A recruitment maneuver increases oxygenation after intubation of hypoxemic intensive care unit patients: a randomized controlled study

International audienc

Mental Health Prevention and Promotion in General Practice Settings: A Protocol for a Feasibility Study

Background A reactive approach is typically taken when addressing and intervening with mental health problems rather than a proactive or preventative one, yet preventative approaches can also reduce mental ill-health. This study protocol aims to evaluate the feasibility of recruiting general practice patients into a randomised feasibility study where they will receive either mental health treatment as usual or a brief psychological intervention for preventing the deterioration of mental health and promoting emotional wellbeing. Methods This is a two-arm RCT, where participants will be randomised to either: treatment-as-usual within GP; or treatment-as-usual within GP plus a mental health prevention and promotion intervention. Sixty patients, aged 16+ from GP surgeries, with mild to moderate mental health difficulties as indicated by the PHQ9 and GAD7 will be recruited. Data on engagement with the intervention will be summarised using descriptive statistics. Regression models will be fitted, using the 12-week post-intervention follow-up data as the outcome variable and age, gender, trial arm and the corresponding baseline data as covariates. Cost-effectiveness will be investigated in an explorative way. Descriptive statistics will be used to analyse participant's resource use and HRQoL. Qualitative data will understand factors that facilitate or challenge the successful implementation of interventions and a process evaluation will provide insight into the intervention's mechanisms of action. Discussion The research team will progress from a feasibility RCT to a larger definitive RCT and disseminate widely across stakeholders (clinical, academic, service users, caregivers, Integrated Care Board (ICB) colleagues), ensuring accessibility in collaboration with the PPI committee

Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets

AbstractDietary supplementations with n-3 polyunsaturated fatty acid (PUFA) have been explored in autism spectrum disorder (ASD) but their efficiency and potential in ameliorating cardinal symptoms of the disease remain elusive. Here, we compared a n-3 long-chain (LC) PUFA dietary supplementation (n-3 supp) obtained from fatty fish with a n-3 PUFA precursor diet (n-3 bal) obtained from plant oils in the valproic acid (VPA, 450 mg/kg at E12.5) ASD mouse model starting from embryonic life, throughout lactation and until adulthood. Maternal and offspring behaviors were investigated as well as several VPA-induced ASD biological features: cerebellar Purkinje cell (PC) number, inflammatory markers, gut microbiota, and peripheral and brain PUFA composition. Developmental milestones were delayed in the n-3 supp group compared to the n-3 bal group in both sexes. Whatever the diet, VPA-exposed offspring did not show ASD characteristic alterations in social behavior, stereotypies, PC number, or gut microbiota dysbiosis while global activity, gait, peripheral and brain PUFA levels as well as cerebellar TNF-alpha levels were differentially altered by diet and treatment according to sex. The current study provides evidence of beneficial effects of n-3 PUFA based diets, including one without LCPUFAs, on preventing several behavioral and cellular symptoms related to ASD

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Structures and dissociation mechanisms of protonated and electron ionized methamidophos

International audienceMethamidophos, 1, is examined by tandem mass spectrometry (Q-TOF) under electrospray ionization in the positive ion mode (ESI-P). Variable collision energy MS-MS mass spectra of protonated methamidophos, 1H(+), reveal that CH2O, CH3SH, CH3OH and NH3 losses occur with comparable threshold energies. Fragmentations leading to m/z 125, 112,110, 94, 79 and m/z 64 ions are explained by combinations of 1,2-elimination reactions and isomerizations via 1,3-proton migrations as supported by B3LYP/6-31+G(d) calculations. The behavior of electron ionized methamidophos, 1(center dot+), particularly its fragmentations by losses of (SCH3)-S-center dot and CH2S, is also explored at the B3LYP/6-31+G(d) level. G4MP2 calculation shows that protonation of 1 occurs preferentially at the oxygen atom of the P=O group with a corresponding proton affinity equal to PA(1) = 897 kJ mol(-1). Calculated G4MP2 ionization energy and heat of formation of methamidophos are IE(1) = 8.77 eV and Delta H-f(298)degrees(1)=-626 kJ mol(-1). (Cop) 2013 Elsevier B.V. All rights reserved

Cortical lesion stimulates adult subventricular zone neural progenitor cell proliferation and migration to the site of injury

International audienceThe subventricular zone (SVZ) is the principal neurogenic niche present in the adult non-human mammalian brain. Neurons generated in the SVZ migrate along the rostral migratory stream to reach the olfactory bulb. Brain injuries stimulate SVZ neurogenesis and direct migration of new progenitors to the sites of injury. To date, cortical injury-induced adult SVZ neurogenesis in mice remains ambiguous and migration of neural progenitors to the site of injury has not been studied in detail. Here we report that aspiration lesion in the motor cortex induces a transient, but significant increase in the proliferation as well as neurogenesis in the SVZ. New neural progenitors migrate ectopically to the injured area with the assistance of blood vessels and reactive astrocytes. The SVZ origin of these progenitors was further confirmed using lentiviral transduction. In addition, we show that astrocyte-assisted ectopic migration is regulated by CXCR4/SDF-1 signaling pathway. Finally, upon reaching the lesion area, these progenitors differentiate mainly into glial cells and, to a lesser extent, mature neurons. These data provide a detailed account of the changes occurring in the SVZ and the cortex following lesion, and indicate the potential of the endogenous neural progenitors in cortical repair

Structural characterization of photoproducts of pyrimethanil

International audiencePyrimethanil is an anilino-pyrimidine fungicide particularly active against gray mold (Botrytis cinerea) and pear scab (Venturia inaequalis and Venturia pirina) on grapes, strawberries, tomatoes, fruits, vegetables and ornamental plants in greenhouses and open field situation.[1-5] According to the European Food Safety Authority, pyrimethanil has no evident mutagenic, genotoxic or carcinogenic potential, but a short-term toxicity study on rats and mice has shown an increase in liver weight accompanied by changes in the histopathology of the liver and thyroid.[6] To avoid these side effects, the concentration of pyrimethanil has been limited by legislation. The European Commission set the Maximum Residue Level of pyrimethanil at 10 mg/l in citrus fruits, 5 mg/l in pome fruits, strawberries, table and wine grapes and 0.05 mg/l in tree nuts (EC/600/2010).[7] It is thus important to increase our knowledge regarding the concentration of pyrimethanil in environmental matrices, its degradability and the factors affecting it. One of these factors is the photo alteration by sunlight, which is known to play a significant role in the degradation of this compound, due to the prolonged half-life (77 days approximately) of pyrimethanil in the environment.[8] Previous studies on the degradation of pyrimethanil were carried out mainly in a waste water treatment context and focused on the photo catalytic degradation using various salts as catalysts. Agüera et al.[9] used TiO2, Vanni et al.[10] and Anfossi et al.[11] added iron III, Navarro et al.[12] added ZnO and Gomis et al.[13] used thiopyrylium. Irradiation was carried out using a mercury or xenon lamp or direct sunlight. These studies have showed that a long irradiation time (between 150 and 1400 min, depending on the conditions and catalyst) is required for total disappearance of pyrimethanil. Degradation of pyrimethanil in water using the technique of photo-Fenton was investigated by Sirtori et al. They reported that the addition of sodium chloride accelerated the reaction and characterized four chlorinated photo-Fenton by-products.[14] The aim of the present study was the identification of UV-visible photo transformation products of pyrimethanil in water. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and gas chromatography coupled with multi stage mass spectrometry (GC-MSn) were used for analysis, with the aim of covering a large range of polarities for the detection of the potential transformation products. Elucidation of the structures of photoproducts was carried out performing high-resolution measurements and collision-induced dissociation (CID) experiments. Photolysis mechanisms have also been proposed to explain the formation of photo products of pyrimethanil in water