Explore the vast range of titles available.

The intestinal microbiota is suspected to play a role in colitis and particularly in inflammatory bowel disease (IBD) pathogenesis. The aim was to compare the fecal microbiota composition of patients with colitis to that of healthy subjects (HS).Methodsfecal samples from 22 active Crohn's disease (A-CD) patients, 10 CD patients in remission (R-CD), 13 active ulcerative colitis (A-UC) patients, 4 UC patients in remission (R-UC), 8 infectious colitis (IC) patients, and 27 HS were analyzed by quantitative real-time polymerase chain reaction (PCR) targeting the 16S rRNA gene. Bacterial counts were transformed to logarithms (Log10 CFU) for statistical analysis.ResultsBacteria of the phylum Firmicutes (Clostridium leptum and Clostridium coccoides groups) were less represented in A-IBD patients (9.7; P = 0.004) and IC (9.4; P = 0.02), compared to HS (10.8). Faecalibacterium prausnitzii species (a major representative of the C. leptum group) had lower counts in A-IBD and IC patients compared to HS (8.8 and 8.3 versus 10.4; P = 0.0004 and P = 0.003). The Firmicutes/Bacteroidetes ratio was lower in A-IBD (1.3; P = 0.0001) and IC patients (0.4; P = 0.002). Compared to HS, Bifidobacteria were less represented in A-IBD and IC (7.9 and 7.7 versus 9.2; P = 0.001 and P = 0.01).ConclusionsThe fecal microbiota of patients with IBD differs from that of HS. The phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A-IBD patients as well as in IC patients. These bacteria could be crucial to gut homeostasis since lower counts of F. prausnitzii are consistently associated with a reduced protection of the gut mucosa.

Background In humans, the intestinal microbiota plays an important role in the maintenance of host health by providing energy, nutrients, and immunological protection. Applying current molecular methods is necessary to surmount the limitations of classical culturing techniques in order to obtain an accurate description of the microbiota composition. Results Here we report on the comparative assessment of human fecal microbiota from three age-groups: infants, adults and the elderly. We demonstrate that the human intestinal microbiota undergoes maturation from birth to adulthood and is further altered with ageing. The counts of major bacterial groups Clostridium leptum, Clostridium coccoides , Bacteroidetes, Bifidobacterium, Lactobacillus and Escherichia coli were assessed by quantitative PCR (qPCR). By comparing species diversity profiles, we observed age-related changes in the human fecal microbiota. The microbiota of infants was generally characterized by low levels of total bacteria. C. leptum and C. coccoides species were highly represented in the microbiota of infants, while elderly subjects exhibited high levels of E. coli and Bacteroidetes . We observed that the ratio of Firmicutes to Bacteroidetes evolves during different life stages. For infants, adults and elderly individuals we measured ratios of 0.4, 10.9 and 0.6, respectively. Conclusion In this work we have confirmed that qPCR is a powerful technique in studying the diverse and complex fecal microbiota. Our work demonstrates that the fecal microbiota composition evolves throughout life, from early childhood to old age.

BackgroundCrohn’s disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined.MethodsPeptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Anti-inflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice.ResultsThe seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-κB pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice.ConclusionsA 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.

Visceral pain and intestinal dysbiosis are associated with Irritable Bowel Syndrome (IBS), a common functional gastrointestinal disorder without available efficient therapies. In this study, a decrease of Faecalibacterium prausnitzii presence has been observed in an IBS-like rodent model induced by a neonatal maternal separation (NMS) stress. Moreover, it was investigated whether F. prausnitzii may have an impact on colonic sensitivity. The A2-165 reference strain, but not its supernatant, significantly decreased colonic hypersensitivity induced by either NMS in mice or partial restraint stress in rats. This effect was associated with a reinforcement of intestinal epithelial barrier. Thus, F. prausnitzii exhibits anti-nociceptive properties, indicating its potential to treat abdominal pain in IBS patients.

The risk of lymphoproliferative disorders (LDs) has become a major concern for clinicians managing patients with inflammatory bowel disease (IBD). Yet it is difficult to distinguish the possible responsibility of immunosuppressive therapy from the background risk due to the inflammatory disorder itself. LDs are clonal B or T cell proliferation showing considerable heterogeneity and the incidence has increased since the 1970s. The strongest and best-established risk factors for LDs are primary and acquired immunodeficiency (HIV, immunosuppressant), notably via defective immune surveillance of Epstein–Barr virus. In many auto-immune diseases (eg, Sjögren’s syndrome), inflammatory diseases (eg, rheumatoid arthritis) or chronic suppuration (chronic pyothorax), the risk of LD is increased. In IBD patients, in general, the risk of LD seems to be similar to or very slightly higher than in the general population. The role of immunosuppressants in lymphomagenesis is difficult to individualise because other factors potentially involved are inter-linked. Concordant data suggest that thiopurine therapy is associated with a moderately increased risk of LD. Data regarding methotrexate are scarce and come from diseases other than IBD but the risk seems low. Data regarding risk of LD in IBD patients receiving anti-tumour necrosis factor α (TNFα) agents are insufficient at this time, mainly because most of the patients are co-treated with thiopurines. The recently individualised risks of hepatosplenic T cell lymphoma and fatal post-mononucleosis LD, in young male patients with IBD who are co-treated with anti-TNFα and thiopurines, and EBV-seronegative IBD males, respectively, are probably low but remain to be better quantified.

Background and aims:A previous study suggested that the presence of myenteric plexitis in the proximal resection margins could be predictive of early endoscopic recurrence after ileocolonic or ileal resection for Crohn’s disease (CD). The aim of the present study was to assess the predictive value of plexitis for early clinical CD recurrence.Methods:All consecutive patients with ileocolonic or ileal resection for active CD in Lariboisière Hospital (Paris) between 1995 and 2006 were included. Clinical, surgical, histological and follow-up data were extracted from medical charts. Early clinical recurrence was defined as the reappearance of CD clinical manifestations requiring a specific treatment within 2 years postsurgery. The proximal resection margin was analysed using haematein eosin saffron (HES) staining and immunochemistry targeting mastocytes (anti-CD117 antibody) and lymphocytes (anti-CD3 antibody). Eosinophils were detected by HES staining. Ten cases of ileocolonic resections for caecal carcinoma served as controls.Results:Data were available from 171 postoperative follow-up periods in 164 patients with CD. Early clinical recurrence of CD occurred in 28.1%. In multivariate analysis, factors associated with postoperative recurrence were active smoking (hazard ratio (HR) = 1.94; 95% CI 1.06 to 3.60; p = 0.033), submucosal plexitis with ⩾3 mastocytes (HR = 1.87; 95% CI 1.00 to 3.46; p = 0.048) and a disease-free resection margin <5 cm (HR = 0.52; 95% CI 0.27 to 1.02; p = 0.059).Conclusions:Submucosal plexitis is associated with early clinical recurrence and could be taken into account in studies searching for new treatment strategies in the immediate postoperative period.

BackgroundTryptophan metabolism alterations have been reported in inflammatory diseases, including rheumatoid arthritis. However, understanding whether these alterations participate RA development and can therefore be considered as putative therapeutic targets remain undetermined.ObjectivesIn this study, we combined quantitative Tryptophan metabolomics in the serum of RA patients and corrective administration of a recombinant enzyme in experimental arthritis to address the question.MethodsTargeted quantitative metabolomics was performed on the serum of 574 treatment naïve early untreated RA patients from the ESPOIR cohort and on 98 healthy subjects. Dosages were also conducted in serum of collagen-induced arthritis mice and controls. A proof-of-concept study evaluating the therapeutic potency of targeting the kynurenine pathway was performed in the collagen-antibody induced arthritis model.ResultsDifferential analysis revealed drastic changes in Trp metabolites levels in RA patients compared to healthy controls. Amongst them, decreased levels of kynurenic (KYNA), xanthurenic (XANA) acids and indoles derivatives as well as an increased level of quinolinic acid in the serum of RA were positively correlated to disease severity (assessed by both circulating biomarkers and disease activity scores) and negatively correlated to quality-of-Life scores. Similar alterations of metabolites of the kynurenine pathway were observed in collagen-induced arthritis. Finally, the administration of the recombinant enzyme Aminoadipate Aminotransferase (AADAT), which is responsible for the generation of XANA and KYNA, was protective in collagen-antibody induced arthritis model.ConclusionAltogether, our clinical and experimental data indicate that Trp metabolism alterations play an active role in RA pathogenesis and might be considered as new therapeutic avenue.AcknowledgementsHS received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (ERC-2016-StG-71577). This project was partly funded by the Region GRAND EST, the FEDER project “Target (Translational research in ARticular and Gastroinstestinal inflammatory diseases in Grand EsT)”.Disclosure of InterestsDavid MOULIN: None declared, Mahdia TAIEB: None declared, Chloe Michaudel: None declared, Anne Aucouturier: None declared, Luis Bermudez-Humaran: None declared, Philippe Langella: None declared, Denis Mulleman: None declared, Xavier Mariette Consultant of: AstraZeneca, Novartis, BMS, Galapagos, Pfizer, GSK, Philippe Dieudé: None declared, Jean-Yves Jouzeau: None declared, Patrick Emond: None declared, Jérémie SELLAM Consultant of: Abbvie, Fresenius Kabi, BMS, Roche Chugai, Sandoz, Lilly, Gilead, Novartis, and Janssen, Grant/research support from: Pfizer, MSD, Schwa Medico, and BMS, Harry SOKOL Shareholder of: Enterome Exeliom-Biosciences, Consultant of: Amgen, Fresenius, IPSEN, Actial, Astellas, Danone, THAC, Biose, BiomX, Eligo, Immusmol, Adare, Nestle, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, Abbvie,

Eligibility criteria for intraoperative radiation therapy (IORT) for breast cancer are being established. Impact of age, one criterion, on short-term complications/outcomes was evaluated. Institutional Review Board approved retrospective review of early-stage breast cancer patients undergoing breast conserving surgery and IORT from January 2011 to June 2013 were reviewed. Data collected were demographics, comorbidities, histopathology, intraoperative data, adjuvant treatment, and outcomes. Local recurrence (LR), re-excision rates, and complications were evaluated by age group using descriptive statistics. The total number of patients was 100 (43 patients <70, 57 patients ≥70). No significant differences existed between groups in tumor size, operative time, estrogen receptor status, nodal status, tumor grade, or margin excision. Wound infection rates were low for both groups (P = .21). Two LR occurred (both patients ≥70). Median follow-up time was 24 months. IORT with its low rate of LR and wound complications may be a reasonable alternative to whole breast irradiation for early-stage breast cancer, regardless of age.

The objective of this work is to elucidate the causes and ramifications of multi-authorship in science by surveying researchers working in the field of Medical Physics. During the first 6 months of 2022, an anonymous survey was disseminated among 956 medical physicists working in Asia, Europe and North America. The survey participants were chosen by using their publications in professional journals. The number of responses to the survey questions varied from 186 (19.5%) to 249 (26%). The obtained responses indicated several important causes of multi-authorship in science. In particular, the respondents indicated the importance of the quid pro quo effect, division of labor, complimentary expertise, and potential bias against 1–2 author papers. The responses also indicated the important role of multi-authorship in developing professional networks and associated career advancement. The responses suggest that besides its potential to significantly increase number of publications, multi-authorship facilitates networking and associated career advancement of researchers. As a result, multi-authorship can be used as a tool to improve chances for promotion and tenure. The negative ramifications of multi-authorship can be dealt with by employing transparent policies to properly assign credit and responsibility for multi-author studies and to restrict number of coauthors except when multi-authorship is justified by the specific needs and/or multidisciplinary nature of the study.