Digital Commons Network^™

Pharmacokinetics Of Moxidectin Combined With Albendazole Or Albendazole Plus Diethylcarbamazine For Bancroftian Filariasis, Yashpal S. Chhonker, Catherine Bjerum, Veenu Bala, Allassane F. Ouattara, Benjamin G. Koudou, Toki P. Gabo, Abdullah Alshehri, Abdoulaye Meïté, Peter U. Fischer, Gary J. Weil, Christopher L. King, Philip J. Budge, Daryl J. Murry

2020-Current year OA Pubs

Moxidectin (MOX) is a milbemycin endectocide recently approved by the U.S. FDA for the treatment of onchocerciasis in persons at least 12 years of age. MOX has been shown to have a good safety profile in recent clinical trials. The efficacy of MOX for the treatment of lymphatic filariasis (LF) and its potential use in mass drug administration protocols for the elimination of LF is currently under evaluation. In the context of a clinical trial, we investigated the pharmacokinetics and drug interactions of a combination of MOX plus albendazole (ALB) with or without diethylcarbamazine (DEC) compared to ivermectin (IVM) plus …

Music Can Be Reconstructed From Human Auditory Cortex Activity Using Nonlinear Decoding Models, Ludovic Bellier, Anaïs Llorens, Déborah Marciano, Aysegul Gunduz, Gerwin Schalk, Peter Brunner, Robert T. Knight

2020-Current year OA Pubs

Music is core to human experience, yet the precise neural dynamics underlying music perception remain unknown. We analyzed a unique intracranial electroencephalography (iEEG) dataset of 29 patients who listened to a Pink Floyd song and applied a stimulus reconstruction approach previously used in the speech domain. We successfully reconstructed a recognizable song from direct neural recordings and quantified the impact of different factors on decoding accuracy. Combining encoding and decoding analyses, we found a right-hemisphere dominance for music perception with a primary role of the superior temporal gyrus (STG), evidenced a new STG subregion tuned to musical rhythm, and defined …

Csf Mtbr-Tau243 Is A Specific Biomarker Of Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Nicolas R Barthélemy, Yan Li, Yingxin He, Benjamin Saef, Charles D Chen, Hong Jiang, Chihiro Sato, Brian A Gordon, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Aggregated insoluble tau is one of two defining features of Alzheimer's disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and …

Cerebrospinal Fluid Proteomics Define The Natural History Of Autosomal Dominant Alzheimer's Disease, Erik C B Johnson, Brian A Gordon, Eric Mcdade, Nicolas R Barthélemy, Celeste M Karch, Chengjie Xiong, Carlos Cruchaga, Richard J Perrin, John C Morris, Tammie L S Benzinger, Randall J Bateman, Anne M Fagan, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes-aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)-are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning …

A High-Performance Speech Neuroprosthesis, Francis R Willett, Erin M Kunz, Chaofei Fan, Donald T Avansino, Guy H Wilson, Eun Young Choi, Foram Kamdar, Matthew F Glasser, Leigh R Hochberg, Shaul Druckmann, Krishna V Shenoy, Jaimie M Henderson

2020-Current year OA Pubs

Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text

Spatial Epidemiologic Analysis And Risk Factors For Nontuberculous Mycobacteria Infections, Missouri, Usa, 2008-2019, Carlos Mejia-Chew, Miguel A Chavez, Min Lian, Angela Mckee, Leighton Garrett, Thomas C Bailey, Andrej Spec, Mansi Agarwal, George Turabelidze

2020-Current year OA Pubs

Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with …

Prospective Role Of Cefiderocol In The Management Of Carbapenem-Resistant Acinetobacter Baumannii Infections: Review Of The Evidence, Marin Kollef, Herve Dupont, David E Greenberg, Pierluigi Viale, Roger Echols, Yoshinori Yamano, David P Nicolau

2020-Current year OA Pubs

Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified by the World Health Organization as being in the critical category of pathogens requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, was designed for the treatment of carbapenem-resistant Gram-negative pathogens, particularly the non-fermenting species A. baumannii and Pseudomonas aeruginosa. Cefiderocol is mostly stable against hydrolysis by serine β-lactamases and metallo-β-lactamases, which are leading causes of carbapenem resistance. This review collates the available evidence on the in vitro activity, pharmacokinetics/pharmacodynamics, and efficacy and safety of cefiderocol, and outlines its current role in the management of CRAB infections. In vitro surveillance …

Framework For Quality Assurance Of Ultrahigh Dose Rate Clinical Trials Investigating Flash Effects And Current Technology Gaps, Wei Zou, Tianyu Zhao, Walter R Bosch, Et Al.

2020-Current year OA Pubs

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology …

Refractory Mogamulizumab-Associated Rash Responding To An Oral Janus Kinase Inhibitor, Carine M Lama, Miguel A Hernandez-Rovira, Neha Mehta-Shah, Aaron Russell, Amy C M Musiek

2020-Current year OA Pubs

No abstract provided.

Positron Emission Tomography And Magnetic Resonance Imaging Methods And Datasets Within The Dominantly Inherited Alzheimer Network (Dian), Nicole S Mckay, Brian A Gordon, Russ C Hornbeck, Aylin Dincer, Shaney Flores, Sarah J Keefe, Nelly Joseph-Mathurin, Peter R Millar, Beau M Ances, Charles D Chen, Alisha Daniels, Diana A Hobbs, Kelley Jackson, Deborah Koudelis, Parinaz Massoumzadeh, Austin Mccullough, Michael L Nickels, Farzaneh Rahmani, Laura Swisher, Qing Wang, Carlos Cruchaga, Jason Hassenstab, Celeste Karch, Eric Mcdade, Richard J Perrin, Chengjie Xiong, John C Morris, Randall J Bateman, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during …

Anesthesia Clinical Workload Estimated From Electronic Health Record Documentation Vs Billed Relative Value Units, Sunny S Lou, Laura R Baratta, Daphne Lew, Derek Harford, Michael S Avidan, Thomas Kannampallil

2020-Current year OA Pubs

IMPORTANCE: Accurate measurements of clinical workload are needed to inform health care policy. Existing methods for measuring clinical workload rely on surveys or time-motion studies, which are labor-intensive to collect and subject to biases.

OBJECTIVE: To compare anesthesia clinical workload estimated from electronic health record (EHR) audit log data vs billed relative value units.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of anesthetic encounters occurring between August 26, 2019, and February 9, 2020, used data from 8 academic hospitals, community hospitals, and surgical centers across Missouri and Illinois. Clinicians who provided anesthetic services for at least 1 surgical encounter were …

Engaging Adolescents In Using Online Patient Portals, Bryan A Sisk, Alison L Antes, Christine Bereitschaft, Madi Enloe, Sunny Lin, Meghana Srinivas, Fabienne Bourgeois, James M Dubois

2020-Current year OA Pubs

IMPORTANCE: Many health care systems offer adolescents access to health information through online patient portals, but few studies have explored how to engage adolescents in using and benefiting from online portals.

OBJECTIVE: To determine how US children's hospitals have attempted to encourage adolescent portal use, barriers to engaging adolescents, and ideal future goals for engagement.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study performed structured qualitative interviews with informatics administrators from children's hospitals across the US between February and July 2022. Informatics administrators were employed by US health care systems that managed a children's hospital with at least 50 dedicated pediatrics …

Effect Of Fecal Microbiota, Live-Jslm (Rebyota [Rbl]) On Health-Related Quality Of Life In Patients With Recurrent Clostridioides Difficile Infection: Results From The Punch Cd3 Clinical Trial, Kevin W Garey, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana García-Horton, Mirko Fillbrunn, Hongjue Wang, Glenn S Tillotson, Lindy L Bancke, Paul Feuerstadt

2020-Current year OA Pubs

BACKGROUND: Recurrence of

METHODS: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3). The disease-specific

RESULTS: Findings were analyzed in a total of 185 patients (RBL, n = 128 [69.2%]; placebo, n = 57 [30.8%]) with available Cdiff32 data. Patients from both arms showed significant improvements in Cdiff32 scores relative to baseline across all outcomes and at all time points (all

CONCLUSIONS: In a phase 3 double-blinded clinical trial, RBL-treated patients reported more substantial and sustained disease-specific HRQL improvements than placebo-treated patients.

CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).

Association Of Soluble Markers Of Inflammation With Peri-Coronary Artery Inflammation In People With And Without Hiv Infection And Without Cardiovascular Disease, Michael L Freeman, Mian B Hossain, Shana A B Burrowes, Jean Jeudy, Ryan Bui, Daniela Moisi, Sarah E Mitchell, Mariam Khambaty, Robert G Weiss, Michael M Lederman, Shashwatee Bagchi

2020-Current year OA Pubs

BACKGROUND: Inflammation is linked to elevated cardiovascular disease (CVD) risk in people with HIV (PWH) on antiretroviral therapy (ART). Fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts CVD risk in HIV-uninfected persons. Whether FAI is associated with soluble inflammatory markers is unknown.

METHODS: Plasma levels of inflammatory markers were measured in 58 PWH and 16 controls without current symptoms or prior known CVD who underwent coronary computed tomography angiography and had FAI measurements. A cross-sectional analysis was performed, and associations of markers with FAI values of the right coronary artery (RCA) and left anterior descending …

Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao

2020-Current year OA Pubs

IMPORTANCE: Alcohol consumption is associated with adverse oncologic and treatment outcomes among individuals with a diagnosis of cancer. As a key modifiable behavioral factor, alcohol consumption patterns among cancer survivors, especially during treatment, remain underexplored in the United States.

OBJECTIVE: To comprehensively characterize alcohol consumption patterns among US cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from May 6, 2018, to January 1, 2022, from the National Institutes of Health All of Us Research Program, a diverse US cohort with electronic health record (EHR) linkage, and included 15 199 participants who reported a cancer diagnosis and 1839 …

Changing Faces: Factors Associated With The Intention To Pursue Plastic Surgery And Practice In Underserved Areas, Mytien Nguyen, Annette Kaminaka, Nicholas N. Brutus, Luis A. Gonzalez, Amit Ratanpal, Michael Alperovich, Donna B. Jeffe, Ashar Ata, Hyacinth R. C. Mason, Paris D. Butler

2020-Current year OA Pubs

UNLABELLED: Improving the number of plastic and reconstructive surgeons who provide care to patients in underserved communities is critical to achieving health equity. We aimed to identify factors associated with graduating medical students' intentions to pursue plastic surgery and practice in underserved areas.

METHODS: De-identified data for US medical school graduates were obtained from the Association of American Medical Colleges for students who matriculated in academic years 2007-2008 and 2011-2012. Data collected included self-reported demographic and future practice intentions. Multivariate analysis was conducted to determine indicators of students' interest in plastic surgery, and their intention to practice in underserved areas. …

The Flipped Classroom Approach In A Pediatric Anesthesiology Fellowship Curriculum, Rachel Moquin, Megan Dewey, Ashley Weinhold, Ottavia Green, Anna Rebecca Young

2020-Current year OA Pubs

Background The flipped classroom approach is well documented to enhance medical education outcomes. Additionally, both the need for online learning materials and the increased demand for medical professionals during the COVID-19 pandemic has made this approach more relevant. The pediatric anesthesiology fellowship curriculum at one institution transitioned from a traditional classroom model to a flipped classroom approach to optimize the educational experience and support learner well-being. Approach Utilizing the American Board of Anesthesiology (ABA) and Accreditation Council for Graduate Medical Education (ACGME) content outlines, a novel, comprehensive curriculum was developed focusing on core clinical material and board review with the …

Long-Term Endothelial Safety Profile With Istent Inject In Patients With Open-Angle Glaucoma, Iqbal Ike K Ahmed, Arsham Sheybani, Ticiana De Francesco, Jonathan H Lass, Beth Ann Benetz, Thomas W Samuelson, Dale Usner, L Jay Katz

2020-Current year OA Pubs

PURPOSE: To report 5-year postoperative safety data of iStent inject, including overall stability, endothelial cell density (ECD), and endothelial cell loss (ECL) in patients with mild-to-moderate primary open-angle glaucoma (POAG).

DESIGN: 5-year follow-up safety study of the prospective, randomized, single-masked, concurrently controlled, multicenter iStent inject pivotal trial.

METHODS: In this 5-year follow-up safety study of the 2-year iStent inject pivotal randomized controlled trial, patients receiving iStent inject placement and phacoemulsification or phacoemulsification alone were studied for the incidence of clinically relevant complications associated with iStent inject placement and stability. Corneal endothelial endpoints were mean change in ECD from screening and …

The Dusp Domain Of Pseudophosphatase Mk-Styx Interacts With G3bp1 To Decrease Stress Granules, Jonathan Smailys, Fei Jiang, Tatiana Prioleau, Kylan Kelley, Olivia Mitchell, Samah Nour, Lina Ali, William Buchser, Lynn Zavada, Shantá D Hinton

2020-Current year OA Pubs

Mitogen activated protein kinase phosphoserine/threonine/tyrosine-binding protein (MK-STYX) is a dual specificity (DUSP) member of the protein tyrosine phosphatase family. It is a pseudophosphatase, which lacks the essential amino acids histidine and cysteine in the catalytic active signature motif (HCX

Hgf/C-Met Pathway Inhibition Combined With Chemotherapy Increases Cytotoxic T-Cell Infiltration And Inhibits Pancreatic Tumour Growth And Metastasis, Alpha Raj Mekapogu, Zhihong Xu, Srinivasa Pothula, Chamini Perera, Tony Pang, S M Zahid Hosen, Vishnu Damalanka, James Janetka, David Goldstein, Romano Pirola, Jeremy Wilson, Minoti Apte

2020-Current year OA Pubs

Pancreatic cancer (PC) is a deadly cancer with a high mortality rate. The unique characteristics of PC, including desmoplasia and immunosuppression, have made it difficult to develop effective treatment strategies. Pancreatic stellate cells (PSCs) play a crucial role in the progression of the disease by interacting with cancer cells. One of the key mediators of PSC - cancer cell interactions is the hepatocyte growth factor (HGF)/c-MET pathway. Using an immunocompetent in vivo model of PC as well as in vitro experiments, this study has shown that a combined approach using HGF/c-MET inhibitors to target stromal-tumour interactions and chemotherapy (gemcitabine) to …

Androgen Deprivation And Radiotherapy With Or Without Docetaxel For Localized High-Risk Prostate Cancer: Long-Term Follow-Up From The Randomized Nrg Oncology Rtog 0521 Trial, Oliver Sartor, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.

OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT.

DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. …

Effects Of A Lpg Stove And Fuel Intervention On Adverse Maternal Outcomes: A Multi-Country Randomized Controlled Trial Conducted By The Household Air Pollution Intervention Network (Hapin), Ashley Younger, Ashley Toenjes, Lindsay Underhill, Et Al.

2020-Current year OA Pubs

Household air pollution from solid cooking fuel use during gestation has been associated with adverse pregnancy and birth outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial of free liquefied petroleum gas (LPG) stoves and fuel in Guatemala, Peru, India, and Rwanda. A primary outcome of the main trial was to report the effects of the intervention on infant birth weight. Here we evaluate the effects of a LPG stove and fuel intervention during pregnancy on spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality compared to women who continued to use solid …

Symbiotic Bacteria, Immune-Like Sentinel Cells, And The Response To Pathogens In A Social Amoeba, Trey J. Scott, Tyler J. Larsen, Debra A. Brock, So Yeon Stacey Uhm, David C. Queller, Joan E. Strassmann

2020-Current year OA Pubs

Some endosymbionts living within a host must modulate their hosts' immune systems in order to infect and persist. We studied the effect of a bacterial endosymbiont on a facultatively multicellular social amoeba host. Aggregates of the amoeba

Cardiovascular And Metabolic Health Is Associated With Functional Brain Connectivity In Middle-Aged And Older Adults: Results From The Human Connectome Project-Aging Study, Barnaly Rashid, Matthew F Glasser, Thomas Nichols, David Van Essen, Meher R Juttukonda, Nadine A Schwab, Douglas N Greve, Essa Yacoub, Allison Lovely, Melissa Terpstra, Michael P Harms, Susan Y Bookheimer, Beau M Ances, David H Salat, Steven E Arnold

2020-Current year OA Pubs

Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36-90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and …

Perceived Utility Of Intracranial Pressure Monitoring In Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis And Recommendations, Randall M. Chesnut, Michael Diringer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed.

OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion.

METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). …

Epigenetic Age Acceleration Mediates The Relationship Between Neighborhood Deprivation And Pain Severity In Adults With Or At Risk For Knee Osteoarthritis Pain, Pamela Jackson, Burel R Goodin, Et Al.

2020-Current year OA Pubs

An estimated 250 million people worldwide suffer from knee osteoarthritis (KOA), with older adults having greater risk. Like other age-related diseases, residents of high-deprivation neighborhoods experience worse KOA pain outcomes compared to their more affluent neighbors. The purpose of this study was to examine the relationship between neighborhood deprivation and pain severity in KOA and the influence of epigenetic age acceleration (EpAA) on that relationship. The sample of 128 participants was mostly female (60.9%), approximately half non-Hispanic Black (49.2%), and had a mean age of 58 years. Spearman bivariate correlations revealed that pain severity positively correlated with EpAA (ρ = …

Sars-Cov-2 Uses Cd4 To Infect T Helper Lymphocytes, Natalia S Brunetti, Louis-Marie Bloyet, Spencer Stumpf, Marjorie C Pontelli, Sean Whelan, Alessandro S Farias, Et Al.

2020-Current year OA Pubs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4

Mettl1 Promotes Tumorigenesis Through Trna-Derived Fragment Biogenesis In Prostate Cancer, Raquel García-Vílchez, Sabine Dietmann, Et Al.

2020-Current year OA Pubs

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N

Subunit Gating Resulting From Individual Protonation Events In Kir2 Channels, Grigory Maksaev, Michael Bründl-Jirout, Anna Stary-Weinzinger, Eva-Maria Zangerl-Plessl, Sun-Joo Lee, Colin G Nichols

2020-Current year OA Pubs

Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K

Using The Sociotechnical Model To Conduct A Focused Usability Assessment Of A Breast Reconstruction Decision Tool, Randi Foraker, Crystal Phommasathit, Kaleigh Clevenger, Clara Lee, Jessica Boateng, Napiera Shareef, Mary C Politi

2020-Current year OA Pubs

INTRODUCTION: BREASTChoice is a web-based breast reconstruction decision aid. The previous clinical trial-prior to the adaptation of this refined tool in which we explored usability-measured decision quality, quality of life, patient activation, shared decision making, and treatment choice. The current usability study was designed to elicit patients' and clinicians' perspectives on barriers and facilitators for implementing BREASTChoice into the clinical workflow.

METHODS: We conducted qualitative interviews with patients and clinicians from two Midwestern medical specialty centers from August 2020 to April 2021. Interviews were first double coded until coders achieved a kappa > 0.8 and percent agreement > 95%, then were coded …