With the evolution of European and French regulations on animal experimentation in higher education, taking greater account of animal welfare, the University of Angers has developed a virtual animal experimentation software named Exavir. Used for practical work (PW) in physiology, pharmacology and toxicology in the Health, Sciences, and engineering curricula, Exavir can be used to simulate various experiments for teaching purposes, in vivo or ex vivo. Thanks to an original approach integrating serious games with different scenarios, students gain autonomy and become directly involved in their learning. In addition, Exavir's collaborative and participative development approach fosters inter-university partnerships and the emergence of innovative teaching methods. A hybrid pilot study carried out on a sample of 22 students in the Pharmacy Department of the Faculty of Health showed that Exavir improved students' acquisition of teaching skills in both physiology and pharmacology, compared with practical work only based on animal organs. These encouraging results demonstrate for the first time the pedagogical advantages of Exavir and confirm the interest in developing such a platform. In this context, it appears that Exavir also opens up the possibility of adapting the practical work offered within universities, and thus responding to the changing ethical issues of the coming decades.
The Optimal Defense Theory (ODT) predicts that the distribution of defenses within a plant should mirror the value and vulnerability of each tissue. Although the ODT has received much experimental support, very few studies have examined defense allocation among reproductive tissues and none assessed simultaneously how these defenses evolve with age. We quantified glucosinolates in perianths, anthers and pistils at different bud maturity stages (i.e., intermediate flower buds, old flower buds and flowers) of undamaged and mechanically damaged plants of an annual brassicaceous species. The youngest leaf was used as a reference for vegetative organs, since it is predicted to be one of the most defended. In line with ODT predictions, reproductive tissues were more defended than vegetative tissues constitutively, and within the former, pistils and anthers more defended than perianths. No change in the overall defense level was found between bud maturity stages, but a significant temporal shift was observed between pistils and anthers. Contrary to ODT predictions, mechanical damage did not induce systemic defenses in leaves but only in pistils. Our results show that defense allocation in plant reproductive tissues occurs at fine spatial and temporal scales, extending the application framework of the ODT. They also demonstrate interactions between space and time in fine-scale defense allocation.
Glucosinolates , Plant Leaves , Flowers , Age Factors
The fungal phytopathogen Leptosphaeria maculans, which causes stem canker (blackleg) of rapeseed (Brassica napus), is mainly controlled worldwide by genetic resistance, which includes major resistance genes (Rlm). This model is one of those for which the highest number of avirulence genes (AvrLm) has been cloned. In many systems, including the L. maculans-B. napus interaction, intense use of resistance genes exerts strong selection pressure on the corresponding avirulent isolates, and the fungi may rapidly escape resistance through various molecular events which modify the avirulence genes. In the literature, the study of polymorphism at avirulence loci is often focused on single genes under selection pressure. In this study, we investigate allelic polymorphism at 11 avirulence loci in a French population of 89 L. maculans isolates collected on a trap cultivar in four geographic locations in the 2017-2018 cropping season. The corresponding Rlm genes have been (i) used for a long time, (ii) recently used, or (iii) unused in agricultural practice. The sequence data generated indicate an extreme diversity of situations. For example, genes submitted to an ancient selection may have either been deleted in populations (AvrLm1) or replaced by a single-nucleotide mutated virulent version (AvrLm2, AvrLm5-9). Genes that have never been under selection may either be nearly invariant (AvrLm6, AvrLm10A, AvrLm10B), exhibit rare deletions (AvrLm11, AvrLm14), or display a high diversity of alleles and isoforms (AvrLmS-Lep2). These data suggest that the evolutionary trajectory of avirulence/virulence alleles is gene-dependent and independent of selection pressure in L. maculans. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Ascomycota , Brassica napus , Brassica , Ascomycota/genetics , Plant Diseases/microbiology , Polymorphism, Genetic , Brassica napus/microbiology
While new targeted therapies have considerably changed the treatment and prognosis of non-small cell lung cancer (NSCLC), they are frequently unsuccessful due to primary or acquired resistances. Chemoresistance is a complex process that combines cancer cell intrinsic mechanisms including molecular and genetic abnormalities, aberrant interactions within the tumor microenvironment, and the pharmacokinetic characteristics of each molecule. From a pharmacological point of view, two levers could improve the response to treatment: (i) developing tools to predict the response to chemo- and targeted therapies and (ii) gaining a better understanding of the influence of the tumor microenvironment. Both personalized medicine approaches require the identification of relevant experimental models and biomarkers to understand and fight against chemoresistance mechanisms. After describing the main therapies in NSCLC, the scope of this review will be to identify and to discuss relevant in vitro and ex vivo experimental models that are able to mimic tumors. In addition, the interests of these models in the predictive responses to proposed therapies will be discussed. Finally, this review will evaluate the involvement of novel secreted biomarkers such as tumor DNA or micro RNA in predicting responses to anti-tumor therapies.
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Biomarkers, Tumor/genetics , Prognosis , Tumor Microenvironment
Breast cancer (BC) occurs less frequently in Asia, where there is high soy consumption. It has been hypothesized that soy isoflavones could be protective against BC recurrence and mortality. At the same time, health organizations in several countries have differing recommendations for soy consumption (soy foods or dietary supplements) in BC survivors. The objective of this review is to analyze the literature and to determine whether it is justified to advise avoiding soy in dietary supplements and/or food in women with a history of BC. We conducted a systematic literature search with the Medline/Pubmed and Web of Science databases. Only prospective cohort studies published since 2009 were retained. The endpoint of studies was BC recurrence and/or mortality, and the association with soy isoflavone intake was specifically targeted. Seven studies were included. None of these studies found statistically significant adverse effects of soy consumption on BC recurrence or mortality (specific or all-cause). Overall, only one study was not able to find beneficial effects of soy intake on BC patients. The other studies concluded that there were positive associations but in very variable ways. Two studies found a decrease in BC recurrence associated with a higher isoflavone intake only for post-menopausal women. The other four studies concluded that there were positive associations regardless of menopausal status. Four studies showed better results on women with hormonal-sensitive cancer and/or patients receiving hormonal treatment. Only one found a stronger association for patients with ER-negative BC. No adverse effects of soy isoflavones on BC mortality/recurrence were found. Soy isoflavones may exert beneficial effects. These results coincide with other recent works and suggest that soy isoflavone intake is safe for BC survivors. Thus, these data no longer seem to coincide with the French recommendations, which could then be brought to evolve. However, in order to confirm the current results, larger studies are needed.
BACKGROUND: Improving crop resistance to insect herbivores is a major research objective in breeding programs. Although genomic technologies have increased the speed at which large populations can be genotyped, breeding programs still suffer from phenotyping constraints. The pollen beetle (Brassicogethes aeneus) is a major pest of oilseed rape for which no resistant cultivar is available to date, but previous studies have highlighted the potential of white mustard as a source of resistance and introgression of this resistance appears to be a promising strategy. Here we present a phenotyping protocol allowing mid-throughput (i.e., increased throughput compared to current methods) acquisition of resistance data, which could then be used for genetic mapping of QTLs. RESULTS: Contrasted white mustard genotypes were selected from an initial field screening and then evaluated for their resistance under controlled conditions using a standard phenotyping method on entire plants. We then upgraded this protocol for mid-throughput phenotyping, by testing two alternative methods. We found that phenotyping on detached buds did not provide the same resistance contrasts as observed with the standard protocol, in contrast to the phenotyping protocol with miniaturized plants. This protocol was then tested on a large panel composed of hundreds of plants. A significant variation in resistance among genotypes was observed, which validates the large-scale application of this new phenotyping protocol. CONCLUSION: The combination of this mid-throughput phenotyping protocol and white mustard as a source of resistance against the pollen beetle offers a promising avenue for breeding programs aiming to improve oilseed rape resistance. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Vaccination against Covid-19 is among the most effective measures to reduce severe forms and deaths from Sars-CoV-2. To improve accessibility to the vaccines, French pharmacists were authorized to prescribe and administer them in March 2021. The PharmaCoVax study, which aims to assess the satisfaction of users who have benefited from this service, was conducted in pharmacies from March 16 to June 30, 2021.
The Dothideomycete Leptosphaeria maculans, causing stem canker (blackleg) of Brassica napus, secretes different cocktails of effectors at specific infection stages. Some effectors ("Late" effectors) are specifically produced during the long asymptomatic phase of stem colonization. By manipulating their expression so that they are overexpressed during cotyledon infection (OEC transformants of the fungus), we previously postulated that resistance genes operating in the stem may be involved in gene-for-gene relationship and thus contribute to quantitative disease resistance (QDR). Here, we selected 10 relevant new effector genes, and we generated OEC transformants to screen a collection of 130 B. napus genotypes, representative of the available diversity in the species. Five B. napus accessions showed a typical hypersensitive response when challenged with effectors LmSTEE98 or LmSTEE6826 at the cotyledon stage, and all belong to the semi-winter type of the diversity panel. In addition, five winter-type genotypes displayed an intermediate response to another late effector, LmSTEE7919. These new interactions now have to be genetically validated to check that they also correspond to gene-for-gene interactions. In all cases, they potentially provide novel resources, easy to breed for, and accounting for part of the quantitative resistance in a species for which we are currently facing limited resistance sources.
Urinary tract infections, especially cystitis, are common infections; they are the second most prevalent cause of antibiotic prescriptions in community pharmacies. To reduce antimicrobial resistance, guidelines are revised regularly. This study aims to assess compliance between prescriptions collected in community pharmacies and French cystitis guidelines. A treatment is considered compliant if the nature, dosage, and duration of the antibiotics are correct. Only women aged 18-65 years with a diagnosis of cystitis were eligible. The participation of 16 pharmacies resulted in 303 prescriptions. Most infections were classified as uncomplicated cystitis (79.2%), general practitioners were the prescribers in more than 9 out of 10 cases, and fosfomycin trometamol was the antibiotic dispensed for 1 in 2 women. An average compliance of 66% was observed, but with disparities according to the type of cystitis. Two-thirds of cases of uncomplicated cystitis and recurrent cystitis followed the recommendations, whereas only 15% of cystitis cases that were at risk of complication did so. The inclusion of a urine examination in uncomplicated cystitis decreased the overall compliance rate to 5.8%. These results show the essential role played by pharmacists; they are the last line of defence before dispensing antibiotics. They must know the recommendations in order to apply them.
The nirmatrelvir-ritonavir (Paxlovid®) is a treatment against Covid-19 available in pharmacies since February 4, 2022. Administered orally, it is intended only for people at very high risk of contracting one or more severe forms of the disease.
The use of short-acting beta-2 agonists (SABAs) is more common in elite athletes than in the general population, especially in endurance sports. The World Anti-Doping Code places some restrictions on prescribing inhaled ß2-agonists. These drugs are used in respiratory diseases (such as asthma) that might reduce athletes' performances. Recently, studies based on the results of the Olympic Games revealed that athletes with confirmed asthma/airway hyperresponsiveness (AHR) or exercise-induced bronchoconstriction (EIB) outperformed their non-asthmatic rivals. This overuse of SABA by high-level athletes, therefore, raises some questions, and many explanatory hypotheses are proposed. Asthma and EIB have a high prevalence in elite athletes, especially within endurance sports. It appears that many years of intensive endurance training can provoke airway injury, EIB, and asthma in athletes without any past history of respiratory diseases. Some sports lead to a higher risk of asthma than others due to the hyperventilation required over long periods of time and/or the high environmental exposure while performing the sport (for example swimming and the associated chlorine exposure). Inhaled corticosteroids (ICS) have a low efficacy in the treatment of asthma and EIB in elite athletes, leading to a much greater use of SABAs. A significant proportion of these high-level athletes suffer from non-allergic asthma, involving the th1-th17 pathway.
BACKGROUND: COVID-19 vaccines are among the most effective measures to reduce serious illness and death from infection with the highly contagious SARS-CoV-2 virus. To improve vaccine accessibility, pharmacists in France have been authorized to administer COVID-19 vaccinations since March 2021. This study aims to assess satisfaction among French people receiving their COVID-19 vaccination from a community pharmacist. METHODOLOGY: The PharmaCoVax study was conducted in French community pharmacies from 16 March to 30 June 2021. Interested pharmacists completed an online participation form, giving them access to the self-administered questionnaire. People receiving a pharmacist-administered COVID-19 vaccination completed this questionnaire in the pharmacy. RESULTS: Among the 442 pharmacists involved, 123 actively participated in the study. Overall, 5733 completed questionnaires were analyzed. A proportion of 59% (n = 3388) of those who received a pharmacist-administered COVID-19 vaccination had previously received their influenza vaccination, most often in the same pharmacy (n = 1744). Only 24% (n = 1370) of people visiting a pharmacy had tried to obtain their COVID-19 vaccination elsewhere. Satisfaction was excellent with a rating of 4.92 out of 5.00, and the net promoter score was 93. CONCLUSIONS: The pharmacist-administered COVID-19 vaccination service was overwhelmingly appreciated by users. The trust placed in pharmacists may explain the desire to have them perform additional vaccinations.
BACKGROUND: Inappropriate medication use or suboptimal medication adherence among polymedicated older patients is a public health concern. To tackle this issue, a pharmacist-led shared medication review (SMR) system was implemented in French community pharmacies in March 2018. SMR is an analysis of the drug treatments of the older patient with multiple medications. SMR takes place in the form of several interviews, at the pharmacy with the pharmacist, in a confidential space. OBJECTIVES: This observational real-world study evaluated the impact of the SMR service on medication adherence among polymedicated older patients in France. The risk of drug-related iatrogenic events in this population and the extent to which pharmacist SMR recommendations were followed by prescribers were also assessed. METHODS: Data were collected using the Observia webtool made by Observia society, a purpose-built digital platform distributed nationwide to community pharmacies to facilitate the SMR process. RESULTS: Data were analyzed from 439 patients (aged 65-75 years or older) who had completed their SMR at one of 297 French community pharmacies equipped with the Observia webtool. Overall, 186 patients had suboptimal adherence before SMR; 47% of these patients (n = 88) improved to have good adherence after completing the review. The rate of SMR-recommended prescription changes implemented by prescribers was low (14.7%; 38 of 258), with changes being implemented precisely as recommended in 47.4% of cases (n = 18). Potential iatrogenic events were identified in 20 patients. CONCLUSIONS: Although the SMR service is in the early stages of implementation in France, this study revealed that the process had a positive impact on medication adherence among older polymedicated patients. However, improvements are needed to reinforce prescriber and patient confidence in the system and further improve health outcomes.
Community Pharmacy Services , Pharmacies , Humans , Medication Adherence , Medication Review , Pharmacists , Retrospective Studies
Plant genomes demonstrate significant presence/absence variation (PAV) within a species; however, the factors that lead to this variation have not been studied systematically in Brassica across diploids and polyploids. Here, we developed pangenomes of polyploid Brassica napus and its two diploid progenitor genomes B. rapa and B. oleracea to infer how PAV may differ between diploids and polyploids. Modelling of gene loss suggests that loss propensity is primarily associated with transposable elements in the diploids while in B. napus, gene loss propensity is associated with homoeologous recombination. We use these results to gain insights into the different causes of gene loss, both in diploids and following polyploidization, and pave the way for the application of machine learning methods to understanding the underlying biological and physical causes of gene presence/absence.
Brassica napus , Brassica , Brassica/genetics , Brassica napus/genetics , Diploidy , Genome, Plant/genetics , Polyploidy
BACKGROUND: Urinary tract infections (UTIs) are among the most common infections that require antibiotic therapy. In December 2015, new guidelines for UTI management were published in France with the aim of reducing antibiotic misuse and the risk of antimicrobial resistance. OBJECTIVES: To analyze changes in antibiotic prescribing behavior for acute uncomplicated UTI in women in France from 2014 to 2019. METHODS: Retrospective study using data extracted from the medico-administrative database 'OpenMedic' that is linked to the French National Health Data System and collects data on the reimbursement of prescribed drugs. The analyses focused on the number of boxes of antibiotics delivered by community pharmacies, the molecule class, and the prescriber's specialty. RESULTS: Overall, antibiotic dispensing by community pharmacies increased by 2% between 2014 and 2019, but with differences in function of the antibiotic class. The use of antibiotics recommended as first-line and second-line treatment increased (+ 41% for fosfomycin and + 7430% for pivmecillinam). Conversely, the dispensing of lomefloxacin and norfloxacin decreased by 80%, and that of ciprofloxacin by 26%. Some antibiotics were mostly prescribed by general practitioners (lomefloxacin, pivmecillinam) and others by secondary care physicians (ofloxacin). Dispensing increased for antibiotics prescribed by secondary care physicians (+ 13% between 2014 and 2019) and decreased for antibiotics prescribed by GPs (- 2% for the same period). CONCLUSION: These data suggest that the new recommendations are followed, as indicated by the increased prescription of fosfomycin and pivmecillinam and decreased prescription of fluoroquinolones. However, the efficient transmission and implementation of new recommendations by practitioners requires time, means and dedicated tools.
General Practitioners , Urinary Tract Infections , Anti-Bacterial Agents/therapeutic use , Female , France/epidemiology , Humans , Practice Patterns, Physicians' , Retrospective Studies , Urinary Tract Infections/drug therapy
The control of stem canker disease of Brassica napus (rapeseed), caused by the fungus Leptosphaeria maculans is based largely on plant genetic resistance: single-gene specific resistance (Rlm genes) or quantitative, polygenic, adult-stage resistance. Our working hypothesis was that quantitative resistance partly obeys the gene-for-gene model, with resistance genes 'recognizing' fungal effectors expressed during late systemic colonization. Five LmSTEE (stem-expressed effector) genes were selected and placed under the control of the AvrLm4-7 promoter, an effector gene highly expressed at the cotyledon stage of infection, for miniaturized cotyledon inoculation test screening of a gene pool of 204 rapeseed genotypes. We identified a rapeseed genotype, 'Yudal', expressing hypersensitive response to LmSTEE98. The LmSTEE98-RlmSTEE98 interaction was further validated by inactivation of the LmSTEE98 gene with a CRISPR-Cas9 approach. Isolates with mutated versions of LmSTEE98 induced more severe stem symptoms than the wild-type isolate in 'Yudal'. This single-gene resistance was mapped in a 0.6 cM interval of the 'Darmor_bzh' × 'Yudal' genetic map. One typical gene-for-gene interaction contributes partly to quantitative resistance when L. maculans colonizes the stems of rapeseed. With numerous other effectors specific to stem colonization, our study provides a new route for resistance gene discovery, elucidation of quantitative resistance mechanisms and selection for durable resistance.
Ascomycota , Brassica napus , Disease Resistance , Plant Diseases , Ascomycota/genetics , Ascomycota/pathogenicity , Brassica napus/genetics , Brassica napus/microbiology , Cotyledon , Disease Resistance/genetics , Genes, Plant , Plant Diseases/genetics , Plant Diseases/microbiology
Tumor cell vasculogenic mimicry (VM), also dubbed vascular mimicry, describes the plasticity of aggressive cancer cells forming de novo vascular networks and is associated with the malignant phenotype and poor clinical outcome. VM is described in a plethora of tumors, including carcinomas, sarcomas, glioblastomas, astrocytomas and melanomas. The presence of VM is associated with a high tumor grade, short survival, invasion and metastasis. A variety of molecular mechanisms and signal pathways participates in VM induction and formation. Due to VM's contribution on tumor progression, more VM-related strategies are being utilized for anticancer treatment. After describing the main features of VM, this review will outline the importance of the tumor microenvironment during this process, and highlight the predominant molecular targets and signaling pathways involved. These data will make it possible to discuss the importance of VM-associated mediators in antitumor therapy and how it could allow to better understand the resistance to anticancer therapy.
Carcinogenesis , Neovascularization, Pathologic , Carcinogenesis/drug effects , Carcinogenesis/pathology , Humans , Neovascularization, Pathologic/drug therapy
