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Full-Text Articles in Medicine and Health Sciences
Dynamic Frailty Risk Assessment Among Older Adults With Multiple Myeloma: A Population-Based Cohort Study, Hira Mian, Tanya M Wildes, Ravi Vij, Matthew J Pianko, Ajay Major, Mark A Fiala
Dynamic Frailty Risk Assessment Among Older Adults With Multiple Myeloma: A Population-Based Cohort Study, Hira Mian, Tanya M Wildes, Ravi Vij, Matthew J Pianko, Ajay Major, Mark A Fiala
2020-Current year OA Pubs
Multiple myeloma (MM) is a cancer of older adults and those who are more frail are at high risk of poor outcomes. Current tools for identifying and categorizing frail patients are often static and measured only at the time of diagnosis. The concept of dynamic frailty (i.e. frailty changing over time) is largely unexplored in MM. In our study, adults with newly-diagnosed MM who received novel drugs between the years 2007-2014 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Using a previously published cumulative deficit approach, a frailty index score was calculated at diagnosis and each …
T Helper 2 Cells Control Monocyte To Tissue-Resident Macrophage Differentiation During Nematode Infection Of The Pleural Cavity, Conor M. Finlay, Gwendalyn J. Randolph, Et Al.
T Helper 2 Cells Control Monocyte To Tissue-Resident Macrophage Differentiation During Nematode Infection Of The Pleural Cavity, Conor M. Finlay, Gwendalyn J. Randolph, Et Al.
2020-Current year OA Pubs
No abstract provided.
Layperson Perception Of Reflux-Related Symptoms, Jakob L. Fischer, Anthony M. Tolisano, Alvaro I. Navarro, Lily Trinh, Waleed M. Abuzeid, Ian M. Humphreys, Nadeem A. Akbar, Sharan Shah, John S. Schneider, Charles A. Riley, Edward D. Mccoul
Layperson Perception Of Reflux-Related Symptoms, Jakob L. Fischer, Anthony M. Tolisano, Alvaro I. Navarro, Lily Trinh, Waleed M. Abuzeid, Ian M. Humphreys, Nadeem A. Akbar, Sharan Shah, John S. Schneider, Charles A. Riley, Edward D. Mccoul
2020-Current year OA Pubs
OBJECTIVE: To assess for differences of intended meaning in the description of reflux-related symptoms among otolaryngology patients and clinicians.
STUDY DESIGN: Cross-sectional survey-based study.
SETTING: Five tertiary, academic otolaryngology practices.
METHODS: Between June 2020 and July 2022, a questionnaire consisting of 20 common descriptors of reflux-related symptoms within four domains (throat-, chest-, stomach-, and sensory-related symptoms) was completed by patients. Attending otolaryngologists at five academic medical centers then completed the same survey. The primary outcome was to assess differences in patient and clinician perceptions of reflux-related symptoms. Differences based on geographic location was a secondary outcome.
RESULTS: A total of …
Rbm47 Regulates Intestinal Injury And Tumorigenesis By Modifying Proliferation, Oxidative Response, And Inflammatory Pathways, Saeed Soleymanjahi, Valerie Blanc, Elizabeth A. Molitor, David M. Alvarado, Yan Xie, Vered Gazit, Jeffrey W. Brown, Kathleen Byrnes, Ta-Chiang Liu, Jason C. Mills, Matthew A. Ciorba, Deborah C. Rubin, Nicholas O. Davidson
Rbm47 Regulates Intestinal Injury And Tumorigenesis By Modifying Proliferation, Oxidative Response, And Inflammatory Pathways, Saeed Soleymanjahi, Valerie Blanc, Elizabeth A. Molitor, David M. Alvarado, Yan Xie, Vered Gazit, Jeffrey W. Brown, Kathleen Byrnes, Ta-Chiang Liu, Jason C. Mills, Matthew A. Ciorba, Deborah C. Rubin, Nicholas O. Davidson
2020-Current year OA Pubs
RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Rbm47-IKO mice exhibited increased proliferation and abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapted to radiation injury and were protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and …
Polarized Localization Of Phosphatidylserine In The Endothelium Regulates Kir2.1, Claire A. Ruddiman, Richard Peckham, Melissa A. Luse, Yen-Lin Chen, Maniselvan Kuppusamy, Bruce A. Corliss, P. Jordan Hall, Chien-Jung Lin, Shayn M. Peirce, Swapnil K. Sonkusare, Robert P. Mecham, Jessica E. Wagenseil, Brant E. Isakson
Polarized Localization Of Phosphatidylserine In The Endothelium Regulates Kir2.1, Claire A. Ruddiman, Richard Peckham, Melissa A. Luse, Yen-Lin Chen, Maniselvan Kuppusamy, Bruce A. Corliss, P. Jordan Hall, Chien-Jung Lin, Shayn M. Peirce, Swapnil K. Sonkusare, Robert P. Mecham, Jessica E. Wagenseil, Brant E. Isakson
2020-Current year OA Pubs
Lipid regulation of ion channels is largely explored using in silico modeling with minimal experimentation in intact tissue; thus, the functional consequences of these predicted lipid-channel interactions within native cellular environments remain elusive. The goal of this study is to investigate how lipid regulation of endothelial Kir2.1 - an inwardly rectifying potassium channel that regulates membrane hyperpolarization - contributes to vasodilation in resistance arteries. First, we show that phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), crucial signaling microdomains that regulate vasodilation in resistance arteries, and in silico data have implied that PS may compete with phosphatidylinositol …
Protocol For Tumor Dissociation And Fluorescence-Activated Cell Sorting Of Human Head And Neck Cancers, Ogoegbunam Okolo, Victoria Yu, Samuel Flashner, Cecilia Martin, Hiroshi Nakagawa, Derrick T Lin, Sidharth V Puram, Anuraag S Parikh
Protocol For Tumor Dissociation And Fluorescence-Activated Cell Sorting Of Human Head And Neck Cancers, Ogoegbunam Okolo, Victoria Yu, Samuel Flashner, Cecilia Martin, Hiroshi Nakagawa, Derrick T Lin, Sidharth V Puram, Anuraag S Parikh
2020-Current year OA Pubs
Tumors originating from the head and neck represent diverse histologies and are comprised of several cell types, including malignant cells, cancer-associated fibroblasts, endothelial cells, and immune cells. In this protocol, we describe a step-by-step approach for the dissociation of fresh human head and neck tumor specimens, followed by isolation of viable single cells using fluorescence-activated cell sorting. Our protocol facilitates the effective downstream use of techniques, including single-cell RNA sequencing and generation of three-dimensional patient-derived organoids. For complete details on the use and execution of this protocol, please refer to Puram et al. (2017)
A Retrospective Multi-Institutional Cohort Analysis Of Clinical Characteristics And Outcomes In Dedifferentiated Chondrosarcoma, Nam Bui, Hilary Dietz, Sheima Farag, Angela C Hirbe, Michael J Wagner, Brian A Van Tine, Kristen Ganjoo, Robin L Jones, Vicki L Keedy, Elizabeth J Davis
A Retrospective Multi-Institutional Cohort Analysis Of Clinical Characteristics And Outcomes In Dedifferentiated Chondrosarcoma, Nam Bui, Hilary Dietz, Sheima Farag, Angela C Hirbe, Michael J Wagner, Brian A Van Tine, Kristen Ganjoo, Robin L Jones, Vicki L Keedy, Elizabeth J Davis
2020-Current year OA Pubs
BACKGROUND: Dedifferentiated chondrosarcoma (DDCS) is a rare subset of chondrosarcoma. It is an aggressive neoplasm characterized by a high rate of recurrent and metastatic disease with overall poor outcomes. Systemic therapy is often used to treat DDCS; however, the optimal regimen and timing are not well defined, with current guidelines recommending following osteosarcoma protocols.
METHODS: We conducted a multi-institutional retrospective analysis of clinical characteristics and outcomes of patients with DDCS. Between 1 January 2004 and 1 January 2022, the databases from five academic sarcoma centers were reviewed. Patient and tumor factors, including age, sex, tumor size, site, location, the treatments …
Short-Term Intensive Lifestyle Therapy In A Worksite Setting Improves Cardiometabolic Health In People With Obesity, George G Schweitzer, David C Beckner, Gordon I Smith, Samuel Klein
Short-Term Intensive Lifestyle Therapy In A Worksite Setting Improves Cardiometabolic Health In People With Obesity, George G Schweitzer, David C Beckner, Gordon I Smith, Samuel Klein
2020-Current year OA Pubs
CONTEXT: The Pritikin Program, which provides intensive lifestyle therapy, has been shown to improve cardiometabolic outcomes when provided as a residential program.
OBJECTIVE: The purpose of the present study was to conduct a short-term, randomized, controlled trial to evaluate the feasibility and clinical efficacy of treatment with the Pritikin Program in an outpatient worksite setting.
METHODS: Cardiometabolic outcomes were evaluated in people with overweight/obesity and ≥2 metabolic abnormalities (high triglycerides, low high-density lipoprotein (HDL) cholesterol, high blood pressure, HbA1c > 5.7%), before and after they were randomized to 6 weeks of standard care (n = 26) or intensive lifestyle therapy, based …
Developments In Stem Cell-Derived Islet Replacement Therapy For Treating Type 1 Diabetes, Nathaniel J Hogrebe, Matthew Ishahak, Jeffrey R Millman
Developments In Stem Cell-Derived Islet Replacement Therapy For Treating Type 1 Diabetes, Nathaniel J Hogrebe, Matthew Ishahak, Jeffrey R Millman
2020-Current year OA Pubs
The generation of islet-like endocrine clusters from human pluripotent stem cells (hPSCs) has the potential to provide an unlimited source of insulin-producing β cells for the treatment of diabetes. In order for this cell therapy to become widely adopted, highly functional and well-characterized stem cell-derived islets (SC-islets) need to be manufactured at scale. Furthermore, successful SC-islet replacement strategies should prevent significant cell loss immediately following transplantation and avoid long-term immune rejection. This review highlights the most recent advances in the generation and characterization of highly functional SC-islets as well as strategies to ensure graft viability and safety after transplantation.
Organizational Readiness To Implement Task-Strengthening Strategy For Hypertension Management Among People Living With Hiv In Nigeria, Juliet Iwelunmor, Daphne Lew, Et Al.
Organizational Readiness To Implement Task-Strengthening Strategy For Hypertension Management Among People Living With Hiv In Nigeria, Juliet Iwelunmor, Daphne Lew, Et Al.
2020-Current year OA Pubs
BACKGROUND: Hypertension (HTN) is highly prevalent among people living with HIV (PLHIV), but there is limited access to standardized HTN management strategies in public primary healthcare facilities in Nigeria. The shortage of trained healthcare providers in Nigeria is an important contributor to the increased unmet need for HTN management among PLHIV. Evidence-based TAsk-Strengthening Strategies for HTN control (TASSH) have shown promise to address this gap in other resource-constrained settings. However, little is known regarding primary health care facilities' capacity to implement this strategy. The objective of this study was to determine primary healthcare facilities' readiness to implement TASSH among PLHIV …
Infection Of Neonatal Mice With The Murine Norovirus Strain Wu23 Is A Robust Model To Study Norovirus Pathogenesis, Amy M Peiper, Emily W Helm, Quyen Nguyen, Matthew Phillips, Caroline G Williams, Dhairya Shah, Sarah Tatum, Neha Iyer, Marco Grodzki, Laura B Eurell, Aqsa Nasir, Megan T Baldridge, Stephanie M Karst
Infection Of Neonatal Mice With The Murine Norovirus Strain Wu23 Is A Robust Model To Study Norovirus Pathogenesis, Amy M Peiper, Emily W Helm, Quyen Nguyen, Matthew Phillips, Caroline G Williams, Dhairya Shah, Sarah Tatum, Neha Iyer, Marco Grodzki, Laura B Eurell, Aqsa Nasir, Megan T Baldridge, Stephanie M Karst
2020-Current year OA Pubs
Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe, with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. The development of the murine norovirus (MNV) model nearly two decades ago has facilitated progress in understanding host-norovirus interactions and norovirus strain …
Associations Between Cannabis Use, Polygenic Liability For Schizophrenia, And Cannabis-Related Experiences In A Sample Of Cannabis Users, Emma C Johnson, Sarah M C Colbert, Paul W Jeffries, Rebecca Tillman, Nicole R Karcher, Elliot C Nelson, Arpana Agrawal, Et Al.
Associations Between Cannabis Use, Polygenic Liability For Schizophrenia, And Cannabis-Related Experiences In A Sample Of Cannabis Users, Emma C Johnson, Sarah M C Colbert, Paul W Jeffries, Rebecca Tillman, Nicole R Karcher, Elliot C Nelson, Arpana Agrawal, Et Al.
2020-Current year OA Pubs
BACKGROUND AND HYPOTHESIS: Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs.
STUDY DESIGN: We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African …
Katp Channels Are Necessary For Glucose-Dependent Increases In Amyloid-Β And Alzheimer's Disease-Related Pathology, John Grizzanti, William R. Moritz, Molly Stanley, Emily E. Caesar, Maria S. Remedi, Celeste M. Karch, Colin G. Nichols, David M. Holtzman, Et Al.
Katp Channels Are Necessary For Glucose-Dependent Increases In Amyloid-Β And Alzheimer's Disease-Related Pathology, John Grizzanti, William R. Moritz, Molly Stanley, Emily E. Caesar, Maria S. Remedi, Celeste M. Karch, Colin G. Nichols, David M. Holtzman, Et Al.
2020-Current year OA Pubs
Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes and Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with cellular excitability, play a role in AD pathogenesis. First, we demonstrate that KATP channel subunits Kir6.2/KCNJ11 and SUR1/ABCC8 were expressed on excitatory and inhibitory neurons in the human brain, and cortical expression of KCNJ11 and ABCC8 changed with AD pathology in humans and mice. Next, we explored whether eliminating neuronal …
State-Level Macro-Economic Factors Moderate The Association Of Low Income With Brain Structure And Mental Health In U.S. Children, David G Weissman, Mark L Hatzenbuehler, Mina Cikara, Deanna M Barch, Katie A Mclaughlin
State-Level Macro-Economic Factors Moderate The Association Of Low Income With Brain Structure And Mental Health In U.S. Children, David G Weissman, Mark L Hatzenbuehler, Mina Cikara, Deanna M Barch, Katie A Mclaughlin
2020-Current year OA Pubs
Macrostructural characteristics, such as cost of living and state-level anti-poverty programs relate to the magnitude of socioeconomic disparities in brain development and mental health. In this study we leveraged data from the Adolescent Brain and Cognitive Development (ABCD) study from 10,633 9-11 year old youth (5115 female) across 17 states. Lower income was associated with smaller hippocampal volume and higher internalizing psychopathology. These associations were stronger in states with higher cost of living. However, in high cost of living states that provide more generous cash benefits for low-income families, socioeconomic disparities in hippocampal volume were reduced by 34%, such that …
Frequency Of Hepatic Metastatic Disease In Patients With Stage Iv Breast Cancer Is Similar For Steatotic And Non-Steatotic Livers, Adeel Haq, Tyler J Fraum, Yu Tao, Farrokh Dehdashti, Maverick Leblanc, Mark J Hoegger, Jingqin Luo, Katherine Weilbaecher, Lindsay L Peterson
Frequency Of Hepatic Metastatic Disease In Patients With Stage Iv Breast Cancer Is Similar For Steatotic And Non-Steatotic Livers, Adeel Haq, Tyler J Fraum, Yu Tao, Farrokh Dehdashti, Maverick Leblanc, Mark J Hoegger, Jingqin Luo, Katherine Weilbaecher, Lindsay L Peterson
2020-Current year OA Pubs
BACKGROUND: Breast cancer is the most common non-cutaneous malignancy and the second leading cause of cancer mortality in the United States. Breast cancer is a heterogeneous disease; diagnosis at an early stage renders it potentially curable, whereas advanced metastatic disease carries a worse prognosis.
OBJECTIVES: To investigate whether hepatic steatosis (HS) is associated with liver metastases in patients with newly diagnosed stage IV female breast cancer patients (either de novo metastatic breast cancer or recurrent metastatic breast cancer) using non-contrast computed tomography (CT) as a marker of HS.
DESIGN: Retrospective analysis.
METHODS: We retrospectively identified 168 patients with stage IV …
Mitos And King's Staging As Clinical Outcome Measures In Als: A Retrospective Analysis Of The Fortitude-Als Trial, Paulos Gebrehiwet, Lisa Meng, Stacy A Rudnicki, Phil Sarocco, Jenny Wei, Andrew A Wolff, Adriano Chiò, Jinsy A Andrews, Angela Genge, Carlayne E Jackson, Noah Lechtzin, Timothy M Miller, Jeremy M Shefner
Mitos And King's Staging As Clinical Outcome Measures In Als: A Retrospective Analysis Of The Fortitude-Als Trial, Paulos Gebrehiwet, Lisa Meng, Stacy A Rudnicki, Phil Sarocco, Jenny Wei, Andrew A Wolff, Adriano Chiò, Jinsy A Andrews, Angela Genge, Carlayne E Jackson, Noah Lechtzin, Timothy M Miller, Jeremy M Shefner
2020-Current year OA Pubs
OBJECTIVE: To evaluate the Milano-Torino staging (MiToS) and King's staging systems as potential outcome measures for clinical trials in amyotrophic lateral sclerosis (ALS) by assessing these outcomes in FORTITUDE-ALS.
METHODS: This was a
RESULTS: The full analysis set consisted of 456 patients randomized 3:1 (
CONCLUSION: This exploratory analysis showed the feasibility of MiToS and King's staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials.
Deep Learning Based On Co-Registered Ultrasound And Photoacoustic Imaging Improves The Assessment Of Rectal Cancer Treatment Response, Yixiao Lin, Sitai Kou, Haolin Nie, Hongbo Luo, Ahmed Eltahir, Will Chapman Jr., Steven Hunt, Matthew Mutch, Quing Zhu
Deep Learning Based On Co-Registered Ultrasound And Photoacoustic Imaging Improves The Assessment Of Rectal Cancer Treatment Response, Yixiao Lin, Sitai Kou, Haolin Nie, Hongbo Luo, Ahmed Eltahir, Will Chapman Jr., Steven Hunt, Matthew Mutch, Quing Zhu
2020-Current year OA Pubs
Identifying complete response (CR) after rectal cancer preoperative treatment is critical to deciding subsequent management. Imaging techniques, including endorectal ultrasound and MRI, have been investigated but have low negative predictive values. By imaging post-treatment vascular normalization using photoacoustic microscopy, we hypothesize that co-registered ultrasound and photoacoustic imaging will better identify complete responders. In this study, we used
Sars-Cov-2 Vaccination In The First Year After Allogeneic Hematopoietic Cell Transplant: A Prospective, Multicentre, Observational Study, Joshua A Hill, Peter Westervelt, Et Al.
Sars-Cov-2 Vaccination In The First Year After Allogeneic Hematopoietic Cell Transplant: A Prospective, Multicentre, Observational Study, Joshua A Hill, Peter Westervelt, Et Al.
2020-Current year OA Pubs
BACKGROUND: The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood.
METHODS: We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States. Participants of any age who were planning to receive a first post-HCT SARS-CoV-2 vaccine within 12 months of HCT were eligible. We obtained blood prior to and after each vaccine dose for up to four vaccine doses, with an end-of-study sample seven to nine months after enrollment. …
Cognitive Function Following Diabetic Ketoacidosis In Young Children With Type 1 Diabetes, Simona Ghetti, Kimberly S Quayle, Et Al.
Cognitive Function Following Diabetic Ketoacidosis In Young Children With Type 1 Diabetes, Simona Ghetti, Kimberly S Quayle, Et Al.
2020-Current year OA Pubs
INTRODUCTION: Young children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure.
METHODS: We prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, …
Independent Study Demonstrates Amyloid Probability Score Accurately Indicates Amyloid Pathology, Ilana Fogelman, Randall J Bateman, David M Holtzman, Et Al.
Independent Study Demonstrates Amyloid Probability Score Accurately Indicates Amyloid Pathology, Ilana Fogelman, Randall J Bateman, David M Holtzman, Et Al.
2020-Current year OA Pubs
BACKGROUND: The amyloid probability score (APS) is the model read-out of the analytically validated mass spectrometry-based PrecivityAD
PURPOSE: This study aimed to provide additional independent evidence that the pre-established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals.
METHODS: The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available.
RESULTS: In a subset of the dataset aligned …
Distinct Effects Of Two Hearing Loss-Associated Mutations In The Sarcomeric Myosin Myh7b, Lindsey A Lee, Samantha K Barrick, Ada E Buvoli, Jonathan Walklate, W Tom Stump, Michael Geeves, Michael J Greenberg, Leslie A Leinwand
Distinct Effects Of Two Hearing Loss-Associated Mutations In The Sarcomeric Myosin Myh7b, Lindsey A Lee, Samantha K Barrick, Ada E Buvoli, Jonathan Walklate, W Tom Stump, Michael Geeves, Michael J Greenberg, Leslie A Leinwand
2020-Current year OA Pubs
For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss-associated mutation and studied …
Blockade Of Trpv Channels By Intracellular Spermine, Grigory Maksaev, Peng Yuan, Colin G Nichols
Blockade Of Trpv Channels By Intracellular Spermine, Grigory Maksaev, Peng Yuan, Colin G Nichols
2020-Current year OA Pubs
The Vanilloid thermoTRP (TRPV1-4) subfamily of TRP channels are involved in thermoregulation, osmoregulation, itch and pain perception, (neuro)inflammation and immune response, and tight control of channel activity is required for perception of noxious stimuli and pain. Here we report voltage-dependent modulation of each of human TRPV1, 3, and 4 by the endogenous intracellular polyamine spermine. As in inward rectifier K channels, currents are blocked in a strongly voltage-dependent manner, but, as in cyclic nucleotide-gated channels, the blockade is substantially reduced at more positive voltages, with maximal blockade in the vicinity of zero voltage. A kinetic model of inhibition suggests two …
Differential Regulation Of Cardiac Sodium Channels By Intracellular Fibroblast Growth Factors, Paweorn Angsutararux, Amal K Dutta, Martina Marras, Carlota Abella, Rebecca L Mellor, Jingyi Shi, Jeanne M Nerbonne, Jonathan R Silva
Differential Regulation Of Cardiac Sodium Channels By Intracellular Fibroblast Growth Factors, Paweorn Angsutararux, Amal K Dutta, Martina Marras, Carlota Abella, Rebecca L Mellor, Jingyi Shi, Jeanne M Nerbonne, Jonathan R Silva
2020-Current year OA Pubs
Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant …
Symptomatic Benefit Of Momelotinib In Patients With Myelofibrosis: Results From The Simplify Phase Iii Studies, Ruben A Mesa, Stephen T Oh, Et Al.
Symptomatic Benefit Of Momelotinib In Patients With Myelofibrosis: Results From The Simplify Phase Iii Studies, Ruben A Mesa, Stephen T Oh, Et Al.
2020-Current year OA Pubs
BACKGROUND: Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy.
METHODS: Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to …
Quantitative Determination Of Slc2a1 Variant Functional Effects In Glut1 Deficiency Syndrome, Naeimeh Tayebi, Brian Leon-Ricardo, Kevin Mccall, Elvisa Mehinovic, Kristin Engelstad, Vincent Huynh, Tychele N Turner, Judy Weisenberg, Liu L Thio, Paul Hruz, Robin S B Williams, Darryl C De Vivo, Vincent Petit, Gabe Haller, Christina A Gurnett
Quantitative Determination Of Slc2a1 Variant Functional Effects In Glut1 Deficiency Syndrome, Naeimeh Tayebi, Brian Leon-Ricardo, Kevin Mccall, Elvisa Mehinovic, Kristin Engelstad, Vincent Huynh, Tychele N Turner, Judy Weisenberg, Liu L Thio, Paul Hruz, Robin S B Williams, Darryl C De Vivo, Vincent Petit, Gabe Haller, Christina A Gurnett
2020-Current year OA Pubs
OBJECTIVE: The goal of this study is to demonstrate the utility of a growth assay to quantify the functional impact of single nucleotide variants (SNVs) in SLC2A1, the gene responsible for Glut1DS.
METHODS: The functional impact of 40 SNVs in SLC2A1 was quantitatively determined in HAP1 cells in which SLC2A1 is required for growth. Donor libraries were introduced into the endogenous SLC2A1 gene in HAP1-Lig4KO cells using CRISPR/Cas9. Cell populations were harvested and sequenced to quantify the effect of variants on growth and generate a functional score. Quantitative functional scores were compared to 3-OMG uptake, SLC2A1 cell surface expression, CADD …
Position Paper: Models Of Post-Transplant Care For Individuals With Cystic Fibrosis, Edward Mckone, Joshua Blatter, Ramsey Hachem, Et Al.
Position Paper: Models Of Post-Transplant Care For Individuals With Cystic Fibrosis, Edward Mckone, Joshua Blatter, Ramsey Hachem, Et Al.
2020-Current year OA Pubs
There is no consensus on the best model of care for individuals with CF to manage the non-pulmonary complications that persist after lung transplant. The CF Foundation virtually convened a group of international experts in CF and lung-transplant care. The committee reviewed literature and shared the post-lung transplant model of care practiced by their programs. The committee then developed a survey that was distributed internationally to both the clinical and individual with CF/family audiences to determine the strengths, weaknesses, and preferences for various models of transplant care. Discussion generated two models to accomplish optimal CF care after transplant. The first …
Remote Global Radiation Oncology Education And Training: A Pathway To Increase Access To High-Quality Radiation Therapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Matthew Schmidt, Tianyu Zhao, Hiram Gay, Jeff Michalski, Geoffrey Hugo, Jacaranda Van Rheenen, Baozhou Sun, Et Al.
Remote Global Radiation Oncology Education And Training: A Pathway To Increase Access To High-Quality Radiation Therapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Matthew Schmidt, Tianyu Zhao, Hiram Gay, Jeff Michalski, Geoffrey Hugo, Jacaranda Van Rheenen, Baozhou Sun, Et Al.
2020-Current year OA Pubs
PURPOSE: There is a vital need to train radiation therapy professionals in low- and middle-income countries (LMICs) to develop sustainable cancer treatment capacity and infrastructure. LMICs have started to introduce intensity modulated radiation therapy (IMRT), which is the standard of care in high-income countries, because of improved outcomes and reduced toxicities. This work reports the efficacy of a complementary asynchronous plus synchronous virtual-training approach on improving radiation therapy professions' self-confidence levels and evaluating participants' attitudes toward asynchronous and synchronous didactic hands-on learning in 3 LMICs.
METHODS AND MATERIALS: Training was provided to 37 participants from Uganda, Guatemala, and Mongolia, which …
Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Nandini Raghuraman, Et Al.
Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Nandini Raghuraman, Et Al.
2020-Current year OA Pubs
IMPORTANCE: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad.
OBJECTIVE: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic …
Examining Mental Health, Education, Employment, And Pain In Sickle Cell Disease, Kelly M Harris, Liliana Preiss, Taniya Varughese, Anna Bauer, Cecelia L Calhoun, Marsha Treadwell, Rita Masese, Jane S Hankins, Faiz Ahmed Hussain, Jeffrey Glassberg, Cathy L Melvin, Robert Gibson, Allison A King, Sickle Cell Disease Implementation Consortium
Examining Mental Health, Education, Employment, And Pain In Sickle Cell Disease, Kelly M Harris, Liliana Preiss, Taniya Varughese, Anna Bauer, Cecelia L Calhoun, Marsha Treadwell, Rita Masese, Jane S Hankins, Faiz Ahmed Hussain, Jeffrey Glassberg, Cathy L Melvin, Robert Gibson, Allison A King, Sickle Cell Disease Implementation Consortium
2020-Current year OA Pubs
IMPORTANCE: Pain related to sickle cell disease (SCD) is complex and associated with social determinants of health. Emotional and stress-related effects of SCD impact daily quality of life and the frequency and severity of pain.
OBJECTIVE: To explore the association of educational attainment, employment status, and mental health with pain episode frequency and severity among individuals with SCD.
DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional analysis of patient registry data collected at baseline (2017-2018) from patients treated at 8 sites of the US Sickle Cell Disease Implementation Consortium. Data analysis was performed from September 2020 to March 2022.
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Perception And Awareness Of Diabetes Risk And Reported Risk-Reducing Behaviors In Adolescents, Patricia Chu, Arya Patel, Vicki Helgeson, Andrea B Goldschmidt, Mary Katherine Ray, Mary Ellen Vajravelu
Perception And Awareness Of Diabetes Risk And Reported Risk-Reducing Behaviors In Adolescents, Patricia Chu, Arya Patel, Vicki Helgeson, Andrea B Goldschmidt, Mary Katherine Ray, Mary Ellen Vajravelu
2020-Current year OA Pubs
IMPORTANCE: Lifestyle change is central to diabetes risk reduction in youth with overweight or obesity. Feeling susceptible to a health threat can be motivational in adults.
OBJECTIVE: To evaluate associations between diabetes risk perception and/or awareness and health behaviors in youth.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2011 to 2018. Participants included youths aged 12 to 17 years with body mass index (BMI) in the 85th percentile or higher without known diabetes. Analyses were conducted from February 2022 to February 2023.
MAIN OUTCOMES AND MEASURES: Outcomes included physical …