrophy of respiratory and limb muscles. Muscle accounts for 40% of the body's total mass and is one of the major sites of glucose and energy absorption. Diet affects skeletal muscle metabolism, which further impacts physiology and signaling pathways. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has shown benefits in patients with a variety of neuromuscular disorders. Patients with …

Erector Spinae Plane Block For Chronic Lumbosacral Pain: A Case Report, Jamal Hasoon, Syed Mahmood, Anvinh Nguyen, Vwaire Orhurhu

Faculty, Staff and Students Publications

Chronic low back pain is a prevalent and debilitating condition that often resists traditional management strategies such as physical therapy, pharmacotherapy, and interventional procedures. The erector spinae plane (ESP) block, a relatively new regional anesthesia technique, has shown promise in managing various types of pain, including chronic conditions. This case report details the use of the ESP block in a male patient in his late 60's with chronic low back pain unresponsive to conventional treatments, including acetaminophen, muscle relaxants, gabapentin, epidural steroid injections, diagnostic medial branch blocks, and sacroiliac joint injections. Given the refractory nature of his pain, a right-sided …

Targeting Sars-Cov-2 Nonstructural Protein 3: Function, Structure, Inhibition, And Perspective In Drug Discovery, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

As a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus drugs. Nonstructural protein (nsp) 3 of CoVs is a large, multifunctional protein, containing a papain-like protease (PLpro) and a macrodomain (Mac1), which are essential for viral replication. Here, we …

Liver Directed Adeno-Associated Viral Vectors To Treat Metabolic Disease, Marcel A Chuecos, William R Lagor

Faculty, Staff and Students Publications

The liver is the metabolic center of the body and an ideal target for gene therapy of inherited metabolic disorders (IMDs). Adeno-associated viral (AAV) vectors can deliver transgenes to the liver with high efficiency and specificity and a favorable safety profile. Recombinant AAV vectors contain only the transgene cassette, and their payload is converted to non-integrating circular double-stranded DNA episomes, which can provide stable expression from months to years. Insights from cellular studies and preclinical animal models have provided valuable information about AAV capsid serotypes with a high liver tropism. These vectors have been applied successfully in the clinic, particularly …

Co-Expression Of Prepulse Inhibition And Schizophrenia Genes In The Mouse And Human Brain, Lillian Garrett, Dietrich Trümbach, Donghyung Lee, Silvia Mandillo, Rodney Samaco, Ann M Flenniken, Michelle Stewart, Impc Consortium, Jacqueline K White, Colin Mckerlie, Lauryl M J Nutter, Igor Vukobradovic, Surabi Veeraragavan, Lisa Yuva, Jason D Heaney, Mary E Dickinson, Hamid Meziane, Yann Hérault, Sara Wells, K C Kent Lloyd, Lynette Bower, Louise Lanoue, Dave Clary, Annemarie Zimprich, Valerie Gailus-Durner, Helmut Fuchs, Steve D M Brown, Elissa J Chesler, Wolfgang Wurst, Martin Hrabě De Angelis, Sabine M Hölter

Faculty, Staff and Students Publications

Schizophrenia is a complex psychiatric disorder with genetic and phenotypic heterogeneity. Accumulating rare and genome-wide association study (GWAS) common risk variant information has yet to yield robust mechanistic insight. Leveraging large-scale gene deletion mouse phenomic data thus has potential to functionally interrogate and prioritize human disease genes. To this end, we applied a cross-species network-based approach to parse an extensive mouse gene set (188 genes) associated with disrupted prepulse inhibition (PPI), a Schizophrenia endophenotype. Integrating PPI genes with high-resolution mouse and human brain transcriptomic data, we identified functional and disease coherent co-expression modules through hierarchical clustering and weighted gene co-expression …

Management Of Depression/Anxiety In Patients With Chronic Liver Disease, Mauro Garcia-Altieri, Keila Carrera-Mejias, Ruben Hernaez

Faculty, Staff and Students Publications

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