Medicine and Health Sciences Commons^™

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 …

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.

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

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.

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 …

Whole-Exome Sequencing Prioritizes Candidate Genes For Hereditary Cataract In The Emory Mouse Mutant, Thomas M Bennett, Yuefang Zhou, Kacie J Meyer, Michael G Anderson, Alan Shiels

2020-Current year OA Pubs

The Emory cataract (Em) mouse mutant has long been proposed as an animal model for age-related or senile cataract in humans-a leading cause of visual impairment. However, the genetic defect(s) underlying the autosomal dominant Em phenotype remains elusive. Here, we confirmed development of the cataract phenotype in commercially available Em/J mice [but not ancestral Carworth Farms White (CFW) mice] at 6-8 months of age and undertook whole-exome sequencing of candidate genes for Em. Analysis of coding and splice-site variants did not identify any disease-causing/associated mutations in over 450 genes known to underlie inherited and age-related forms of cataract and other …

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

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

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 …

Urinary Tract Infections Trigger Synucleinopathy Via The Innate Immune Response, Wouter Peelaerts, Scott J Hultgren, Tom J Hannan, Et Al.

2020-Current year OA Pubs

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also …

Association Of Sex With Neurobehavioral Markers Of Executive Function In 2-Year-Olds At High And Low Likelihood Of Autism, Tanya St John, Natasha Marrus, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored.

OBJECTIVE: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL …

Tumor-Derived Interleukin-1Α And Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis, Derek A. G. Barisas, Ashraf Ul Kabir, Jun Wu, Karen Krchma, Minseo Kim, Madhav Subramanian, Bernd H. Zinselmeyer, Colin L. Stewart, Kyunghee Choi

2020-Current year OA Pubs

Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, …

A Randomized, Open-Label Study Of The Tolerability And Efficacy Of One Or Three Daily Doses Of Ivermectin Plus Diethylcarbamazine And Albendazole (Ida) Versus One Dose Of Ivermectin Plus Albendazole (Ia) For Treatment Of Onchocerciasis, Nicholas O. Opoku, Nicole Fetcho, Kerstin Fischer, Peter U. Fischer, Charles W. Goss, Augustine R. Hong, Daphne Lew, Gary J. Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis.

METHODS AND FINDINGS: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with …

Effect Of Trainee Level On Surgical Time And Postoperative Complications Of Anterior Cruciate Ligament Reconstruction, Priyanka Parameswaran, Yash Tarkunde, J. Sam Broughton, Michael G. Rizzo, Jake H. Goldfarb, Robert H. Brophy

2020-Current year OA Pubs

PURPOSE: The objective of this study was to investigate the association between trainee level and surgical time and postoperative complications of anterior cruciate ligament reconstruction (ACLR).

METHODS: A retrospective chart review of patients who underwent ACLR at an academic orthopaedic ambulatory surgery center collected demographic and clinical information, including the number of trainees present and trainee level. Unadjusted and adjusted regression analyses assessed the association between trainee number and level with surgical time (time from skin incision to closure) and postoperative complications.

RESULTS: Of 799 patients in this study operated on by one of five academic sports surgeons, 87% had …

Influence Of Environmental Temperature And Heatwaves On Surgical Site Infection After Hip And Knee Arthroplasty: A Nationwide Study, L Damonti, A Atkinson, L Fontannaz, J P Burnham, P Jent, N Troillet, A Widmer, J Marschall, For Swissnoso, National Center For Infection Control

2020-Current year OA Pubs

BACKGROUND: Previous studies reported higher incidence of surgical site infection (SSI) after procedures performed in summer or with high temperatures. However, no study used detailed climate data to assess this risk after hip and knee arthroplasty, and no study specifically investigated the role of heatwaves.

AIM: To assess the impact of higher environmental temperatures and heatwaves on SSI rates after hip and knee arthroplasty.

METHODS: Data on hip and knee arthroplasty procedures performed between January 2013 and September 2019 in hospitals participating in the Swiss SSI surveillance were linked to climate data extracted from weather stations located in their vicinity. …

Polygenic Risk Score Penetrance & Recurrence Risk In Familial Alzheimer Disease, Min Qiao, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To compute penetrance and recurrence risk using a genome-wide PRS (including and excluding the APOE region) in families with Alzheimer's disease.

METHODS: Genotypes from the National Institute on Aging Late-Onset Alzheimer's Disease Family-Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE-ε4 carriers …

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 …

Immunotherapeutic Approach To Reduce Senescent Cells And Alleviate Senescence-Associated Secretory Phenotype In Mice, Niraj Shrestha, Mark Foster, Lynne Marsala, Pamela Wong, Celia C Cubitt, Jennifer A Foltz, Jennifer Tran, Timothy Schappe, Melissa M Berrien-Elliott, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and …

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 …

Comparing Genomic And Epigenomic Features Across Species Using The Washu Comparative Epigenome Browser, Xiaoyu Zhuo, Silas Hsu, Deepak Purushotham, Prashant Kumar Kuntala, Jessica K Harrison, Alan Y Du, Samuel Chen, Daofeng Li, Ting Wang

2020-Current year OA Pubs

Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over …

Steady-State Memory-Phenotype Conventional Cd4+ T Cells Exacerbate Autoimmune Neuroinflammation In A Bystander Manner Via The Bhlhe40/Gm-Csf Axis, Min-Ji Cho, Hong-Gyun Lee, Jae-Won Yoon, Gil-Ran Kim, Ja-Hyun Koo, Reshma Taneja, Brian T Edelson, You Jeong Lee, Je-Min Choi

2020-Current year OA Pubs

Memory-phenotype (MP) CD4

Effects Of A Combination Economic Empowerment And Family Strengthening Intervention On Psychosocial Well-Being Among Ugandan Adolescent Girls And Young Women: Analysis Of A Cluster Randomized Controlled Trial (Suubi4her), Lindsey M Filiatreau, Nhial Tutlam, Rachel Brathwaite, William Byansi, Flavia Namuwonge, Abel Mwebembezi, Ozge Sensoy-Bahar, Proscovia Nabunya, Torsten B Neilands, Patricia Cavazos-Rehg, Mary Mckay, Fred M Ssewamala

2020-Current year OA Pubs

PURPOSE: Economic empowerment and family strengthening interventions have shown promise for improving psychosocial well-being in a range of populations. This study investigates the effect of a combination economic and family strengthening intervention on psychosocial well-being among Ugandan adolescent girls and young women (AGYW).

METHODS: We harnessed data from a three-arm cluster randomized controlled trial among AGYW aged 14-17 years in 47 Ugandan secondary schools. Schools were randomized to either a youth development account intervention (YDA) [N = 16 schools], YDA plus a multiple family group intervention (YDA + MFG) [N = 15 schools], or bolstered standard of care (BSOC) [N …

Circulating Markers Of Microbial Translocation And Host Response To Bacteria With Risk Of Colorectal Cancer: A Prospective, Nested Case-Control Study In Men, Mengyao Shi, Xiaoyu Zong, Jinhee Hur, Brenda M Birmann, Otoniel Martinez-Maza, Marta Epeldegui, Andrew T Chan, Edward L Giovannucci, Yin Cao

2020-Current year OA Pubs

BACKGROUND: Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited.

METHODS: We conducted a prospective, nested case-control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993-2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 …

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. …

Pregnancy And Neonatal Outcomes Among Women With Early-Onset Colorectal Cancer: A Nationwide Case-Control Study, Yin Cao, Stephanie Zhao, Tomas S Bexelius, Jonas Söderling, Mengyao Shi, Bjorn Roelstraete, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

BACKGROUND: Early-onset colorectal cancer has risen worldwide, leaving more women with colorectal cancer at reproductive ages. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among women with early-onset colorectal cancer.

METHODS: We conducted a nationwide, matched case-control study of maternal/pregnancy outcomes including pre-eclampsia and Cesarean delivery (C-section) as well as neonatal outcomes including preterm birth among 207 births in women with early-onset colorectal cancer (ages 18-49) and 1019 births in women without colorectal cancer in Sweden (1992-2019). Early-onset colorectal cancer cases were identified through the Cancer Register, and outcome data were retrieved through linkage to Medical …

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, …

Propranolol Reduces Ifn-Γ Driven Pd-L1 Immunosuppression And Improves Anti-Tumour Immunity In Ovarian Cancer, M Falcinelli, G Al-Hity, S Baron, M Mampay, M C Allen, M Samuels, W Jones, C Cilibrasi, Renee L Flaherty, G Giamas, P H Thaker, M S Flint

2020-Current year OA Pubs

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and …

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.

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 …

Bk Channels Of Five Different Subunit Combinations Underlie The De Novo Kcnma1 G375r Channelopathy, Yanyan Geng, Ping Li, Alice Butler, Bill Wang, Lawrence Salkoff, Karl L Magleby

2020-Current year OA Pubs

The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, …