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The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby‐Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs‐Buder et al., Acta Anaesthesiol Scand 2007, 51, 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three‐dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high‐quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus‐based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception. [ABSTRACT FROM AUTHOR]

Mars Express and Mars Atmosphere and Volatile Evolution (MAVEN) observations have demonstrated the influence of Mars's spatially variable crustal magnetic fields upon the configuration of the plasma in the ionosphere. This influence furthermore leads to variations in ionospheric escape, conceivably in part through the modification of the plasma density and electron temperature in the upper ionosphere. In this study, we examine MAVEN Langmuir Probe and Waves data, finding a clear correspondence between the structure of the crustal fields and both the measured electron temperatures and densities, by first constructing an "average" profile from which departures can be quantified. Electron temperatures are shown to be lower in regions of strong crustal fields over a wide altitude range. We extend previous analyses to cover the nightside ionosphere, finding the same effects present to a lesser degree, in contrast to previous studies where the opposite relationship was found between densities and crustal fields. We further determine the altitude range over which this coupling between both plasma density (and temperature) and crustal fields is effective and use measurements made by MAVEN in the solar wind to explore the dependence of this crustal field control on the coupling to the solar wind and the interplanetary magnetic field (IMF). Based on this, there is some suggestion that variations in the solar wind dynamic pressure are associated with modulation of the effects of the crustal fields on plasma density, whereas the strength of the IMF modulates the crustal fields effects on both electron densities and temperatures. Plain Language Summary: Mars's atmosphere is exposed to ultra‐violet light from the Sun, forming a layer of plasma at high altitudes around the planet. This plasma layer, termed the ionosphere, is strongly affected in terms of its density and temperature, both by external factors like the solar wind and the interplanetary magnetic field (IMF), and internal factors, like Mars's crustal magnetic field. Here, we study how effective the crustal magnetic fields are at shaping the ionosphere in both density and temperature, by first determining the average structure of the ionosphere, and then examining departures from this average. We find that plasma densities are elevated and temperatures reduced in regions where the crustal field is stronger. We also find the same effect on the nightside. This result is in apparent opposition to previous related studies, now based on a much larger data set, which we suggest may be the result of poor seasonal sampling in earlier studies. We further investigate how this crustal field control varies with the solar wind and IMF, and see evidence for weak modulation according to both the dynamic pressure exerted by the solar wind, and the strength of the IMF. Key Points: We present a statistical analysis of Mars Atmosphere and Volatile Evolution Langmuir Probe and Wave densities and temperatures at MarsDensities are elevated and temperatures reduced in strong crustal field regions, on both the dayside and nightsideVariations in the driving solar wind conditions are able to affect these correlations to a modest degree [ABSTRACT FROM AUTHOR]

On 6–8 June 2015, the Ion and Electron Sensor on board Rosetta observed keV‐range water‐group pickup ions arriving from the solar direction. Based on magnetic field intensification and variations, the appearance of the ions was likely to have been caused by a coronal mass ejection. During the 3‐day period when Rosetta was 200 km from the comet, peak ion energy/charge (E/q) varied over a range from 50 eV to 1 keV in concert with neutral gas density variations caused by the rotation of the comet and its variable solar illumination. Thermal ion densities showed the same variations. The neutral density variations provided a unique opportunity to observe the repeated slowing of the solar wind by mass loading caused by charge exchange between energetic water‐group ions and thermal water‐group molecules. Such solar wind slowing was observed previously only by flyby missions that provided single events. Plain Language Summary: The Rosetta orbiter carried a number of instruments to measure the properties of the neutral and ionized gas surrounding the nucleus. Included in these were plasma instruments to measure the characteristics of the charged particles. The Ion and Electron Sensor was one of them. Also on board were the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis, the Ion Composition Analyzer, and the Langmuir Probe. This paper discusses some of the results of measurements by these instruments and their relation to each other. It was found that the neutral gas emitted by the comet nucleus and the resulting positively charged ions interact in such a way to produce slowing down of the solar wind as a result of what is called "charge exchange", in which an electron is transferred from a neutral molecule to an ion. Key Points: Charge exchange of energetic water group pickup ions with coma water molecules is observed within the solar wind cavity of Comet 67P Churyumov‐GerasimenkoRotation of the comet produced variations in the neutral density at the spacecraft causing strong charge‐exchange deceleration of the incoming ions within the density peaksRecovery to the initial water‐group ion beam as minimum neutral densities, again appeared, was shown to result from pickup of thermal ions in the coma [ABSTRACT FROM AUTHOR]

Background: Apnoeic oxygenation using Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE) during general anaesthesia prolongs the safe apnoeic period. However, there is a gap of knowledge how THRIVE‐induced hyperoxia and hypercapnia impact vital organs. The primary aim of this randomised controlled trial was to characterise oxidative stress and, secondary, vital organ function biomarkers during THRIVE compared to mechanical ventilation (MV). Methods: Thirty adult patients, American Society of Anesthesiologists (ASA) 1–2, undergoing short laryngeal surgery under general anaesthesia were randomised to THRIVE, FIO2 1.0, 70 L min−1 during apnoea or MV. Blood biomarkers for oxidative stress, malondialdehyde and TAC and vital organ function were collected (A) preoperatively, (B) at procedure completion and (C) at PACU discharge. Results: Mean apnoea time was 17.9 (4.8) min and intubation to end‐of‐surgery time was 28.1 (12.8) min in the THRIVE and MV group, respectively. Malondialdehyde increased from 11.2 (3.1) to 12.7 (3.1) µM (P =.02) and from 9.5 (2.2) to 11.6 (2.6) µM (P =.003) (A to C) in the THRIVE and MV group, respectively. S100B increased from 0.05 (0.02) to 0.06 (0.02) µg L−1 (P =.005) (A to C) in the THRIVE group. No increase in TAC, CRP, leukocyte count, troponin‐T, NTproBNP, creatinine, eGFRcrea or NSE was demonstrated during THRIVE. Conclusion: While THRIVE and MV was associated with increased oxidative stress, we found no change in cardiac, inflammation or kidney biomarkers during THRIVE. Further evaluation of stress and inflammatory response and cerebral and cardiac function during THRIVE is needed. [ABSTRACT FROM AUTHOR]

Wakes behind spacecraft caused by supersonic drifting positive ions are common in plasmas and disturb in situ measurements. We review the impact of wakes on observations by the Electric Field and Wave double‐probe instruments on the Cluster satellites. In the solar wind, the equivalent spacecraft charging is small compared to the ion drift energy and the wake effects are caused by the spacecraft body and can be compensated for. We present statistics of the direction, width, and electrostatic potential of wakes, and we compare with an analytical model. In the low‐density magnetospheric lobes, the equivalent positive spacecraft charging is large compared to the ion drift energy and an enhanced wake forms. In this case observations of the geophysical electric field with the double‐probe technique becomes extremely challenging. Rather, the wake can be used to estimate the flux of cold (eV) positive ions. For an intermediate range of parameters, when the equivalent charging of the spacecraft is similar to the drift energy of the ions, also the charged wire booms of a double‐probe instrument must be taken into account. We discuss an example of these effects from the MMS spacecraft near the magnetopause. We find that many observed wake characteristics provide information that can be used for scientific studies. An important example is the enhanced wakes used to estimate the outflow of ionospheric origin in the magnetospheric lobes to about 1026 cold (eV) ions/s, constituting a large fraction of the mass outflow from planet Earth. Plain Language Summary: Wakes caused by spacecraft motion or drifting plasma are common behind spacecraft with scientific instruments and disturb in situ observations of space plasmas. We review the impact of wakes on observations by the Electric Field and Wave double‐probe instruments on the Cluster satellites. In the solar wind, the wake behind a Cluster spacecraft is caused by the spacecraft body, is narrow, and can partly be compensated for when analyzing data. In the regions above the Earth's polar regions, the wake behind a Cluster spacecraft is caused by an electrostatic structure around the positively charged spacecraft, causing an enhanced wake. The charging stops positive ions from reaching the spacecraft. Rather, this wake can be used to estimate the flux of cold (eV) positive ions escaping from the ionosphere. Above the poles the flux is about 1026 ions/s, constituting a large fraction of the mass outflow from planet Earth. For an intermediate range of parameters, when the drift energy of the ions is comparable to the equivalent charge of the spacecraft, also the charged wire booms of a double‐probe instrument must be taken into account. We discuss an example from the MMS spacecraft near the magnetopause. Key Points: Plasma wakes are common behind scientific spacecraftWakes in the solar wind can be compensated for in data analysisEnhanced wakes in the polar lobes can be used to detect cold outflowing ions [ABSTRACT FROM AUTHOR]

Objectives: Humoral and cellular immunity to SARS‐CoV‐2 following COVID‐19 will likely contribute to protection from reinfection or severe disease. It is therefore important to characterise the initiation and persistence of adaptive immunity to SARS‐CoV‐2 amidst the ongoing pandemic. Methods: Here, we conducted a longitudinal study on hospitalised moderate and severe COVID‐19 patients from the acute phase of disease into convalescence at 5 and 9 months post‐symptom onset. Utilising flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune responses during and after human SARS‐CoV‐2 infection. Results: During acute COVID‐19, we observed an increase in germinal centre activity, a substantial expansion of antibody‐secreting cells and the generation of SARS‐CoV‐2‐neutralising antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralising antibody titres as well as robust specific memory B cell responses and polyfunctional T cell responses at 5 and 9 months after symptom onset in both moderate and severe COVID‐19 patients. Conclusion: Our findings describe the initiation and, importantly, persistence of cellular and humoral SARS‐CoV‐2‐specific immunological memory in hospitalised COVID‐19 patients long after recovery, likely contributing towards protection against reinfection. [ABSTRACT FROM AUTHOR]

Background: Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID‐19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID‐19 admitted to ICU. Methods: We included all 260 patients with COVID‐19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in‐hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination. Results: Of 260 ICU patients with COVID‐19, 208 (80.0%) were men, the median age was 59 (IQR 51‐65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8‐14) days. Sixty‐two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6‐18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality. Conclusion: This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID‐19 admitted to ICU in a large tertiary hospital in Sweden. [ABSTRACT FROM AUTHOR]

We report the detection of large‐amplitude, quasi‐harmonic density fluctuations with associated magnetic field oscillations in the region surrounding the diamagnetic cavity of comet 67P. Typical frequencies are ∼0.1 Hz, corresponding to ∼10 times the water and ≲0.5 times the proton gyro‐frequencies, respectively. Magnetic field oscillations are not always clearly observed in association with these density fluctuations, but when they are, they consistently have wave vectors perpendicular to the background magnetic field, with the principal axis of polarization close to field‐aligned and with a ∼90° phase shift with respect to the density fluctuations. The fluctuations are observed in association with asymmetric plasma density and magnetic field enhancements previously found in the region surrounding the diamagnetic cavity, occurring predominantly on their descending slopes. This is a new type of waves not previously observed at comets. They are likely ion Bernstein waves, and we propose that they are excited by unstable ring, ring‐beam, or spherical shell distributions of cometary ions just outside the cavity boundary. These waves may play an important role in redistributing energy between different particle populations and reshape the plasma environment of the comet. Key Points: Large‐amplitude low‐frequency (around 0.1 Hz) plasma density fluctuations are observed at comet 67PThey coincide with the plasma density and magnetic field enhancements surrounding the diamagnetic cavityThis is a new type of waves at comets, probably ion Bernstein waves, possibly driven by velocity space anisotropies arising near the cavity [ABSTRACT FROM AUTHOR]

Objectives: The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is unknown. Understanding the immune response in COVID‐19 could contribute to unravel the pathogenesis and identification of treatment targets. Here, we describe the phenotypic landscape of circulating ILCs in COVID‐19 patients and identified ILC phenotypes correlated to serum biomarkers, clinical markers and laboratory parameters relevant in COVID‐19. Methods: Blood samples collected from moderately (n = 11) and severely ill (n = 12) COVID‐19 patients, as well as healthy control donors (n = 16), were analysed with 18‐parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID‐19 patients, and serum biomarkers were analysed with multiplex immunoassays. Results: Innate lymphoid cells were largely depleted from the circulation of COVID‐19 patients compared with healthy controls. Remaining circulating ILCs revealed decreased frequencies of ILC2 in severe COVID‐19, with a concomitant decrease of ILC precursors (ILCp) in all patients, compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID‐19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity. Conclusion: This study provides insights into the potential role of ILCs in immune responses against SARS‐CoV‐2, particularly linked to the severity of COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE) using high‐flow 100% oxygen during apnoea has gained increased use during difficult airway management and laryngeal surgery due to a slower carbon dioxide rise compared to traditional apnoeic oxygenation. We have previously demonstrated high arterial oxygen partial pressures and an increasing arterial‐alveolar carbon dioxide difference during THRIVE. Primary aim of this study was to characterise lung volume changes measured with electrical impedance tomography during THRIVE compared to mechanical ventilation. Methods: Thirty adult patients undergoing laryngeal surgery under general anaesthesia were randomised to THRIVE or mechanical ventilation. Subjects were monitored with electrical impedance tomography and repeated blood gas measurement perioperatively. The THRIVE group received 100% oxygen at 70 l min−1 during apnoea. The mechanical ventilation group was intubated and normoventilated with an FiO2 of 0.4. Results: Mean age were 48.2 (19.9) and 51.3 (12.3) years, and BMI 26.0 (4.5) and 26.0 (3.9) in the THRIVE and mechanical ventilation group respectively. Mean apnoea time in the THRIVE group was 17.9 (4.8) min. Mean apnoea to end‐of‐surgery time was 28.1 (12.8) min in the mechanical ventilation group. No difference in delta End Expiratory Lung Impedance was seen between groups over time. In the THRIVE group all but three subjects were well oxygenated during apnoea. THRIVE was discontinued for the three patients who desaturated. Conclusions: No difference in lung volume change over time, measured by electrical impedance tomography, was detected when using THRIVE compared to mechanical ventilation during laryngeal surgery. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Are carotid bodies (CBs) modulated by the damage‐associated molecular patterns (DAMPs) and humoral factors of aseptic tissue injury?What are the main findings and their importance?DAMPs (HMGB1, S100 A8/A9) and blood plasma from rats subjected to tibia surgery, a model of aseptic injury, stimulate the release of neurotransmitters (ATP, dopamine) and TNF‐α from ex vivo rat CBs. All‐thiol HMGB1 mediates upregulation of immune‐related biological pathways. These data suggest regulation of CB function by endogenous mediators of innate immunity. The glomus cells of carotid bodies (CBs) are the primary sensors of arterial partial O2 and CO2 tensions and moreover serve as multimodal receptors responding also to other stimuli, such as pathogen‐associated molecular patterns (PAMPs) produced by acute infection. Modulation of CB function by excessive amounts of these immunomodulators is suggested to be associated with a detrimental hyperinflammatory state. We have hypothesized that yet another class of immunomodulators, endogenous danger‐associated molecular patterns (DAMPs), released upon aseptic tissue injury and recognized by the same pathogen recognition receptors as PAMPs, might modulate the CB activity in a fashion similar to PAMPs. We have tested this hypothesis by exposing rat CBs to various DAMPs, such as HMGB1 (all‐thiol and disulfide forms) and S100 A8/A9 in a series of ex vivo experiments that demonstrated the release of dopamine and ATP, neurotransmitters known to mediate CB homeostatic responses. We observed a similar response after incubating CBs with conditioned blood plasma obtained from the rats subjected to tibia surgery, a model of aseptic injury. In addition, we have investigated global gene expression in the rat CB using an RNA sequencing approach. Differential gene expression analysis showed all‐thiol HMGB1‐driven upregulation of a number of prominent pro‐inflammatory markers including Il1α and Il1β. Interestingly, conditioned plasma had a more profound effect on the CB transcriptome resulting in inhibition rather than activation of the immune‐related pathways. These data are the first to suggest potential modulation of CB function by endogenous mediators of innate immunity. [ABSTRACT FROM AUTHOR]

We calculate the momentum flux and pressure of ions measured by the Ion Composition Analyzer (ICA) on the Rosetta mission at comet 67P/Churyumov‐Gerasimenko. The total momentum flux stays roughly constant over the mission, but the contributions of different ion populations change depending on heliocentric distance. The magnetic pressure, calculated from Rosetta magnetometer measurements, roughly corresponds with the cometary ion momentum flux. When the spacecraft enters the solar wind ion cavity, the solar wind fluxes drop drastically, while the cometary momentum flux becomes roughly 10 times the solar wind fluxes outside of the ion cavity, indicating that pickup ions behave similarly to the solar wind ions in this region. We use electron density from the Langmuir probe to calculate the electron pressure, which is particularly important close to the comet nucleus where flow changes from antisunward to radially outward. Plain Language Summary: To understand the atmosphere of a comet, we must understand how its charged particles interact with the solar wind. Here we look at momentum flux, the amount of momentum carried by particles flowing through a certain area, measured at the comet 67P/Churyumov‐Gerasimenko by the Rosetta spacecraft. We find that the total momentum flux changes the amount we would expect from the comet getting closer to the Sun. When in the part of the atmosphere with no solar wind, the ions coming from the comet have more momentum flux than the solar wind ions elsewhere in the comet atmosphere. The increase matches what we expect from the comet getting closer to the Sun, which increases the total density of the comet atmosphere. The cometary ions replace the solar wind ions in the atmosphere, so the total stays the same. The magnetic field varies with the cometary ions. We find electron pressure with measured electron data. It is higher than the momentum flux, especially in the part of the atmosphere close to the comet nucleus. This means that the atmosphere here is primarily moving outward from the comet, while farther away from the nucleus it is mainly flowing away from the Sun. Key Points: Momentum flux of Rosetta ion data shows the evolution of a cometary ionosphere, including boundary regionsMagnetic pressure is on the order of the total ion momentum flux and roughly corresponds with cometary ion momentum fluxThe cometary pickup ions in the solar wind ion cavity take over the role of the solar wind ions outside the cavity [ABSTRACT FROM AUTHOR]

Objective: Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long-term cognitive decline at 3 months postsurgery.Methods: Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively.Results: Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio).Interpretation: Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370-382. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected. [ABSTRACT FROM AUTHOR]

We present the electron density (ne) altitude profiles of Saturn's ionosphere at near‐equatorial latitudes from all 23 orbits of Cassini's Grand Finale. The data are collected by the Langmuir probe part of the Radio and Plasma Wave Science investigation. A high degree of variability in the electron density profiles is observed. However, organizing them by consecutive altitude ranges revealed clear differences between the southern and northern hemispheres. The ne profiles are shown to be more variable and connected to the D‐ring below 5,000 km in the southern hemisphere compared to the northern hemisphere. This observed variability is explained to be a consequence of an electrodynamic interaction with the D‐ring. Moreover, a density altitude profile is constructed for the northern hemisphere indicating the presence of three different ionospheric layers. Similar properties were observed during Cassini's final plunge, where the main ionospheric peak is crossed at ∼1,550‐km altitude. Plain Language Summary: The Cassini Langmuir probe measured directly the uppermost layer of Saturn's atmosphere, the ionosphere, during its Grand Finale. The observations revealed a layered electron density altitude profile with evidence in the southern hemisphere of an electrodynamic type of interaction with the planet innermost D‐ring. Moreover, the main peak of the ionosphere is observed for the first time in the final plunge around 1,550 km. Key Points: Cassini RPWS observations during the Grand Finale show an electrodynamic type of interaction between the topside ionosphere and the D‐ring in the southern hemisphereA layered electron density profile is observed, characterized by at least a diffusive and a chemical equilibrium regionThe main ionospheric peak is observed around 1,550 km in the final plunge [ABSTRACT FROM AUTHOR]

Introduction: We evaluated whether hospitalization with or without surgery increases risk for dementia or Alzheimer's disease. Methods: A clinical sample (843 clinically diagnosed dementia cases; 1686 matched nondemented individuals) was identified from Swedish Twin Registry studies. A register‐based sample (4293 cases; 21,465 matched controls) was identified by linkage of Swedish Twin Registry to Swedish Patient Registry records. Apolipoprotein E (APOE) status and within‐pair comparisons of dementia discordant twins indicated genetic susceptibility. Results: Nonsurgical hospitalization is associated with greater dementia risk than hospitalization with surgical intervention. In the register sample, thoracic, abdominal, and major orthopedic procedures entailed dementia risk; in the clinical sample, orthopedic alone. Within‐pair analyses indicate that associations in part reflect genetic susceptibility in common to hospitalization and dementia. Potential gene‐environment interactions were indicated by greater risk due to hospitalization among APOE ε4 noncarriers. Discussion: We confirm hospitalization as a risk factor for dementia, with repeated hospitalizations a more important risk factor than surgery. [ABSTRACT FROM AUTHOR]

Measurements of electrons and ions in Saturn's ionosphere down to 1,500‐km altitudes as well as the ring crossing region above the ionosphere obtained by the Langmuir probe onboard the Cassini spacecraft are presented. Five nearly identical deep ionosphere flybys during the Grand Finale orbits and the Final plunge orbit revealed a rapid increase in the plasma densities and discrepancies between the electrons and ions densities (Ne and Ni) near the closest approach. The small Ne/Ni ratio indicates the presence of a dusty plasma, a plasma which charge carrier is dominated by negatively charged heavy particles. Comparison of the Langmuir probe obtained density with the light ion density obtained by the Ion and Neutral Mass Spectrometer confirmed the presence of heavy ions. An unexpected positive floating potential of the probe was also observed when Ne/Ni ≪ 1. This suggests that Saturn's ionosphere near the density peak is in a dusty plasma state consisting of negatively and positively charged heavy cluster ions. The electron temperature (Te) characteristics in the ionosphere are also investigated and unexpectedly high electron temperature value, up to 5000 K, has been observed below 2,500‐km altitude in a region where electron‐neutral collisions should be prominent. A well‐defined relationship between Te and Ne/Ni ratio was found, implying that the electron heating at low altitudes is related to the dusty plasma state of the ionosphere. Plain Language Summary: Cassini Langmuir probe measurements revealed ion densities in excess of the electron densities, indicative of a dusty plasma, in Saturn's ionosphere below 2,500‐km altitude. Comparison of the Langmuir probe measurements with those of the Ion and Neutral Mass Spectrometer, sensitive to only lighter ions during this period, showed that heavy ions dominate in this region. Positive spacecraft potentials were also found, suggesting that Saturn's ionosphere contains dusty plasma of negatively and positively charged heavy ions. Key Points: In situ measurements of Saturn's ionospheric plasma densities down to 1,500 km and the ring above the ionosphere is presentedCharge imbalance in the ions and electrons, evidence of the negatively charged heavy particles, has been observed below 2,500 kmObservations suggest that Saturn's ionosphere consists of a significant amount of negatively and positively charged heavy ions [ABSTRACT FROM AUTHOR]

The spacecraft potential is often used to infer rapid changes in the thermal plasma density. The variations in spacecraft potential associated with large‐amplitude Langmuir and upper hybrid waves are investigated with the Magnetospheric Multiscale (MMS) mission. When large‐amplitude Langmuir and upper hybrid waves are observed, the spacecraft potential increases. The changes in spacecraft potential are shown to be due to enhanced photoelectron escape from the spacecraft when the wave electric fields reach large amplitude. The fluctuations in spacecraft potential follow the envelope function of the Langmuir and upper hybrid waves. Comparison with the high‐resolution electron moments shows that the changes in spacecraft potential associated with the waves are not due to density perturbations. Indeed, using the spacecraft potential as a density probe leads to unphysically large density fluctuations. In addition, the changes in spacecraft potential are shown to increase as density decreases: larger spacecraft potential changes are observed in the magnetosphere, than in the magnetosheath and solar wind. These results show that external electric fields can lead to unphysical results when the spacecraft potential is used as a density probe. The results suggest that fluctuations in the spacecraft potential alone cannot be used to determine whether nonlinear processes associated with Langmuir and upper hybrid waves, such as the ponderomotive force and three‐wave decay, are occurring. Key Points: The electric field of Langmuir and upper hybrid waves increases the spacecraft potential due to enhanced photoelectron escapeIncreased spacecraft potentials associated with Langmuir and upper hybrid waves are not due to density depletions or ponderomotive forceThe magnitude of the changes in spacecraft potential due to Langmuir and upper hybrid waves becomes larger as density decreases [ABSTRACT FROM AUTHOR]

Abstract: A major point of interest in cometary plasma physics has been the diamagnetic cavity, an unmagnetized region in the innermost part of the coma. Here we combine Langmuir and Mutual Impedance Probe measurements to investigate ion velocities and electron temperatures in the diamagnetic cavity of comet 67P, probed by the Rosetta spacecraft. We find ion velocities generally in the range 2–4 km/s, significantly above the expected neutral velocity ≲1 km/s, showing that the ions are (partially) decoupled from the neutrals, indicating that ion‐neutral drag was not responsible for balancing the outside magnetic pressure. Observations of clear wake effects on one of the Langmuir probes showed that the ion flow was close to radial and supersonic, at least with respect to the perpendicular temperature, inside the cavity and possibly in the surrounding region as well. We observed spacecraft potentials ≲ − 5 V throughout the cavity, showing that a population of warm (∼5 eV) electrons was present throughout the parts of the cavity reached by Rosetta. Also, a population of cold ( ≲ 0 . 1 eV) electrons was consistently observed throughout the cavity, but less consistently in the surrounding region, suggesting that while Rosetta never entered a region of collisionally coupled electrons, such a region was possibly not far away during the cavity crossings. [ABSTRACT FROM AUTHOR]

Polar wind outflow is an important process through which the ionosphere supplies plasma to the magnetosphere. The main source of energy driving the polar wind is solar illumination of the ionosphere. As a result, many studies have found a relation between polar wind flux densities and solar EUV intensity, but less is known about their relation to the solar zenith angle at the ionospheric origin, certainly at higher altitudes. The low energy of the outflowing particles and spacecraft charging means it is very difficult to measure the polar wind at high altitudes. We take advantage of an alternative method that allows estimations of the polar wind flux densities far in the lobes. We analyze measurements made by the Cluster spacecraft at altitudes from 4 up to 20 R E. We observe a strong dependence on the solar zenith angle in the ion flux density and see that both the ion velocity and density exhibit a solar zenith angle dependence as well. We also find a seasonal variation of the flux density. [ABSTRACT FROM AUTHOR]

Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function.Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [11 C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed.Results: Patients showed a global downregulation of gray matter [11 C]PBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in [11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [11 C]PBR28 binding (p = 0.027).Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572-582. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate calf muscle endurance in a seated position 3 months after an Achilles tendon rupture and to evaluate how the ability to perform standardized seated heel-rises correlated to the single-leg standing heel-rise test and to patient-reported symptoms evaluated with the Achilles tendon Total Rupture Score ( ATRS) 3 and 6 months after the injury. Ninety-three patients were included from a cohort of 101 patients participating in a prospective, randomized controlled trial comparing surgical and nonsurgical treatment after Achilles tendon rupture. Forty-seven patients were treated surgically and 46 nonsurgically. Ninety-one patients out of 93 (98%) could perform the standardized seated heel-rises. At the 3-month follow-up, there was a significant difference ( P < 0.001) between the injured and the healthy side performing standardized seated heel-rises. There were also significant correlations ( r = 0.29-0.37, P = < 0.05) between the standardized seated heel-rises and ATRS 3 and 6 months after injury in the group who could not perform single-leg standing heel-rises. There were no significant differences between the surgical and nonsurgical treatment groups. The evaluation of standardized seated heel-rises appears to be a useful tool to quantify progress and predict future functional performance and patient-reported symptoms. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive manifestations of the coronavirus disease 2019 (COVID‐19) have been reported in the acute phase, especially in critically ill patients. The potential mechanisms underlying these symptoms are not fully understood but probably involves the inflammatory, vascular, and neurotropic effect of the coronavirus. While short‐, mid‐and long‐term consequences remain unclear, patients with neurocognitive sequelae reminiscent of other cognitive disorders, including AD have been reported. The aim of this study is to investigate if there is an increased risk for long‐term cognitive dysfunction/impairment, biochemical and structural brain changes after a severe COVID‐19. Method: This is a prospective cohort study of 80 patients surviving intensive‐care for COVID‐19 at Karolinska University Hospital, Stockholm, Sweden. They will be examined at 3, 6 and 12 months after hospital discharge using neurological and neuropsychological (NP) tests combined with novel quantitative brain MRI and serial blood sampling to described relevant blood‐borne molecular patterns. This presentation focuses on NP testing, cognitive, mental, and neurological aspects at 3 months follow‐up. Cognitive testing and questionnaires (NP) include Rey Auditory Verbal Learning Test Rey Complex Figure test, Verbal Fluency Test, Category flow, Trail Making Test Symbol Digit Modalities Test, Mental Fatigue Scale, the Hospital Anxiety and Depression Scale, RAND‐36, AD8 Dementia Screening Interview and Subjective cognitive decline questions. A detailed neurological examination (neurologist), including Expanded Disability Status Scale, an adapted version of the Unified Parkinson's Disease Rating Scale for extrapyramidal dysfunction, and a brief smell test. Results: At present, 28 participants have completed the 3‐months follow‐up visit, including neuropsychological and neurological examinations. Mean age (SD) at baseline was 57.8 (11.1) years, and 68% were men. Several patients expressed cognitive and/or mental concerns and fatigue. The neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Brain MRI revealed mainly microvascular pathology. Detailed analyses, including blood biomarkers for neuronal injury and astrocytic activation, based on the 3‐months examination will be presented. Conclusions: Repeated examinations will allow further analyses on longer term impact on cognition and underlying mechanisms. This may identify patients at risk and possible ways to mitigate cognitive complications, which is of great importance to reduce the pandemic's negative effects and socioeconomic burden. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Data on human carotid body (CB) function are limited. The aim of this study was therefore to investigate whether the human CB releases acetylcholine, ATP or cytokines during hypoxia., What is the main finding and its importance? Using human CBs, we demonstrate hypoxia-induced acetylcholine and ATP release, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. Moreover, the human CB releases cytokines upon hypoxia and expresses cytokine receptors as well as hypoxia-inducible factor proteins HIF-1α and HIF-2α in glomus cells, indicating their role in immune signalling and oxygen sensing, respectively, in accordance with previous animal data., Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)-1β, IL-4, IL-6, IL-8 and IL-10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia-inducible factor-1α and hypoxia-inducible factor-2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information suggesting that the carotid body may play a role in detecting inflammation, providing a link between the immune system and the nervous system. [ABSTRACT FROM AUTHOR]

This study evaluated the short-term recovery of function after an acute Achilles tendon rupture, measured by a single-legged heel-rise test, with main emphasis on the relation to the patient-reported outcomes and fear of physical activity and movement (kinesiophobia). Eighty-one patients treated surgically or non-surgically with early active rehabilitation after Achilles tendon rupture were included in the study. Patient's ability to perform a single-legged heel-rise, physical activity level, patient-reported symptoms, general health, and kinesiophobia was evaluated 12 weeks after the injury. The heel-rise test showed that 40 out of 81 (49%) patients were unable to perform a single heel-rise 12 weeks after the injury. We found that patients who were able to perform a heel-rise were significantly younger, more often of male gender, reported a lesser degree of symptoms, and also had a higher degree of physical activity at 12 weeks. There was also a significant negative correlation between kinesiophobia and all the patient-reported outcomes and the physical activity level. The heel-rise ability appears to be an important early achievement and reflects the general level of healing, which influences patient-reported outcome and physical activity. Future treatment protocols focusing on regaining strength early after the injury therefore seem to be of great importance. Kinesiophobia needs to be addressed early during the rehabilitation process. [ABSTRACT FROM AUTHOR]

Hospitalization for major surgery or critical illness often associates with cognitive decline. Inflammation and dysregulation of the innate immune system can exert broad effects in the periphery and central nervous system (CNS), yet the mechanisms underlying memory impairment after surgery remain poorly understood and without effective therapy. Endogenous regulation of acute inflammation is providing novel approaches to treat several disease states including sepsis, pain, obesity and diabetes. Resolvins are potent endogenous lipid mediators biosynthesized during the resolution phase of acute inflammation that display immunoresolvent actions. Here, using a mouse model of surgery-induced cognitive decline we report that orthopedic surgery affects hippocampal neuronal-glial function, including synaptic transmission and plasticity. Systemic prophylaxis with aspirin-triggered resolvin D1 (AT-RvD1: 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Zdocosahexaenoic acid, as little as 100 ng dose per mouse) improved memory decline following surgery and abolished signs of synaptic dysfunction. Moreover, delayed administration 24 h after surgery also attenuated signs of neuronal dysfunction postoperatively. AT-RvD1 also limited peripheral damage by modulating the release of systemic interleukin (IL)-6 and improved other clinical markers of tissue injury. Collectively, these results demonstrate a novel role of AT-RvD1 in modulating the proinflammatory milieu after aseptic injury and protecting the brain from neuroinflammation, synaptic dysfunction and cognitive decline. These findings provide novel and safer approaches to treat postoperative cognitive decline and potentially other forms of memory dysfunctions. [ABSTRACT FROM AUTHOR]

Key points The carotid body (CB) is the key oxygen sensor and governs the ventilatory response to hypoxia., CB oxygen sensing and signalling gene expression is well described in animals whereas human data are absent., Here we have characterized the human CB global gene expression in comparison with functionally related tissues and mouse CB gene expression., We show that the human CB expresses oxygen sensing genes in common with mice but also differs on key genes such as certain K+ channels. There is moreover increased expression of inflammatory response genes in human and mouse CBs in comparison with related tissues., The study establishes similarities but also important differences between animal and human CB gene expression profiles and provides a platform for future functional studies on human CBs., Abstract The carotid body (CB) is the key oxygen sensing organ. While the expression of CB specific genes is relatively well studied in animals, corresponding data for the human CB are missing. In this study we used five surgically removed human CBs to characterize the CB transcriptome with microarray and PCR analyses, and compared the results with mice data. In silico approaches demonstrated a unique gene expression profile of the human and mouse CB transcriptomes and an unexpected upregulation of both human and mouse CB genes involved in the inflammatory response compared to brain and adrenal gland data. Human CBs express most of the genes previously proposed to be involved in oxygen sensing and signalling based on animal studies, including NOX2, AMPK, CSE and oxygen sensitive K+ channels. In the TASK subfamily of K+ channels, TASK-1 is expressed in human CBs, while TASK-3 and TASK-5 are absent, although we demonstrated both TASK-1 and TASK-3 in one of the mouse reference strains. Maxi-K was expressed exclusively as the spliced variant ZERO in the human CB. In summary, the human CB transcriptome shares important features with the mouse CB, but also differs significantly in the expression of a number of CB chemosensory genes. This study provides key information for future functional investigations on the human carotid body. [ABSTRACT FROM AUTHOR]

Background Volatile anaesthetics are known to affect cholinergic receptors. Perturbation of cholinergic signalling can cause cognitive deficits. In this study, we wanted to evaluate acetylcholine-induced intracellular signalling following sevoflurane exposure. Methods Pheochromocytoma12 PC12 cells were exposed to 4.6% sevoflurane for 2 h. Subsequently, Western blotting was used to measure acetylcholine-induced phosphorylation of extracellular signal-regulated kinase 1/2 ( ERK) 1/2 and basal Protein kinase B ( AKT) phosphorylation. Results After exposure, acetylcholine-induced ERK 1/2 phosphorylation was reduced to 58 ± 8% [95% confidence interval ( CI): 38-77%, P = 0.003] compared with non-exposed controls. At 30 min after the end of sevoflurane administration [at 0.7% sevoflurane (0.102 mM)], ERK 1/2 phosphorylation remained reduced to 57 ± 7% (95% CI: 39-74%, P = 0.001) and was at 120 min [0.02% (0.003 mM] still reduced to 63 ± 10% (95% CI: 37-88%, P = 0.01), compared with control. At 360 min after exposure, acetylcholine-induced ERK 1/2 phosphorylation had recovered to 98 ± 16% (95% CI: 45-152%, P = 0.98) compared with control. In contrast, immediately after sevoflurane exposure, basal AKT phosphorylation was increased by 228 ± 37% (95% CI: 133-324%, P = 0.02) but had returned to control levels at 30 min after exposure, 172 ± 67% (95% CI: 0-356%, P = 0.34). Conclusion Sevoflurane exposure has differential effects on different intracellular signalling pathways. On one hand, we observed a prolonged attenuation of acetylcholine-induced ERK 1/2 phosphorylation that persisted even when sevoflurane concentrations close to detection level. On the other hand, basal AKT phosphorylation was increased twofold during sevoflurane exposure, with a rapid return to baseline levels after exposure. We speculate that the effects on acetylcholine-induced intracellular signalling observed in our in vitro model could be of relevance also for cholinergic signalling in vivo following sevoflurane exposure. [ABSTRACT FROM AUTHOR]

Objective: Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved. Methods: C57BL/6J, Ccr2RFP/+Cx3cr1GFP/+, IkkF/F mice and LysM-Cre/IkkF/F mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood-brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied. Results: Peripheral surgery disrupts the BBB via release of tumor necrosis factor-alpha (TNFα), which facilitates the migration of macrophages into the hippocampus. Macrophage-specific deletion of Ikappa B kinase (IKK)β, a central coordinator of TNFα signaling through activation of nuclear factor (NF) κB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the α7 subtype of nicotinic acetylcholine receptors, an endogenous inflammation-resolving pathway, prevents TNFα-induced NF-κB activation, macrophage migration into the hippocampus, and cognitive decline following surgery. Interpretation: These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and/or resolve postoperative neuroinflammation and cognitive decline. ANN NEUROL 2011;70:986-995 [ABSTRACT FROM AUTHOR]

Background Coordination of breathing and swallowing is essential for airway protection and dyscoordination may cause morbidity and mortality. Methods Using a recently developed technique for high accuracy respiratory measurements of airflow during swallowing, we investigated the effects of body position (upright vs left lateral), bolus type (spontaneously swallowed saliva vs water), and respiratory drive (normo- vs hypercapnia) on coordination of breathing and swallowing in 32 healthy volunteers. Key Results Swallows were in all cases (100%) proceded by expiration and 98% were also followed by expiration, regardless of body position, bolus type, or respiratory drive. While the endpoint of postswallow apnea correlated well to the endpoint of pharyngeal swallowing, duration of preswallow apnea was highly variable. In a small fraction of swallows followed by inspiration (3%), the expiratory phase before swallowing and duration of postswallow apnea was significantly longer. Body position and respiratory drive affected the increase in upper esophageal sphincter tone during inspiration. Increased respiratory drive also reduced swallowing frequency and shortened duration of preswallow apnea. Water swallows had longer duration of preswallow apnea. Conclusions & Inferences Swallowing occurs during the expiratory phase of respiration, and the fraction of swallows preceded and followed by expiration approach 100% in healthy humans. This integration between breathing and swallowing remains unchanged regardless of body position, bolus characteristics, or respiratory drive. Our results provide a platform for future studies aiming at understanding how this integration is changed by aging, diseases, and drugs. [ABSTRACT FROM AUTHOR]

The coordination of swallowing and respiration is essential for a safe swallow. Swallowing consists of several subsecond events. To study this, it is important to use modalities with high temporal resolution. In this study, we have examined young healthy individuals with simultaneous videofluoroscopy, videomanometry and respiratory recording, all with high temporal resolution. The onset of 13 predetermined swallowing and respiratory events and the surrounding respiratory phase pattern were studied in different body positions and during different respiratory drives. An increased respiratory drive was induced by breathing 5% CO2. The results demonstrated a highly repeatable and fixed temporal coordination of the swallowing pattern despite body position and respiratory drive. Previous studies have demonstrated a period of centrally controlled apnoea during swallowing. This apnoea period has a variable length, varying from 1 to 5 s. During increased respiratory drive, we could demonstrate a significantly shorter period of apnoea during swallowing, mainly due to an earlier resumption of respiration. The high temporal recordings in this study have revealed that swallowing during expiration is present basically in all healthy individuals. This swallowing respiratory pattern seems to be appropriate for a safe swallow. This knowledge will be used as a reference for future studies on how swallowing and respiratory coordination might be altered due to ageing and diseases. [ABSTRACT FROM AUTHOR]

Co-ordination of breathing and swallowing is essential for normal pharyngeal function and to protect the airway. To allow for safe passage of a bolus through the pharynx, respiration is interrupted (swallowing apnoea); however, the control of airflow and diaphragmatic activity during swallowing and swallowing apnoea are not fully understood. Here, we validated a new airflow discriminator for detection of respiratory airflow and used it together with diaphragmatic and abdominal electromyography (EMG), spirometry and pharyngeal and oesophageal manometry. Co-ordination of breathing and spontaneous swallowing was examined in six healthy volunteers at rest, during hypercapnia and when breathing at 30 breaths min–1. The airflow discriminator proved highly reliable and enabled us to determine timing of respiratory airflow unambiguously in relation to pharyngeal and diaphragmatic activity. During swallowing apnoea, the passive expiration of the diaphragm was interrupted by static activity, i.e. an ‘active breath holding’, which preserved respiratory volume for expiration after swallowing. Abdominal EMG increased throughout pre- and post-swallowing expiration, more so during hyper- than normocapnia, possibly to assist expiratory airflow. In these six volunteers, swallowing was always preceded by expiration, and 93 and 85% of swallows were also followed by expiration in normo- and hypercapnia, respectively, indicating that, in man, swallowing during the expiratory phase of breathing may be even more predominant than previously believed. This co-ordinated pattern of breathing and swallowing potentially reduces the risk for aspiration. Insights from these measurements in healthy volunteers and the airflow discriminator will be used for future studies on airway protection and effects of disease, drugs and ageing. [ABSTRACT FROM AUTHOR]

Neuromuscular transmission at the skeletal muscle occurs when a quantum of acetylcholine from the nerve ending is released and binds to the nicotinic acetylcholine receptors on the postjunctional muscle membrane. The nicotinic acetylcholine receptors on the endplate respond by opening channels for the influx of sodium ions and subsequent endplate depolarisation leads to muscle contraction. The acetylcholine immediately detaches from the receptor and is hydrolysed by acetylcholinesterase enzyme. Suxamethonium is a cholinergic agonist stimulating the muscle nicotinic acetylcholine receptors prior to causing neuromuscular block. Non-depolarising neuromuscular blocking drugs bind to the nicotinic acetylcholine receptors preventing the binding of acetylcholine. Non-depolarising neuromuscular blocking drugs also inhibit prejunctional α3β2 nicotinic acetylcholine autoreceptors, which can be seen in the clinical setting as train-of-four fade. In some pathological states such as denervation, burns, immobilisation, inflammation and sepsis, there is expression of other subtypes of nicotinic acetylcholine receptors with upregulation of these receptors throughout the muscle membrane. The responses of these receptors to suxamethonium and non-depolarising neuromuscular blocking drugs are different and explain some of the aberrant responses to neuromuscular blocking drugs. [ABSTRACT FROM AUTHOR]

The set of guidelines for good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents, which was developed following an international consensus conference in Copenhagen, has been revised and updated following the second consensus conference in Stockholm in 2005. It is hoped that these guidelines will continue to help researchers in the field and assist the pharmaceutical industry and equipment manufacturers in enhancing the standards of the studies they sponsor. [ABSTRACT FROM AUTHOR]

The present approach to the diagnosis, management and follow-up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia. The recommendations are based on the best available evidence in the literature, which, owing to the rare and unforeseeable nature of anaphylaxis, mainly includes case series and expert opinion (grade of evidence IV and V). These guidelines include an overview of the epidemiology of anaphylactic reactions during anaesthesia. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline (epinephrine) and fluid therapy as first-line treatment. Recommendations for primary and secondary follow-up are given, bearing in mind that there are variations in geography and resources in the different countries. A list of National Centres from which anaesthesiologists can seek advice concerning follow-up procedures is provided. In addition, an algorithm is included with advice on how to manage patients with previous suspected anaphylaxis during anaesthesia. Lastly, Appendix 2 provides an overview of the incidence, mechanisms and possibilities for follow-up for some common drug groups. [ABSTRACT FROM AUTHOR]