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Articles 4741 - 4770 of 10551

Full-Text Articles in Medicine and Health Sciences

Blockade Of Trpv Channels By Intracellular Spermine, Grigory Maksaev, Peng Yuan, Colin G Nichols May 2023

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 …


Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Nandini Raghuraman, Et Al. May 2023

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 May 2023

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.

MAIN …


Neighborhood Deprivation And Association With Neonatal Intensive Care Unit Mortality And Morbidity For Extremely Premature Infants, Brynne A Sullivan, Ayush Doshi, Pavel Chernyavskiy, Ameena Husain, Alexandra Binai, Rakesh Sahni, Karen D Fairchild, J Randall Moorman, Colm P Travers, Zachary A Vesoulis May 2023

Neighborhood Deprivation And Association With Neonatal Intensive Care Unit Mortality And Morbidity For Extremely Premature Infants, Brynne A Sullivan, Ayush Doshi, Pavel Chernyavskiy, Ameena Husain, Alexandra Binai, Rakesh Sahni, Karen D Fairchild, J Randall Moorman, Colm P Travers, Zachary A Vesoulis

2020-Current year OA Pubs

IMPORTANCE: Socioeconomic status affects pregnancy and neurodevelopment, but its association with hospital outcomes among premature infants is unknown. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses US Census Bureau data on income, educational level, employment, and housing quality.

OBJECTIVE: To determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 4 level IV NICUs in the US Northeast, Mid-Atlantic, Midwest, and South regions. Non-Hispanic White and Black infants with gestational age of less than 29 …


Psychosis Brain Subtypes Validated In First-Episode Cohorts And Related To Illness Remission: Results From The Phenom Consortium, Dominic B Dwyer, Ganesh B Chand, Aristeidis Sotiras, Et Al. May 2023

Psychosis Brain Subtypes Validated In First-Episode Cohorts And Related To Illness Remission: Results From The Phenom Consortium, Dominic B Dwyer, Ganesh B Chand, Aristeidis Sotiras, Et Al.

2020-Current year OA Pubs

Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups-a 'lower brain volume' subgroup (SG1) and an 'higher striatal volume' subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping …


Transition To Surgery After Pessary Among Female Medicare Beneficiaries With Pelvic Organ Prolapse, Melanie R L Meister, Oyomoare L Osazuwa-Peters, Jerry L Lowder, Victoria L Handa May 2023

Transition To Surgery After Pessary Among Female Medicare Beneficiaries With Pelvic Organ Prolapse, Melanie R L Meister, Oyomoare L Osazuwa-Peters, Jerry L Lowder, Victoria L Handa

2020-Current year OA Pubs

BACKGROUND: The American College of Obstetricians and Gynecologists recommends offering a vaginal pessary to women seeking treatment of pelvic organ prolapse. However, single-institution series have suggested that a sizable proportion of women fitted with a pessary will transition to surgery within the first year.

OBJECTIVE: This study aimed to estimate the proportion of female US Medicare beneficiaries with pelvic organ prolapse who undergo surgery after pessary fitting, to describe the median time to surgery from pessary fitting, and to identify factors associated with the transition from pessary to surgery.

STUDY DESIGN: The Medicare 5% Limited Data Set was queried from …


Identifying Regions Of Interest In Mammogram Images, Shu Jiang, Jiguo Cao, Graham A. Colditz May 2023

Identifying Regions Of Interest In Mammogram Images, Shu Jiang, Jiguo Cao, Graham A. Colditz

2020-Current year OA Pubs

Screening mammography is the primary preventive strategy for early detection of breast cancer and an essential input to breast cancer risk prediction and application of prevention/risk management guidelines. Identifying regions of interest within mammogram images that are associated with 5- or 10-year breast cancer risk is therefore clinically meaningful. The problem is complicated by the irregular boundary issue posed by the semi-circular domain of the breast area within mammograms. Accommodating the irregular domain is especially crucial when identifying regions of interest, as the true signal comes only from the semi-circular domain of the breast region, and noise elsewhere. We address …


First-In-Human Phase Ib Trial Of M9241 (Nhs-Il12) Plus Avelumab In Patients With Advanced Solid Tumors, Including Dose Expansion In Patients With Advanced Urothelial Carcinoma, Julius Strauss, Russell K. Pachynski, Et Al. May 2023

First-In-Human Phase Ib Trial Of M9241 (Nhs-Il12) Plus Avelumab In Patients With Advanced Solid Tumors, Including Dose Expansion In Patients With Advanced Urothelial Carcinoma, Julius Strauss, Russell K. Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: In preclinical studies, combining M9241 (a novel immunocytokine containing interleukin (IL)-12 heterodimers) with avelumab (anti-programmed death ligand 1 antibody) resulted in additive or synergistic antitumor effects. We report dose-escalation and dose-expansion results from the phase Ib JAVELIN IL-12 trial investigating M9241 plus avelumab.

METHODS: In the dose-escalation part of JAVELIN IL-12 (NCT02994953), eligible patients had locally advanced or metastatic solid tumors; in the dose-expansion part, eligible patients had locally advanced or metastatic urothelial carcinoma (UC) that had progressed with first-line therapy. Patients received M9241 at 4, 8, 12, or 16.8 µg/kg every 4 weeks (Q4W) plus avelumab 10 mg/kg …


Usefulness Of The Lupus Low Disease Activity State As A Treatment Target In Childhood-Onset Sle, Ellen M. Cody, Bridget E. Wilson, Ekemini A. Ogbu, Jennifer L. Huggins, Chen Chen, Tingting Qiu, Tracy V. Ting, Francisco Flores, Bin Huang, Hermine I. Brunner May 2023

Usefulness Of The Lupus Low Disease Activity State As A Treatment Target In Childhood-Onset Sle, Ellen M. Cody, Bridget E. Wilson, Ekemini A. Ogbu, Jennifer L. Huggins, Chen Chen, Tingting Qiu, Tracy V. Ting, Francisco Flores, Bin Huang, Hermine I. Brunner

2020-Current year OA Pubs

OBJECTIVE: Treat-to-target (T2T) strategies are advocated to improve prognosis in childhood-onset SLE (cSLE). Proposed T2T states include SLEDAI score of

METHODS: Longitudinal data from 165 patients enrolled in the Cincinnati Lupus Registry were included. LN presence was based on renal biopsy, and patients were followed up until 18 years of age.

RESULTS: The 165 patients (LN: 45, white: 95) entered the registry within a median of 0 (IQR: 0-1) year post diagnosis and were followed up for a median of 4 (IQR: 2-5) years during which 80%, 92% and 94% achieved LLDAS, low-CS and SLEDAI-LD. Patients with LN were significantly …


The Complement System And Human Autoimmune Diseases, Samantha L Coss, Danlei Zhou, Gilbert T. Chua, Rabheh Abdul Aziz, Robert P. Hoffman, Yee Ling Wu, Stacy P. Ardoin, John P. Atkinson, Chack-Yung Yu May 2023

The Complement System And Human Autoimmune Diseases, Samantha L Coss, Danlei Zhou, Gilbert T. Chua, Rabheh Abdul Aziz, Robert P. Hoffman, Yee Ling Wu, Stacy P. Ardoin, John P. Atkinson, Chack-Yung Yu

2020-Current year OA Pubs

Genetic deficiencies of early components of the classical complement activation pathway (especially C1q, r, s, and C4) are the strongest monogenic causal factors for the prototypic autoimmune disease systemic lupus erythematosus (SLE), but their prevalence is extremely rare. In contrast, isotype genetic deficiency of C4A and acquired deficiency of C1q by autoantibodies are frequent among patients with SLE. Here we review the genetic basis of complement deficiencies in autoimmune disease, discuss the complex genetic diversity seen in complement C4 and its association with autoimmune disease, provide guidance as to when clinicians should suspect and test for complement deficiencies, and outline …


Leveraging Innovation To Mitigate Risk During Heart Surgery, Marc R Moon, Puja Kachroo May 2023

Leveraging Innovation To Mitigate Risk During Heart Surgery, Marc R Moon, Puja Kachroo

2020-Current year OA Pubs

No abstract provided.


Influence Of Genomic Landscape On Cancer Immunotherapy For Newly Diagnosed Ovarian Cancer: Biomarker Analyses From The Imagyn050 Randomized Clinical Trial, Charles N Landen, Premal H Thaker, Et Al. May 2023

Influence Of Genomic Landscape On Cancer Immunotherapy For Newly Diagnosed Ovarian Cancer: Biomarker Analyses From The Imagyn050 Randomized Clinical Trial, Charles N Landen, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.

PATIENTS AND METHODS: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations …


Genomic Complexity Predicts Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Hormone Receptor-Positive (Hr+)/Her2-Negative Metastatic Breast Cancer, Andrew A Davis, Jingqin Luo, Rama Suresh, Foluso O Ademuyiwa, Caron Rigden, Timothy P Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Tracy Summa, Brittney Haas, Shana Thomas, Leonel F Hernandez-Aya, Lindsay L Peterson, Cynthia X Ma, Et Al. May 2023

Genomic Complexity Predicts Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Hormone Receptor-Positive (Hr+)/Her2-Negative Metastatic Breast Cancer, Andrew A Davis, Jingqin Luo, Rama Suresh, Foluso O Ademuyiwa, Caron Rigden, Timothy P Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Tracy Summa, Brittney Haas, Shana Thomas, Leonel F Hernandez-Aya, Lindsay L Peterson, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance.

EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome …


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 May 2023

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


A Phase 1 First-In-Human Study Of Gs-0189, An Anti-Signal Regulatory Protein Alpha (Sirpα) Monoclonal Antibody, In Patients With Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (Nhl), Mayur Narkhede, Nancy L Bartlett, Sami Ibrahimi, Leslie Popplewell, Anna Seto, Jamie Bates, Yeonju Lee, Vaishnavi Ganti, Ling Han, Tianling Chen, Manish R Patel May 2023

A Phase 1 First-In-Human Study Of Gs-0189, An Anti-Signal Regulatory Protein Alpha (Sirpα) Monoclonal Antibody, In Patients With Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (Nhl), Mayur Narkhede, Nancy L Bartlett, Sami Ibrahimi, Leslie Popplewell, Anna Seto, Jamie Bates, Yeonju Lee, Vaishnavi Ganti, Ling Han, Tianling Chen, Manish R Patel

2020-Current year OA Pubs

Signal regulatory protein alpha (SIRPα) is the receptor for cluster of differentiation (CD)47, a potent "don't eat me" signal for macrophages. Disruption of CD47-SIRPα signaling in the presence of prophagocytic signals can lead to enhanced phagocytosis of tumor cells, resulting in a direct antitumor effect; agents targeting this pathway have shown efficacy in non-Hodgkin lymphoma (NHL) and other tumor types. GS-0189 is a novel anti-SIRPα humanized monoclonal antibody. Here we report: (1) clinical safety, preliminary activity, and pharmacokinetics of GS-0189 as monotherapy and in combination with rituximab from a phase 1 clinical trial in patients with relapsed/refractory NHL (NCT04502706, SRP001); …


Food Insecurity, Snap Participation And Glycemic Control In Low-Income Adults With Predominantly Type 2 Diabetes: A Cross-Sectional Analysis Using Nhanes 2007-2018 Data, Oluwatobi Alawode, Sarah Humble, Cynthia J Herrick May 2023

Food Insecurity, Snap Participation And Glycemic Control In Low-Income Adults With Predominantly Type 2 Diabetes: A Cross-Sectional Analysis Using Nhanes 2007-2018 Data, Oluwatobi Alawode, Sarah Humble, Cynthia J Herrick

2020-Current year OA Pubs

INTRODUCTION: Diabetes, characterized by elevated blood glucose levels, affects 13% of US adults, 95% of whom have type 2 diabetes (T2D). Social determinants of health (SDoH), such as food insecurity, are integral to glycemic control. The Supplemental Nutrition Assistance Program (SNAP) aims to reduce food insecurity, but it is not clear how this affects glycemic control in T2D. This study investigated the associations between food insecurity and other SDoH and glycemic control and the role of SNAP participation in a national socioeconomically disadvantaged sample.

RESEARCH DESIGN AND METHODS: Adults with likely T2D and income

RESULTS: The study population included 2084 …


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 May 2023

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 …


Provisional Practice Recommendation For The Management Of Myopathy In Vcp-Associated Multisystem Proteinopathy, Bhaskar Roy, Conrad Chris Weihl, Et Al. May 2023

Provisional Practice Recommendation For The Management Of Myopathy In Vcp-Associated Multisystem Proteinopathy, Bhaskar Roy, Conrad Chris Weihl, Et Al.

2020-Current year OA Pubs

Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on …


Ligand And G-Protein Selectivity In The Κ-Opioid Receptor, Jianming Han, Jingying Zhang, Antonina L Nazarova, Sarah M Bernhard, Brian E Krumm, Lei Zhao, Jordy Homing Lam, Vipin A Rangari, Susruta Majumdar, David E Nichols, Vsevolod Katritch, Peng Yuan, Jonathan F Fay, Tao Che May 2023

Ligand And G-Protein Selectivity In The Κ-Opioid Receptor, Jianming Han, Jingying Zhang, Antonina L Nazarova, Sarah M Bernhard, Brian E Krumm, Lei Zhao, Jordy Homing Lam, Vipin A Rangari, Susruta Majumdar, David E Nichols, Vsevolod Katritch, Peng Yuan, Jonathan F Fay, Tao Che

2020-Current year OA Pubs

The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders


A Draft Human Pangenome Reference, Wen-Wei Liao, Haley J Abel, Robert S Fulton, Chad Tomlinson, Lucinda L Antonacci-Fulton, Sarah Cody, Allison A Regier, Ting Wang, Et Al. May 2023

A Draft Human Pangenome Reference, Wen-Wei Liao, Haley J Abel, Robert S Fulton, Chad Tomlinson, Lucinda L Antonacci-Fulton, Sarah Cody, Allison A Regier, Ting Wang, Et Al.

2020-Current year OA Pubs

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals


Functional Screening Of Lysosomal Storage Disorder Genes Identifies Modifiers Of Alpha-Synuclein Neurotoxicity, Meigen Yu, Hui Ye, Ruth B. De-Paula, Carl Grant Mangleburg, Timothy Wu, Tom V. Lee, Yarong Li, Duc Duong, Bridget Phillips, Carlos Cruchaga, Genevera I. Allen, Nicholas T. Seyfried, Ismael Al-Ramahi, Juan Botas, Joshua M. Shulman May 2023

Functional Screening Of Lysosomal Storage Disorder Genes Identifies Modifiers Of Alpha-Synuclein Neurotoxicity, Meigen Yu, Hui Ye, Ruth B. De-Paula, Carl Grant Mangleburg, Timothy Wu, Tom V. Lee, Yarong Li, Duc Duong, Bridget Phillips, Carlos Cruchaga, Genevera I. Allen, Nicholas T. Seyfried, Ismael Al-Ramahi, Juan Botas, Joshua M. Shulman

2020-Current year OA Pubs

Heterozygous variants in the glucocerebrosidase (GBA) gene are common and potent risk factors for Parkinson's disease (PD). GBA also causes the autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, and emerging evidence from human genetics implicates many other LSD genes in PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 human LSD genes for requirements in the aging adult Drosophila brain and for potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms Lewy body pathology in PD. Our screen identifies 15 genetic enhancers of αSyn-induced progressive locomotor dysfunction, including knockdown of fly homologs of GBA …


Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski May 2023

Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski

2020-Current year OA Pubs

Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric …


Symptomatic Benefit Of Momelotinib In Patients With Myelofibrosis: Results From The Simplify Phase Iii Studies, Ruben A Mesa, Stephen T Oh, Et Al. May 2023

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 …


Gluteus Maximus Transfer For Hip Abductor Deficiency, Paul M Inclan, Maria T Schwabe, Bryant M Song, Andrew W Kuhn, Daniel R Layon, John C Clohisy, Cecilia Pascual-Garrido May 2023

Gluteus Maximus Transfer For Hip Abductor Deficiency, Paul M Inclan, Maria T Schwabe, Bryant M Song, Andrew W Kuhn, Daniel R Layon, John C Clohisy, Cecilia Pascual-Garrido

2020-Current year OA Pubs

Hip abductor deficiency resulting from gluteus medius and minimus pathology is increasingly recognized as a generator of lateral-sided hip pain. In the setting of a failed gluteus medius repair or in patients with irreparable tears, transfer of the anterior portion of the gluteus maximus muscle can be performed to treat gluteal abductor deficiency. The classic description of the gluteus maximus transfer technique relies solely on bone tunnel fixation. This article describes a reproducible technique that incorporates the addition of a distal row to the tendon transfer, which may improve fixation by both compressing the tendon transfer to the greater trochanter …


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 May 2023

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 …


Patterns In Use And Transplant Outcomes Among Adult Recipients Of Kidneys From Deceased Donors With Covid-19, Mengmeng Ji, Amanda J Vinson, Su-Hsin Chang, Massini Merzkani, Krista L Lentine, Yasar Caliskan, Kristin Progar, Nicole Nesselhauf, Casey Dubrawka, Tarek Alhamad May 2023

Patterns In Use And Transplant Outcomes Among Adult Recipients Of Kidneys From Deceased Donors With Covid-19, Mengmeng Ji, Amanda J Vinson, Su-Hsin Chang, Massini Merzkani, Krista L Lentine, Yasar Caliskan, Kristin Progar, Nicole Nesselhauf, Casey Dubrawka, Tarek Alhamad

2020-Current year OA Pubs

IMPORTANCE: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown.

OBJECTIVE: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs …


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 May 2023

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 …


Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen May 2023

Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen

2020-Current year OA Pubs

Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would …


Chemotherapy-Induced Toxicities: An Imaging Primer, Nikhil S. Patil, Natasha Larocque, Christian B. Van Der Pol, Carlos Torres, Demetrios A. Raptis, Michael N. Patlas May 2023

Chemotherapy-Induced Toxicities: An Imaging Primer, Nikhil S. Patil, Natasha Larocque, Christian B. Van Der Pol, Carlos Torres, Demetrios A. Raptis, Michael N. Patlas

2020-Current year OA Pubs

The Coronavirus Disease of 2019 (COVID-19) pandemic has caused significant delays in the delivery of cancer treatments in Canada. As cancer treatment and imaging volumes return to normal, radiologists will encounter more cases of chemotherapy-induced toxicities. These toxicities have varied appearances on imaging, and can affect multiple organ systems. The purpose of this review is to offer a unified resource for general radiologists regarding the imaging appearances of chemotherapy-induced toxicities.


Clerkship Director Confidence In Medical Student Career Advising In Obstetrics And Gynecology, Shireen Madani Sims, Susan M Cox, Rashmi Bhargava, Elise N Everett, Angela Fleming, Scott Graziano, Helen K Morgan, Laura Baecher-Lind, Celeste Royce, Tammy S Sonn, Jill M Sutton, Christopher M Morosky May 2023

Clerkship Director Confidence In Medical Student Career Advising In Obstetrics And Gynecology, Shireen Madani Sims, Susan M Cox, Rashmi Bhargava, Elise N Everett, Angela Fleming, Scott Graziano, Helen K Morgan, Laura Baecher-Lind, Celeste Royce, Tammy S Sonn, Jill M Sutton, Christopher M Morosky

2020-Current year OA Pubs

BACKGROUND: Given the increasing complexities of the residency application processes, there is an ever-increasing need for faculty to serve in the role of fourth-year medical student career advisors.

OBJECTIVE: This study aimed to investigate obstetrics and gynecology clerkship directors' confidence and fulfillment with serving in the role of faculty career advisors.

STUDY DESIGN: A 25-item electronic survey was developed and distributed to the 225 US obstetrics and gynecology clerkship directors in university-based and community-based medical schools with active memberships in the Association of Professors of Gynecology and Obstetrics. Items queried respondents on demographics, confidence in fourth-year advising, satisfaction with this …