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Abstract Background Urinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score. Methods PharmaCyst’ is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student’s t-test. The qualitative data will be described using numbers and percentages and compared using chi2 test (or Fisher’s exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population. Discussion PharmaCyst’ is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol. Trial registration The protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

IntroductionAnimal nutritional strategies have been extensively studied in vertebrates, where generalism at the individual scale is the rule. In insect herbivores, the determinants of the nutritional strategy of individual-scale generalists remain poorly studied, and the focus has been placed mainly on the influence of plant defense. Moreover, the integration of a physiological dimension in such studies remains rare. Here, we investigated the determinants of the nutritional strategy of pre-diapausing pollen beetles, Brassicogethes aeneus, with a focus on the influence of macronutrients. Before their diapause, pollen beetles are known to feed from plants belonging to many different families. This raises three questions: (i) Is the generalism of pollen beetles a populational consequence of individuals specialized on different plant families? (ii) Do individuals feed at random on flowers available or do they have a particular nutritional strategy? and (iii) In case of non-random feeding choices, do pollen macronutrients explain this nutritional strategy?MethodsTo answer these questions, we used a series of laboratory experiments including feeding choice tests on flowers and artificial substrates, quantification of pollen nutrient content, quantification of the insect energetic budget, and performance experiments.ResultsWe show that pollen beetles are generalist at the individual scale, and that clear and stable food preferences are established over a few hours in a multi-choice context. Pollen beetles prefer to feed on flowers with a carbohydrate-rich pollen, and this preference is adaptive since performance correlates positively with the plant carbohydrate content. This better performance may be explained by the fact that individuals feeding on carbohydrate-rich resources accumulate more glycogen and total energetic reserves.DiscussionThis study represents one of the few evidences of generalism at the individual scale in an herbivorous insect. It provides a better understanding of the nutritional strategy of a non-bee pollen feeder and shows the importance of carbohydrates in this strategy. It highlights the need to combine assessments of the plant macronutrient content and insect energetic budget in an adaptive framework to better understand the nutritional strategies of herbivores.

Abstract 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.

Abstract 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.

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.

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 β2-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.

Red wine polyphenol compounds (RWPC) exert paradoxical effects depending on the dose on post-ischemic neovascularisation. Low dose RWPC (0.2 mg/kg/day) is pro-angiogenic, whereas high dose (20 mg/kg/day) is anti-angiogenic. We recently reported that the endothelial effect of RWPC is mediated through the activation of a redox-sensitive pathway, mitochondrial biogenesis and the activation of α isoform of the estrogen receptor (ERα). Here, we investigated the implication of ERα on angiogenic properties of RWPC. Using ovariectomized mice lacking ERα treated with high dose of RWPC after hindlimb ischemia, we examined blood flow reperfusion, vascular density, nitric oxide (NO) production, expression and activation of proteins involved in angiogenic process and muscle energy sensing network. As expected, high dose of RWPC treatment reduced both blood flow and vascular density in muscles of mice expressing ERα. These effects were associated with reduced NO production resulting from diminished activity of eNOS. In the absence of RWPC, ERα deficient mice showed a reduced neo-vascularisation associated with a decreased NO production. Surprisingly in mice lacking ERα, high dose of RWPC increased blood flow and capillary density in conjunction with increased NO pathway and production as well as VEGF expression. Of particular interest is the activation of Sirt-1, AMPKα and PGC-1α/β axis in ischemic hindlimb from both strains. Altogether, the results highlight a pro-angiogenic property of RWPC via an ERα-independent mechanism that is associated with an up-regulation of energy sensing network. This study brings a corner stone of a novel pathway for RWPC to correct cardiovascular diseases associated with failed neovascularisation.

Progress in extending the life expectancy of cystic fibrosis (CF) patients remains jeopardized by the increasing incidence of fungal respiratory infections. Pseudallescheria boydii (P. boydii), an emerging pathogen of humans, is a filamentous fungus frequently isolated from the respiratory secretions of CF patients. It is commonly believed that infection by this fungus occurs through inhalation of airborne conidia, but the mechanisms allowing the adherence of Pseudallescheria to the host epithelial cells and its escape from the host immune defenses remain largely unknown. Given that the cell wall orchestrates all these processes, we were interested in studying its dynamic changes in conidia as function of the age of cultures. We found that the surface hydrophobicity and electronegative charge of conidia increased with the age of culture. Melanin that can influence the cell surface properties, was extracted from conidia and estimated using UV-visible spectrophotometry. Cells were also directly examined and compared using electron paramagnetic resonance (EPR) that determines the production of free radicals. Consistent with the increased amount of melanin, the EPR signal intensity decreased suggesting polymerization of melanin. These results were confirmed by flow cytometry after studying the effect of melanin polymerization on the surface accessibility of mannose-containing glycoconjugates to fluorescent concanavalin A. In the absence of melanin, conidia showed a marked increase in fluorescence intensity as the age of culture increased. Using atomic force microscopy, we were unable to find rodlet-forming hydrophobins, molecules that can also affect conidial surface properties. In conclusion, the changes in surface properties and biochemical composition of the conidial wall with the age of culture highlight the process of conidial maturation. Mannose-containing glycoconjugates that are involved in immune recognition, are progressively masked by polymerization of melanin, an antioxidant that is commonly thought to allow fungal escape from the host immune defenses.

Endothelial dysfunction precedes atherosclerosis. Vasodilation induced by acetylcholine (ACh) is a specific test of endothelial function. Reproducibility of laser techniques such as laser-Doppler-flowmetry (LDF) and Laser-speckle-contrast-imaging (LSCI) to detect ACh vasodilation is debated and results expressions lack standardization. We aimed to study at a 7-day interval (i) the inter-subject reproducibility, (ii) the intra-subjects reproducibility, and (iii) the effect of the results expressions over variability.Using LDF and LSCI simultaneously, we performed two different ACh-iontophoresis protocols. The maximal ACh vasodilation (peak-ACh) was expressed as absolute or normalized flow or conductance values. Inter-subject reproducibility was expressed as coefficient of variation (inter-CV,%). Intra-subject reproducibility was expressed as within subject coefficients of variation (intra-CV,%), and intra-class correlation coefficients (ICC). Fifteen healthy subjects were included. The inter-subject reproducibility of peak-ACh depended upon the expression of the results and ranged from 55% to 162% for LDF and from 17% to 83% for LSCI. The intra-subject reproducibility (intra-CV/ICC) of peak-ACh was reduced when assessed with LSCI compared to LDF no matter how the results were expressed and whatever the protocol used. The highest intra-subject reproducibility was found using LSCI. It was 18.7%/0.87 for a single current stimulation (expressed as cutaneous vascular conductance) and 11.4%/0.61 for multiple current stimulations (expressed as absolute value).ACh-iontophoresis coupled with LSCI is a promising test to assess endothelial function because it is reproducible, safe, and non-invasive. N°: NCT01664572.

We aimed to characterize circulating microparticles in association with arterial stiffness, inflammation and endothelial dysfunction in aldosterone-salt-induced hypertension in rats and to investigate the preventive effects of red wine polyphenols. Uninephrectomized male Sprague-Dawley rats were treated with aldosterone-salt (1 µg.h(-1)), with or without administration of either red wine polyphenols, Provinols™ (20 mg.kg(-1).day(-1)), or spironolactone (30 mg.kg(-1).day(-1)) for 4 weeks. Microparticles, arterial stiffness, nitric oxide (NO) spin trapping, and mesenteric arterial function were measured. Aldosterone-salt rats showed increased microparticle levels, including those originating from platelets, endothelium and erythrocytes. Hypertension resulted in enhanced aortic stiffness accompanied by increased circulating and aortic NO levels and an upregulation of aortic inducible NO-synthase, NFκB, superoxide anions and nitrotyrosine. Flow-induced dilatation was reduced in mesenteric arteries. These effects were prevented by spironolactone. Provinols™ did not reduce arterial stiffness or systolic hypertension but had effects similar to those of spironolactone on endothelial function assessed by flow-mediated vasodilatation, microparticle generation, aortic NO levels and oxidative stress and apoptosis in the vessel wall. Neither the contractile response nor endothelium-dependent relaxation in mesenteric arteries differed between groups. The in vivo effects of Provinols™ were not mediated by mineralocorticoid receptors or changes in shear stress. In conclusion, vascular remodelling and endothelial dysfunction in aldosterone-salt-mediated hypertension are associated with increased circulating microparticles. Polyphenols prevent the enhanced release of microparticles, macrovascular inflammation and oxidative stress, and microvascular endothelial dysfunction independently of blood pressure, shear stress and mineralocorticoid receptor activation in a model of hyperaldosteronism.

Microparticles are membrane vesicles with pro-inflammatory properties. Circulating levels of microparticles have previously been found to be elevated in patients with metabolic syndrome (MetS). The present study aimed to evaluate the effects of in vivo treatment with microparticles, from patients with MetS and from healthy subjects (HS), on ex vivo vascular function in mice. Microparticles isolated from MetS patients or HS, or a vehicle were intravenously injected into mice, following which vascular reactivity in response to vasoconstrictor agonists was assessed by myography with respect to cyclo-oxygenase pathway, oxidative and nitrosative stress. Injection of microparticles from MetS patients into mice induced vascular hypo-reactivity in response to serotonin. Hypo-reactivity was associated with up-regulation of inducible NO-synthase and increased production of NO, and was reversed by the NO-synthase inhibitor (N(G)-nitro-L-arginine). The selective COX-2 inhibitor (NS398) reduced the contractile effect of serotonin in aortas from mice treated with vehicle or HS microparticles; however, this was not observed within mice treated with MetS microparticles, probably due to the ability of MetS microparticles to enhance prostacyclin. MetS microparticle-mediated vascular dysfunction was associated with increased reactive oxygen species (ROS) and enhanced expression of the NADPH oxidase subunits. Neutralization of the pro-inflammatory pathway Fas/FasL completely prevented vascular hypo-reactivity and the ability of MetS microparticles to enhance both inducible NO-synthase and monocyte chemoattractant protein-1 (MCP-1). Our data provide evidence that microparticles from MetS patients induce ex vivo vascular dysfunction by increasing both ROS and NO release and by altering cyclo-oxygenase metabolites and MCP-1 through the Fas/FasL pathway.