Medical Specialties Commons^™

Prosthetic Valve Endocarditis From Trichosporon Asahii In An Immunocompetent Patient, Lizy Marial Paniagua, Deepthi Sudhakar, Lara Erika Perez, David Miranda, Pedro Urena, Igor Gregoric, Biswajit Kar, Hani Jneid, Jonalis Ramirez, David Paniagua

Faculty, Staff and Students Publications

Fungal endocarditis is a rare clinical entity. This report describes an unusual case of fungal endocarditis caused by infection with Trichosporon asahii in a 20-year-old immunocompetent man who received the diagnosis 1 year following biological aortic valve replacement. (Level of Difficulty: Beginner.)

A Descriptive Study Of Racial Inequalities In Mortality From Hepatocellular Cancer Before And After Licensure Of Lifesaving Drugs For Hepatitis C Virus In The United States, Robert S Levine, Maria C Mejia, Jason L Salemi, Sandra J Gonzalez, Muktar H Aliyu, Baqar A Husaini, Roger J Zoorob, Charles H Hennekens

Faculty, Staff and Students Publications

BACKGROUND: Since 1979, mortality from hepatocellular cancer (HCC) has doubled in the United States (US). Lifesaving drugs, prohibitively expensive for some, were approved and marketed to treat hepatitis C virus (HCV), a major risk factor for HCC, beginning in 1997. After the prior introduction of other lifesaving innovations, including active retroviral drug therapy for human immunodeficiency virus and surfactant for respiratory distress syndrome of the newborn, racial inequalities in their mortalities increased in the US. In this descriptive study, we explored racial inequalities in mortality from HCC before and after licensure of HCV drugs in the US.

METHODS: The US …

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

Metabolic-Sensing Of The Skeletal Muscle Clock Coordinates Fuel Oxidation, Hongshan Yin, Weini Li, Somik Chatterjee, Xuekai Xiong, Pradip Saha, Vijay Yechoor, Ke Ma

Faculty, Staff and Students Publications

Circadian clock confers temporal control in metabolism, with its disruption leading to the development of insulin resistance. Metabolic substrate utilization in skeletal muscle is coordinated with diurnal nutrient cycles. However, whether the molecular clock is involved in this coordination is largely unknown. Using a myocyte-selective genetic ablation mouse model of the essential clock activator Bmal1, here we identify muscle-intrinsic clock as a sensor of feeding cues to orchestrate skeletal muscle oxidation required for global nutrient flux. Bmal1 in skeletal muscle responds robustly to feeding in vivo and insulin induces its expression. Muscle Bmal1 deficiency impaired the transcriptional control of glucose …

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …

Implementing Inter-Professional Patient-Family Centered Plan Of Care Meetings On An Inpatient Hospital Unit, Nicolas Hernandez, Alice Fornari, Sage Rose, Leanne Tortez

Patient Experience Journal

Inpatient plan of care meetings support efforts to encourage collaborative practice and patient-family centered care and result in an effective strategy to enhance communication and patient satisfaction. Clinical team members participated in patient/family centered plan of care meetings at a community hospital in a selected inpatient unit with full time hospitalist physicians. Quantitative data were gathered pre/post implementation from the external Hospital Consumer Assessment of Health Care Providers (HCAHPS) survey. HCAHPS data were collected independently, specifically for questions related to communication between patients, family members/guardians and the medical team and also the effects of care transition. There was a slow …

Association Of Aβ With Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity, Ahmed Elsherbini, Alexander S. Kirov, Michael B. Dinkins, Guanghu Wang, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich

Physiology Faculty Publications

Amyloid-β (Aβ) associates with extracellular vesicles termed exosomes. It is not clear whether and how exosomes modulate Aβ neurotoxicity in Alzheimer's disease (AD). We show here that brain tissue and serum from the transgenic mouse model of familial AD (5xFAD) and serum from AD patients contains ceramide-enriched and astrocyte-derived exosomes (termed astrosomes) that are associated with Aβ. In Neuro-2a cells, primary cultured neurons, and human induced pluripotent stem cell-derived neurons, Aβ-associated astrosomes from 5xFAD mice and AD patient serum were specifically transported to mitochondria, induced mitochondrial clustering, and upregulated the fission protein Drp-1 at a concentration corresponding to 5 femtomoles …

Giving Credence To The Experience Of X-Linked Hypophosphatemia In Adulthood: An Interprofessional Mixed-Methods Study, Melissa Hughes, Carolyn Macica, Catherine Meriano, Maya Doyle

Journal of Patient-Centered Research and Reviews

Purpose: X-linked hypophosphatemia (XLH) is a rare X-linked dominant metabolic bone disease, often diagnosed in childhood but causing increasing physical debilitation and pain in adulthood. Physical comorbidities of XLH in adulthood include pervasive and early-onset degenerative arthritis, mineralizing enthesophytes and osteophytes, osteomalacia and pseudofracture, dental abscesses, and hearing loss.

Methods: This mixed-methods analysis included physical findings, diagnostic imaging, occupational and physical therapy assessments, and semi-structured interviews by social work to understand the functional outcomes and lived experience of XLH in adulthood, through connections between qualitative data obtained by social work and occupational therapy with the quantitative findings from other disciplines. …

Myocardial Work Index: A Novel Method For Assessment Of Myocardial Function In South Asian Recreational Athletes, Shantanu Sengupta, Renuka Jain, Nitin Burkule, Susan Olet, Bijoy K. Khandheria

Journal of Patient-Centered Research and Reviews

Purpose: We used a novel noninvasive method based on speckle-tracking echocardiography to evaluate myocardial performance in South Asian recreational athletes who completed a half marathon.

Methods: Transthoracic echocardiography was performed on 24 recreational athletes 48 hours before they took part in a half marathon (premarathon), within 2 hours of half marathon completion (postmarathon), and 72 hours after completion. Clinical, laboratory, and echocardiographic variables were collected. Speckle-tracking echocardiography was performed in all subjects to characterize myocardial mechanics.

Results: Mean age of participants was 41.8 ± 7.4 years, and 23 (95.8%) were male. No subject had a prior history of coronary artery …

Challenges Of Pediatric Disease In Adulthood, Dennis J. Baumgardner, Brian Chicoine

Journal of Patient-Centered Research and Reviews

Some chronic diseases — such as the rare bone disease X-linked hypophosphatemia, the impetus for a study reported within Volume 7, Issue 2 of the Journal of Patient-Centered Research and Reviews — are diagnosed in childhood but become more symptomatic in adulthood. In this editorial, the challenges, pitfalls, and opportunities regarding the care of adults with childhood-onset chronic diseases are examined using Down syndrome, cystic fibrosis, congenital heart disease, and Hirschsprung disease as examples.

Dancing During Labor: Social Media Trend Or Future Practice?, Caroline P. Toberna, Drew Horter, Kayla Heslin, Marie M. Forgie, Emily Malloy, Jessica J. F. Kram

Journal of Patient-Centered Research and Reviews

Over the past 30 years, medical interventions in pregnancy and childbirth have increased. Some pregnant women seek less invasive and nonpharmacological options to manage discomforts during labor. While exercise during pregnancy is recommended, less is known about exercise, specifically dancing, during labor. While anecdotal evidence is supportive, little is known about the implications of exercise and dance during the first stage of labor for pain reduction and labor progression. Some movements common in dance, such as expanding hip circles that loosen and relax muscles of the pelvic floor, may be beneficial to women during labor. Available evidence suggests that dancing …

How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi K. Kamepalli Md,Fidsa,Cwsp

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Adverse Aftereffects Of Methotrexate As Chemotherapy On Cognitive Deficits In Rat Models, Jubin Kang

Senior Honors Theses

Patients with acute lymphoblastic leukemia have a high five-year survival rate thanks to methotrexate (MTX). However, cognitive side effects are reported, characterized as chemo brain. The study investigated if impulsiveness is part of the aberrant cognitive functions after being exposed to MTX in the early stage of physical development. Adolescent rats were injected with either phosphate-buffered saline (PBS) or MTX. The novel object recognition (NOR) task was conducted a month after the injections to measure the memory deficits. The discounting task was performed after the rats completed training on a fixed-ratio one schedule for both levers. The NOR test showed …

Efficacy Of Quality Improvement And Patient Safety Workshops For Students: A Pilot Study, Kevin P Shah, Shreya Goyal, Vignesh Ramachandran, Jaden R Kohn, Jonathan A Go, Zachary Wiley, Anoosha Moturu, Meera K Namireddy, Anjali Kumar, Ryan C Jacobs, Matthew Stampfl, Jesal R Shah, Justin Fu, Weijie V Lin, Brandon Ho, Grace Wey, Sophie Y Lin, Andrew C Caruso, Lindsey Jordan Gay, Diana E Stewart, Sara Andrabi

Faculty, Staff and Students Publications

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes.

METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause …

Increasing Patient Adherence To Gestational Weight Gain Goals In Pregnancy, Annie Vining

Dissertations

Abstract

Problem: The inability to maintain healthy weight gain during pregnancy may contribute to multiple pregnancy-related complications. Nutritional education and support may improve nutrition and vitamin consumption, and recommendations for healthy gestational weight gains have been published. However, pregnant women have reported minimal advice regarding healthy weight gain during pregnancy. A personalized, nutritional counseling program was initiated in a Midwestern, suburban OB-GYN private practice.

Methods: A quality improvement descriptive, correlational design was used. A cohort of pregnant women first trimester through six-weeks postpartum received individual counseling and face-to-face interaction at an office visit each trimester.

Results: Twenty ( …

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

Process Monitoring Of Moisture Content And Mass Transfer Rate In A Fluidised Bed With A Low Cost Inline Mems Nir Sensor, Claudio R Avila, Joan Ferré, Rodrigo Rocha De Oliveira, Anna De Juan, Wayne E Sinclair, Faiz M Mahdi, Ali Hassanpour, Timothy N Hunter, Richard A Bourne, Frans L Muller

Faculty, Staff and Students Publications

PURPOSE: The current trend for continuous drug product manufacturing requires new, affordable process analytical techniques (PAT) to ensure control of processing. This work evaluates whether property models based on spectral data from recent Fabry-Pérot Interferometer based NIR sensors can generate a high-resolution moisture signal suitable for process control.

METHODS: Spectral data and offline moisture content were recorded for 14 fluid bed dryer batches of pharmaceutical granules. A PLS moisture model was constructed resulting in a high resolution moisture signal, used to demonstrate (i) endpoint determination and (ii) evaluation of mass transfer performance.

RESULTS: The sensors appear robust with respect to …

Genetic Relationships And Therapeutic Options For Relapsed Acute Lymphoblastic Leukemia, Hailie Shertzer

Senior Honors Theses

Acute lymphoblastic leukemia (ALL) is the most common form of cancer among children and can be lethal to the adult population. Though 80% of patients with ALL reach complete remission after treatment, about 20% of those diagnosed fail to remain cancer-free. Genetic rearrangements are the hallmark of relapsed ALL, but the mechanism by which these rearrangements occur is still unclear. Recent research suggests these mutations may be detectable during initial diagnosis. If researchers are able to accurately assess the probability of relapse during diagnosis by analyzing the genome of the leukemic cells, the likelihood of administering effective therapy would increase. …

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

Modulating The Rate Of Fibrin Formation And Clot Structure Attenuates Microvascular Thrombosis In Systemic Inflammation, Christian Valladolid, Marina Martinez-Vargas, Nitin Sekhar, Fong Lam, Cameron Brown, Timothy Palzkill, Alexander Tischer, Mathew Auton, K Vinod Vijayan, Rolando E Rumbaut, Trung C Nguyen, Miguel A Cruz

Faculty, Staff and Students Publications

Systemic inflammation can lead to coagulopathy and disseminated intravascular coagulation (DIC). In prior studies, the recombinant A2 domain of human von Willebrand factor (VWF; A2 protein) attenuated DIC and decreased mortality in lipopolysaccharide (LPS)-treated mice. Here, we performed studies to dissect the mechanism by which the A2 protein moderates DIC. We used confocal microscopy to analyze the fibrin clot structure in plasma from healthy humans and endotoxemic mice, turbidity assays to examine fibrin polymerization, and a murine model for LPS-induced DIC and introduced a loss-of-function mutation into the A2 protein for fibrin. The mutation of the residue E1567 located in …

The Implementation Of Exercise For Chronic Kidney Disease And Dialysis Patients, Syed Ahmad Rizvi

Honors College Theses

While commonly known to be the organ that helps with urine production within the human body, the kidney plays one of the most crucial roles in maintaining homeostasis. When establishing all of the roles the kidney has on keeping humans healthy, there is the question of how does the body cope when a patient is diagnosed with kidney failure. One of the more common treatment options that allows the body to continue to function without a kidney is by beginning a patient on a form of dialysis. However, as with any treatment, there will always be a list of side …

Tetralogy Of Fallot: A Clinical Review, Jacob Wooten, Joshua Bahos Silva

Student Scholar Showcase

Tetralogy of Fallot is a congenital heart disease that is associated with structural abnormalities during fetal development 1. The incidence of Tetralogy of Fallot in the United States is approximately 3-5 cases per 10,000 live births and is considered one of the most common cyanotic congenital heart diseases 2. The exact etiology of Tetralogy of Fallot is unknown, however it is thought to be associated with untreated maternal diabetes, maternal use of retinoids, as well as chromosomal abnormalities 2. The main components of this disease state include a right ventricular outflow obstruction, interventricular communication in the form of a ventricular …

Regenerative Medicine Therapy: Adipose Derived Extracellular Vesicles In Viral Myocarditis, David Gorelov, Damian N. Di Florio, Gary R. Salomon, Angita Jain, Nick E. Saikaili, Danielle J. Beetler, Swikriti Shrestha, Ming Tian, Joy Wolfram Phd, Delisa Fairweather Phd, Katelyn Bruno Phd, Judith D. Ochrietor Phd

Showcase of Osprey Advancements in Research and Scholarship (SOARS)

Objective: Myocarditis, inflammation of the heart muscle, is an autoimmune heart disease that can be caused by viruses, bacteria and toxins. Myocarditis can lead to dilated cardiomyopathy (DCM) and heart failure. Currently there are no disease-specific therapies for treating myocarditis or preventing progression to DCM. Adipose Extracellular Vesicles (AEVs) are lipid bilayer nanoparticles that are released into the outside environment of adipocytes and provide promising regenerative potential for inflammatory diseases like myocarditis.

Methods: Lipoaspirate was obtained from women and men and AEVs isolated from the lipoaspirate using tangential flow filtration. We injected wild type male BALB/c mice with 250uL AEVs …

First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill

Sanders-Brown Center on Aging Faculty Publications

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes …

Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Yujing Gao, Lijia Chen, Yali Han, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng

Faculty, Staff and Students Publications

As approximately 70% of human breast tumors are estrogen receptor α (ERα)-positive, estrogen and ERα play essential roles in breast cancer development. By interrupting the ERα signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERα) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting …

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …

Principles Of Rna Processing From Analysis Of Enhanced Clip Maps For 150 Rna Binding Proteins, Eric L Van Nostrand, Gabriel A Pratt, Brian A Yee, Emily C Wheeler, Steven M Blue, Jasmine Mueller, Samuel S Park, Keri E Garcia, Chelsea Gelboin-Burkhart, Thai B Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R Graveley, Gene W Yeo

Faculty, Staff and Students Publications

BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types.

RESULTS: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA …

Compassion And Suppression In Caregivers: Twin Masks Of Tragedy And Joy Of Caring, Emanuele Maria Merlo, Sean M. Mcnabney, Fabio Frisone, Federica Sicari, Mihai Paunica, Catalina Motofei, Salvatore Settineri

Journal of Mind and Medical Sciences

Background: Compassionate caregiving is a critical skill for workers among the helping professions, but the degree of empathy required by caregivers can place high demands on their mental and emotional resources. While many professionals employ successful coping strategies to mitigate these stressors, others experience compassion fatigue or burnout from emotional exhaustion. The objective of this research was to evaluate the relationships between caregivers’ demographic/career variables, compassion satisfaction, compassion fatigue, and psychodynamic defense mechanisms such as suppression, repressive function, regression in the service of the Ego, and rationalization. Methods: Participants were 250 caregivers with 178 (71,2%) women and 72 men (28,8%) …

Phosphoinositides In Retinal Function And Disease, Theodore G Wensel

Faculty, Staff and Students Publications

Phosphatidylinositol and its phosphorylated derivatives, the phosphoinositides, play many important roles in all eukaryotic cells. These include modulation of physical properties of membranes, activation or inhibition of membrane-associated proteins, recruitment of peripheral membrane proteins that act as effectors, and control of membrane trafficking. They also serve as precursors for important second messengers, inositol (1,4,5) trisphosphate and diacylglycerol. Animal models and human diseases involving defects in phosphoinositide regulatory pathways have revealed their importance for function in the mammalian retina and retinal pigmented epithelium. New technologies for localizing, measuring and genetically manipulating them are revealing new information about their importance for the …

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …