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Article: Longitudinal intravital imaging through clear silicone windows

Maiorino, Laura / Shevik, Margaret / Adrover, José M. / Han, Xiao / Georgas, Elias / Wilkinson, John Erby / Seidner, Harrison / Foerschner, Leonie / Tuveson, David A. / Qin, Yi-Xian / Egeblad, Mikala

Journal of visualized experiments. 2022 Jan. 05, , no. 179

2022

Abstract: Intravital microscopy (IVM) enables visualization of cell movement, division, and death at single-cell resolution. IVM through surgically inserted imaging windows is particularly powerful because it allows longitudinal observation of the same tissue over ...

Abstract	Intravital microscopy (IVM) enables visualization of cell movement, division, and death at single-cell resolution. IVM through surgically inserted imaging windows is particularly powerful because it allows longitudinal observation of the same tissue over days to weeks. Typical imaging windows comprise a glass coverslip in a biocompatible metal frame sutured to the mouse’s skin. These windows can interfere with the free movement of the mice, elicit a strong inflammatory response, and fail due to broken glass or torn sutures, any of which may necessitate euthanasia. To address these issues, windows for long-term abdominal organ and mammary gland imaging were developed from a thin film of polydimethylsiloxane (PDMS), an optically clear silicone polymer previously used for cranial imaging windows. These windows can be glued directly to the tissues, reducing the time needed for insertion. PDMS is flexible, contributing to its durability in mice over time—up to 35 days have been tested. Longitudinal imaging is imaging of the same tissue region during separate sessions. A stainless-steel grid was embedded within the windows to localize the same region, allowing the visualization of dynamic processes (like mammary gland involution) at the same locations, days apart. This silicone window also allowed monitoring of single disseminated cancer cells developing into micro-metastases over time. The silicone windows used in this study are simpler to insert than metal-framed glass windows and cause limited inflammation of the imaged tissues. Moreover, embedded grids allow for straightforward tracking of the same tissue region in repeated imaging sessions.
Keywords	cell movement ; death ; durability ; euthanasia ; films (materials) ; glass ; inflammation ; mammary glands ; mice ; microscopy ; polydimethylsiloxane ; stainless steel
Language	English
Dates of publication	2022-0105
Size	p. e62757.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/62757
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection.

Adrover, Jose M / Carrau, Lucia / Daßler-Plenker, Juliane / Bram, Yaron / Chandar, Vasuretha / Houghton, Sean / Redmond, David / Merrill, Joseph R / Shevik, Margaret / tenOever, Benjamin R / Lyons, Scott K / Schwartz, Robert E / Egeblad, Mikala

JCI insight

2022 Volume 7, Issue 5

Abstract: Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no ... ...

Abstract	Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no drug preventing NET formation has completed clinical development. Here, we report that disulfiram - an FDA-approved drug for alcohol use disorder - dramatically reduced NETs, increased survival, improved blood oxygenation, and reduced lung edema in a transfusion-related acute lung injury (TRALI) mouse model. We then tested whether disulfiram could confer protection in the context of SARS-CoV-2 infection, as NETs are elevated in patients with severe COVID-19. In SARS-CoV-2-infected golden hamsters, disulfiram reduced NETs and perivascular fibrosis in the lungs, and it downregulated innate immune and complement/coagulation pathways, suggesting that it could be beneficial for patients with COVID-19. In conclusion, an existing FDA-approved drug can block NET formation and improve disease course in 2 rodent models of lung injury for which treatment options are limited.
MeSH term(s)	Acetaldehyde Dehydrogenase Inhibitors/pharmacology ; Acute Lung Injury/drug therapy ; Acute Lung Injury/etiology ; Animals ; COVID-19/complications ; COVID-19/virology ; Disease Models, Animal ; Disulfiram/pharmacology ; Extracellular Traps/drug effects ; Extracellular Traps/immunology ; Lung/immunology ; Rodentia ; SARS-CoV-2
Chemical Substances	Acetaldehyde Dehydrogenase Inhibitors ; Disulfiram (TR3MLJ1UAI)
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.157342
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Longitudinal Intravital Imaging Through Clear Silicone Windows.

Maiorino, Laura / Shevik, Margaret / Adrover, José M / Han, Xiao / Georgas, Elias / Wilkinson, John Erby / Seidner, Harrison / Foerschner, Leonie / Tuveson, David A / Qin, Yi-Xian / Egeblad, Mikala

Journal of visualized experiments : JoVE

2022 , Issue 179

Abstract	Intravital microscopy (IVM) enables visualization of cell movement, division, and death at single-cell resolution. IVM through surgically inserted imaging windows is particularly powerful because it allows longitudinal observation of the same tissue over days to weeks. Typical imaging windows comprise a glass coverslip in a biocompatible metal frame sutured to the mouse's skin. These windows can interfere with the free movement of the mice, elicit a strong inflammatory response, and fail due to broken glass or torn sutures, any of which may necessitate euthanasia. To address these issues, windows for long-term abdominal organ and mammary gland imaging were developed from a thin film of polydimethylsiloxane (PDMS), an optically clear silicone polymer previously used for cranial imaging windows. These windows can be glued directly to the tissues, reducing the time needed for insertion. PDMS is flexible, contributing to its durability in mice over time-up to 35 days have been tested. Longitudinal imaging is imaging of the same tissue region during separate sessions. A stainless-steel grid was embedded within the windows to localize the same region, allowing the visualization of dynamic processes (like mammary gland involution) at the same locations, days apart. This silicone window also allowed monitoring of single disseminated cancer cells developing into micro-metastases over time. The silicone windows used in this study are simpler to insert than metal-framed glass windows and cause limited inflammation of the imaged tissues. Moreover, embedded grids allow for straightforward tracking of the same tissue region in repeated imaging sessions.
MeSH term(s)	Animals ; Cell Movement ; Diagnostic Imaging ; Intravital Microscopy/methods ; Mice ; Silicones ; Skull
Chemical Substances	Silicones
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/62757
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Traditional African remedies induce hemolysis in a glucose-6-phopshate dehydrogenase deficient zebrafish model.

Arogbokun, Olufunmilayo / Shevik, Margaret / Slusher, Tina / Farouk, Zubaida / Elfstrum, Alexis / Weber, Jenna / Cusick, Sarah E / Lund, Troy

Scientific reports

2020 Volume 10, Issue 1, Page(s) 19172

Abstract: Traditional remedies are widely used throughout Africa in routine care for infants. However, such remedies could have detrimental effects. Acute bilirubin encephalopathy (ABE) and kernicterus spectrum disorder (KSD) are common newborn health conditions ... ...

Abstract	Traditional remedies are widely used throughout Africa in routine care for infants. However, such remedies could have detrimental effects. Acute bilirubin encephalopathy (ABE) and kernicterus spectrum disorder (KSD) are common newborn health conditions in the developing world, contributing to substantial neonatal mortality and morbidity. They frequently occur in children with glucose-6-phopshate dehydrogenase (G6PD) deficiency. Using our established zebrafish model of G6PD deficiency, we tested the effects of three traditional compounds used in the care of the newborn umbilical cord: eucalyptus oil, methylated spirits, and Yoruba herbal tea. We found that eucalyptus oil induced a 13.4% increase in a hemolytic phenotype versus control, while methylated spirits showed a 39.7% increase in affected phenotype. Yoruba herbal tea exposure showed no effect. While methylated spirits are already a known pro-oxidant, these data indicate that eucalyptus oil may also be a hemolytic trigger in those with G6PD deficiency. Discovering which agents may contribute to the pathophysiology of G6PD deficiency is critical to eliminate ABE and KSD, especially in countries with a high prevalence of G6PD deficiency. The next step in elucidating the role of these agents is to determine the clinical correlation between the use of these agents and ABE/KSD.
MeSH term(s)	Animals ; Disease Models, Animal ; Eucalyptus Oil/administration & dosage ; Eucalyptus Oil/adverse effects ; Glucosephosphate Dehydrogenase Deficiency/blood ; Hematologic Tests ; Hemolysis/drug effects ; Medicine, African Traditional/adverse effects ; Oxidative Stress/drug effects ; Zebrafish
Chemical Substances	Eucalyptus Oil (2R04ONI662)
Language	English
Publishing date	2020-11-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-75823-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Impact of serological and PCR testing requirements on the selection of COVID-19 convalescent plasma donors.

Carter, Jason A / Freedenberg, Alex T / Romeiser, Jamie L / Talbot, Lillian R / Browne, Nicholas J / Cosgrove, Megan E / Shevik, Margaret E / Generale, Laura M / Rago, Molly G / Caravella, Giuseppina A / Ahmed, Tahmeena / Mamone, Linda J / Bennett-Guerrero, Elliott

Transfusion

2021 Volume 61, Issue 5, Page(s) 1461–1470

Abstract: Background: Convalescent plasma is undergoing randomized trials as a potential therapeutic option for COVID-19 infection. Little empirical evidence exists regarding the determination of donor eligibility and experiences with donor selection.: Study ... ...

Abstract	Background: Convalescent plasma is undergoing randomized trials as a potential therapeutic option for COVID-19 infection. Little empirical evidence exists regarding the determination of donor eligibility and experiences with donor selection. Study design and methods: This prospective study was conducted at a tertiary care hospital in New York to select plasma donors for a randomized, double-blind, controlled convalescent plasma trial. Clearance for donation required successful completion of an online questionnaire and an in-person screening visit, which included (a) completion of a Donor Health Questionnaire (DHQ), (b) Immunoglobulin G (IgG) antibody testing using an immunochromatographic anti- severe acute respiratory coronavirus 2 (SARS-CoV-2) test, (c) Polymerase chain reaction (PCR) testing if <28 days from symptom resolution, and (d) routine blood bank testing. Results: After receiving 3093 online questionnaires, 521 individuals presented for in-person screening visits, with 40.1% (n = 209) fully qualifying. Subjects (n = 312) failed to progress due to the following reasons: disqualifying answer from DHQ (n = 30, 9.6%), insufficient antibodies (n = 198, 63.5%), persistent positive PCR tests (n = 14, 4.5%), and blood donation testing labs (n = 70, 22.4%). Importantly, 24.6% and 11.1% of potential donors who reported having PCR-diagnosed infection had low or undetectable SARS-CoV-2 antibody levels, respectively. Surprisingly, 62.9% (56/89) of subjects had positive PCR tests 14-27 days after symptom resolution, with 13 individuals continuing to be PCR positive after 27 days. Conclusion: It is feasible for a single site to fully qualify a large number of convalescent plasma donors in a short period of time. Among otherwise qualified convalescent plasma donors, we found high rates of low or undetectable antibody levels and many individuals with persistently positive PCR tests.
MeSH term(s)	Adult ; Blood Donors ; COVID-19/blood ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Convalescence ; Donor Selection ; Female ; Humans ; Male ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction
Language	English
Publishing date	2021-02-08
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16293
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 284: Show issues

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Article ; Online: TP53 Modulates Oxidative Stress in Gata1

Kramer, Ashley C / Weber, Jenna / Zhang, Ying / Tolar, Jakub / Gibbens, Ying Y / Shevik, Margaret / Lund, Troy C

Stem cell reports

2017 Volume 8, Issue 2, Page(s) 360–372

Abstract: Metabolism of oxidative stress is necessary for cellular survival. We have previously utilized the zebrafish as a model of the oxidative stress response. In this study, we found that gata1-expressing erythroid cells contributed to a significant ... ...

Abstract	Metabolism of oxidative stress is necessary for cellular survival. We have previously utilized the zebrafish as a model of the oxidative stress response. In this study, we found that gata1-expressing erythroid cells contributed to a significant proportion of total-body oxidative stress when animals were exposed to a strong pro-oxidant. RNA-seq of zebrafish under oxidative stress revealed the induction of tp53. Zebrafish carrying tp53 with a mutation in its DNA-binding domain were acutely sensitive to pro-oxidant exposure and displayed significant reactive oxygen species (ROS) and tp53-independent erythroid cell death resulting in an edematous phenotype. We found that a major contributing factor to ROS was increased basal mitochondrial respiratory rate without reserve. These data add to the concept that tp53, while classically a tumor suppressor and cell-cycle regulator, has additional roles in controlling cellular oxidative stress.
Language	English
Publishing date	2017-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2016.12.025
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Article: Candida parapsilosis

Gonia, Sara / Archambault, Linda / Shevik, Margaret / Altendahl, Marie / Fellows, Emily / Bliss, Joseph M / Wheeler, Robert T / Gale, Cheryl A

Frontiers in pediatrics

2017 Volume 5, Page(s) 54

Abstract: ... ...

Abstract	Candida
Language	English
Publishing date	2017-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2017.00054
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Article ; Online: Severe Acute Respiratory Syndrome Coronavirus 2 Convalescent Plasma Versus Standard Plasma in Coronavirus Disease 2019 Infected Hospitalized Patients in New York: A Double-Blind Randomized Trial.

Bennett-Guerrero, Elliott / Romeiser, Jamie L / Talbot, Lillian R / Ahmed, Tahmeena / Mamone, Linda J / Singh, Sunitha M / Hearing, Janet C / Salman, Huda / Holiprosad, Dishaw D / Freedenberg, Alex T / Carter, Jason A / Browne, Nicholas J / Cosgrove, Megan E / Shevik, Margaret E / Generale, Laura M / Andrew, Margaret A / Nachman, Sharon / Fries, Bettina C

Critical care medicine

2021 Volume 49, Issue 7, Page(s) 1015–1025

Abstract: Objectives: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To ... ...

Abstract	Objectives: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome. Design: Double-blind randomized controlled trial. Setting: Hospital in New York. Patients: Patients with polymerase chain reaction documented coronavirus disease 2019 infection. Interventions: Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients. Measurements and main results: Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2-28) versus 28 (0-28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small. Conclusions: Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.
MeSH term(s)	Aged ; Antibodies, Neutralizing/blood ; COVID-19/therapy ; Double-Blind Method ; Female ; Humans ; Immunization, Passive ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Male ; Middle Aged ; New York/epidemiology ; SARS-CoV-2 ; Treatment Outcome ; COVID-19 Serotherapy
Chemical Substances	Antibodies, Neutralizing ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2021-04-22
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000005066
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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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Article: Longitudinal intravital imaging through clear silicone windows

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Article ; Online: Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection.

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Article ; Online: Longitudinal Intravital Imaging Through Clear Silicone Windows.

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Article ; Online: Traditional African remedies induce hemolysis in a glucose-6-phopshate dehydrogenase deficient zebrafish model.

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Article ; Online: Impact of serological and PCR testing requirements on the selection of COVID-19 convalescent plasma donors.

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Article ; Online: TP53 Modulates Oxidative Stress in Gata1

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Article: Candida parapsilosis

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Article ; Online: Severe Acute Respiratory Syndrome Coronavirus 2 Convalescent Plasma Versus Standard Plasma in Coronavirus Disease 2019 Infected Hospitalized Patients in New York: A Double-Blind Randomized Trial.

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