Efficacy of self-management program associated with a spa therapy for knee osteoarthritis patients (GETT 2): a research protocol for a randomized trial.

INTRODUCTION: Osteoarthritis is a chronic pathology that involves multidisciplinary management. Self-management for patients is an essential element, present in all international guidelines. During the time of the spa therapy, the patient is receptive to take the advantage of self-management workshops. The aim of this study is to assess the effects of 18 days spa therapy associated with a self-management intervention in patients with knee osteoarthritis in comparison with spa therapy alone on a priority objective, personalized and determined with the patient, chosen in the list of 5 objectives determined during the self-management initial assessment. METHODS AND ANALYSIS: Two hundred fifty participants with knee osteoarthritis will participate to this multicenter, prospective, randomized, controlled study. All patients will benefit 18 days of spa therapy and patients randomized in the intervention group will participate to 6 self-management workshops. Randomization will be centralized. The allocation ratio will be 1:1. Data analysts and assessor will be blinded. The primary outcome is the effectiveness of the educational workshops associated with spa therapy in comparison with spa therapy alone on a priority objective, measured by Goal Attainment Scaling (GAS). The secondary outcomes are disability, health-related quality of life, and pain intensity. ETHICS AND DISSEMINATION: Ethics were approved by the CPP Sud-Méditerranée II. The results will be disseminated in a peer-reviewed journal and disseminated at PRM, rheumatology, and orthopedics conferences. The results will also be disseminated to patients. TRIAL REGISTRATION: Trial registration number NCT03550547. Registered 8 June 2018. Date and version identifier of the protocol. Version N°6 of March 12, 2018.

Comparative study of the insecticidal activity of a high green plant (Spinacia oleracea) and a chlorophytae algae (Ulva lactuca) extracts against Drosophila melanogaster fruit fly.

OBJECTIVES: Currently, the global interests tend to take advantage of the plant world as a renewable source of a natural and effective molecule, to find an eco-friendly, cost-effective, and less toxic alternative to the current synthetic pesticide. In this context, the present research was carried out in an attempt to study the insecticidal activity of extracts and pigments derived from the green plant Spinacia oleracea and the green alga Ulva lactuca against the fruit fly Drosophila melanogaster as an alternative to chemical insecticide. METHODS: The toxicity of the aqueous, acetonic and ethanolic extracts as well as of the purified pigments (Chlorophylls and carotenoids) was determined by complementary in vivo tests (application by spraying oranges, toxicity by ingestion and repellent activity). Interestingly, each one of these methods corresponds to a specific mode of exposure. RESULTS: Results showed that acetone extracts, which are rich in green pigments, present the best insecticidal activities. On the other hand, the purified chlorophyllian pigments exhibited an interesting activity only by spraying method. Regarding the repellent activity, the aqueous extract of spinach displayed higher effectiveness. CONCLUSION: Our study suggests the potential of tested plant and algal extracts, as well as of chlorophyllian pigments, to provide a safer alternative way to the use of synthetic pesticides.

Characterisation of Cutibacterium acnes phylotypes in acne and in vivo exploratory evaluation of Myrtacine®.

OBJECTIVE: Our main objective was to compare Cutibacterium acnes (C. acnes) skin colonisation in patients with mild to moderate acne versus healthy controls and secondly, to evaluate a Myrtacine® -based cream on C. acnes total population and antibioresistant Cutibacteria in patients with acne. METHODS: In 60 acne patients (Global Acne Severity Scale, GEA grades 2-3), of mean age 20 [15-30] years and in 24 age- and sex- matched healthy controls, forehead strips samplings were performed for microbiological analysis of comedones by colony forming unit (CFU) counts of global C. acnes and erythromycin (EryR) or clindamycin-resistant (ClnR) populations of Cutibacterium and determination of phylotypes by MALTI-TOF. Clinical evaluations of acne patients (GEA, lesion count, porphyrin fluorescence) were performed at baseline and after 56 days of twice-daily application of a Myrtacine® -based cream. RESULTS: We first showed (i) high and similar levels of C. acnes colonisation in superficial pilosebaceous follicles and detection of EryR and ClnR strains in both acne and control groups; (ii) different repartition of phylotypes in acne patients versus healthy control, with a predominance of phylotype IA in acne patients and a link between phylotype IA and erythromycin resistance. Besides, after treatment with the Myrtacine® -based cream in acne patients, there was no change in C. acnes total load, but a significant decrease of EryR Cutibacteria, reduced porphyrin production by C. acnes, a decrease in acne severity (GEA), associated with reduced retentional and inflammatory lesions. CONCLUSION: Cutibacterium acnes colonisation was not significantly different in acne versus control groups. Phylotype IA was predominant in acne patient and in EryR C. acnes. A Myrtacine® -based cream significantly reduced the level of EryR Cutibacteria in vivo and improved acne lesions.

Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates.

While the commensal bacterium Propionibacterium acnes (P. acnes) is involved in the maintenance of a healthy skin, it can also act as an opportunistic pathogen in acne vulgaris. The latest findings on P. acnes shed light on the critical role of a tight equilibrium between members of its phylotypes and within the skin microbiota in the development of this skin disease. Indeed, contrary to what was previously thought, proliferation of P. acnes is not the trigger of acne as patients with acne do not harbour more P. acnes in follicles than normal individuals. Instead, the loss of the skin microbial diversity together with the activation of the innate immunity might lead to this chronic inflammatory condition. This review provides results of the most recent biochemical and genomic investigations that led to the new taxonomic classification of P. acnes renamed Cutibacterium acnes (C. acnes), and to the better characterisation of its phylogenetic cluster groups. Moreover, the latest data on the role of C. acnes and its different phylotypes in acne are presented, providing an overview of the factors that could participate in the virulence and in the antimicrobial resistance of acne-associated strains. Overall, this emerging key information offers new perspectives in the treatment of acne, with future innovative strategies focusing on C. acnes biofilms and/or on its acne-associated phylotypes.

Antimicrobial activity of metal oxide microspheres: an innovative process for homogeneous incorporation into materials.

AIMS: To investigate the potent control of microbial surface contamination of an innovative process which consists in incorporating metal oxide microspheres homogeneously into materials. METHODS AND RESULTS: Spherical microspheres containing zinc and magnesium oxides synthesized via a one-step manufacturing process (Pyrolyse Pulvérisée® ) and incorporated into different plastic matrices were evaluated for their antimicrobial activity according to JIS Z 2801 standard. A significant activity was observed for microsphere-added polyethylene coupons with a reduction of all tested bacteria populations, including Gram negative and Gram positive even expressing acquired antibiotic resistance (Escherichia coli ESBL, Staphylococcus aureus metiR). An antiviral activity higher than 2 log of reduction was also observed on H1N1 and HSV-1 viruses. This antimicrobial effect was dose-dependent and time-dependent for both polyethylene and polypropylene matrices. Antimicrobial activity was maintained after exposition to disinfectants and totally preserved 50 months after the preparation of the coupons. CONCLUSIONS: Incorporated into plastic matrices, metal oxide microspheres showed significant antibacterial and antiviral activities. SIGNIFICANCE AND IMPACT OF STUDY: This is, to our knowledge, the first report on an original process incorporating metal oxide microspheres, which have specific physico-chemical and antimicrobial properties, into materials that could be used for surface contamination prevention.

Adsorption properties of BSA and DsRed proteins deposited on thin SiO2 layers: optically non-absorbing versus absorbing proteins.

Protein adsorption on solid surfaces is of interest for many industrial and biomedical applications, where it represents the conditioning step for micro-organism adhesion and biofilm formation. To understand the driving forces of such an interaction we focus in this paper on the investigation of the adsorption of bovine serum albumin (BSA) (optically non-absorbing, model protein) and DsRed (optically absorbing, naturally fluorescent protein) on silica surfaces. Specifically, we propose synthesis of thin protein layers by means of dip coating of the dielectric surface in protein solutions with different concentrations (0.01-5.0 g l-1). We employed spectroscopic ellipsometry as the most suitable and non-destructive technique for evaluation of the protein layers' thickness and optical properties (refractive index and extinction coefficient) after dehydration, using two different optical models, Cauchy for BSA and Lorentz for DsRed. We demonstrate that the thickness, the optical properties and the wettability of the thin protein layers can be finely controlled by proper tuning of the protein concentration in the solution. These results are correlated with the thin layer morphology, investigated by AFM, FTIR and PL analyses. It is shown that the proteins do not undergo denaturation after dehydration on the silica surface. The proteins arrange themselves in a lace-like network for BSA and in a rod-like structure for DsRed to form mono- and multi-layers, due to different mechanisms driving the organization stage.

Significant Change in Marine Plankton Structure and Carbon Production After the Addition of River Water in a Mesocosm Experiment.

Rivers are known to be major contributors to eutrophication in marine coastal waters, but little is known on the short-term impact of freshwater surges on the structure and functioning of the marine plankton community. The effect of adding river water, reducing the salinity by 15 and 30%, on an autumn plankton community in a Mediterranean coastal lagoon (Thau Lagoon, France) was determined during a 6-day mesocosm experiment. Adding river water brought not only nutrients but also chlorophyceans that did not survive in the brackish mesocosm waters. The addition of water led to initial increases (days 1-2) in bacterial production as well as increases in the abundances of bacterioplankton and picoeukaryotes. After day 3, the increases were more significant for diatoms and dinoflagellates that were already present in the Thau Lagoon water (mainly Pseudo-nitzschia spp. group delicatissima and Prorocentrum triestinum) and other larger organisms (tintinnids, rotifers). At the same time, the abundances of bacterioplankton, cyanobacteria, and picoeukaryote fell, some nutrients (NH4+, SiO43-) returned to pre-input levels, and the plankton structure moved from a trophic food web based on secondary production to the accumulation of primary producers in the mesocosms with added river water. Our results also show that, after freshwater inputs, there is rapid emergence of plankton species that are potentially harmful to living organisms. This suggests that flash flood events may lead to sanitary issues, other than pathogens, in exploited marine areas.

Proteobacteria from the human skin microbiota: Species-level diversity and hypotheses.

The human skin microbiota is quantitatively dominated by Gram-positive bacteria, detected by both culture and metagenomics. However, metagenomics revealed a huge variety of Gram-negative taxa generally considered from environmental origin. For species affiliation of bacteria in skin microbiota, clones of 16S rRNA gene and colonies growing on diverse culture media were analyzed. Species-level identification was achieved for 81% of both clones and colonies. Fifty species distributed in 26 genera were identified by culture, mostly belonging to Actinobacteria and Firmicutes, while 45 species-level operational taxonomic units distributed in 30 genera were detected by sequencing, with a high diversity of Proteobacteria. This mixed approach allowed the detection of 100% of the genera forming the known core skin Gram-negative microbiota and 43% of the known diversity of Gram-negative genera in human skin. The orphan genera represented 50% of the current skin pan-microbiota. Improved culture conditions allowed the isolation of Roseomonas mucosa, Aurantimonas altamirensis and Agrobacterium tumefaciens strains from healthy skin. For proteobacterial species previously described in the environment, we proposed the existence of skin-specific ecotypes, which might play a role in the fine-tuning of skin homeostasis and opportunistic infections but also act as a shuttle between environmental and human microbial communities. Therefore, skin-associated proteobacteria deserve to be considered in the One-Health concept connecting human health to the health of animals and the environment.

Bacterial colonization status of cystic fibrosis children's toothbrushes: A pilot study.

BACKGROUND: Pseudomonas aeruginosa and Staphylococcus aureus toothbrush contamination in cystic fibrosis (CF) is unknown. This pilot study aimed to determine their prevalence and the potential involvement of toothbrushes in pulmonary infection. METHODS: Toothbrush bacteriological analysis for children aged 8-18 years was conducted on 27 CF patients, 15 healthy siblings, and 15 healthy children from the general population. RESULTS: S. aureus was detected on 22% of the patients' toothbrushes, and 13% of healthy children's toothbrushes and P. aeruginosa on 15% of patients' toothbrushes and 0-13% of healthy children's toothbrushes. There was no statistical correlation between pulmonary colonization and toothbrush contamination. P. aeruginosa genotyping showed two identical clones on the patients' toothbrushes and in their sputum, and between one patient's sputum and his sibling's toothbrush. CONCLUSION: S. aureus and P. aeruginosa can colonize CF patients' toothbrushes. The impact on pulmonary colonization remains unknown. Toothbrush decontamination methods need to consider these bacteria in CF patients.

Phenotypic and genotypic characterization of lactic acid bacteria isolated from raw goat milk and effect of farming practices on the dominant species of lactic acid bacteria.

Lactic acid bacteria, in particular Lactococcus lactis, play a decisive role in the cheese making process and more particularly in lactic cheeses which are primarily produced on goat dairy farms. The objective of this study was therefore to identify the main lactic acid bacteria found in raw goats' milk from three different regions in France and evaluate if certain farming practices have an effect on the distribution of species of lactic acid bacteria in the various milk samples. Identification at genus or species level was carried out using phenotypic tests and genotypic methods including repetitive element REP-PCR, species-specific PCR and 16S rRNA gene sequencing. The distribution of the main bacterial species in the milk samples varied depending on farms and their characteristics. Out of the 146 strains identified, L. lactis was the dominant species (60% of strains), followed by Enterococcus (38%) of which Enterococcus faecalis and Enterococcus faecium. Within the species L. lactis, L. lactis subsp lactis was detected more frequently than L. lactis subsp cremoris (74% vs. 26%). The predominance of L. lactis subsp cremoris was linked to geographical area studied. It appears that the animals' environment plays a role in the balance between the dominance of L. lactis and enterococci in raw goats' milk. The separation between the milking parlor and the goat shed (vs no separation) and only straw in the bedding (vs straw and hay) seems to promote L. lactis in the milk (vs enterococci).

Bactericidal activity of 3 cutaneous/mucosal antiseptic solutions in the presence of interfering substances: Improvement of the NF EN 13727 European Standard?

OBJECTIVE: There is no standard protocol for the evaluation of antiseptics used for skin and mucous membranes in the presence of interfering substances. Our objective was to suggest trial conditions adapted from the NF EN 13727 standard, for the evaluation of antiseptics used in gynecology and dermatology. METHODS: Three antiseptic solutions were tested in vitro: a chlorhexidine-benzalkonium (CB) combination, a hexamidine-chlorhexidine-chlorocresol (HCC) combination, and povidone iodine (P). The adaptation of trial conditions to the standard involved choosing dilutions, solvent, and interfering substances. The activity of solutions was assessed on the recommended strains at concentrations of 97% (pure solution), 50%, and 10% (diluted solution), and 1%. A logarithmic reduction ≥ 5 was expected after 60seconds of contact, to meet requirements of bactericidal activity. RESULTS: HCC did not present any bactericidal activity except on P. aeruginosa at a concentration of 97%. P was not bactericidal on E. hirae at any concentration and on S. aureus at 97%. CB had the most homogeneous bactericidal activity with a reduction>5 log on the 4 bacterial strains at concentrations of 97%, 50% and 10%. CONCLUSION: Adapting the NF EN 13727 standard allowed assessing the 3 tested solutions: only CB was bactericidal in dirty conditions. This study proved the possibility of validating antiseptic choice in vitro, in current practice conditions, for adjunctive treatment of skin and mucous membranes disorders, primarily of bacterial origin or with a potential of superinfection.

Crenobalneotherapy (spa therapy) in patients with knee and generalized osteoarthritis: a post-hoc subgroup analysis of a large multicentre randomized trial.

OBJECTIVE: To determine whether the addition of spa therapy to home exercises provides any benefit over exercises and the usual treatment alone in the management of generalised osteoarthritis associated with knee osteoarthritis. METHODS: This study was a post-hoc subgroup analysis of our randomised multicentre trial (www.clinicaltrial.gov: NCT00348777). Participants who met the inclusion criteria of generalized osteoarthritis (Kellgren, American College of Rheumatology, or Dougados criteria) were extracted from the original randomised controlled trial. They had been randomised using Zelen randomisation. The treatment group received 18days of spa treatment in addition to a home exercise programme. Main outcome was number of patients achieving minimal clinically important improvement at six months (MCII) (≥-19.9mm on the VAS pain scale and/or ≥-9.1 points in a WOMAC function subscale), and no knee surgery. Secondary outcomes included the "patient acceptable symptom state" (PASS) defined as VAS pain ≤32.3mm and/or WOMAC function subscale ≤31 points. RESULTS: From the original 462 participants, 214 patients could be categorized as having generalised osteoarthritis. At sixth month, 182 (88 in control and 94 in SA group) patients, were analysed for the main criteria. MCII was observed more often in the spa group (n=52/94 vs. 38/88, P=0.010). There was no difference for the PASS (n=19/88 vs. 26/94, P=0.343). CONCLUSIONS: This study indicates that spa therapy with home exercises may be superior to home exercise alone in the management of patients with GOA associated with knee OA.

Impact of tortuous flow on bacteria streamer development in microfluidic system during filtration.

The way in which bacterial communities colonize flow in porous media is of importance, but basic knowledge on the dynamic of these phenomena is still missing. The aim of this work is to develop microfluidic experiments in order to progress in the understanding of bacteria capture in filters and membranes. PDMS microfluidic devices mimicking filtration processes have been developed to allow a direct dynamic observation of bacteria across 10 or 20 µm width microchannels. When filtered in such devices, bacteria behave surprisingly: Escherichia coli, Pseudomonas aeruginosa or Staphylococcus aureus accumulate in the downstream zone of the filter and form large streamers which oscillate in the flow. In this study, streamer formation is put in evidence for bacteria suspension in non nutritive conditions in less than 1 h. This result is totally different from the one observed in same system with "inert" particles or dead bacteria which are captured in the bottleneck zone and are accumulated in the upstream zone. Observations within different flow geometries (straight channels, connected channels, and staggered row pillars) show that the bacteria streamer development is influenced by the flow configuration and, particularly by the presence of tortuosity within the microchannels zone. These results are discussed at the light of 3D flow simulations. In confined systems and in laminar flow, there is secondary flow (z-velocities) superimposed to the streamwise motion (in xy plane). The presence of the secondary flow in the microsystems has an effect on the bacterial adhesion. A scenario in three steps is established to describe the formation of the streamers and to explain the positive effect of tortuous flow on the development kinetics.

Preventive effects of an original combination of grape seed polyphenols with amine fluoride on dental biofilm formation and oxidative damage by oral bacteria.

AIMS: To investigate the preventive effects of an original combination of a grape seed extract (GSE) with an amine fluoride (Fluorinol(®) ) on dental plaque formation and oxidative damage caused by oral bacteria. METHODS AND RESULTS: The antibacterial activity of the compounds was assessed using the broth macrodilution method, and their antiplaque activity was evaluated on a multispecies biofilm grown on saliva-coated hydroxyapatite discs. The effect on glucosyltransferases activity was analysed through reductions in the overall reaction and the quantity of insoluble glucan synthesized. The combination of 2000 µg ml(-1) of GSE with 10·2 mg ml(-1) of Fluorinol(®) significantly decreased the biofilm formation (up to 4·76 log10 of reduction) and inhibited by 97·4% the insoluble glucan synthesis by glucosyltransferases. The antioxidant activity of this combination, alone or incorporated into a formulated mouthwash (Eludril daily(®) ), was determined using the Trolox equivalent antioxidant capacity assay (TEAC), and both showed significantly greater antioxidant capacity than vitamin C. CONCLUSIONS: The GSE/Fluorinol(®) combination showed both a significant antiplaque activity and an important antioxidant capacity in vitro, without any bactericidal effects. SIGNIFICANCE AND IMPACT OF THE STUDY: This is, to our knowledge, the first report on the properties of an original combination of a polyphenolic extract with amine fluoride that could be used for the prevention of oral diseases and oxidative damage associated.

Activity of Drill® lozenges on the main microorganisms responsible for upper respiratory tract infections.

OBJECTIVES: The treatment of sore throat, considered to be essentially due to viral infection, does not require the use of antibiotics. The recommended treatment is therefore based on the use of topical anaesthetics and antiseptics. Throat lozenges play a leading role in topical treatment by allowing immediate, massive and persistent release of the active molecule at the site of infection. The objective of this study was to demonstrate the short-term and long-term in vitro antimicrobial efficacy of Drill(®) lozenges in relation to the main pathogens responsible for upper respiratory tract infections. MATERIAL AND METHOD: The bactericidal and virucidal activity in relation to the main microorganisms responsible for upper respiratory tract infections, including the H1N1 influenza virus, was evaluated after short (5 minutes) and long (3h) contact times, according to a methodology complying with European standards for the evaluation of chemical antiseptics and disinfectants. In parallel, the global antibacterial activity was determined on 30 strains representative of the resident flora by determination of maximum inhibitory dilutions (MID) and maximum bactericidal dilutions (MBD). RESULTS: Drill(®) lozenges presented an antibacterial activity inducing significant (>90%) destruction of the main upper respiratory tract pathogens after a 5-minute contact time at high concentration and after a 3-hour contact time after dilution. Drill(®) lozenges also exerted an antiviral activity inducing 2 log (99%) destruction of the H1N1 virus after a 5-min contact time at high concentration, with maintenance of this activity after dilution (3h). A homogeneous antibacterial activity was observed on the resident flora. CONCLUSION: These in vitro tests confirm the value of chlorhexidine lozenges in the treatment of upper respiratory tract infections such as sore throat.

Bifunctional silica nanoparticles for the exploration of biofilms of Pseudomonas aeruginosa.

Luminescent silica nanoparticles are frequently employed for biotechnology applications mainly because of their easy functionalization, photo-stability, and biocompatibility. Bifunctional silica nanoparticles (BSNPs) are described here as new efficient tools for investigating complex biological systems such as biofilms. Photoluminescence is brought about by the incorporation of a silylated ruthenium(II) complex. The surface properties of the silica particles were designed by reaction with amino-organosilanes, quaternary ammonium-organosilanes, carboxylate-organosilanes and hexamethyldisilazane. BSNPs were characterized extensively by DRIFT, (13)C and (29)Si solid state NMR, XPS, and photoluminescence. Zeta potential and contact angle measurements exhibited various surface properties (hydrophilic/hydrophobic balance and electric charge) according to the functional groups. Confocal laser scanning microscopy (CLSM) measurements showed that the spatial distribution of these nanoparticles inside a biofilm of Pseudomonas aeruginosa PAO1 depends more on their hydrophilic/hydrophobic characteristics than on their size. CLSM observations using two nanosized particles (25 and 68 nm) suggest that narrow diffusion paths exist through the extracellular polymeric substances matrix.