Medicine and Health Sciences Commons^™

Structural And Biophysical Characterization Of The Secreted, Β-Helical Adhesin Etpa Of Enterotoxigenic Escherichia Coli, Clifford Manyo Ntui, James M. Fleckenstein, Wolf-Dieter Schubert

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) is a diarrhoeal pathogen associated with high morbidity and mortality especially among young children in developing countries. At present, there is no vaccine for ETEC. One candidate vaccine antigen, EtpA, is a conserved secreted adhesin that binds to the tips of flagellae to bridge ETEC to host intestinal glycans. EtpA is exported through a Gram-negative, two-partner secretion system (TPSS, type Vb) comprised of the secreted EtpA passenger (TpsA) protein and EtpB (TpsB) transporter that is integrated into the outer bacterial membrane. TpsA proteins share a conserved, N-terminal TPS domain followed by an extensive C-terminal domain with …

Eating Disorders In Weight-Related Therapy (Edit): Protocol For A Systematic Review With Individual Participant Data Meta-Analysis Of Eating Disorder Risk In Behavioural Weight Management, Hiba Jebeile, Denise E. Wilfley, Et Al.

2020-Current year OA Pubs

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of …

Evaluation Of A Large-Scale Health Department Naloxone Distribution Program: Per Capita Naloxone Distribution And Overdose Morality, Caroline E. Freiermuth, Rachel M. Ancona, Jennifer L. Brown, Brittany E. Punches, Shawn A. Ryan, Tim Ingram, Michael S. Lyons

2020-Current year OA Pubs

OBJECTIVES: To report per-capita distribution of take-home naloxone to lay bystanders and evaluate changes in opioid overdose mortality in the county over time.

METHODS: Hamilton County Public Health in southwestern Ohio led the program from Oct 2017-Dec 2019. Analyses included all cartons distributed within Hamilton County or in surrounding counties to people who reported a home address within Hamilton County. Per capita distribution was estimated using publicly available census data. Opioid overdose mortality was compared between the period before (Oct 2015-Sep 2017) and during (Oct 2017-Sep 2019) the program.

RESULTS: A total of 10,416 cartons were included for analyses, with …

Simulation-Free Radiation Therapy: An Emerging Form Of Treatment Planning To Expedite Plan Generation For Patients Receiving Palliative Radiation Therapy, Joshua P Schiff, Tianyu Zhao, Yi Huang, Baozhou Sun, Geoffrey D Hugo, Matthew B Spraker, Christopher D Abraham

2020-Current year OA Pubs

PURPOSE: Herein we report the clinical and dosimetric experience for patients with metastases treated with palliative simulation-free radiation therapy (SFRT) at a single institution.

METHODS AND MATERIALS: SFRT was performed at a single institution. Multiple fractionation regimens were used. Diagnostic imaging was used for treatment planning. Patient characteristics as well as planning and treatment time points were collected. A matched cohort of patients with conventional computed tomography simulation radiation therapy (CTRT) was acquired to evaluate for differences in planning and treatment time. SFRT dosimetry was evaluated to determine the fidelity of SFRT. Descriptive statistics were calculated on all variables and …

Patterns Of Utilization And Clinical Adoption Of 0.35 Tesla Mr-Guided Radiation Therapy In The United States - Understanding The Transition To Adaptive, Ultra-Hypofractionated Treatments, Michael D Chuong, Lauren E Henke, Et Al.

2020-Current year OA Pubs

PURPOSE/OBJECTIVE: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology.

MATERIALS/METHODS: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems.

RESULTS: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details …

Substance Use Treatment Utilization Among Women With And Without Human Immunodeficiency Virus, Ayako W Fujita, Aditi Ramakrishnan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Substance use (SU) contributes to poor health outcomes, yet limited data exist to inform strategies to optimize SU treatment among persons with human immunodeficiency virus (HIV). We describe SU and SU treatment utilization among women with and without HIV in the Women's Interagency HIV Study (WIHS).

METHODS: We included data from women enrolled in WIHS from 2013 to 2020. Current SU was self-reported, nonmedical use of drugs in the past year, excluding use of only marijuana. SU treatment utilization was self-reported use of a drug treatment program in the past year. Multivariable regression models were used to investigate associations …

Nonalcoholic Fatty Liver Disease Is A Risk Factor For Thiopurine Hepatotoxicity In Crohn's Disease, Alvin T George, Matthew Glover, Quazim Alayo, Maria Zulfiqar, Daniel R Ludwig, Matthew A Ciorba, Scott Mchenry, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

METHODS: In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a …

Prevalence Of Bourbon And Heartland Viruses In Field Collected Ticks At An Environmental Field Station In St. Louis County, Missouri, Usa, Ishmael D. Aziati, Derek Mcfarland Jr., Avan Antia, Astha Joshi, Anahi Aviles-Gamboa, Preston Lee, Houda Harastani, David Wang, Solny A. Adalsteinsson, Adrianus C M Boon

2020-Current year OA Pubs

Heartland and Bourbon viruses are pathogenic tick-borne viruses putatively transmitted by Amblyomma americanum, an abundant tick species in Missouri. To assess the prevalence of these viruses in ticks, we collected 2778 ticks from eight sampling sites at Tyson Research Center, an environmental field station within St. Louis County and close to the City of St. Louis, from May - July in 2019 and 2021. Ticks were pooled according to life stage and sex, grouped by year and sampling site to create 355 pools and screened by RT-qPCR for Bourbon and Heartland viruses. Overall, 14 (3.9%) and 27 (7.6%) of the …

Circulatory Arrest For Traumatic Brachiocephalic Artery Pseudoaneurysm Repair, Conor F Hynes, Kunal D Kotkar

2020-Current year OA Pubs

Blunt traumatic injuries to the brachiocephalic artery require surgical management. The operative technique used depends on the location of the injury, the patient's hemodynamic stability, and the surgeon's experience. Perfusion strategy can facilitate vascular control of the aortic arch and branch vessels. This report presents an urgent repair of a proximal posterior blunt traumatic brachiocephalic artery injury under circulatory arrest, with an excellent outcome.

Efficacy Of Laser Interstitial Thermal Therapy For Biopsy-Proven Radiation Necrosis In Radiographically Recurrent Brain Metastases, Michael Chan, Albert H Kim, Eric Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.

METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.

RESULTS: Ninety patients met …

Health Utilities And Quality-Adjusted Life Years For Patients With Amyotrophic Lateral Sclerosis Receiving Reldesemtiv Or Placebo In Fortitude-Als, Paulos Gebrehiwet, Lisa Meng, Stacy A Rudnicki, Phil Sarocco, Jenny Wei, Andrew A Wolff, Michael Butzner, Adriano Chiò, Jinsy A Andrews, Angela Genge, Dyfrig A Hughes, Carlayne E Jackson, Noah Lechtzin, Timothy M Miller, Jeremy M Shefner

2020-Current year OA Pubs

AIMS: To estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving

MATERIALS AND METHODS: We performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated

RESULTS: The full analysis set consisted of 456 patients (

CONCLUSIONS: This post hoc analysis of FORTITUDE-ALS suggests that

CLINICALTRIALS.GOV IDENTIFIER: NCT03160898.

Mri-Based Classification Of Idh Mutation And 1p/19q Codeletion Status Of Gliomas Using A 2.5d Hybrid Multi-Task Convolutional Neural Network, Satrajit Chakrabarty, Pamela Lamontagne, Joshua Shimony, Daniel S Marcus, Aristeidis Sotiras

2020-Current year OA Pubs

BACKGROUND: IDH mutation and 1p/19q codeletion status are important prognostic markers for glioma that are currently determined using invasive procedures. Our goal was to develop artificial intelligence-based methods to noninvasively determine molecular alterations from MRI.

METHODS: Pre-operative MRI scans of 2648 glioma patients were collected from Washington University School of Medicine (WUSM;

RESULTS: For IDH, the best-performing model achieved areas under the receiver operating characteristic (AUROC) of 0.925, 0.874, 0.933 and areas under the precision-recall curves (AUPRC) of 0.899, 0.702, 0.853 on the internal, WUSM, and EGD test sets, respectively. For 1p/19q, the best model achieved AUROCs of 0.782, 0.754, …

Aberrant T-Cell Exhaustion In Severe Combined Immunodeficiency Survivors With Poor T-Cell Reconstitution After Transplantation, Roxane Labrosse, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

BACKGROUND: Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes.

OBJECTIVE: We hypothesized that CD4

METHODS: We analyzed markers of exhaustion in blood samples from 61 SCID patients at a median of 10.4 years after HCT.

RESULTS: Compared to post-HCT SCID patients with normal CD4

CONCLUSIONS: Recipients of unconditioned HCT for SCID may develop late post-HCT T-cell exhaustion as a result of diminished production of T-lineage …

Necrotic Cardiac Myocytes Skew Macrophage Polarization Towards A Classically Activated Phenotype, Wenlong Jiang, Luigi Adamo, Kenji Lim, Scot J Matkovich, Sarah Evans, Cibele Rocha-Resende, Douglas L. Mann

2020-Current year OA Pubs

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide …

The History And Organization Of The Workshop On Population And Speciation Genomics, Julia M I Barth, Scott A Handley, Daniel Kintzl, Guy Leonard, Milan Malinsky, Michael Matschiner, Britta S Meyer, Walter Salzburger, Jan Stefka, Emiliano Trucchi

2020-Current year OA Pubs

With the advent of high-throughput genome sequencing, bioinformatics training has become essential for research in evolutionary biology and related fields. However, individual research groups are often not in the position to teach students about the most up-to-date methodology in the field. To fill this gap, extended bioinformatics courses have been developed by various institutions and provide intense training over the course of two or more weeks. Here, we describe our experience with the organization of a course in one of the longest-running extended bioinformatics series of workshops, the Evomics Workshop on Population and Speciation Genomics that takes place biennially in …

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Amplitudes Of Resting-State Functional Networks - Investigation Into Their Correlates And Biophysical Properties, Soojin Lee, Janine D Bijsterbosch, Fidel Alfaro Almagro, Lloyd Elliott, Paul Mccarthy, Bernd Taschler, Roser Sala-Llonch, Christian F Beckmann, Eugene P Duff, Stephen M Smith, Gwenaëlle Douaud

2020-Current year OA Pubs

Resting-state fMRI studies have shown that multiple functional networks, which consist of distributed brain regions that share synchronised spontaneous activity, co-exist in the brain. As these resting-state networks (RSNs) have been thought to reflect the brain's intrinsic functional organization, intersubject variability in the networks' spontaneous fluctuations may be associated with individuals' clinical, physiological, cognitive, and genetic traits. Here, we investigated resting-state fMRI data along with extensive clinical, lifestyle, and genetic data collected from 37,842 UK Biobank participants, with the object of elucidating intersubject variability in the fluctuation amplitudes of RSNs. Functional properties of the RSN amplitudes were first examined by …

Expanded Analysis Of High-Grade Astrocytoma With Piloid Features Identifies An Epigenetically And Clinically Distinct Subtype Associated With Neurofibromatosis Type 1, Patrick J Cimino, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

High-grade astrocytoma with piloid features (HGAP) is a recently recognized glioma type whose classification is dependent on its global epigenetic signature. HGAP is characterized by alterations in the mitogen-activated protein kinase (MAPK) pathway, often co-occurring with CDKN2A/B homozygous deletion and/or ATRX mutation. Experience with HGAP is limited and to better understand this tumor type, we evaluated an expanded cohort of patients (n = 144) with these tumors, as defined by DNA methylation array testing, with a subset additionally evaluated by next-generation sequencing (NGS). Among evaluable cases, we confirmed the high prevalence CDKN2A/B homozygous deletion, and/or ATRX mutations/loss in this tumor …

Predictors Of Nonadherence Among Patients With Infectious Complications Of Substance Use Who Are Discharged On Parenteral Antimicrobial Therapy, Shivakumar Narayanan, Patrick R Ching, Edward C Traver, Nivya George, Anthony Amoroso, Shyam Kottilil

2020-Current year OA Pubs

BACKGROUND: The management of invasive infections related to substance use disorder (SUD) needing parenteral antimicrobial therapy is challenging and may have poor treatment outcomes including nonadherence and lack of completion of parenteral antimicrobial therapy.

METHODS: In this retrospective cohort of 201 patients with invasive infections related to SUD, we looked at frequency and determinants of unfavorable outcomes including nonadherence.

RESULTS: Seventy-nine percent of patients with SUD-related infection completed parenteral antibiotic therapy in skilled nursing facilities. A total of 21.5% of patient episodes had documentation of nonadherence. Nonadherence was higher in patients with active injection drug use (IDU) (28.5% versus 15% …

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Armin Ghobadi, Amanda Cashen, Et Al.

2020-Current year OA Pubs

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

A Single-Molecule Method For Measuring Fluorophore Labeling Yields For The Study Of Membrane Protein Oligomerization In Membranes, Melanie Ernst, Tugba N. Ozturk, Janice L. Robertson

2020-Current year OA Pubs

Membrane proteins are often observed as higher-order oligomers, and in some cases in multiple stoichiometric forms, raising the question of whether dynamic oligomerization can be linked to modulation of function. To better understand this potential regulatory mechanism, there is an ongoing effort to quantify equilibrium reactions of membrane protein oligomerization directly in membranes. Single-molecule photobleaching analysis is particularly useful for this as it provides a binary readout of fluorophores attached to protein subunits at dilute conditions. However, any quantification of stoichiometry also critically requires knowing the probability that a subunit is fluorescently labeled. Since labeling uncertainty is often unavoidable, we …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Higher Dose Oral Fluconazole For The Treatment Of Aids-Related Cryptococcal Meningitis (Hiflac)--Report Of A5225, A Multicentre, Phase I/Ii, Two-Stage, Dose-Finding, Safety, Tolerability And Efficacy Randomised, Amphotericin B-Controlled Trial Of The Aids Clinical Trials Group, Umesh G. Lalloo, David B. Clifford, Et Al.

2020-Current year OA Pubs

BACKGROUND: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.

METHODS: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant …

Small Molecule Inhibiting Microglial Nitric Oxide Release Could Become A Potential Treatment For Neuroinflammation, Philipp Jordan, Amanda Costa, Et Al.

2020-Current year OA Pubs

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or …

The Circular Rna Landscape In Multiple Sclerosis: Disease-Specific Associated Variants And Exon Methylation Shape Circular Rna Expression Profile, Giulia Cardamone, Elvezia Maria Paraboschi, Giulia Soldà, Giuseppe Liberatore, Valeria Rimoldi, Javier Cibella, Federica Airi, Veronica Tisato, Claudia Cantoni, Francesca Gallia, Donato Gemmati, Laura Piccio, Stefano Duga, Eduardo Nobile-Orazio, Rosanna Asselta

2020-Current year OA Pubs

BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs increasingly emerging as crucial actors in the pathogenesis of human diseases, including autoimmune and neurological disorders as multiple sclerosis (MS). Despite several efforts, the mechanisms regulating circRNAs expression are still largely unknown and the circRNA profile and regulation in MS-relevant cell models has not been completely investigated. In this work, we aimed at exploring the global landscape of circRNA expression in MS patients, also evaluating a possible correlation with their genetic and epigenetic background.

METHODS: We performed RNA-seq experiments on circRNA-enriched samples, derived from peripheral blood mononuclear cells (PBMCs) of …

Oral Low-Dose Naltrexone In The Treatment Of Grontal Fibrosing Alopecia And Lichen Planopilaris: An Uncontrolled Open-Label Prospective Study, Remi K. Hamel, Ling Chen, Cailin O'Connell, Caroline Mann

2020-Current year OA Pubs

Background Frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) is scarring alopecias with limited evidence supporting their treatment options. We investigated the use of low-dose naltrexone (3 mg oral daily) as adjunctive therapy in the treatment of FFA and LPP. Methods A single-center, uncontrolled open-label prospective study was performed, with 26 patients who took low-dose naltrexone for one year included in the per-protocol analysis. Both patient-reported (pruritus and burning/pain) and physician-assessed (erythema, scale, and scalp involvement) outcomes were analyzed. Results There were decreases in erythema and scale for the overall longitudinal outcomes using linear mixed effects model analysis. However, only …

Sex-Related Differences In Premature Cardiovascular Disease In Familial Hypercholesterolemia, Anandita Agarwala, Elena Deych, Laney K Jones, Amy C Sturm, Karen Aspry, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg

2020-Current year OA Pubs

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors.

OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH.

METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and …

An Analysis Of Major Target Deviations In Craniospinal Irradiation Treatment Plans For Patients With Intermediate-Risk Medulloblastoma Within A Phase 3 Clinical Trial (Children's Oncology Group Study Acns0331), Joshua P Schiff, Yimei Lee, Yu Wang, Stephanie M Perkins, Sandy K Kessel, Thomas J Fitzgerald, Nicole A Larrier, Jeff M Michalski

2020-Current year OA Pubs

PURPOSE: Craniospinal irradiation remains an essential and yet difficult part of the treatment of patients with medulloblastoma. Whereas technological advances offer promise of increased conformity, realiance on advanced technology is not without risk, and it remains critical to carefully delineate targets. We describe examples of target deviations (TDs) in craniospinal irradiation treatment plans for postoperative patients with medulloblastoma in a phase 3 clinical trial (ACNS 0331).

METHODS AND MATERIALS: The principal investigator independently performed a review of the treatment plans and portal films of enrolled patients and evaluated the plans for TDs. TDs of dose, dose uniformity, and volume were …

Glaucoma And Microglia-Induced Neuroinflammation, Makoto Ishikawa, Yukitoshi Izumi, Kota Sato, Taimu Sato, Charles F Zorumski, Hiroshi Kunikata, Toru Nakazawa

2020-Current year OA Pubs

Glaucoma is a multifactorial neurodegenerative disease characterized by a progressive optic neuropathy resulting in visual field defects. Elevated intraocular pressure (IOP) is the greatest risk factor for the development of glaucoma, and IOP reduction therapy is the only treatment currently available. However, there are many cases in which retinal degeneration progresses despite sufficient control of IOP. Therefore, it is important to elucidate the pathophysiology of glaucoma that is resistant to current IOP lowering therapies. Experiments using animal glaucoma models show the relationships between microglial neuroinflammatory responses and damage of retinal ganglion cells (RGCs). Inhibition of neuroinflammatory pathways associated with microglial …