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Article: Inappropriate Ventilatory Homeostatic Responses in Hospitalized COVID-19 Patients.

Jareonsettasin, Prem / Zeicu, Claudia / Diehl, Beate / Harper, Ronald M / Astin, Rónan

2022 Volume 13, Page(s) 909915

Abstract: Background: The clinical presentation of COVID-19 suggests altered breathing control - tachypnoea, relative lack of dyspnoea, and often a discrepancy between severity of clinical and radiological findings. Few studies characterize and analyse the ... ...

Abstract	Background: The clinical presentation of COVID-19 suggests altered breathing control - tachypnoea, relative lack of dyspnoea, and often a discrepancy between severity of clinical and radiological findings. Few studies characterize and analyse the contribution of breathing drivers and their ventilatory and perceptual responses. Aim: To establish the prevalence of inappropriate ventilatory and perceptual response in COVID-19, by characterizing the relationships between respiratory rate (RR), dyspnoea and arterial blood gas (ABG) in a cohort of COVID-19 patients at presentation to hospital, and their post-Covid respiratory sequelae at follow-up. Methods: We conducted a retrospective cohort study including consecutive adult patients admitted to hospital with confirmed COVID-19 between 1st March 2020 and 30th April 2020. In those with concurrent ABG, RR and documented dyspnoea status on presentation, we documented patient characteristics, disease severity, and outcomes at hospital and 6-week post-discharge. Results: Of 492 admissions, 194 patients met the inclusion criteria. Tachypnoea was present in 75% pronounced (RR>30) in 36%, and persisted during sleep. RR correlated with heart rate (HR) (r = 0.2674), temperature (r = 0.2824), CRP (r = 0.2561), Alveolar-arterial (A-a) gradient (r = 0.4189), and lower PaO Conclusions: Impaired homeostatic control of ventilation i.e., tachypnoea, despite hypocapnia to the point of alkalosis appears prevalent in patients admitted to hospital with COVID-19, a finding typically accompanying more severe disease. Tachypnoea prevalence was between 12 and 29%. Data suggest that excessive tachypnoea is driven by both peripheral and central mechanisms, but not hypoxia. Over a third of patients with impaired homeostatic ventilatory control did not experience dyspnoea despite tachypnoea. A subset of followed-up patients developed post-covid breathing pattern disorder.
Language	English
Publishing date	2022-06-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.909915
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Quantifying Motor Impairment in Movement Disorders.

FitzGerald, James J / Lu, Zhongjiao / Jareonsettasin, Prem / Antoniades, Chrystalina A

Frontiers in neuroscience

2018 Volume 12, Page(s) 202

Abstract: Until recently the assessment of many movement disorders has relied on clinical rating scales that despite careful design are inherently subjective and non-linear. This makes accurate and truly observer-independent quantification difficult and limits the ...

Abstract	Until recently the assessment of many movement disorders has relied on clinical rating scales that despite careful design are inherently subjective and non-linear. This makes accurate and truly observer-independent quantification difficult and limits the use of sensitive parametric statistical methods. At last, devices capable of measuring neurological problems quantitatively are becoming readily available. Examples include the use of oculometers to measure eye movements and accelerometers to measure tremor. Many applications are being developed for use on smartphones. The benefits include not just more accurate disease quantification, but also consistency of data for longitudinal studies, accurate stratification of patients for entry into trials, and the possibility of automated data capture for remote follow-up. In this mini review, we will look at movement disorders with a particular focus on Parkinson's disease, describe some of the limitations of existing clinical evaluation tools, and illustrate the ways in which objective metrics have already been successful.
Language	English
Publishing date	2018-04-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2018.00202
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Article ; Online: Growth cone collapse assay.

Cook, Geoffrey M W / Jareonsettasin, Prem / Keynes, Roger J

Methods in molecular biology (Clifton, N.J.)

2014 Volume 1162, Page(s) 73–83

Abstract: The growth cone collapse assay has proved invaluable in detecting and purifying axonal repellents. Glycoproteins/proteins present in detergent extracts of biological tissues are incorporated into liposomes, added to growth cones in culture and changes in ...

Abstract	The growth cone collapse assay has proved invaluable in detecting and purifying axonal repellents. Glycoproteins/proteins present in detergent extracts of biological tissues are incorporated into liposomes, added to growth cones in culture and changes in morphology are then assessed. Alternatively purified or recombinant molecules in aqueous solution may be added directly to the cultures. In both cases after a defined period of time (up to 1 h), the cultures are fixed and then assessed by inverted phase contrast microscopy for the percentage of growth cones showing a collapsed profile with loss of flattened morphology, filopodia, and lamellipodia.
MeSH term(s)	Animals ; Cell Culture Techniques/methods ; Cells, Cultured ; Chickens ; Ganglia, Spinal/cytology ; Ganglia, Spinal/drug effects ; Ganglia, Spinal/metabolism ; Growth Cones/drug effects ; Growth Cones/metabolism ; Growth Cones/ultrastructure ; Microscopy, Phase-Contrast/methods ; Proteins/administration & dosage ; Proteins/metabolism ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/metabolism ; Tissue Fixation/methods
Chemical Substances	Proteins ; Recombinant Proteins
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-0777-9_6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Magnetic Vestibular Stimulation (MVS) As a Technique for Understanding the Normal and Diseased Labyrinth.

Ward, Bryan K / Otero-Millan, Jorge / Jareonsettasin, Prem / Schubert, Michael C / Roberts, Dale C / Zee, David S

Frontiers in neurology

2017 Volume 8, Page(s) 122

Abstract: Humans often experience dizziness and vertigo around strong static magnetic fields such as those present in an MRI scanner. Recent evidence supports the idea that this effect is the result of inner ear vestibular stimulation and that the mechanism is a ... ...

Abstract	Humans often experience dizziness and vertigo around strong static magnetic fields such as those present in an MRI scanner. Recent evidence supports the idea that this effect is the result of inner ear vestibular stimulation and that the mechanism is a magnetohydrodynamic force (Lorentz force) that is generated by the interactions between normal ionic currents in the inner ear endolymph and the strong static magnetic field of MRI machines. While in the MRI, the Lorentz force displaces the cupula of the lateral and anterior semicircular canals, as if the head was rotating with a constant acceleration. If a human subject's eye movements are recorded when they are in darkness in an MRI machine (i.e., without fixation), there is a persistent nystagmus that diminishes but does not completely disappear over time. When the person exits the magnetic field, there is a transient aftereffect (nystagmus beating in the opposite direction) that reflects adaptation that occurred in the MRI. This magnetic vestibular stimulation (MVS) is a useful technique for exploring set-point adaptation, the process by which the brain adapts to a change in its environment, which in this case is vestibular imbalance. Here, we review the mechanism of MVS, how MVS produces a unique stimulus to the labyrinth that allows us to explore set-point adaptation, and how this technique might apply to the understanding and treatment of vestibular and other neurological disorders.
Language	English
Publishing date	2017-04-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2017.00122
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Article ; Online: Regulation of nerve growth and patterning by cell surface protein disulphide isomerase.

Cook, Geoffrey Mw / Sousa, Catia / Schaeffer, Julia / Wiles, Katherine / Jareonsettasin, Prem / Kalyanasundaram, Asanish / Walder, Eleanor / Casper, Catharina / Patel, Serena / Chua, Pei Wei / Riboni-Verri, Gioia / Raza, Mansoor / Swaddiwudhipong, Nol / Hui, Andrew / Abdullah, Ameer / Wajed, Saj / Keynes, Roger J

eLife

2020 Volume 9

Abstract: Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they ... ...

Abstract	Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.
MeSH term(s)	Animals ; Astrocytes/physiology ; Axon Guidance/physiology ; Cell Line ; Chick Embryo ; Chickens ; Developmental Biology ; Gene Knockdown Techniques ; Growth Cones/physiology ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Neurosciences ; Nitric Oxide/metabolism ; Procollagen-Proline Dioxygenase/genetics ; Procollagen-Proline Dioxygenase/metabolism ; Protein Disulfide-Isomerases/genetics ; Protein Disulfide-Isomerases/metabolism ; Rats ; Signal Transduction ; Somites/embryology ; Somites/physiology ; Spinal Nerves/embryology ; Spinal Nerves/physiology
Chemical Substances	Membrane Proteins ; Nitric Oxide (31C4KY9ESH) ; Procollagen-Proline Dioxygenase (EC 1.14.11.2) ; P4HB protein, human (EC 5.3.4.1) ; Protein Disulfide-Isomerases (EC 5.3.4.1)
Language	English
Publishing date	2020-05-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.54612
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Article ; Online: Multiple Time Courses of Vestibular Set-Point Adaptation Revealed by Sustained Magnetic Field Stimulation of the Labyrinth.

Jareonsettasin, Prem / Otero-Millan, Jorge / Ward, Bryan K / Roberts, Dale C / Schubert, Michael C / Zee, David S

Current biology : CB

2016 Volume 26, Issue 10, Page(s) 1359–1366

Abstract: A major focus in neurobiology is how the brain adapts its motor behavior to changes in its internal and external environments [1, 2]. Much is known about adaptively optimizing the amplitude and direction of eye and limb movements, for example, but little ...

Abstract	A major focus in neurobiology is how the brain adapts its motor behavior to changes in its internal and external environments [1, 2]. Much is known about adaptively optimizing the amplitude and direction of eye and limb movements, for example, but little is known about another essential form of learning, "set-point" adaptation. Set-point adaptation balances tonic activity so that reciprocally acting, agonist and antagonist muscles have a stable platform from which to launch accurate movements. Here, we use the vestibulo-ocular reflex-a simple behavior that stabilizes the position of the eye while the head is moving-to investigate how tonic activity is adapted toward a new set point to prevent eye drift when the head is still [3, 4]. Set-point adaptation was elicited with magneto-hydrodynamic vestibular stimulation (MVS) by placing normal humans in a 7T MRI for 90 min. MVS is ideal for prolonged labyrinthine activation because it mimics constant head acceleration and induces a sustained nystagmus similar to natural vestibular lesions [5, 6]. The MVS-induced nystagmus diminished slowly but incompletely over multiple timescales. We propose a new adaptation hypothesis, using a cascade of imperfect mathematical integrators, that reproduces the response to MVS (and more natural chair rotations), including the gradual decrease in nystagmus as the set point changes over progressively longer time courses. MVS set-point adaptation is a biological model with applications to basic neurophysiological research into all types of movements [7], functional brain imaging [8], and treatment of vestibular and higher-level attentional disorders by introducing new biases to counteract pathological ones [9].
Language	English
Publishing date	2016-05-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2016.03.066
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Article ; Online: Regulation of nerve growth and patterning by cell surface protein disulphide isomerase

Geoffrey MW Cook / Catia Sousa / Julia Schaeffer / Katherine Wiles / Prem Jareonsettasin / Asanish Kalyanasundaram / Eleanor Walder / Catharina Casper / Serena Patel / Pei Wei Chua / Gioia Riboni-Verri / Mansoor Raza / Nol Swaddiwudhipong / Andrew Hui / Ameer Abdullah / Saj Wajed / Roger J Keynes

eLife, Vol

2020 Volume 9

Abstract	Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.
Keywords	spinal nerve ; repeat patterning ; somite ; axon guidance ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protein synthesis dependence of growth cone collapse induced by different Nogo-A-domains.

Manns, Richard / Schmandke, Andre / Schmandke, Antonio / Jareonsettasin, Prem / Cook, Geoffrey / Schwab, Martin E / Holt, Christine / Keynes, Roger

PloS one

2014 Volume 9, Issue 1, Page(s) e86820

Abstract: Background: The protein Nogo-A regulates axon growth in the developing and mature nervous system, and this is carried out by two distinct domains in the protein, Nogo-A-Δ20 and Nogo-66. The differences in the signalling pathways engaged in axon growth ... ...

Abstract	Background: The protein Nogo-A regulates axon growth in the developing and mature nervous system, and this is carried out by two distinct domains in the protein, Nogo-A-Δ20 and Nogo-66. The differences in the signalling pathways engaged in axon growth cones by these domains are not well characterized, and have been investigated in this study. Methodology/principal findings: We analyzed growth cone collapse induced by the Nogo-A domains Nogo-A-Δ20 and Nogo-66 using explanted chick dorsal root ganglion neurons growing on laminin/poly-lysine substratum. Collapse induced by purified Nogo-A-Δ20 peptide is dependent on protein synthesis whereas that induced by Nogo-66 peptide is not. Nogo-A-Δ20-induced collapse is accompanied by a protein synthesis-dependent rise in RhoA expression in the growth cone, but is unaffected by proteasomal catalytic site inhibition. Conversely Nogo-66-induced collapse is inhibited ∼ 50% by proteasomal catalytic site inhibition. Conclusion/significance: Growth cone collapse induced by the Nogo-A domains Nogo-A-Δ20 and Nogo-66 is mediated by signalling pathways with distinguishable characteristics concerning their dependence on protein synthesis and proteasomal function.
MeSH term(s)	Animals ; Anisomycin/pharmacology ; Chick Embryo ; Ganglia, Spinal/drug effects ; Ganglia, Spinal/metabolism ; Ganglia, Spinal/pathology ; Gene Expression Regulation, Developmental ; Growth Cones/drug effects ; Growth Cones/metabolism ; Growth Cones/pathology ; Laminin ; Leupeptins/pharmacology ; Myelin Proteins/genetics ; Myelin Proteins/metabolism ; Myelin Proteins/pharmacology ; Nogo Proteins ; Polylysine ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Inhibitors/pharmacology ; Protein Biosynthesis/drug effects ; Protein Structure, Tertiary ; Protein Synthesis Inhibitors/pharmacology ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Recombinant Proteins/pharmacology ; Signal Transduction ; Tissue Culture Techniques ; rhoA GTP-Binding Protein/genetics ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	Laminin ; Leupeptins ; Myelin Proteins ; Nogo Proteins ; Proteasome Inhibitors ; Protein Synthesis Inhibitors ; Recombinant Proteins ; acetylleucyl-leucyl-norleucinal (110044-82-1) ; Polylysine (25104-18-1) ; Anisomycin (6C74YM2NGI) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2014-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0086820
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Protein synthesis dependence of growth cone collapse induced by different Nogo-A-domains.

Richard Manns / Andre Schmandke / Antonio Schmandke / Prem Jareonsettasin / Geoffrey Cook / Martin E Schwab / Christine Holt / Roger Keynes

PLoS ONE, Vol 9, Iss 1, p e

2014 Volume 86820

Abstract: The protein Nogo-A regulates axon growth in the developing and mature nervous system, and this is carried out by two distinct domains in the protein, Nogo-A-Δ20 and Nogo-66. The differences in the signalling pathways engaged in axon growth cones by these ...

Abstract	The protein Nogo-A regulates axon growth in the developing and mature nervous system, and this is carried out by two distinct domains in the protein, Nogo-A-Δ20 and Nogo-66. The differences in the signalling pathways engaged in axon growth cones by these domains are not well characterized, and have been investigated in this study.We analyzed growth cone collapse induced by the Nogo-A domains Nogo-A-Δ20 and Nogo-66 using explanted chick dorsal root ganglion neurons growing on laminin/poly-lysine substratum. Collapse induced by purified Nogo-A-Δ20 peptide is dependent on protein synthesis whereas that induced by Nogo-66 peptide is not. Nogo-A-Δ20-induced collapse is accompanied by a protein synthesis-dependent rise in RhoA expression in the growth cone, but is unaffected by proteasomal catalytic site inhibition. Conversely Nogo-66-induced collapse is inhibited ∼ 50% by proteasomal catalytic site inhibition.Growth cone collapse induced by the Nogo-A domains Nogo-A-Δ20 and Nogo-66 is mediated by signalling pathways with distinguishable characteristics concerning their dependence on protein synthesis and proteasomal function.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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