Medicine and Health Sciences Commons^™

Biallelic Prmt7 Pathogenic Variants Are Associated With A Recognizable Syndromic Neurodevelopmental Disorder With Short Stature, Obesity, And Craniofacial And Digital Abnormalities, Elisa Cali, Mohnish Suri, Marcello Scala, Matteo P Ferla, Shahryar Alavi, Eissa Ali Faqeih, Emilia K Bijlsma, Kristen M Wigby, Diana Baralle, Mohammad Y V Mehrjardi, Jennifer Schwab, Konrad Platzer, Katharina Steindl, Mais Hashem, Marilyn Jones, Dmitriy M Niyazov, Jennifer Jacober, Rebecca Okashah Littlejohn, Denisa Weis, Neda Zadeh, Lance Rodan, Alice Goldenberg, François Lecoquierre, Marina Dutra-Clarke, Gabriella Horvath, Dana Young, Naama Orenstein, Shahad Bawazeer, Anneke T Vulto-Van Silfhout, Yvan Herenger, Mohammadreza Dehghani, Seyed Mohammad Seyedhassani, Amir Bahreini, Mahya E Nasab, A Gulhan Ercan-Sencicek, Zahra Firoozfar, Mojtaba Movahedinia, Stephanie Efthymiou, Pasquale Striano, Ehsan Ghayoor Karimiani, Vincenzo Salpietro, Jenny C Taylor, Melody Redman, Alexander P A Stegmann, Andreas Laner, Ghada Abdel-Salam, Megan Li, Mario Bengala, Amelie Johanna Müller, Maria C Digilio, Anita Rauch, Murat Gunel, Hannah Titheradge, Daniela N Schweitzer, Alison Kraus, Irene Valenzuela, Scott D Mclean, Chanika Phornphutkul, Mustafa Salih, Amber Begtrup, Rhonda E Schnur, Erin Torti, Tobias B Haack, Carlos E Prada, Fowzan S Alkuraya, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.

METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 …

Reward Sensitivity Predicts The Response To Cognitive Behavioral Therapy For Children With Autism And Anxiety, Matthew J Hollocks, Jeffrey J Wood, Eric A Storch, An-Chuen Cho, Connor M Kerns, Philip C Kendall

Faculty, Staff and Students Publications

Objective: Cognitive-behavioral therapy (CBT) is an effective treatment for anxiety in youth with autism spectrum disorder (ASD). However, research has yet to examine what cognitive characteristics may influence treatment response. The current study investigated decision-making ability and social cognition as potential (a) predictors of differential treatment response to two versions of CBT and (b) moderators of the effect of treatment condition.

Method: The study included 148 children (mean age = 9.8 years) with interfering anxiety and a diagnosis of ASD who were enrolled in a randomized clinical trial comparing two versions of CBT for anxiety (standard and adapted for ASD). …

Novel Banana Lectin Car-T Cells To Target Pancreatic Tumors And Tumor-Associated Stroma, Mary K Mckenna, Ada Ozcan, Daniel Brenner, Norihiro Watanabe, Maureen Legendre, Dafydd G Thomas, Christopher Ashwood, Richard D Cummings, Challice Bonifant, David M Markovitz, Malcolm K Brenner

Faculty, Staff and Students Publications

BACKGROUND: Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and by heterogeneous expression of tumor target antigens. We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a 'hallmark' of both malignant and associated stromal cells. We have expressed in T cells a modified lectin from banana, H84T BanLec, attached to a chimeric antigen receptor (H84T-CAR) that recognizes high-mannose (asparagine residue with five to nine mannoses). Here, we tested the efficacy of our novel H84T CAR in models of pancreatic ductal …

Transcriptomic Analyses Of Ovarian Clear-Cell Carcinoma With Concurrent Endometriosis, Kaitlyn E Collins, Xiyin Wang, Yuliya Klymenko, Noah B Davis, Maria C Martinez, Chi Zhang, Kaman So, Aaron Buechlein, Douglas B Rusch, Chad J Creighton, Shannon M Hawkins

Faculty, Staff and Students Publications

INTRODUCTION: Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC).

METHODS: To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing.

RESULTS: Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment …

Gene Expression Profiles In Cancers And Their Therapeutic Implications, Chad J Creighton

Faculty, Staff and Students Publications

The vast amount of gene expression profiling data of bulk tumors and cell lines available in the public domain represents a tremendous resource. For any major cancer type, expression data can identify molecular subtypes, predict patient outcome, identify markers of therapeutic response, determine the functional consequences of somatic mutation, and elucidate the biology of metastatic and advanced cancers. This review provides a broad overview of gene expression profiling in cancer (which may include transcriptome and proteome levels) and the types of findings made using these data. This review also provides specific examples of accessing public cancer gene expression data sets …

Multiomics In Primary And Metastatic Breast Tumors From The Aurora Us Network Finds Microenvironment And Epigenetic Drivers Of Metastasis, Susana Garcia-Recio, Toshinori Hinoue, Gregory L Wheeler, Benjamin J Kelly, Ana C Garrido-Castro, Tomas Pascual, Aguirre A De Cubas, Youli Xia, Brooke M Felsheim, Marni B Mcclure, Andrei Rajkovic, Ezgi Karaesmen, Markia A Smith, Cheng Fan, Paula I Gonzalez Ericsson, Melinda E Sanders, Chad J Creighton, Jay Bowen, Kristen Leraas, Robyn T Burns, Sara Coppens, Amy Wheless, Salma Rezk, Amy L Garrett, Joel S Parker, Kelly K Foy, Hui Shen, Ben H Park, Ian Krop, Carey Anders, Julie Gastier-Foster, Mothaffar F Rimawi, Rita Nanda, Nancy U Lin, Claudine Isaacs, P Kelly Marcom, Anna Maria Storniolo, Fergus J Couch, Uma Chandran, Michael Davis, Jonathan Silverstein, Alexander Ropelewski, Minetta C Liu, Susan G Hilsenbeck, Larry Norton, Andrea L Richardson, W Fraser Symmans, Antonio C Wolff, Nancy E Davidson, Lisa A Carey, Adrian V Lee, Justin M Balko, Katherine A Hoadley, Peter W Laird, Elaine R Mardis, Tari A King, Charles M Perou

Faculty, Staff and Students Publications

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER

Allogeneic Haematopoietic Cell Transplant In Patients With Relapsed/Refractory Anaplastic Large Cell Lymphoma, Fateeha Furqan, Kwang W Ahn, Yue Chen, Manmeet Kaur, Syed A Abutalib, Nausheen Ahmed, Sairah Ahmed, Mohamed A Kharfan-Dabaja, Johnathan Friedberg, Tara Gregory, Laquisa Hill, Cole Sterling, Stephan K Barta, Mazyar Shadman, Miguel-Angel Perales, Jasmine Zain, Alex F Herrera, Craig Sauter, Mehdi Hamadani

Faculty, Staff and Students Publications

The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3-148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS …

Weight Strategy In Older Adults With Obesity: Calorie Restriction Or Not?, Georgia Colleluori, Dennis T Villareal

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults.

RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. …

Indices Of Sarcopenic Obesity Are Important Predictors Of Finite Element Analysis-Derived Bone Strength In Older Adults With Obesity, Giulia Gregori, Arjun Paudyal, Yoann Barnouin, Alessandra Celli, Martha Belen Segoviano-Escobar, Reina Armamento-Villareal, Nicola Napoli, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

BACKGROUND: The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT).

METHODS: One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m

RESULTS: Both ALM/W and HGS were positively correlated explaining 28% …

A Multicenter Study To Evaluate Pain Characteristics In Osteogenesis Imperfecta, Mercedes Rodriguez Celin, Karen M Kruger, Angela Caudill, Chaya N Murali, Sandesh C S Nagamani, Peter A Smith, Gerald F Harris

Faculty, Staff and Students Publications

The objective was to describe pain characteristics and treatments used in individuals with varying severity of osteogenesis imperfecta (OI) and investigate pain-associated variables. This work was derived from a multicenter, longitudinal, observational, natural history study of OI conducted at 12 clinical sites of the NIH Rare Diseases Clinical Research Network's Brittle Bone Disorders Consortium. Children and adults with a clinical, biochemical, or molecular diagnosis of OI were enrolled in the study. We did a cross-sectional analysis of chronic pain prevalence, characteristics, and treatments used for pain relief and longitudinal analysis to find the predictors of chronic pain. We included 861 …

Intermel: An International Biorepository And Clinical Database To Uncover Predictors Of Survival In Early-Stage Melanoma, Irene Orlow, Keimya D Sadeghi, Sharon N Edmiston, Jessica M Kenney, Cecilia Lezcano, James S Wilmott, Anne E Cust, Richard A Scolyer, Graham J Mann, Tim K Lee, Hazel Burke, Valerie Jakrot, Ping Shang, Peter M Ferguson, Tawny W Boyce, Jennifer S Ko, Peter Ngo, Pauline Funchain, Judy R Rees, Kelli O'Connell, Honglin Hao, Eloise Parrish, Kathleen Conway, Paul B Googe, David W Ollila, Stergios J Moschos, Eva Hernando, Douglas Hanniford, Diana Argibay, Christopher I Amos, Jeffrey E Lee, Iman Osman, Li Luo, Pei-Fen Kuan, Arshi Aurora, Bonnie E Gould Rothberg, Marcus W Bosenberg, Meg R Gerstenblith, Cheryl Thompson, Paul N Bogner, Ivan P Gorlov, Sheri L Holmen, Elise K Brunsgaard, Yvonne M Saenger, Ronglai Shen, Venkatraman Seshan, Eduardo Nagore, Marc S Ernstoff, Klaus J Busam, Colin B Begg, Nancy E Thomas, Marianne Berwick, Intermel Consortium

Faculty, Staff and Students Publications

INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.

METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for …

The Nr2f2-Hand2 Signaling Axis Regulates Progesterone Actions In The Uterus At Early Pregnancy, Yeongseok Oh, Elvis Quiroz, Tianyuan Wang, Yassmin Medina-Laver, Skylar Montague Redecke, Francisco Dominguez, John P Lydon, Francesco J Demayo, San-Pin Wu

Faculty, Staff and Students Publications

Endometrial function is dependent on a tight crosstalk between the epithelial and stromal cells of the endometrium. This communication is critical to ensure a fertile uterus and relies on progesterone and estrogen signaling to prepare a receptive uterus for embryo implantation in early pregnancy. One of the key mediators of this crosstalk is the orphan nuclear receptor NR2F2, which regulates uterine epithelial receptivity and stromal cell differentiation. In order to determine the molecular mechanism regulated by NR2F2, RNAseq analysis was conducted on the uterus of

The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert

Faculty, Staff and Students Publications

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …

The Role Of Hyperexcitability In Gliomagenesis, Eric A Goethe, Benjamin Deneen, Jeffrey Noebels, Ganesh Rao

Faculty, Staff and Students Publications

Glioblastoma is the most common malignant primary brain tumor. Recent studies have demonstrated that excitatory or activity-dependent signaling-both synaptic and non-synaptic-contribute to the progression of glioblastoma. Glutamatergic receptors may be stimulated via neuron-tumor synapses or release of glutamate by the tumor itself. Ion currents generated by these receptors directly alter the structure of membrane adhesion molecules and cytoskeletal proteins to promote migratory behavior. Additionally, the hyperexcitable milieu surrounding glioma increases the rate at which tumor cells proliferate and drive recurrent disease. Inhibition of excitatory signaling has shown to effectively reduce its pro-migratory and -proliferative effects.

Unmet Needs And Coping Strategies Of Older Underserved Veterans During The Covid-19 Pandemic, Trenton M Haltom, Joyce Tiong, Tracy L Evans, Nipa Kamdar, Gala True, Mark E Kunik

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic has had profound impacts on people with diabetes, a group with high morbidity and mortality. Factors like race, age, income, Veteran-status, and limited or interrupted resources early in the COVID-19 pandemic compounded risks for negative health outcomes. Our objective was to characterize the experiences and needs of under-resourced Veterans with type 2 diabetes during the COVID-19 pandemic.

METHODS: We conducted semi-structured qualitative interviews (March through September 2021) with U.S. military Veterans with diabetes. Transcripts were analyzed using a team-based, iterative process of summarizing and coding to identify key themes. Participants included Veterans (n = 25) who …

Non-Invasive And Objective Tear Film Breakup Detection On Interference Color Images Using Convolutional Neural Networks, Yasushi Kikukawa, Shin Tanaka, Takuya Kosugi, Stephen C Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: Dry eye disease affects hundreds of millions of people worldwide and is one of the most common causes for visits to eye care practitioners. The fluorescein tear breakup time test is currently widely used to diagnose dry eye disease, but it is an invasive and subjective method, thus resulting in variability in diagnostic results. This study aimed to develop an objective method to detect tear breakup using the convolutional neural networks on the tear film images taken by the non-invasive device KOWA DR-1α.

METHODS: The image classification models for detecting characteristics of tear film images were constructed using transfer …

Pediatric Otolaryngology Trends In Patient Care Volume During Covid-19: A Survey Study, William R Pellegrini, Anna H Messner, Jessica R Levi

Faculty, Staff and Students Publications

PURPOSE: To assess changes in outpatient clinic, inpatient consult, and operative volumes among pediatric otolaryngologists in response to the COVID-19 pandemic.

MATERIALS AND METHODS: An online questionnaire was distributed to 535 active members of the American Society of Pediatric Otolaryngology from April 21, 2020, to May 4, 2020. The questionnaire assessed operative and clinical volumes during a two-week period between April 6, 2020, to April 20, 2020, while restrictions on elective surgery were in place, as compared to an average two-week period before the start of the COVID-19 pandemic.

RESULTS: Both outpatient clinic and inpatient consult visit volume decreased significantly …

Cannabis Use Disorder, Suicide Attempts, And Self-Harm Among Adolescents: A National Inpatient Study Across The United States, Adeolu Funso Oladunjoye, Elijah Li, Kammarauche Aneni, Edore Onigu-Otite

Faculty, Staff and Students Publications

Background: Suicide is among the top three causes of adolescent mortality. There is a scarcity of research examining cannabis use and suicidal behavior in adolescents.

Objectives: To determine the association between cannabis use disorder (CUD) and suicide attempt/self-harm in a hospitalized sample of adolescents.

Methods: We conducted a cross-sectional observation study using data from the Nationwide Inpatient Sample collected over four years from January 1, 2016, through December 31, 2019. We included adolescents aged 10-19 hospitalized during the above period (N = 807,105). The primary outcome was suicide attempt/self-harm and the main predictor was CUD. The International Classification of Diseases …

Advanced Photon Counting Ct Imaging Pipeline For Cardiac Phenotyping Of Apolipoprotein E Mouse Models, Alex J Allphin, Ali Mahzarnia, Darin P Clark, Yi Qi, Zay Y Han, Prajwal Bhandari, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT).

Methods: 123 mice grouped based on APOE genotype (APOE2, APOE3, APOE4, APOE knockout (KO)), gender, human NOS2 factor, and diet (control or high fat) were used in this study. The pipeline included PCCT imaging on a custom-built system with contrast-enhanced in vivo imaging and intrinsic cardiac gating, spectral and temporal iterative reconstruction, spectral decomposition, and deep learning cardiac …

Protocol Of Detection Of West Nile Virus In Clinical Samples, Hephzibah Nwanosike, Freedom M Green, Kristy O Murray, Jill E Weatherhead, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) is one of the leading causes of arboviral encephalitis in the United States but is often underdiagnosed. Despite the wide breadth of WNV-induced clinical disease syndromes, many of the symptoms associated with WNV are nonspecific at the time of presentation; thus, choosing the right diagnostic tool is essential to not only understand the true burden of disease but also provide pathogen-directed interventions for WNV-infected patients. In this chapter, we briefly discuss the three most common types of diagnostic methods for WNV in human clinical samples: nucleic acid detection, enzyme-linked immunoassay (ELISA), and plaque reduction neutralization test …

Obicetrapib Plus Ezetimibe As An Adjunct To High-Intensity Statin Therapy: A Randomized Phase 2 Trial, Christie M Ballantyne, Marc Ditmarsch, John Jp Kastelein, Adam J Nelson, Douglas Kling, Andrew Hsieh, Danielle L Curcio, Kevin C Maki, Michael H Davidson, Stephen J Nicholls

Faculty, Staff and Students Publications

Background: Obicetrapib, a selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein particles, and apolipoproteins, when added to high-intensity statin in patients with dyslipidemia.

Objective: To evaluate the safety and lipid-altering efficacy of obicetrapib plus ezetimibe combination therapy as an adjunct to high-intensity statin therapy.

Methods: This double-blind, randomized, phase 2 trial administered 10 mg obicetrapib plus 10 mg ezetimibe (n = 40), 10 mg obicetrapib (n = 39), or placebo (n = 40) for 12 weeks to patients with LDL-C >70 mg/dL and triglycerides (TG) < 400 mg/dL, on stable high-intensity statin. Endpoints included concentrations of lipids, apolipoproteins, lipoprotein particles, and proprotein convertase subtilisin kexin type 9 (PCSK9), safety, and tolerability.

Results: Ninety-seven patients were included in …

Religion, Spirituality, And Coping During The Pandemic: Perspectives Of Dementia Caregivers, Katherine Carroll Britt, Kathy C Richards, Kavita Radhakrishnan, Andrea Vanags-Louredo, Eunice Park, Nalaka S Gooneratne, Liam Fry

Faculty, Staff and Students Publications

Religious and spiritual (R/S) practices support individuals during difficult situations. The COVID-19 social distancing restrictions may have limited access to R/S practices for older adults with Alzheimer’s disease related dementia (ADRD) and their caregivers, affecting coping and well-being. This qualitative study explored the impact of social distancing on R/S practices and coping in ADRD-caregiver dyads from the perspective of caregivers. Interviews were conducted with 11 family caregivers of older adults with ADRD residing in nursing homes (n = 4) or private homes (n = 7). Caregivers continued individual and started virtual R/S practices which improved their ability to …

Imaging Synaptic Density In Depression, Sophie E Holmes, Chadi Abdallah, Irina Esterlis

Faculty, Staff and Students Publications

Major depressive disorder is a prevalent and heterogeneous disorder with treatment resistance in at least 50% of individuals. Most of the initial studies focused on the monoamine system; however, recently other mechanisms have come under investigation. Specific to the current issue, studies show synaptic involvement in depression. Other articles in this issue report on reductions in synaptic density, dendritic spines, boutons and glia associated with stress and depression. Importantly, it appears that some drugs (e.g., ketamine) may lead to rapid synaptic restoration or synaptogenesis. Direct evidence for this comes from preclinical work. However, neuroimaging studies, such as magnetic resonance imaging …

Donepezil Alone And Combined With Intensive Language-Action Therapy On Depression And Apathy In Chronic Post-Stroke Aphasia: A Feasibility Study, Marcelo L Berthier, Lisa Edelkraut, Francisco J López-González, Diana López-Barroso, Bettina Mohr, Friedemann Pulvermüller, Sergio E Starkstein, Ricardo E Jorge, María José Torres-Prioris, Guadalupe Dávila

Faculty, Staff and Students Publications

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be feasible to implement. Large treatment effects were found. Donepezil alone and combined with ILAT reduced aphasia severity, while apathy and depression …

Clinical Trial Design Challenges And Opportunities For Emerging Treatments For Opioid Use Disorder: A Review, Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer, Roland R Griffiths, Andrew S Huhn, Matthew W Johnson, Kyle M Kampman, Marco Pravetoni, Kenzie L Preston, Ryan Vandrey, Cecilia L Bergeria, Michael P Bogenschutz, Randall T Brown, Kelly E Dunn, Robert H Dworkin, Patrick H Finan, Peter S Hendricks, Elisabeth J Houtsmuller, Thomas R Kosten, Dustin C Lee, Frances R Levin, Aimee Mcrae-Clark, Charles L Raison, Kurt Rasmussen, Dennis C Turk, Roger D Weiss, Eric C Strain

Faculty, Staff and Students Publications

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous μ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, …

Habenular Molecular Targets For Depression, Impulsivity, And Addiction, Snigdha Srivastava, Benjamin R Arenkiel, Ramiro Salas

Faculty, Staff and Students Publications

No abstract provided.

Pediatric Bipolar Disorder: Evolution In Clinical And Biological Markers And Future Perspectives, Kirti Saxena, Kiki Chang, Gabriele Sani

Faculty, Staff and Students Publications

No abstract provided.

Gastrointestinal Organoids In The Study Of Viral Infections, J Thomas Gebert, Francesca Scribano, Kristen A Engevik, Jacob L Perry, Joseph M Hyser

Faculty, Staff and Students Publications

Viruses are among the most prevalent enteric pathogens. Although virologists historically relied on cell lines and animal models, human intestinal organoids (HIOs) continue to grow in popularity. HIOs are nontransformed, stem cell-derived, ex vivo cell cultures that maintain the cell type diversity of the intestinal epithelium. They offer higher throughput than standard animal models while more accurately mimicking the native tissue of infection than transformed cell lines. Here, we review recent literature that highlights virological advances facilitated by HIOs. We discuss the variations and limitations of HIOs, how HIOs have allowed for the cultivation of previously uncultivatable viruses, and how …

The Effect Of Multi-Material Architecture On The Ex Vivo Osteochondral Integration Of Bioprinted Constructs, Matthew L Bedell, Ziwen Wang, Katie J Hogan, Angelica L Torres, Hannah A Pearce, Letitia K Chim, K Jane Grande-Allen, Antonios G Mikos

Faculty, Staff and Students Publications

Extrusion bioprinted constructs for osteochondral tissue engineering were fabricated to study the effect of multi-material architecture on encapsulated human mesenchymal stem cells’ tissue-specific matrix deposition and integration into an ex vivo porcine osteochondral explant model. Two extrusion fiber architecture groups with differing transition regions and degrees of bone- and cartilage-like bioink mixing were employed. The gradient fiber (G-Fib) architecture group showed an increase in chondral integration over time, 18.5 ± 0.7 kPa on Day 21 compared to 9.6 ± 1.6 kPa on Day 1 for the required peak push-out force, and the segmented fiber (S-Fib) architecture group did not, which …

Brain Monoamine Vesicular Transport Disease Caused By Homozygous Slc18a2 Variants: A Study In 42 Affected Individuals, Ken Saida, Reza Maroofian, Toru Sengoku, Tadahiro Mitani, Alistair T Pagnamenta, Dana Marafi, Maha S Zaki, Thomas J O'Brien, Ehsan Ghayoor Karimiani, Rauan Kaiyrzhanov, Marina Takizawa, Sachiko Ohori, Huey Yin Leong, Gulsen Akay, Hamid Galehdari, Mina Zamani, Ratna Romy, Christopher J Carroll, Mehran Beiraghi Toosi, Farah Ashrafzadeh, Shima Imannezhad, Hadis Malek, Najmeh Ahangari, Hoda Tomoum, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, David Murphy, Natalia Dominik, Hasnaa M Elbendary, Karima Rafat, Sanem Yilmaz, Seda Kanmaz, Mine Serin, Deepa Krishnakumar, Alice Gardham, Anna Maw, Tekki Sreenivasa Rao, Sarah Alsubhi, Myriam Srour, Daniela Buhas, Tamison Jewett, Rachel E Goldberg, Hanan Shamseldin, Eirik Frengen, Doriana Misceo, Petter Strømme, José Ricardo Magliocco Ceroni, Chong Ae Kim, Gozde Yesil, Esma Sengenc, Serhat Guler, Mariam Hull, Mered Parnes, Dilek Aktas, Banu Anlar, Yavuz Bayram, Davut Pehlivan, Jennifer E Posey, Shahryar Alavi, Seyed Ali Madani Manshadi, Hamad Alzaidan, Mohammad Al-Owain, Lama Alabdi, Ferdous Abdulwahab, Futoshi Sekiguchi, Kohei Hamanaka, Atsushi Fujita, Yuri Uchiyama, Takeshi Mizuguchi, Satoko Miyatake, Noriko Miyake, Reem M Elshafie, Kamran Salayev, Ulviyya Guliyeva, Fowzan S Alkuraya, Joseph G Gleeson, Kristin G Monaghan, Katherine G Langley, Hui Yang, Mahsa Motavaf, Saeid Safari, Mozhgan Alipour, Kazuhiro Ogata, André E X Brown, James R Lupski, Henry Houlden, Naomichi Matsumoto

Faculty, Staff and Students Publications

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants.

Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat …