Digital Commons Network^™

Opportunities For Penicillin Allergy Evaluation In Dental Clinics, Amanda Vivo, Michael J. Durkin, Iboula Kale, Taylor Boyer, Margaret A. Fitzpatrick, Charlesnika T. Evans, Marianne M. Jurasic, Gretchen Gibson, Katie J. Suda

Open Access Publications

No abstract provided.

Establishment Of Novel Neuroendocrine Carcinoma Patient-Derived Xenograft Models For Receptor Peptide-Targeted Therapy, Catherine G Tran, Jacqueline L Mudd, Ramaswamy Govindan, Paul F Cliften, Ryan C Fields

Open Access Publications

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for studying GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of six mice developed tumors (NEC913 and NEC1452). Over 80% of NEC913 and NEC1452 tumor cells stained positive for Ki67. …

Mendelian Randomization Supports Bidirectional Causality Between Telomere Length And Clonal Hematopoiesis Of Indeterminate Potential, Tetsushi Nakao, C Charles Gu, Lisa De Las Fuentes, Et Al

Open Access Publications

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD.

Connectomic Profiling And Vagus Nerve Stimulation Outcomes Study (Connectivos): A Prospective Observational Protocol To Identify Biomarkers Of Seizure Response In Children And Youth, Lauren Siegel, Matthew D Smyth, Et Al

Open Access Publications

INTRODUCTION: Vagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy.

METHODS AND ANALYSIS: In this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and …

Targeting Fatty Acid Β-Oxidation Impairs Monocyte Differentiation And Prolongs Heart Allograft Survival, Yuehui Zhu, Hao Dun, Li Ye, Yuriko Terada, Leah P. Shriver, Gary J. Patti, Daniel Kreisel, Andrew E. Gelman, Brian W. Wong

Open Access Publications

Monocytes play an important role in the regulation of alloimmune responses after heart transplantation (HTx). Recent studies have highlighted the importance of immunometabolism in the differentiation and function of myeloid cells. While the importance of glucose metabolism in monocyte differentiation and function has been reported, a role for fatty acid β-oxidation (FAO) has not been explored. Heterotopic HTx was performed using hearts from BALB/c donor mice implanted into C57BL/6 recipient mice and treated with etomoxir (eto), an irreversible inhibitor of carnitine palmitoyltransferase 1 (Cpt1), a rate-limiting step of FAO, or vehicle control. FAO inhibition prolonged HTx survival, reduced early T …

Laser Interstitial Thermal Therapy In Grade 2/3 Idh1/2 Mutant Gliomas: A Preliminary Report And Literature Review, Gabrielle W Johnson, Rowland H Han, Matthew D Smyth, Eric C Leuthardt, Albert H Kim

Open Access Publications

Laser interstitial thermal therapy (LITT) has become an increasingly utilized alternative to surgical resection for the treatment of glioma in patients. However, treatment outcomes in isocitrate dehydrogenase 1 and 2 (

Frequency Of The Dopamine Receptor D3 (Rs6280) Vs. Opioid Receptor Μ1 (Rs1799971) Polymorphic Risk Alleles In Patients With Opioid Use Disorder: A Preponderance Of Dopaminergic Mechanisms?, Marjorie C Gondré-Lewis, Igor Elman, Tanya Alim, Edwin Chapman, Beverlyn Settles-Reaves, Carine Galvao, Mark S Gold, David Baron, Shan Kazmi, Eliot Gardner, Ashim Gupta, Catherine Dennen, Kenneth Blum

Open Access Publications

While opioids are a powerful class of drugs that inhibit transmission of pain signals, their use is tarnished by the current epidemic of opioid use disorder (OUD) and overdose deaths. Notwithstanding published reports, there remain gaps in our knowledge of opioid receptor mechanisms and their role in opioid seeking behavior. Thus, novel insights into molecular, neurogenetic and neuropharmacological bases of OUD are needed. We propose that an addictive endophenotype may not be entirely specific to the drug of choice but rather may be generalizable to altered brain reward circuits impacting net mesocorticolimbic dopamine release. We suggest that genetic or epigenetic …

Brain Charts For The Human Lifespan, R A I Bethlehem, J Seidlitz, S R White, C Ortinau, C D Smyser, Et Al

Open Access Publications

No abstract provided.

Protein Kinase C (Pkc)-Δ Mediates Arginine-Induced Glucagon Secretion In Pancreatic Α-Cells, Norikiyo Honzawa, Kei Fujimoto, Masaki Kobayashi, Daisuke Kohno, Osamu Kikuchi, Hiromi Yokota-Hashimoto, Eri Wada, Yuichi Ikeuchi, Yoko Tabei, Gerald W Dorn Ii, Kazunori Utsunomiya, Rimei Nishimura, Tadahiro Kitamura

Open Access Publications

The pathophysiology of type 2 diabetes involves insulin and glucagon. Protein kinase C (Pkc)-δ, a serine-threonine kinase, is ubiquitously expressed and involved in regulating cell death and proliferation. However, the role of Pkcδ in regulating glucagon secretion in pancreatic α-cells remains unclear. Therefore, this study aimed to elucidate the physiological role of Pkcδ in glucagon secretion from pancreatic α-cells. Glucagon secretions were investigated in Pkcδ-knockdown InR1G9 cells and pancreatic α-cell-specific Pkcδ-knockout (αPkcδKO) mice. Knockdown of Pkcδ in the glucagon-secreting cell line InR1G9 cells reduced glucagon secretion. The basic amino acid arginine enhances glucagon secretion via voltage-dependent calcium channels (VDCC). Furthermore, …

A Benzodiazepine Activator Locks K V 7.1 Channels Open By Electro-Mechanical Uncoupling, Julian A Schreiber, Melina Möller, Mark Zaydman, Lu Zhao, Zachary Beller, Sebastian Becker, Nadine Ritter, Panpan Hou, Jingyi Shi, Jon Silva, Eva Wrobel, Nathalie Strutz-Seebohm, Niels Decher, Nicole Schmitt, Sven G Meuth, Martina Düfer, Bernhard Wünsch, Jianmin Cui, Guiscard Seebohm

Open Access Publications

Loss-of-function mutations in K

The Role Of Whole Blood Transfusions In Civilian Trauma: A Review Of Literature In Military And Civilian Trauma, Shane Kronstedt, Joon Lee, David Millner, Connor Mattivi, Halli Lafrankie, Lorenzo Paladino, Jeffrey Siegler

Open Access Publications

Resuscitation techniques for the management of adult trauma patients have evolved over the 20th century. Whole blood transfusions were previously used as the standard of care, whereas blood component therapy is the current method employed across most trauma centers across the United States. Prior to the transition, no studies were conducted to show improved efficacy of hemostatic potential in trauma patients. Recent conflicts in Iraq and Afghanistan have challenged the dogma that whole blood transfusions are not the standard of care and have shown potential as the superior transfusion product for adult trauma patients. The purpose of this review is …

Delphi Consensus Recommendation For Optimization Of Pulmonary Hypertension Therapy Focusing On Switching From A Phosphodiesterase 5 Inhibitor To Riociguat, Franck Rahaghi, Vijay Balasubramanian, Robert Bourge, Charles Burger, Murali Chakinala, Michael Eggert, Jean Elwing, Jeremy Feldman, Christopher King, James Klinger, Stephen Mathai, John Mcconnell, Harold Palevsky, Ricardo Restrepo-Jaramillo, Zeenat Safdar, Jeffrey Sager, Namita Sood, Roxana Sulica, R. James White, Nicholas Hill

Open Access Publications

No abstract provided.

Failed Targeted Muscle Reinnervation: Findings At Revision Surgery And Concepts For Success, John M Felder, Stahs Pripotnev, Ivica Ducic, Rachel Skladman, Austin Y Ha, Mitchell A Pet

Open Access Publications

Although it was initially described for improved myoelectric control, targeted muscle reinnervation (TMR) has quickly gained popularity as a technique for neuroma control. With this rapid increase in utilization has come broadening indications and variability in the described technique. As a result, it becomes difficult to interpret published outcomes. Furthermore, there is no literature discussing the management of failed cases which are undoubtedly occurring.

Methods: This is a retrospective case series of two patients who underwent revision surgery for failed TMR. The authors also review the current literature on TMR and outline technical and conceptual pitfalls and pearls based on …

The Siea Shrimp Flap: An Ultrathin Axial Pattern Free Flap Useable In Obese Patients, John M Felder 3rd, Brooke E Willborg, William Y Zhu

Open Access Publications

The reconstruction of distal extremity wounds poses a unique surgical challenge. In free tissue transfer, a thin, pliable skin flap is the ideal. Obese patients have a paucity of thin skin donor sites. Herein we report the discovery of a free SHRIMP flap (Superthin Harvest of a Reliable Islanded Medial Pannus flap) based on the SIEA vessels, harvested from a thick abdominal pannus at the time of cosmetic abdominoplasty. A 61-year-old woman with a chronic wound of the right Achilles tendon was evaluated for reconstruction after failing conservative measures. At the time of consultation, the patient expressed interest in abdominoplasty. …

Uncertainty Analysis Of Chest X-Ray Lung Height Measurements And Size Matching For Lung Transplantation, Rodrigo Vazquez Guillamet, Maria C. Vazquez Guillamet, Ashraf Rjob, Andrew Bierhals, Irene Bello, Alberto Jauregui Abularach, Laneshia Tague, Michael Wallendorf, Gary F. Marklin, Chad Witt, Derek E. Byers, Daniel Kreisel, Ruben Nava, Varun Puri, Ramsey Hachem, Elbert P Trulock

Open Access Publications

Background: Errors in measuring chest X-ray (CXR) lung heights could contribute to the occurrence of size-mismatched lung transplant procedures.

Methods: We first used Bland-Altman analysis for repeated measures to evaluate contributors to measurement error of chest X-ray lung height. We then applied error propagation theory to assess the impact of measurement error on size matching for lung transplantation.

Results: A total 387 chest X-rays from twenty-five donors and twenty-five recipients were measured by two raters. Individual standard deviation for lung height differences were independent of age, sex, donor

Conclusions: Individual chest X-ray lung heights are imprecise for the purpose of …

Measuring Retention Within The Adolescent Brain Cognitive Development (Abcd)Sm Study, Sarah W Feldstein Ewing, Genevieve F Dash, Wesley K Thompson, Chase Reuter, Vanessa G Diaz, Andrey Anokhin, Linda Chang, Linda B Cottler, Gayathri J Dowling, Kimberly Leblanc, Robert A Zucker, Susan F Tapert, Sandra A Brown, Hugh Garavan

Open Access Publications

The Adolescent Brain Cognitive Development (ABCD)

Molecular Dissection Of Rbpa-Mediated Regulation Of Fidaxomicin Sensitivity In Mycobacteria, Jerome Prusa, Dennis X Zhu, Aidan J Flynn, Drake Jensen, Ana Ruiz Manzano, Eric A Galburt, Christina L Stallings

Open Access Publications

RNA polymerase (RNAP) binding protein A (RbpA) is essential for mycobacterial viability and regulates transcription initiation by increasing the stability of the RNAP-promoter open complex (RP

Tumor-Associated Macrophages In Multiple Myeloma: Advances In Biology And Therapy, Jennifer Sun, Chaelee Park, Nicole Guenthner, Shannon Gurley, Luna Zhang, Berit Lubben, Ola Adebayo, Hannah Bash, Yixuan Chen, Mina Maksimos, Barbara Muz, Abdel Kareem Azab

Open Access Publications

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow (BM) and represents the second most common hematological malignancy in the world. The MM tumor microenvironment (TME) within the BM niche consists of a wide range of elements which play important roles in supporting MM disease progression, survival, proliferation, angiogenesis, as well as drug resistance. Together, the TME fosters an immunosuppressive environment in which immune recognition and response are repressed. Macrophages are a central player in the immune system with diverse functions, and it has been long established that macrophages play a critical role in both inducing …

Socioeconomic Risk Markers Of Arthropod-Borne Virus (Arbovirus) Infections: A Systematic Literature Review And Meta-Analysis, Grace M Power, Aisling M Vaughan, Luxi Qiao, Nuria Sanchez Clemente, Julia M Pescarini, Enny S Paixão, Ludmila Lobkowicz, Amber I Raja, André Portela Souza, Mauricio Lima Barreto, Elizabeth B Brickley

Open Access Publications

INTRODUCTION: Arthropod-borne viruses (arboviruses) are of notable public health importance worldwide, owing to their potential to cause explosive outbreaks and induce debilitating and potentially life-threatening disease manifestations. This systematic review and meta-analysis aims to assess the relationship between markers of socioeconomic position (SEP) and infection due to arboviruses with mosquito vectors.

METHODS: We conducted a systematic search on PubMed, Embase, and LILACS databases to identify studies published between 1980 and 2020 that measured the association of SEP markers with arbovirus infection. We included observational studies without geographic location or age restrictions. We excluded studies from grey literature, reviews and ecological …

Current And Future Nonstimulants In The Treatment Of Pediatric Adhd: Monoamine Reuptake Inhibitors, Receptor Modulators, And Multimodal Agents, Andrew J Cutler, Gregory W Mattingly, Rakesh Jain, Welton O'Neal

Open Access Publications

Attention-deficit/hyperactivity disorder (ADHD), the single most common neuropsychiatric disorder with cognitive and behavioral manifestations, often starts in childhood and usually persists into adolescence and adulthood. Rarely seen alone, ADHD is most commonly complicated by other neuropsychiatric disorders that must be factored into any intervention plan to optimally address ADHD symptoms. With more than 30 classical Schedule II (CII) stimulant preparations available for ADHD treatment, only three nonstimulants (atomoxetine and extended-release formulations of clonidine and guanfacine) have been approved by the United States Food and Drug Administration (FDA), all of which focus on modulating the noradrenergic system. Given the heterogeneity and …

Early Expression Of Mmp-9 Predicts Recovery Of Tibialis Anterior After Sciatic Nerve Crush Injury, David M Brogan, Christopher J Dy, Jason Wever, Tony Lee, Samuel Achilefu

Open Access Publications

Background: The purpose of this study was to assess the expression of molecular markers and epineural blood flow after differing degrees of nerve injury to identify potential tools to predict nerve recovery in a rat sciatic nerve model.

Methods: A total of 72 rats were divided into nine groups. Each group was subjected to one of three crush injuries, created by applying one of three vascular clamps for 30 seconds. Vascularity was assessed with laser Doppler flowmetry before and after crush, and at nonsurvival surgery. Nonsurvival surgeries were performed 6 hours, 2 weeks, or 6 weeks later with nerve conduction …

Applying Implementation Science To Improve Care For Familial Hypercholesterolemia, Laney K Jones, Ross C Brownson, Marc S Williams

Open Access Publications

PURPOSE OF REVIEW: Improving care of individuals with familial hypercholesteremia (FH) is reliant on the synthesis of evidence-based guidelines and their subsequent implementation into clinical care. This review describes implementation strategies, defined as methods to improve translation of evidence into FH care, that have been mapped to strategies from the Expert Recommendations for Implementing Change (ERIC) compilation.

RECENT FINDINGS: A search using the term 'familial hypercholesterolemia' returned 1350 articles from November 2018 to July 2021. Among these, there were 153 articles related to improving FH care; 1156 were excluded and the remaining 37 were mapped to the ERIC compilation of …

Vestibular Rehabilitation For Peripheral Vestibular Hypofunction: An Updated Clinical Practice Guideline From The Academy Of Neurologic Physical Therapy Of The American Physical Therapy Association, Courtney D Hall, Joel A Goebel, Et Al

Open Access Publications

BACKGROUND: Uncompensated vestibular hypofunction can result in symptoms of dizziness, imbalance, and/or oscillopsia, gaze and gait instability, and impaired navigation and spatial orientation; thus, may negatively impact an individual's quality of life, ability to perform activities of daily living, drive, and work. It is estimated that one-third of adults in the United States have vestibular dysfunction and the incidence increases with age. There is strong evidence supporting vestibular physical therapy for reducing symptoms, improving gaze and postural stability, and improving function in individuals with vestibular hypofunction. The purpose of this revised clinical practice guideline is to improve quality of care …

Study Protocol: Myofit46-The Cardiac Sub-Study Of The Mrc National Survey Of Health And Development, Matthew Webber, Yoram Rudy, Et Al

Open Access Publications

BACKGROUND: The life course accumulation of overt and subclinical myocardial dysfunction contributes to older age mortality, frailty, disability and loss of independence. The Medical Research Council National Survey of Health and Development (NSHD) is the world's longest running continued surveillance birth cohort providing a unique opportunity to understand life course determinants of myocardial dysfunction as part of MyoFit46-the cardiac sub-study of the NSHD.

METHODS: We aim to recruit 550 NSHD participants of approximately 75 years+ to undertake high-density surface electrocardiographic imaging (ECGI) and stress perfusion cardiovascular magnetic resonance (CMR). Through comprehensive myocardial tissue characterization and 4-dimensional flow we hope to …

Global Variation In Studies Of Articular Cartilage Procedures Of The Knee: A Systematic Review, R. Garrett Steinmetz, J. Jared Guth, Matthew J Matava, Matthew V Smith, Robert H Brophy

Open Access Publications

OBJECTIVE: The objective of this study was to determine whether there are significant differences in terms of indications, techniques, patient variables, and objective and subjective outcome scores as a function of the geographic locale of published studies of knee articular cartilage surgery.

METHODS: An electronic database search was performed of clinical studies evaluating knee articular cartilage procedures from 2000 to 2021. Studies were separated into global regions (Europe, Asia, North America, and South America) based on the study country. All cartilage-based treatments in each region were recorded. Patient age and sex, mechanism of injury, cartilage lesion size and location, follow-up …

Combination Of Sulindac And Eflornithine Delays The Need For Lower Gastrointestinal Surgery In Patients With Familial Adenomatous Polyposis: Post Hoc Analysis Of A Randomized Clinical Trial, Francesc Balaguer, Paul E Wise, Et Al

Open Access Publications

BACKGROUND: Colectomy and proctocolectomy are the initial standard of care for patients with familial adenomatous polyposis. Pharmacotherapy to prevent the progression of polyposis and surgeries in the lower GI tract would be beneficial to patients with this disease.

OBJECTIVE: This analysis aimed to evaluate the impact of eflornithine-sulindac combination versus monotherapy in delaying time to disease progression in the lower GI tract of patients with familial adenomatous polyposis.

DESIGN: This is a post hoc analysis of a randomized phase 3 trial.

SETTING: This study was conducted in 21 hospitals in 7 countries treating patients with familial adenomatous polyposis.

PATIENTS: Adults …

Reduced Neural Activity But Improved Coding In Rodent Higher-Order Visual Cortex During Locomotion, Amelia J Christensen, Jonathan W Pillow

Open Access Publications

Running profoundly alters stimulus-response properties in mouse primary visual cortex (V1), but its effect in higher-order visual cortex is under-explored. Here we systematically investigate how visual responses vary with locomotive state across six visual areas and three cortical layers using a massive dataset from the Allen Brain Institute. Although previous work has shown running speed to be positively correlated with neural activity in V1, here we show that the sign of correlations between speed and neural activity varies across extra-striate cortex, and is even negative in anterior extra-striate cortex. Nevertheless, across all visual cortices, neural responses can be decoded more …

Dlmm As A Lossless One-Shot Algorithm For Collaborative Multi-Site Distributed Linear Mixed Models, Chongliang Luo, Et Al

Open Access Publications

Linear mixed models are commonly used in healthcare-based association analyses for analyzing multi-site data with heterogeneous site-specific random effects. Due to regulations for protecting patients' privacy, sensitive individual patient data (IPD) typically cannot be shared across sites. We propose an algorithm for fitting distributed linear mixed models (DLMMs) without sharing IPD across sites. This algorithm achieves results identical to those achieved using pooled IPD from multiple sites (i.e., the same effect size and standard error estimates), hence demonstrating the lossless property. The algorithm requires each site to contribute minimal aggregated data in only one round of communication. We demonstrate the …

Comparison Of Bioelectrical Impedance Analysis With Dxa In Adolescents With Cystic Fibrosis Before And After A Resistance Training Intervention, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados

Open Access Publications

BACKGROUND: The purpose of this pilot study was to compare body composition metrics obtained by two portable bioelectrical impedance analysis (BIA) devices with dual-energy X-ray absorptiometry (DXA) among adolescents with cystic fibrosis (CF) before and after a resistance exercise training program.

METHODS: Participants with CF were assessed using DXA, single-frequency BIA (SFBIA), and multiple-frequency BIA (MFBIA) to quantify percent body fat (%Fat), fat mass (FM), and fat-free mass (FFM) at baseline and after a home-based resistance training intervention comprised of 36, 1 h sessions completed in 12-14 weeks. Repeated measures analysis of variance, paired samples

RESULTS: Ten participants (15.8 ± …

Continuous Care Intervention With Carbohydrate Restriction Improves Physical Function Of The Knees Among Patients With Type 2 Diabetes: A Non-Randomized Study, Kade S Lyman, Shaminie J Athinarayanan, Amy L Mckenzie, Camy L Pearson, Rebecca N Adams, Sarah J Hallberg, James P Mccarter, Jeff S Volek, Stephen D Phinney, John P Andrawis

Open Access Publications

BACKGROUND: In a previous study, we assessed a novel, remotely monitored carbohydrate restricted diet regimen including nutritional ketosis in patients with type 2 diabetes and reported significant improvements in weight, glycemic control, abdominal fat and inflammation from baseline to 2 years. Knee outcome measures were collected as a secondary outcome in the trial. This study aims to assess the effect of this intervention on knee functional scores and to identify if changes in weight, central abdominal fat (CAF), glycemic status and high sensitivity C-reactive protein (hsCRP) were associated with its improvement.

METHODS: This prospective analysis included continuous care intervention (CCI, …