First-year French medical students consume antidepressants and anxiolytics while second-years consume non-medical drugs.

International audienc

Fungal microbiota from rain water and pathogenicity of Fusarium species isolated from atmospheric dust and rainfall dust

In order to determine the presence of Fusarium spp. in atmospheric dust and rainfall dust, samples were collected during September 2007, and July, August, and October 2008. The results reveal the prevalence of airborne Fusarium species coming from the atmosphere of the South East coast of Spain. Five different Fusarium species were isolated from the settling dust: Fusarium oxysporum, F. solani, F. equiseti, F. dimerum, and F. proliferatum. Moreover, rainwater samples were obtained during significant rainfall events in January and February 2009. Using the dilution-plate method, 12 fungal genera were identified from these rainwater samples. Specific analyses of the rainwater revealed the presence of three species of Fusarium: F. oxysporum, F. proliferatum and F. equiseti. A total of 57 isolates of Fusarium spp. obtained from both rainwater and atmospheric rainfall dust sampling were inoculated onto melon (Cucumis melo L.) cv. Piñonet and tomato (Lycopersicon esculentum Mill.) cv. San Pedro. These species were chosen because they are the main herbaceous crops in Almeria province. The results presented in this work indicate strongly that spores or propagules of Fusarium are able to cross the continental barrier carried by winds from the Sahara (Africa) to crop or coastal lands in Europe. Results show differences in the pathogenicity of the isolates tested. Both hosts showed root rot when inoculated with different species of Fusarium, although fresh weight measurements did not bring any information about the pathogenicity. The findings presented above are strong indications that long-distance transmission of Fusarium propagules may occur. Diseases caused by species of Fusarium are common in these areas. They were in the past, and are still today, a problem for greenhouses crops in Almería, and many species have been listed as pathogens on agricultural crops in this region. Saharan air masses dominate the Mediterranean regions. The evidence of long distance dispersal of Fusarium spp. by atmospheric dust and rainwater together with their proved pathogenicity must be taken into account in epidemiological studies

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints

Background: Genomic disorders are caused by copy number changes that may exhibit recurrent breakpoints processed by nonallelic homologous recombination. However, region-specific disease-associated copy number changes have also been observed which exhibit non-recurrent breakpoints. The mechanisms underlying these non-recurrent copy number changes have not yet been fully elucidated. Results: We analyze large NF1 deletions with non-recurrent breakpoints as a model to investigate the full spectrum of causative mechanisms, and observe that the

ESGAP inventory of target indicators assessing antibiotic prescriptions: A cross-sectional survey

Background A variety of indicators is commonly used to monitor antibiotic prescriptions as part of national antimicrobial stewardship (AMS) programmes. Objectives To make an inventory of indicators that assess antibiotic prescriptions and are linked to specific targets and incentives, at a national level. Methods A cross-sectional survey (three-item questionnaire) was conducted in 2017 among all ESGAP (ESCMID Study Group for Antimicrobial stewardshiP) members, coming from 23 European countries and 16 non-European countries. Results Almost all (20/23, 87%) European countries belonging to the ESGAP network participated, as well as one non-European country. Computerized systems routinely linking antibiotic prescriptions to clinical diagnoses were reported for only two countries (Turkey and Croatia). Only 6/21 (29%) countries had national indicators with both clear targets and incentives (Bulgaria, Croatia, France, the Netherlands, Norway and Portugal). We identified a total of 21 different indicators used in these countries, 16 concerning inpatients (9 quality indicators and 7 quantity metrics) and 8 concerning outpatients (all quantity metrics); some indicators were used in both settings. Three types of incentives were used: financing mechanism, hospitals' accreditation and public reporting. Some respondents reported that such indicators with both clear targets and incentives were used at a regional level in their country (e.g. Andalusia in Spain and England in the UK). Conclusions National indicators, with clear targets and incentives, are not commonly used in Europe and we observed wide variations between countries regarding the selected indicators, the units of measure and the chosen targets

Status and future development of Heating and Current Drive for the EU DEMO

The European DEMO is a pulsed device with pulse length of 2 hours. The functions devoted to the heating and current drive system are: plasma breakdown, plasma ramp-up to the flat-top where fusion reactions occur, the control of the plasma during the flat-top phase, and finally the plasma ramp-down. The EU-DEMO project was in a Pre-Concept Design Phase during 2014-2020, meaning that in some cases, the design values of the device and the precise requirements from the physics point of view were not yet frozen. A total of 130 MW was considered for the all phases of the plasma: in the flat top, 30 MW is required for neoclassical tearing modes (NTM) control, 30 MW for burn control, and 70 MW for the control of thermal instability (TI), without any specific functions requested from each system, Electron Cyclotron (EC), Ion Cyclotron (IC), or Neutral Beam (NB) Injection. At the beginning of 2020, a strategic decision was taken, to consider EC as the baseline for the next phase (in 2021 and beyond). R&D on IC and NB will be risk mitigation measures. In parallel with progresses in Physics modelling, a decision point on the heating strategy will be taken by 2024. This paper describes the status of the R&D development during the period 2014-2020. It assumes that the 3 systems EC, IC and NB will be needed. For integration studies, they are assumed to be implemented at a power level of at least 50 MW. This paper describes in detail the status reached by the EC, IC and NB at the end of 2020. It will be used in the future for further development of the baseline heating method EC, and serves as starting point to further develop IC and NB in areas needed for these systems to be considered for DEMO

IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation

The beneficial effects of insulin and insulin-like growth factor I on cognition have been documented in humans and animal models. Conversely, obesity, hyperinsulinemia, and diabetes increase the risk for neurodegenerative disorders including Alzheimer's disease (AD). However, the mechanisms by which insulin regulates synaptic plasticity are not well understood. Here, we report that complete disruption of insulin receptor substrate 2 (Irs2) in mice impairs long-term potentiation (LTP) of synaptic transmission in the hippocampus. Basal synaptic transmission and paired-pulse facilitation were similar between the 2 groups of mice. Induction of LTP by high-frequency conditioning tetanus did not activate postsynaptic N-methyl-D-aspartate (NMDA) receptors in hippocampus slices from Irs2−/− mice, although the expression of NR2A, NR2B, and PSD95 was equivalent to wild-type controls. Activation of Fyn, AKT, and MAPK in response to tetanus stimulation was defective in Irs2−/− mice. Interestingly, IRS2 was phosphorylated during induction of LTP in control mice, revealing a potential new component of the signaling machinery which modulates synaptic plasticity. Given that IRS2 expression is diminished in Type 2 diabetics as well as in AD patients, these data may reveal an explanation for the prevalence of cognitive decline in humans with metabolic disorders by providing a mechanistic link between insulin resistance and impaired synaptic transmission