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IntroductionPrimary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction. No therapeutic strategy is sufficient on its own for the management of dry mouth and therapeutic innovations are required.MethodsThis Predelfi study was a single-center, prospective, comparative, randomized, double-blind, cross-over controlled study with the primary objective of assessing the tolerance to and effectiveness of two adhesive biofilms (containing prebiotics and, sodium alginate, respectively) in patients with pSS and hyposialia (#NCT04206826 in ClinicalTrials.gov). Secondary objectives were to obtain initial data regarding the clinical effectiveness of such biofilms in the improvement of signs and symptoms related to dry mouth and potential changes in the oral microbiota. Ten pSS patients with pSS were included (9 females and 1 male) with a mean age of 58.1 ± 14.0 years.Results and discussionTolerance to the prebiotic and sodium alginate biofilms was assessed by the patients (visual analog scale [VAS] score 66.7 and 87.6, respectively) and the practitioner (90 and 100, respectively). The absolute changes in the VAS scores at the start and end of each treatment period highlighted an improvement in mouth dryness for the sodium alginate versus the prebiotic biofilm. The VAS scores for other parameters (mouth burning sensation; taste alteration; chewing; swallowing and speech difficulties) remained globally comparable between the two groups. Unstimulated salivary flow showed no changes regardless of the biofilm used. Regarding the oral microbiota, the sodium alginate biofilm increased the abundance of the Treponema genus, whereas the use of the prebiotic biofilm as the first treatment increased the abundance of the genera Veillonella and Prevotella. Nevertheless, the prebiotic biofilm appeared to stimulate “milder” genera with regard to periodontal infections. Furthermore, pre-treatment with the prebiotic biofilm prevented the emergence of the Treponema genus induced by subsequent treatment with the sodium alginate biofilm, suggesting a potential protective effect.

In patients suffering from chronic liver disease, the hepatic metabolism of drugs is perturbed and the metabolic capacity is difficult to assess. Midazolam could be used as a phenotypical probe to predict the metabolic capacity of CYP3A to adjust dosages of drug substrates of this cytochrome. In this context, a prospective clinical trial is going to be conducted in our institution and a hospital preparation of midazolam capsules suitable for the clinical trial was developed. The objective of the present work was to assess the physicochemical stability of the formulation over 12 months to set shelf life.

IntroductionWomen are under-represented in senior academic and hospital positions in many countries. The authors aim to assess the place and the evolution of all appointed female and male health practitioners' working in French public Hospitals.Materials and methodsData of this observational study were collected from the National Management Centre (Centre National de Gestion) from 2015 up to January 1, 2020. First, the authors described demographic characteristics and specialties of all appointed medicine, pharmacy, and dentistry doctors' working as Hospital Practitioners, Associate Professors, and Full Professors in French General and University-affiliated Hospitals in 2020. Then, they retrospectively reported the annual incidence of new entrance according to gender and professional status from 1999 to 2019 thanks to the appointment date of all practitioners in activity between 2015 and 2020.ResultsIn 2020, 51 401 appointed practitioners (49.7% of female) were in activity in French public hospitals with a large majority being medical doctors (92.4%) compared to pharmacists (6%) and dentists (1.6%). Women represented 52.5% of the Hospital Practitioners, 48.6% of the Associate Professors, and 22.0% of the Full Professors (p < 0.001). There were disparities between the rates of female Full Professors in medicine (20.6%), pharmacy (36.1%), and dentistry (44.3%, p < 0.001). Women were appointed Hospital Practitioners and Associate Professors earlier than men (respectively 37.1 versus 38.8 years, p < 0.001 and 36.1 versus 36.5 years, p = 0.04), and at a later age among Full Professors (43.7 versus 41.9 years, p < 0.001). Compared to men, the annual proportion of appointed women varied significantly between 1999 and 2019 from 47.6% to 60.4% for Hospital Practitioners, from 50.0% to 44.6% for Associate Professors, and from 11.2% to 33.3% for Full Professors (p < 0.001 for trend).ConclusionsAlthough more and more women occupy positions in French hospitals, there is still a gender gap regarding access to Full Professor status in medicine and pharmacy, but not in dentistry. The disparity in numbers makes comparison difficult. Despite a trend towards gender equality during the last twenty years, it has not yet been achieved regarding access to the highest positions.

Background: Porphyromonas gingivalis strain W83, one of the most widely investigated, is considered virulent in the context of periodontitis. The recently isolated P. gingivalis TDC60 has been reported to be highly pathogenic, although it has not yet been investigated in a mouse periodontitis model by oral gavage. Aim: Our aim was to compare the virulence of both strains by evaluating their impact on alveolar bone loss and the composition of oral microbiota. Methods: We inoculated by oral gavage C57BL/6 mice with either one of the two P. gingivalis strains and compared to a sham-treated group, without antibiotics pre-treatment. The mandibular alveolar bone of treated mice and controls were assessed, one month after the final inoculation, by microCT measurements. Moreover, at this time, we characterized their oral microbiota by 16S rRNA gene sequencing. Results: While P. gingivalis W83 successfully initiated periodontitis, TDC60-treated mice only experienced moderate lesions. Furthermore, only W83-treated mice exhibited a specific distinct microbiota, with significantly lower richness and evenness than other samples, and decreased proportions of taxa usually found in healthy individuals. Conclusion: This association between alveolar bone loss and a major persistent shift of the oral microbiota gives insights into virulence discrepancies among these bacterial strains.

Prednisone is a corticosteroid used in several inflammatory diseases and cancers. In France, no available prednisone drinkable formulation exists. Instead, an oral syrup of prednisone with ethanol, sodium benzoate and simple syrup is produced. However, sodium benzoate can induce neonatal icterus and alcohol is not authorized for children below 3 years of age. The aim of this study was to determine the stability of 5 mg/mL prednisone oral suspension in a commercial compounding excipient: Syrspend® SF PH4.

Nitrendipine is prescribed to children for the treatment of primary hypertension (off-label use). Available specialties (Nidrel®, Baypress® and others generic drugs) are only marketed in tablet form, which is unsuitable for pediatric use. A hospital preparation of nitrendipine oral suspension at 5 mg/mL was developed. The aim of the study was to determine physicochemical and microbiological stability of the nitrendipine oral suspension in order to set a shelf life for the preparation.

Background: Periodontitis is a set of chronic inflammatory diseases affecting the supporting structures of the teeth, during which a persistent release of lytic enzymes and inflammatory mediators causes a self-perpetuating vicious cycle of tissue destruction and repair. A matrix-based therapy using a heparan sulfate (HS) analogue called ReGeneraTing Agent (RGTA) replaces destroyed HS by binding to available heparin-binding sites of structural molecules, leading to restoration of tissue homeostasis in several inflammatory tissue injuries, including a hamster periodontitis model. Methods: The ability of RGTA to restore the periodontium was tested in a model of Porphyromonas gingivalis-infected Balb/cByJ mice. After 12 weeks of disease induction, mice were treated weekly with saline or RGTA (1.5 mg/kg) for 8 weeks. Data were analyzed by histomorphometry. Results: RGTA treatment restored macroscopic bone loss. This was related to (1) a significant reduction in gingival inflammation assessed by a decrease in infiltrated connective tissue, particularly in cells expressing interleukin 1ß, an inflammatory mediator selected as a marker of inflammation; (2) a normalization of bone resorption parameters, i.e. number, activation and activity of osteoclasts, and number of preosteoclasts; (3) a powerful bone formation reaction. The Sharpey's fibers of the periodontal ligament recovered their alkaline phosphatase coating. This was obtained while P. gingivalis infection was maintained throughout the treatment period. Conclusions: RGTA treatment was able to control the chronic inflammation characteristic of periodontitis and blocked destruction of periodontal structures. It ensured tissue regeneration with recovery of the periodontium's anatomy.

Periodontitis are bacterial inflammatory diseases, where the bacterial biofilms present on the tooth-supporting tissues switch from a healthy state towards a pathogenic state. Among bacterial species involved in the disease, Porphyromonas gingivalis has been shown to induce dysbiosis, and to induce virulence of otherwise healthy bacteria like Streptococcus gordonii. During biofilm development, primary colonizers such as S. gordonii first attach to the surface and allow the subsequent adhesion of periodontal pathogens such as P. gingivalis. Interactions between those two bacteria have been extensively studied during the adhesion step of the biofilm. The aim of the study was to understand interactions of both species during the growing phase of the biofilm, for which little knowledge is available, using a mathematical model. This two-species biofilm model was based on a substrate-dependent growth, implemented with damage parameters, and validated thanks to data obtained on experimental biofilms. Three different hypothesis of interactions were proposed and assayed using this model: independence, competition between both bacteria species, or induction of toxicity by one species for the other species. Adequacy between experimental and simulated biofilms were found with the last hypothetic mathematical model. This new mathematical model of two species bacteria biofilms, dependent on different substrates for growing, can be applied to any bacteria species, environmental conditions, or steps of biofilm development. It will be of great interest for exploring bacterial interactions in biofilm conditions.

The differentiation of human B lymphocytes into plasma cells is one of the most stirring questions with regard to adaptive immunity. However, the terminal differentiation and survival of plasma cells are still topics with much to be discovered, especially when targeting switched memory B lymphocytes. Plasma cells can migrate to the bone marrow in response to a CXCL12 gradient and survive for several years while secreting antibodies. In this study, we aimed to get closer to niches favoring plasma cell survival. We tested low oxygen concentrations and coculture with mesenchymal stem cells (MSC) from human bone marrow. Besides, all cultures were performed using an animal protein-free medium. Overall, our model enables the generation of high proportions of CD38+CD138+CD31+ plasma cells (≥50%) when CD40-activated switched memory B lymphocytes were cultured in direct contact with mesenchymal stem cells. In these cultures, the secretion of CXCL12 and TGF-β, usually found in the bone marrow, was linked to the presence of MSC. The level of oxygen appeared less impactful than the contact with MSC. This study shows for the first time that expanded switched memory B lymphocytes can be differentiated into plasma cells using exclusively a serum-free medium.

Introducción. Porphyromonas gingivalis es el principal agente etiológico de la periodontitis. El gen fimA ha sido relacionado con la virulencia del microorganismo, lo cual sugiere la participación de dicho gen en la capacidad del microorganismo para alcanzar el torrente sanguíneo. Objetivo. Estudiar la distribución de los tipos de fimA de P. gingivalis en muestras de placa subgingival y de sangre obtenidas durante bacteriemias después de raspaje y alisado radicular. Materiales y métodos. Se practicó un alisado radicular a 15 pacientes con periodontitis. Se obtuvieron aislamientos clínicos de P. gingivalis de la placa subgingival y durante la bacteriemia inducida por el procedimiento. Para la genotipificación se utilizó la técnica de reacción en cadena de la polimerasa (PCR) específica para fimA. En los aislamientos no clasificables por PCR se realizó secuenciación del gen fimA. Resultados. Seis pacientes fueron positivos para bacteriemia por P. gingivalis. La distribución de fimA evaluada en 30 aislamientos de placa subgingival y de sangre mostró una mayor frecuencia del fimA tipo II de P. gingivalis. En los aislamientos de placa subgingival, la detección de fimA tipo II fue seguida por Ib, III y IV; sin embargo, en los aislamientos de sangre el tipo II fue seguido por los tipos IV, Ib y III. Conclusión. En los aislamientos de sangre y de placa subgingival de pacientes con periodontitis el fimA más frecuente fue el tipo II; no fue posible correlacionar el tipo de fimA con la bacteriemia inducida por el alisado radicular. Los resultados de la secuenciación del gen fimA no concuerdan con los obtenidos por PCR.

Porphyromonas gingivalis is an etiologic agent of periodontal disease in humans. The disease is associated with the formation of a mixed oral biofilm which is exposed to oxygen and environmental stress, such as oxidative stress. To investigate possible roles for cytochrome bd oxidase in the growth and persistence of this anaerobic bacterium inside the oral biofilm, mutant strains deficient in cytochrome bd oxidase activity were characterized. This study demonstrated that the cytochrome bd oxidase of Porphyromonas gingivalis, encoded by cydAB, was able to catalyse O2 consumption and was involved in peroxide and superoxide resistance, and dioxygen tolerance.

For tRNA-dependent protein biosynthesis, amino acids are first activated by aminoacyl-tRNA synthetases (aaRSs) yielding the reaction intermediates aminoacyl-AMP (aa-AMP). Stable analogues of aa-AMP, such as aminoacyl-sulfamoyl-adenosines, inhibit their cognate aaRSs. Glutamyl-sulfamoyl-adenosine (Glu-AMS) is the best known inhibitor of Escherichia coli glutamyl-tRNA synthetase (GluRS). Thermodynamic parameters of the interactions between Glu-AMS and E. coli GluRS were measured in the presence and in the absence of tRNA by isothermal titration microcalorimetry. A significant entropic contribution for the interactions between Glu-AMS and GluRS in the absence of tRNA or in the presence of the cognate tRNAGlu or of the non-cognate tRNAPhe is indicated by the negative values of -TΔSb, and by the negative value of ΔCp. On the other hand, the large negative enthalpy is the dominant contribution to ΔGb in the absence of tRNA. The affinity of GluRS for Glu-AMS is not altered in the presence of the non-cognate tRNAPhe, but the dissociation constant Kd is decreased 50-fold in the presence of tRNAGlu; this result is consistent with molecular dynamics results indicating the presence of an H-bond between Glu-AMS and the 3'-OH oxygen of the 3'-terminal ribose of tRNAGlu in the Glu-AMS•GluRS•tRNAGlu complex. Glu-AMS being a very close structural analogue of Glu-AMP, its weak binding to free GluRS suggests that the unstable Glu-AMP reaction intermediate binds weakly to GluRS; these results could explain why all the known GluRSs evolved to activate glutamate only in the presence of tRNAGlu, the coupling of glutamate activation to its transfer to tRNA preventing unproductive cleavage of ATP.

B lymphocyte differentiation into long-lived plasma cells is the keystone event for the production of long-term protective antibodies. CD40-CD154 and CD27-CD70 interactions are involved in human B lymphocyte differentiation into CD38hiCD138+ cells in vivo as well as in vitro. In this study, we have compared these interactions in their capacity to drive switched-memory B lymphocytes differentiation into CD38hiCD138+ plasma cells. The targeted B lymphocytes were isolated from human peripheral blood, expanded for 19 days, and then submitted to CD70 or CD154 interactions for 14 days. The expanded B lymphocytes were constitutively expressing CD39, whereas CD31’s expression was noticed only following the in vitro differentiation step (day 5) and was exclusively present on the CD38hi cell population. Furthermore, the generated CD38hiCD138+ cells showed a higher proportion of CD31+ cells than the CD38hiCD138- cells. Besides, analyses done with human blood and bone marrow plasma cells showed that in vivo and de novo generated CD38hiCD138+ cells have a similar CD31 expression profile but are distinct according to their reduced CD39 expression level. Overall, we have evidences that in vitro generated plasma cells are heterogeneous and appear as CD39+ precursors to the ones present in bone marrow niches.

The purpose of this study was to evaluate various biological effects of silver-zeolite and a polyphenol-rich extract of A. nodosum (ASCOP) to prevent and/or treat biofilm-related oral diseases. Porphyromonas gingivalis and Streptococcus gordonii contribute to the biofilm formation associated with chronic periodontitis. In this study, we evaluated in vitro antibacterial and anti-biofilm effects of silver-zeolite (Ag-zeolite) combined to ASCOP on P. gingivalis and S. gordonii growth and biofilm formation capacity. We also studied the anti-inflammatory and antioxidant capacities of ASCOP in cell culture models. While Ag-zeolite combined with ASCOP was ineffective against the growth of S. gordonii, it showed a strong bactericidal effect on P. gingivalis growth. Ag-zeolite combined with ASCOP was able to completely inhibit S. gordonii monospecies biofilm formation as well as to reduce the formation of a bi-species S. gordonii/P. gingivalis biofilm. ASCOP alone was ineffective towards the growth and/or biofilm formation of S. gordonii and P. gingivalis while it significantly reduced the secretion of inflammatory cytokines (TNFα and IL-6) by LPS-stimulated human like-macrophages. It also exhibited antioxidant properties and decreased LPS induced lipid peroxidation in gingival epithelial cells. These findings support promising use of these products in future preventive or therapeutic strategies against periodontal diseases.

BACKGROUND: Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. METHODS AND FINDINGS: Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. CONCLUSIONS: Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression.

Abstract Background The aim of this study was to evaluate the prevalence of beta-lactamase-producing Capnocytophaga isolates in young children hospitalized in the Pediatric Oncology Department of Hôpital Sud (Rennes, France) over a ten-year period (1993–2002). Methods In neutropenic children, a periodic survey of the oral cavity allows a predictive evaluation of the risk of systemic infections by Capnocytophaga spp. In 449 children with cancer, 3,053 samples were collected by oral swabbing and plated on TBBP agar. The susceptibility of Capnocytophaga isolates to five beta-lactams was determined. Results A total of 440 strains of Capnocytophaga spp. were isolated, 309 (70%) of which were beta-lactamase producers. The beta-lactamase-producing strains were all resistant to cefazolin, 86% to amoxicillin, and 63% to ceftazidime. The proportion of strains resistant to third-generation cephalosporins remained high throughout the ten-year study, while susceptibility to imipenem and amoxicillin combined with clavulanic acid was always conserved. Conclusion These results highlight the risk of antibiotic failure in Capnocytophaga infections and the importance of monitoring immunosuppressed patients and testing for antibiotic susceptibility and beta-lactamase production.

L'hypertrophie bénigne de la prostate est une pathologie qui touche une proportion importante des hommes, notamment des plus de 60 ans. Elle se traduit par des symptômes qui impactent la qualité de vie des patients. Des règles hygiéno-diététiques peuvent être préconisées, mais si l'inconfort devient trop marqué ou que des complications surviennent, des traitements médicaux ou une chirurgie pourront être proposés. Benign prostatic hyperplasia is a condition that affects a significant proportion of men, especially those over 60 years of age. It results in symptoms that impact patients' quality of life. Hygienic and dietary rules may be recommended, but if the discomfort becomes too severe or if complications occur, medical treatments or surgery may be suggested. [ABSTRACT FROM AUTHOR]

Candida species are usually found as commensal microorganisms in the oral cavity of healthy people. During chemotherapy, cytostatic drugs lead to depletion of the oral flora with the emergence of a dominant bacterial species. The transition from commensal to pathogenic state, further associated with yeast colonization and oral mucositis implies a replacement of the dominant microorganism by Candida albicans. This process goes plausibly through cooperation between C. albicans and bacteria. This study focused on the first step of cooperation between microorganisms isolated from the same oral flora either of leukemic or healthy children. C. albicans isolated from 8/20 children were cultured to display their noninvasive blastosporic yeast form and mixed with their dominant bacteria to study the capacity of planktonic aggregation and the early state of biofilm formation. None of the dominant bacteria opposed the presence of yeast, on the contrary, an interesting cooperation was observed. This behavior is apparently different from that observed when mixing the type strains. In fact, three mutated C. albicans strains display, by their spontaneous ability to form filament, enhanced risks of virulence for leukemic ill carriers. Despite such risks, neither oral nor systemic pathology were observed in ill patients probably because the study was conducted during the first course of chemotherapy and Candida colonization is related to the number of chemotherapeutic cycles. The presence of C. albicans during the initial cycle represents, by its ability to interact with oral bacteria, an actual threat for further cures. [ABSTRACT FROM AUTHOR]

Copyright of Futuribles is the property of Futuribles SARL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Futuribles is the property of Futuribles SARL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Inside the biofilm, antimicrobial agents must overcome high cell density, an increased number of resistant mutants, substance delivery, molecular exchanges, such as high levels of beta-lactamases or inducers of efflux pump expression, and specific adaptive cells, so-called persisters. The environment within the biofilm modulates the response to antibiotics, especially when the SOS response or DNA repair systems are involved. Exposure to subinhibitory concentrations of antibiotics can enhance biofilm formation and mutagenesis. Thus, a global response to cell stress seems to be responsible for antibiotic-induced biofilm formation. [Copyright &y& Elsevier]

Copyright of Futuribles is the property of Futuribles SARL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Futuribles is the property of Futuribles SARL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue de Stomatologie & de Chirurgie Maxillo-Faciale is the property of Masson SPA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Quaternary ammonium compounds (QACs) are cationic surfactants used as preservatives and environmental disinfectants. Limited data are available regarding the effect of QACs in the clinical setting. We performed a prospective cohort study in 153 patients with Escherichia coli bacteraemia from February to September 2008 at University Hospital in Rennes. The minimum inhibitory concentrations (MICs) of antibiotics and QACs alkyldimethylbenzylammonium chloride (ADBAC) and didecyldimethylammonium chloride (DDAC) were determined by the agar dilution method. The capacity of biofilm production was assayed using the Crystal Violet method, and mutation frequencies by measuring the capacity of strains to generate resistance to rifampicin. Logistic regression analysis showed that one of the significant factors related to low MICs for ADBAC (≤16mg/L) and DDAC (≤8mg/L), was cotrimoxazole susceptibility (odds ratio: 3.72; 95% confidence interval: 1.22–11.24; P =0.02 and OR: 3.61; 95% CI: 1.56–7.56; P <0.01, respectively). Antibiotic susceptibility to cotrimoxazole was strongly associated with susceptibility to amoxicillin and nalidixic acid (P <0.01). Community-acquired or healthcare-associated bacteraemia, severity of bacteraemia, and patient outcome were independent of the MICs of ADBAC and DDAC. Our findings demonstrate an epidemiological relationship between higher MIC values of QACs in clinical E. coli isolates and antibiotic resistance. [ABSTRACT FROM AUTHOR]