287 results on '"Donovan, J.."'
Search Results
2. Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial
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Charles A Thornton, Richard Thomas Moxley, Katy Eichinger, Chad Heatwole, Laurence Mignon, W David Arnold, Tetsuo Ashizawa, John W Day, Gersham Dent, Matthew K Tanner, Tina Duong, Ericka P Greene, Laura Herbelin, Nicholas E Johnson, Wendy King, John T Kissel, Doris G Leung, Donovan J Lott, Daniel A Norris, Evan M Pucillo, Wendy Schell, Jeffrey M Statland, Nikia Stinson, Sub H Subramony, Shuting Xia, Kathie M Bishop, and C Frank Bennett
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Neurology (clinical) - Published
- 2023
3. From Protein Sequence to Structure: The Next Frontier in Cross‐Species Extrapolation for Chemical Safety Evaluations
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Carlie A. LaLone, Donovan J. Blatz, Marissa A. Jensen, Sara M. F. Vliet, Sally Mayasich, Kali Z. Mattingly, Thomas R. Transue, Wilson Melendez, Audrey Wilkinson, Cody W. Simmons, Carla Ng, Chengxin Zhang, and Yang Zhang
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Health, Toxicology and Mutagenesis ,Environmental Chemistry - Abstract
Computational screening for potentially bioactive molecules using advanced molecular modeling approaches including molecular docking and molecular dynamic simulation is mainstream in certain fields like drug discovery. Significant advances in computationally predicting protein structures from sequence information have also expanded the availability of structures for non-model species. Therefore, the objective of this work was to develop an analysis pipeline to harness the power of these bioinformatics approaches for cross-species extrapolation for evaluating chemical safety. The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool compares protein-sequence similarity across species for conservation of known chemical targets, providing an initial line of evidence for extrapolation of toxicity knowledge. However, with the development of structural models from tools like the Iterative Threading ASSEmbly Refinement (ITASSER), analyses of protein structural conservation can be included to add additional lines of evidence and generate protein models across species. Models generated through such a pipeline could then be used for advanced molecular modeling approaches in the context of species extrapolation. Two case examples illustrating this pipeline from SeqAPASS sequences to ITASSER generated protein structures were created for human liver fatty acid binding protein (LFABP) and androgen receptor (AR). Ninety-nine LFABP and 268 AR protein models representing diverse species, were generated and analyzed for conservation using TM-align. The results from the structural comparisons were in line with the sequence-based SeqAPASS workflow adding further evidence of LFABL and AR conservation across vertebrate species. This analysis lays the foundation for expanding the capabilities of the web-based SeqAPASS tool to include structural comparisons for species extrapolation, facilitating more rapid and efficient toxicological assessments among species with limited or no existing toxicity data. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2022;00:0-0. © 2022 SETAC.
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- 2023
4. Defining the Biologically Plausible Taxonomic Domain of Applicability of an Adverse Outcome Pathway: A Case Study Linking Nicotinic Acetylcholine Receptor Activation to Colony Death
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Marissa A. Jensen, Donovan J. Blatz, and Carlie A. LaLone
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Health, Toxicology and Mutagenesis ,Environmental Chemistry - Abstract
For the majority of developed adverse outcome pathways (AOPs), the taxonomic domain of applicability (tDOA) is typically narrowly defined with a single or a handful of species. Defining the tDOA of an AOP is critical for use in regulatory decision-making, particularly when considering protection of untested species. Structural and functional conservation are two elements that can be considered when defining the tDOA. Publicly accessible bioinformatics approaches, such as the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool, take advantage of existing and growing databases of protein sequence and structural information to provide lines of evidence toward structural conservation of key events (KEs) and KE relationships (KERs) of an AOP. It is anticipated that SeqAPASS results could readily be combined with data derived from empirical toxicity studies to provide evidence of both structural and functional conservation, to define the tDOA for KEs, KERs, and AOPs. Such data could be incorporated in the AOP-Wiki as lines of evidence toward biological plausibility for the tDOA. We present a case study describing the process of using bioinformatics to define the tDOA of an AOP using an AOP linking the activation of the nicotinic acetylcholine receptor to colony death/failure in Apis mellifera. Although the AOP was developed to gain a particular biological understanding relative to A. mellifera health, applicability to other Apis bees, as well as non-Apis bees, has yet to be defined. The present study demonstrates how bioinformatics can be utilized to rapidly take advantage of existing protein sequence and structural knowledge to enhance and inform the tDOA of KEs, KERs, and AOPs, focusing on providing evidence of structural conservation across species. Environ Toxicol Chem 2023;42:71-87. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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- 2022
5. An Ethyl Acetate Extract of Eryngium carlinae Inflorescences Attenuates Oxidative Stress and Inflammation in the Liver of Streptozotocin-Induced Diabetic Rats
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Cristian M. Trejo-Hurtado, Cinthia I. Landa-Moreno, Jenaro Lemus-De la Cruz, Donovan J. Peña-Montes, Rocío Montoya-Pérez, Rafael Salgado-Garciglia, Salvador Manzo-Avalos, Christian Cortés-Rojo, Juan Luis Monribot-Villanueva, José Antonio Guerrero-Analco, and Alfredo Saavedra-Molina
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Secondary metabolites such as flavonoids are considered to be promising in the treatment of NAFLD, which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated with regard to their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from STZ-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose-dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver TG levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.
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- 2023
6. Delayed cortical thinning in children and adolescents with prenatal alcohol exposure
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Blake A. Gimbel, Donovan J. Roediger, Abigail M. Ernst, Mary E. Anthony, Erik de Water, Bryon A. Mueller, Madeline N. Rockhold, Moss J. Schumacher, Sarah N. Mattson, Kenneth L. Jones, Kelvin O. Lim, and Jeffrey R. Wozniak
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Psychiatry and Mental health ,Medicine (miscellaneous) ,Toxicology - Published
- 2023
7. A Multi-Level Examination of Cognitive Control in Adolescents with Non-suicidal Self-Injury
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Zeynep Başgöze, Lauren Demers, Michelle Thai, Chloe A. Falke, Bryon A. Mueller, Mark B. Fiecas, Donovan J. Roediger, Kathleen M. Thomas, Bonnie Klimes-Dougan, and Kathryn R. Cullen
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General Medicine - Published
- 2023
8. Dearomatization of Heteroarenium Salts with ArBpin Reagents. Application to the Total Synthesis of a Nuphar Alkaloid
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Donovan J. Robinson, Kacey G. Ortiz, Nathan P. O’Hare, and Rashad R. Karimov
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Alkaloids ,Organic Chemistry ,Indicators and Reagents ,Salts ,Physical and Theoretical Chemistry ,Biochemistry ,Catalysis ,Nuphar - Abstract
Rhodium-catalyzed enantioselective addition of aryl and heteroaryl boron pinacol esters to pyridinium and quinolinium salts is developed for the synthesis of enantioenrichred dihydroheteroarenes. The methodology has enabled the synthesis of 2-heteroaryl-substituted dihydropyridines in high yield and ee, which provided efficient synthetic access to a nuphar alkaloid.
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- 2022
9. A Life-Cycle Framework to Manage Collaboration and Knowledge Exchange in Open Organisations
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Guertler, M, Adams, N, Caldwell, G, Donovan, J, Hopf, A, and Roberts, J
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Successful research and development requires interdisciplinary collaboration, often across organisational boundaries and for extended timeframes, such as in innovation networks or ecosystems. Open Organisation (OO) research can support collaboration and knowledge exchange in such situations. It builds on established concepts of Open Innovation through enhancing the exchange of knowledge by the exchange of humans. This paper contributes to OO research by presenting an OO lifecycle framework, which analyses evolving organisational and collaboration characteristics and resulting management needs.
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- 2022
10. Commentaries on Viewpoint: Hoping for the best, prepared for the worst: can we perform remote data collection in sport sciences?
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Julien, Louis, Sam, Bennett, Daniel J, Owens, Eve, Tiollier, Franck, Brocherie, Marcelo A. S., Carneiro, Paulo Ricardo P., Nunes, Bruna, Costa, Pâmela, Castro-e-Souza, Luís A., Lima, Felipe, Lisboa, Gersiel, Oliveira-Júnior, Witalo, Kassiano, Edilson S., Cyrino, Fábio L., Orsatti, Arthur Henrique, Bossi, Guilherme, Matta, Géssyca, Tolomeu de Oliveira, Ferreira, Renato Melo, Everton, Rocha Soares, Bruno, Ocelli Ungheri, Matheus, Daros Pinto, James L., Nuzzo, Christopher, Latella, Daniel, van den Hoek, Alistair, Mallard, Jemima, Spathis, Justin A., DeBlauw, Stephen J., Ives, Nicholas, Ravanelli, Benjamin J., Narang, Tadej, Debevec, Liliana C., Baptista, Ana Isabel, Padrão, José, Oliveira, Jorge, Mota, Rodrigo, Zacca, Pantelis T., Nikolaidis, Donovan J., Lott, Sean C., Forbes, Korey, Cooke, Tanja, Taivassalo, Steven J., Elmer, John J., Durocher, Ricardo J., Fernandes, Gonçalo, Silva, and Mário J., Costa
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Physiology ,Physiology (medical) ,Data Collection ,Sports - Published
- 2022
11. Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes
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Blake A. Gimbel, Mary E. Anthony, Abigail M. Ernst, Donovan J. Roediger, Erik de Water, Judith K. Eckerle, Christopher J. Boys, Joshua P. Radke, Bryon A. Mueller, Anita J. Fuglestad, Steven H. Zeisel, Michael K. Georgieff, and Jeffrey R. Wozniak
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Cognitive Neuroscience ,White Matter ,Choline ,Corpus Callosum ,Pathology and Forensic Medicine ,Pregnancy ,Fetal Alcohol Spectrum Disorders ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Humans ,Female ,Neurology (clinical) ,Child ,Follow-Up Studies - Abstract
Background Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. Methods The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5 to 5 year olds with FASD. Participants in this long-term follow-up study include 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11.0 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up included measures of executive functioning and an MRI scan. Results Children who received choline had better performance on several tasks of lower-order executive function (e.g., processing speed) and showed higher white matter microstructure organization (i.e., greater axon coherence) in the splenium of the corpus callosum compared to the placebo group. Conclusions These preliminary findings, although exploratory at this stage, highlight potential long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that choline may affect white matter development, representing a potential target of choline in this population. Trial registration Prior to enrollment, this trial was registered with clinicaltrials.gov (NCT01149538) on June 23, 2010.
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- 2022
12. Evaluating Genetic Modifiers of Duchenne Muscular Dystrophy Disease Progression Using Modeling and MRI
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Alison M Barnard, David W Hammers, William T Triplett, Sarah Kim, Sean C Forbes, Rebecca J Willcocks, Michael J Daniels, Claudia R Senesac, Donovan J Lott, Ishu Arpan, William D Rooney, Richard T Wang, Stanley F Nelson, H Lee Sweeney, Krista Vandenborne, and Glenn A Walter
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Dystrophin ,Muscular Dystrophy, Duchenne ,Disease Progression ,Humans ,Exons ,Neurology (clinical) ,Magnetic Resonance Imaging ,Research Article - Abstract
Background and Objectives:Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder with a well-characterized disease phenotype but considerable interindividual heterogeneity that is not well understood. The aim of the study was to evaluate the effects of dystrophin mutations and genetic modifiers of DMD on rate and age of muscle replacement by fat.Methods:175 corticosteroid treated participants from the ImagingDMD natural history study underwent repeated magnetic resonance spectroscopy (MRS) of the vastus lateralis (VL) and soleus (SOL) to determine muscle fat fraction. MRS was performed annually in the majority of instances; however, some individuals had additional visits at 3 or 6 month intervals. Fat fraction changes over time were modeled using nonlinear mixed effects to estimate disease trajectories based on the age that the VL or SOL reached half-maximum change in fat fraction (mu) and the time required for fat fraction change (sigma). Computed mu and sigma values were evaluated for dystrophin mutations that have demonstrated the ability to lead to a mild phenotype as well as compared between different genetic polymorphism groups.Results:Participants with dystrophin gene deletions amenable to exon 8 skipping (n=4) had minimal increases in SOL fat fraction and had an increase in VL mu value by 4.4 years compared to a reference cohort (p=0.039). Participants with nonsense mutations within exons that may produce milder phenotypes (n=11) also had minimal increases in SOL and VL fat fractions. No differences in estimated fat fraction trajectories were seen for individuals amenable to exon 44 skipping (n=10). Modeling of the SPP1, LTBP4, and THBS1 genetic modifiers did not result in significant differences in muscle fat fraction trajectories between genotype groups (p>0.05); however, trends were noted for the polymorphisms associated with long-range regulation of LTBP4 and THBS1 that deserve further follow-up.Discussion:The results of this study link the historically mild phenotypes seen in individuals amenable to exon 8 skipping and with certain nonsense mutations with alterations in trajectories of lower extremity muscle replacement by fat.
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- 2022
13. Control Barrier Functions for Safe Admittance Control of a Rehabilitation Cycle for DMD
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Emily J. Griffis, Waniiku A. Makumi, Hannah M. Sweatland, Kimberly J. Stubbs, Tanja Taivassalo, Donovan J. Lott, and Warren E. Dixon
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- 2022
14. The Genomic Characterization of Two Microbacterium foliorum–Specific Bacteriophages, QuadZero and AnnaLie
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Jennifer Cook-Easterwood, Donovan J. Bethel, Irene Kurikose, and Joanna Katsanos
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Immunology and Microbiology (miscellaneous) ,Genetics ,Molecular Biology - Abstract
The microbacteriophages QuadZero and AnnaLie were isolated from soil samples from Charlotte, NC, and were classified into EA and EB clusters, respectively. QuadZero has a 40,140 base-pair double-stranded DNA genome with 62 predicted protein coding genes, whereas AnnaLie has a 41,665-bp genome with 71 predicted protein coding genes.
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- 2022
15. 266. Frontal TDCS Reduces Alcohol Relapse Rates by Increasing Connections From Left Dorsolateral Prefrontal Cortex to Addiction Networks
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Y. Jazmin Camchong, Mark Fiecas, Casey Gilmore, Matt Kushner, Erich Kummerfeld, Bryon A. Mueller, Donovan J. Roediger, and Kelvin O. Lim
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Biological Psychiatry - Published
- 2023
16. Combined Single-Cell Transcriptomics and Mitochondrial Lineage Tracing Identify IL-6 Signaling Responses in TET2 Clonal Hematopoiesis of Indeterminate Potential
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Pawan Bhat, J. Brett Heimlich, Alyssa Parker, Matthew T. Jenkins, Chad R. Potts, Jessica Ulloa, Alexander J. Silver, Donovan J. Brown, Peter Van Galen, Michael R. Savona, Alexander G. Bick, and Brent Ferrell
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
17. Lactate Utilization Provides a Metabolic Escape to Resist the Antileukemic Activity of BET Inhibition in Acute Myeloid Leukemia
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Andrew J. Monteith, Haley E. Ramsey, Dalton Greenwood, Maria P. Arrate, Londa Fuller, Agnieszka E. Gorska, Alexander J. Silver, Donovan J. Brown, Sarah D. Olmstead, Jackson Watke, Matthew J. Stubbs, Jeffrey C. Rathmell, and Michael R. Savona
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
18. Primary HSPC-Derived Monocytes with DNMT3A p.R882H Exhibit Activated Myeloid Cell Gene Signatures
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Alexander J. Silver, Donovan J. Brown, Maria P. Arrate, Yu Wang, Melissa A. Fischer, Pawan Bhat, J. Brett Heimlich, Alexander G. Bick, P. Brent Ferrell, Yaomin Xu, and Michael R. Savona
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
19. High prescribing and state-level variation in z-drug use among Medicare patients
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Kaitlin E. Anderson, James L. Basting, Rachel I. Gifeisman, Donovan J. Harris, Antonica R. Rajan, Kenneth L. McCall, and Brain J. Piper
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BackgroundZ-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance that have been shown to increase the risk of fall-related injuries in patients aged 65 and older. The American Geriatrics Society Beers criteria classifies them as a high-risk medication and strongly recommends avoiding prescribing z-drugs to the elderly due to adverse effects. The objective of this study was to determine the prevalence of Z-drug prescribing among Medicare patients.MethodsZ-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data (CMS SDUD) for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions prescribed by providers within each specialty was also determined.ResultsZolpidem was the most prescribed z-drug, making up 95.0% of all z-drug prescriptions. Prescriptions per 100 enrollees were significantly elevated in Utah (28.2) and Arkansas (26.7) and significantly lower in Hawaii (9.3) relative to the national average (17.5). The specialties family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly elevated for psychiatry relative to other specialties.ConclusionsContrary to the Beers criteria, z-drugs are being prescribed to Medicare enrollees over age 65 at high rates. While sleep disturbances in the elderly should not be ignored, alternative therapies must be considered to avoid the serious adverse effects of z-drugs.Key PointsMore than one-half million Medicare patients received z-drug prescriptions in 2018 that were inconsistent with the Beers criteria.Z-drug prescriptions per 100,000 Medicare patients were significantly elevated in Utah and Arkansas.Family Medicine had the highest number of prescriptions out of all medical specialties.Psychiatry had a significantly higher number of prescriptions per provider compared to all other specialties.
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- 2022
20. Sex and age variations in the impact of puberty on cortical thickness and associations with internalizing symptoms and suicidal ideation in early adolescence
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Andrea Wiglesworth, Mark B. Fiecas, Meng Xu, Aidan T. Neher, Laura Padilla, Katherine A. Carosella, Donovan J. Roediger, Bryon A. Mueller, Monica Luciana, Bonnie Klimes-Dougan, and Kathryn R. Cullen
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Cognitive Neuroscience - Abstract
The childhood-to-adolescence transition is a notable period of change including pubertal development, neurodevelopment, and psychopathology onset, that occurs in divergent patterns between sexes. This study examined the effects of sex and puberty on cortical thickness (CT) in children and explored whether CT changes over time related to emergence of psychopathology in early adolescence.We used longitudinal data (baseline ages 9-10 and Year 2 [Y2] ages 11-12) from the ABCD Study (n = 9985). Linear and penalized function-on-function regressions modeled the impact of puberty, as it interacts with sex, on CT. Focusing on regions that showed sex differences, linear and logistic regressions modeled associations between change in CT and internalizing problems and suicide ideation.We identified significant sex differences in the inverse relation between puberty and CT in fifteen primarily posterior brain regions. Nonlinear pubertal effects across age were identified in the fusiform, isthmus cingulate, paracentral, and precuneus. All effects were stronger for females relative to males during this developmental window. We did not identify associations between CT change and early adolescent clinical outcomes.During this age range, puberty is most strongly associated with regional changes in CT in females, which may have implications for the later emergence of psychopathology.
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- 2022
21. Restoring RUNX1 deficiency in RUNX1 familial platelet disorder by inhibiting its degradation
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Jin Dai, Sara Borst, Jean Ann Maguire, Pamela S. Becker, Sylvia Chien, Sioban Keel, Deborah L. French, Michelle C Krutein, Michaela R. DelPriore, Marshall S. Horwitz, Donovan J. Anderson, Matthew R. Hart, Jasmin Jeffery, Paul Gadue, Eirini P. Papapetrou, and Andriana G. Kotini
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Blood Platelets ,Myeloid Neoplasia ,Myeloid ,Chemistry ,Platelet disorder ,Myeloid leukemia ,Hematology ,Protein degradation ,medicine.disease ,Leukemia, Myeloid, Acute ,Leukemia ,chemistry.chemical_compound ,Blood Coagulation Disorders, Inherited ,medicine.anatomical_structure ,RUNX1 ,hemic and lymphatic diseases ,Core Binding Factor Alpha 2 Subunit ,embryonic structures ,medicine ,Cancer research ,Humans ,Blood Platelet Disorders ,Induced pluripotent stem cell - Abstract
RUNX1 familial platelet disorder (RUNX1-FPD) is an autosomal dominant disorder caused by a monoallelic mutation of RUNX1, initially resulting in approximately half-normal RUNX1 activity. Clinical features include thrombocytopenia, platelet functional defects, and a predisposition to leukemia. RUNX1 is rapidly degraded through the ubiquitin-proteasome pathway. Moreover, it may autoregulate its expression. A predicted kinetic property of autoregulatory circuits is that transient perturbations of steady-state levels result in continued maintenance of expression at adjusted levels, even after inhibitors of degradation or inducers of transcription are withdrawn, suggesting that transient inhibition of RUNX1 degradation may have prolonged effects. We hypothesized that pharmacological inhibition of RUNX1 protein degradation could normalize RUNX1 protein levels, restore the number of platelets and their function, and potentially delay or prevent malignant transformation. In this study, we evaluated cell lines, induced pluripotent stem cells derived from patients with RUNX1-FPD, RUNX1-FPD primary bone marrow cells, and acute myeloid leukemia blood cells from patients with RUNX1 mutations. The results showed that, in some circumstances, transient expression of exogenous RUNX1 or inhibition of steps leading to RUNX1 ubiquitylation and proteasomal degradation restored RUNX1 levels, thereby advancing megakaryocytic differentiation in vitro. Thus, drugs retarding RUNX1 proteolytic degradation may represent a therapeutic avenue for treating bleeding complications and preventing leukemia in RUNX1-FPD.
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- 2021
22. Safety, feasibility, and efficacy of strengthening exercise in <scp>Duchenne</scp> muscular dystrophy
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Barry J. Byrne, Hyunjun Park, Glenn A. Walter, Donovan J. Lott, Tanja Taivassalo, Zahra Moslemi, Krista Vandenborne, Abhinandan Batra, Korey D. Cooke, and Sean C. Forbes
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Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Duchenne muscular dystrophy ,Hamstring Muscles ,Isometric exercise ,030105 genetics & heredity ,Article ,Quadriceps Muscle ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Stairs ,Physiology (medical) ,medicine ,Humans ,Muscle Strength ,Functional ability ,Child ,Muscle, Skeletal ,Creatine Kinase ,Exercise ,biology ,Knee extensors ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,Exercise Therapy ,Intensity (physics) ,Muscular Dystrophy, Duchenne ,Treatment Outcome ,Ambulatory ,biology.protein ,Physical therapy ,Feasibility Studies ,Creatine kinase ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
INTRODUCTION: This two-part study explored the safety, feasibility, and efficacy of a mild-moderate resistance isometric leg exercise program in ambulatory boys with Duchenne Muscular Dystrophy (DMD). METHODS: First, we used a dose escalation paradigm with varying intensity and frequency of leg isometric exercise to determine the dose response and safety in 10 boys. Second, we examined safety and feasibility of a 12-week in-home, remotely-supervised, mild-moderate intensity strengthening program in 8 boys. Safety measures included T(2) MRI, creatine kinase levels, and pain. Peak strength and function (time to ascend/descend 4 stairs) were also measured. RESULTS: Dose-escalation revealed no signs of muscle damage. Seven of the 8 boys completed the 12-week in-home program with a compliance of 84.9%, no signs of muscle damage, and improvements in strength (knee extensors p < 0.01; knee flexors p < 0.05) and function (descending steps p < 0.05). DISCUSSION: An in-home, mild-moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory boys with DMD.
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- 2020
23. Antilipidemic and Hepatoprotective Effects of Ethanol Extract of
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Marina, Murillo-Villicaña, Ruth, Noriega-Cisneros, Donovan J, Peña-Montes, Maribel, Huerta-Cervantes, Asdrubal, Aguilera-Méndez, Christian, Cortés-Rojo, Rafael, Salgado-Garciglia, Rocío, Montoya-Pérez, Héctor, Riveros-Rosas, and Alfredo, Saavedra-Molina
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Blood Glucose ,Male ,Ethanol ,Plant Extracts ,Antioxidants ,Streptozocin ,Diabetes Mellitus, Experimental ,Rats ,Oxidative Stress ,Justicia ,Animals ,Humans ,Hypoglycemic Agents ,Rats, Wistar - Abstract
Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment.
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- 2022
24. Additional file 4 of Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging
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Batra, Abhinandan, Barnard, Alison M., Lott, Donovan J., Willcocks, Rebecca J., Forbes, Sean C., Chakraborty, Saptarshi, Daniels, Michael J., Arbogast, Jannik, Triplett, William, Henricson, Erik K., Dayan, Jonathan G., Schmalfuss, Carsten, Sweeney, Lee, Byrne, Barry J., McDonald, Craig M., Vandenborne, Krista, and Walter, Glenn A.
- Abstract
Additional file 4: Peak and global mid ventricular strain (εcc %) in unaffected controls (n=15) and individuals with DMD (n=46) at baseline (UF Cohort).
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- 2022
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25. Additional file 2 of Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging
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Batra, Abhinandan, Barnard, Alison M., Lott, Donovan J., Willcocks, Rebecca J., Forbes, Sean C., Chakraborty, Saptarshi, Daniels, Michael J., Arbogast, Jannik, Triplett, William, Henricson, Erik K., Dayan, Jonathan G., Schmalfuss, Carsten, Sweeney, Lee, Byrne, Barry J., McDonald, Craig M., Vandenborne, Krista, and Walter, Glenn A.
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Additional file 2: Longitudinal changes in global strain in DMD. Solid line for global strain was defined based on normal zone cut off of -17% as given by HARP software. Red lines indicates subjects with more than 5 years data, filled triangles represent unaffected controls.
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- 2022
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26. Additional file 6 of Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging
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Batra, Abhinandan, Barnard, Alison M., Lott, Donovan J., Willcocks, Rebecca J., Forbes, Sean C., Chakraborty, Saptarshi, Daniels, Michael J., Arbogast, Jannik, Triplett, William, Henricson, Erik K., Dayan, Jonathan G., Schmalfuss, Carsten, Sweeney, Lee, Byrne, Barry J., McDonald, Craig M., Vandenborne, Krista, and Walter, Glenn A.
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musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities - Abstract
Additional file 6: Comparison of cardiac function in control and DMD subjects at baseline (UF Cohort).
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- 2022
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27. Additional file 3 of Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging
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Batra, Abhinandan, Barnard, Alison M., Lott, Donovan J., Willcocks, Rebecca J., Forbes, Sean C., Chakraborty, Saptarshi, Daniels, Michael J., Arbogast, Jannik, Triplett, William, Henricson, Erik K., Dayan, Jonathan G., Schmalfuss, Carsten, Sweeney, Lee, Byrne, Barry J., McDonald, Craig M., Vandenborne, Krista, and Walter, Glenn A.
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musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,sense organs ,skin and connective tissue diseases ,nervous system diseases - Abstract
Additional file 3: Longitudinal change in global strain for mid ventricle of DMD.
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- 2022
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28. Additional file 5 of Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging
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Batra, Abhinandan, Barnard, Alison M., Lott, Donovan J., Willcocks, Rebecca J., Forbes, Sean C., Chakraborty, Saptarshi, Daniels, Michael J., Arbogast, Jannik, Triplett, William, Henricson, Erik K., Dayan, Jonathan G., Schmalfuss, Carsten, Sweeney, Lee, Byrne, Barry J., McDonald, Craig M., Vandenborne, Krista, and Walter, Glenn A.
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musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities - Abstract
Additional file 5: Strain for each LV segment in controls and individuals with DMD (n=46) at baseline (UF cohort).
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- 2022
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29. Additional file 1 of Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging
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Batra, Abhinandan, Barnard, Alison M., Lott, Donovan J., Willcocks, Rebecca J., Forbes, Sean C., Chakraborty, Saptarshi, Daniels, Michael J., Arbogast, Jannik, Triplett, William, Henricson, Erik K., Dayan, Jonathan G., Schmalfuss, Carsten, Sweeney, Lee, Byrne, Barry J., McDonald, Craig M., Vandenborne, Krista, and Walter, Glenn A.
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musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities - Abstract
Additional file 1: Global mid ventricular strain (εcc %) in unaffected controls (n=15) and individuals with DMD (n=58) at baseline.
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- 2022
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30. Effects of dietary iron restriction on kidney mitochondria function and oxidative stress in streptozotocin-diabetic rats
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Donovan J. Peña-Montes, Xóchitl Trujillo, Miguel Huerta, Maribel Huerta-Cervantes, Mónica Ríos-Silva, Alfredo Saavedra-Molina, and Christian Cortés-Rojo
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Male ,0301 basic medicine ,medicine.medical_specialty ,Iron ,Cell Respiration ,Mitochondrion ,medicine.disease_cause ,Streptozocin ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,parasitic diseases ,medicine ,Animals ,Rats, Wistar ,Respiratory system ,Molecular Biology ,Kidney ,business.industry ,Iron Deficiencies ,Cell Biology ,Glutathione ,Streptozotocin ,medicine.disease ,Mitochondria ,Rats ,Oxidative Stress ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Molecular Medicine ,business ,Iron, Dietary ,030217 neurology & neurosurgery ,Function (biology) ,Oxidative stress ,medicine.drug - Abstract
Diabetes mellitus is characterized by chronic hyperglycemia causing mitochondrial dysfunction and kidney iron overload has been observed during diabetes. We evaluated the effects of an iron-restricted diet (IRD) on mitochondrial function, oxidative stress, and mitochondrial iron levels in the kidneys of Wistar rats with streptozotocin-induced diabetes. IRD ameliorated mitochondrial dysfunction in diabetic rats by restoring mitochondrial respiration and respiratory complex activity, improving oxidative stress and glutathione status in kidney mitochondria. We also observed mitochondrial iron overload. Our data suggest that elevated iron levels were attenuated by IRD, resulting in modulation of oxidative stress and mitochondrial function in the kidney.
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- 2020
31. Eryngium carlinaeEthanol Extract Corrects Lipid Abnormalities in Wistar Rats with Experimental Diabetes
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Miguel Huerta, Rafael Torres-Martínez, Rafael Salgado-Garciglia, Alfredo Saavedra-Molina, Salvador Manzo-Avalos, Ruth Noriega-Cisneros, Donovan J. Peña-Montes, and Maribel Huerta-Cervantes
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0301 basic medicine ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Ethanol ,business.industry ,Cholesterol ,Atorvastatin ,Medicine (miscellaneous) ,Lipid metabolism ,Disease ,Pharmacology ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,Diabetes mellitus ,medicine ,business ,Eryngium carlinae ,Experimental diabetes ,medicine.drug - Abstract
Abnormalities in lipid metabolism, associated with increased risk of cardiovascular disease (CVD), frequently occur in people with diabetes. Eryngium carlinae is a plant used in traditional medicin...
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- 2020
32. Magnetic Resonance Imaging Studies in Duchenne Muscular Dystrophy: Linking Findings to the Physical Therapy Clinic
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Glenn A. Walter, Alison M. Barnard, Kirsten L. Zilke, Rebecca J. Willcocks, Kavya S Nair, Claudia R. Senesac, William D. Rooney, Krista Vandenborne, Ann T. Harrington, and Donovan J. Lott
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Male ,musculoskeletal diseases ,medicine.medical_specialty ,Degenerative Disorder ,Duchenne muscular dystrophy ,Physical Therapy, Sports Therapy and Rehabilitation ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Muscle pathology ,medicine ,Humans ,Early childhood ,Child ,Muscle, Skeletal ,Physical Therapy Modalities ,Muscle Weakness ,medicine.diagnostic_test ,business.industry ,Muscle weakness ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Muscular Dystrophy, Duchenne ,Perspective ,Disease Progression ,Physical therapy ,Contracture ,medicine.symptom ,Exercise prescription ,business ,030217 neurology & neurosurgery - Abstract
Duchenne muscular dystrophy (DMD) is a muscle degenerative disorder that manifests in early childhood and results in progressive muscle weakness. Physical therapists have long been an important component of the multidisciplinary team caring for people with DMD, providing expertise in areas of disease assessment, contracture management, assistive device prescription, and exercise prescription. Over the last decade, magnetic resonance imaging of muscles in people with DMD has led to an improved understanding of the muscle pathology underlying the clinical manifestations of DMD. Findings from magnetic resonance imaging (MRI) studies in DMD, paired with the clinical expertise of physical therapists, can help guide research that leads to improved physical therapist care for this unique patient population. The 2 main goals of this perspective article are to (1) summarize muscle pathology and disease progression findings from qualitative and quantitative muscle MRI studies in DMD and (2) link MRI findings of muscle pathology to the clinical manifestations observed by physical therapists with discussion of any potential implications of MRI findings on physical therapy management.
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- 2020
33. Upper and Lower Extremities in Duchenne Muscular Dystrophy Evaluated with Quantitative MRI and Proton MR Spectroscopy in a Multicenter Cohort
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Ann T. Harrington, John F. Brandsema, Glenn A. Walter, Rebecca J. Willcocks, Harneet Arora, Michael J. Daniels, William T. Triplett, Gihan Tennekoon, Krista Vandenborne, Claudia R. Senesac, Erika Finanger, H. Lee Sweeney, Alison M. Barnard, Donovan J. Lott, William D. Rooney, Sean C. Forbes, Dah Jyuu Wang, and Umar Alabasi
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Male ,In vivo magnetic resonance spectroscopy ,Adolescent ,Proton Magnetic Resonance Spectroscopy ,Duchenne muscular dystrophy ,Deltoid curve ,Thigh ,Biceps ,030218 nuclear medicine & medical imaging ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Forearm ,Outcome Assessment, Health Care ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Muscular dystrophy ,Child ,Muscle, Skeletal ,Prospective cohort study ,Original Research ,Leg ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,Muscular Dystrophy, Duchenne ,Cross-Sectional Studies ,medicine.anatomical_structure ,Case-Control Studies ,030220 oncology & carcinogenesis ,Arm ,Disease Progression ,Feasibility Studies ,business ,Nuclear medicine - Abstract
BACKGROUND: Upper extremity MRI and proton MR spectroscopy are increasingly considered to be outcome measures in Duchenne muscular dystrophy (DMD) clinical trials. PURPOSE: To demonstrate the feasibility of acquiring upper extremity MRI and proton ((1)H) MR spectroscopy measures of T2 and fat fraction in a large, multicenter cohort (ImagingDMD) of ambulatory and nonambulatory individuals with DMD; compare upper and lower extremity muscles by using MRI and (1)H MR spectroscopy; and correlate upper extremity MRI and (1)H MR spectroscopy measures to function. MATERIALS AND METHODS: In this prospective cross-sectional study, MRI and (1)H MR spectroscopy and functional assessment data were acquired from participants with DMD and unaffected control participants at three centers (from January 28, 2016, to April 24, 2018). T2 maps of the shoulder, upper arm, forearm, thigh, and calf were generated from a spin-echo sequence (repetition time msec/echo time msec, 3000/20–320). Fat fraction maps were generated from chemical shift-encoded imaging (eight echo times). Fat fraction and (1)H(2)O T2 in the deltoid and biceps brachii were measured from single-voxel (1)H MR spectroscopy (9000/11–243). Groups were compared by using Mann-Whitney test, and relationships between MRI and (1)H MR spectroscopy and arm function were assessed by using Spearman correlation. RESULTS: This study evaluated 119 male participants with DMD (mean age, 12 years ± 3 [standard deviation]) and 38 unaffected male control participants (mean age, 12 years ± 3). Deltoid and biceps brachii muscles were different in participants with DMD versus control participants in all age groups by using quantitative T2 MRI (P < .001) and (1)H MR spectroscopy fat fraction (P < .05). The deltoid, biceps brachii, and triceps brachii were affected to the same extent (P > .05) as the soleus and medial gastrocnemius. Negative correlations were observed between arm function and MRI (T2: range among muscles, ρ = −0.53 to −0.73 [P < .01]; fat fraction, ρ = −0.49 to −0.70 [P < .01]) and (1)H MR spectroscopy fat fraction (ρ = −0.64 to −0.71; P < .01). CONCLUSION: This multicenter study demonstrated early and progressive involvement of upper extremity muscles in Duchenne muscular dystrophy (DMD) and showed the feasibility of MRI and (1)H MR spectroscopy to track disease progression over a wide range of ages in participants with DMD. © RSNA, 2020 Online supplemental material is available for this article.
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- 2020
34. Modeling disease trajectory in Duchenne muscular dystrophy
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William T. Triplett, Sean C. Forbes, Barry S. Russman, Claudia R. Senesac, G. Tennekoon, Harneet Arora, Rebecca J. Willcocks, Erika Finanger, Michael J. Daniels, Dah Jyuu Wang, Richard S. Finkel, William D. Rooney, Yosef A. Berlow, Elliott O'Brien, Donovan J. Lott, Saptarshi Chakraborty, Brendan Moloney, Alison M. Barnard, Krista Vandenborne, H. Lee Sweeney, Ishu Arpan, and Glenn A. Walter
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Male ,0301 basic medicine ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Adolescent ,Duchenne muscular dystrophy ,Population ,Corticosteroid treatment ,Walking ,Article ,03 medical and health sciences ,0302 clinical medicine ,Adrenal Cortex Hormones ,Internal medicine ,medicine ,Humans ,Muscular dystrophy ,Child ,Muscle, Skeletal ,education ,Leg ,education.field_of_study ,medicine.diagnostic_test ,Disease trajectory ,business.industry ,Disease progression ,Therapeutic effect ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Muscular Dystrophy, Duchenne ,030104 developmental biology ,Child, Preschool ,Disease Progression ,Cardiology ,Female ,Neurology (clinical) ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
ObjectiveTo quantify disease progression in individuals with Duchenne muscular dystrophy (DMD) using magnetic resonance biomarkers of leg muscles.MethodsMRI and magnetic resonance spectroscopy (MRS) biomarkers were acquired from 104 participants with DMD and 51 healthy controls using a prospective observational study design with patients with DMD followed up yearly for up to 6 years. Fat fractions (FFs) in vastus lateralis and soleus muscles were determined with 1H MRS. MRI quantitative T2 (qT2) values were measured for 3 muscles of the upper leg and 5 muscles of the lower leg. Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach.ResultsMRS FF and MRI qT2 increased with DMD disease duration, with the progression time constants differing markedly between individuals and across muscles. The average age at half-maximal muscle involvement (μ) occurred 4.8 years earlier in vastus lateralis than soleus, and these measures were strongly associated with loss-of-ambulation age. Corticosteroid treatment was found to delay μ by 2.5 years on average across muscles, although there were marked differences between muscles with more slowly progressing muscles showing larger delay.ConclusionsMRS FF and MRI qT2 provide sensitive noninvasive measures of DMD progression. Modeling changes in these biomarkers across multiple muscles can be used to detect and monitor the therapeutic effects of corticosteroids on disease progression and to provide prognostic information on functional outcomes. This modeling approach provides a method to transform these MRI biomarkers into well-understood metrics, allowing concise summaries of DMD disease progression at individual and population levels.ClinicalTrials.gov identifier:NCT01484678.
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- 2020
35. Enantioselective Synthesis of Dihydropyridines Containing Quaternary Stereocenters Through Dearomatization of Pyridinium Salts
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John D. Gorden, Donovan J. Robinson, Sean P. Spurlin, and Rashad R. Karimov
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chemistry.chemical_compound ,010405 organic chemistry ,Chemistry ,Enantioselective synthesis ,General Chemistry ,Pyridinium ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Stereocenter - Abstract
Enantioselective synthesis of nonaromatic heterocycles containing a fully substituted stereogenic center is a challenging synthetic problem. We describe a strategy toward this problem involving dea...
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- 2019
36. Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging
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Abhinandan Batra, Alison M. Barnard, Donovan J. Lott, Rebecca J. Willcocks, Sean C. Forbes, Saptarshi Chakraborty, Michael J. Daniels, Jannik Arbogast, William Triplett, Erik K. Henricson, Jonathan G. Dayan, Carsten Schmalfuss, Lee Sweeney, Barry J. Byrne, Craig M. McDonald, Krista Vandenborne, and Glenn A. Walter
- Subjects
Duchenne muscular dystrophy ,Duchenne/ Becker Muscular Dystrophy ,Adolescent ,Intellectual and Developmental Disabilities (IDD) ,Left ,Magnetic Resonance Imaging, Cine ,Cardiorespiratory Medicine and Haematology ,Cardiovascular ,Ventricular Function, Left ,Rare Diseases ,Clinical Research ,Cardiac circumferential strain ,Ventricular Function ,Humans ,Muscular Dystrophy ,Prospective Studies ,Preschool ,Child ,Cardiac magnetic resonance imaging ,Pediatric ,Stroke Volume ,Duchenne ,Magnetic Resonance Imaging ,Brain Disorders ,Muscular Dystrophy, Duchenne ,Heart Disease ,Cardiovascular System & Hematology ,Cine ,Child, Preschool ,Biomedical Imaging ,Cardiology and Cardiovascular Medicine ,Cardiomyopathies - Abstract
Background The lack of dystrophin in cardiomyocytes in Duchenne muscular dystrophy (DMD) is associated with progressive decline in cardiac function eventually leading to death by 20–40 years of age. The aim of this prospective study was to determine rate of progressive decline in left ventricular (LV) function in Duchenne muscular dystrophy (DMD) over 5 years. Methods Short axis cine and grid tagged images of the LV were acquired in individuals with DMD (n = 59; age = 5.3–18.0 years) yearly, and healthy controls at baseline (n = 16, age = 6.0–18.3 years) on a 3 T MRI scanner. Grid-tagged images were analyzed for composite circumferential strain (ℇcc%) and ℇcc% in six mid LV segments. Cine images were analyzed for left ventricular ejection fraction (LVEF), LV mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), LV atrioventricular plane displacement (LVAPD), and circumferential uniformity ratio estimate (CURE). LVM, EDV, and ESV were normalized to body surface area for a normalized index of LVM (LVMI), EDV (EDVI) and ESV (ESVI). Results At baseline, LV ℇcc% was significantly worse in DMD compared to controls and five of the six mid LV segments demonstrated abnormal strain in DMD. Longitudinal measurements revealed that ℇcc% consistently declined in individuals with DMD with the inferior segments being more affected. LVEF progressively declined between 3 to 5 years post baseline visit. In a multivariate analysis, the use of cardioprotective drugs trended towards positively impacting cardiac measures while loss of ambulation and baseline age were associated with negative impact. Eight out of 17 cardiac parameters reached a minimal clinically important difference with a threshold of 1/3 standard deviation. Conclusion The study shows a worsening of circumferential strain in dystrophic myocardium. The findings emphasize the significance of early and longitudinal assessment of cardiac function in DMD and identify early biomarkers of cardiac dysfunction to help design clinical trials to mitigate cardiac pathology. This study provides valuable non-invasive and non-contrast based natural history data of cardiac changes which can be used to design clinical trials or interpret the results of current trials aimed at mitigating the effects of decreased cardiac function in DMD.
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- 2021
37. Multimodal assessment of sustained threat in adolescents with nonsuicidal self-injury
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Mark Fiecas, Bryon A. Mueller, Timothy Hendrickson, Michelle Thai, Donovan J. Roediger, Anna M Parenteau, Thanharat Silamongkol, Zeynep Başgöze, Kathryn R. Cullen, Melinda Westlund Schreiner, Salahudeen A. Mirza, Conner A. Falke, Bonnie Klimes-Dougan, and Dawson Hill
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Suicide attempt ,Adolescent ,Hydrocortisone ,Left amygdala ,Functional connectivity ,Suicide, Attempted ,Right amygdala ,Amygdala ,Psychiatry and Mental health ,medicine.anatomical_structure ,Cross-Sectional Studies ,nervous system ,Developmental and Educational Psychology ,Trier social stress test ,medicine ,Humans ,Female ,Psychology ,Prefrontal cortex ,Self-Injurious Behavior ,Clinical psychology - Abstract
Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity (N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala–mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala–mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI.
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- 2021
38. Antidiabetic and antioxidant effect of silver nanoparticles synthesized from the aqueous extract of Eryngium carlinae in the brain of streptozotocin‐induced diabetic rats
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Jenaro Lemus‐de la Cruz, Rafael Salgado-Garciglia, Cinthia Itzel Landa Moreno, Gerardo Rosas‐Trejo, Donovan J. Peña-Montes, Rocío Montoya-Pérez, Alfredo Saavedra-Molina, Salvador Manzo-Avalos, Maribel Huerta-Cervantes, Cristian Mitchell Trejo‐Hurtado, and Christian Cortés-Rojo
- Subjects
Aqueous extract ,Antioxidant ,Chemistry ,medicine.medical_treatment ,Streptozotocin ,Biochemistry ,Silver nanoparticle ,Genetics ,medicine ,Molecular Biology ,Eryngium carlinae ,Biotechnology ,Nuclear chemistry ,medicine.drug - Published
- 2021
39. Effect of the Ethyl Acetate Extract of Justicia spicigera and Biotin in Liver of Diabetic Rats
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Christian Cortés-Rojo, Rocío Montoya-Pérez, Maribel Huerta-Cervantes, Alfredo Saavedra-Molina, Marina Murillo-Villicaña, Donovan J. Peña-Montes, Salvador Manzo-Avalos, Rafael Salgado-Garciglia, Asdrúbal Aguilera-Méndez, and Ruth Noriega-Cisneros
- Subjects
chemistry.chemical_compound ,biology ,Traditional medicine ,Biotin ,Chemistry ,Genetics ,Ethyl acetate ,Justicia spicigera ,biology.organism_classification ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2021
40. Antioxidant Activity of the Ethyl Acetate Extract of Potentilla indica on Kidneys of Streptozotocin‐Induced Diabetic Rats
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Cristian Mitchell Trejo‐Hurtado, Cinthia Itzel Landa-Moreno, Rocío Montoya-Pérez, Alfredo Saavedra-Molina, Donovan J. Peña-Montes, Rafael Salgado-Garciglia, Jenaro Lemus‐de la Cruz, Maribel Huerta-Cervantes, and Salvador Manzo-Avalos
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Antioxidant ,Traditional medicine ,medicine.medical_treatment ,Ethyl acetate ,Streptozotocin ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Genetics ,medicine ,Potentilla indica ,Molecular Biology ,Biotechnology ,medicine.drug - Published
- 2021
41. Antioxidant and Anti‐Inflammatory Activity of the Ethyl Acetate Extract of Eryngium Carlinae on the Liver of Streptozotocin‐Induced Diabetes Rats
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Rafael Salgado-Garciglia, Cinthia Itzel Landa-Moreno, Rocío Montoya-Pérez, Alfredo Saavedra-Molina, Cristian Mitchell Trejo‐Hurtado, Maribel Huerta-Cervantes, Salvador Manzo-Avalos, Jenaro Lemus‐de la Cruz, and Donovan J. Peña-Montes
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Antioxidant ,medicine.drug_class ,medicine.medical_treatment ,Ethyl acetate ,Pharmacology ,medicine.disease ,Streptozotocin ,Biochemistry ,Anti-inflammatory ,chemistry.chemical_compound ,chemistry ,Diabetes mellitus ,Genetics ,medicine ,Molecular Biology ,Eryngium carlinae ,Biotechnology ,medicine.drug - Published
- 2021
42. Imaging respiratory muscle quality and function in Duchenne muscular dystrophy
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Abhinandan Batra, Krista Vandenborne, William T. Triplett, Barbara K. Smith, Glenn A. Walter, Rebecca J. Willcocks, Donovan J. Lott, Samuel L. Riehl, Sean C. Forbes, and Alison M. Barnard
- Subjects
Diagnostic Imaging ,Thorax ,medicine.medical_specialty ,Movement ,Duchenne muscular dystrophy ,Thoracic Cavity ,Article ,Pulmonary function testing ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Respiratory muscle ,Humans ,Medicine ,Respiratory function ,030212 general & internal medicine ,Respiratory system ,Muscular dystrophy ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,Respiratory Muscles ,Muscular Dystrophy, Duchenne ,Cross-Sectional Studies ,Neurology ,Breathing ,Cardiology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
OBJECTIVE: Duchenne muscular dystrophy (DMD) is characterized by damage to muscles including the muscles involved in respiration. Dystrophic muscles become weak and infiltrated with fatty tissue, resulting in progressive respiratory impairment. The objective of this study was to assess respiratory muscle quality and function in DMD using magnetic resonance imaging and to determine the relationship to clinical respiratory function. METHODS: Individuals with DMD (n=36) and unaffected controls (n=12) participated in this cross-sectional magnetic resonance imaging study. Participants underwent dynamic imaging of the thorax to assess diaphragm and chest wall mobility and chemical shift-encoded imaging of the chest and abdomen to determine fatty infiltration of the accessory respiratory muscles. Additionally, clinical pulmonary function measures were obtained. RESULTS: Thoracic cavity area was decreased in individuals with DMD compared to controls during tidal and maximal breathing. Individuals with DMD had reduced chest wall movement in the anterior-posterior direction during maximal inspirations and expirations, but diaphragm descent during maximal inspirations (normalized to height) was only decreased in a subset of individuals with maximal inspiratory pressures less than 60% predicted. Muscle fat fraction was elevated in all three expiratory muscles assessed (p
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- 2019
43. Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing
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Donovan J. Anderson, Marshall S. Horwitz, Jay Shendure, Aaron McKenna, Florian M. Pauler, and Simon Hippenmeyer
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Genetics ,Transcriptome ,Loss of heterozygosity ,Cell type ,Lineage (genetic) ,Somatic cell ,Progenitor cell ,Biology ,Gene ,Genome - Abstract
Acquired mutations are sufficiently frequent such that the genome of a single cell offers a record of its history of cell divisions. Among more common somatic genomic alterations are loss of heterozygosity (LOH). Large LOH events are potentially detectable in single cell RNA sequencing (scRNA-seq) datasets as tracts of monoallelic expression for constitutionally heterozygous single nucleotide variants (SNVs) located among contiguous genes. We identified runs of monoallelic expression, consistent with LOH, uniquely distributed throughout the genome in single cell brain cortex transcriptomes of F1 hybrids involving different inbred mouse strains. We then phylogenetically reconstructed single cell lineages and simultaneously identified cell types by corresponding gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. Compared to engineered recording systems, LOH events accumulate throughout the genome and across the lifetime of an organism, affording tremendous capacity for encoding lineage information and increasing resolution for later cell divisions. This approach can conceivably be computationally incorporated into scRNA-seq analysis and may be useful for organisms where genetic engineering is prohibitive, such as humans.
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- 2021
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44. Constance Baker Motley���s Forgotten Housing Legacy
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Stone, Donovan J.
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- 2021
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45. Fractures and resilience of agri-food value chains in the context of COVID-19: A review of recent evidence
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Marenya P., Stoian D., and Donovan J.
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- 2021
46. Contributors
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Mohammad Abdollahi, Siddhesh Aras, Luiz Roberto G. Britto, Christian Cortés-Rojo, Majid Dadmehr, Ana Flávia Fernandes Ferreira, Lawrence I. Grossman, Somayeh Handali, Reza Heidari, Maribel Huerta-Cervantes, Zhaleh Jamali, Rocío Montoya-Pérez, Taraneh Mousavi, Shilan Mozaffari, Hossein Niknahad, Mohammad Mehdi Ommati, Donovan J. Peña-Montes, Jalal Pourahmad, Neeraja Purandare, Mohsen Rezaei, Alfredo Saavedra-Molina, Rafael Salgado-Garciglia, Ahmad Salimi, Monique Patrício Singulani, and Bahareh Sadat Yousefsani
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- 2021
47. Bridging research and practice: Toward impactful value chain development
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Stoian D. and Donovan J.
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- 2021
48. Mitochondrial metabolism in diabetes
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Alfredo Saavedra-Molina, Rocío Montoya-Pérez, Maribel Huerta-Cervantes, Rafael Salgado-Garciglia, Christian Cortés-Rojo, and Donovan J. Peña-Montes
- Subjects
Kidney ,business.industry ,Metabolic disorder ,Mitochondrion ,medicine.disease ,Bioinformatics ,medicine.disease_cause ,Nephropathy ,medicine.anatomical_structure ,Diabetes mellitus ,Heart failure ,medicine ,Myocardial infarction ,business ,Oxidative stress - Abstract
Diabetes mellitus (DM) is a heterogeneous set of multifactorial pathogenesis syndrome where the common nexus is metabolic disorder, mainly chronic hyperglycemia and alterations in lipid and protein metabolism. The effects of DM, include long-term damage, dysfunction, and failure of various organs. It especially affects eyes, kidneys, muscle, nerves, heart, and blood vessels. The primary goal of diabetes treatment is the prevention of macrovascular complications (e.g., myocardial infarction, heart failure, and ischemic stroke) as well as the microvascular complications (e.g., retinopathy, neuropathy, and nephropathy). Abnormalities in mitochondrial function are common in the pathophysiology of diabetes that include modifications in the redox state and oxidative and nitrosative stress, as well dysregulation of mitochondrial complex activities. Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment. Identification of major compounds in extracts of medicinal plants can contribute to ameliorate hyperglycemia and oxidative stress due to exacerbated mitochondrial dysfunction in diabetes. The growing need to find alternatives for the treatment of diabetes justifies the study of medicinal plants used in traditional medicine. In this study, we aimed to review information related to possible treatments with bioactive compounds from medicinal plants on diabetes that affect several organs, including liver, heart, brain, muscle, and kidney with exacerbated oxidative stress originated mainly in mitochondria.
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- 2021
49. Host directed therapies for tuberculous meningitis [version 2; peer review: 1 approved, 1 approved with reservations]
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Davis, A, Donovan, J, Bremer, M, Van Toorn, R, Schoeman, J, Dadabhoy, A, Lai, RPJ, Cresswell, F, Boulware, D, Wilkinson, R, Thuong, NTT, Thwaites, G, Bahr, N, and Tuberculous Meningitis International Research Consortium
- Subjects
Tuberculous Meningitis International Research Consortium ,urologic and male genital diseases - Abstract
A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.
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- 2020
50. Para-limbic Structural Abnormalities Are Associated With Internalizing Symptoms in Children With Prenatal Alcohol Exposure
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Christopher A. Boys, Jeffrey R. Wozniak, Timothy Hendrickson, Donovan J. Roediger, Edward P. Riley, Sarah N. Mattson, Alyssa M. Krueger, Bryon A. Mueller, Kenneth L. Jones, Kelvin O. Lim, and Mariah J. Schumacher
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,animal structures ,Adolescent ,Significant group ,030508 substance abuse ,Medicine (miscellaneous) ,Hippocampus ,Anxiety ,Toxicology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Limbic system ,Pregnancy ,Magnetic resonance imaging of the brain ,medicine ,Limbic System ,Humans ,Child ,Depression (differential diagnoses) ,medicine.diagnostic_test ,Ethanol ,business.industry ,Depression ,Putamen ,Central Nervous System Depressants ,Organ Size ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,medicine.anatomical_structure ,Prenatal alcohol exposure ,Prenatal Exposure Delayed Effects ,Female ,medicine.symptom ,Caudate Nucleus ,0305 other medical science ,business ,030217 neurology & neurosurgery - Abstract
Background Prenatal alcohol exposure (PAE) is associated with a variety of structural abnormalities in the brain, including several within the para-limbic system. Children with PAE have higher rates of internalizing disorders, including depression and anxiety, which may be related to underlying limbic system anomalies. Methods Children aged 8 to 16 with PAE (n = 41) or without PAE (n = 36) underwent an magnetic resonance imaging of the brain and parents completed behavioral questionnaires about their children. Semi-automated procedures (FreeSurfer) were used to derive para-limbic volumes from T1-weighted anatomical images. Results There were significant group differences (PAE vs. nonexposed controls) in the caudate, hippocampus, and the putamen; children with PAE had smaller volumes in these regions even after controlling for total intracranial volume. A trend-level association was seen between caudate volume and internalizing symptoms in children with PAE; smaller caudate volumes (presumably reflecting less optimal neurodevelopment) were associated with higher levels of anxiety and depression symptoms in these children. Conclusions Caudate structure may be disproportionately affected by PAE and may be associated with the later development of internalizing symptoms in those affected by PAE.
- Published
- 2020
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