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Article: Functional analysis of cyclic diguanylate-modulating proteins in

Isenberg, Ruth Y / Holschbach, Chandler S / Gao, Jing / Mandel, Mark J

bioRxiv : the preprint server for biology

2023

Abstract: As bacterial symbionts transition from a motile free-living state to a sessile biofilm state, they must coordinate behavior changes suitable to each lifestyle. Cyclic diguanylate (c-di-GMP) is an intracellular signaling molecule that can regulate this ... ...

Abstract	As bacterial symbionts transition from a motile free-living state to a sessile biofilm state, they must coordinate behavior changes suitable to each lifestyle. Cyclic diguanylate (c-di-GMP) is an intracellular signaling molecule that can regulate this transition, and it is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. Generally, c-di-GMP inhibits motility and promotes biofilm formation. While c-di-GMP and the enzymes that contribute to its metabolism have been well-studied in pathogens, considerably less focus has been placed on c-di-GMP regulation in beneficial symbionts.
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.24.550417
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Article ; Online: AJP-Cell Physiology

Hawke, Thomas J / Isenberg, Jeffrey S

American journal of physiology. Cell physiology

2020 Volume 318, Issue 5, Page(s) C831

MeSH term(s)	Humans ; Inflammation ; Signal Transduction
Language	English
Publishing date	2020-03-25
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00111.2020
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Article ; Online: A Retrospective Matched Comparison Study of Prolonged Seizures in ECT.

Isenberg, Keith / Dinwiddie, Stephen H / Song, Jing / North, Carol S

The journal of ECT

2023 Volume 40, Issue 1, Page(s) 37–40

Abstract: Objective: This study assessed the incidence of and risk factors for prolonged seizures (>180 sec) in electroconvulsive therapy (ECT).: Method: In 611 adult patients undergoing 6697 ECT treatments administered over a 2.5-year study period, 29 ... ...

Abstract	Objective: This study assessed the incidence of and risk factors for prolonged seizures (>180 sec) in electroconvulsive therapy (ECT). Method: In 611 adult patients undergoing 6697 ECT treatments administered over a 2.5-year study period, 29 individuals experienced 42 prolonged seizures. A comparison sample (n = 29) was matched on sex, age, and treatment, and compared on psychiatric and medical diagnoses, as well as current medications. To examine the association between the characteristics and prolonged seizure, conditional logistic regression models or exact McNemar tests were conducted. Results: Prolonged seizures occurred on average in 1 of every 167 treatments. No specific psychiatric disorders or medical conditions were associated with the prolonged seizure group. Antipsychotic drugs were used in a higher proportion of the comparison group than in the prolonged seizure group, suggesting a protective effect. Atropine was used in a lower proportion of the long seizure group than in the comparison group. No untoward sequelae occurred, and no progression to status epilepticus was observed. Conclusions: Prolonged seizures appear to be an uncommon complication of ECT in adults. The characteristics examined in this study suggest limited association of psychotropic medications with prolonged seizures. Treatment of prolonged seizures was straightforward. Prolonged seizures had no impact on the course of treatment. Further exploration of prolonged seizures would enhance the generalizability of the findings from this single site study.
MeSH term(s)	Adult ; Humans ; Electroconvulsive Therapy/adverse effects ; Retrospective Studies ; Status Epilepticus ; Seizures/epidemiology ; Seizures/etiology ; Risk Factors
Language	English
Publishing date	2023-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1426385-3
ISSN	1533-4112 ; 1095-0680
ISSN (online)	1533-4112
ISSN	1095-0680
DOI	10.1097/YCT.0000000000000951
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Article ; Online: Adverse events of treatment with rituximab in patients with myositis.

Gilaberte, Sergio / Rua, Joana / Isenberg, David

Rheumatology (Oxford, England)

2022 Volume 62, Issue 2, Page(s) e16–e17

MeSH term(s)	Humans ; Rituximab/adverse effects ; Myositis/chemically induced ; Myositis/drug therapy ; Antirheumatic Agents/adverse effects ; Treatment Outcome
Chemical Substances	Rituximab (4F4X42SYQ6) ; Antirheumatic Agents
Language	English
Publishing date	2022-07-09
Publishing country	England
Document type	Letter
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keac398
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Article ; Online: Association between opioid use disorder and palliative care: a cohort study using linked health administrative data in Ontario, Canada.

Lau, Jenny / Scott, Mary M / Everett, Karl / Gomes, Tara / Tanuseputro, Peter / Jennings, Sheila / Bagnarol, Rebecca / Zimmermann, Camilla / Isenberg, Sarina R

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne

2024 Volume 196, Issue 16, Page(s) E547–E557

Abstract: Background: People with opioid use disorder (OUD) are at risk of premature death and can benefit from palliative care. We sought to compare palliative care provision for decedents with and without OUD.: Methods: We conducted a cohort study using ... ...

Abstract	Background: People with opioid use disorder (OUD) are at risk of premature death and can benefit from palliative care. We sought to compare palliative care provision for decedents with and without OUD. Methods: We conducted a cohort study using health administrative databases in Ontario, Canada, to identify people who died between July 1, 2015, and Dec. 31, 2021. The exposure was OUD, defined as having emergency department visits, hospital admissions, or pharmacologic treatments suggestive of OUD within 3 years of death. Our primary outcome was receipt of 1 or more palliative care services during the last 90 days before death. Secondary outcomes included setting, initiation, and intensity of palliative care. We conducted a secondary analysis excluding sudden deaths (e.g., opioid toxicity, injury). Results: Of 679 840 decedents, 11 200 (1.6%) had OUD. Compared with people without OUD, those with OUD died at a younger age and were more likely to live in neighbourhoods with high marginalization indices. We found people with OUD were less likely to receive palliative care at the end of their lives (adjusted relative risk [RR] 0.84, 95% confidence interval [CI] 0.82-0.86), but this difference did not exist after excluding people who died suddenly (adjusted RR 0.99, 95% CI 0.96-1.01). People with OUD were less likely to receive palliative care in clinics and their homes regardless of cause of death. Interpretation: Opioid use disorder can be a chronic, life-limiting illness, and people with OUD are less likely to receive palliative care in communities during the 90 days before death. Health care providers should receive training in palliative care and addiction medicine to support people with OUD.
MeSH term(s)	Humans ; Ontario/epidemiology ; Opioid-Related Disorders/epidemiology ; Opioid-Related Disorders/mortality ; Opioid-Related Disorders/therapy ; Male ; Female ; Palliative Care/statistics & numerical data ; Middle Aged ; Adult ; Cohort Studies ; Aged ; Databases, Factual ; Aged, 80 and over
Language	English
Publishing date	2024-04-28
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	215506-0
ISSN	1488-2329 ; 0008-4409 ; 0820-3946
ISSN (online)	1488-2329
ISSN	0008-4409 ; 0820-3946
DOI	10.1503/cmaj.231419
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Article: A label-free approach for relative spatial quantitation of c-di-GMP in microbial biofilms.

McCaughey, Catherine S / Trebino, Michael A / McAtamney, Allyson / Isenberg, Ruth / Mandel, Mark J / Yildiz, Fitnat H / Sanchez, Laura M

bioRxiv : the preprint server for biology

2023

Abstract: Microbial biofilms represent an important lifestyle for bacteria and are dynamic three dimensional structures. Cyclic dimeric guanosine monophosphate (c-di-GMP) is a ubiquitous signaling molecule that is known to be tightly regulated with biofilm ... ...

Abstract	Microbial biofilms represent an important lifestyle for bacteria and are dynamic three dimensional structures. Cyclic dimeric guanosine monophosphate (c-di-GMP) is a ubiquitous signaling molecule that is known to be tightly regulated with biofilm processes. While measurements of global levels of c-di-GMP have proven valuable towards understanding the genetic control of c-di-GMP production, there is a need for tools to observe the local changes of c-di-GMP production in biofilm processes. We have developed a label-free method for the direct detection of c-di-GMP in microbial colony biofilms using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). We applied this method to the enteric pathogen
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.10.561783
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Article ; Online: Metastatic Large-Cell Neuroendocrine Lung Carcinoma With ALK Fusion Oncogene With Partial Response to Alectinib.

Leblanc, Andréanne / Owen, Scott / Fiset, Pierre Olivier / Gomez Corrador, Andrea Liliam / Isenberg, Jordan / Bouganim, Nathaniel

JCO precision oncology

2022 Volume 5, Page(s) 802–807

MeSH term(s)	Adult ; Anaplastic Lymphoma Kinase/analysis ; Carbazoles/therapeutic use ; Carcinoma, Large Cell/chemistry ; Carcinoma, Large Cell/drug therapy ; Carcinoma, Large Cell/secondary ; Carcinoma, Neuroendocrine/chemistry ; Carcinoma, Neuroendocrine/drug therapy ; Carcinoma, Neuroendocrine/secondary ; Humans ; Lung Neoplasms/chemistry ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Male ; Piperidines/therapeutic use ; Treatment Outcome
Chemical Substances	Carbazoles ; Piperidines ; ALK protein, human (EC 2.7.10.1) ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; alectinib (LIJ4CT1Z3Y)
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Case Reports ; Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.20.00348
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Article: CD47 is Required for Mesenchymal Progenitor Proliferation and Fracture Repair.

Hankenson, Kurt / Zondervan, Robert / Capobianco, Christina / Jenkins, Daniel / Reicha, John / Frederick, Livia / Lam, Charles / Isenberg, Jeffery / Ahn, Jaimo / Marcucio, Ralph S

Research square

2024

Abstract: ... F), significantly less proliferation, and fewer cells in S-phase, although osteoblast ...

Abstract	CD47 is a ubiquitous and pleiotropic cell-surface receptor. Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries. In a murine closed-fracture model, CD47-null mice showed decreased callus bone volume, bone mineral content, and tissue mineral content as assessed by microcomputed tomography 10 days post-fracture, and increased fibrous volume as determined by histology. To understand the cellular basis for this phenotype, mesenchymal progenitors (MSC) were harvested from bone marrow. CD47-null MSC showed decreased large fibroblast colony formation (CFU-F), significantly less proliferation, and fewer cells in S-phase, although osteoblast differentiation was unaffected. However, consistent with prior research, CD47-null endothelial cells showed increased proliferation relative to WT cells. Similarly, in a murine ischemic fracture model, CD47-null mice showed reduced fracture callus bone volume and bone mineral content relative to WT. Consistent with our In vitro results, in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice, while staining for CD31 and endomucin demonstrated increased endothelial cell mass. Finally, WT mice administered a CD47 morpholino, which blocks CD47 protein production, showed a callus phenotype similar to that of non-ischemic and ischemic fractures in CD47-null mice, suggesting the phenotype was not due to developmental changes in the knockout mice. Thus, inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing, in part, by decreasing MSC proliferation. Furthermore, the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-4022423/v1
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Article ; Online: Association of virtual end-of-life care with healthcare outcomes before and during the COVID-19 pandemic: A population-based study.

Lapp, John M / Stukel, Thérèse A / Chung, Hannah / Bell, Chaim M / Bhatia, R Sacha / Detsky, Allan S / Downar, James / Isenberg, Sarina R / Lee, Douglas S / Stall, Nathan / Tanuseputro, Peter / Quinn, Kieran L

PLOS digital health

2024 Volume 3, Issue 3, Page(s) e0000463

Abstract: The use of virtual care for people at the end-of-life significantly increased during the COVID-19 pandemic, but its association with acute healthcare use and location of death is unknown. The objective of this study was to measure the association between ...

Abstract	The use of virtual care for people at the end-of-life significantly increased during the COVID-19 pandemic, but its association with acute healthcare use and location of death is unknown. The objective of this study was to measure the association between the use of virtual end-of-life care with acute healthcare use and an out-of-hospital death before vs. after the introduction of specialized fee codes that enabled broader delivery of virtual care during the COVID-19 pandemic. This was a population-based cohort study of 323,995 adults in their last 90 days of life between January 25, 2018 and December 31, 2021 using health administrative data in Ontario, Canada. Primary outcomes were acute healthcare use (emergency department, hospitalization) and location of death (in or out-of-hospital). Prior to March 14, 2020, 13,974 (8%) people received at least 1 virtual end-of-life care visit, which was associated with a 16% higher rate of emergency department use (adjusted Rate Ratio [aRR] 1.16, 95%CI 1.12 to 1.20), a 17% higher rate of hospitalization (aRR 1.17, 95%CI 1.15 to 1.20), and a 34% higher risk of an out-of-hospital death (aRR 1.34, 95%CI 1.31 to 1.37) compared to people who did not receive virtual end-of-life care. After March 14, 2020, 104,165 (71%) people received at least 1 virtual end-of-life care visit, which was associated with a 58% higher rate of an emergency department visit (aRR 1.58, 95%CI 1.54 to 1.62), a 45% higher rate of hospitalization (aRR 1.45, 95%CI 1.42 to 1.47), and a 65% higher risk of an out-of-hospital death (aRR 1.65, 95%CI 1.61 to 1.69) compared to people who did not receive virtual end-of-life care. The use of virtual end-of-life care was associated with higher acute healthcare use in the last 90 days of life and a higher likelihood of dying out-of-hospital, and these rates increased during the pandemic.
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Journal Article
ISSN	2767-3170
ISSN (online)	2767-3170
DOI	10.1371/journal.pdig.0000463
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Article: CD47 is Required for Mesenchymal Progenitor Proliferation and Fracture Repair.

Zondervan, Robert L / Capobianco, Christina A / Jenkins, Daniel C / Reicha, John D / Fredrick, Livia M / Lam, Charles / Isenberg, Jeffery S / Ahn, Jaimo / Marcucio, Ralph S / Hankenson, Kurt D

bioRxiv : the preprint server for biology

2024

Abstract: ... F), significantly less proliferation, and fewer cells in S-phase, although osteoblast ...

Abstract	CD47 is a ubiquitous and pleiotropic cell-surface receptor. Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries. In a murine closed-fracture model, CD47-null mice showed decreased callus bone volume, bone mineral content, and tissue mineral content as assessed by microcomputed tomography 10 days post-fracture, and increased fibrous volume as determined by histology. To understand the cellular basis for this phenotype, mesenchymal progenitors (MSC) were harvested from bone marrow. CD47-null MSC showed decreased large fibroblast colony formation (CFU-F), significantly less proliferation, and fewer cells in S-phase, although osteoblast differentiation was unaffected. However, consistent with prior research, CD47-null endothelial cells showed increased proliferation relative to WT cells. Similarly, in a murine ischemic fracture model, CD47-null mice showed reduced fracture callus bone volume and bone mineral content relative to WT. Consistent with our
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.06.583756
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