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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
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. …
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
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 (
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
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
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 …
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
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 …
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
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, …
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
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 …
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
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 …
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
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 …
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
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
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
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.
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
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 …
The Siea Shrimp Flap: An Ultrathin Axial Pattern Free Flap Useable In Obese Patients, John M Felder 3rd, Brooke E Willborg, William Y Zhu
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. …
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
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 …
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
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 …
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
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 …
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
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 …
Dlmm As A Lossless One-Shot Algorithm For Collaborative Multi-Site Distributed Linear Mixed Models, Chongliang Luo, Et Al
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
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 ± …
The Effects Of The Combination Of Mesenchymal Stromal Cells And Nanofiber-Hydrogel Composite On Repair Of The Contused Spinal Cord, Agnes E Haggerty, Ines Maldonado-Lasunción, Yohshiro Nitobe, Kentaro Yamane, Megan M Marlow, Hua You, Chi Zhang, Brian Cho, Xiaowei Li, Sashank Reddy, Hai-Quan Mao, Martin Oudega
The Effects Of The Combination Of Mesenchymal Stromal Cells And Nanofiber-Hydrogel Composite On Repair Of The Contused Spinal Cord, Agnes E Haggerty, Ines Maldonado-Lasunción, Yohshiro Nitobe, Kentaro Yamane, Megan M Marlow, Hua You, Chi Zhang, Brian Cho, Xiaowei Li, Sashank Reddy, Hai-Quan Mao, Martin Oudega
Open Access Publications
A bone marrow-derived mesenchymal stromal cell (MSC) transplant and a bioengineered nanofiber-hydrogel composite (NHC) have been shown to stimulate nervous tissue repair in the contused spinal cord in rodent models. Here, these two modalities were combined to assess their repair effects in the contused spinal cord in adult rats. Cohorts of contused rats were treated with MSC in NHC (MSC-NHC), MSC in phosphate-buffered saline (MSC-PBS), NHC, or PBS injected into the contusion site at 3 days post-injury. One week after injury, there were significantly fewer CD68+ cells in the contusion with MSC-NHC and NHC, but not MSC-PBS. The reduction in …
Constructing An Adapted Cascade Of Diabetes Care Using Inpatient Admissions Data: Cross-Sectional Study, Irene Ryan, Cynthia Herrick, Mary F E Ebeling, Randi Foraker
Constructing An Adapted Cascade Of Diabetes Care Using Inpatient Admissions Data: Cross-Sectional Study, Irene Ryan, Cynthia Herrick, Mary F E Ebeling, Randi Foraker
Open Access Publications
BACKGROUND: The diabetes mellitus cascade of care has been constructed to evaluate diabetes care at a population level by determining the percentage of individuals diagnosed and linked to care as well as their reported glycemic control.
OBJECTIVE: We sought to adapt the cascade of care to an inpatient-only setting using the electronic health record (EHR) data of 81,633 patients with type 2 diabetes.
METHODS: In this adaptation, linkage to care was defined as prescription of diabetes medications within 3 months of discharge, and control was defined as hemoglobin A
RESULTS: We found that out of 81,633 patients, 28,716 (35.2%) were …
Structural And Molecular Rationale For The Diversification Of Resistance Mediated By The Antibiotic_Nat Family, Peter J Stogios, Emily Bordeleau, Zhiyu Xu, Tatiana Skarina, Elena Evdokimova, Sommer Chou, Luke Diorio-Toth, Alaric W D'Souza, Sanket Patel, Gautam Dantas, Gerard D Wright, Alexei Savchenko
Structural And Molecular Rationale For The Diversification Of Resistance Mediated By The Antibiotic_Nat Family, Peter J Stogios, Emily Bordeleau, Zhiyu Xu, Tatiana Skarina, Elena Evdokimova, Sommer Chou, Luke Diorio-Toth, Alaric W D'Souza, Sanket Patel, Gautam Dantas, Gerard D Wright, Alexei Savchenko
Open Access Publications
The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical …
Sorl1 Polymorphisms In Mexican Patients With Alzheimer's Disease, Danira Toral-Rios, Elizabeth Ruiz-Sánchez, Nancy Lucero Martínez Rodríguez, Marlene Maury-Rosillo, Óscar Rosas-Carrasco, Fernando Becerril-Pérez, Francisco Mena-Barranco, Rosa Carvajal-García, Daniela Silva-Adaya, Yair Delgado-Namorado, Gerardo Ramos-Palacios, Carmen Sánchez-Torres, Victoria Campos-Peña
Sorl1 Polymorphisms In Mexican Patients With Alzheimer's Disease, Danira Toral-Rios, Elizabeth Ruiz-Sánchez, Nancy Lucero Martínez Rodríguez, Marlene Maury-Rosillo, Óscar Rosas-Carrasco, Fernando Becerril-Pérez, Francisco Mena-Barranco, Rosa Carvajal-García, Daniela Silva-Adaya, Yair Delgado-Namorado, Gerardo Ramos-Palacios, Carmen Sánchez-Torres, Victoria Campos-Peña
Open Access Publications
The present study evaluated the risk effect of 12 Single Nucleotide Polymorphisms in the SORL1 gene in the Mexican population using Late-Onset Alzheimer's Disease (LOAD) and control subjects. Considering APOE as the strongest genetic risk factor for LOAD, we conducted interaction analyses between single nucleotide polymorphisms (SNPs) and the APOE genotype.
METHODS: Patients were interviewed during their scheduled visits at neurologic and geriatric clinics from different institutions. The LOAD diagnosis included neurological, geriatric, and psychiatric examinations, as well as the medical history and neuroimaging. Polymorphisms in
RESULTS: The A/A genotype in rs1784933 might be associated with an increased LOAD risk. …
Maternal Obesogenic Diet Enhances Cholestatic Liver Disease In Offspring, Michael D Thompson, Holly Hinrichs, Austin Faerber, Phillip I Tarr, Nicholas O Davidson
Maternal Obesogenic Diet Enhances Cholestatic Liver Disease In Offspring, Michael D Thompson, Holly Hinrichs, Austin Faerber, Phillip I Tarr, Nicholas O Davidson
Open Access Publications
Human and animal model data show that maternal obesity promotes nonalcoholic fatty liver disease in offspring and alters bile acid (BA) homeostasis. Here we investigated whether offspring exposed to maternal obesogenic diets exhibited greater cholestatic injury. We fed female C57Bl6 mice conventional chow (CON) or high fat/high sucrose (HF/HS) diet and then bred them with lean males. Offspring were fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 2 weeks to induce cholestasis, and a subgroup was then fed CON for an additional 10 days. Additionally, to evaluate the role of the gut microbiome, we fed antibiotic-treated mice cecal contents from CON or HF/HS offspring, …
Therapeutic Drug Monitoring In Perianal Fistulizing Crohn's Disease, Mir Zulqarnain, Parakkal Deepak, Andres J Yarur
Therapeutic Drug Monitoring In Perianal Fistulizing Crohn's Disease, Mir Zulqarnain, Parakkal Deepak, Andres J Yarur
Open Access Publications
Perianal fistulas are a common complication of Crohn's disease (CD) that has, historically, been challenging to manage. Despite the strong available evidence that anti-tumor necrosis factor (anti-TNF) agents are useful in the treatment of perianal fistulizing Crohn's disease (PFCD), a significant number of these patients do not respond to therapy. The use of therapeutic drug monitoring (TDM) in patients with CD receiving biologic agents has evolved and is currently positioned as an important tool to optimize and guide biologic treatment. Considering the treatment of PFCD can represent a challenge; identifying novel tools to improve the efficacy of current treatments is …
Micrornas In Pulmonary Hypertension, From Pathogenesis To Diagnosis And Treatment, Junhua Xu, John Linneman, Yanfeng Zhong, Haoyang Yin, Qinyi Xia, Kang Kang, Deming Gou
Micrornas In Pulmonary Hypertension, From Pathogenesis To Diagnosis And Treatment, Junhua Xu, John Linneman, Yanfeng Zhong, Haoyang Yin, Qinyi Xia, Kang Kang, Deming Gou
Open Access Publications
Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. …
Increasing Dorsal Tilt In Distal Radius Fractures Does Not Increase Median Nerve Strain, Chukwuka Obiofuma, Christopher Dy, Leanne E Iannucci, Spencer P Lake, David Brogan
Increasing Dorsal Tilt In Distal Radius Fractures Does Not Increase Median Nerve Strain, Chukwuka Obiofuma, Christopher Dy, Leanne E Iannucci, Spencer P Lake, David Brogan
Open Access Publications
Although extensive research shows an association between distal radius fractures and the development of median nerve related pathologies such as carpal tunnel syndrome, none directly track how the resulting angular deformity relates to likelihood of development of median nerve pathology.
Methods: Median nerve strain was measured with a custom-built system using a camera, optical markers, and a proprietary segmentation algorithm. After initial validation of the system in a cadaver model, our system was used to assess strain in 10 cadaver arms with a simulated distal radius fracture and increasing dorsal angulation. The measured strain at each angle was then analyzed …
Spherical Nucleic Acids As Precision Therapeutics For The Treatment Of Cancer—From Bench To Bedside, Akanksha S Mahajan, Alexander H Stegh
Spherical Nucleic Acids As Precision Therapeutics For The Treatment Of Cancer—From Bench To Bedside, Akanksha S Mahajan, Alexander H Stegh
Open Access Publications
Spherical Nucleic Acids (SNAs) emerged as a new class of nanotherapeutics consisting of a nanoparticle core densely functionalized with a shell of radially oriented synthetic oligonucleotides. The unique three-dimensional architecture of SNAs protects the oligonucleotides from nuclease-mediated degradation, increases oligonucleotide bioavailability, and in the absence of auxiliary transfection agents, enables robust uptake into tumor and immune cells through polyvalent association with cell surface pattern recognition receptors. When composed of gene-regulatory small interfering (si)RNA or immunostimulatory DNA or RNA oligonucleotides, SNAs silence gene expression and induce immune responses superior to those raised by the oligonucleotides in their "free" form. Early phase …
Facing The Realities Of Pragmatic Design Choices In Environmental Health Studies: Experiences From The Household Air Pollution Intervention Network Trial, William Checkley, Victor G Davila-Roman, Et Al
Facing The Realities Of Pragmatic Design Choices In Environmental Health Studies: Experiences From The Household Air Pollution Intervention Network Trial, William Checkley, Victor G Davila-Roman, Et Al
Open Access Publications
No abstract provided.
The Bacterial Microbiota Regulates Normal Hematopoiesis Via Metabolite-Induced Type 1 Interferon Signaling, Hannah Yan, Forrest C Walker, Arushana Ali, Hyojeong Han, Lin Tan, Lucas Veillon, Philip L Lorenzi, Megan T Baldridge, Katherine Y King
The Bacterial Microbiota Regulates Normal Hematopoiesis Via Metabolite-Induced Type 1 Interferon Signaling, Hannah Yan, Forrest C Walker, Arushana Ali, Hyojeong Han, Lin Tan, Lucas Veillon, Philip L Lorenzi, Megan T Baldridge, Katherine Y King
Open Access Publications
Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. We reported previously that STAT1 signaling is necessary for microbiota-dependent hematopoiesis, but the precise mechanisms by which the gut microbiota signals to the host bone marrow to regulate hematopoiesis remain undefined. We sought to identify the cell type(s) through which STAT1 promotes microbiota-mediated hematopoiesis and to elucidate which upstream signaling pathways trigger STAT1 signaling. Using conditional knockout and chimeric mice, we …