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Article ; Online: Vagus Nerve Stimulation

Eric Azabou / Guillaume Bao / Rania Bounab / Nicholas Heming / Djillali Annane

Frontiers in Medicine, Vol

A Potential Adjunct Therapy for COVID-19

2021 Volume 8

Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through excessive end organ inflammation. Despite improved understanding of the pathophysiology, management, and the great efforts worldwide ...

Abstract	The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through excessive end organ inflammation. Despite improved understanding of the pathophysiology, management, and the great efforts worldwide to produce effective drugs, death rates of COVID-19 patients remain unacceptably high, and effective treatment is unfortunately lacking. Pharmacological strategies aimed at modulating inflammation in COVID-19 are being evaluated worldwide. Several drug therapies targeting this excessive inflammation, such as tocilizumab, an interleukin (IL)-6 inhibitor, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, and intravenous immunoglobulin have been identified as potentially useful and reliable approaches to counteract the cytokine storm. However, little attention is currently paid for non-drug therapeutic strategies targeting inflammatory and immunological processes that may be useful for reducing COVID-19-induced complications and improving patient outcome. Vagus nerve stimulation attenuates inflammation both in experimental models and preliminary data in human. Modulating the activity of cholinergic anti-inflammatory pathways (CAPs) described by the group of KJ Tracey has indeed become an important target of therapeutic research strategies for inflammatory diseases and sepsis. Non-invasive transcutaneous vagal nerve stimulation (t-VNS), as a non-pharmacological adjuvant, may help reduce the burden of COVID-19 and deserve to be investigated. VNS as an adjunct therapy in COVID-19 patients should be investigated in clinical trials. Two clinical trials on this topic are currently underway (NCT04382391 and NCT04368156). The results of these trials will be informative, but additional larger studies are needed.
Keywords	COVID-19 ; cytokine storm ; inflammation ; non-drug therapy ; vagus nerve stimulation ; neuromodulation ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vasopressor Therapy and the Brain

Nicholas Heming / Aurélien Mazeraud / Eric Azabou / Pierre Moine / Djillali Annane

Frontiers in Medicine, Vol

Dark Side of the Moon

2020 Volume 6

Abstract: Sepsis, a leading cause of morbidity and mortality, is caused by a deregulated host response to pathogens, and subsequent life-threatening organ dysfunctions. All major systems, including the cardiovascular, respiratory, renal, hepatic, hematological, ... ...

Abstract	Sepsis, a leading cause of morbidity and mortality, is caused by a deregulated host response to pathogens, and subsequent life-threatening organ dysfunctions. All major systems, including the cardiovascular, respiratory, renal, hepatic, hematological, and the neurological system may be affected by sepsis. Sepsis associated neurological dysfunction is triggered by multiple factors including neuro-inflammation, excitotoxicity, and ischemia. Ischemia results from reduced cerebral blood flow, caused by extreme variations of blood pressure, occlusion of cerebral vessels, or more subtle defects of the microcirculation. International guidelines comprehensively describe the initial hemodynamic management of sepsis, revolving around the normalization of systemic hemodynamics and of arterial lactate. By contrast, the management of sepsis patients suffering from brain dysfunction is poorly detailed, the only salient point being mentioned is that sedation and analgesia should be optimized. However, sepsis and the hemodynamic consequences thereof as well as vasopressors may have severe untoward neurological consequences. The current review describes the general neurological complications, as well as the consequences of vasopressor therapy on the brain and its circulation and addresses methods for cerebral monitoring during sepsis.
Keywords	sepsis associated encephalopathy ; delirium ; coma ; sepsis ; septic shock ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Randomized Controlled Study Evaluating Efficiency of Low Intensity Transcranial Direct Current Stimulation (tDCS) for Dyspnea Relief in Mechanically Ventilated COVID-19 Patients in ICU

Eric Azabou / Guillaume Bao / Nicholas Heming / Rania Bounab / Pierre Moine / Sylvain Chevallier / Sylvie Chevret / Matthieu Resche-Rigon / Shidaps Siami / Tarek Sharshar / Frederic Lofaso / Djillali Annane

Frontiers in Medicine, Vol

The tDCS-DYSP-COVID Protocol

2020 Volume 7

Abstract: The severe respiratory distress syndrome linked to the new coronavirus disease (COVID-19) includes unbearable dyspneic suffering which contributes to the deterioration of the prognosis of patients in intensive care unit (ICU). Patients are put on ... ...

Abstract	The severe respiratory distress syndrome linked to the new coronavirus disease (COVID-19) includes unbearable dyspneic suffering which contributes to the deterioration of the prognosis of patients in intensive care unit (ICU). Patients are put on mechanical ventilation to reduce respiratory suffering and preserve life. Despite this mechanical ventilation, most patients continue to suffer from dyspnea. Dyspnea is a major source of suffering in intensive care and one of the main factors that affect the prognosis of patients. The development of innovative methods for its management, especially non-drug management is more than necessary. In recent years, numerous studies have shown that transcranial direct current stimulation (tDCS) could modulate the perception of acute or chronic pain. In the other hand, it has been shown that the brain zones activated during pain and dyspnea are close and/or superimposed, suggesting that brain structures involved in the integration of aversive emotional component are shared by these two complex sensory experiences. Therefore, it can be hypothesized that stimulation by tDCS with regard to the areas which, in the case of pain have activated one or more of these brain structures, may also have an effect on dyspnea. In addition, our team recently demonstrated that the application of tDCS on the primary cortical motor area can modulate the excitability of the respiratory neurological pathways. Indeed, tDCS in anodal or cathodal modality reduced the excitability of the diaphragmatic cortico-spinal pathways in healthy subjects. We therefore hypothesized that tDCS could relieve dyspnea in COVID-19 patients under mechanical ventilation in ICU. This study was designed to evaluate effects of two modalities of tDCS (anodal and cathodal) vs. placebo, on the relief of dyspnea in COVID-19 patients requiring mechanical ventilation in ICU.Trial Registration: This protocol is derived from the tDCS-DYSP-REA project registered on ClinicalTrials.gov NCT03640455. It will however be registered under ...
Keywords	COVID-19 ; acute respiratory distress syndrome (ARDS) ; tDCS ; dyspnea relief ; brain ; neuromodulation ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Eculizumab as an emergency treatment for adult patients with severe COVID-19 in the intensive care unit

Djillali Annane / Nicholas Heming / Lamiae Grimaldi-Bensouda / Véronique Frémeaux-Bacchi / Marie Vigan / Anne-Laure Roux / Armance Marchal / Hugues Michelon / Martin Rottman / Pierre Moine

EClinicalMedicine, Vol 28, Iss , Pp 100590- (2020)

A proof-of-concept study

2020

Abstract: Background: Complement pathway inhibition may provide benefit for severe acute respiratory illnesses caused by viral infections such as COVID-19. We present results from a nonrandomized proof-of-concept study of complement C5 inhibitor eculizumab for ... ...

Abstract	Background: Complement pathway inhibition may provide benefit for severe acute respiratory illnesses caused by viral infections such as COVID-19. We present results from a nonrandomized proof-of-concept study of complement C5 inhibitor eculizumab for treatment of severe COVID-19. Methods: All patients (N = 80) with confirmed SARS-CoV-2 infection and severe COVID-19 admitted to our intensive care unit between March 10 and May 5, 2020 were included. Forty-five patients were treated with standard care and 35 with standard care plus eculizumab through expanded-access emergency treatment. The prespecified primary outcome was day-15 survival. Clinical laboratory values and biomarkers, complement levels, and treatment-emergent serious adverse events (TESAEs) were also assessed. Findings: At day 15, estimated survival was 82.9% (95% CI: 70.4%‒95.3%) with eculizumab and 62.2% (48.1%‒76.4%) without eculizumab (log-rank test, P = 0.04). Patients treated with eculizumab experienced a significantly more rapid decrease in lactate, blood urea nitrogen, total and conjugated bilirubin levels and a significantly more rapid increase in platelet count, prothrombin time, and in the ratio of arterial oxygen tension over fraction of inspired oxygen versus patients treated without eculizumab. Eculizumab-associated changes in complement levels, laboratory values, and biomarkers were consistent with terminal complement inhibition, reduced hypoxia, and decreased inflammation. TESAEs of special interest occurring in >5% of patients treated with/without eculizumab were ventilator-associated pneumonia (51%/24%), bacteremia (11%/2%), gastroduodenal hemorrhage (14%/16%), and hemolysis (3%/18%). Interpretation: Findings from this proof-of-concept study suggest eculizumab may improve survival and reduce hypoxia in patients with severe COVID-19. Randomized studies evaluating the efficacy and safety of this treatment approach are needed. Funding: Programme d'Investissements d'Avenir: ANR-18-RHUS60004.
Keywords	Coronavirus ; Pneumonia ; Acute respiratory distress syndrome ; Sepsis ; Complement pathway ; C5 inhibitor ; Medicine (General) ; R5-920
Subject code	610 ; 616
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Metabolomics of exhaled breath in critically ill COVID-19 patients

Stanislas Grassin-Delyle, Ph.D. / Camille Roquencourt, M.S. / Pierre Moine, M.D. / Gabriel Saffroy / Stanislas Carn / Nicholas Heming, M.D. / Jérôme Fleuriet, Ph.D. / Hélène Salvator, M.D. / Emmanuel Naline, Ph.D. / Louis-Jean Couderc, M.D. / Philippe Devillier, M.D. / Etienne A. Thévenot, Ph.D. / Djillali Annane, M.D.

EBioMedicine, Vol 63, Iss , Pp 103154- (2021)

A pilot study

1478

Abstract: Background: Early diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19. Methods: In ... ...

Abstract	Background: Early diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19. Methods: In this prospective observational study, we used real-time, online, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of expired air from adults undergoing invasive mechanical ventilation in the intensive care unit due to severe COVID-19 or non-COVID-19 acute respiratory distress syndrome (ARDS). Findings: Between March 25th and June 25th, 2020, we included 40 patients with ARDS, of whom 28 had proven COVID-19. In a multivariate analysis, we identified a characteristic breathprint for COVID-19. We could differentiate between COVID-19 and non-COVID-19 ARDS with accuracy of 93% (sensitivity: 90%, specificity: 94%, area under the receiver operating characteristic curve: 0•94-0•98, after cross-validation). The four most prominent volatile compounds in COVID-19 patients were methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal. Interpretation: The real-time, non-invasive detection of methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal in exhaled breath may identify ARDS patients with COVID-19. Funding: The study was funded by Agence Nationale de la Recherche (SoftwAiR, ANR-18-CE45-0017 and RHU4 RECORDS, Programme d'Investissements d'Avenir, ANR-18-RHUS-0004), Région Île de France (SESAME 2016), and Fondation Foch.
Keywords	COVID-19 ; Intensive care ; Mechanical ventilation ; Breath analysis ; Metabolomics ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of standard prophylactic, intermediate prophylactic and therapeutic anticoagulation in patients with severe COVID-19

Étienne Audureau / Vincent Labbe / Bruno Megarbane / Jean-François Timsit / Damien Contou / Emmanuel Vivier / Martin Dres / Muriel Fartoukh / Keyvan Razazi / Nicholas Heming / Bertrand Souweine / Armand Mekontso Dessap / Guillaume Voiriot / Denis Doyen / Florence Boissier / Noémie Zucman / Mehran Monchi / Hafid Ait-Oufella / Serge Carreira /

Alexandre Robert / Mohamed Fejjal / Sebastien Preau / Elise Noel-Savina / Santiago Alberto Picos / William Juguet / Eric Mariotte / Matthieu Turpin / Ségolène Gendreau / Samia Baloul

BMJ Open, Vol 12, Iss

protocol for the ANTICOVID multicentre, parallel-group, open-label, randomised controlled trial

2022 Volume 4

Keywords	Medicine ; R
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Population pharmacodynamic modeling and simulation of the respiratory effect of acetazolamide in decompensated COPD patients.

Nicholas Heming / Saïk Urien / Virginie Fulda / Ferhat Meziani / Arnaud Gacouin / Marc Clavel / Benjamin Planquette / Christophe Faisy

PLoS ONE, Vol 9, Iss 1, p e

2014 Volume 86313

Abstract: Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis.619 time-respiratory (minute ventilation, tidal ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis.619 time-respiratory (minute ventilation, tidal volume and respiratory rate) and 207 time-PaCO2 observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug.The effect of acetazolamide on minute ventilation and PaCO2 levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO2 levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily) was required to significantly increase minute ventilation (P<.001 vs pre-acetazolamide administration). Based on our model, 1000 mg per day of acetazolamide would increase minute ventilation by >0.75 L min(-1) in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day.Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
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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Article ; Online: Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS)

Shidasp Siami / Charlène Le Moal / Thomas DAIX / Sylvie Chevret / Yonatan Perez / Constance Vuillard / Damien Roux / Jonathan Messika / Stephan Ehrmann / Jean-Pierre Quenot / Dalila Benzekri / Gwenhaël Colin / Thierry Boulain / Julie Mankikian / Laura Federici / Jean Reignier / Jean-Paul Mira / Marie-Ange Azais / Djillali Annane /

Jean-Claude Lacherade / Grégoire Muller / Christine Lebert / Nicholas Heming / Arthur Bailly / Emmanuelle Mercier / Jean-Baptiste Lascarrou / Julio Badie / Louis-Marie Dumont / Gaetan Plantefeve / Francis Schneider / Patrice Tirot / Isabelle Vinatier / Mickael Landais / Michel Djibré / Bruno Francois / Alexandra Monnier / Francois Barbier / Ferhat Meziani / Hamid Merdji / Pascal Andreu / Julie Helms / Laetitia Bodet-Contentin / Nicolas Pichon / Noémie Zucman / Mehran Monchi / Xavier Monnet / Marie Labruyère / Denis Garot / Hassène Rahmani / Jérôme Fleuriet

BMJ Open, Vol 13, Iss

study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial

2023 Volume 3

Abstract: Introduction Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients’ response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes ... ...

Abstract	Introduction Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients’ response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids.Methods and analysis RECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%–10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids’ effect in each subset, and (2) measure of interaction.Ethics and dissemination The protocol was approved by the Ethics Committee (Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals.Trial registration number ClinicalTrials.gov Registry (NCT04280497).
Keywords	Medicine ; R
Subject code	310
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD89 Is a Potent Innate Receptor for Bacteria and Mediates Host Protection from Sepsis

Christian de Tymowski / Nicholas Heming / Mario D.T. Correia / Lilia Abbad / Nathalie Chavarot / Marie-Bénédicte Le Stang / Heloise Flament / Julie Bex / Erwan Boedec / Carine Bounaix / Rafael Soler-Torronteras / Erick Denamur / Lionel Galicier / Eric Oksenhendler / Hans Joerg Fehling / Fabiano Pinheiro da Silva / Marc Benhamou / Renato C. Monteiro / Sanae Ben Mkaddem

Cell Reports, Vol 27, Iss 3, Pp 762-775.e

2019 Volume 5

Abstract: Summary: Direct bacterial recognition by innate receptors is crucial for bacterial clearance. Here, we show that the IgA receptor CD89 is a major innate receptor that directly binds bacteria independently of its cognate ligands IgA and c-reactive protein ...

Abstract	Summary: Direct bacterial recognition by innate receptors is crucial for bacterial clearance. Here, we show that the IgA receptor CD89 is a major innate receptor that directly binds bacteria independently of its cognate ligands IgA and c-reactive protein (CRP). This binding is only partially inhibited by serum IgA and induces bacterial phagocytosis by CD11c+ dendritic cells and monocytes and/or macrophages, suggesting a physiological role in innate host defense. Blood phagocytes from common variable immunodeficiency patients bind, internalize, and kill bacteria in a CD89-dependent manner, confirming the IgA independence of this mechanism. In vivo, CD89 transgenic mice are protected in two different models of sepsis: a model of pneumonia and the cecal ligation and puncture (CLP) polymicrobial model of infection. These data identify CD89 as a first-line innate receptor for bacterial clearance before adaptive responses can be mounted. Fc receptors may emerge as a class of innate receptors for various bacteria with pleiotropic roles. : de Tymowski et al. demonstrate that CD89 serves as an innate receptor during the early phase of infection. During the late phase, the receptor acts in both innate and adaptive immune responses through double interaction with IgA- or CRP-opsonized and non-opsonized bacteria. Keywords: Fc receptor, innate receptor, sepsis, ITAM, host defense
Keywords	Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality.

Benjamin Rohaut / Raphael Porcher / Tarik Hissem / Nicholas Heming / Patrick Chillet / Kamel Djedaini / Guy Moneger / Stanislas Kandelman / Jeremy Allary / Alain Cariou / Romain Sonneville / Andréa Polito / Marion Antona / Eric Azabou / Djillali Annane / Shidasp Siami / Fabrice Chrétien / Jean Mantz / Tarek Sharshar

PLoS ONE, Vol 12, Iss 4, p e

2017 Volume 0176012

Abstract: Deep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of ... ...

Abstract	Deep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients.Observational prospective multicenter cohort study of 148 non-brain injured deeply sedated patients, defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR) was also assessed. Primary outcome measure was 28-day mortality. A "Brainstem Responses Assessment Sedation Score" (BRASS) was generated.Two distinct sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity were identified (accounting for respectively 54.6% and 45.4% of patients). Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression. Heterogeneous sub-phenotype was a predictor of increased risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63-15.8]; p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] = 5.02 [2.01-12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28-day mortality (c-index [95%CI] = 0.69 [0.54-0.84] and 0.65 [0.49-0.80] respectively).In this prospective cohort study, around half of all deeply sedated critically ill patients displayed an early particular neurological sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the brainstem.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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