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Live Imaging Reveals The Cellular Events Downstream Of Sarm1 Activation, Kwang Woo Ko, Laura Devault, Yo Sasaki, Jeffrey Milbrandt, Aaron Diantonio

Open Access Publications

SARM1 is an inducible NAD

Intestinal Goblet Cells Sample And Deliver Lumenal Antigens By Regulated Endocytic Uptake And Transcytosis, Jenny K. Gustafsson, Jazmyne E. Davis, Tracy Rappai, Keely G. Mcdonald, Devesha H. Kulkarni, Kathryn A. Knoop, Simon P. Hogan, James A.J. Fitzpatrick, Wayne I. Lencer, Rodney D. Newberry

Open Access Publications

Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis - in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and …

A Representational Similarity Analysis Of Cognitive Control During Color-Word Stroop, Michael C. Freund, Julie M. Bugg, Todd S. Braver

Open Access Publications

Progress in understanding the neural bases of cognitive control has been supported by the paradigmatic color-word Stroop task, in which a target response (color name) must be selected over a more automatic, yet potentially incongruent, distractor response (word). For this paradigm, models have postulated complementary coding schemes: dorsomedial frontal cortex (DMFC) is proposed to evaluate the demand for control via incongruency-related coding, whereas dorsolateral PFC (DLPFC) is proposed to implement control via goal and target-related coding. Yet, mapping these theorized schemes to measured neural activity within this task has been challenging. Here, we tested for these coding schemes relatively directly, …

Mechanical Overstimulation Causes Acute Injury And Synapse Loss Followed By Fast Recovery In Lateral-Line Neuromasts Of Larval Zebrafish, Melanie Holmgren, Michael E. Ravicz, Kenneth E. Hancock, Olga Strelkova, Dorina Kallogjeri, Artur A. Indzhykulian, Mark E. Warchol, Lavinia Sheets

Open Access Publications

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced …

A Novel Precision Approach To Overcome The "Addiction Pandemic" By Incorporating Genetic Addiction Risk Severity (Gars) And Dopamine Homeostasis Restoration, Kenneth Blum, Shan Kazmi, Edward J Modestino, Bill William Downs, Debasis Bagchi, David Baron, Thomas Mclaughlin, Richard Green, Rehan Jalali, Panayotis K Thanos, Igor Elman, Rajendra D Badgaiyan, Abdalla Bowirrat, Mark S Gold

Open Access Publications

This article describes a unique therapeutic precision intervention, a formulation of enkephalinase inhibitors, enkephalin, and dopamine-releasing neuronutrients, to induce dopamine homeostasis for detoxification and treatment of individuals genetically predisposed to developing reward deficiency syndrome (RDS). The formulations are based on the results of the addiction risk severity (GARS) test. Based on both neurogenetic and epigenetic evidence, the test evaluates the presence of reward genes and risk alleles. Existing evidence demonstrates that the novel genetic risk testing system can successfully stratify the potential for developing opioid use disorder (OUD) related risks or before initiating opioid analgesic therapy and RDS risk for …

Monitoring The Variation In The Gut Microbiota Of Captive Woolly Monkeys Related To Changes In Diet During A Reintroduction Process, Camilo Quiroga-González, Luis Alberto Chica Cardenas, Mónica Ramírez, Alejandro Reyes, Camila González, Pablo R. Stevenson

Open Access Publications

No abstract provided.

Inflammatory Signaling Sensitizes Piezo1 Mechanotransduction In Articular Chondrocytes As A Pathogenic Feed-Forward Mechanism In Osteoarthritis, Whasil Lee, Robert J. Nims, Alireza Savadipour, Qiaojuan Zhang, Holly A. Leddy, Fang Liu, Amy L. Mcnulty, Yong Chen, Farshid Guilak, Wolfgang B. Liedtke

Open Access Publications

No abstract provided.

Leishmania Sexual Reproductive Strategies As Resolved Through Computational Methods Designed For Aneuploid Genomes, Jahangheer S Shaik, Deborah E Dobson, David L Sacks, Stephen M Beverley

Open Access Publications

A cryptic sexual reproductive cycle in

Factors Predicting Chronic Opioid Use After Orthopedic Surgical Procedures, Basavana Goudra, Arjun Guthal, Preet Mohinder Singh

Open Access Publications

BACKGROUND: Opioid abuse has been an increasing problem since the 1990s. With over 47,000 opioid related deaths recorded in 2017 alone, concerns have been raised regarding the dangers of introducing opioids perioperatively to patients undergoing major surgeries.

OBJECTIVES: The present study proposes to examine the frequency, amount, and trends in post-operative opioid consumption in patients undergoing orthopedic surgical procedures.

STUDY DESIGN: This was a randomized, retrospective questionnaire-based study.

SETTING: Patients who underwent any type of orthopedic surgery at the University of Pennsylvania Presbyterian Hospital from 1/1/2018 to 3/12/2019 were randomly selected and called during the summer of 2019.

METHODS: In …

Cannabis-Induced Hypodopaminergic Anhedonia And Cognitive Decline In Humans: Embracing Putative Induction Of Dopamine Homeostasis, Kenneth Blum, Jag Khalsa, Jean Lud Cadet, David Baron, Abdalla Bowirrat, Brent Boyett, Lisa Lott, Raymond Brewer, Marjorie Gondré-Lewis, Gregory Bunt, Shan Kazmi, Mark S Gold

Open Access Publications

Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young …

Comprehensive Mirnome-Wide Profiling In A Neuronal Cell Model Of Synucleinopathy Implies Involvement Of Cell Cycle Genes, Elisabeth Findeiss, Sigrid C Schwarz, Valentin Evsyukov, Thomas W Rösler, Matthias Höllerhage, Tasnim Chakroun, Niko-Petteri Nykänen, Yimin Shen, Wolfgang Wurst, Michael Kohl, Jörg Tost, Günter U Höglinger

Open Access Publications

Growing evidence suggests that epigenetic mechanisms like microRNA-mediated transcriptional regulation contribute to the pathogenesis of parkinsonism. In order to study the influence of microRNAs (miRNAs), we analyzed the miRNome 2 days prior to major cell death in α-synuclein-overexpressing Lund human mesencephalic neurons, a well-established cell model of Parkinson's disease (PD), by next-generation sequencing. The expression levels of 23 miRNAs were significantly altered in α-synuclein-overexpressing cells, 11 were down- and 12 upregulated (

Myosin V Regulates Spatial Localization Of Different Forms Of Neurotransmitter Release In Central Synapses, Dario Maschi, Michael W Gramlich, Vitaly A Klyachko

Open Access Publications

Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition …

Sensible Introduction Of Mr-Guided Radiotherapy: A Warm Plea For The Rct, Helena M Verkooijen, Lauren E Henke

Open Access Publications

Magnetic resonance guided radiotherapy (MRgRT) is the newest face of technology within a field long-characterized by continual technologic advance. MRgRT may offer improvement in the therapeutic index of radiation by offering novel planning types, like online adaptation, and improved image guidance, but there is a paucity of randomized data or ongoing randomized controlled trials (RCTs) to demonstrate clinical gains. Strong clinical evidence is needed to confirm the theoretical advantages of MRgRT and for the rapid dissemination of (and reimbursement for) appropriate use. Although some future evidence for MRgRT may come from large registries and non-randomized studies, RCTs should make up …

The Valproate Mediates Radio-Bidirectional Regulation Through Rfwd3-Dependent Ubiquitination On Rad51, Guochao Liu, David Lim, Zuchao Cai, Wenwen Ding, Zhujun Tian, Chao Dong, Fengmei Zhang, Gongshe Guo, Xiaowei Wang, Pingkun Zhou, Zhihui Feng

Open Access Publications

Ionizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related …

Clinical Prediction Rule For Sars-Cov-2 Infection From 116 U.S. Emergency Departments 2-22-2021, Jeffrey A. Kline, Stacey House, Et Al.

Open Access Publications

OBJECTIVES: Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care.

METHODS: Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records …

Resting-State Functional Connectivity Disruption As A Pathological Biomarker In Autosomal Dominant Alzheimer Disease, Robert X. Smith, Jeremy F. Strain, Aaron Tanenbaum, Anne M. Fagan, Jason Hassenstab, Eric Mcdade, Suzanne E. Schindler, Brian A. Gordon, Chengjie Xiong, Celeste Karch, David M. Holtzman, Daniel S. Marcus, John C. Morris, Tammie L.S. Benzinger, Randall J. Bateman, Beau M. Ances, Et Al.

Open Access Publications

No abstract provided.

Recent Developments In Devices Used For Gastrointestinal Endoscopy Sedation, Basavana Goudra, Gowri Gouda, Preet Mohinder Singh

Open Access Publications

No abstract provided.

Old Vaccines For New Infections: Exploiting Innate Immunity To Control Covid-19 And Prevent Future Pandemics, Konstantin Chumakov, Michael S. Avidan, Christine S. Benn, Stefano M. Bertozzi, Lawrence Blatt, Angela Y. Chang, Dean T. Jamison, Shabaana A. Khader, Shyam Kottilil, Mihai G. Netea, Annie Sparrow, Robert C. Gallo

Open Access Publications

No abstract provided.

A Domestic Cat Whole Exome Sequencing Resource For Trait Discovery, Alana R. Rodney, Rueben M. Buckley, Robert S. Fulton, Catrina Fronick, Todd Richmond, Christopher R. Helps, Peter Pantke, Dianne J. Trent, Karen M. Vernau, John S. Munday, Andrew C. Lewin, Rondo Middleton, Leslie A. Lyons, Wesley C. Warren

Open Access Publications

No abstract provided.

A Cross-Sectional Comparison Of Physical Activity During Covid-19 In A Sample Of Rural And Non-Rural Participants In The Us, Alan M Beck, Amanda S Gilbert, Dixie D Duncan, Eric M Wiedenman

Open Access Publications

Physical activity (PA) pre-COVID-19 was lower in rural areas compared to non-rural areas. The purpose of this study was to determine COVID-19's impact on PA in rural and non-rural residents. A cross-sectional study consisting of a convenience sample of 278 participants (50% rural, 50% non-rural) from 25 states completed an online survey describing their PA behaviors and perceptions during COVID-19. The global physical activity questionnaire was used to determine PA in various domains and summed to determine if the participant met the PA guidelines. Rural participants had a significantly higher body mass index, lower income, and a lower educational attainment. …

Advantages Of 18f-Fdg Pet/Ct Imaging Over Modified Duke Criteria And Clinical Presumption In Patients With Challenging Suspicion Of Infective Endocarditis, Valentin Pretet, Cyrille Blondet, Yvon Ruch, Matias Martinez, Soraya El Ghannudi, Olivier Morel, Yves Hansmann, Thomas H Schindler, Alessio Imperiale

Open Access Publications

According to European Society of Cardiology guidelines (ESC2015) for infective endocarditis (IE) management, modified Duke criteria (mDC) are implemented with a degree of clinical suspicion degree, leading to grades such as "possible" or "rejected" IE despite a persisting high level of clinical suspicion. Herein, we evaluate the

Left Ventricle Phenotyping Utilizing Tissue Doppler Imaging In Premature Infants With Varying Severity Of Bronchopulmonary Dysplasia, Eunice Torres, Philip T Levy, Afif El-Khuffash, Hongjie Gu, Aaron Hamvas, Gautam K Singh

Open Access Publications

Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities (s', e', a'), isovolumetric relaxation time (IVRT), and myocardial performance index with TDI …

Procaspase-Activating Compound-1 Synergizes With Trail To Induce Apoptosis In Established Granulosa Cell Tumor Cell Line (Kgn) And Explanted Patient Granulosa Cell Tumor Cells In Vitro, Powel Crosley, Anniina Farkkila, Adrianne L Jenner, Chloé Burlot, Olivia Cardinal, Kyle G Potts, Kate Agopsowicz, Marjut Pihlajoki, Markku Heikinheimo, Morgan Craig, Yangxin Fu, Mary M Hitt

Open Access Publications

Granulosa cell tumors (GCT) constitute only ~5% of ovarian neoplasms yet have significant consequences, as up to 80% of women with recurrent GCT will die of the disease. This study investigated the effectiveness of procaspase-activating compound 1 (PAC-1), an activator of procaspase-3, in treating adult GCT (AGCT) in combination with selected apoptosis-inducing agents. Sensitivity of the AGCT cell line KGN to these drugs, alone or in combination with PAC-1, was tested using a viability assay. Our results show a wide range in cytotoxic activity among the agents tested. Synergy with PAC-1 was most pronounced, both empirically and by mathematical modelling, …

Pre-Clinical Common Data Elements For Traumatic Brain Injury Research: Progress And Use Cases, Michelle C. Laplaca, Stuart H. Friess, Et Al.

Open Access Publications

No abstract provided.

Impact Of Intrauterine Fetal Resuscitation With Oxygen On Oxidative Stress In The Developing Rat Brain, Jia Jiang, Tusar Giri, Nandini Raghuraman, Alison G. Cahill, Arvind Palanisamy

Open Access Publications

No abstract provided.

Electronic Health Record-Embedded Individualized Pain Plans For Emergency Department Treatment Of Vaso-Occlusive Episodes In Adults With Sickle Cell Disease: Protocol For A Preimplementation And Postimplementation Study, Lingzi Luo, Allison A King, Christopher R Carpenter, Lisa Klesges, Et Al

Open Access Publications

BACKGROUND: Individuals living with sickle cell disease often require aggressive treatment of pain associated with vaso-occlusive episodes in the emergency department. Frequently, pain relief is poor. The 2014 National Heart, Lung, and Blood Institute evidence-based guidelines recommended an individualized treatment and monitoring protocol to improve pain management of vaso-occlusive episodes.

OBJECTIVE: This study will implement an electronic health record-embedded individualized pain plan with provider and patient access in the emergency departments of 8 US academic centers to improve pain treatment for adult patients with sickle cell disease. This study will assess the overall effects of electronic health record-embedded individualized pain …

Attitudinal Acceptance Of Intimate Partner Violence And Mental Health Outcomes For Female Survivors In Sub-Saharan Africa, Reine-Marcelle Ibala, Ilana Seff, Lindsay Stark

Open Access Publications

While current literature evidences a strong association between gender-based violence exposure and adverse mental health outcomes, few studies have explored how attitudinal acceptance of intimate partner violence (IPV) might impact this relationship. This analysis employed data from 13-24-year-old females as part of the Violence Against Children Surveys in Nigeria, Uganda, and Malawi. Mental health status, defined by the Kessler Screening Scale for Psychological Distress, and suicide ideation served as outcome measures. Predictors of interest included lifetime experiences of IPV and attitudinal acceptance of IPV. Country-stratified logistic and ordinary least squares regressions were used to predict outcomes and included interactions between …

Radiosynthesis And Evaluation Of Talazoparib And Its Derivatives As Parp-1-Targeting Agents, Dong Zhou, Huaping Chen, Cedric Mpoy, Sadia Afrin, Buck E Rogers, Joel R Garbow, John A Katzenellenbogen, Jinbin Xu

Open Access Publications

Poly (ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme in the DNA repair process and the target of several FDA-approved inhibitors. Several of these inhibitors have been radiolabeled for non-invasive imaging of PARP-1 expression or targeted radiotherapy of PARP-1 expressing tumors. In particular, derivatives of olaparib and rucaparib, which have reduced trapping potency by PARP-1 compared to talazoparib, have been radiolabeled for these purposes. Here, we report the first radiosynthesis of [

Modular Network Between Postrhinal Visual Cortex, Amygdala, And Entorhinal Cortex, Andrew M. Meier, Quanxin Wang, Weiqing Ji, Jehan Ganachaud, Andreas Burkhalter

Open Access Publications

The postrhinal area (POR) is a known center for integrating spatial with nonspatial visual information and a possible hub for influencing landmark navigation by affective input from the amygdala. This may involve specific circuits within muscarinic acetylcholine receptor 2 (M2)-positive (M2

Is The Intestine A Portal Of Entry For The Serious Covid-19 Complications Of Endotoxemia And Thrombosis?, David H. Alpers

Open Access Publications

No abstract provided.