Seismic displacement analysis of homogeneous slopes: a review of existing simplified methods with reference to Italian seismicity.

The simplified displacement-based procedures for seismic slope stability represent a good-working balance between simplicity and reliability, since both slope ductility (i.e. the capacity of sustain permanent displacements) and deformability (basically affecting the asynchronous slope motion) are accounted for. In this paper the procedure proposed by Bray & Rathje (1998) is reviewed with particular reference to Italian seismicity on a set of subsoil models, representative of the different soil classes specified by Italian and European codes. The relationship expressing the decrease of the equivalent acceleration with increasing earthquake/soil frequency ratio is then obtained by means of dynamic 1D site response analyses. Statistical correlations between calculated Newmark displacements, significant ground motion parameters and the ratio of seismic load resistance to peak demand are then derived and compared to similar relationships proposed in literature

Respiratory Tract Infections in Inflammatory Bowel Disease Patients Taking Vedolizumab: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The ongoing COVID-19 pandemic has raised concerns about the risk of SARS-CoV-2 infection in patients with Crohn's disease (CD) and patients with ulcerative colitis (UC) taking immunosuppressants or biologics. We conducted a systematic review and meta-analysis to assess the risk of respiratory infections in patients with inflammatory bowel disease (IBD) treated with vedolizumab. We searched PubMed, EMBASE and Scopus to identify randomized controlled trials (RCT) comparing vedolizumab to placebo in patients with IBD. Outcomes were the rate of respiratory tract infections (RTI), upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) among patients receiving vedolizumab as compared with placebo. Pooled rates were reported as Odds Ratios (OR) with 95% Confidence Interval (CI). Eight RCT involving 3,287 patients (1873 CD and 1415 UC) were analyzed; 2,493 patients received vedolizumab and 794 received placebo. The rates of RTI and URTI were statistically higher in vedolizumab-treated patients compared to placebo [OR = 1.63; 95% CI (1.07-2.49); OR = 1.64 95% CI (1.07-2.53) respectively]. UC patients, but not CD patients, receiving vedolizumab had a higher risk to develop RTI and URTI [OR = 1.98; 95% CI (1.41-2.77); OR = 2.02; 95% CI (1.42-2.87)] compared to placebo-treated patients. The number of LRTI was small in both treatment groups. Data confirm the good safety profile of vedolizumab even though RTI were more frequent in patients receiving vedolizumab and the risk of URTIs was significantly higher in patients with UC

Involvement of smad7 in inflammatory diseases of the gut and colon cancer

In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-beta 1 (TGF-beta 1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-beta 1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune-inflammatory responses. In patients with Crohn's disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-beta 1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-beta 1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer

Interleukin-34 promotes tumorigenic signals for colon cancer cells

Colorectal carcinoma (CRC) is one of the most common forms of malignancy in the Western world. Accumulating evidence indicates that colon carcinogenesis is tightly controlled by tumour-associated immune cells and stromal cells, which can either stimulate or suppress CRC cell growth and survival, mainly via the production of cytokines. Interleukin-34 (IL-34), a cytokine known to regulate mainly monocyte/macrophage survival and function, is highly produced within the CRC microenvironment by several cell types, including cancer cells, tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), and regulates the pro-tumoural functions of such cells. In this article, we summarize the available data supporting the multiple effects of IL-34 in human CRC

Difficult Biliary Stones: A Comprehensive Review of New and Old Lithotripsy Techniques

Biliary stones represent the most common indication for therapeutic endoscopic retrograde cholangiopancreatography. Many cases are successfully managed with biliary sphincterotomy and stone extraction with balloon or basket catheters. However, more complex conditions secondary to the specific features of stones, the biliary tract, or patient's needs could make the stone extraction with the standard techniques difficult. Traditionally, mechanical lithotripsy with baskets has been reported as a safe and effective technique to achieve stone clearance. More recently, the increasing use of endoscopic papillary large balloon dilation and the diffusion of single-operator cholangioscopy with laser or electrohydraulic lithotripsy have brought new, safe, and effective therapeutic possibilities to the management of such challenging cases. We here summarize the available evidence about the endoscopic management of difficult common bile duct stones and discuss current indications of different lithotripsy techniques

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs, and beyond

Metastatic colorectal cancer harboring a mutation in codon 12 or 13 of the KRAS gene does not benefit from therapy with antibodies targeting the epidermal growth factor receptor (EGFR). The implementation of community KRAS testing is generating a rapid flow of new data that have implications for the pathologist and testing guidelines, besides the physician. Therefore, it seems timely to draw together the threads of this large body of information in order that pathologists can be knowledgeable partners in the multidisciplinary process of targeted cancer therapy, and to help refine current testing guidelines. This review addresses: (1) the most relevant methodological and technical aspects of KRAS testing in terms of sample site (primary/metastatic), test specimens (resection/biopsy/cytology), and the diverse molecular methods available; (2) issues related to daily practice, namely the timing of the test, its turnaround time and the quality control procedures; and (3) the evidence related to the relationship between KRAS genetic intratumoral heterogeneity, clinical sensitivity of mutational detection tools and anti-EGFR treatment outcome. Hopefully, in the near future, elucidation of the potential of biomarker panels, and of the mechanisms underlying primary and acquired resistance to anti-EGFR therapy will refine even further personalized treatment regimes for patients with metastatic colorectal cancer

An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity.

BACKGROUND: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. METHODS: From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. RESULTS: In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. CONCLUSIONS: This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86

PHK from phenol hydroxylase of Pseudomonas sp. OX1. Insight into the role of an accessory protein in bacterial multicomponent monooxygenases

Bacterial multicomponent monooxygenases (BMMs) are members of a wide family of diiron enzymes that use molecular oxygen to hydroxylate a variety of aromatic compounds. The presence of genes encoding for accessory proteins not involved in catalysis and whose role is still elusive, is a common feature of the gene clusters of several BMMs, including phenol hydroxylases and several soluble methane monooxygenases. In this study we have expressed, purified, and partially characterized the accessory component PHK of the phenol hydroxylase from Pseudomonas sp. OX1, a bacterium able to degrade several aromatic compounds. The phenol hydroxylase (ph) gene cluster was expressed in Escherichia coli/JM109 cells in the absence and in the presence of the phk gene. The presence of the phk gene lead to an increase in the hydroxylase activity of whole recombinant cells with phenol. PHK was assessed for its ability to interact with the active hydroxylase complex. Our results show that PHK is neither involved in the catalytic activity of the phenol hydroxylase complex nor required for the assembly of apo-hydroxylase. Our results suggest instead that this component may be responsible for enhancing iron incorporation into the active site of the apo-hydroxylase

Fine-needle aspiration biopsy and flow cytometry immunophenotyping of lymphoid and myeloproliferative disorders of the spleen.

BACKGROUND: Flow cytometry (FC) is a useful adjunct to fine-needle aspiration biopsy (FNAB) in the evaluation of lymphoproliferative disorders. The application of FC to FNAB of the spleen (sFNAB) is reported. METHODS: Flow cytometry was performed on 18 sFNAB collected over 3 years. The series comprised 10 cases of non- Hodgkin lymphomas (NHL), 2 cases insufficient for diagnosis, 2 cases of reactive hyperplasia (RH), and 4 cases of myeloid metaplasia (MM). FNAB was performed under ultrasound guidance using a 22-gauge needle. One or two passes were sufficient to prepare a conventional smear that was immediately evaluated to select the cases studied and to prepare a cell suspension for FC. The following fluoresceinated antibodies were used: CD3, CD19/kappa/lambda, FMC7/CD23/CD19, Bcl-2, and CD13/HLA-DR. In six cases, cytospins were also prepared for immunocytochemistry and were tested for CD20 (L26), CD45Ro, and kappa and lambda light chain expression. RESULTS: Flow cytometry contributed to the diagnosis of all cases of NHL by assessing light chain restriction. The specific subtype was also diagnosed by CD19/CD5 and CD 19/CD10 coexpression in two cases. Flow cytometry quantified the percentage of myeloid cells in MM cases and contributed to the cytologic diagnosis showing a polyclonal light chain expression in RH cases.Immunocytochemistry was effective and concordant in four cases. Patients tolerated the sFNAB well and no complications were reported. Cytologic and FC diagnoses were confirmed by follow-up and by histologic evaluation in cases in which splenectomy was performed for therapeutic purposes. CONCLUSION: Flow cytometry applied to sFNAB corroborates the cytologic diagnosis in lymphoid and myeloproliferative disorders of the spleen and allows therapeutic decisions avoiding splenectomy

Prevalence of disordered eating behaviors in adolescents with type 1 diabetes: Results of multicenter Italian Nationwide study

Objective: To assess the prevalence of disordered eating behaviors (DEBs) in a large sample of Italian adolescents with type 1 diabetes and to explore potential demographic, clinical, and psychological differences (understood as emotional and behavioral problems) among adolescents with and without DEBs. Method: Adolescents (11–19 years) with type 1 diabetes completed the Diabetes Eating Problems Survey-revised (DEPS-r) and the Youth Self Report (YSR). Demographic and clinical data were also collected. Results: Of 690 adolescents with type 1 diabetes (mean age 14.97 ± 1.81, n = 337 girls) assessed in this study, 28.1% (21% boys, 35% girls) were DEPS-r positive (score ≥ 20). Girls had higher DEPS-r total scores (p <.0001, d =.42) than boys, although no age differences were found in mean DEPS-r total scores (p =.961). In both genders, adolescents with DEBs had significantly higher zBMI (p <.0001, d =.52) and HbA1c values (p <.0001, d =.54) and showed more emotional and behavioral problems (both as internalizing and externalizing problems) than those without DEBs (all p <.0001). These differences were largely confirmed in all age groups. Adolescents reporting insulin misuse had higher HbA1c values (p =.001, d =.26), higher DEPS-r mean scores (p <.0001, d = 1.07), and greater psychological problems (all p <.001) than those who did not. Discussion: DEBs are prevalent among adolescents with type 1 diabetes, and those with eating problems showed adverse clinical and psychological conditions. Routine screening for DEBs and of general psychological condition should be a fundamental part of diabetes care, especially during adolescence. Public significance statement: This nationwide study indicated that DEBs are common in adolescents with T1D, and those suffering from them show poorer clinical conditions and higher emotional and behavioral problems. As such, it offers important contributions for those working with EDs and in the T1D field, as it provides a deeper understanding of the co-occurring DEBs–emotional/behavioral problems in youths with T1D and highlights the importance of continuous monitoring of their psychological condition by a multidisciplinary team