Influence of the Emitter Shape on the Field-of-View in Atom Probe Tomography.

Atom probe tomography (APT) is a unique analytical technique that offers three-dimensional elemental mapping with a spatial resolution down to the sub-nanometer. When APT is applied on complex heterogenous systems and/or under certain experimental conditions, that is, laser illumination, the specimen shape can deviate from an ideal hemisphere. Insufficient consideration of this aspect can introduce artifacts in the reconstructed dataset, ultimately degrading its spatial accuracy. So far, there has been limited investigation into the detailed evolution of emitter shape and its impact on the field-of-view (FOV). In this study, we numerically and experimentally investigated the FOV for asymmetric emitters and its evolution throughout the analysis depth. Our analysis revealed that, for asymmetric emitters, the ions evaporated from the topmost region of the specimen (summit) project approximately to the detector center. Furthermore, we demonstrated the implications of this finding on the FOV location for asymmetric emitters. Based on our findings, the location of the center of the FOV can deviate from the specimen central axis with an evolution depending on the evolution of the emitter shape. This study highlights the importance of accounting for the specimen shape when developing advanced data reconstruction schemes to enhance spatial resolution and accuracy.

Catastrophizing and rumination mediate the link between functional disabilities and anxiety/depression in fibromyalgia. A double-mediation model.

Fibromyalgia can be considered to be a model of chronic pain resulting from dysregulation of pain processing. From a psychological point of view, it is possible to consider transdiagnostic processes that would participate in both the dysregulation of pain and associated emotions. OBJECTIVE: The aim of this study was to test the links that exist between the tendency to Repetitive Negative Thinking (RNT) and the anxious-depressive manifestations in fibromyalgia. More specifically, we wanted to test a double mediation model where RNT would mediate the link between pain and depression/anxiety via catastrophizing. METHOD: Eighty-two patients with fibromyalgia completed a series of questionnaires evaluating their level of depression, anxiety, disability related to pain, catastrophizing as well as various measures of Repetitive Thoughts. RESULTS: The results showed strong correlations between RNT levels, pain, and anxious-depressive manifestations in this population. Moreover, the links between pain and depression/anxiety were mediated by catastrophizing and RNT in serial. CONCLUSION: Results support the interest of studying RNT as a transdiagnostic process in fibromyalgia pain. Considering RNT in fibromyalgia allows a better understanding of tthe links that exist between pain and emotional disorders in this population and thus to better understand the psychopathological comorbidity of fibromyalgia.

Telephone Assessment of Suicidal Risk at Prehospital Emergency Medical Services: A Direct Comparison with Face-to-Face Evaluation at Psychiatric Emergency Service.

OBJECTIVE: Assessment of suicidal risk is one of the most challenging tasks faced by health professionals, notably in emergency care. We compared telephone suicide risk assessment at prehospital Emergency Medical Services Dispatch Center (EMS-DC), with subsequent face-to-face evaluation at Psychiatric Emergency Service (PES), using French national Risk-Urgency-Danger standards (RUD). METHOD: Data were collected for all suicidal adult patients (N = 80) who were addressed by EMS-DC to PES between December 2018 and August 2019 and benefited from RUD assessment at both services. Suicidal risk was given a score of 1, 2, 3 or 4, in order of severity. RESULTS: Mean of the differences between the RUD score at EMS-DC and PES was -0.825 (SD = 1.19), and was found to be significant (p < 0.01). The average time between RUD assessments was 420 min (SD = 448) and was negatively correlated with the difference in the RUD score (r = -0.295, p = 0.008). Associated suicide attempt increased the odds of a decrease in the RUD score (OR = 2.989; 95% CI = 1.141-8.069; p < 0.05). CONCLUSIONS: Telephone evaluation of suicidal risk using RUD at EMS-DC yielded moderately higher scores than those obtained by a subsequent face-to face evaluation at PES, with this difference partially explained by the time between assessments, and by clinical and contextual factors.

Association between the Cardiac Arrest Hospital Prognosis (CAHP) score and reason for death after successfully resuscitated cardiac arrest.

Individualize treatment after cardiac arrest could potentiate future clinical trials selecting patients most likely to benefit from interventions. We assessed the Cardiac Arrest Hospital Prognosis (CAHP) score for predicting reason for death to improve patient selection. Consecutive patients in two cardiac arrest databases were studied between 2007 and 2017. Reasons for death were categorised as refractory post-resuscitation shock (RPRS), hypoxic-ischaemic brain injury (HIBI) and other. We computed the CAHP score, which relies on age, location at OHCA, initial cardiac rhythm, no-flow and low-flow times, arterial pH, and epinephrine dose. We performed survival analyses using the Kaplan-Meier failure function and competing-risks regression. Of 1543 included patients, 987 (64%) died in the ICU, 447 (45%) from HIBI, 291 (30%) from RPRS, and 247 (25%) from other reasons. The proportion of deaths from RPRS increased with CAHP score deciles; the sub-hazard ratio for the tenth decile was 30.8 (9.8-96.5; p < 0.0001). The sub-hazard ratio of the CAHP score for predicting death from HIBI was below 5. Higher CAHP score values were associated with a higher proportion of deaths due to RPRS. This score may help to constitute uniform patient populations likely to benefit from interventions assessed in future randomised controlled trials.

Investigation of Potential Injury Patterns and Occupant Kinematicsin Frontal Impact with PMHS in Reclined Postures.

The reality of the autonomous vehicle in a near future is growing and is expected to induce significant change inthe occupant posture with respect to a standard driving posture. The delegated driving would allow sleeping and/or resting in a seatwith a reclined posture. However, the data in the literature are rare on the body kinematics, human tolerance, and injury types insuch reclined postures. The current study aims at increasing the knowledge in the domain and providing useful data to assess therelevance of the standard injury assessment tools such as anthropomorphic test devices or finite element human body models. For that purpose, a test series of three male Post-Mortem Human Subjects (PMHS) were performed in frontal impact at a 13.4 m/sdelta V. The backseat inclination was 58 degrees with respect to the vertical axis. The semi-rigid seat developed by Uriot et al.(2015) was used with a stiffer seat ramp. The restraint was composed of a lap belt equipped with two 3.5 kN load limiters, and ofa shoulder belt equipped of a 4 kN load limiter on the upper anchorage placed in the vicinity of the shoulder. The belts, the semi-rigid seat, and the footrest were equipped with force sensors. The rotations of the seat pan and of the seat ramp were also measured. The PMHS were instrumented with multi-axis accelerometers and Y angular velocity sensors attached to the head, thorax (T1 andT12 vertebrae), and sacrum. Strain gauges were glued onto the anterior face of the L1 to L5 lumbar vertebrae and onto the anteriorface of the iliac wings. To estimate the pelvis kinematics, a rigid support equipped with targets was fixed onto the femur shaft. Prior to test, X-ray imagery was performed to exhibit the initial curvature of the lumbar spine. After the tests, an in-depth necropsywas done, with a specific attention to the lumbar spine. In the chosen test conditions, no lap-belt submarining was observed for the three PMHS. One PMHS sustained an AIS2 pelvic ringfracture and another one sustained an AIS4 injury with complete separation of the left and right sacroiliac joints. Lumbar discruptures and vertebral fractures were observed for the three PMHS (AIS 2 and AIS3 coding). The number of separated rib fractureswere very different from one PMHS to another (0, 6 and 33). Response corridors for the external forces and kinematics were builtand are presented in the paper. The results are discussed by comparing with existing data for which the backseat was in standardposture.

Prevention of hypothermia in trauma victims - the HYPOTRAUM 2 study.

INTRODUCTION: Hypothermia is common in trauma patients. It contributes to increasing mortality rate. Hypothermia is multifactorial, favoured by exposure to cold, severity of the patient's state and interventions such as infusion of fluids at room temperature. AIM: To demonstrate that specific management of hypothermia (or of the risk of hypothermia) increases the number of trauma patients arriving at the hospital with a temperature >35°C. DESIGN: This is a prospective, multicentre, open-label, pragmatic, cluster randomized clinical trial of an expected 1,200 trauma patients included by 12 out-of-hospital mobile intensive care units (MICU). Trauma patients are included in a prehospital setting if they present at least one of the following criteria known to be associated with an increased incidence of hypothermia: ambient temperature <18°C, Glasgow coma scale <15, systolic arterial blood pressure <100 mm Hg or body temperature <35°C. Patients are randomized, by cluster, to receive a conventional management or 'interventional' nursing management associating: continuous epitympanic temperature monitoring, early installation in the heated ambulance (temperature target >30°C controlled by infrared thermometer), protection by a survival blanket, and use of heated solutes (temperature objective >35°C controlled by infrared thermometer). The primary end point is the prevalence of hypothermia on arrival at the hospital. The hypothesis tested is a reduction from 20% to 13% in the prevalence of hypothermia. Secondary end points are to evaluate the interaction between the effectiveness of the measures taken and: (1) the severity of the patients assessed by the Revised Trauma Score; (2) the meteorological conditions when they are managed; (3) the time of care; and (4) therapeutic interventions. DISCUSSION: This trial will assess the effectiveness of an invasive, out-of-hospital, temperature management on the onset of hypothermia in moderate to severe trauma patients. IMPACT: Specific management of hypothermia is expected to decrease hypothermia in trauma patients.

THOR-05F Response in Sled Tests Inducing Submarining and Comparison with PMHS Response Corridors.

The Test Device for Human Occupant Restraint (THOR) is an advanced crash test dummy designed for frontal impact. Originally released in a 50th percentile male version (THOR-50M), a female 5th version (THOR-05F) was prototyped in 2017 (Wang et al., 2017) and compared with biofidelity sub-system tests (Wang et al., 2018). The same year, Trosseille et al. (2018) published response corridors using nine 5th percentile female Post Mortem Human Subjects (PMHS) tested in three sled configurations, including both submarining and non-submarining cases. The goal of this paper is to provide an initial evaluation of the THOR-05F biofidelity in a full-scale sled test, by comparing its response with the PMHS corridors published by Trosseille et al. (2018). Significant similarities between PMHS and THOR-05F were observed: as in Trosseille et al. (2018), the THOR-05F did not submarine in configuration 1, and submarined in configurations 2 and 3. The lap belt tension and seat forces were similar in magnitude. For configurations 2 and 3, the pelvis excursions were of the same order of magnitude between both human surrogates. However, significant differences were also observed: compared to the PMHS, the THOR-05F showed shoulder belt forces that were 1.6 to 2.1 times higher in magnitude, and lap belt force time histories that were delayed by 10 to 20 ms. In configuration 1, the chest and pelvis resultant accelerations of the dummy were delayed as well, and the pelvis excursion and rotation more than doubled that of the PMHS.

Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study.

Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (<4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients. Methods: This study included 28 patients (24 AIS and 4 TIA) and 29 controls. The blood and urine samples of patient were collected within 4.5 h of symptoms onset (day 0, D0), then at 24 h and 3 months. Control blood and urine samples were collected once (D0). The TSK axis markers measured were platelet serotonin transporter (SERT) and 5-HT2A receptor (5-HT2AR) densities and platelet, plasma, and urinary 5-HT, plasma and urinary 5-hydroxyindole acetic acid (5-HIAA), and plasma kynurenine and tryptophan (TRP) levels. Results: At D0, patients exhibited a lower (p = 10-5) platelet SERT density, higher (p < 10-6) platelet 5-HT2AR density, higher (p = 10-5) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (p = 0.011) and 5-HIAA (p = 0.003) levels than controls. Conclusions: We observed, for the first time, a hyperacute dysregulation of the serotonergic axis, and hyperacute and long-lasting activation of the tryptophan-kynurenine pathway in brain ischemia.

Geometrical and Mechanical Characterization of the Abdominal Fold of Obese Post Mortem Human Subjects for Use in Human Body Modelling.

Obese vehicle occupants sustain specific injury patterns in case of accidents in which the interaction between the seat belt and the abdomen may play a role. This study aimed to collect geometrical characteristics and to investigate the mechanical responses of the abdomen of obese subjects. Four Post Mortem Human Subjects (PMHS) with BMI ranging from 31 to 46 kg/m2 were collected. CT-scans performed in the seated position revealed that the antero-posterior depth of the abdominal fold (from the inguinal region to the most anterior point of the abdominal surface) was much greater (170 mm max., 127 mm average) than the thickness of subcutaneous adipose tissues (85 max., 38 mm in average). Each PMHS was subjected to three infra-injurious antero-posterior belt pulls in a seated posture with a lap belt positioned (C1) superior to the umbilicus, (C2) inferior to the umbilicus, (C3) inside the abdominal fold between the abdomen and the thigh. During the C1 and C2 tests, the belt moved cranially, and the abdominal fold opened widely especially in C2. Forces remained below 1800 N, for maximum applied displacements ranging from 89 to 151 mm for C1 and C2, and 37 to 66 mm for C3. Finally, sled tests were conducted on two PMHS seated on a semi-rigid seat and restrained by a three-point belt equipped with pretensioners and a 3.5 kN force limitation at the shoulder. The first PMHS (BMI 39 kg/m2) was tested at 49 km/h (39 g peak) and sustained severe injuries (AIS 4 pelvis dislocation, AIS 3 bilateral femur fractures) attributed to the combined loading of the seat and lap belt force (about 11 kN and 7 kN, respectively). The second PMHS (BMI 46 kg/m2) was subjected to a 29 km/h test (8 g plateau) and sustained no injury. The lap belt slid inside the abdominal fold in the first case and deformed the lower abdomen in the second, providing limited restraint forces during that interaction and leading to a large body excursion for the first test. The results highlight the possible relevance of the abdominal fold at the abdomen thigh junction to model and study the restraint conditions of obese occupants using Human Body Models (HBM).

Esmolol Compared with Amiodarone in the Treatment of Recent-Onset Atrial Fibrillation (RAF): An Emergency Medicine External Validity Study.

BACKGROUND: Recent-onset atrial fibrillation (RAF) is the most frequent supraventricular dysrhythmia in emergency medicine. Severely compromised patients require acute treatment with injectable drugs OBJECTIVE: The main purpose of this external validity study was to compare the short-term efficacy of esmolol with that of amiodarone to treat severe RAF in an emergency setting. METHODS: This retrospective survey was conducted in mobile intensive care units by analyzing patient records between 2002 and 2013. We included RAF with (one or more) severity factors including: clinical shock, angina pectoris, ST shift, and very rapid ventricular rate. A blind matching procedure was used to constitute esmolol group (n = 100) and amiodarone group (n = 200), with similar profiles for age, gender, initial blood pressure, heart rate, severity factors, and treatment delay. The main outcome measure was the percentage of patients with a ventricular rate control defined as heart frequency ≤ 100 beats/min. More stringent (rhythm control) and more humble indicators (20% heart rate reduction) were analyzed at from 10 to 120 min after treatment initiation. RESULTS: Patient characteristics were comparable for both groups: age 66 ± 16 years, male 71%, treatment delay < 1 h 36%, 1-2 h 29%, > 2 h 35%, chest pain 61%, ST shift 62%, ventricular rate 154 ± 26 beats/min, and blood pressure 126/73 mm Hg. The superiority of esmolol was significant at 40 min (64% rate control with esmolol vs. 25% with amiodarone) and for all indicators from 10 to 120 min after treatment onset. CONCLUSION: In "real life emergency medicine," esmolol is better than amiodarone in the treatment of RAF.

Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice.

The globally used herbicide glufosinate-ammonium (GLA) is structurally analogous to the excitatory neurotransmitter glutamate, and is known to interfere with cellular mechanisms involved in the glutamatergic system. In this report, we used an in vitro model of murine primary neural stem cell culture to investigate the neurotoxicity of GLA and its main metabolite, 4-methylphosphinico-2-oxobutanoic acid (PPO). We demonstrated that GLA and PPO disturb ependymal wall integrity in the ventricular-subventricular zone (V-SVZ) and alter the neuro-glial differentiation of neural stem cells. GLA and PPO impaired the formation of cilia, with reduced Celsr2 expression after PPO exposure. GLA promoted the differentiation of neuronal and oligodendroglial cells while PPO increased B1 cell population and impaired neuronal fate of neural stem cells. These results confirm our previous in vivo report that developmental exposure to GLA alters neurogenesis in the SVZ, and neuroblast migration along the rostral migratory stream. They also highlight the importance of investigating the toxicity of pesticide degradation products. Indeed, not only GLA, but also its metabolite PPO disrupts V-SVZ homeostasis and provides a novel cellular mechanism underlying GLA-induced neurodevelopmental toxicity. Furthermore, we were able to demonstrate a neurotoxic activity of a metabolite of GLA different from that of GLA active substance for the very first time.

Comparison of etomidate and sodium thiopental for induction during rapid sequence intubation in convulsive status epilepticus: A retrospective single-center study.

PURPOSE: Few outcome data are available about morbidity associated with endotracheal intubation modalities in critically ill patients with convulsive status epilepticus. We compared etomidate versus sodium thiopental for emergency rapid sequence intubation in patients with out-of-hospital convulsive status epilepticus. METHODS: Patients admitted to our intensive care unit in 2006-2015 were studied retrospectively. The main outcome measure was seizure and/or status epilepticus recurrence within 12 h after rapid sequence intubation. RESULTS: We included 97 patients (60% male; median age, 59 years [IQR, 48-70]). Median time from seizure onset to first antiepileptic drug was 60 min [IQR, 35-90]. Reasons for intubation were coma in 95 (98%), acute respiratory distress in 18 (19%), refractory convulsive status epilepticus in 9 (9%), and shock in 6 (6%) patients; 50 (52%) patients had more than one reason. The hypnotic drugs used were etomidate in 54 (56%) and sodium thiopental in 43 (44%) patients. Seizure and/or status epilepticus recurred in 13 (56%) patients in the etomidate group and 11 patients (44%) in the sodium thiopental group (adjusted common odds ratio [aOR], 0.98; 95%CI, 0.36-2.63; P = 0.97). The two groups were not significantly different for proportions of patients with hemodynamic instability after intubation (aOR, 0.60; 95%CI, 0.23-1.58; P = 0.30) or with difficult endotracheal intubation (OR, 1.28; 95% CI 0.23 to 7.21; P=0.77). CONCLUSIONS: Our findings argue against a difference in seizure and/or status epilepticus recurrences rates between critically ill patients with convulsive status epilepticus given etomidate vs. sodium thiopental as the induction agent for emergency intubation.

Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of-Hospital Cardiorespiratory Arrest: A Randomized Clinical Trial.

Importance: Bag-mask ventilation (BMV) is a less complex technique than endotracheal intubation (ETI) for airway management during the advanced cardiac life support phase of cardiopulmonary resuscitation of patients with out-of-hospital cardiorespiratory arrest. It has been reported as superior in terms of survival. Objectives: To assess noninferiority of BMV vs ETI for advanced airway management with regard to survival with favorable neurological function at day 28. Design, Settings, and Participants: Multicenter randomized clinical trial comparing BMV with ETI in 2043 patients with out-of-hospital cardiorespiratory arrest in France and Belgium. Enrollment occurred from March 9, 2015, to January 2, 2017, and follow-up ended January 26, 2017. Intervention: Participants were randomized to initial airway management with BMV (n = 1020) or ETI (n = 1023). Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 28 days defined as cerebral performance category 1 or 2. A noninferiority margin of 1% was chosen. Secondary end points included rate of survival to hospital admission, rate of survival at day 28, rate of return of spontaneous circulation, and ETI and BMV difficulty or failure. Results: Among 2043 patients who were randomized (mean age, 64.7 years; 665 women [32%]), 2040 (99.8%) completed the trial. In the intention-to-treat population, favorable functional survival at day 28 was 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, -1.64% to infinity]; P for noninferiority = .11). Survival to hospital admission (294/1018 [28.9%] in the BMV group vs 333/1022 [32.6%] in the ETI group; difference, -3.7% [95% CI, -7.7% to 0.3%]) and global survival at day 28 (55/1018 [5.4%] in the BMV group vs 54/1022 [5.3%] in the ETI group; difference, 0.1% [95% CI, -1.8% to 2.1%]) were not significantly different. Complications included difficult airway management (186/1027 [18.1%] in the BMV group vs 134/996 [13.4%] in the ETI group; difference, 4.7% [95% CI, 1.5% to 7.9%]; P = .004), failure (69/1028 [6.7%] in the BMV group vs 21/996 [2.1%] in the ETI group; difference, 4.6% [95% CI, 2.8% to 6.4%]; P < .001), and regurgitation of gastric content (156/1027 [15.2%] in the BMV group vs 75/999 [7.5%] in the ETI group; difference, 7.7% [95% CI, 4.9% to 10.4%]; P < .001). Conclusions and Relevance: Among patients with out-of-hospital cardiorespiratory arrest, the use of BMV compared with ETI failed to demonstrate noninferiority or inferiority for survival with favorable 28-day neurological function, an inconclusive result. A determination of equivalence or superiority between these techniques requires further research. Trial Registration: clinicaltrials.gov Identifier: NCT02327026.

Reference PMHS Sled Tests to Assess Submarining of the Small Female.

In the last decade, extensive efforts have been made to understand the physics of submarining and its consequences in terms of abdominal injuries. For that purpose, 27 Post Mortem Human Subject (PMHS) tests were performed in well controlled conditions on a sled and response corridors were provided to assess the biofidelity of dummies or human body models. All these efforts were based on the 50th percentile male. In parallel, efforts were initiated to transfer the understanding of submarining and the prediction criteria to the THOR dummies. Both the biofidelity targets and the criteria were scaled down from the 50th percentile male to the 5th percentile THOR female. The objective of this project was to run a set of reference PMHS tests in order to check the biofidelity of the THOR F05 in terms of submarining. Three series of tests were performed on nine PMHS, the first one was designed to avoid submarining, the second and third ones were designed to result in submarining. In the first configuration, no submarining was observed in 3 cases out of 4 and only one iliac wing fracture occurred in one subject. In the second and third configurations, all subjects but one sustained submarining. In addition, two subjects out of three in the third configuration sustained substantial iliac wing fractures. Nevertheless, all configurations can be represented by at least one or several cases without any pelvis fracture. Corridors were constructed for the external forces and the PMHS kinematics. They are provided in this paper as new experimental references to assess the biofidelity of small female human surrogates in different configurations where submarining did or did not occur.

In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study.

Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications - the synthetic pyrethroid cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring's early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring's brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.

Influence of body mass index on the prognosis of patients successfully resuscitated from out-of-hospital cardiac arrest treated by therapeutic hypothermia.

BACKGROUND: Obesity prevalence has dramatically increased over recent years and is associated with cardiovascular diseases, but data are lacking on its prognostic impact in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Data of all consecutive OHCA patients admitted in two cardiac arrest centers from Paris and suburbs between 2005 and 2012 were prospectively collected. Patients treated by therapeutic hypothermia (TH) were included in the analysis. Logistic and Cox regression analyses were used to quantify the association between body mass index (BMI) at hospital admission and day-30 and 1-year mortality respectively. RESULTS: 818 patients were included in the study (median age 60.9 [50.8-72.7] year, 70.2% male). Obese patients (BMI>30kgm-2) were older, more frequently male and evidenced more frequently cardiovascular risk factors than normally (18.530kgm-2 was independently associated with day-30 mortality (Odds ratio [OR] in comparison with normally weight patients 2.45; 95% confidence interval [95%CI: 1.32-4.56; p<0.01]). Obesity was not associated with one-year mortality (Hazard ratio [HR] 0.99, 95%CI 0.21,4.67; p=0.99) while underweight was associated with one-year mortality in this subgroup of patients (Hazard ratio [HR] 3.94, 95%CI 1.11,14.01; p=0.03). CONCLUSION: In the present study, obesity was independently associated with day-30 mortality in successfully resuscitated ICU TH OHCA patients. Further studies are needed to understand the mechanisms that underpin this finding.

Perinatal Exposure to Glufosinate Ammonium Herbicide Impairs Neurogenesis and Neuroblast Migration through Cytoskeleton Destabilization.

Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.

Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.

Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1ß (IL-1ß) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice.

Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial.

BACKGROUND: Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs. OBJECTIVES: The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial. METHODS: The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects. RESULTS: In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01). CONCLUSIONS: In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583).