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Article: Direct Detection of Glycated Human Serum Albumin and Hyperglycosylated IgG3 in Serum, by MALDI-ToF Mass Spectrometry, as a Predictor of COVID-19 Severity.

Iles, Ray K / Iles, Jason K / Lacey, Jonathan / Gardiner, Anna / Zmuidinaite, Raminta

2022 Volume 12, Issue 10

Abstract: The prefusion spike protein of SARS-CoV-2 binds advanced glycation end product (AGE)-glycated human serum albumin (HSA) and a higher mass (hyperglycosylated/glycated) immunoglobulin (Ig) G3, as determined by matrix assisted laser desorption mass ... ...

Abstract	The prefusion spike protein of SARS-CoV-2 binds advanced glycation end product (AGE)-glycated human serum albumin (HSA) and a higher mass (hyperglycosylated/glycated) immunoglobulin (Ig) G3, as determined by matrix assisted laser desorption mass spectrometry (MALDI-ToF). We set out to investigate if the total blood plasma of patients who had recovered from acute respiratory distress syndrome (ARDS) as a result of COVID-19, contained more glycated HSA and higher mass (glycosylated/glycated) IgG3 than those with only clinically mild or asymptomatic infections. A direct serum dilution, and disulphide bond reduction, method was developed and applied to plasma samples from SARS-CoV-2 seronegative (
Language	English
Publishing date	2022-10-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics12102521
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Article ; Online: Airway management in the adult patient with an unstable cervical spine.

d'Arville, Asha / Walker, Matthew / Lacey, Jonathan / Lancman, Benn / Hendel, Simon

Current opinion in anaesthesiology

2021 Volume 34, Issue 5, Page(s) 597–602

Abstract: Purpose of review: The ideal airway management of patients with unstable spinal injury presents a perennial challenge for anaesthesiologists. With competing interests, potentially catastrophic complications, and a scarcity of evidence to support common ... ...

Abstract	Purpose of review: The ideal airway management of patients with unstable spinal injury presents a perennial challenge for anaesthesiologists. With competing interests, potentially catastrophic complications, and a scarcity of evidence to support common practices, it is an area rich with dogma and devoid of data. This review seeks to highlight recent evidence that improves our assurance that what we do to manage the airway in the unstable cervical spine is supported by data. Recent findings: The increasing range of available technology for intubation provides important opportunities to investigate the superiority (or otherwise) of various techniques - and a chance to challenge accepted practice. Long-held assumptions regarding spinal immobilisation in the context of airway management may require refinement as a true base of evidence develops. Summary: Video laryngoscopy may replace direct laryngoscopy as the default technique for endotracheal intubation in patients with suspected or confirmed spinal instability. Immobilisation of the unstable cervical spine, manually or with rigid cervical collars, is increasingly controversial. It may be that hard collars are used in specific circumstances, rather than as universal precaution in the future.There are no recent data of significantly high quality to warrant wholesale changes to recommended airway management practice and in the absence of new information, limiting movement (in the suspected or confirmed unstable cervical spine) remains the mainstay of clinical practice advice.
MeSH term(s)	Adult ; Airway Management ; Cervical Vertebrae ; Humans ; Intubation, Intratracheal/adverse effects ; Laryngoscopy ; Spinal Injuries
Language	English
Publishing date	2021-07-24
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645203-6
ISSN	1473-6500 ; 0952-7907
ISSN (online)	1473-6500
ISSN	0952-7907
DOI	10.1097/ACO.0000000000001040
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Article ; Online: Mass casualty, intentional vehicular trauma and anaesthesia.

Walker, Matthew / d'Arville, Asha / Lacey, Jonathan / Lancman, Benn / Moloney, John / Hendel, Simon

British journal of anaesthesia

2021 Volume 128, Issue 2, Page(s) e190–e199

Abstract: The use of motor vehicles to initiate mass casualty incidents is increasing in frequency and such events are called intentional vehicular assaults. Perpetrators are inspired by a range of terrorist ideologies or have extremist views, criminal intent, or ... ...

Abstract	The use of motor vehicles to initiate mass casualty incidents is increasing in frequency and such events are called intentional vehicular assaults. Perpetrators are inspired by a range of terrorist ideologies or have extremist views, criminal intent, or mental health issues. Assaults using a motor vehicle as the principal weapon of attack are easy to launch and require little to no forward planning. This makes them difficult for police and security agencies to predict, prevent, or interdict. With the increasing frequency of intentional vehicular assaults, anaesthesiologists in various settings may be involved in caring for victims and should be engaged in preparing for them. This narrative review examines the literature on vehicle assaults committed around the world and provides an overview of the unique injury patterns and considerations for the pre-hospital, perioperative, and critical care management of victims of these mass casualty events. The article discusses planning, education, and training in an attempt to reduce the mortality and morbidity of intentional vehicular assaults.
Language	English
Publishing date	2021-10-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2021.08.030
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Article ; Online: SARS-CoV-2 Spike Protein Binding of Glycated Serum Albumin-Its Potential Role in the Pathogenesis of the COVID-19 Clinical Syndromes and Bias towards Individuals with Pre-Diabetes/Type 2 Diabetes and Metabolic Diseases.

Iles, Jason / Zmuidinaite, Raminta / Sadee, Christoph / Gardiner, Anna / Lacey, Jonathan / Harding, Stephen / Ule, Jernej / Roblett, Debra / Heeney, Jonathan / Baxendale, Helen / Iles, Ray K

International journal of molecular sciences

2022 Volume 23, Issue 8

Abstract: The immune response to SARS-CoV-2 infection requires antibody recognition of the spike protein. In a study designed to examine the molecular features of anti-spike and anti-nucleocapsid antibodies, patient plasma proteins binding to pre-fusion stabilised ...

Abstract	The immune response to SARS-CoV-2 infection requires antibody recognition of the spike protein. In a study designed to examine the molecular features of anti-spike and anti-nucleocapsid antibodies, patient plasma proteins binding to pre-fusion stabilised complete spike and nucleocapsid proteins were isolated and analysed by matrix-assisted laser desorption ionisation-time of flight (MALDI-ToF) mass spectrometry. Amongst the immunoglobulins, a high affinity for human serum albumin was evident in the anti-spike preparations. Careful mass comparison revealed the preferential capture of advanced glycation end product (AGE) forms of glycated human serum albumin by the pre-fusion spike protein. The ability of bacteria and viruses to surround themselves with serum proteins is a recognised immune evasion and pathogenic process. The preference of SARS-CoV-2 for AGE forms of glycated serum albumin may in part explain the severity and pathology of acute respiratory distress and the bias towards the elderly and those with (pre)diabetic and atherosclerotic/metabolic disease.
MeSH term(s)	Aged ; Antibodies, Viral ; COVID-19 ; Diabetes Mellitus, Type 2 ; Humans ; Prediabetic State ; SARS-CoV-2 ; Serum Albumin ; Serum Albumin, Human ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Antibodies, Viral ; Serum Albumin ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Serum Albumin, Human (ZIF514RVZR)
Language	English
Publishing date	2022-04-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23084126
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Article ; Online: Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding-Who Is Binding Who and Why?

Iles, Jason K / Zmuidinaite, Raminta / Sadee, Christoph / Gardiner, Anna / Lacey, Jonathan / Harding, Stephen / Wallis, Gregg / Patel, Roshani / Roblett, Debra / Heeney, Jonathan / Baxendale, Helen / Iles, Ray Kruse

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: The involvement of immunoglobulin (Ig) G3 in the humoral immune response to SARS-CoV-2 infection has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) in COVID-19. The exact molecular mechanism is unknown, but it is ... ...

Abstract	The involvement of immunoglobulin (Ig) G3 in the humoral immune response to SARS-CoV-2 infection has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) in COVID-19. The exact molecular mechanism is unknown, but it is thought to involve this IgG subtype's differential ability to fix, complement and stimulate cytokine release. We examined the binding of convalescent patient antibodies to immobilized nucleocapsids and spike proteins by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. IgG3 was a major immunoglobulin found in all samples. Differential analysis of the spectral signatures found for the nucleocapsid versus the spike protein demonstrated that the predominant humoral immune response to the nucleocapsid was IgG3, whilst for the spike protein it was IgG1. However, the spike protein displayed a strong affinity for IgG3 itself, as it would bind from control plasma samples, as well as from those previously infected with SARS-CoV-2, similar to the way protein G binds IgG1. Furthermore, detailed spectral analysis indicated that a mass shift consistent with hyper-glycosylation or glycation was a characteristic of the IgG3 captured by the spike protein.
MeSH term(s)	Antibodies, Viral ; COVID-19 ; Humans ; Immunoglobulin G ; Nucleocapsid ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-05-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23116050
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Article ; Online: Thirst-guided participant-controlled intravenous fluid rehydration: a single blind, randomised crossover study.

Lacey, Jonathan / Corbett, Jo / Shepherd, Ant / Dubois, Andre / Hughes, Fintan / White, Danny / Tipton, Mike / Mythen, Michael / Montgomery, Hugh

British journal of anaesthesia

2020 Volume 124, Issue 4, Page(s) 403–410

Abstract: Background: Dehydration is common in hospitals and is associated with increased mortality and morbidity. Clinical assessment and diagnostic measures of dehydration are unreliable. We sought to investigate the novel concept that individuals might control ...

Abstract	Background: Dehydration is common in hospitals and is associated with increased mortality and morbidity. Clinical assessment and diagnostic measures of dehydration are unreliable. We sought to investigate the novel concept that individuals might control their own intravenous rehydration, guided by thirst. Methods: We performed a single-blind, counterbalanced, randomised cross-over trial. Ten healthy male volunteers of mean age 26 (standard deviation [sd] 10.5) yr were dehydrated by 3-5% of their baseline body mass via exercising in the heat (35°C, 60% humidity). This was followed by a 4 h participant-controlled intravenous rehydration: individuals triggered up to six fluid boluses (4% dextrose in 0.18% sodium chloride) per hour in response to thirst. Participants undertook two blinded rehydration protocols which differed only by bolus volume: 50 ml (low volume [LV]) or 200 ml (high volume [HV]). Each hour during the rehydration phase, plasma osmolality (pOsm) was measured and thirst score recorded. Nude body mass was measured at baseline, after dehydration, and after the rehydration phase. Results: In both conditions, the mean dehydration-related body mass loss was 3.9%. Thirst score was strongly associated with pOsm (within-subject r=0.74) and demand for fluid decreased as pOsm corrected. In the HV condition, participants rapidly rehydrated themselves (mean fluid delivered 3060 vs 981 ml in the LV condition) to body mass and pOsm no different to their euhydrated state. Conclusion: Healthy individuals appear able to rely on thirst to manage intravenous fluid intake. Future work must now focus on whether patient-controlled intravenous fluids could represent a paradigm shift in the management of hydration in the clinical setting. Clinical trial registration: NCT03932890.
Language	English
Publishing date	2020-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2019.12.008
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Article ; Online: Validation of a MALDI-TOF MS method for SARS-CoV-2 detection on the Bruker Biotyper and nasopharyngeal swabs. A Brazil - UK collaborative study.

Lovison, Otavio von Ameln / Grigaite, Raminta / Zempulski Volpato, Fabiana Carolina / Iles, Jason Kruse / Lacey, Jonathan / Barreto, Fabiano / Pandiri, Sai Rahul / Balzan, Lisiane da Luz Rocha / Cantarelli, Vlademir Vicente / Barth, Afonso Luis / Martins, Andreza Francisco / Iles, Raymond Kruse

medRxiv

Abstract: We had developed a MALDI-TOF mass spectrometry method for detection of SARS-CoV-2 virus in saliva-gargle samples using Shimadzu MALDI-TOF mass spectrometers in the UK. This was validated in the USA to CLIA-LDT standards for asymptomatic infection ... ...

Abstract	We had developed a MALDI-TOF mass spectrometry method for detection of SARS-CoV-2 virus in saliva-gargle samples using Shimadzu MALDI-TOF mass spectrometers in the UK. This was validated in the USA to CLIA-LDT standards for asymptomatic infection detection remotely via sharing protocols, shipping key reagents, video conference and data exchange. In Brazil, more so than in the UK and USA, there is a need to develop non-PCR dependent rapid affordable SARS-CoV-2 infection screening tests, which also identify variant SARS-CoV-2 and other virus infections. Travel restrictions necessitated remote collaboration with validation on the available Clinical MALDI-TOF - the Bruker Biotyper (microflex LT/SH) - and on nasopharyngeal swab samples, as salivary gargle samples were not available. The Bruker Biotyper was shown to be almost log10^3 more sensitive at detection of high molecular weight spike proteins. A protocol for saline swab soaks out was developed and duplicate swab samples collected in Brazil were analysed by MALDI-TOF MS. The swab collected sample spectra varied from that of gargle-saliva in three additional mass peaks in the mass region expected for IgG heavy chains and human serum albumin. A subset of clinical samples with additional high mass, probably Spike-related proteins, were also found. Spectral data comparisons and analysis, subjected to machine learning algorithms in order to resolve RT-qPCR positive from RT-qPCR negative swab samples, showed a 78% agreement with RT-qPCR scoring for SARS-CoV-2 infection.
Keywords	covid19
Language	English
Publishing date	2023-01-11
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.01.09.23284367
Database	COVID19

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Article ; Online: Direct detection of humoral marker corelates of COVID-19, glycated HSA and hyperglycosylated IgG3, by MALDI-ToF mass spectrometry.

Iles, Raymond Kruse / Iles, Jason Kruse / Zmuidinaite, Raminta / Gardiner, Anna / Lacey, Jonathan / Harding, Stephen / Heeney, Jonathan Luke / Baxendale, Dr HE

medRxiv

Abstract: The prefusion Spike protein of SARS-CoV2 binds advanced glycation end product (AGE) glycated human serum albumin (HSA) and a higher mass, hyperglycosylated/glycated, IgG3, as determined by matrix assisted laser desorption mass spectrometry (MALDI-ToF MS). ...

Abstract	The prefusion Spike protein of SARS-CoV2 binds advanced glycation end product (AGE) glycated human serum albumin (HSA) and a higher mass, hyperglycosylated/glycated, IgG3, as determined by matrix assisted laser desorption mass spectrometry (MALDI-ToF MS). We set out to investigate if the total blood plasma of patients who had recovered from acute respiratory distress as a result of COVID-19, contained more glycated HSA and higher mass (glycosylated/glycated) IgG3 than those with only clinically mild or asymptomatic infections. A direct dilution and disulphide bond reduction method was development and applied to plasma samples from SARS-CoV2 seronegative (N = 30) and seropositive (N = 31) healthcare workers and 38 convalescent plasma samples from patients who had been admitted with acute respiratory distress syndrome (ARDS) associated with COVID-19. Patients recovering from COVID-19 ARDS had significantly higher mass, AGE-glycated HSA and higher mass IgG3 levels. This would indicate that increased levels and/or ratios of hyper-glycosylation (probably terminal sialic acid) IgG3 and AGE glycated HSA may be predisposition markers for development of ARDS as a result of COVID-19 infection. Furthermore, rapid direct analysis of plasma samples by MALDI-ToF MS for such humoral immune correlates of COVID-19 presents a feasible screening technology for the most at risk; regardless of age or known health conditions.
Keywords	covid19
Language	English
Publishing date	2021-07-10
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.07.08.21260186
Database	COVID19

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Article: Reduction of Pythium Damping-Off in Soybean by Biocontrol Seed Treatment.

Pimentel, Mirian F / Arnao, Erika / Warner, Amanda J / Rocha, Leonardo F / Subedi, Arjun / Elsharif, Nariman / Chilvers, Martin I / Matthiesen, Rashelle / Robertson, Alison E / Bradley, Carl A / Neves, Danilo L / Pedersen, Dianne K / Reuter-Carlson, Ursula / Lacey, Jonathan V / Bond, Jason P / Fakhoury, Ahmad M

Plant disease

2022 Volume 106, Issue 9, Page(s) 2403–2414

Abstract: ... ...

Abstract	Pythium
MeSH term(s)	Fungicides, Industrial/pharmacology ; Plant Diseases/parasitology ; Plant Diseases/prevention & control ; Pythium/physiology ; Seedlings ; Seeds ; Glycine max
Chemical Substances	Fungicides, Industrial
Language	English
Publishing date	2022-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	754182-x
ISSN	0191-2917
ISSN	0191-2917
DOI	10.1094/PDIS-06-21-1313-RE
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Article: Reduction of Pythium Damping-Off in Soybean by Biocontrol Seed Treatment

Pimentel, Mirian F. / Arnao, Erika / Warner, Amanda J. / Rocha, Leonardo F. / Subedi, Arjun / Elsharif, Nariman / Chilvers, Martin I. / Matthiesen, Rashelle / Robertson, Alison E. / Bradley, Carl A. / Neves, Danilo L. / Pedersen, Dianne K. / Reuter-Carlson, Ursula / Lacey, Jonathan V. / Bond, Jason P. / Fakhoury, Ahmad M.

Plant disease. 2022 Sept. 01, v. 106, no. 9

2022

Abstract: Pythium spp. is one of the major groups of pathogens that cause seedling diseases on soybean, leading to both preemergence and postemergence damping-off and root rot. More than 100 species have been identified within this genus, with Pythium irregulare, ... ...

Abstract	Pythium spp. is one of the major groups of pathogens that cause seedling diseases on soybean, leading to both preemergence and postemergence damping-off and root rot. More than 100 species have been identified within this genus, with Pythium irregulare, P. sylvaticum, P. ultimum var ultimum, and P. torulosum being particularly important for soybean production given their aggressiveness, prevalence, and abundance in production fields. This study investigated the antagonistic activity of potential biological control agents (BCAs) native to the U.S. Midwest against Pythium spp. First, in vitro screening identified BCAs that inhibit P. ultimum var. ultimum growth. Scanning electron microscopy demonstrated evidence of mycoparasitism of all potential biocontrol isolates against P. ultimum var. ultimum and P. torulosum, with the formation of appressorium-like structures, short hyphal branches around host hyphae, hook-shaped structures, coiling, and parallel growth of the mycoparasite along the host hyphae. Based on these promising results, selected BCAs were tested under field conditions against six different Pythium spp. Trichoderma afroharzianum 26 used alone and a mix of T. hamatum 16 + T. afroharzianum 19 used as seed treatments protected soybean seedlings from Pythium spp. infection, as BCA-treated plots had on average 15 to 20% greater plant stand and vigor than control plots. Our results also indicate that some of these potential BCAs could be added with a fungicide seed treatment with minimum inhibition occurring, depending on the fungicide active ingredient. This research highlights the need to develop tools incorporating biological control as a facet of soybean seedling disease management programs. The harnessing of native BCAs could be integrated with other management strategies to provide efficient control of seedling diseases.
Keywords	Pythium irregulare ; Trichoderma ; active ingredients ; biological control ; damping off ; disease control ; electron microscopy ; fungicides ; hyphae ; mycoparasites ; root rot ; seed treatment ; seedlings ; soybeans ; vigor ; Midwestern United States
Language	English
Dates of publication	2022-0901
Size	p. 2403-2414.
Publishing place	The American Phytopathological Society
Document type	Article
ZDB-ID	754182-x
ISSN	0191-2917
ISSN	0191-2917
DOI	10.1094/PDIS-06-21-1313-RE
Database	NAL-Catalogue (AGRICOLA)

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