Medicine and Health Sciences Commons^™

The Tfiis N-Terminal Domain (Tnd): A Transcription Assembly Module At The Interface Of Order And Disorder, Katerina Cermakova, Vaclav Veverka, H Courtney Hodges

Faculty, Staff and Students Publications

Interaction scaffolds that selectively recognize disordered protein strongly shape protein interactomes. An important scaffold of this type that contributes to transcription is the TFIIS N-terminal domain (TND). The TND is a five-helical bundle that has no known enzymatic activity, but instead selectively reads intrinsically disordered sequences of other proteins. Here, we review the structural and functional properties of TNDs and their cognate disordered ligands known as TND-interacting motifs (TIMs). TNDs or TIMs are found in prominent members of the transcription machinery, including TFIIS, super elongation complex, SWI/SNF, Mediator, IWS1, SPT6, PP1-PNUTS phosphatase, elongin, H3K36me3 readers, the transcription factor MYC, and …

Impact Of Penicillin Allergy Labels On Children Treated For Outpatient Respiratory Infections, Torsten Joerger, Margaret G Taylor, Yun Li, Debra L Palazzi, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Penicillin allergy is the most common antibiotic allergy, yet most children labeled as allergic tolerate penicillin. The impact of inaccurate penicillin allergy labels (PALs) on pediatric outpatients is unknown. The objective of this study was to compare outcomes between children with and without a PAL after treatment for outpatient respiratory tract infections (RTI).

METHODS: A retrospective, longitudinal birth cohort study was performed in children who received care in 90 pediatric primary care practices in Philadelphia and Houston metropolitan areas. Prescribing and clinical outcomes of children with a PAL at the time of an RTI were compared to non-allergic children, …

Developing Consensus On Clinical Outcomes For Children With Mild Pneumonia: A Delphi Study, Todd A Florin, Joy Melnikow, Melissa Gosdin, Ryan Ciuffetelli, Jillian Benedetti, Dustin Ballard, Marianne Gausche-Hill, Matthew P Kronman, Lisa A Martin, Rakesh D Mistry, Mark I Neuman, Debra L Palazzi, Sameer J Patel, Wesley H Self, Samir S Shah, Sonal N Shah, Susan Sirota, Andrea T Cruz, Richard Ruddy, Jeffrey S Gerber, Nathan Kuppermann

Faculty, Staff and Students Publications

BACKGROUND: The absence of consensus for outcomes in pediatric antibiotic trials is a major barrier to research harmonization and clinical translation. We sought to develop expert consensus on study outcomes for clinical trials of children with mild community-acquired pneumonia (CAP).

METHODS: Applying the Delphi method, a multispecialty expert panel ranked the importance of various components of clinical response and treatment failure outcomes in children with mild CAP for use in research. During Round 1, panelists suggested additional outcomes in open-ended responses that were added to subsequent rounds of consensus building. For Rounds 2 and 3, panelists were provided their own …

Uncovering Novel Regulators Of Memory Using C Elegans Genetic And Genomic Analysis, Katie L Brandel-Ankrapp, Rachel N Arey

Faculty, Staff and Students Publications

How organisms learn and encode memory is an outstanding question in neuroscience research. Specifically, how memories are acquired and consolidated at the level of molecular and gene pathways remains unclear. In addition, memory is disrupted in a wide variety of neurological disorders; therefore, discovering molecular regulators of memory may reveal therapeutic targets for these disorders. C. elegans are an excellent model to uncover molecular and genetic regulators of memory. Indeed, the nematode's invariant neuronal lineage, fully mapped genome, and conserved associative behaviors have allowed the development of a breadth of genetic and genomic tools to examine learning and memory. In …

Mecp2 Regulates Gdf11, A Dosage-Sensitive Gene Critical For Neurological Function, Sameer S Bajikar, Ashley G Anderson, Jian Zhou, Mark A Durham, Alexander J Trostle, Ying-Wooi Wan, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss- and gain-of-function of MeCP2 causes Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. MeCP2 binds methyl-cytosines to finely tune gene expression in the brain, but identifying genes robustly regulated by MeCP2 has been difficult. By integrating multiple transcriptomics datasets, we revealed that MeCP2 finely regulates growth differentiation factor 11 (Gdf11). Gdf11 is down-regulated in RTT mouse models and, conversely, up-regulated in MDS mouse models. Strikingly, genetically normalizing Gdf11 dosage levels improved several behavioral deficits in a mouse model of MDS. Next, we discovered that losing one copy of Gdf11 alone was sufficient to cause multiple neurobehavioral …

Trpv1-Mediated Sonogenetic Neuromodulation Of Motor Cortex In Freely Moving Mice, Kevin Xu, Yaoheng Yang, Zhongtao Hu, Yimei Yue, Yan Gong, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen

2020-Current year OA Pubs

No abstract provided.

Long-Term Intensive Endurance Exercise Training Is Associated To Reduced Markers Of Cellular Senescence In The Colon Mucosa Of Older Adults, Marco Demaria, Beatrice Bertozzi, Nicola Veronese, Francesco Spelta, Edda Cava, Valeria Tosti, Laura Piccio, Dayna S Early, Luigi Fontana

2020-Current year OA Pubs

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly …

Care Of Bullet-Related Injuries: A Cross-Sectional Study Of Instructions And Prescriptions Provided On Discharge From The Emergency Department, Jane M. Hayes, L J. Punch, Kristen L. Mueller

2020-Current year OA Pubs

INTRODUCTION: There are more than 80,000 emergency department (ED) visits for non-fatal bullet-related injuries (BRI) per year in the United States. Approximately half of these patients are discharged home from the ED. Our objective in this study was to characterize the discharge instructions, prescriptions, and follow-up plans provided to patients discharged from the ED after BRI.

METHODS: This was a single-center, cross-sectional study of the first 100 consecutive patients who presented to an urban, academic, Level I trauma center ED with an acute BRI beginning on January 1, 2020. We queried the electronic health record for patient demographics, insurance status, …

Orthodenticle Homeobox 2 Is Transported To Lysosomes By Nuclear Budding Vesicles, Jun Woo Park, Eun Jung Lee, Eunyoung Moon, Hong-Lim Kim, In-Beom Kim, Didier Hodzic, Namsuk Kim, Hee-Seok Kweon, Jin Woo Kim

2020-Current year OA Pubs

Transcription factors (TFs) are transported from the cytoplasm to the nucleus and disappear from the nucleus after they regulate gene expression. Here, we discover an unconventional nuclear export of the TF, orthodenticle homeobox 2 (OTX2), in nuclear budding vesicles, which transport OTX2 to the lysosome. We further find that torsin1a (Tor1a) is responsible for scission of the inner nuclear vesicle, which captures OTX2 using the LINC complex. Consistent with this, in cells expressing an ATPase-inactive Tor1aΔE mutant and the LINC (linker of nucleoskeleton and cytoskeleton) breaker KASH2, OTX2 accumulated and formed aggregates in the nucleus. Consequently, in the mice expressing …

Heart Rate Variability (Hrv) Loss And Other Ekg Changes Prior To A Cardiopulmonary Event In Children Admitted To The Icu At A Tertiary Care Children’S Hospital, Sabrina R. Orta, Shreya Chandran, Utpal Bhalala

MEDI 9331 Scholarly Activities Clinical Years

Introduction: HRV and EKG changes prior to cardiopulmonary events (CPEs) occurring in children in intensive care unit (ICU) settings is not well documented. We assess if substantial losses of HRV and/or other EKG changes, if any, may be detectable prior to a CPE occurring in children admitted to the ICU.

Methods: A prospective observational cohort study was conducted in the ICU from January to February of 2023 at Driscoll Children’s Hospital. A “CPE” was defined as a change in the clinical status of a child warranting a cardiopulmonary intervention. Demographic and clinical data from each patient was collected, …

Kras-Mutant Lung Cancer: Targeting Molecular And Immunologic Pathways, Therapeutic Advantages And Restrictions, Nastaran Karimi, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

RAS mutations are among the most common oncogenic mutations in human cancers. Among RAS mutations, KRAS has the highest frequency and is present in almost 30% of non-small-cell lung cancer (NSCLC) patients. Lung cancer is the number one cause of mortality among cancers as a consequence of outrageous aggressiveness and late diagnosis. High mortality rates have been the reason behind numerous investigations and clinical trials to discover proper therapeutic agents targeting KRAS. These approaches include the following: direct KRAS targeting; synthetic lethality partner inhibitors; targeting of KRAS membrane association and associated metabolic rewiring; autophagy inhibitors; downstream inhibitors; and immunotherapies and …

The Association Between Time Spent On Screens And Reading With Myopia, Premyopia And Ocular Biometric And Anthropometric Measures In 6- To 7-Year-Old Schoolchildren In Ireland, Síofra Harrington, Veronica O'Dwyer

Articles

Purpose More time spent on near tasks has consistently been associated with the promotion of myopia. The World Health Organization advises limiting daily screentime to less than 2 h for children aged five and over. This study explored the relationship between time spent on screens and reading/writing with refractive status, ocular biometric and anthropometric factors in 6-to 7-year- olds in Ireland.

Methods Participants were 723 schoolchildren (377 boys [51.8%]), mean age 7.08 (0.45) years. The examination included cycloplegic autorefraction (1% cyclopentolate hydrochloride), ocular biometry (Zeiss IOLMaster), height (cm) and weight (kg). Screentime and reading/writing time were reported by parents/legal guardians …

Allopathic And Osteopathic Residents Perform Similarly On The Orthopedic In-Training Examination (Oite)., Carolina Gomez, Rachel Ranson, Arianna Gianakos, Cadence Miskimin, Mary K Mulcahey

Health Sciences Education Research

INTRODUCTION: There is a bias in the medical community that allopathic training is superior to osteopathic training, despite the lack of substantiation. The orthopedic in-training examination (OITE) is a yearly exam evaluating educational advancement and orthopedic surgery resident's scope of knowledge. The purpose of this study was to compare OITE scores between doctor of osteopathic medicine (DO) and medical doctor (MD) orthopedic surgery residents to determine whether any appreciable differences exist in the achievement levels between the 2 groups.

METHODS: The American Academy of Orthopedic Surgeons 2019 OITE technical report, which reports the scores from the 2019 OITE for MDs …

Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background

Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.

Methods

CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and …

Differential Expression Of Interferon-Induced Protein With Tetratricopeptide Repeats 3 (Ifit3) In Alzheimer's Disease And Hiv-1 Associated Neurocognitive Disorders, Armando Garces, Bryan Martinez, Roberto De La Garza, Deepa Roy, Kaylie-Anna Vallee, Jerel Adam Fields, David J. Moore, Hansapani Rodrigo, Upal Roy

Health & Biomedical Sciences Faculty Publications

The United Nations projects that one in every six people will be over the age of 65 by the year 2050. With a rapidly aging population, the risk of Alzheimer's disease (AD) becomes a major concern. AD is a multifactorial disease that involves neurodegeneration in the brain with mild dementia and deficits in memory and other cognitive domains. Additionally, it has been established that individuals with Human Immunodeficiency Virus-1 (HIV-1) experience a 5 to 10-year accelerated aging and an increased risk of developing HIV-associated neurocognitive disorders (HAND). Despite a significant amount of clinical evidence pointing towards a potential overlap between …

Impact Of Timing To Initiate Adjuvant Therapy On Survival Of Elderly Glioblastoma Patients Using The Seer-Medicare And National Cancer Databases, Ping Zhu, Xianglin L Du, Lu-Yu Hwang, David Lairson, Ruosha Li, Yoshua Esquenazi, Jay-Jiguang Zhu

Faculty, Staff and Student Publications

The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), ≤ 15, 16-26, 27-37, and ≥ 38 …

First‐Pass Effect With Aspiration Thrombectomy With The Penumbra System In Patients With Acute Ischemic Stroke: A Core Laboratory–Adjudicated Subset Analysis Of The Complete Registry, Johanna T. Fifi, Stavros Matsoukas, Ameer E. Hassan, Osama O. Zaidat

School of Medicine Publications

Background

In patients with acute ischemic stroke, minimizing the time to revascularization can minimize neuronal death. First‐pass effect (FPE), defined as successful or complete revascularization of an occluded target vessel with 1 pass of a mechanical thrombectomy device(s), reduces the time to revascularization. The objective of this study was to determine the FPE rate, compare cases in which FPE was versus was not achieved, and determine predictors of good functional outcome at 90 days, in patients with large‐vessel occlusion acute ischemic stroke treated with the Penumbra System (Penumbra, Inc).

Methods

This study is a subset analysis of the COMPLETE (International …

Recent Advances In Psychopharmacology: From Bench To Bedside Novel Trends In Schizophrenia, Asim A Shah, Syed Z Iqbal

Faculty, Staff and Students Publications

Research in the field of psychopharmacology is ongoing to develop novel compounds which can revolutionize the treatment of psychiatric disorders. The concept of bench-to-bedside is a tedious process, transforming the initial research performed in the laboratories into novel treatment options. Schizophrenia (SCZ) is a chronic psychiatric illness with significant morbidity and mortality. SCZ not only presents with psychotic symptoms including hallucinations and delusions but also with negative and cognitive symptoms. The negative symptoms include the diminished ability to express emotions, loss of pleasure, and motivation with minimal social interactions. Conventional antipsychotics primarily target positive symptoms with minimal therapeutic benefits for …

Membrane Phospholipids Control Gating Of The Mechanosensitive Potassium Leak Channel Trek1, Philipp A M Schmidpeter, John T Petroff 2nd, Leila Khajoueinejad, Aboubacar Wague, Cheryl Frankfater, Wayland W L Cheng, Crina M Nimigean, Paul M Riegelhaupt

2020-Current year OA Pubs

Tandem pore domain (K2P) potassium channels modulate resting membrane potentials and shape cellular excitability. For the mechanosensitive subfamily of K2Ps, the composition of phospholipids within the bilayer strongly influences channel activity. To examine the molecular details of K2P lipid modulation, we solved cryo-EM structures of the TREK1 K2P channel bound to either the anionic lipid phosphatidic acid (PA) or the zwitterionic lipid phosphatidylethanolamine (PE). At the extracellular face of TREK1, a PA lipid inserts its hydrocarbon tail into a pocket behind the selectivity filter, causing a structural rearrangement that recapitulates mutations and pharmacology known to activate TREK1. At the cytoplasmic …

4 Eyes On Skin: A Standardized Electronic Documentation Of 2 Rn Skin Assessment To Reduce Hospital-Acquired Pressure Injuries On A Progressive Care Unit, Jerome Codilla, Jamie Mae Yema

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Development Of A Rn Clinical Coach Program To Improve Retention Of Icu Residents And Fellows, Megan Jones, Sarah Sumner, Kristen Mayberry

Providence Nursing Research Conference 2023 – Present

Development of a RN Clinical Coach program to improve retention of ICU residents and fellows

Background:
The COVID-19 pandemic caused contributed to significant increases in ICU nurse turnover. To restore the ICU nursing workforce and rebuild a healthy work environment, evidence-based strategies are needed to provide social support and ongoing clinical skills development for large cohorts of ICU residents and fellows.

Purpose:
The purpose of the Clinical Coach program was to increase retention of ICU residents and fellows and foster a healthy work environment at a ministry in Southern California.

Methods:
In September 2021 the ICU manager at Providence Saint …

Stand By Me: Using An Enhanced Recovery After Surgery (Eras) Checklist To Guide Early Mobility Of Postoperative Craniotomy Patients On A Progressive Care Unit, Jerome Codilla, Alyssa Mooney, Joanna Arraiza, Sohl Chapman, Nkiru Chukwudi, Ronald Rosales

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Using The Escape Room Theme For Education, Suzanne Bañuelos

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Interprofessional Collaboration Optimizes Oncology Navigation Efficiency And Value​, Lauri Ledbeter, Whitney Daws, Rebekah Hart, Lindsay Shimizu

Providence Nursing Research Conference 2023 – Present

Background: Oncology navigation programs have evolved to include services for addressing cancer care barriers, focusing on care coordination, patient experience, and care value, and may include nurses, social workers, and non-licensed trained workers as care navigators. The 2023 Enhancing Oncology Payment Model (EOPM) requires navigation services and emphasizes improving care value and outcomes. Effective healthcare navigation and collaboration can improve value by reducing care duplication, missed appointments, and emergency admissions; identifying and addressing health-related social needs; addressing health inequities; and improving time-to-treatment initiation and patient retention. The Institute of Medicine also advocates for healthcare professionals to work interprofessionally, implement quality …

Factors Influencing Instrumental Birth Rates: An Evidence Based Project, Douglas Nanu, Gabriel Alemayehu, Chase Eby, Teresa Rangel

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Creation And Implementation Of A Trauma Informed Care Safety Tool In An Inpatient Mental Health Unit, Katie Rhea, Jeremy Williams, Teresa Rangel

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Chaplains And Hospital Staff Stressors: A Qualitative Framework, Teresa Rangel, Alexa Powell, Sarah Sumner, Kavya Vaitla, Karen Colorafi

Providence Nursing Research Conference 2023 – Present

No abstract provided.

A Quality Improvement Project: An Educational Program For Nurses To Improve The Care For Patients Diagnosed With Alcohol Withdrawal Syndrome, Daniel Davidson, Teresa Rangel, Kallie Anderson, Tobi Bryan, Cassie Baune

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Certification Champion Pilot Project To Increase Rn Specialty Certification Rates, Ari Meyers, Trisha Saul

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Improve Exclusive Breastfeeding Rates Through Early Breastfeeding Initiation, Camille Chua, Beverly Holland

Providence Nursing Research Conference 2023 – Present

No abstract provided.