1,513 results on '"I., Martin"'
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2. Chimeric Peptidomimetic Antibiotic Efficiently Neutralizes Lipopolysaccharides (LPS) and Bacteria-Induced Activation of RAW Macrophages
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Ali Javed, Cornelis J. Slingerland, Thomas M. Wood, Nathaniel I. Martin, Femke Broere, Markus H. Weingarth, Edwin J. A. Veldhuizen, Immunologie, Sub NMR Spectroscopy, Interne geneeskunde GD, and CS_Welfare & emerging diseases
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sepsis ,Infectious Diseases ,LPS neutralization ,peptides ,immunomodulation ,innate immunity - Abstract
Peptide antibiotics have gathered attention given the urgent need to discover antimicrobials with new mechanisms of action. Their extended role as immunomodulators makes them interesting candidates for the development of compounds with dual mode of action. The objective of this study was to test the anti-inflammatory capacity of a recently reported chimeric peptidomimetic antibiotic (CPA) composed of polymyxin B nonapeptide (PMBN) and a macrocyclic β-hairpin motif (MHM). We investigated the potential of CPA to inhibit lipopolysaccharide (LPS)-induced activation of RAW264.7 macrophages. In addition, we elucidated which structural motif was responsible for this activity by testing CPA, its building blocks, and their parent compounds separately. CPA showed excellent LPS neutralizing activity for both smooth and rough LPSs. At nanomolar concentrations, CPA completely inhibited LPS-induced nitric oxide, TNF-α, and IL-10 secretion. Murepavadin, MHM, and PMBN were incapable of neutralizing LPS in this assay, while PMB was less active compared to CPA. Isothermal titration calorimetry showed strong binding between the CPA and LPS with similar binding characteristics also found for the other compounds, indicating that binding does not necessarily correlate with neutralization of LPS. Finally, we showed that CPA-killed bacteria caused significantly less macrophage activation than bacteria killed with gentamicin, heat, or any of the other compounds. This indicates that the combined killing activity and LPS neutralization of CPA can prevent unwanted inflammation, which could be a major advantage over conventional antibiotics. Our data suggests that immunomodulatory activity can further strengthen the therapeutic potential of peptide antibiotics and should be included in the characterization of novel compounds.
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- 2023
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3. No Increased Risk of Nonunion with Bisphosphonate Use in a Medicare Claims Cohort Following Operatively Treated Long-Bone Fractures
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Tyler J. Thorne, Lillia Steffenson, Dillon C. O’Neill, Lucas S. Marchand, Brook I. Martin, and Justin M. Haller
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Orthopedics and Sports Medicine ,Surgery ,General Medicine - Published
- 2023
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4. Transcranial Photobiomodulation Treatment: Significant Improvements in Four Ex-Football Players with Possible Chronic Traumatic Encephalopathy
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Margaret A. Naeser, Paula I. Martin, Michael D. Ho, Maxine H. Krengel, Yelena Bogdanova, Jeffrey A. Knight, Michael R. Hamblin, Andrea E. Fedoruk, Luke G. Poole, ChiaHsin Cheng, and BangBon Koo
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Psychiatry and Mental health ,Clinical Psychology ,General Neuroscience ,Geriatrics and Gerontology - Abstract
Background: Chronic traumatic encephalopathy, diagnosed postmortem (hyperphosphorylated tau), is preceded by traumatic encephalopathy syndrome with worsening cognition and behavior/mood disturbances, over years. Transcranial photobiomodulation (tPBM) may promote improvements by increasing ATP in compromised/stressed cells and increasing local blood, lymphatic vessel vasodilation. Objective: Aim 1: Examine cognition, behavior/mood changes Post-tPBM. Aim 2: MRI changes - resting-state functional-connectivity MRI: salience, central executive, default mode networks (SN, CEN, DMN); magnetic resonance spectroscopy, cingulate cortex. Methods: Four ex-players with traumatic encephalopathy syndrome/possible chronic traumatic encephalopathy, playing 11– 16 years, received In-office, red/near-infrared tPBM to scalp, 3x/week for 6 weeks. Two had cavum septum pellucidum. Results: The three younger cases (ages 55, 57, 65) improved 2 SD (p
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- 2023
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5. Elucidation of complex triplet excited state dynamics in Pd(<scp>ii</scp>) biladiene tetrapyrroles
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Shea M. Martin, Gil M. Repa, Robert C. Hamburger, Craig A. Pointer, Kaytlin Ward, Trong-Nhan Pham, Maxwell I. Martin, Joel Rosenthal, Lisa A. Fredin, and Elizabeth R. Young
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General Physics and Astronomy ,Physical and Theoretical Chemistry - Abstract
Pd(ii) biladienes have been developed over the last five years as non-aromatic oligotetrapyrrole complexes that support a rich triplet photochemistry.
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- 2023
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6. Chemical Proteomics Reveals Antibiotic Targets of Oxadiazolones in MRSA
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Alexander T. Bakker, Ioli Kotsogianni, Liza Mirenda, Verena M. Straub, Mariana Avalos, Richard J. B. H. N. van den Berg, Bogdan I. Florea, Gilles P. van Wezel, Antonius P. A. Janssen, Nathaniel I. Martin, and Mario van der Stelt
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Colloid and Surface Chemistry ,General Chemistry ,Biochemistry ,Catalysis - Abstract
Phenotypic screening is a powerful approach to identify novel antibiotics, but elucidation of the targets responsible for the antimicrobial activity is often challenging in the case of compounds with a polypharmacological mode of action. Here, we show that activity-based protein profiling maps the target interaction landscape of a series of 1,3,4-oxadiazole-3-ones identified in a phenotypic screen to have high antibacterial potency against multidrug-resistant
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- 2022
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7. Construction and Use of an Inexpensive, Free-Hand, Pedicle Screw Placement Model
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Allyn Morris, Leila Alvandi, Jaime Gomez, I. Martin Levy, and Jacob Schulz
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This manuscript describes the construction and use of a free-hand pedicle screw placement model. This model is used to teach residents and other learners proper handling of the tools used to place pedicle screws. Additionally, it is intended to simulate the tactile feel of pedicle screw placement.
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- 2022
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8. An efficient synthesis of substituted hexahydrobenzo[f]thieno[c]quinoline; an advanced intermediate of analog of A-86929, a dopamine D1 full agonist
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Sukanta Bar and Maxwell I. Martin
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Organic Chemistry ,General Chemistry ,Catalysis - Abstract
An efficient synthesis of substituted hexahydrobenzo[ f]thieno[ c]quinolines was achieved via catalytic one-pot aziridination followed by Friedel–Crafts cyclization and a mild Pictet–Spengler cyclization protocol. Cu(OTf)2 was an effective catalyst for both aziridination followed by Friedel–Crafts cyclization with excellent diastereoselectivity (dr: >99:1) and high yield (75%).
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- 2022
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9. The Fungal Intestinal Microbiota Predict the Development of Bronchopulmonary Dysplasia in Very Low Birthweight Newborns
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K.A. Willis, M. Silverberg, A. Abdelgawad, I. Martin, K. Tanaka, B. Halloran, E. Myers, C.V. Lal, N. Ambalavanan, T. Jilling, L. Tipton, J. Pierre, and A. Talati
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- 2023
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10. Mouse Model of Neutrophilic Asthma Reveals an Epithelium-Lymphocyte-Neutrophil Communication Circuit Underlying Destructive Allergic Airway Neutrophilia
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A.T. Shenoy, F.T. Korkmaz, C. Lyon De Ana, F.-Z. Shao, C. Odom, K. Barker, A. Ramanujan, W. Goltry, I. Martin, C. Ha, L.J. Quinton, M.R. Jones, A. Fine, F. Chen, A. Belkina, and J.P. Mizgerd
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- 2023
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11. Recent Advances in the Development of Semisynthetic Glycopeptide Antibiotics: 2014–2022
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Emma van Groesen, Paolo Innocenti, and Nathaniel I. Martin
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Methicillin-Resistant Staphylococcus aureus ,Infectious Diseases ,Vancomycin ,Glycopeptides ,Gram-Positive Bacteria ,Anti-Bacterial Agents - Abstract
The accelerated appearance of drug-resistant bacteria poses an ever-growing threat to modern medicine's capacity to fight infectious diseases. Gram-positive species such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae continue to contribute significantly to the global burden of antimicrobial resistance. For decades, the treatment of serious Gram-positive infections relied upon the glycopeptide family of antibiotics, typified by vancomycin, as a last line of defense. With the emergence of vancomycin resistance, the semisynthetic glycopeptides telavancin, dalbavancin, and oritavancin were developed. The clinical use of these compounds is somewhat limited due to toxicity concerns and their unusual pharmacokinetics, highlighting the importance of developing next-generation semisynthetic glycopeptides with enhanced antibacterial activities and improved safety profiles. This Review provides an updated overview of recent advancements made in the development of novel semisynthetic glycopeptides, spanning the period from 2014 to today. A wide range of approaches are covered, encompassing innovative strategies that have delivered semisynthetic glycopeptides with potent activities against Gram-positive bacteria, including drug-resistant strains. We also address recent efforts aimed at developing targeted therapies and advances made in extending the activity of the glycopeptides toward Gram-negative organisms.
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- 2022
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12. Is ultradistance sport healthy? A descriptive observational study of a cohort of ultradistance runners
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Inhar Esnaola, Ricardo Palenzuela, Maite Urcelay, Nerea Sarriegi, José I Martin, and Haritz Esnal
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Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine - Abstract
Objective: To describe the physical and physiological characteristics of a group formed by ultra-distance runners, to compare their training habits with the guidelines established by the WHO and to study the possible harmful consequences of the high volume of physical activity performed. Material and method: The sample was formed by runners who repeated their participation in the “Ehunmilak” ultra-distance race in 2017 and 2018. Data collected through the medical certificates of the race and an own questionnaire were analyzed. For the analysis of variables, the Mann-Whitney U and Chi-square tests were used, with a 95% confidence interval. A value of p
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- 2022
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13. A Direct Assay for Measuring the Activity and Inhibition of Coactivator-Associated Arginine Methyltransferase 1
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Yurui Zhang, Matthijs J. van Haren, Nils Marechal, Nathalie Troffer-Charlier, Vincent Cura, Jean Cavarelli, and Nathaniel I. Martin
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Biochemistry - Abstract
Coactivator-associated arginine methyltransferase 1 (CARM1) is a member of the family of protein arginine methyltransferases. CARM1 catalyzes methyl group transfer from the cofactor S-adenosyl-L-methionine (AdoMet) to both histone and nonhistone protein substrates. CARM1 is involved in a range of cellular processes, mainly involving RNA transcription and gene regulation. As the aberrant expression of CARM1 has been linked to tumorigenesis, the enzyme is a potential therapeutic target, leading to the development of inhibitors and tool compounds engaging with CARM1. To evaluate the effects of these compounds on the activity of CARM1, sensitive and specific analytical methods are needed. While different methods are currently available to assess the activity of methyltransferases, these assays mainly focus on either the measurement of the cofactor product S-adenosyl-L-homocysteine (AdoHcy) or employ radioactive or expensive reagents, each with their own advantages and limitations. To complement the tools currently available for the analysis of CARM1 activity, we here describe the development of a convenient assay employing peptide substrates derived from poly(A)-binding protein 1 (PABP1). This operationally straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approach allows for the direct detection of substrate methylation with minimal workup. The method was validated, and its value in characterizing CARM1 activity and inhibition was demonstrated through a comparative analysis involving a set of established small molecules and peptide-based CARM1 inhibitors.
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- 2022
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14. To Go or Not to Go: Factors That Influence Health Care Use Among Trans Adults in a Non-Representative U.S. Sample
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Justin E. Lerner, James I. Martin, and Gabriella Silva Gorsky
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Arts and Humanities (miscellaneous) ,General Psychology - Published
- 2022
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15. Trauma-Informed Care in the Classroom: Our Experience with a Content Warning in a Medical School Course
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Julianne Stout and Angelika I. Martin
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Monograph ,Medicine (miscellaneous) ,Education - Abstract
Trauma is now recognized as a common human experience that has consequences, including adverse effects on learning outcomes. Principles of trauma-informed care include awareness of the impact of trauma and use of strategies to prevent retraumatization. While well-described in medical and mental health care, these principles have been inconsistently applied in the medical education classroom. Content warnings can be part of a trauma-informed classroom approach that notifies learners about potentially distressing topics, allows individuals to employ self-care, and seeks to resist retraumatization. This article describes our experience integrating a content warning about reproductive topics in a second-year medical school course. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-022-01559-0.
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- 2022
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16. Primary lymphoma of the prostate: A report of two cases
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V. López Prior, I. Martin García, P. Pelechano Gómez, and M. Barrios Benito
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Radiological and Ultrasound Technology ,Biophysics ,Radiology, Nuclear Medicine and imaging - Published
- 2022
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17. CHROMATIN ACTIVATION PROFILING OF STEREOTYPED CHRONIC LYMPHOCYTIC LEUKEMIAS REVEALS A SUBSET #8 SPECIFIC SIGNATURE
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Maria Tsagiopoulou, Vicente Chapaprieta, Nuria Russiñol, Beatriz García-Torre, Nikolaos Pechlivanis, Ferran Nadeu, Nikos Papakonstantinou, Niki Stavroyianni, Anastasia Chatzidimitriou, Fotis Psomopoulos, Elías Campo, Kostas Stamatopoulos, and Jose I. Martin-Subero
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
The chromatin activation landscape of chronic lymphocytic leukemia (CLL) with stereotyped B-cell receptor immunoglobulin is currently unknown. Here, we report the results of a whole-genome chromatin profiling of histone 3 lysine 27 acetylation of 22 CLLs from major subsets which were compared against non-stereotyped CLLs and normal B cell subpopulations. Although subsets #1, #2, and #4 did not differ much from their non-stereotyped CLL counterparts, subset #8 displayed a remarkably distinct chromatin activation profile. In particular, we identified 209 de novo active regulatory elements in this subset, which showed similar patterns with U-CLLs undergoing Richter transformation. These regions were enriched for binding sites of 9 overexpressed transcription factors. In 78/209 regions, we identified 113 candidate overexpressed target genes, being 11 regions associated with more than two adjacent genes. These included blocks of up to 7 genes, suggesting a local co-upregulation within the same genome compartment. Our findings further underscore the uniqueness of subset #8 CLLs, notable for the highest risk of Richter's transformation amongst all CLL, and provide additional clues to decipher the molecular basis of its clinical behavior.
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- 2023
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18. Glucocorticoids increase tissue cell protection against pore-forming toxins from pathogenic bacteria
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Thomas J. R. Ormsby, Sian E. Owens, Matthew L. Turner, James G. Cronin, John J. Bromfield, and I. Martin Sheldon
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Medicine (miscellaneous) ,General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology - Abstract
Many species of pathogenic bacteria damage tissue cells by secreting toxins that form pores in plasma membranes. Here we show that glucocorticoids increase the intrinsic protection of tissue cells against pore-forming toxins. Dexamethasone protected several cell types against the cholesterol-dependent cytolysin, pyolysin, from Trueperella pyogenes. Dexamethasone treatment reduced pyolysin-induced leakage of potassium and lactate dehydrogenase, limited actin cytoskeleton alterations, reduced plasma membrane blebbing, and prevented cytolysis. Hydrocortisone and fluticasone also protected against pyolysin-induced cell damage. Furthermore, dexamethasone protected HeLa and A549 cells against the pore-forming toxins streptolysin O from Streptococcus pyogenes, and alpha-hemolysin from Staphylococcus aureus. Dexamethasone cytoprotection was not associated with changes in cellular cholesterol or activating mitogen-activated protein kinase (MAPK) cell stress responses. However, cytoprotection was dependent on the glucocorticoid receptor and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR). Collectively, our findings imply that glucocorticoids could be exploited to limit tissue damage caused by pathogens secreting pore-forming toxins.
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- 2023
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19. Endoscopic-Assisted En Bloc Pterygomaxillectomy: Identifying an Efficient and Safe Location for the Pterygoid Osteotomy
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Ainhoa García-Lliberós, Daniel I. Martin-Jimenez, Ronsard J. Mondesir, Edoardo Agosti, A. Yohan Alexander, Garret Choby, Maria Peris-Celda, and Carlos D. Pinheiro-Neto
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- 2023
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20. Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, non-neutropenic, adult patients: An update including COVID-19 data
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Matteo Bassetti, Valentina Zuccaro, Erika Asperges, Luigia Scudeller, Daniele Roberto Giacobbe, M. Akova, A. Alastruey-Izquierdo, S. Arikan-Akdagli, E. Azoulay, S. Blot, A. Cortegiani, O.A. Cornely, C. Grecchi, C. Lass-Flörl, P. Koehler, M. Cuenca-Estrella, D.W. de Lange, F.G. De Rosa, J.J. De Waele, G. Dimopoulos, J. Garnacho-Montero, M. Hoenigl, S.S. Kanj, F. Lamoth, J. Maertens, I. Martin-Loeches, P. Muñoz, B.J. Kullberg, C. Agvald-Ohman, G. Poulakou, C. Rebuffi, J. Rello, M. Sanguinetti, F.S. Taccone, J-F. Timsit, A. Torres, J.A. Vazquez, J. Wauters, T. Calandra, S. Tejada, I. Karaiskos, M. Peghin, A. Vena, K.L. Mortensen, C. Lebihan, T. Mercier, Bassetti, Matteo, Zuccaro, Valentina, Asperges, Erika, Scudeller, Luigia, Giacobbe, Daniele Roberto, and FUNDICU investigators (collaborators): M Akova, A Alastruey-Izquierdo, S Arikan-Akdagli, E Azoulay, S Blot, A Cortegiani, O A Cornely, C Grecchi, C Lass-Flörl, P Koehler, M Cuenca-Estrella, D W de Lange, F G De Rosa, J J De Waele, G Dimopoulos, J Garnacho-Montero, M Hoenigl, S S Kanj, F Lamoth, J Maertens, I Martin-Loeches, P Muñoz, B J Kullberg, C Agvald-Ohman, G Poulakou, C Rebuffi, J Rello, M Sanguinetti, F S Taccone, J-F Timsit, A Torres, J A Vazquez, J Wauters, T Calandra, S Tejada, I Karaiskos, M Peghin, A Vena, K L Mortensen, C Lebihan, T Mercier
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Microbiology (medical) ,Adult ,Invasive Pulmonary Aspergillosis ,Intensive Care Units ,Aspergillus ,Infectious Diseases ,COVID-19 Testing ,Critical Illness ,Aspergillosis ,COVID-19 ,Humans ,Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA ,Invasive Fungal Infections - Published
- 2022
21. Is Discretionary Care Associated with Safety Among Medicare Beneficiaries Undergoing Spine Surgery?
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Hyunkyu Ko, Darrel S. Brodke, Megan E. Vanneman, Andrew J. Schoenfeld, and Brook I. Martin
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Aged, 80 and over ,Male ,General Medicine ,Medicare ,Spine ,United States ,Spinal Fusion ,Humans ,Female ,Spinal Diseases ,Orthopedics and Sports Medicine ,Surgery ,Health Expenditures ,Aged ,Retrospective Studies - Abstract
Spine surgery and its corresponding costs have increased in recent years and are variable across geographic regions. Discretionary care is the component of spending variation that is independent of illness severity, age, and regional pricing. It is unknown whether greater discretionary care is associated with improved safety for patients undergoing spine surgery, as we would expect from value-based health care.We conducted an analysis of 5 spine surgery cohorts based on Medicare claims from 2013 to 2017. Patients were grouped into quintiles based on the Dartmouth Atlas End-of-Life Inpatient Care Index (EOL), reflecting regional spending variation attributed to discretionary care. Multivariable regression examined the association between discretionary care and safety measures while controlling for age, sex, race, comorbidity, and hospital features.We observed a threefold to fourfold variation in 90-day episode-of-care cost across regions, depending on the cohort. Spine-specific spending was correlated with EOL quintile, confirming that spending variation is due more to discretionary care than it is to pricing, age, or illness severity. Greater spending across EOL quintiles was not associated with improved safety, and, in fact, was associated with poorer safety in some cohorts. For example, all-cause readmission was greater in the high-spending EOL quintile relative to the low-spending EOL quintile among the "fusion, except cervical" cohort (14.2% vs. 13.1%; OR = 1.10; 95% CI = 1.05 to 1.20), the "complex fusion" cohort (28.0% vs. 25.4%; OR = 1.15; 95% CI = 1.01 to 1.30), and the "cervical fusion" cohort (15.0% vs. 13.6%; OR = 1.12; 95% CI = 1.05 to 1.20).Wide variation in spending was not explained by differences in illness severity, age, or pricing, and increased discretionary care did not enhance safety. These findings point to inefficient use of health-care resources, a potential focus of reform.Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.
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- 2021
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22. Structure–Activity Studies with Bis-Amidines That Potentiate Gram-Positive Specific Antibiotics against Gram-Negative Pathogens
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Shanice Veraar, Samantha Lok, Cornelis J Slingerland, Nathaniel I. Martin, and Charlotte M J Wesseling
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Acinetobacter baumannii ,outer membrane disruption ,Klebsiella pneumoniae ,medicine.drug_class ,Antiparasitic ,Polymyxin ,Antibiotics ,Amidines ,medicine.disease_cause ,01 natural sciences ,Article ,Microbiology ,03 medical and health sciences ,Gram-Negative Bacteria ,medicine ,bis-amidines ,Novobiocin ,030304 developmental biology ,0303 health sciences ,biology ,010405 organic chemistry ,Chemistry ,Pseudomonas aeruginosa ,checkerboard assays ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,3. Good health ,Infectious Diseases ,antibiotic synergy ,Pentamidine ,medicine.drug - Abstract
Pentamidine, an FDA-approved antiparasitic drug, was recently identified as an outer membrane disrupting synergist that potentiates erythromycin, rifampicin, and novobiocin against Gram-negative bacteria. The same study also described a preliminary structure–activity relationship using commercially available pentamidine analogues. We here report the design, synthesis, and evaluation of a broader panel of bis-amidines inspired by pentamidine. The present study both validates the previously observed synergistic activity reported for pentamidine, while further assessing the capacity for structurally similar bis-amidines to also potentiate Gram-positive specific antibiotics against Gram-negative pathogens. Among the bis-amidines prepared, a number of them were found to exhibit synergistic activity greater than pentamidine. These synergists were shown to effectively potentiate the activity of Gram-positive specific antibiotics against multiple Gram-negative pathogens such as Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, including polymyxin- and carbapenem-resistant strains.
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- 2021
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23. Mapping the influence of ligand electronics on the spectroscopic and 1O2 sensitization characteristics of Pd(<scp>ii</scp>) biladiene complexes bearing phenyl–alkynyl groups at the 2- and 18-positions
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Maxwell I. Martin, Trong-Nhan Pham, Kaytlin N. Ward, Anthony T. Rice, Phoebe R. Hertler, Glenn P. A. Yap, Philip H. Gilmartin, and Joel Rosenthal
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Inorganic Chemistry - Abstract
Extension of biladiene complexes via introduction of phenyl-alkynyl groups at the 2- and 18-positions generates new platforms that efficiently sensitize formation of 1O2 using long-visible light.
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- 2023
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24. Contributors
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Vidushi Agnihotri, Sampan Attri, Neha Baliyan, Ashok Kumar Bansal, Aditya Banyal, Hafiza Sidra Bashir, Dattatray Bedade, Manya Behl, Tek Chand Bhalla, Kulsajan Bhatia, Ravi Kant Bhatia, Shashi Kant Bhatia, Arvind Kumar Bhatt, Pradip Kumar Biswas, Abhishek Chaudhary, Dharam Paul Chaudhary, Shivani Chauhan, Debanko Das, Bindu Devi, Sarita Devi, Krunal Dholiya, Kiran Dindhoria, Subhasish Dutta, Hemant Ghai, Komaljeet Gill, Gunjan Goel, Ashutosh Gupta, Mahesh Kumar Gupta, Mahinder Kumar Gupta, Aakarsha Handa, Arshad Jawed, Christine Jeyaseelan, Prakriti Jhilta, Gopal Krishna Joshi, Rajesh Kaushal, Aman Kumar, Anil Kumar, Krishan Kumar, Neeraj Kumar, Pankaj Kumar, Pradeep Kumar, Raj Kumar, Rakshak Kumar, Vijay Kumar, Virender Kumar, Hannah I. Martin, Gillipsie Minhas, Srijana Mukhia, Tanya Munjal, Gitika Nagrath, Shivanti Negi, Deepak Pandey, Parmjit S. Panesar, Ashesh Parmar, Shruti Pathania, Debarati Paul, Shweta Pawar, Chayanika Putatunda, Paulraj Rajamani, Govindarajan Ramadoss, Babita Rana, Neerja Rana, Deepak Sakhuja, Kumar Sandeep, Aurijit Sarkar, Thirupathi Kumara Raja Selvaraj, Amit Seth, Saravanan Ramiah Shanmugam, Shashwat Sharad, Ajay Sharma, Arushi Sharma, Deep Raj Sharma, Deepak Sharma, Minakshi Sharma, Neel Kamal Sharma, Nisha Sharma, Nivedita Sharma, Pushpinder Sharma, Rupali Sharma, Shakshi Sharma, null Sheetal, Alla Singh, Ankit Singh, Archana Singh, Gunjan Singh, Jagdish Singh, Pranjali Singh, Sweta Sinha, Preeti Solanki, Gaurav Sood, Saurabh Thakar, Neerja Thakur, Abhishek Walia, Durgavati Yadav, Yung-Hun Yang, and Ragothaman M. Yennamalli
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- 2023
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25. In vivo Biodistribution of Kinetically Stable Pt2L4 Nanospheres that Show Anti-Cancer Activity
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Joost N. H. Reek, Eduard Bobylev, Renzo Knol, Simon Mathew, David PooleIII, Ioli Kotsogianni, Nathaniel I. Martin, Bas de Bruin, and Alexander Kros
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General Chemistry - Abstract
There is an increasing interest in the application of coordination-based spherical assemblies (CBSAs) in a bio medicinal context, as they can offer non-classical distribution in organisms compared to molecular substrates...
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- 2023
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26. A beginner’s guide to measuring binding affinity during biomolecular interactions
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Hannah I. Martin, Vidushi Agnihotri, Ragothaman M. Yennamalli, and Aurijit Sarkar
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- 2023
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27. Targeting membrane-bound bacterial cell wall precursors: a tried and true antibiotic strategy in nature and the clinic
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Ned P. Buijs, Eilidh J. Matheson, Stephen A. Cochrane, and Nathaniel I. Martin
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Materials Chemistry ,Metals and Alloys ,Ceramics and Composites ,General Chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Abstract
The bacterial cell wall is assembled via a coordinated biosynthetic cycle employing various membrane-anchored precursors. Sequestration of these uniquely bacterial building blocks remains a highly effective antibiotic strategy.
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- 2023
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28. The plant stress hormone jasmonic acid evokes defensive responses in streptomycetes
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Anne van der Meij, Somayah S. M. A. Elsayed, Chao Du, Joost Willemse, Thomas M. Wood, Nathaniel I. Martin, Jos M. Raaijmakers, and Gilles P. van Wezel
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Actinobacteria are prevalent in the rhizosphere and phyllosphere of diverse plant species where they help to enhance tolerance of plants against biotic and abiotic stresses. Here, we show that the plant hormones jasmonic acid (JA) and methyljasmonate (MeJA) alter growth, development and specialized metabolism ofStreptomyces. Challenge ofStreptomyces coelicolorwith JA or MeJA led to strongly enhanced production of the polyketide antibiotic actinorhodin. JA is toxic toStreptomycetaceae, whereby members of the genusStreptacidiphilusare generally more sensitive than streptomycetes. As a defensive response, extensive amino acid conjugation of JA was observed; the most prevalent conjugation was with glutamine (Gln), while conjugates with Val, Tyr, Phe and Leu/Ile were identified after longer exposure to JA. Synthetic JA conjugates failed to activate antibiotic production and had strongly reduced toxicity, strongly suggesting that conjugation inactivates JA and serves to detoxify the hormone. Thus, for the first time we provide evidence that plant hormones modulate growth, development and secondary metabolism of streptomycetes, whereby amino acid conjugation serves as a defense strategy by the bacteria to circumvent plant hormone toxicity.IMPORTANCEMicroorganisms that live on or inside plants greatly influence plant health. Streptomycetes are considered to have an important role in defense against plant diseases, but the mechanisms through which they protect plants are currently not fully understood. It has been suggested that streptomycetes respond to changes in the plant’s physiology, among others by producing protective molecules; however, little is known of the signal transduction from plant to bacterium. We here demonstrate that the plant hormones jasmonic acid (JA) and methyljasmonate (MeJA) directly influence the life cycle of streptomycetes by modulating antibiotic synthesis and promoting faster development. Moreover, the plant hormones specifically stimulate the synthesis of the polyketide antibiotic actinorhodin inStreptomyces coelicolor. Jasmonic acid is then modified in the cell by amino acid conjugation, which reduces the bioactivity of the hormone and thus quenches the signal. To the best of our knowledge, this has not been reported previously. Collectively, these results suggest a relationship between plant physiological changes and the response of streptomycetes in multiple ways.
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- 2022
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29. Loss of glutamatergic signalling from <scp>MCH</scp> neurons reduced anxiety‐like behaviours in novel environments
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Aditi S. Sankhe, Dillon Bordeleau, Diana I. Martin Alfonso, Gábor Wittman, and Melissa J. Chee
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Cellular and Molecular Neuroscience ,Endocrinology ,Endocrine and Autonomic Systems ,Endocrinology, Diabetes and Metabolism - Abstract
Melanin-concentrating hormone (MCH) neurons within the hypothalamus are heterogeneous and can coexpress additional neuropeptides and transmitters. The majority of MCH neurons express vesicular transporters to package glutamate for synaptic release, and MCH neurons can directly innervate downstream neurons via glutamate release. Although glutamatergic signalling from MCH neurons may support physiological and behavioural roles that are independent of MCH (e.g., in glucose homeostasis and nutrient-sensing), it can also mediate similar roles to MCH in the regulation of energy balance. In addition to energy balance, the MCH system has also been implicated in mood disorders, as MCH receptor antagonists have anxiolytic and anti-depressive effects. However, the contribution of glutamatergic signalling from MCH neurons to mood-related functions have not been investigated. We crossed Mch-cre mice with floxed-Vglut2 mice to delete the expression of the vesicular glutamate transporter 2 (Vglut2) and disable glutamatergic signalling specifically from MCH neurons. The resulting Mch-Vglut2-KO mice showed Vglut2 deletion from over 75% of MCH neurons, and although we did not observe changes in depressive-like behaviours, we found that Mch-Vglut2-KO mice displayed anxiety-like behaviours. Mch-Vglut2-KO mice showed reduced exploratory activity when placed in a new cage and were quicker to consume food placed in the centre of a novel open arena. These findings showed that Vglut2 deletion from MCH neurons resulted in anxiolytic actions and suggested that the anxiogenic effects of glutamate are similar to those of the MCH peptide. Taken together, these findings suggest that glutamate and MCH may synergize to regulate and promote anxiety-like behaviour.
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- 2022
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30. Synthesis, Electrochemistry, and Photophysics of Pd(II) Biladiene Complexes Bearing Varied Substituents at the sp3-Hybridized 10-Position
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An Yu, Craig A. Pointer, Brendan Davies, Elizabeth R. Young, Kaytlin Ward, Qiuqi Cai, Glenn P. A. Yap, Anthony T. Rice, Joel Rosenthal, Maxwell I. Martin, Phoebe R. Hertler, and Molly C. Warndorf
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Inorganic Chemistry ,chemistry.chemical_compound ,Geminal ,Chemistry ,Singlet oxygen ,Ultrafast laser spectroscopy ,Physical and Theoretical Chemistry ,Absorption (chemistry) ,Isostructural ,Electrochemistry ,Spectroscopy ,Medicinal chemistry - Abstract
A set of Pd(II) biladiene complexes bearing different combinations of methyl- and phenyl-substituents on the sp3-hybridized meso-carbon (the 10-position of the biladiene framework) was prepared and studied. In addition to a previously described Pd(II) biladiene complex bearing geminal dimethyl substituents a the 10-position (Pd[DMBil]), homologous Pd(II) biladienes bearing geminal methyl and phenyl substituents (Pd[MPBil1]) and geminal diphenyl groups(Pd[DPBil1]) were prepared and structurally characterized. Detailed electrochemical as well as steady-state and time-resolved spectroscopic experiments were undertaken to evaluate the influence of the substituents on the biladiene's tetrahedral meso-carbon. Although all three biladiene homologues are isostructural, Pd[MPBil1] and Pd[DPBil1] display more intense absorption profiles that shift slightly toward lower energies as geminal methyl groups are replaced by phenyl rings. All three biladiene homologues support a triplet photochemistry, and replacement of the geminal dimethyl substituents of Pd[DMBil1] (ΦΔ = 54%) with phenyl groups improves the ability of Pd[MPBil1] (ΦΔ = 76%) and Pd[DPBil1] (ΦΔ = 66%) to sensitize 1O2. Analysis of the excited-state dynamics of the Pd(II) biladienes by transient absorption spectroscopy shows that each complex supports a long-lived triplet excited-state (i.e., τ > 15 μs for each homologue) but that the ISC quantum yields (ΦT) varied as a function of biladiene substitution. The observed trend in ISC efficiency matches that for singlet oxygen sensitization quantum yields (ΦΔ) across the biladiene series considered in this work. The results of this study provide new insights to guide future development of biladiene based agents for PDT and other photochemical applications.
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- 2021
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31. Family Conflicts, Coping Skills, Depressive Symptoms, and Gender Among Korean American Adolescents: Mediating Effects of Self-Esteem
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James I. Martin, So-Young Park, Tazuko Shibusawa, Michelle A. Williams, and Yeddi Park
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Coping (psychology) ,Sociology and Political Science ,media_common.quotation_subject ,Korean americans ,Self-esteem ,Family conflict ,Psychology ,Social Sciences (miscellaneous) ,Depressive symptoms ,media_common ,Clinical psychology - Abstract
Objective: This study examines the prevalence of depressive symptoms among Korean American (KA) adolescents and explores the complex relationships among family conflicts, coping skills, sel...
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- 2021
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32. A Developmental Biology Inspired Osteoarthritis 3din Vitromicro-Cartilage Model To Study Effects Of Pro-Anabolic And Anti-Inflammatory Factors On Tissue Homeostasis
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L. Dönges, M. Schönenberger, T. Bock, C. Egloff, I. Martin, and A. Barbero
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Rheumatology ,Biomedical Engineering ,Orthopedics and Sports Medicine - Published
- 2023
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33. Towards Modelling The Joint On A Chip: A Mechanically Active Microfluidic System Designed For Engineered 3d Multi-Layer Osteochondral Tissues
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A. Mainardi, P. Occhetta, I. Martin, M. Rasponi, and A. Barbero
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Rheumatology ,Biomedical Engineering ,Orthopedics and Sports Medicine - Published
- 2023
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34. Leveraging Baird aromaticity for advancement of bioimaging applications
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Maxwell I. Martin, Avik K. Pati, Chathura S. Abeywickrama, Sukanta Bar, Zeliha Kilic, Roger B. Altman, and Scott C. Blanchard
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Organic Chemistry ,Physical and Theoretical Chemistry - Published
- 2022
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35. How Does the Effect of the Comprehensive Care for Joint Replacement Model Vary Based on Surgical Volume and Costs of Care?
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Hyunkyu Ko, Brook I. Martin, Richard E. Nelson, and Christopher E. Pelt
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Public Health, Environmental and Occupational Health - Abstract
The Center for Medicare and Medicaid Innovation revised the comprehensive Care for Joint Replacement (CJR) program, a mandatory 90-day bundled payment for lower extremity joint replacement, in December 2017, retaining 34 of the original 67 metropolitan statistical areas with higher volume and historic episode payments.We describe differences in costs, quality, and patient selection between hospitals that continued to participate compared with those that withdrew from CJR before and after the implementation of CJR.We used a triple difference approach to compare the magnitude of the policy effect for elective admissions between hospitals that were retained in the CJR revision or not, before and after the implementation of CJR, and compared with hospitals in nonparticipant metropolitan statistical areas.694,275 Medicare beneficiaries undergoing elective lower extremity joint replacement from January 1, 2013 to August 31, 2017.The treatment effect heterogeneity of CJR.Hospitals retained in the CJR policy revision had a greater reduction in 90-day episode-of-care cost compared with those that were allowed to discontinue (-$846, 95% CI: -$1,338, -$435) and had greater cost reductions in the more recent year (2017). We also found evidence that retained CJR hospitals disproportionately reduced treating patients who were older than 85 years.Hospitals that continued to participate in CJR after the policy revision achieved a greater cost reduction. However, the cost reductions were partly attributed to avoiding potential higher - cost patients, suggesting that a bundled payment policy might induce disparities in care delivery.
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- 2022
36. Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose Associated 90-day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE-III)
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Yahya Shehabi, Ary Serpa Neto, Rinaldo Bellomo, Belinda D. Howe, Yaseen M. Arabi, Michael Bailey, Frances E. Bass, Suhaini Bin Kadiman, Colin J. McArthur, Michael C. Reade, Ian M. Seppelt, Jukka Takala, Matt P. Wise, Steve A. Webb, C. Mashonganyika, H. McKee, A. Tonks, A. Donnelly, N. Hemmings, S. O’Kane, A. Blakemore, M. Butler, K. Cowdrey, J. Dalton, E. Gilder, S. Long, L. McCarthy, S. McGuinness, R. Parke, Y. Chen, C. McArthur, R. McConnochie, L. Newby, R. Bellomo, G. Eastwood, L. Peck, H. Young, C. Boschert, J. Edington, J. Fletcher, J. Smith, K. Nand, A. Raza, T. Sara, J. Bennett-Britton, J. Bewley, V. Bodenham, L. Cole, K. Driver, L. Grimmer, L. Howie, C. Searles, K. Sweet, D. Webster, A. van Berkel, H. Connor, J. Dennett, M. van Der Graaff, S. Henderson, J. Mehrtens, K. Miller, E. Minto, A. Morris, S. Noble, K. Parker, L. Bulfin, N. Hart, K. Shepherd, S. Vij, S. Dickson, E. Elloway, C. Ferguson, R. Jackson, P. MacNaughton, M. Marner, R. Squire, S. Waddy, P. Wafer, J. Welbourne, P. Ashcroft, D. Chambler, S. Dukes, A. Harris, S. Horton, S. Sharpe, P. Williams, S. Williams, M. Bailey, E. Blazquez, D. France, R. Hutchison, A. O’Connor, G. Comadira, M. Gough, M. Tallott, M. Bastick, R. Cameron, S. Donovan, K. Ellis, A. Gaur, R. Gregory, J. Naumoff, E. Turner, M. White, K. F. J. Au, J. Fratzia, S. Treloar, C. H. Lim, Y. Maseeda, A. P. Tan, C. L. Tang, C. Y. Yong, M. Akaltan, S. Berger, D. Blaser, L. Fazlija, M. L. Jong, M. Lensch, R. Ludwig, T. Merz, K. Nettelbeck, M. Roth, M. Schafer, J. Takala, A. Wehr, D. Zacharias, R. Amran, H. N. Ashraf, N. Azmi, N. Basri, H. Burhanuddin, Y. Hadinata, A. Hamdan, S. Kadiman, A. I. Y. M. Rashid, I. N. Sabran, S. Sulaiman, I. N. Zabidi, A. Al-Dawood, M. Aljuaid, H. Al Anizi, A. Al Saeedi, Y. Arabi, M. Dbsawy, A. Deeb, M. Hegazy, I. Magdi, E. Clarey, E. Corcoran, C. Finney, C. Harris, P. Hopkins, H. Noble, L. Thompson, T. Williams, L. A. Dumlao, R. Bassam, M. A. Hassan, N. Naseem, M. H. Al-Kurdi, A. M. Al-Harthy, S. Bernard, L. Sebafundi, C. Serban, S. K. Lim, N. Mazidah, N. Saidin, N. Sjamsuddin, I. T. A. Tan, N. Zabidi, M. Brain, S. Mineall, M. Kanhere, N. Soar, N. Abd Kadir, N. H. Abdullah, R. Awang, Z. Emperan, N. S. Husin, N. I. Ismail, S. Z. Ismail, F. N. A. Mohd Khadzali, M. F. Norddin, J. Aguila, C. Bold, B. Clatworthy, A. Dias, C. Hogan, A. Kazemi, V. Lai, R. Song, A. Williams, D. Bhatia, S. Elliot, P. Galt, K. Lavrans, P. Ritchie, A. Wang, R. Gresham, J. Lowrey, K. Masters, P. Palejs, I. Seppelt, F. Symonds, L. Weisbrodt, C. Whitehead, M. Babio-Galan, V. Calder, I. Clement, A. Harrison, I. McCullagh, C. Scott, R. Bevan, S. Caniba, D. Hacking, L. Maher, M. L. Azzolini, P. Beccaria, S. Colombo, G. Landoni, C. Leggieri, C. Luca, D. Mamo, E. Moizo, G. Monti, M. Mucci, A. Zangrillo, M. Albania, S. Arora, Y. Shi, A. Abudayah, G. Almekhlafi, E. Al Amodi, S. Al Samarrai, M. Badawi, R. Cubio Caba, O. Elffaki, Y. Mandourah, J. Valerio, C. Joyce, J. Meyer, E. Saylor, B. Venkatesh, E. Venz, J. Walsham, K. Wetzig, T. M. Khoo, J. E. S. Liew, A. N. Sakthi, A. Zulkurnain, A. Bamford, C. Bergin, R. Carrera, L. Cooper, L. Despy, S. Harkett, L. Mee, E. Reeves, C. Snelson, E. Spruce, G. Cooper, R. Hodgson, D. Pearson, M. Rosbergen, M. N. Ali, N. I. Bahar, A. Ismail, W. N. W. Ismail, N. M. Samat, N. S. M. Piah, R. Abd Rahman, M. Duroux, M. Ratcliffe, T. Warhurst, U. Buehner, E. Williams, N. Jacques, L. Keating, S. Macgill, K. L. Tamang, N. Tolan, A. Walden, R. Bower, J. Cranshaw, K. Molloy, S. Pitts, J. Butler, R. Dunlop, C. Fourie, P. Jarrett, M. Lassig-Smith, A. Livermore, S. O’Donoghue, M. Reade, T. Starr, J. Stuart, L. Campbell, M. Phillips, D. Stephens, J. Thomas, D. Cooper, R. McAllister, G. Andrew, L. Barclay, H. Dawson, D. M. Griffith, D. Hope, G. Wojcik, C. McCulloch, R. Paterson, L. Ascough, C. Paisley, J. Patrick-Heselton, D. Shaw, V. Waugh, K. Williams, I. Welters, D. Barge, A. Jordan, C. MacIsaac, T. Rechnitzer, F. Bass, J. Gatward, N. Hammond, P. Janin, W. Stedman, E. Yarad, N. A. Razak, N. Dzulkipli, S. L. Jong, K. Asen, W. L. Voon, S. Liew, J. Ball, V. Barnes, C. Dalton, S. Farnell-Ward, H. Farrah, K. Maher, J. Mellinghoff, C. Ryan, P. Shirley, L. Conlon, A. Glover, I. Martin-Loeches, E. O’Toole, J. Ewan, J. Ferrier, E. Litton, S. A. Webb, W. Berry, U. Blanco Alonso, A. Bociek, S. Campos, S. Jawara, F. Hanks, A. Kelly, K. Lei, C. McKenzie, M. Ostermann, R. Wan, S. Al-Soufi, S. Leow, K. McCann, C. Reynolds, K. Brickell, C. Fahey, L. Hays, N. Hyde, A. Nichol, D. Ryan, J. Brailsford, A. Buckley, L. Forbes, T. Maguire, J. Moore, L. Murray, A. Ghosh, M. Park, S. Said, A. Visser, H. Z. Abidin, S. Ali, M. H. Hassan, S. C. Omar, W. F. W. Shukeri, D. Brealey, G. Bercades, E. Blackburn, N. Macallum, A. Macklin, J. H. Ryu, K. Tam, D. Smyth, A. Arif, C. Bassford, C. Morgan, C. Swann, G. Ward, L. Wild, A. Bone, T. Elderkin, D. Green, D. Sach, T. Salerno, N. Simpson, F. Brohi, M. Clark, L. Williams, J. Brooks, E. Cocks, J. Cole, J. Curtin, R. Davies, H. Hill, M. Morgan, N. Palmer, C. Whitton, M. Wise, P. Baskaran, M. S. Hasan, L. Y. Tham, R. Sol Cruz, D. Dinsdale, S. Edney, C. Firkin, F. FitzJohn, G. Hill, A. Hunt, S. Hurford, G. Jones, H. Judd, C. Latimer-Bell, C. Lawrence, E. Lesona, L. Navarra, Y. Robertson, H. Smellie, A. M. Vucago, P. Young, P. Clark, J. Kong, J. Ho, V. Nayyar, and C. Skelly
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Pulmonary and Respiratory Medicine ,Critical Care and Intensive Care Medicine - Abstract
Sedation Practice in Intensive Care Evaluation (SPICE-III) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation.to quantify the association of different infusion rates of dexmedetomidine or propofol, given in combination, with mortality and if this is modified by age.We included 1177 patients randomized in SPICE-III to receive dexmedetomidine and given supplemental propofol, stratified by age (65 or ≤65 years). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine, while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression, adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality.Younger patients 598/1177(50.8%) received a significantly higher dose of both sedatives compared with older patients, to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 mcg/kg/h) was associated with reduced adjusted mortality in younger, but not older patients. This was consistent with multivariable regression modelling [hazard ratio: 0.59(95% Confidence Interval 0.43-0.78),P0.0001], adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality [HR:1.30(95%CI 1.03-1.65), P=0.029].In patients ≤ 65 years sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registration available at www.gov, ID: NCT01728558.
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- 2022
37. Global and regional left ventricular deformation evaluation with feature tracking in transthyretin cardiac amyloidosis. Comparison with echocardiographic findings
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D Bastidas Plaza, E Pozo Osinalde, F Islas, L Perez De Isla, P Marcos-Alberca, P Hernandez, I Martin-Lores, M Luaces Mendez, J J Gomez De Diego, A Bustos, J Perez-Villacastin, and J A De Agustin
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Cardiology and Cardiovascular Medicine - Abstract
Background Diagnosis of cardiac amyloidosis (CA) is basically based on imaging techniques. Transthoracic echocardiography (TTE) is crucial to raise suspicion of this disease through detection of the classical features. An specific left ventricular (LV) deformation pattern with apical sparing (“cherry on top”) has been described on speckle tracking (ST) TTE. However, there is no data regarding the role of the LV global and regional analysis with the new tool feature tracking (FT) of cardiac magnetic resonance (CMR) in CA. Purpose Our aim is to analyze the concordance of LV deformation between ST-TTE and FT-CMR. Methods Consecutive patients with definitive diagnosis of transthyretin (TTR) CA, based on DPD scintigraphy, and imaging evaluation with TTE and CMR were retrospectively included. LV volumes and ejection were calculated from both TTE and CMR following the ongoing recommendations. Global and segmental longitudinal strain values were obtained from apical 2-, 3- and 4-chambers projections on TTE, while the same parameters were calculated on the same cine views of CMR using a dedicated software of FT analysis. Student t-test was used to compared mean measurements derived from both imaging techniques. Apical index was calculated as the ratio between apical and basal-mid longitudinal values. Moreover, agreement was established using Passing-Bablok regression analysis. Results 27 patients (80 years-old, 88% men) with definitive diagnosis of TTR CA from our tertiary hospital were included. Regarding echocardiographic findings, 80% showed concentric LV hypertrophy with low normal ejection fraction in the majority (52±10%). When longitudinal LV strain parameters were compared (Table 1), no differences were noted in global and apical values whereas basal and mid measurements were higher from CRM resulting in different apical indexes. Although 42% showed a typical “cherry on top” pattern in ST analysis, in only 18% of the FT apical sparing was detected. Consistently, decremental pattern was observed in 60% of TTE and in 20% of CMR. Concordance analysis with Passing-Bablok showed no constant or proportional differences, meaning both techniques were comparable. Conclusions Among patients with TTR CA there were no differences in global longitudinal LV strain analysis between ST-TTE and FT-CMR. Nevertheless, discordance in regional parameters resulted in a less frequent detection of apical sparing in CMR. Funding Acknowledgement Type of funding sources: None.
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- 2022
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38. Efficacy and safety of selexipag in real-life in patients with pulmonary arterial hypertension: early results of RAMPHA study
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R Bravo Marques, V Becerra Munoz, A J Walls Rodriguez, F Espildora Hernandez, J L Callejas Rubio, J I Morgado Garcia De Polavieja, I Martin Suarez, J L Bonilla Palomas, F Rivas-Ruiz, and A Recio Mayoral
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Cardiology and Cardiovascular Medicine - Abstract
Background Pulmonary arterial hypertension (PAH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and leading to right heart failure and death. Selexipag, an oral prostacyclin IP receptor agonist, has been shown to decrease morbidity and mortality compared to patients treated with placebo. Purpose Our aim was to evaluate the efficacy and safety of Selexipag in patients with PAH in real-life. Methods The RAMPHA study was a multicenter, observational and retrospective trial of patients who had PAH and began taking Selexipag between 2017–2021. We analyzed baseline characteristics, risk profiles, clinical assessments that were used for risk stratification and events in follow-up time. Results 29 patients aged 48±14 were initially studied. 23 (79%) were women. Within the pulmonary hypertension-classification, 10 (34,5%) had PAH associated-congenital heart disease, 9 (31%) had idiopathic HAP, 7 (24,1%) had PAH associated with connective tissue disease, 1 had PAH associated to HIV and 2 heritable PAH. The time from PAH diagnoses to the beginning of Selexipag treatment was 54 months (IQR 89). 89,7% (26) were in treatment with doubled combination therapy with PDE5i+ARE; Sildenafil was the most widely used PDE5i and bosentan (37,9%) the most used ARE. No patients were under treatment with intravenous prostacyclin analogue, but 3 were with Treprostinil (1 of them subcutaneous and 2 inhaled) and 2 patients with iloprost. Most patients were categorized in intermediate risk profile (figure 1), using the risk stratification strategy of ESC/ERS PH guidelines. In the approach of risk assessment before start with Selexipag, clinical, functional, exercise (with 6MWT) and echocardiographic variables were used in all the patients. Biochemical variables with NT-proBNP were used in 93% of the patients. Only 15 patients had a right catheterization to get haemodynamic parameters before the treatment. At follow up, 11 patients (38%) improved functional class, only 1 patient got worst (p=0,001). 3 patients improved risk-profile in the exercise test and, in the others, a quantitative improvement was found. NT-proBNP levels were not significant better (924ng/l IQR 1209 vs 760ng/l IQR 1397). There were not changes in RV function in the echocardiographic parameters. Selexipag was well-tolerated, 86% of the patients experienced side effects, but none had to discountinue the treatment. The most common side effect was headache. The titration lasted 68 days (IQR 72) and 38% of the patients got maximum doses. At the medium-term follow-up of 52 months, the free-event survival (worsening of PAH that resulted in hospitalization; initiation of parenteral prostanoid therapy or death to PAH; or any cause) was 80% (Figure 2). Conclusion Selexipag, added as triple combination therapy in patients with PAH intermediate risk, improved risk variables, was well tolerated and achieved a medium-long-term free-event survival greater than 80%. Funding Acknowledgement Type of funding sources: None.
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- 2022
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39. Self-withdrawal from scheduled bariatric surgery: Qualitative study exploring patient and healthcare provider perspectives
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Mary I. Martin, Vanessa Ha, Laurie Fasola, Nancy Dalgarno, and Boris Zevin
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Endocrinology, Diabetes and Metabolism - Abstract
The objective of the study was to explore the experience of patients who self-withdrew from their scheduled bariatric surgery (BS) after completing the lengthy multidisciplinary assessment and optimization process, and to examine how these withdrawals affect healthcare providers (HCPs) in a Bariatric Centre of Excellence (BCoE). Interviews were conducted with patients who self-withdrew, within 1 month, from scheduled BS. Additionally, a focus group with HCPs from the same BCoE was completed. The data were analysed using an inductive, emergent thematic approach with open coding in NVivo 12, with comparative analysis to identify common themes between groups. Eleven patients and 14 HCPs participated. HCPs identified several behavioural and logistical red flags among patients who self-withdrew from scheduled BS. Patients and HCPs felt the decision was appropriate, owing to a patient's lack of mental preparedness for change, social supports, or fears of postoperative complications. HCPs reported frustration and described negative impacts on clinic efficiency. Additional mental health resources for patients contemplating self-withdrawal, such as peer support, were suggested. In conclusion, a patient's decision to self-withdraw from a scheduled BS is often sudden, definite, and associated with anxiety, fear of surgical risks and post-operative complications. Additional mental health resources at a BCoE may be beneficial to support patients at risk of self-withdrawal from scheduled BS.
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- 2022
40. PSP kinetics in the prediction of VAP diagnosis
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A Ceccato, M Camprubi, L Bos, P Povoa, I Martin-Loeches, A Areny, E Campaña, L Morales, P Ramirez, M Esperatti, A Torres, and A Artigas
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- 2022
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41. Genomic profiling for clinical decision making in lymphoid neoplasms
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Laurence de Leval, Ash A. Alizadeh, P. Leif Bergsagel, Elias Campo, Andrew Davies, Ahmet Dogan, Jude Fitzgibbon, Steven M. Horwitz, Ari M. Melnick, William G. Morice, Ryan D. Morin, Bertrand Nadel, Stefano A. Pileri, Richard Rosenquist, Davide Rossi, Itziar Salaverria, Christian Steidl, Steven P. Treon, Andrew D. Zelenetz, Ranjana H. Advani, Carl E. Allen, Stephen M. Ansell, Wing C. Chan, James R. Cook, Lucy B. Cook, Francesco d’Amore, Stefan Dirnhofer, Martin Dreyling, Kieron Dunleavy, Andrew L. Feldman, Falko Fend, Philippe Gaulard, Paolo Ghia, John G. Gribben, Olivier Hermine, Daniel J. Hodson, Eric D. Hsi, Giorgio Inghirami, Elaine S. Jaffe, Kennosuke Karube, Keisuke Kataoka, Wolfram Klapper, Won Seog Kim, Rebecca L. King, Young H. Ko, Ann S. LaCasce, Georg Lenz, José I. Martin-Subero, Miguel A. Piris, Stefania Pittaluga, Laura Pasqualucci, Leticia Quintanilla-Martinez, Scott J. Rodig, Andreas Rosenwald, Gilles A. Salles, Jesus San-Miguel, Kerry J. Savage, Laurie H. Sehn, Gianpietro Semenzato, Louis M. Staudt, Steven H. Swerdlow, Constantine S. Tam, Judith Trotman, Julie M. Vose, Oliver Weigert, Wyndham H. Wilson, Jane N. Winter, Catherine J. Wu, Pier L. Zinzani, Emanuele Zucca, Adam Bagg, and David W. Scott
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Lymphoma ,Neoplasms ,Immunology ,Clinical Decision-Making ,Humans ,High-Throughput Nucleotide Sequencing ,Cell Biology ,Hematology ,Genomics ,Precision Medicine ,Biochemistry - Abstract
With the introduction of large-scale molecular profiling methods and high-throughput sequencing technologies, the genomic features of most lymphoid neoplasms have been characterized at an unprecedented scale. Although the principles for the classification and diagnosis of these disorders, founded on a multidimensional definition of disease entities, have been consolidated over the past 25 years, novel genomic data have markedly enhanced our understanding of lymphomagenesis and enriched the description of disease entities at the molecular level. Yet, the current diagnosis of lymphoid tumors is largely based on morphological assessment and immunophenotyping, with only few entities being defined by genomic criteria. This paper, which accompanies the International Consensus Classification of mature lymphoid neoplasms, will address how established assays and newly developed technologies for molecular testing already complement clinical diagnoses and provide a novel lens on disease classification. More specifically, their contributions to diagnosis refinement, risk stratification, and therapy prediction will be considered for the main categories of lymphoid neoplasms. The potential of whole-genome sequencing, circulating tumor DNA analyses, single-cell analyses, and epigenetic profiling will be discussed because these will likely become important future tools for implementing precision medicine approaches in clinical decision making for patients with lymphoid malignancies.
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- 2022
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42. Improving Designer Learning in Design Space Exploration by Adapting to the Designer’s Learning Goals
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Antoni Virós-i-Martin and Daniel Selva
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Design space exploration is a design method by which the designer tries to learn important information about a design problem (e.g., main design trade-offs, sensitivities, common features among good designs) to help them make better design decisions. This paper presents preliminary results of a study characterizing the effects on a designer’s learning of an AI assistant that adapts to the designer’s goals during design space exploration. Specifically, we compare the designer’s learning when the AI assistant adapts to explicit learning goals shared by the designer versus when it does not adapt. The AI assistant used for the study is Daphne, which helps engineers design Earth observation satellite systems. The designer’s learning process is modeled as an iterative hypothesis generation and testing process. First, the designer shares with Daphne a certain learning goal in the form of a hypothesis (e.g., designs with feature F are more likely to be on the Pareto front). Then, Daphne adapts to this goal by searching for more designs that have the feature being tested and showing the user the extent to which the data supports their hypothesis. The participants in the preliminary study are N = 10 students from Texas A&M University. We ask each participant to design earth observation satellite constellations to meet a set of requirements while trying to learn about the design problem. The results show that participants with the adaptive AI assistant consistently score higher on their learning about the design task compared to the baseline design assistant as measured by a post-task test. A negative effect is observed on task performance with the adaptive AI assistant condition due to a smaller number of design creation actions, which is consistent with findings from previous studies. Recommendations are provided for the design of similar future AI assistants based on the results of this study. Finally, a power study is done to set a goal for statistical validity of the study.
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- 2022
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43. Synthesis, Spectroscopic, and 1O2 Sensitization Characteristics of Extended Pd(II) 10,10-Dimethylbiladiene Complexes Bearing Alkynyl–Aryl Appendages
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Glenn P. A. Yap, Maxwell I. Martin, Molly C. Warndorf, Anthony T. Rice, and Joel Rosenthal
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Singlet oxygen ,medicine.medical_treatment ,Aryl ,Sonogashira coupling ,chemistry.chemical_element ,Photodynamic therapy ,Conjugated system ,Tetrapyrrole ,Combinatorial chemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,medicine ,Physical and Theoretical Chemistry ,Visible spectrum ,Palladium - Abstract
Photodynamic therapy (PDT), which involves the photoinduced sensitization of singlet oxygen, is an attractive treatment for certain types of cancer. The development of new photochemotherapeutic agents remains an important area of research. Macrocyclic tetrapyrrole compounds including porphyrins, phthalocyanines, chlorins, and bacteriochlorins have been pursued as sensitizers of singlet oxygen for PDT applications but historically are difficult to prepare/purify and can also suffer from high nonspecific dark toxicity, poor solubility in biological media, and/or slow clearance from biological tissues. In response to these shortcomings, we have developed a series of novel linear tetrapyrrole architectures complexed to late transition metals as potential PDT agents. We find that these dimethylbiladiene (DMBil1) tetrapyrrole complexes can efficiently photosensitize generation of 1O2 oxygen upon irradiation with visible light. To extend the absorption profile of the DMBil1 platform, alkynyl-aryl groups have been conjugated to the periphery of the tetrapyrrole using Sonogashira methods. Derivatives of this type containing ancillary phenyl (DMBil-PE), naphthyl (DMBil-NE), and anthracenyl (DMBil-AE) groups have been prepared and characterized. In addition to structurally characterizing Pd[DMBil-NE] and Pd[DMBil-AE], we find that extension of the tetrapyrrole conjugation successfully red-shifts the absorption of the DMBil-Ar family of biladienes further into the phototherapeutic window (i.e., 600-900 nm). Photochemical sensitization studies demonstrate that our series of new palladium biladiene complexes (Pd[DMBil-Ar]) can sensitize the formation of 1O2 with quantum yields in the range ΦΔ = 0.59-0.73 upon irradiation with light of λ ≥ 650 nm. The improved absorption properties of the Pd[DMBil-Ar] complexes in the phototherapeutic window, together with their high 1O2 quantum yields, highlight the promise of these compounds as potential agents for PDT.
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- 2021
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44. Synthesis, structure, electronic characterization, and halogenation of gold(III) phlorin complexes
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Maxwell I. Martin, Glenn P. A. Yap, Allen J. Pistner, and Joel Rosenthal
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010405 organic chemistry ,Metalation ,Halogenation ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Tetrapyrrole ,Redox ,0104 chemical sciences ,Characterization (materials science) ,chemistry.chemical_compound ,Gold iii ,chemistry ,Polymer chemistry ,Spectroscopy - Abstract
The metalation chemistry of the phlorin, which is a non-aromatic tetrapyrrole macrocycle containing a single sp3-hybridized meso-carbon has remained underdeveloped, as compared to that of more traditional tetrapyrroles such as porphyrins, corroles and phthalocyanines. There have been few prior efforts to prepare metallophlorins, and those that have been reported have relied on either reduction or nucleophilic attack of parent metalloporphyrins, rather than direct metalation of freebase phlorin constructs. In this work, an alternate synthetic approach for preparation of gold(III) phlorin complexes that involves the first direct metalation of two different freebase phlorin derivatives (3H(Phl[Formula: see text] and 3H(Phl[Formula: see text] with AuBr3 to produce the stable and fully isolable gold(III) phlorin complexes Au(Phl[Formula: see text] and Au(Phl[Formula: see text] is reported. The first structural characterization of a metallophlorin bearing geminal dimethyl substituents at the sp3-hybridized meso-carbon via X-ray crystallography is also reported. In addition to the preparation of Au(Phl[Formula: see text] and Au(Phl[Formula: see text], the UV-vis absorption and redox properties of these two gold(III) phlorins in comparison to those of their freebase homologues is also detailed. Notably, the metallophlorins are characterized by panchromatic absorbance profiles and intense and broad bands that span the long-visible and into the near-IR regions, as well as two fully reversible oxidation and reduction waves as probed by cyclic voltammetry. Finally, the chlorination of Au(Phl[Formula: see text] using PhI(Cl[Formula: see text] was probed and it was found that this regioslective reaction generates monochlorinated (Au(Phl[Formula: see text]Cl)) and dichlorinated (Au(Phl[Formula: see text]Cl[Formula: see text] products, which were both structurally characterized by X-ray crystallography.
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- 2021
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45. Niveles de vitamina D en sangre materna y su relación con el consumo de pescado y los parámetros antropométricos de los recién nacidos en una cohorte de parejas madre/hijos de Sevilla
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B. Dahiri, P. Carbonero-Aguilar, I. Martin-Carrasco, R. Carrillo, N. Florez, L. Cerrillos, R. Ostos, J. Bautista, and I. Moreno
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Reproductive Medicine ,Obstetrics and Gynecology - Published
- 2023
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46. Tissue Engineering: GOOD MANUFACTURING PRACTICE-COMPLIANT CHANGE OF RAW MATERIAL IN THE MANUFACTURING PROCESS OF A CLINICALLY USED ADVANCED THERAPY MEDICINAL PRODUCT: A COMPARABILITY STUDY
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A. Wixmerten, S. Miot, P. Bittorf, F. Wolf, S. Feliciano, S. Hackenberg, S. Häusner, W. Krenger, M. Haug, I. Martin, O. Pullig, and A. Barbero
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Cancer Research ,Transplantation ,Oncology ,Immunology ,Immunology and Allergy ,Cell Biology ,Genetics (clinical) - Published
- 2023
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47. Tissue Engineering: AUTOLOGOUS TISSUE ENGINEERED GRAFT FOR PHALANX CONSTRUCTION IN CHILDREN WITH SYMBRACHYDACTYLY, A PROOF OF CONCEPT
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R. Schaller, M. Chaaban, G. Zhang, D. Schäfer, A. Kaempfen, I. Martin, A. Scherberich, and A. Moya
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Cancer Research ,Transplantation ,Oncology ,Immunology ,Immunology and Allergy ,Cell Biology ,Genetics (clinical) - Published
- 2023
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48. Eye-tracking as a window into assembled phonology in native and non-native reading
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Alan Juffs and Katherine I. Martin
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050101 languages & linguistics ,Linguistics and Language ,First language ,media_common.quotation_subject ,05 social sciences ,Grapheme ,Phonology ,Pronunciation ,050105 experimental psychology ,Language and Linguistics ,Linguistics ,Education ,Reading comprehension ,Reading (process) ,Eye tracking ,0501 psychology and cognitive sciences ,Psychology ,Word (group theory) ,media_common - Abstract
The past 30 years of reading research has confirmed the importance of bottom-up processing. Rather than a psycholinguistic guessing game (Goodman, 1967), reading is dependent on rapid, accurate recognition of written forms. In fluent first language (L1) readers, this is seen in the automatic activation of a word’s phonological form, impacting lexical processing (Perfetti & Bell, 1991; Rayner, Sereno, Lesch & Pollatsek, 1995). Although the influence of phonological form is well established, less clear is the extent to which readers are sensitive to the possible pronunciations of a word (Lesch & Pollatsek, 1998), derived from the varying consistency of grapheme-to-phoneme correspondences (GPCs) (e.g., although ‘great’ has only one pronunciation, [ɡɹeɪt], the grapheme within it has multiple possible pronunciations: [i] in [plit] ‘pleat’, [ɛ] in [bɹɛθ] ‘breath’; Parkin, 1982). Further, little is known about non-native readers’ sensitivity to such characteristics. Non-native readers process text differently from L1 readers (Koda & Zehler, 2008; McBride-Chang, Bialystok, Chong & Li, 2004), with implications for understanding L2 reading comprehension (Rayner, Chace, Slattery & Ashby, 2006). The goal of this study was thus to determine whether native and non-native readers are sensitive to the consistency of a word’s component GPCs during lexical processing and to compare this sensitivity among readers from different L1s.
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- 2021
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49. P740 Dual biologic therapy for patients with Inflammatory Bowel Disease in a single reference center in Spain
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M T Diz Lois Palomares, Á Porta Sánchez, B González Conde, E Estévez Prieto, M T Vázquez Rey, L Elberdin Pazos, P Alonso Aguirre, and I Martin Herranz
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Gastroenterology ,General Medicine - Abstract
Background In the last 5 years, the therapeutic arsenal in IBD has been expanded. Four different groups of effective biologic/new small molecules therapies, according to the target (anti-TNF, anti-integrin, anti-IL-12/23; and JAK inhibitors), are being widely used. There is still a significant number of patients who do not respond. In the last years, in tertiary centers, two simultaneous biologic therapies have been associated in a few IBD patients in clinical practice, in order to treat two different patient profiles: patients with IBD and concurrent extraintestinal manifestations (EIMs) which did not respond to the same biologic treatment, and second, refractory-IBD patients. It seems to add efficacy in case-series. However, safety concerns limit its use. We aim to describe the 6 patients treated in a single reference center in A Coruña, Spain. Methods The IBD Unit in A Coruña Universitary Hospital is the reference center for a 550000 patient population. Advance therapy with biologics is centralized in this IBD Unit, with approximately 630 patients having been treated with biologic therapy. Since 2020, we have treated 6 patients with dual biologic therapy (DBT), after discussing the case in the multidisciplinar IBD-Committee and with the informed consent of the patients. We describe this case-series. Results Our 6 patients proposed to DBT had long-standing IBD, and presented failure to 3-5 previous advanced lines of therapy. Two had ≥ 2 previous resection surgeries, and for 3 patients the surgery option would include a permanent stoma, or high risk of short bowel syndrome because of extensive disease. We describe in table 1 patient’s demographics, IBD characteristics, and the DBT combinations. In table 2 we further describe DBT and response to treatment. Main indication for DBT was refractory IBD in 5/6 patients. DBT was intensified in all these cases. It added efficacy in 2/5 cases, however without achieving deep remission. Three patients (3/5) were co-treated with steroids. One patient had a serious infectious adverse event that required hospitalisation. In 1/6 patient the indication for DBT was IBD and concurrent EIMs, each one responding to different biologic, this patient was initially co-treated with IMM and steroids; dual therapy was effective and safe, with standard doses. Conclusion Our experience is in line with that described by other authors. DBT in clinical practice is offered to long-standing and refractory IBD. In these cases, effectiveness seems limited, with concerns on infectious adverse events, but surgery probably carries worse prospects. For the indication of IBD with EIMs not responding to the same biologic, DBT seems more effective. More data is needed to know in which cases and what combinations could be beneficial.
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- 2023
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50. Prepartum heat stress in dairy cows increases postpartum inflammatory responses in blood of lactating dairy cows
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Paula C.C. Molinari, Brittney D. Davidson, Jimena Laporta, Geoffrey E. Dahl, I. Martin Sheldon, and John J. Bromfield
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Genetics ,Animal Science and Zoology ,Food Science - Abstract
Uterine diseases and heat stress (HS) are major challenges for the dairy cow. Heat stress alters host immune resilience, making cows more susceptible to the development of uterine disease. Although HS increases the incidence of uterine disease, the mechanisms by which this occurs are unclear. We hypothesize that evaporative cooling (CL) to alleviate HS in prepartum cows has carry-over effects on postpartum innate immunity. Nulliparous pregnant Holstein heifers were assigned to receive either forced CL that resulted in cool conditions (shade with water soakers and fans; n = 14) or to remain under HS conditions (barn shade only; n = 16) for 60 d prepartum. Postpartum, all cows were housed in a freestall barn equipped with shade, water soakers, and fans. Respiratory rate and rectal temperature during the prepartum period were greater in HS heifers compared with CL heifers, indicative of HS. Although milk production was decreased in HS cows compared with CL cows, the incidence of uterine disease and content of total or pathogenic bacteria in vaginal mucus on d 7 or d 21 postpartum was not affected by treatment. Whole blood was collected on d 21 and subjected to in vitro stimulation with lipopolysaccharide. Lipopolysaccharide-induced accumulation of IL-1β, IL-10, and MIP-1α was greater in blood collected from HS cows compared with CL cows. Our results imply that prepartum HS during late pregnancy has carry-over effects on postpartum innate immunity, which may contribute to the increased incidence of uterine disease observed in cows exposed to prepartum HS.
- Published
- 2022
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