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Article ; Online: Breath Analysis of COVID-19 Patients in a Tertiary UK Hospital by Optical Spectrometry: The E-Nose CoVal Study.

Laird, Steven / Debenham, Luke / Chandla, Danny / Chan, Cathleen / Daulton, Emma / Taylor, Johnathan / Bhat, Palashika / Berry, Lisa / Munthali, Peter / Covington, James A

Biosensors

2023 Volume 13, Issue 2

Abstract: Throughout the SARS-CoV-2 pandemic, diagnostic technology played a crucial role in managing outbreaks on a national and global level. One diagnostic modality that has shown promise is breath analysis, due to its non-invasive nature and ability to give a ... ...

Abstract	Throughout the SARS-CoV-2 pandemic, diagnostic technology played a crucial role in managing outbreaks on a national and global level. One diagnostic modality that has shown promise is breath analysis, due to its non-invasive nature and ability to give a rapid result. In this study, a portable FTIR (Fourier Transform Infra-Red) spectrometer was used to detect chemical components in the breath from Covid positive symptomatic and asymptomatic patients versus a control cohort of Covid negative patients. Eighty-five patients who had a nasopharyngeal polymerase chain reaction (PCR) test for the detection of SARS-CoV-2 within the last 5 days were recruited to the study (36 symptomatic PCR positive, 23 asymptomatic PCR positive and 26 asymptomatic PCR negative). Data analysis indicated significant difference between the groups, with SARS-CoV-2 present on PCR versus the negative PCR control group producing an area under the curve (AUC) of 0.87. Similar results were obtained comparing symptomatic versus control and asymptomatic versus control. The asymptomatic results were higher than the symptomatic (0.88 vs. 0.80 AUC). When analysing individual chemicals, we found ethanol, methanol and acetaldehyde were the most important, with higher concentrations in the COVID-19 group, with symptomatic patients being higher than asymptomatic patients. This study has shown that breath analysis can provide significant results that distinguish patients with or without COVID-19 disease/carriage.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Electronic Nose ; United Kingdom ; Hospitals
Language	English
Publishing date	2023-01-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios13020165
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Article ; Online: The association of amygdala-insula functional connectivity and adolescent e-cigarette use via sleep problems and depressive symptoms.

Sutherland, Benjelene D / Viera Perez, Patricio M / Crooks, Katharine E / Flannery, Jessica S / Hill-Bowen, Lauren D / Riedel, Michael C / Laird, Angela R / Trucco, Elisa M / Sutherland, Matthew T

Addictive behaviors

2022 Volume 135, Page(s) 107458

Abstract: Background: Adolescent electronic cigarette (e-cigarette) use remains high. Elucidating ... As such, we hypothesized that amygdala's rsFC with the insula would be associated with e-cigarette use via sleep problems ... insula subregions (i.e., ventral insula [vI], dorsal insula [dI]), sleep problems, depression levels, and ...

Abstract	Background: Adolescent electronic cigarette (e-cigarette) use remains high. Elucidating contributing factors may enhance prevention strategies. Neurobiologically, amygdala-insula resting-state functional connectivity (rsFC) has been linked with aspects of sleep, affect, and substance use (SU). As such, we hypothesized that amygdala's rsFC with the insula would be associated with e-cigarette use via sleep problems and/or depression levels. Methods: An adolescent sample (N = 146) completed a rs-fMRI scan at time 1 and self-reports at time 2 (∼15 months later). Given consistent associations between mental health outcomes and the rsFC of the laterobasal amygdala (lbAMY) with the anterior insula, we utilized a seed region (lbAMY) to region of interest (ROI) analysis approach to characterize brain-behavior relationships. Two serial mediation models tested the interrelations between amygdala's rsFC with distinct anterior insula subregions (i.e., ventral insula [vI], dorsal insula [dI]), sleep problems, depression levels, and days of e-cigarette use. Results: An indirect effect was observed when considering the lbAMY's rsFC with the vI. Greater rsFC predicted more sleep problems, more sleep problems were linked with greater depressive symptoms, and greater depressive symptoms were associated with more e-cigarette use (indirect effect = 0.08, CI [0.01,0.21]). Indicative of a neurobiological dissociation, a similar indirect effect linking these variables was not observed when considering the lbAMY's rsFC with the dI (indirect effect = 0.03, CI [-0.001,0.10]). Conclusions: These outcomes highlight functional interactions between the amygdala and insula as a neurobiological contributor to sleep problems, depressive symptoms, and ultimately SU thereby suggesting potential intervention points to reduce teen e-cigarette use.
MeSH term(s)	Adolescent ; Amygdala/diagnostic imaging ; Cerebral Cortex/diagnostic imaging ; Depression ; Electronic Nicotine Delivery Systems ; Humans ; Magnetic Resonance Imaging ; Sleep Wake Disorders/diagnostic imaging ; Vaping
Language	English
Publishing date	2022-08-12
Publishing country	England
Document type	Journal Article
ZDB-ID	197618-7
ISSN	1873-6327 ; 0306-4603
ISSN (online)	1873-6327
ISSN	0306-4603
DOI	10.1016/j.addbeh.2022.107458
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Article ; Online: Rational Drug Design of Targeted and Enzyme-Cleavable Vitamin E Analogs as a Neoadjuvant to Chemotherapy:

Pandurangi, Raghu S / Cseh, Orsolya / Luchman, Hema Artee / Ma, Cynthia Xiuguang / Senadheera, Sanjeewa N / Forrest, Marcus Laird

ACS pharmacology & translational science

2023 Volume 6, Issue 3, Page(s) 372–386

Abstract: ... Several vitamin E derivatives (AMP-001, AMP-002, AMP-003, and AMP-004) were synthesized, characterized, and ...

Abstract	Traditional drug design focuses on specific biological targets where specific receptors or biomarkers are overexpressed by cancer cells. Cancer cells circumvent the interventions by activating survival pathways and/or downregulating cell death pathways for their survival. A priori activation of apoptosis pathways of tumor (AAAPT) is a novel tumor-sensitizing technology that sensitizes tumor cells that are not responding well to the current treatments by targeting specific survival pathways involved in the desensitization of tumor cells and tries to revive them selectively in cancer cells, sparing normal cells. Several vitamin E derivatives (AMP-001, AMP-002, AMP-003, and AMP-004) were synthesized, characterized, and studied for their anti-tumorigenic properties and their synergistic potential with the standard chemotherapy doxorubicin in various cancer cells including brain cancer stem cells
Language	English
Publishing date	2023-02-06
Publishing country	United States
Document type	Journal Article
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.2c00091
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Article: Nicotine, THC, and Dolutegravir Modulate E-Cigarette-Induced Changes in Addiction- and Inflammation-Associated Genes in Rat Brains and Astrocytes.

Kulbe, Jacqueline Renee / Nguyen, Lauren / Le, Alexandra Anh / Laird, Anna Elizabeth / Taffe, Michael A / Nguyen, Jacques D / Fields, Jerel Adam

Brain sciences

2023 Volume 13, Issue 11

Abstract: E-cigarette use has been marketed as a safer alternative to traditional cigarettes, as a means ... synaptic plasticity, inflammation, and neurodegeneration. This study showed that 10 days of exposure to e ... Specifically, the e-cigarette solvent vapor propylene glycol (PG) downregulated EGR2 and ARC mRNA expression ...

Abstract	E-cigarette use has been marketed as a safer alternative to traditional cigarettes, as a means of smoking cessation, and are used at a higher rate than the general population in people with HIV (PWH). Early growth receptor 2 (EGR2) and Activity-Regulated Cytoskeleton-Associated Protein (ARC) have a role in addiction, synaptic plasticity, inflammation, and neurodegeneration. This study showed that 10 days of exposure to e-cigarette vapor altered gene expression in the brains of 6-month-old, male, Sprague Dawley rats. Specifically, the e-cigarette solvent vapor propylene glycol (PG) downregulated EGR2 and ARC mRNA expression in frontal cortex, an effect which was reversed by nicotine (NIC) and THC, suggesting that PG could have a protective role against NIC and cannabis dependence. However, in vitro, PG upregulated EGR2 and ARC mRNA expression at 18 h in cultured C6 rat astrocytes suggesting that PG may have neuroinflammatory effects. PG-induced upregulation of EGR2 and ARC mRNA was reversed by NIC but not THC. The HIV antiretroviral DTG reversed the effect NIC had on decreasing PG-induced upregulation of EGR2, which is concerning because EGR2 has been implicated in HIV latency reversal, T-cell apoptosis, and neuroinflammation, a process that underlies the development of HIV-associated neurocognitive disorders.
Language	English
Publishing date	2023-11-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci13111556
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Article: Authors E. Laird et al comment on response to their article entitled: “Vitamin D and inflammation - Potential implications for severity of Covid-19”

Laird, E. / Rhodes, J. / Kenny, R. A.

Irish Medical Journal

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #774659
Database	COVID19

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Article ; Online: Transgenic expression of human leukocyte antigen-E attenuates GalKO.hCD46 porcine lung xenograft injury.

Laird, Christopher T / Burdorf, Lars / French, Beth M / Kubicki, Natalia / Cheng, Xiangfei / Braileanu, Gheorghe / Sun, Wenji / O'Neill, Natalie A / Cimeno, Arielle / Parsell, Dawn / So, Edward / Bähr, Andrea / Klymiuk, Nikolai / Phelps, Carol J / Ayares, David / Azimzadeh, Agnes M / Pierson, Richard N

Xenotransplantation

2017 Volume 24, Issue 2

Abstract: ... inhibitory ligand HLA-E and β2 microglobulin inhibits GalTKO.hCD46 pig cell injury or prolongs lung function ... and GalTKO.hCD46.HLA-E (n=5) were harvested and perfused with human blood until failure or elective ... cytotoxicity assays using human NK cells.: Results: HLA-E expression on GalTKO.hCD46 PAECs was associated ...

Abstract	Background: Lung xenografts remain susceptible to loss of vascular barrier function within hours in spite of significant incremental advances based on genetic engineering to remove the Gal 1,3-αGal antigen (GalTKO) and express human membrane cofactor protein (hCD46). Natural killer cells rapidly disappear from the blood during perfusion of GalTKO.hCD46 porcine lungs with human blood and presumably are sequestered within the lung vasculature. Here we asked whether porcine expression of the human NK cell inhibitory ligand HLA-E and β2 microglobulin inhibits GalTKO.hCD46 pig cell injury or prolongs lung function in two preclinical perfusion models. Methods: Lungs from pigs modified to express GalTKO.hCD46 (n=37) and GalTKO.hCD46.HLA-E (n=5) were harvested and perfused with human blood until failure or elective termination at 4 hours. Airway pressures and pulmonary artery hemodynamics were recorded in real time. Blood samples were also collected throughout the experiment for analysis. Porcine aortic endothelial cells (PAECs) from each genotype were cultured in monolayers in microfluidic channels and used in fluorescent cytotoxicity assays using human NK cells. Results: HLA-E expression on GalTKO.hCD46 PAECs was associated with significantly decreased antibody-dependent and antibody-independent NK-mediated cytotoxicity under in vitro conditions simulating physiologic shear stress. Relative to GalTKO.hCD46 pig lungs perfused with human blood on an ex vivo platform, additional expression of HLA-E increased median lung survival (>4 hours, vs 162 minutes, P=.012), and was associated with attenuated rise in pulmonary vascular resistance, and decreased platelet activation and histamine elaboration. As expected, HLA-E expression was not associated with a significant difference in NK cell adhesion to endothelial cells in vitro, or NK cell and neutrophil sequestration during organ perfusion. Conclusions: We conclude human NK cell activation contributes significantly to GalTKO.hCD46 pig endothelial injury and lung inflammation and show that expression of HLA-E is associated with physiologically meaningful protection of GalTKO.hCD46 cells and organs exposed to human blood.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Cytotoxicity, Immunologic/immunology ; Endothelial Cells/immunology ; Galactosyltransferases/genetics ; Graft Survival/genetics ; Graft Survival/immunology ; HLA Antigens/genetics ; HLA Antigens/immunology ; Heterografts/immunology ; Humans ; Killer Cells, Natural/immunology ; Leukocytes/immunology ; Lung Injury/immunology ; Lung Injury/therapy ; Membrane Cofactor Protein/genetics ; Membrane Cofactor Protein/immunology ; Swine ; Transplantation, Heterologous/methods
Chemical Substances	HLA Antigens ; Membrane Cofactor Protein ; Galactosyltransferases (EC 2.4.1.-)
Language	English
Publishing date	2017-03
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1236298-0
ISSN	1399-3089 ; 0908-665X
ISSN (online)	1399-3089
ISSN	0908-665X
DOI	10.1111/xen.12294
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Article ; Online: P- and E-selectin receptor antagonism prevents human leukocyte adhesion to activated porcine endothelial monolayers and attenuates porcine endothelial damage.

Laird, Christopher T / Hassanein, Wessam / O'Neill, Natalie A / French, Beth M / Cheng, Xiangfei / Fogler, William E / Magnani, John L / Parsell, Dawn / Cimeno, Arielle / Phelps, Carol J / Ayares, David / Burdorf, Lars / Azimzadeh, Agnes M / Pierson, Richard N

Xenotransplantation

2018 Volume 25, Issue 2, Page(s) e12381

Abstract: ... and rPSGL1.Fc were tested as E- and P- selectin antagonists, respectively. Cellular adhesion and ... rolled and tethered. Both E-and P-selectin antagonism significantly reduced the number of neutrophils ...

Abstract	Background: Alongside the need to develop more effective and less toxic immunosuppression, the shortage of human organs available for organ transplantation is one of the major hurdles facing the field. Research into xenotransplantation, as an alternative source of organs, has unveiled formidable challenges. Porcine lungs perfused with human blood rapidly sequester the majority of circulating neutrophils and platelets, which leads to inflammation and organ failure within hours, and is not significantly attenuated by genetic modifications to the pig targeted to diminish antibody binding and complement and coagulation cascade activation. Methods: Here, we model the interaction of freshly isolated human leukocytes with xenotransplanted vasculature under physiologic flow conditions using microfluidic channels coated with porcine endothelial cells. Both isolated human neutrophils and whole human blood were perfused over transgenic pig aortic endothelial cells that had been activated with rhTNF-α or rhIL-4 using the BioFlux system. Novel compounds GMI-1271 and rPSGL1.Fc were tested as E- and P- selectin antagonists, respectively. Cellular adhesion and rolling events were tracked using FIJI (imageJ). Results: Porcine endothelium activated with either rhTNF-α or rhIL-4 expressed high amounts of selectins, to which isolated human neutrophils readily rolled and tethered. Both E-and P-selectin antagonism significantly reduced the number of neutrophils rolling and rolling distance in a dose-dependent manner, with near total inhibition at higher doses (P < .001). Similarly, with whole human blood, selectin blocking compounds exhibited dose-dependent inhibition of prevalent leukocyte adhesion and severe endothelial injury (Untreated: 394 ± 97 PMNs/hpf, 57 ± 6% loss EC; GMI1271+rPSGL1.Fc: 23 ± 9 PMNs/hpf, 8 ± 6% loss EC P < .01). Conclusions: Selectin blockade may be useful as part of an integrated strategy to prevent neutrophil-mediated organ xenograft injury, especially during the early time points following reperfusion.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Cell Adhesion/physiology ; E-Selectin/metabolism ; Endothelial Cells/immunology ; Humans ; Leukocytes/immunology ; Neutrophils/immunology ; P-Selectin/metabolism ; Swine ; Transplantation, Heterologous/methods
Chemical Substances	E-Selectin ; P-Selectin ; SELE protein, human ; SELP protein, human
Language	English
Publishing date	2018-01-23
Publishing country	Denmark
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1236298-0
ISSN	1399-3089 ; 0908-665X
ISSN (online)	1399-3089
ISSN	0908-665X
DOI	10.1111/xen.12381
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Article ; Online: Use of disposable reactors to generate inoculum cultures for E. coli production fermentations.

Mahajan, Ekta / Matthews, Timothy / Hamilton, Ryan / Laird, Michael W

Biotechnology progress

2010 Volume 26, Issue 4, Page(s) 1200–1203

Abstract: ... however, it has not yet been thoroughly tested for E. coli production because of the high oxygen demand and ... process to generate inoculum for E. coli production fermentations in a WAVE bioreactor. We opted not ... E. coli production processes. Instead, the WAVE bioreactor 20/50 system was evaluated at laboratory ...

Abstract	Disposable technology is being used more each year in the biotechnology industry. Disposable bioreactors allow one to avoid expenses associated with cleaning, assembly and operations, as well as equipment validation. The WAVE bioreactor is well established for Chinese Hamster Ovary (CHO) production, however, it has not yet been thoroughly tested for E. coli production because of the high oxygen demand and temperature maintenance requirements of that platform. The objective of this study is to establish a robust process to generate inoculum for E. coli production fermentations in a WAVE bioreactor. We opted not to evaluate the WAVE system for production cultures because of the high cell densities required in our current E. coli production processes. Instead, the WAVE bioreactor 20/50 system was evaluated at laboratory scale (10-L) to generate inoculum with target optical densities (OD(550)) of 15 within 7-9 h (pre-established target for stainless steel fermentors). The maximum settings for rock rate (40 rpm) and angle (10.5) were used to maximize mass transfer. The gas feed was also supplemented with additional oxygen to meet the high respiratory demand of the culture. The results showed that the growth profiles for the inoculum cultures were similar to those obtained from conventional stainless steel fermentors. These inoculum cultures were subsequently inoculated into 10-L working volume stainless steel fermentors to evaluate the inocula performance of two different production systems during recombinant protein production. The results of these production cultures using WAVE inocula showed that the growth and recombinant protein production was comparable to the control data set. Furthermore, an economic analysis showed that the WAVE system would require less capital investment for installation and operating expenses would be less than traditional stainless steel systems.
MeSH term(s)	Animals ; Bioreactors/microbiology ; CHO Cells ; Cricetinae ; Cricetulus ; Escherichia coli/growth & development ; Fermentation/physiology
Language	English
Publishing date	2010-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	165657-0
ISSN	1520-6033 ; 8756-7938
ISSN (online)	1520-6033
ISSN	8756-7938
DOI	10.1002/btpr.414
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Article ; Online: Characterization of a nutrient feed precipitate from an E. coli fermentation process.

Speciner, Lauren / Mallon, Erin / Leung, Susan / Laird, Michael W / Esue, Osigwe

Biotechnology progress

2010 Volume 26, Issue 5, Page(s) 1290–1294

Abstract: Metalloproteins require soluble metal ions such as zinc to properly fold into their native and active state to maintain stability and biological activity. When protein products are produced during microbial fermentations, metals are made available to the ...

Abstract	Metalloproteins require soluble metal ions such as zinc to properly fold into their native and active state to maintain stability and biological activity. When protein products are produced during microbial fermentations, metals are made available to the metalloproteins via nutrient supplements. During the production at the manufacturing-scale of a recombinant product that required zinc as a cofactor, an insoluble precipitate formed in the preparation tank after steam sterilization of the nutrient feed containing methionine, glycerophosphate, and zinc sulfate (MGZ). The precipitated nutrient feed was believed to be the cause for not enough zinc delivered to the production fermentor, leading to poor product assembly and stabilization. This article explores several analytical techniques such as capillary zone electrophoresis, inductively coupled plasma and phosphate molybdate assays to identify and quantify the composition of the precipitate. Our results show that the glycerophosphate component of the combined MGZ nutrient feed contains inorganic phosphate, which precipitates zinc from the feed media.
MeSH term(s)	Electrophoresis, Capillary ; Escherichia coli/metabolism ; Fermentation/physiology ; Glycerophosphates/metabolism ; Mass Spectrometry ; Methionine/metabolism ; Zinc Sulfate/metabolism
Chemical Substances	Glycerophosphates ; Zinc Sulfate (7733-02-0) ; Methionine (AE28F7PNPL)
Language	English
Publishing date	2010-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	165657-0
ISSN	1520-6033 ; 8756-7938
ISSN (online)	1520-6033
ISSN	8756-7938
DOI	10.1002/btpr.419
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Article ; Online: Direct Measurement of the Key E_{c.m.}=456 keV Resonance in the Astrophysical ^{19}Ne(p,γ)^{20}Na Reaction and Its Relevance for Explosive Binary Systems.

Wilkinson, R / Lotay, G / Lennarz, A / Ruiz, C / Christian, G / Akers, C / Catford, W N / Chen, A A / Connolly, D / Davids, B / Hutcheon, D A / Jedrejcic, D / Laird, A M / Martin, L / McNeice, E / Riley, J / Williams, M

Physical review letters

2017 Volume 119, Issue 24, Page(s) 242701

Abstract: ... definitely measured for the first time at E_{c.m.}=456_{-2}^{+5} keV with an associated strength of 17_{-5 ...

Abstract	We have performed a direct measurement of the ^{19}Ne(p,γ)^{20}Na reaction in inverse kinematics using a beam of radioactive ^{19}Ne. The key astrophysical resonance in the ^{19}Ne+p system has been definitely measured for the first time at E_{c.m.}=456_{-2}^{+5} keV with an associated strength of 17_{-5}^{+7} meV. The present results are in agreement with resonance strength upper limits set by previous direct measurements, as well as resonance energies inferred from precision (^{3}He, t) charge exchange reactions. However, both the energy and strength of the 456 keV resonance disagree with a recent indirect study of the ^{19}Ne(d, n)^{20}Na reaction. In particular, the new ^{19}Ne(p,γ)^{20}Na reaction rate is found to be factors of ∼8 and ∼5 lower than the most recent evaluation over the temperature range of oxygen-neon novae and astrophysical x-ray bursts, respectively. Nevertheless, we find that the ^{19}Ne(p,γ)^{20}Na reaction is likely to proceed fast enough to significantly reduce the flux of ^{19}F in nova ejecta and does not create a bottleneck in the breakout from the hot CNO cycles into the rp process.
Language	English
Publishing date	2017-12-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.119.242701
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