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Article ; Online: Pharmaceutical Considerations and Metabolic Fate of Parenteral Lipid Nanoparticle Dosage Forms.

Driscoll, David F / Bistrian, Bruce R

2024

Abstract: The physical stability of parenteral dispersions for delivery of drugs to patients is of particular clinical importance, given their general overall superior bioavailability compared to other routes of administration. Although official pharmacopeial ... ...

Abstract	The physical stability of parenteral dispersions for delivery of drugs to patients is of particular clinical importance, given their general overall superior bioavailability compared to other routes of administration. Although official pharmacopeial methods for lipid injectable emulsions have been established for triglyceride oil-in-water dispersions (i.e., "mini-emulsions") through USP Chapter <729>, no pharmaceopeial guidance exists for lipid nanoparticle (LNP)-based "micro-emulsions". At present, there are several LNP-based drugs approved for clinical use, including mRNA vaccines. Moreover, the increased interest in using mRNA as a platform technology for an array of potential therapeutic drug candidates increases the importance of developing appropriate methods to ensure their physical stability, safety and efficacy. For all dispersions and by various detection mechanisms (e.g., electrical, mechanical, mathematical), the fusion or growth of droplets/particles in the large-diameter tails of the particle size distribution (PSD) signals the onset of instability. Consequently, the measurement for LNP dispersions will require the use of a modified optical detection design in order to extend the lower particle detection limit into the "relative" large-diameter tail of the PSD for both light extinction and light-scattering methods based on single-particle optical sensing techniques. Fortunately, the technology is currently available and capable of providing the requisite quantitative analysis.
Language	English
Publishing date	2024-04-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	3151-3
ISSN	1520-6017 ; 0022-3549
ISSN (online)	1520-6017
ISSN	0022-3549
DOI	10.1016/j.xphs.2024.04.027
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Article ; Online: Cytokine storm associated with severe COVID-19 infections: The potential mitigating role of omega-3 fatty acid triglycerides in the ICU.

Driscoll, David F / Bistrian, Bruce R

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2023 Volume 37, Issue 8, Page(s) e23066

Abstract: Cytokine storm during severe COVID-19 infection increases the risk of mortality in critically ill patients in the intensive care unit. Multiple therapeutic proposals include, for example, anti-inflammatory and immunosuppressive agents, selective ... ...

Abstract	Cytokine storm during severe COVID-19 infection increases the risk of mortality in critically ill patients in the intensive care unit. Multiple therapeutic proposals include, for example, anti-inflammatory and immunosuppressive agents, selective inhibitors of key pro-inflammatory receptors, and key enzymes necessary for viral replication. Unfortunately, safe and effective therapy remains an elusive goal. An alternative anti-inflammatory approach vis á vis omega-3 fatty acids, which yields less pro-inflammatory mediators by altering eicosanoid metabolism, has been proposed. Although theoretically promising, enteral tube delivery or oral capsules containing specific doses of omega-3 fatty acids take precious time (7 days to 6 weeks) to be incorporated in plasma cell membranes to be most effective, making this route of administration in the acute care setting an unfeasible therapeutic approach. Parenteral administration of precise doses of omega-3 fatty acid triglycerides in an injectable emulsion can greatly accelerate the incorporation and potential therapeutic effects (within hours), but at present, there is no commercially available product designed for this purpose. We describe a potential formulation that may address this deficiency, while recognizing that the high incidence of hyperlipidemia that occurs during severe COVID-19 infection must be recognized as a complicating factor, and, therefore, caution is advised.
MeSH term(s)	Humans ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/etiology ; COVID-19 ; Intensive Care Units ; Cell Membrane ; Fatty Acids, Omega-3/therapeutic use
Chemical Substances	Fatty Acids, Omega-3
Language	English
Publishing date	2023-06-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202300396R
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Book ; Online: Accumulation rates of sediments and main sedimentary components in ODP Leg 121 holes on Broken Ridge, supplementary data to: Rea, David K; Dehn, Jonathan; Driscoll, Neal W; Farrell, John W; Janecek, Thomas R; Owen, Robert M; Pospichal, James J; Resiwati, Purtyasti (1990): Paleoceanography of the eastern Indian Ocean from ODP Leg 121 drilling on Broken Ridge. Geological Society of America Bulletin, 102(5), 679-690

Rea, David K / Dehn, Jonathan / Driscoll, Neal W / Farrell, John W / Janecek, Thomas R / Owen, Robert M / Pospichal, James J / Resiwati, Purtyasti

1990

Abstract: Broken Ridge, in the eastern Indian Ocean,is overlain by about 1600 m of middle Cretaceous to Pleistocene tuffaceous and carbonate sediments that record the oceanographic history of southern hemisphere mid-to high-latitude regions. Prior to about 42 Ma, ... ...

Abstract	Broken Ridge, in the eastern Indian Ocean,is overlain by about 1600 m of middle Cretaceous to Pleistocene tuffaceous and carbonate sediments that record the oceanographic history of southern hemisphere mid-to high-latitude regions. Prior to about 42 Ma, Broken Ridge formed the northern part of the broad Kerguelen-Broken Ridge Plateau. During the middle Eocene, this feature was split by the newly forming Southeast Indian Ocean Ridge; since then, Broken Ridge has drifted north from about 55° to 31°S. The lower part of the sedimentary section is characterized by Turonian to Santonian tuffs that contain abundant glauconite and some carbonate. The tuffs record a large but apparently local volcanic input that characterized the central part of Broken Ridge into the early Tertiary. Maestrichtian shallow-water(several hundred to 1000 m depth) limestones and cherts accumulated at some of the highest rates ever documented from the open ocean, 4 to 5 g/cm**2/kyr. A complete (with all biostratigraphic zones) Cretaceous-Tertiary boundary section was recovered from site 752. The first 1.5 m.y. of the Tertiary is characterized by an order-of-magnitude reduction in the flux of biogenic sediments, indicating a period of sharply reduced biological productivity at 55°S, following which the carbonate and silica sedimentation rates almost reach the previous high values of the latest Cretaceous. We recovered a complete section through the Paleocene that contains all major fossil groups and is more than 300 m thick, perhaps the best pelagic Paleocene section encountered in ocean drilling. About 42 Ma, Broken Ridge was uplifted 2500 m in response to the intra-plateau rifting event; subsequent erosion and deposition has resulted in a prominent Eocene angular unconformity atop the ridge. An Oligocene disconformity characterized by a widespread pebble layer probably represents the 30 Ma sea-level fall. The Neogene pelagic ooze on Broken Ridge has been winnowed, and thus its grain size provides a direct physical record of the energy of the southern hemisphere drift current in the Indian Ocean for the past 30 m.y.
Language	English
Dates of publication	1990-9999
Size	Online-Ressource
Publisher	PANGAEA - Data Publisher for Earth & Environmental Science
Publishing place	Bremen/Bremerhaven
Document type	Book ; Online
Note	This dataset is supplement to doi:10.1130/0016-7606(1990)102<0679:POTEIO>2.3.CO;2
DOI	10.1594/PANGAEA.720962
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Omega-3 Fatty Acids as Antiarrhythmic Drugs: Upstream Target Modulators Affecting Acute and Long-Term Pathological Alterations in Cardiac Structure and Function.

Driscoll, David F / Welty, Francine K / Bistrian, Bruce R

Critical care explorations

2023 Volume 5, Issue 10, Page(s) e0977

Abstract: Objectives: Postoperative atrial fibrillation (POAF) is a common complication in the acute care period following coronary artery bypass grafting (CABG) surgery that is associated with significant morbidity and mortality in both short-term and long-term ... ...

Abstract	Objectives: Postoperative atrial fibrillation (POAF) is a common complication in the acute care period following coronary artery bypass grafting (CABG) surgery that is associated with significant morbidity and mortality in both short-term and long-term settings. Recently, the Vaughn Williams Classification of antiarrhythmic agents, first proposed in 1975 and widely viewed as the authoritative description of their electrophysiologic actions, was updated and notably omega-3 fatty acids (Ω-3 fatty acids) have been included in class VII, described as "upstream target modulators," to mitigate pathological structural and electrophysiological remodeling changes in the aged and/or injured myocardium. Data sources: A PubMed literature search was performed. Study selection: Studies examining the significance of complications in patients undergoing isolated CABG surgery were selected for inclusion. Data extraction: Relevant data were qualitatively assessed and narratively summarized. Data synthesis: POAF occurs in approximately 30% of patients, and inflammation from chronic coronary artery disease preoperatively, as well as acute atrial inflammation from surgery postoperatively are the leading causes. Inflammation underlies its pathophysiology; therefore Ω-3 fatty acids not only exhibit antiarrhythmic properties but are an effective anti-inflammatory treatment that may reduce the clinical risks of POAF. Conclusions: At present no effective prophylaxis is available to address POAF following CABG surgery. Clinical approaches that focus on the inflammatory response in this setting may optimize the response to treatment. The current literature supports the hypothesis that Ω-3 fatty acids may acutely reduce the inflammatory response via favorable alterations in the metabolism of prostaglandins and leukotrienes (eicosanoids) and specialized pro-resolving mediators.
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2639-8028
ISSN (online)	2639-8028
DOI	10.1097/CCE.0000000000000977
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Article: Non-invasive Urinary Biomarkers in Moyamoya Disease.

Sesen, Julie / Driscoll, Jessica / Moses-Gardner, Alexander / Orbach, Darren B / Zurakowski, David / Smith, Edward R

Frontiers in neurology

2021 Volume 12, Page(s) 661952

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2021-04-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.661952
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Article ; Online: Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation and Novel Mutations in Cerebral Cavernous Malformations: In Vitro and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell Pathophysiology.

Sesen, Julie / Ghalali, Aram / Driscoll, Jessica / Martinez, Tyra / Lupieri, Adrien / Zurakowski, David / Alexandrescu, Sanda / Smith, Edward R / Fehnel, Katie P

Cellular and molecular neurobiology

2023 Volume 44, Issue 1, Page(s) 12

Abstract: Intracranial vascular malformations manifest on a continuum ranging from predominantly arterial to predominantly venous in pathology. Cerebral cavernous malformations (CCMs) are capillary malformations that exist at the midpoint of this continuum. The ... ...

Abstract	Intracranial vascular malformations manifest on a continuum ranging from predominantly arterial to predominantly venous in pathology. Cerebral cavernous malformations (CCMs) are capillary malformations that exist at the midpoint of this continuum. The axon guidance factor Ephrin B2 and its receptor EphB4 are critical regulators of vasculogenesis in the developing central nervous system. Ephrin B2/EphB4 dysregulation has been implicated in the pathogenesis of arterial-derived arteriovenous malformations and vein-based vein of Galen malformations. Increasing evidence supports the hypothesis that aberrant Ephrin B2/EphB4 signaling may contribute to developing vascular malformations, but their role in CCMs remains largely uncharacterized. Evidence of Ephrin dysregulation in CCMs would be important to establish a common link in the pathogenic spectrum of EphrinB2/Ephb4 dysregulation. By studying patient-derived primary CCM endothelial cells (CCMECs), we established that CCMECs are functionally distinct from healthy endothelial cell controls; CCMECs demonstrated altered patterns of migration, motility, and impaired tube formation. In addition to the altered phenotype, the CCMECs also displayed an increased ratio of EphrinB2/EphB4 compared to the healthy endothelial control cells. Furthermore, whole exome sequencing identified mutations in both EphrinB2 and EphB4 in the CCMECs. These findings identify functional alterations in the EphrinB2/EphB4 ratio as a feature linking pathophysiology across the spectrum of arterial, capillary, and venous structural malformations in the central nervous system while revealing a putative therapeutic target.
MeSH term(s)	Humans ; Receptor, EphB4/genetics ; Receptor, EphB2/genetics ; Hemangioma, Cavernous, Central Nervous System/genetics ; Endothelial Cells/pathology ; Primary Cell Culture ; Exome Sequencing ; Male ; Female ; Child, Preschool ; Child ; Adolescent
Chemical Substances	EPHB4 protein, human ; Receptor, EphB4 (EC 2.7.10.1) ; Receptor, EphB2 (EC 2.7.10.1) ; EPHB2 protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	283404-2
ISSN	1573-6830 ; 0272-4340
ISSN (online)	1573-6830
ISSN	0272-4340
DOI	10.1007/s10571-023-01447-0
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Article ; Online: Cannabidiol modulation of oxidative stress and signalling.

Pereira, Sónia R / Hackett, Becky / O'Driscoll, David N / Sun, Melody Cui / Downer, Eric J

Neuronal signaling

2021 Volume 5, Issue 3, Page(s) NS20200080

Abstract: Cannabidiol (CBD), one of the primary non-euphoric components in ... ...

Abstract	Cannabidiol (CBD), one of the primary non-euphoric components in the
Language	English
Publishing date	2021-08-24
Publishing country	England
Document type	Journal Article ; Review
ISSN	2059-6553
ISSN (online)	2059-6553
DOI	10.1042/NS20200080
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Article ; Online: Health Disparity Metrics for Transplant Centers: Theoretical and Practical Considerations.

Ross-Driscoll, Katie / Adams, Andrew / Caicedo, Juan / Gordon, Elisa J / Kirk, Alan D / McElroy, Lisa M / Taber, David / Patzer, Rachel

Transplantation

2024

Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004973
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Article ; Online: A multi-institutional phase I study of acetazolamide with temozolomide in adults with newly diagnosed

Driscoll, Riley K / Lyne, Sean B / Voce, David J / Maraka, Stefania / Gondi, Vinai / Chmura, Steven J / Dixit, Karan S / Kumthekar, Priya U / Karrison, Theodore G / Pytel, Peter / Collins, John M / Stupp, Roger / Merrell, Ryan T / Lukas, Rimas V / Yamini, Bakhtiar

Neuro-oncology advances

2024 Volume 6, Issue 1, Page(s) vdae014

Abstract: ... 2 months vs N.R., : Conclusions: The addition of acetazolamide is safe and tolerable in GBM ...

Abstract	Background: A significant unmet need exists for the treatment of glioblastoma, Methods: A total of 24 patients (GBM, Results: No patient had a dose-limiting toxicity. Adverse events were consistent with known sequelae of acetazolamide and TMZ. In the 23 WHO Grade 4 patients, the median overall survival (OS) was 30.1 months and the median progression-free survival was 16.0 months. The 2-year OS was 60.9%. In total 37% of the study population had high BCL-3 staining and trended toward shorter OS (17.2 months vs N.R., Conclusions: The addition of acetazolamide is safe and tolerable in GBM patients receiving standard TMZ. Survival results compare favorably to historical data from randomized trials in patients with
Language	English
Publishing date	2024-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdae014
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Article ; Online: Causes of Early Hip Revision Vary by Age and Gender: Analysis of Data From a Statewide Quality Registry.

Markel, Jacob F / Driscoll, John Adam / Zheng, Thomas H / Hughes, Richard E / Moore, Drew D / Hallstrom, Brian R / Markel, David C

The Journal of arthroplasty

2022 Volume 37, Issue 7S, Page(s) S616–S621

Abstract: Background: While total hip arthroplasty (THA) is extremely successful, early failures do occur. The purpose of this study was to determine the cause of revision in specific patient demographic groups at 3 time points to potentially help decrease the ... ...

Abstract	Background: While total hip arthroplasty (THA) is extremely successful, early failures do occur. The purpose of this study was to determine the cause of revision in specific patient demographic groups at 3 time points to potentially help decrease the revision risk. Methods: Data for cases performed between 2012 and 2018 from a statewide, quality improvement arthroplasty registry were used. The database included 79,205 THA cases and 1,433 revisions with identified etiology (1,584 in total). All revisions performed at <5 years from the primary THA were reviewed. Six groups, men/women, <65, 65-75, and >75 years, were compared at revision time points <6 months, <1 year, and <5 years. Results: There were obvious and significant differences between subgroups based on demographics and time points (P < .0001). Seven hundred and fifty-six (53%) of all revisions occurred within 6 months. The most common etiologies within 6 months (756 revisions) were fracture (316, 41.8%), dislocation/instability (194, 25.7%), and infection (98, 12.9%). At this early time point, the most common revision cause was fracture for all age/gender-stratified groups, ranging from 27.6% in young men to 60% in older women. Joint instability became the leading cause for revision after 1 year in all groups. Conclusion: This quality improvement project demonstrated clinically meaningful differences in the reason for THA revision between gender, age, and time from surgery. Strategies based on these data should be employed by surgeons to minimize the factors that lead to revision.
MeSH term(s)	Aged ; Arthroplasty, Replacement, Hip ; Female ; Hip Prosthesis/adverse effects ; Humans ; Male ; Prosthesis Design ; Prosthesis Failure ; Registries ; Reoperation ; Risk Factors
Language	English
Publishing date	2022-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2022.03.014
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