Medical Specialties Commons^™

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 …

Can Mild Traumatic Brain Injury Alter Cognition Chronically? A Limbic-Cenc Multicenter Study, William C Walker, Maya E O'Neil, Zhining Ou, Terri K Pogoda, Heather G Belanger, Randall S Scheibel, Angela P Presson, Shannon R Miles, Elisabeth A Wilde, David F Tate, Maya Troyanskaya, Mary Jo Pugh, Amy Jak, David X Cifu

Faculty, Staff and Students Publications

Objective: While outcome from mild traumatic brain injury (mTBI) is generally favorable, concern remains over potential negative long-term effects, including impaired cognition. This study examined the link between cognitive performance and remote mTBIs within the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) multicenter, observational study of Veterans and service members (SMs) with combat exposure.

Method: Baseline data of the participants passing all cognitive performance validity tests (n = 1,310) were used to conduct a cross-sectional analysis. Using multivariable regression models that adjusted for covariates, including age and estimated preexposure intellectual function, positive mTBI history …

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, …

Use Of Lithium In Pediatric Bipolar Disorders And Externalizing Childhood- Related Disorders: A Systematic Review Of Randomized Controlled Trials, Delfina Janiri, Lorenzo Moccia, Silvia Montanari, Valentina Zani, Claudia Prinari, Laura Monti, Daniela Chieffo, Marianna Mazza, Alessio Simonetti, Georgios D Kotzalidis, Luigi Janiri

Faculty, Staff and Students Publications

Background: Lithium is the standard treatment for bipolar disorders (BD) in adults. There is a dearth of data on its use in the pediatric age. This review aimed to investigate the use of lithium in pediatric bipolar disorder (BD) and other externalizing childhood-related disorders.

Methods: We applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA) to identify randomized controlled trials evaluating the use of lithium in pediatric (BD), conduct disorder (CD), attention deficit hyperactivity disorder, oppositional defiant disorder, and disruptive mood dysregulation disorder. The primary outcome of our study was to evaluate the efficacy of lithium compared …

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 …

Dantrolene Inhibits Lysophosphatidylcholine-Induced Valve Interstitial Cell Calcific Nodule Formation Via Blockade Of The Ryanodine Receptor, Christopher B Sylvester, Farshad Amirkhosravi, Angelina S Bortoletto, William J West, Jennifer P Connell, K Jane Grande-Allen

Faculty, Staff and Students Publications

Calcific aortic valve disease (CAVD), a fibrocalcific thickening of the aortic valve leaflets causing obstruction of the left ventricular outflow tract, affects nearly 10 million people worldwide. For those who reach end-stage CAVD, the only treatment is highly invasive valve replacement. The development of pharmaceutical treatments that can slow or reverse the progression in those affected by CAVD would greatly advance the treatment of this disease. The principal cell type responsible for the fibrocalcific thickening of the valve leaflets in CAVD is valvular interstitial cells (VICs). The cellular processes mediating this calcification are complex, but calcium second messenger signaling, regulated …

Cooperation Of Chromatin Remodeling Swi/Snf Complex And Pioneer Factor Ap-1 Shapes 3d Enhancer Landscapes, Bennett K Wolf, Yanding Zhao, Andrew Mccray, William H Hawk, Luke T Deary, Nicholas W Sugiarto, Ian S Lacroix, Scott A Gerber, Chao Cheng, Xiaofeng Wang

Faculty, Staff and Students Publications

The mechanism controlling the dynamic targeting of SWI/SNF has long been postulated to be coordinated by transcription factors (TFs), yet demonstrating a specific TF influence has proven difficult. Here we take a multi-omics approach to interrogate transient SWI/SNF interactors, chromatin targeting and the resulting three-dimensional epigenetic landscape. We utilize the labeling technique TurboID to map the SWI/SNF interactome and identify the activator protein-1 (AP-1) family members as critical interacting partners for SWI/SNF complexes. CUT&RUN profiling demonstrates SWI/SNF targeting enrichment at AP-1 bound loci, as well as SWI/SNF-AP-1 cooperation in chromatin targeting. HiChIP reveals AP-1-SWI/SNF-dependent restructuring of the three-dimensional promoter-enhancer architecture …

Protocol For The Promoting Resilience In Stress Management (Prism) Intervention: A Multi-Site Randomized Controlled Trial For Adolescents With Type 1 Diabetes, Maeve B O'Donnell, Samantha R Scott, Britney M Ellisor, Viena T Cao, Chuan Zhou, Miranda C Bradford, Catherine Pihoker, Daniel J Desalvo, Faisal S Malik, Marisa E Hilliard, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

BACKGROUND: Adolescents with type 1 diabetes (T1D) are at high risk for elevated diabetes distress, which greatly impacts diabetes management, glycemic outcomes and overall quality of life. Developing protective skills and "resilience resources" to navigate adversity and manage diabetes distress has high potential to help adolescents with T1D achieve optimal behavioral, psychological, and health outcomes. The "Promoting Resilience in Stress Management" (PRISM) program is a manualized, brief, skills-based intervention delivered over 6 months via two 45-60 min one-on-one sessions and a family meeting with a PRISM coach, and supplemented by booster calls and a digital app. This trial (PRISM versus …

Long-Term Neuropsychological Outcomes In Children With Febrile Infection-Related Epilepsy Syndrome (Fires) Treated With Anakinra, Anima Shrestha, E Lynne Wood, Gretchen Berrios-Siervo, Coral M Stredny, Katrina Boyer, Clemente Vega, Srishti Nangia, Eyal Muscal, Krista Eschbach

Faculty, Staff and Students Publications

BACKGROUND: Febrile-infection related epilepsy syndrome (FIRES) is a rare epilepsy syndrome in which a previously healthy individual develops refractory status epilepticus in the setting of a preceding febrile illness. There are limited data regarding detailed long-term outcomes. This study aims to describe the long-term neuropsychological outcomes in a series of pediatric patients with FIRES.

METHODS: This is a retrospective multi-center case series of pediatric patients with a diagnosis of FIRES treated acutely with anakinra who had neuropsychological testing at least 12 months after status epilepticus onset. Each patient underwent comprehensive neuropsychological evaluation as part of routine clinical care. Additional data …

Advances In Upper Gastrointestinal Surgery: Management And Diagnostic Techniques, Gregory L. Falk

Theses

Upper gastrointestinal surgery has progressively moved from the surgically open abdomen to minimally invasive surgery, largely due to technological improvements in instrumentation. A direct result of this Gestalt has been improved patient comfort, rapid recovery and significantly less length of stay in the hospital and therefore significant cost-savings. This was the key impetus to my development of many of the skills in minimally invasive surgery and the subsequent dissemination to other surgeons in an organized and well-recognized teaching system. Many of the novel techniques of this type of surgery led to several publications both in the English and French oncological …

Establishing An Online Resource To Facilitate Global Collaboration And Inclusion Of Underrepresented Populations: Experience From The Mjff Global Genetic Parkinson’S Disease Project, Eva-Juliane Vollstedt, Harutyun Madoev, Anna Aasly, Azlina Ahmad-Annuar, Bashayer Al-Mubarak, Roy N Alcalay, Victoria Alvarez, Ignacio Amorin, Grazia Annesi, David Arkadir, Soraya Bardien, Roger A Barker, Melinda Barkhuizen, A Nazli Basak, Vincenzo Bonifati, Agnita Boon, Laura Brighina, Kathrin Brockmann, Andrea Carmine Belin, Jonathan Carr, Jordi Clarimon, Mario Cornejo-Olivas, Leonor Correia Guedes, Jean-Christophe Corvol, David Crosiers, Joana Damásio, Parimal Das, Patricia De Carvalho Aguiar, Anna De Rosa, Jolanta Dorszewska, Sibel Ertan, Rosangela Ferese, Joaquim Ferreira, Emilia Gatto, Gençer Genç, Nir Giladi, Pilar Gómez-Garre, Hasmet Hanagasi, Nobutaka Hattori, Faycal Hentati, Dorota Hoffman-Zacharska, Sergey N Illarioshkin, Joseph Jankovic, Silvia Jesús, Valtteri Kaasinen, Anneke Kievit, Peter Klivenyi, Vladimir Kostic, Dariusz Koziorowski, Andrea A Kühn, Anthony E Lang, Shen-Yang Lim, Chin-Hsien Lin, Katja Lohmann, Vladana Markovic, Mika Henrik Martikainen, George Mellick, Marcelo Merello, Lukasz Milanowski, Pablo Mir, Özgür Öztop-Çakmak, Márcia Mattos Gonçalves Pimentel, Teeratorn Pulkes, Andreas Puschmann, Ekaterina Rogaeva, Esther M Sammler, Maria Skaalum Petersen, Matej Skorvanek, Mariana Spitz, Oksana Suchowersky, Ai Huey Tan, Pichet Termsarasab, Avner Thaler, Vitor Tumas, Enza Maria Valente, Bart Van De Warrenburg, Caroline H Williams-Gray, Ruey-Mei Wu, Baorong Zhang, Alexander Zimprich, Justin Solle, Shalini Padmanabhan, Christine Klein

Faculty, Staff and Students Publications

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, …

A Systematic Review And Meta-Analysis Of Long Term Physical And Mental Sequelae Of Covid-19 Pandemic: Call For Research Priority And Action, Na Zeng, Yi-Miao Zhao, Wei Yan, Chao Li, Qing-Dong Lu, Lin Liu, Shu-Yu Ni, Huan Mei, Kai Yuan, Le Shi, Peng Li, Teng-Teng Fan, Jun-Liang Yuan, Michael V Vitiello, Thomas Kosten, Alexandra L Kondratiuk, Hong-Qiang Sun, Xiang-Dong Tang, Mei-Yan Liu, Ajit Lalvani, Jie Shi, Yan-Ping Bao, Lin Lu

Faculty, Staff and Students Publications

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% …

Hippocampal Δfosb Expression Is Associated With Cognitive Impairment In A Subgroup Of Patients With Childhood Epilepsies, Chia-Hsuan Fu, Jason C You, Carrie Mohila, Robert A Rissman, Daniel Yoshor, Angela N Viaene, Jeannie Chin

Faculty, Staff and Students Publications

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is often comorbid with other neurological and neurodegenerative diseases, such as Alzheimer's disease (AD). Patients with recurrent seizures often present with cognitive impairment. However, it is unclear how seizures, even when infrequent, produce long-lasting deficits in cognition. One mechanism may be seizure-induced expression of ΔFosB, a long-lived transcription factor that persistently regulates expression of plasticity-related genes and drives cognitive dysfunction. We previously found that, compared with cognitively-intact subjects, the activity-dependent expression of ΔFosB in the hippocampal dentate gyrus (DG) was increased in individuals with mild cognitive impairment (MCI) and …

The Tmem106b T186s Coding Variant Increases Neurite Arborization And Synaptic Density In Primary Hippocampal Neurons, Quynh Nguyen, Caleb A Wood, Peter J Kim, Joanna L Jankowsky

Faculty, Staff and Students Publications

The lysosomal protein TMEM106B was identified as a risk modifier of multiple dementias including frontotemporal dementia and Alzheimer’s disease. The gene comes in two major haplotypes, one associated with disease risk, and by comparison, the other with resilience. Only one coding polymorphism distinguishes the two alleles, a threonine-to-serine substitution at residue 185 (186 in mouse), that is inherited in disequilibrium with multiple non-coding variants. Transcriptional studies suggest synaptic, neuronal, and cognitive preservation in human subjects with the protective haplotype, while murine in vitro studies reveal dramatic effects of TMEM106B deletion on neuronal development. Despite this foundation, the field has not …

5-Aminolevulinic Acid, Fluorescein Sodium, And Indocyanine Green For Glioma Margin Detection: Analysis Of Operating Wide-Field And Confocal Microscopy In Glioma Models Of Various Grades, Evgenii Belykh, Liudmila Bardonova, Irakliy Abramov, Vadim A Byvaltsev, Talgat Kerymbayev, Kwanha Yu, Debbie R Healey, Ernesto Luna-Melendez, Benjamin Deneen, Shwetal Mehta, James K Liu, Mark C Preul

Faculty, Staff and Students Publications

INTRODUCTION: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques.

METHODS: Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an

RESULTS: Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of …

Semi-Automated Construction Of Patient-Specific Aortic Valves From Computed Tomography Images, Dan Lior, Charles Puelz, Colin Edwards, Silvana Molossi, Boyce E Griffith, Ravi K Birla, Craig G Rusin

Faculty, Staff and Students Publications

This paper presents a semi-automatic method for the construction of volumetric models of the aortic valve using computed tomography angiography images. Although the aortic valve typically cannot be segmented directly from a computed tomography angiography image, the method described herein uses manually selected samples of an aortic segmentation derived from this image to inform the construction. These samples capture certain physiologic landmarks and are used to construct a volumetric valve model. As a demonstration of the capabilities of this method, valve models for 25 pediatric patients are created. A selected valve anatomy is used to perform fluid-structure interaction simulations using …

Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare

Faculty, Staff and Students Publications

OBJECTIVE: We describe the characteristics and outcomes of pediatric rapid response team (RRT) events within a single institution, categorized by reason for RRT activation (RRT triggers). We hypothesized that events with multiple triggers are associated with worse outcomes.

PATIENTS AND METHODS: Retrospective 3-year study at a high-volume tertiary academic pediatric hospital. We included all patients with index RRT events during the study period.

RESULTS: Association of patient and RRT event characteristics with outcomes including transfers to ICU, need for advanced cardiopulmonary support, ICU and hospital length of stay (LOS), and mortality were studied. We reviewed 2,267 RRT events from 2,088 …

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Research Priorities, Robert T Russell, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, Christine M Leeper, Julie C Leonard, Jennifer A Muszynski, Kathleen K Nicol, Daniel K Nishijima, Paul A Stricker, Adam M Vogel, Trisha E Wong, Philip C Spinella

Faculty, Staff and Students Publications

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock.

METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were …

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Recommendations, Robert T Russell, Joseph R Esparaz, Michael A Beckwith, Peter J Abraham, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, Christine Leeper, Julie C Leonard, Jennifer A Muszynski, Kathleen K Nicol, Daniel K Nishijima, Paul A Stricker, Adam M Vogel, Trisha E Wong, Philip C Spinella

Faculty, Staff and Students Publications

Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization …

Diagnostic Performance Of Point-Of-Use Ultrasound Of Resuscitation Outcomes: A Systematic Review And Meta-Analysis Of 3265 Patients, Maciej Dudek, Lukasz Szarpak, Frank W Peacock, Aleksandra Gasecka, Tomasz Michalski, Pawel Wroblewski, Halla Kaminska, Gabriela Borkowska, Ewa Skrzypek, Adam Smereka, Jaroslaw Meyer-Szary, Sylwia Marciniak, Mariola Malecka

Faculty, Staff and Students Publications

BACKGROUND: Echocardiography in the setting of resuscitation can provide information as to the cause of the cardiac arrest, as well as indicators of futility. This systematic review and meta-analysis were performed to determine the value of point-of-care ultrasonography (PoCUS) in the assessment of survival for adult patients with cardiac arrest.

METHODS: This meta-analysis was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Web of Science, Cochrane have been searched from databases inception until March 2nd 2021. The search was limited to adult patients with cardiac arrest and without publication dates or …

Meta-Analysis Of Chest Compression-Only Versus Conventional Cardiopulmonary Resuscitation By Bystanders For Adult With Out-Of-Hospital Cardiac Arrest, Karol Bielski, Jacek Smereka, Jaroslaw Chmielewski, Michal Pruc, Francesco Chirico, Aleksandra Gasecka, Nataliia Litvinova, Milosz J Jaguszewski, Grazyna Nowak-Starz, Zubaid Rafique, Frank W Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: According to the guidelines of cardiopulmonary resuscitation (CPR) conducted by bystanders, two methods of CPR are feasible: standard CPR (sCPR) with mouth-to-mouth ventilations and continuous chest compression-only CPR (CCC) without rescue breathing. The goal herein, was to evaluate the effect of sCPR (30:2) and CCC on resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA) patients.

METHODS: This study was a systematic review and meta-analysis. Using standardized criteria, Pub- Med, Web of Science, Scopus, EMBASE and Cochrane Collaboration were searched for trials assessing the effect of sCPR vs. CCC on resuscitation outcomes after adult OHCA. Random-effects model meta-analysis was …

Optimizing Human Performance In Extreme Environments Through Precision Medicine: From Spaceflight To High-Performance Operations On Earth, Michael A Schmidt, Jeffrey A Jones, Christopher E Mason

Faculty, Staff and Students Publications

Humans operating in extreme environments often conduct their operations at the edges of the limits of human performance. Sometimes, they are required to push these limits to previously unattained levels. As a result, their margins for error in execution are much smaller than that found in the general public. These same small margins for error that impact execution may also impact risk, safety, health, and even survival. Thus, humans operating in extreme environments have a need for greater refinement in their preparation, training, fitness, and medical care. Precision medicine (PM) is uniquely suited to address the needs of those engaged …

Color Doppler Ultrasound Imaging In Varicoceles: Is The Difference In Venous Diameter Encountered During Valsalva Predictive Of Palpable Varicocele Grade?, Kelly Lehner, Catherine Ingram, Utsav Bansal, Colleen Baca, Adithya Balasubramanian, Nannan Thirumavalavan, Jason M Scovell, Saneal Rajanahally, Matthew Pollard, Larry I Lipshultz

Faculty, Staff and Students Publications

OBJECTIVE: The clinical grading system for varicoceles is subjective and dependent on clinician experience. Color Doppler ultrasound (US) has not been standardized in the diagnosis of varicoceles. We aimed to determine if US measurement of varicocele could be predictive of World Health Organization (WHO) varicocele grade.

METHODS: Men who presented for either scrotal pain or infertility to a tertiary men's health clinic underwent physical examination, and varicoceles were graded following WHO criteria (0=subclinical, 1, 2, 3). US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver. Receiver operator characteristic curve analysis …

Tissue-Specific Dna Methylation Variability And Its Potential Clinical Value, Ryan H Miller, Chad A Pollard, Kristin R Brogaard, Andrew C Olson, Ryan C Barney, Larry I Lipshultz, Erica B Johnstone, Yetunde O Ibrahim, James M Hotaling, Enrique F Schisterman, Sunni L Mumford, Kenneth I Aston, Tim G Jenkins

Faculty, Staff and Students Publications

Complex diseases have multifactorial etiologies making actionable diagnostic biomarkers difficult to identify. Diagnostic research must expand beyond single or a handful of genetic or epigenetic targets for complex disease and explore a broader system of biological pathways. With the objective to develop a diagnostic tool designed to analyze a comprehensive network of epigenetic profiles in complex diseases, we used publicly available DNA methylation data from over 2,400 samples representing 20 cell types and various diseases. This tool, rather than detecting differentially methylated regions at specific genes, measures the intra-individual methylation variability within gene promoters to identify global shifts away from …

Peyronie's Disease: An Outcomes-Based Guide To Non-Surgical And Novel Treatment Modalities, Amit G Reddy, Michelle C Dai, Jeffrey J Song, Hudson M Pierce, Sagar R Patel, Larry I Lipshultz

Faculty, Staff and Students Publications

The clinical landscape of Peyronie's disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie's disease, it can be challenging to gain a thorough understanding of this body of literature. …

Massive Saddle Embolus Following Bilateral Lung Transplantation Discovered With Transesophageal Echocardiogram, Alex Bui, Jamal Hasoon, Sandeep Markan, Anvinh Nguyen

Faculty, Staff and Students Publications

No abstract provided.

Anaesthetic Considerations: Management Of Pulmonary Hypertension And Difficult Airway In A Patient Undergoing Radical Nephrectomy For Renal Cell Carcinoma, Kyle Gashler, Tommy Li, Justo Gonzalez, Jamal Hasoon, Anvinh Nguyen

Faculty, Staff and Students Publications

No abstract provided.

Combined Immunodeficiency Caused By Pathogenic Variants In The Zap70 C-Terminal Sh2 Domain, Cédric Mongellaz, Rita Vicente, Lenora M Noroski, Nelly Noraz, Valérie Courgnaud, Javier Chinen, Emilia Faria, Valérie S Zimmermann, Naomi Taylor

Faculty, Staff and Students Publications

INTRODUCTION: ZAP-70, a protein tyrosine kinase recruited to the T cell receptor (TCR), initiates a TCR signaling cascade upon antigen stimulation. Mutations in the ZAP70 gene cause a combined immunodeficiency characterized by low or absent CD8+ T cells and nonfunctional CD4+ T cells. Most deleterious missense ZAP70 mutations in patients are located in the kinase domain but the impact of mutations in the SH2 domains, regulating ZAP-70 recruitment to the TCR, are not well understood.

METHODS:Genetic analyses were performed on four patients with CD8 lymphopenia and a high resolution melting screening for ZAP70 mutations was developed. The impact of SH2 …

The Epidemiology Of Cephalosporin Allergy Labels In Pediatric Primary Care, Torsten Joerger, Margaret G Taylor, Debra L Palazzi, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Recent studies have sought to understand the epidemiology and impact of beta-lactam allergy labels on children; however, most of these studies have focused on penicillin allergy labels. Fewer studies assess cephalosporin antibiotic allergy labels in children. The objective of this study was to determine the prevalence, factors associated with, and impact of cephalosporin allergy labels in children cared for in the primary care setting.

METHODS: Cephalosporin allergy labels were reviewed among children in a dual center, retrospective, birth cohort who were born between 2010 and 2020 and followed in 90 pediatric primary care practices. Antibiotic prescriptions for acute otitis …