Publications by authors named "Richard O"

184 Publications

Reviews on mechanisms of in vitro antioxidant, antibacterial and anticancer activities of water-soluble plant polysaccharides.

Int J Biol Macromol 2021 Jul 29;183:2262-2271. Epub 2021 May 29.

School of Applied Science and Technology, Department of Food and Postharvest Technology, Cape Coast Technical University, PMB, Cape Coast, DL 50, Ghana.

Degenerative diseases such as cancer and cardiovascular diseases, and antimicrobial resistance are becoming prominent health problems needing utmost public health attention. Curative interventions such as the use of pharmaceutical drugs and alternative plant medicines are increasingly being explored. Plant polysaccharides have gained attention for their promising bioactivities such as antioxidant, antimicrobial and anticancer activities. Bioactive plant polysaccharides are also being preferred for their relatively few side effects compared to conventional pharmaceuticals. The elucidation of the bioactive potential of plant polysaccharides in disease treatment entails an understanding of the factors that determine their biofunctional properties using functional and mechanistic assays. This review summarizes the literature on the composition, structural, functional, and mechanistic determinations of the antioxidant, anticancer and antimicrobial activities of plant polysaccharides. The outcome of this review highlights the leading trends in the elucidation of the antioxidant, anticancer and antimicrobial activities of plant polysaccharides and underscores the promising health benefits of plant polysaccharides.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.181DOI Listing
July 2021

The Impact of Supervisor-Subordinate Incongruence in Power Distance Orientation on Subordinate Job Strain and Subsequent Job Performance.

J Bus Psychol 2021 Apr 5:1-15. Epub 2021 Apr 5.

RSM, Erasmus University, Rotterdam, Netherlands.

Employee strain is estimated to cost American companies as much as $500 billion in lost productivity annually, and a leading cause of workforce stress is disagreements with other people (Cook, 2017; Mental Health America, 2017). In this study, we investigate supervisor-subordinate value incongruence as a cause of employee strain. Specifically, this study examines the effect of supervisor-subordinate power distance orientation incongruence on the subordinate's job strain which, in turn, influences the subordinate's job performance. Using a sample of 172 supervisor-subordinate dyads, we find that incongruence on power distance orientation increases subordinate job strain. Supervisor-subordinate incongruence resulted in more job strain which, in turn, resulted in lower job performance. Results reveal that the alignment of subordinates' cultural values with those of their supervisors may mitigate negative experiences and facilitate more positive work outcomes.
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http://dx.doi.org/10.1007/s10869-021-09738-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021442PMC
April 2021

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

J Adv Nurs 2021 Jun 19;77(6):2908-2915. Epub 2021 Mar 19.

URC F-Widal/Lariboisière-Saint Louis, Paris, France.

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.
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http://dx.doi.org/10.1111/jan.14818DOI Listing
June 2021

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

Stapp Car Crash J 2020 Nov;64:213-267

LAB PSA Peugeot Citroën Renault (France).

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/m 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/m) 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/m) 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).
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November 2020

Fatal avian malaria in captive Atlantic puffins () in Switzerland.

Int J Parasitol Parasites Wildl 2021 Apr 18;14:97-106. Epub 2021 Jan 18.

Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012, Bern, Switzerland.

Avian malaria is a vector-borne disease caused by species which may affect a broad spectrum of bird families worldwide. In most endemic and migratory birds, infections seem not to cause severe harm; however, non-indigenous species kept in human care such as penguins may experience high morbidity and mortality rates. Fatal avian malaria may also occur in other non-native seabirds such as puffins ( spp.), but reported cases are scarce. The aim of this study was to analyze seven cases of sudden death in captive Atlantic puffins () at Berne Animal Park in Switzerland between 2010 and 2020, and to determine the involvement of haemosporidian parasites in the fatal outcome. In all cases, lymphoplasmacytic inflammation, necrotic lesions in several organs and presence of protozoan stages within tissues/erythrocytes or accumulation of iron-based pigment were observed histologically. A one-step multiplex PCR designed to simultaneously detect and discriminate haemosporidia belonging to the genera , and and a nested PCR detecting and infections were performed on DNA extracted from formalin-fixed and paraffin-embedded (FFPE) or fresh liver and spleen tissues from five and two birds, respectively. spp. DNA was detected in the tissues from six of seven birds by the one-step multiplex PCR and in five of seven individuals by the nested PCR protocol. Direct sequencing of the amplification products allowed the molecular identification of SGS1 as the involved species in three individuals and LINN1 in two of these fatal cases. In one bird, no haemosporidian DNA could be amplified from FFPE tissues despite of suggestive histopathological findings. These results indicate that avian malaria represents an important cause of death in captive puffins and it should be considered as a differential diagnosis in unclear or fatal cases in this threatened bird species.
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http://dx.doi.org/10.1016/j.ijppaw.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848291PMC
April 2021

A case report: Actinobaculum suis infection associated with formation of pyogranuloma, epididymitis and azoospermia in a boar.

BMC Vet Res 2021 Jan 6;17(1). Epub 2021 Jan 6.

Department of Clinical Veterinary Medicine, Clinic for Swine, Vetsuisse Faculty, University of Bern, CH, Bern, Switzerland.

Background: Actinobaculum suis is a bacterium known to cause infections of the urogenital tract of sows. Infection can occur through close contact to boars, who frequently carry the pathogen in their preputial diverticulum but do not become clinically diseased themselves. In the current case, Actinobaculum suis was isolated from pyogranuloma of inflamed epididymis in a boar with poor fertility.

Case Presentation: Increased return to oestrus rate, which worsened after the purchase of a new boar, was reported in an organic farm in Switzerland. During herd examination, azoospermia of the boar was diagnosed, and slaughter, followed by examination of its urogenital tract, was carried out. Pathologically, pyogranuloma formation and epididymitis were diagnosed. Bacteriology of the pyogranulomas showed growth of Actinobaculum suis and mixed flora. After the boar was replaced, the return to oestrus rate improved tremendously.

Conclusion: A close relative of Actinobaculum suis, namely Actinotignum schaalii, has already been associated with epididymitis in humans. Considering the present case and the parallels in human medicine, Actinobaculum suis should be included in the list of differentials of boars with poor fertility.
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http://dx.doi.org/10.1186/s12917-020-02680-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788979PMC
January 2021

Presenting features and molecular genetics of primary hyperparathyroidism in the paediatric population.

Eur J Endocrinol 2021 Feb;184(2):347-355

Paediatric Unit, Limoges University Hospital, Limoges, France.

Aim: To describe the presenting features and molecular genetics of primary hyperparathyroidism (PHPT) in the paediatric population.

Methods: Retrospective study of 63 children diagnosed with primary PHPT from 1998 to 2018.

Results: Compared to older children, infants were often asymptomatic (54% vs 15%, P = 0.002) with a milder form of PHPT. When symptomatic, children and adolescents mostly presented with non-specific complaints such as asthenia, depression, weight loss, vomiting or abdominal pain. A genetic cause of PHPT was identified in about half of this cohort (52%). The infancy period was almost exclusively associated with mutation in genes involved in the calcium-sensing receptor (CaSR) signalling pathway (i.e. CaSR and AP2S1 genes, 'CaSR group'; 94% of infants with mutations) whereas childhood and adolescence were associated with mutation in genes involved in parathyroid cell proliferation (i.e. MEN1, CDC73, CDKN1B and RET genes, 'cell proliferation group'; 69% of children and adolescents with mutations). Although serum calcium levels did not differ between the two groups (P = 0.785), serum PTH levels and the urinary calcium/creatinine ratio were significantly higher in 'cell proliferation group' patients compared to those in the 'CaSR group' (P = 0.001 and 0.028, respectively).

Conclusion: Although far less common than in adults, PHPT can develop in children and is associated with significant morbidity. Consequently, this diagnosis should be considered in children with non-specific complaints and lead to monitoring of mineral homeostasis parameters. A genetic cause of PHPT can be identified in about half of these patients.
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http://dx.doi.org/10.1530/EJE-20-1119DOI Listing
February 2021

Detection of antibiotic resistance genes among multiple drug resistant pseudomonas aeruginosa isolated from clinical sources in selected health institutions in kwara state.

Infect Disord Drug Targets 2020 Nov 15. Epub 2020 Nov 15.

Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Osogbo. Nigeria.

Background: Pseudomonas aeruginosa (P. aeruginosa) is a frequent nosocomial pathogen that causes severe diseases in many clinical and community settings. Strains of P. aeruginosa are associated with increased morbidity, mortality and healthcare costs. The rapid emergence of antimicrobial resistance among these strains is a public health crisis. Moreover, there is paucity of data on characterization of P. aeruginosa isolates from human clinical samples in Kwara State.

Objectives: The objectives are to investigate the occurrence of metallo β-lactamase enzyme, multiple antibiotic resistant P. aeruginosa among clinical samples and detection of antibiotic resistance genes among them.

Methods: Two hundred and thirty-five samples comprising of 145 males and 90 females human clinical specimens were collected aseptically from five selected health institutions within Kwara state, Nigeria. The samples were cultured immediately using standard microbiological procedures. Multiple drug resistance patterns of the micro-organisms to different antibiotics were determined using the Bauer Kirby disc diffusion technique. Metallo β-lactamase production was determined using E - test strip and the DNA samples of the multiple resistant P. aeruginosa strains were extracted and subjected to Polymerase Chain Reaction (PCR) for resistant genes determination. Data were subjected to descriptive statistics using Statistical Package for Social Sciences (SPSS) software.

Results: A total of 145 isolates were identified for P. aeruginosa from the clinical samples .Thirty were positive for metallo β-lactamase production; 11 (8 %) males and 19 (13 %) females. Absolute resistance to ceftazidime (100 %), gentamicin (100 %), ceftriaxone (100 %) were observed while low resistance to ciprofloxacin (12.4 %), piperacillin (6.9 %) and imipenem (6.9 %). All isolates were sensitive to colistin. The prevalence of various encoding genes blaVIM, , blaCTX-M and blaTEM were 34.4 %, 46.7 %, 16.7 % and 37.7 % respectively.

Conclusion: This study has shown that there is a high occurrence of metallo β-lactamase enzyme producing and antibioticresistant strains of P. aeruginosa in clinical specimens from the studied area. Necessary measures must therefore be implemented to stop the problems of this antibiotic resistance.
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http://dx.doi.org/10.2174/1871526520666201116103625DOI Listing
November 2020

Whole-Blood Resuscitation of Injured Patients' Plasma.

JAMA Surg 2021 Jan;156(1):101

TraumaBase PréHospitalière, Hôpitaux Universitaires Henri Mondor, Créteil, France.

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http://dx.doi.org/10.1001/jamasurg.2020.4109DOI Listing
January 2021

Thrombocytopenic purpura on an organic farm with pen mating: a case report on the re-emergence of an old disease.

Porcine Health Manag 2020 4;6:18. Epub 2020 Aug 4.

Clinic for Swine, Department of Clinical Veterinary Science, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.

Background: Thrombocytopenia is an immune-mediated disease, which affects suckling piglets. Piglets are pale and inactive, show multiple hemorrhages and often die within days. Pathological examination reveals severe haemorrhages and oedema in several organs. Severe thrombocytopenia and elongated bleeding time characterize the disease haematologically.The sow produces antibodies against the thrombocyte antigens of the boar, which are present in the blood of the piglets. These isoimmune antibodies attack the platelets and megakaryocytes of the piglets, causing thrombocytopenia in succeeding matings of the same boar and sow. There is no known therapy against this condition. In the last few decades, the disease has become rare due to the increase of artificial insemination.

Case Presentation: On an organic breeding farm in Switzerland with a high percentage of natural pen matings, piglets of three litters showed haemorrhages on the skin, prolonged bleeding time and were generally in a reduced general state. A pathological examination revealed multifocal haemorrhages in the stomach, kidneys, dermis, mesenterium and spinal cord. Haematology showed a massive thrombocytopenia and regenerative anaemia. Due to these findings the diagnosis of thrombocytopenic purpura was established.To avoid further matings of the same boar and sow and thus more affected piglets, out of three possible boars the responsible sire had to be determined. This was achieved through array genotyping and subsequent computation of identity by descent and calculation of Mendelian errors for parentage verification. Thereby the responsible boar was identified and as a consequence removed from the farm. Further preventive measures, that had been established, included the recording of all matings and regular exchange of boars.

Conclusion: The decreased number of natural matings with the surge of artificial insemination has probably reduced the number of cases of thrombocytopenic purpura and thus the disease awareness of farmers and veterinarians. However, as consumers wish for better animal welfare and higher ecological standards we may see a rise in natural matings and thus a return of the disease. In case of affected litters, genetic testing was proven a valid method for investigation and prevention of more cases and may be used more in the future.
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http://dx.doi.org/10.1186/s40813-020-00157-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401201PMC
August 2020

Impairment in oral medical comprehension in multiple sclerosis.

Rev Neurol (Paris) 2021 Jan-Feb;177(1-2):65-72. Epub 2020 Jul 4.

Maison-Blanche hospital, Neurology department, Reims, France.

In multiple sclerosis (MS), medical comprehension of website information and informed consent is reported to be impaired. The aim of the present study was to investigate oral medical comprehension of literal, figurative and humorous language in MS through videos of physician-patient exchanges. A group of 35 MS patients was compared to a control group (38 healthy participants). Participants were shown twelve filmed sketches consisting of a patient's question followed by the doctor's response and had to choose the meaning of the physician's response among three possibilities. Group analyses (non-parametric tests, Mann-Whitney) revealed significantly lower scores for MS patients compared to controls for figurative and humorous items. The opposite was observed for literal items. At the individual level, 17% of MS patients were impaired in their comprehension of figurative items and 32% for humorous items. Among them, 20% were impaired in both categories, 20% selectively in figurative comprehension and 60% selectively in humorous comprehension. These preliminary results suggest that a high proportion of MS patients (40%) may be impaired in the non-literal comprehension of simple medical responses. The better performances obtained for literal items suggest a more concrete linguistic decoding in MS. On a theoretical level, the double dissociations shown between figurative and humorous items in patients are not compatible with a serial model of linguistic processing.
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http://dx.doi.org/10.1016/j.neurol.2020.03.024DOI Listing
August 2021

Vaccination against type C enteritis in pigs: a field study using an adapted vaccination scheme.

Porcine Health Manag 2019 15;5:20. Epub 2019 Aug 15.

1Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Längassstrasse 122, 3012 Bern, Switzerland.

Background: type C induced necrotizing enteritis (NE) causes high mortality in newborn piglets. Immunization programs employing commercially available vaccines are used to prevent disease. Sows are vaccinated during every gestation period and piglets take up antibodies from the colostrum. Antibodies against the major clostridial toxin beta-toxin (CPB) are considered essential for protective immunity. Because the pathogen can persist for several years on farms, continuous vaccination is essential to protect pig herds from the re-occurrence of NE.

Results: In two field trials using commercially available vaccines we monitored neutralizing anti-CPB antibodies in pigs after vaccination. The first trial compared antibody titers in primiparous (gilts) and multiparous sows and their piglets after vaccination. A proportion of gilts and their piglets' showed no or low antibody titers. All multiparous sows developed significantly higher serum and colostrum antibody titers after a booster vaccination shortly before their next farrowing. These colostral antibody titer highly correlated with the serum antibody titer of their piglets after consumption of colostrum. In a second field trial, we adapted the vaccination schemes using 3 instead of 2 initial vaccinations before the first farrowing of gilts. This significantly increased serum and colostrum antibody titers in gilts and serum antibody titers in piglets.

Conclusion: We demonstrate that despite following recommended vaccination protocols, a proportion of gilts might not sufficiently seroconvert to provide efficient passive immunity to their offsprings. A simple adaptation of the vaccination scheme can however improve passive protection of piglets from NE.
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http://dx.doi.org/10.1186/s40813-019-0127-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694488PMC
August 2019

Chromosomal imbalance in pigs showing a syndromic form of cleft palate.

BMC Genomics 2019 May 8;20(1):349. Epub 2019 May 8.

Institute of Genetics, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3012, Bern, Switzerland.

Background: Palatoschisis or cleft palate is a known anomaly in pigs resulting in their death. However, little is known about its aetiology. A detailed description of the phenotype was derived from necropsy and by computed tomography revealing that all 20 cases also exhibited hypodontia and renal cysts. Furthermore, a genetic origin was assumed due to dominant inheritance as all 20 recorded cases were confirmed offspring of a single boar.

Results: Single nucleotide variant (SNV) genotyping data were used to map the defect in the porcine genome and led to the detection of a chromosomal imbalance in the affected offspring. Whole genome sequencing of an affected piglet and a normal full sib was used to identify a chromosomal translocation and to fine map the breakpoints in the genome. Finally, we proved that the boar, which sired the malformed piglets, carried a balanced translocation. The detected translocation of Mb-sized segments of chromosome 8 and 14 had not been previously observed during karyotyping. All affected offspring were shown to be carriers of a partial trisomy of chromosome 14 including the FGFR2 gene, which is associated with various dominant inherited craniofacial dysostosis syndromes in man, and partial monosomy of chromosome 8 containing MSX1 known to be associated with tooth agenesis and orofacial clefts in other species.

Conclusions: This study illustrates the usefulness of recently established genomic resources in pigs. In this study, the application of genome-wide genotyping and sequencing methods allowed the identification of the responsible boar and the genetic cause of the observed defect. By implementing systematic surveillance, it is possible to identify genetic defects at an early stage and avoid further distribution of congenital disorders.
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http://dx.doi.org/10.1186/s12864-019-5711-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505205PMC
May 2019

Air pollution and humidity as triggering factors for stroke. Results of a 12-year analysis in the West Paris area.

Rev Neurol (Paris) 2019 Dec 25;175(10):614-618. Epub 2019 Apr 25.

Department of Neurology and Stroke Center, Versailles Hospital Center, 177, rue de Versailles, 78150 Le Chesnay, Versailles, France; Université Versailles Saint-Quentin en Yvelines et Paris Saclay, 78000 Versailles, France; Inserm LVTS (Laboratory for Vascular Translational Science), 1148 Paris, France. Electronic address:

Background And Purpose: Previous studies have suggested an association between stroke and meteorological factors, air pollution and acute respiratory infections as triggering factors. Often, these factors have been evaluated separately. We evaluated the association between all these environmental triggering factors and calls for suspected stroke in a suburb in west Paris from 2004 to 2015.

Methods: We used data from the emergency medical dispatching center of all calls for suspected stroke (SAMU 78), climatic parameters (MétéoFrance), pollution (AIRPARIF), and data from influenza epidemic surveillance networks (GROG and Sentinelles). The association between short-term exposure (1-day lag) to environmental triggering factors and stroke occurrence was analyzed using negative-binomial log linear regression model for counting time series.

Results: Between 2004 and 2015, a total of 11,037 calls for suspected stroke were recorded. In bivariate analysis, there were associations between calls for suspected stroke and temperature (mean, maximum and minimum), humidity and influenza epidemic. In multivariable analysis, only two variables were associated with calls for suspected stroke: humidity [3.93% excess relative risk (ERR) of stroke per 10% increase in humidity; 95% confidence interval (CI), 1.42 to 6.51; P<0.002] and pollution on the "Air Parif Atmo" scale (2.86% ERR of stroke per 1 unit increase; 95% CI, 1.01 to 4.75; P=0.002).

Conclusions: This study suggests that short-term exposure to air pollution and a high level of humidity are associated with a significant excess relative risk of calls for suspected stroke.
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http://dx.doi.org/10.1016/j.neurol.2019.03.002DOI Listing
December 2019

Application of an Endothelial Cell Culture Assay for the Detection of Neutralizing Anti-Clostridium Perfringens Beta-Toxin Antibodies in a Porcine Vaccination Trial.

Toxins (Basel) 2019 04 15;11(4). Epub 2019 Apr 15.

Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.

Background: Beta-toxin (CPB) is the major virulence factor of type C, causing hemorrhagic enteritis in newborn pigs but also other animals and humans. Vaccines containing inactivated CPB are known to induce protective antibody titers in sow colostrum and neutralization of the CPB activity is thought to be essential for protective immunity in newborn piglets. However, no method is available to quantify the neutralizing effect of vaccine-induced antibody titers in pigs. (2) Methods: We developed a novel assay for the quantification of neutralizing anti-CPB antibodies. Sera and colostrum of sows immunized with a commercial type A and C vaccine was used to determine neutralizing effects on CPB induced cytotoxicity in endothelial cells. Antibody titers of sows and their piglets were determined and compared to results obtained by an ELISA. (3) Results: Vaccinated sows developed neutralizing antibodies against CPB in serum and colostrum. Multiparous sows developed higher serum and colostrum antibody titers after booster vaccinations than uniparous sows. The antibody titers of sows and those of their piglets correlated highly. Piglets from vaccinated sows were protected against intraperitoneal challenge with type C supernatant. (4) Conclusions: The test based on primary porcine endothelial cells quantifies neutralizing antibody activity in serum and colostrum of vaccinated sows and could be used to reduce and refine animal experimentation during vaccine development.
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http://dx.doi.org/10.3390/toxins11040225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520926PMC
April 2019

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

J Emerg Med 2019 Mar 30;56(3):308-318. Epub 2019 Jan 30.

SAMU 78, Centre Hospitalier de Versailles, André Mignot, Le Chesnay, France.

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.
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http://dx.doi.org/10.1016/j.jemermed.2018.12.010DOI Listing
March 2019

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

Stapp Car Crash J 2018 Nov;62:93-118

Université René Descartes, Paris.

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.
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November 2018

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

Neurotoxicology 2018 12 10;69:152-163. Epub 2018 Oct 10.

Immunologie et Neurogénétique Expérimentales et Moléculaires, UMR7355, 3B rue de la Férollerie, F-45071, ORLEANS CEDEX 2, France; Université d'Orléans, ORLEANS, France.

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.
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http://dx.doi.org/10.1016/j.neuro.2018.10.001DOI Listing
December 2018

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

Seizure 2018 Oct 28;61:170-176. Epub 2018 Aug 28.

Intensive Care Unit, Centre Hospitalier de Versailles - Site André Mignot, 177 rue de Versailles, 78150 Le Chesnay Cedex, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; INSERM U970, Paris Cardiovascular Research Center, Paris, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.seizure.2018.08.022DOI Listing
October 2018

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

JAMA 2018 02;319(8):779-787

AP-HP, SAMU 93, Hôpital Avicenne, Inserm U942, Bobigny, France.

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.
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http://dx.doi.org/10.1001/jama.2018.0156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838565PMC
February 2018

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.

PLoS One 2017 11;12(10):e0184475. Epub 2017 Oct 11.

Immunologie et Neurogénétique Expérimentales et Moléculaires - UMR7355 CNRS - Orléans, France.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184475PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636066PMC
October 2017

Structural characterization of SnS crystals formed by chemical vapour deposition.

J Microsc 2017 12 28;268(3):276-287. Epub 2017 Sep 28.

Imec, Leuven, Belgium.

The crystal and defect structure of SnS crystals grown using chemical vapour deposition for application in electronic devices are investigated. The structural analysis shows the presence of two distinct crystal morphologies, that is thin flakes with lateral sizes up to 50 μm and nanometer scale thickness, and much thicker but smaller crystallites. Both show similar Raman response associated with SnS. The structural analysis with transmission electron microscopy shows that the flakes are single crystals of α-SnS with [010] normal to the substrate. Parallel with the surface of the flakes, lamellae with varying thickness of a new SnS phase are observed. High-resolution transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), first-principles simulations (DFT) and nanobeam diffraction (NBD) techniques are employed to characterise this phase in detail. DFT results suggest that the phase is a strain stabilised β' one grown epitaxially on the α-SnS crystals. TEM analysis shows that the crystallites are also α-SnS with generally the [010] direction orthogonal to the substrate. Contrary to the flakes the crystallites consist of two to four grains which are tilted up to 15° relative to the substrate. The various grain boundary structures and twin relations are discussed. Under high-dose electron irradiation, the SnS structure is reduced and β-Sn formed. It is shown that this damage only occurs for SnS in direct contact with SiO .
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http://dx.doi.org/10.1111/jmi.12652DOI Listing
December 2017

Little differences in digestive efficiency for protein and fat in mammals of different trophic guilds and digestive strategies: data constraints or fundamental functional similarity?

J Anim Physiol Anim Nutr (Berl) 2017 Jun;101 Suppl 1:127-141

Clinic for Zoo Animals, Exotic Pets and Wildlife, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Carnivores do not vary markedly in their digestive efficiency for protein and fat, but whether they resemble other trophic guilds (omnivores and herbivores) in this respect has not been evaluated. We collated data on apparent crude protein (CP) and crude fat (ether extracts, EE) digestibility in 157 mammal species, applying the Lucas principle of regressing digestible nutrient content against nutrient content, where the slope of the regression equation represents the true digestibility and the intercept the metabolic losses per unit dry matter intake. The data collection is marked by the evident uneven distribution of dietary nutrient contents across trophic guilds and differences in the nutrient range by which different species have been evaluated, making statistical interpretation difficult. Results indicate a lower true digestibility of CP in herbivores compared to carnivores, most likely due to a lower digestibility of fibre-bound protein in herbivore diets. Metabolic CP losses did not appear to differ between trophic guilds, but herbivores had higher metabolic EE losses, compatible with the hypothesis that a higher proportion of metabolic CP losses were bound in microbes that also contain lipids in herbivores. Among herbivores, no clear pattern was evident that would indicate a difference in metabolic losses associated with microbes between digestive strategies (coprophagy, foregut/hindgut fermentation). Foregut fermenters had a lower true EE digestibility, possibly linked to the hydrogenation of lipids in their forestomach prior to digestion. The results do not demonstrate clear differences in digestive efficiency and metabolic losses for protein and fat between mammalian trophic guilds and digestive strategies, leading to the hypothesis that the process of CP and EE digestion is not physiologically challenging and hence does not lead to a noticeable differentiation between species or species groups.
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http://dx.doi.org/10.1111/jpn.12657DOI Listing
June 2017

X-ray absorption in pillar shaped transmission electron microscopy specimens.

Ultramicroscopy 2017 Jun 7;177:58-68. Epub 2017 Mar 7.

Imec, Kapeldreef 75, 3001 Leuven, Belgium; Instituut voor Kern- en Stralingsfysica, KU Leuven, 3001 Leuven, Belgium.

The dependence of the X-ray absorption on the position in a pillar shaped transmission electron microscopy specimen is modeled for X-ray analysis with single and multiple detector configurations and for different pillar orientations relative to the detectors. Universal curves, applicable to any pillar diameter, are derived for the relative intensities between weak and medium or strongly absorbed X-ray emission. For the configuration as used in 360° X-ray tomography, the absorption correction for weak and medium absorbed X-rays is shown to be nearly constant along the pillar diameter. Absorption effects in pillars are about a factor 3 less important than in planar specimens with thickness equal to the pillar diameter. A practical approach for the absorption correction in pillar shaped samples is proposed and its limitations discussed. The modeled absorption dependences are verified experimentally for pillars with HfO and SiGe stacks.
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http://dx.doi.org/10.1016/j.ultramic.2017.03.006DOI Listing
June 2017

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

Resuscitation 2016 12 12;109:49-55. Epub 2016 Oct 12.

Intensive Care Unit, CH Versailles, Le Chesnay (78), France. Electronic address:

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) were older, more frequently male and evidenced more frequently cardiovascular risk factors than normally (18.530kgm 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.
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http://dx.doi.org/10.1016/j.resuscitation.2016.09.011DOI Listing
December 2016

Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case-control study.

BMC Public Health 2016 Sep 29;16(1):1021. Epub 2016 Sep 29.

INSERM U1169, Hôpital Bicêtre, Université Paris-Sud, Kremlin-Bicêtre, France.

Background: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D.

Methods: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child's environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods.

Results: We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age.

Conclusions: The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas.

Trial Registration: Clinical-Trial.gov NCT02212522 . Registered August 6, 2014.
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http://dx.doi.org/10.1186/s12889-016-3690-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041527PMC
September 2016

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

Front Cell Neurosci 2016 9;10:191. Epub 2016 Aug 9.

UMR7355, Centre National de la Recherche ScientifiqueOrleans, France; Immunologie et Neurogénétique Expérimentales et Moléculaires, Experimental and Molecular Immunology and Neurogenetics, University of OrleansOrleans, France.

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.
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http://dx.doi.org/10.3389/fncel.2016.00191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977287PMC
August 2016

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

Clin Sci (Lond) 2016 11 22;130(21):1939-54. Epub 2016 Aug 22.

UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France

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 1β (IL-1β) 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.
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http://dx.doi.org/10.1042/CS20160530DOI Listing
November 2016

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

J Am Coll Cardiol 2016 07;68(1):40-9

Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Paris, France.

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).
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http://dx.doi.org/10.1016/j.jacc.2016.04.040DOI Listing
July 2016

Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium.

Neuroreport 2016 May;27(7):532-41

aFrench Armed Forces Biomedical Research Institute, Brétigny-sur-Orge bUMR7355, CNRS, Orléans cDepartment of Experimental and Molecular Immunology and Neurogenetics, University of Orleans dDepartment of Genetics, Regional Hospital, Orléans eCNRS, UMR-5203, Institute for Functional Genomics, Montpellier, France fDepartments of Internal Medicine Specialities and of Pathology-Immunology, Division of Rheumatology, University of Geneva School of Medicine, Geneva, Switzerland.

Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.
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http://dx.doi.org/10.1097/WNR.0000000000000578DOI Listing
May 2016
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