Lactase persistence, NOD2 status and <it>Mycobacterium avium</it> subsp. <it>paratuberculosis</it> infection associations to Inflammatory Bowel Disease

Abstract Background Inflammatory Bowel Disease (IBD), which includes both Crohn’s disease (CD) and ulcerative colitis (UC), is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP) is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP) and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD. Methods In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT) and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes. Results As for LP, no association was found with IBD, although UC patients were less likely to present the T/T−13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP). NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2%) compared to CD patients (21.38%) and UC patients (19.04%) and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6%) compared to the Basque CD cohort (15.5%), differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status. Conclusions We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually interacting associations with IBD.</p

Instrucciones christianas sobre las dominicas de el año

Sign.: [calderón]\p8\s, 2[calderón]\p4\s, A-B\p4\s, C-Z\p8\s, 2A-2P\p8\s, 2Q\p2\sTexto a dos colPort. con orla tip. y grab. xi

Creation of a multidisciplinary and multicenter study group for the use of 3D printing in general thoracic surgery: lessons learned in our first year experience

Introduction: In recent years, the use of 3D printing in medicine has grown exponentially, but the use of 3D technology has not been equally adopted by the different medical specialties. Published 3D printing activity in general thoracic surgery is scarce and has been mostly limited to case reports. The aim of this report was to reflect on the results and lessons learned from a newly created multidisciplinary and multicenter 3D unit of the Spanish Society of Thoracic Surgery (SECT). Methods: This is a pilot study to determine the feasibility and usefulness of printing 3D models for patients with thoracic malignancy or airway complications, based on real data. We designed a point-of-care 3D printing workflow involving thoracic surgeons, radiologists with experience in intrathoracic pathology, and engineers with experience in additive manufacturing. Results: In the first year of operation we generated 26 three-dimensional models out of 27 cases received (96.3%). In 9 cases a virtual model was sufficient for optimal patient handling, while in 17 cases a 3D model was printed. Per pathology, cases were classified as airway stenosis after lung transplantation (7 cases, 25.9%), tracheal pathology (7 cases, 25.9%), chest tumors (6 cases, 22.2%) carcinoid tumors (4 cases, 14.8%), mediastinal tumors (2 cases, 7.4%) and Pancoast tumors (one case, 3.7%). Conclusion: A multidisciplinary 3D laboratory is feasible in a hospital setting, and working as a multicenter group increases the number of cases and diversity of pathologies thus providing further opportunity to study the benefits of the 3D printing technology in general thoracic surgery

Ex vivo maturation of 3D-Printed, chondrocyte-laden, polycaprolactone-based scaffolds prior to transplantation improves engineered cartilage substitute properties and integration

The surgical management of nasal septal defects due to perforations, malformations, congenital cartilage absence, traumatic defects, or tumors would benefit from availability of optimally matured septal cartilage substitutes. Here, we aimed to improve in vitro maturation of 3-dimensional (3D)-printed, cell-laden polycaprolactone (PCL)-based scaffolds and test their in vivo performance in a rabbit auricular cartilage model

Creation of a multidisciplinary and multicenter study group for the use of 3D printing in general thoracic surgery: lessons learned in our first year experience

Introduction: In recent years, the use of 3D printing in medicine has grown exponentially, but the use of 3D technology has not been equally adopted by the different medical specialties. Published 3D printing activity in general thoracic surgery is scarce and has been mostly limited to case reports. The aim of this report was to reflect on the results and lessons learned from a newly created multidisciplinary and multicenter 3D unit of the Spanish Society of Thoracic Surgery (SECT). Methods: This is a pilot study to determine the feasibility and usefulness of printing 3D models for patients with thoracic malignancy or airway complications, based on real data. We designed a point-of-care 3D printing workflow involving thoracic surgeons, radiologists with experience in intrathoracic pathology, and engineers with experience in additive manufacturing. Results: In the first year of operation we generated 26 three-dimensional models out of 27 cases received (96.3%). In 9 cases a virtual model was sufficient for optimal patient handling, while in 17 cases a 3D model was printed. Per pathology, cases were classified as airway stenosis after lung transplantation (7 cases, 25.9%), tracheal pathology (7 cases, 25.9%), chest tumors (6 cases, 22.2%) carcinoid tumors (4 cases, 14.8%), mediastinal tumors (2 cases, 7.4%) and Pancoast tumors (one case, 3.7%). Conclusion: A multidisciplinary 3D laboratory is feasible in a hospital setting, and working as a multicenter group increases the number of cases and diversity of pathologies thus providing further opportunity to study the benefits of the 3D printing technology in general thoracic surgery

Isolation and characterization of myogenic precursor cells from human cremaster muscle

Human myogenic precursor cells have been isolated and expanded from a number of skeletal muscles, but alternative donor biopsy sites must be sought after in diseases where muscle damage is widespread. Biopsy sites must be relatively accessible, and the biopsied muscle dispensable. Here, we aimed to histologically characterize the cremaster muscle with regard number of satellite cells and regenerative fibres, and to isolate and characterize human cremaster muscle-derived stem/precursor cells in adult male donors with the objective of characterizing this muscle as a novel source of myogenic precursor cells. Cremaster muscle biopsies (or adjacent non-muscle tissue for negative controls; N = 19) were taken from male patients undergoing routine surgery for urogenital pathology. Myosphere cultures were derived and tested for their in vitro and in vivo myogenic differentiation and muscle regeneration capacities. Cremaster-derived myogenic precursor cells were maintained by myosphere culture and efficiently differentiated to myotubes in adhesion culture. Upon transplantation to an immunocompromised mouse model of cardiotoxin-induced acute muscle damage, human cremaster-derived myogenic precursor cells survived to the transplants and contributed to muscle regeneration. These precursors are a good candidate for cell therapy approaches of skeletal muscle. Due to their location and developmental origin, we propose that they might be best suited for regeneration of the rhabdosphincter in patients undergoing stress urinary incontinence after radical prostatectomy

On the prevalence of M. avium subspecies paratuberculosis DNA in the blood of healthy individuals and patients with inflammatory bowel disease.

BACKGROUND: Mycobacteria, such as M. leprae and M. tuberculosis infect billions of humans. However, because of appropriate immune responses and antibiotic therapy, overt mycobacterial diseases occur far less frequently. M. avium subspecies paratuberculosis (MAP) causes Johne's disease in ruminants, an affliction evocative of inflammatory bowel disease (IBD). Several agents used to treat IBD (5-ASA, methotrexate, azathioprine and its metabolite 6-MP) have recently been shown to be antiMAP antibiotics. We herein evaluate the prevalence of MAP DNA in healthy individuals and compare them with IBD patients on antiMAP antibiotics. METHODS: We studied 100 healthy individuals (90 blood donors) and 246 patients with IBD. IS900 MAP DNA was identified using a nested primer PCR in the buffy coat of blood. Positive signal was confirmed as MAP by DNA sequence analysis. PCR positive results frequencies were compared according to medications used. Significance was accepted at p<0.05. RESULTS: 47% (47/100) healthy controls and 16% (40/246) IBD patients were IS900 positive (p<0.0001). MAP DNA was identified in 17% of 143 patients receiving mesalamine and 6% of 16 receiving sulfasalazine. None of the IBD patients receiving methotrexate (n = 9), 6-MP (n = 3), ciprofloxacin (n = 5) or Tacrolimus (n = 3) had MAP DNA detectable in their blood. DISCUSSION: We found a disquietingly large percentage of healthy individuals have MAP DNA in their blood, the significance of which remains to be determined. Counter-intuitively, the incidence of MAP DNA was significantly lower in patients with IBD. Agents with the most potent in vitro antiMAP activity were associated with clearance of blood MAP DNA. We posit that the use antiMAP antibiotics was responsible for the decreased prevalence of MAP DNA in patients with IBD