Chron's Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions ...influenced by a complex pathogenesis in which inflammation plays a key role. Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a T
1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence.
Introduction. Postoperative recurrence after surgery for Crohn’s disease (CD) is virtually inevitable, and its mechanism is poorly known. Aim. To review the numerous factors involved in CD ...postoperative recurrence (POR) pathogenesis, focusing on single immune system components as well as the immune system as a whole and highlighting the clinical significance in terms of preventive strategies and future perspectives. Methods. A systematic literature search on CD POR, followed by a review of the main findings. Results. The immune system plays a pivotal role in CD POR, with many different factors involved. Memory T-lymphocytes retained in mesenteric lymph nodes seem to represent the main driving force. New pathophysiology-based preventive strategies in the medical and surgical fields may help reduce POR rates. In particular, surgical strategies have already been developed and are currently under investigation. Conclusions. POR is a complex phenomenon, whose driving mechanisms are gradually being unraveled. New preventive strategies addressing these mechanisms seem promising.
An altered balance between effector and regulatory factors is supposed to sustain the tissue-damaging immune response in inflammatory bowel disease (IBD). Several studies demonstrate that severe ...active inflammation is a strong predictor for surgical complications and recurrence. Indeed, bowel resection in Crohn’s disease (CD) patients has a high surgical recurrence rate. In this review, we examined the IBD inflammatory pathways, the current surgical treatments, and the almost inevitable recurrence. The question that might arise is if the cure of intestinal CD is to be found in the surgical approach. A selective search of two databases (PubMed and the Cochrane Library) has been carried out without considering a specific time horizon as inclusion criteria. The scope of this literature review was investigating on the role of inflammation in the management of CD. The following key words have been used to develop the query string: (i) inflammation; (ii) Crohn’s disease; (iii) surgery; and (iv) postsurgical recurrence.
Background. One-third of Crohn’s disease (CD) patients present perianal fistula. The gold standard in the diagnosis and treatment of symptomatic perianal disease (PAD) in CD is the exploration of the ...anal canal and distal rectum under anesthesia (EUA). This procedure is mainly conducted as a day case surgery. Unfortunately, it is not always possible to proceed within the ideal timing and any delay may well represent a relevant clinical issue. The aim of this study was to evaluate the feasibility of outpatient treatment of symptomatic perianal fistulas in CD patients. Methods. All CD patients under regular follow-up at our inflammatory bowel disease referral center, presenting with symptomatic perianal fistulas, were offered surgical consultation. The data of patients were prospectively collected for three years (February 2014 to February 2017) for the purpose of the study. All clinical information, including previous EUA and/or records from MRI and endoscopic ultrasound, was included. Outpatient anal canal and distal rectum exploration and treatment (OE) were undertaken during the specialist surgical consultation. Fistulas were classified according to Parks’s classification; the type of outpatient treatment and compliance of patients were recorded. Pain was assessed by VAS at the time of the procedure and during the first control. Patients were followed up in the surgical clinic in relation to the study. Results. Ninety-two CD patients with symptomatic perianal fistulas had surgical consultation during the study period. OE was offered to all but 18 patients who fulfilled the exclusion criteria or had an extremely severe disease; six patients refused the OE (8.11%). Of the 68 patients undergoing OE, eleven (16.18%) had previous surgery for perianal disease. The OE was accomplished in sixty-one patients (89.71%), while in 7 patients, it was abandoned for scarce compliance. Nine patients (14.75%) underwent drainage of perianal abscess; in 3 of them, it was possible to probe the fistula tract, find the internal orifice, and pass a loose seton. Overall, setonage was performed in 50 patients (81.97%). Rectovaginal setons were placed in 3 patients and more than one seton (up to 3) in 6 cases. Fistulotomy was performed in 4 simple subcutaneous fistulous tracts. Concordance with the preoperative findings was found in 54 out of 61 patients. EUA was scheduled at the time of OE for the 7 patients who did not complete the procedure. All sixty-one patients who had the OE were followed up for a minimum of 12 months. Conclusions. This preliminary study indicates that OE in CD patients with symptomatic perianal fistulas is safe and feasible in a high-volume referral center. It might provide several benefits, including patients’ logistics, reduce or remove patients’ symptoms and discomfort, allow for a timely start of medical therapy, and avoid further complications.
The SSR profiles of 67 soybean genotypes of various origins have been detected by 188 alleles at the 18 SSR loci. From 4 to 21 alleles were found at each of these loci (average 10.4 per locus) and ...the gene diversity averaged 0.71. Differentiation of all 67 genotypes each from others has been successful by using of even only 6 of SSR markers (Sat001, Satt005, Satt038, Satt173, Satt177, Satt534) with gene diversity from 0.66 to 0.89. The cumulated probability of obtaining identical soybean SSR profile was 1.11 x 10**-9 , which confirms a high potential of SSRs for differentiation of soybean accessions in collections. Clustering of genotypes partially reflects the origin and pedigree of analysed soybean accessions.
Cultivar Agrus, possessing a chromosomal substitution, and cultivar Sunnan, possessing a translocation from Thinopyrum ponticum (= Agropyron elongatum, 2n = 10x) with leaf rust resistance gene Lr19 ...against Puccinia triticina, were crossed with the susceptible winter wheat cultivars Sofia, Simona and Livia to transfer Lr19 into agronomically better genotypes by marker-assisted selection. Altogether 304 individuals of the F2 progeny were screened for endopeptidase phenotypes. We found null endopeptidase allele Ep-D1c (marker tightly linked with resistance gene Lr19) in 49 plants. The progenies of 40 plants of the F2 generation (with Ep-D1c) were reselected with the same marker and tested for leaf rust reaction. Results achieved with the isozyme marker corresponded with those of the resistance tests. We obtained 28 F3 families with resistance gene Lr19 confirmed by presence of the null endopeptidase allele and by tests for leaf rust reaction. Field tests showed that Agrus increased the height of plants in the progenies, and the smallest negative effect on yield components was observed in both crosses with cultivar Sunnan.
The article aims to investigate two fragmentary manuscript witnesses to Bono Giamboni’s vernacular Italian translation of Paulus Orosius’
. Neither of these witnesses has been studied until now. The ...article provides an edition of the shorter fragment, preserved in MS Vatican Library Barb. Lat. 4119, and a full description of the second codex, MS British Library Add. 16554, a multi-text codex that contains a large anthology of Orosius’
. Among the works preserved in this latter manuscript, particularly noteworthy is the presence of an unknown vernacular Italian version of Sallust’s
. The article also provides some new insights into the early printed editions of the Italian vernacular translation of Orosius and the authorship of the printed text.
The strictly regulated expression of most pleiotropic developmental control genes is critically dependent on the activity of long-range cis-regulatory elements. This was revealed by the ...identification of individuals with a genetic condition lacking coding-region mutations in the gene commonly associated with the disease but having a variety of nearby chromosomal abnormalities, collectively described as cis-ruption disease cases. The congenital eye malformation aniridia is caused by haploinsufficiency of the developmental regulator PAX6. We discovered a de novo point mutation in an ultraconserved cis-element located 150 kb downstream from PAX6 in an affected individual with intact coding region and chromosomal locus. The element SIMO acts as a strong enhancer in developing ocular structures. The mutation disrupts an autoregulatory PAX6 binding site, causing loss of enhancer activity, resulting in defective maintenance of PAX6 expression. These findings reveal a distinct regulatory mechanism for genetic disease by disruption of an autoregulatory feedback loop critical for maintenance of gene expression through development.
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