Inflammation in irritable bowel syndrome:Myth or newtreatment target?

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.

Could JC virus provoke metastasis in colon cancer?

AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test.RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction(PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant(χ2 = 9.55, P = 0.002).CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.

Use of artificial intelligence in improving adenoma detection rate during colonoscopy:Might both endoscopists and pathologists be further helped

Colonoscopy remains the standard strategy for screening for colorectal cancer around the world due to its efficacy in both detecting adenomatous or precancerous lesions and the capacity to remove them intra-procedurally.Computeraided detection and diagnosis(CAD),thanks to the brand new developed innovations of artificial intelligence,and especially deep-learning techniques,leads to a promising solution to human biases in performance by guarantying decision support during colonoscopy.The application of CAD on real-time colonoscopy helps increasing the adenoma detection rate,and therefore contributes to reduce the incidence of interval cancers improving the effectiveness of colonoscopy screening on critical outcome such as colorectal cancer related mortality.Furthermore,a significant reduction in costs is also expected.In addition,the assistance of the machine will lead to a reduction of the examination time and therefore an optimization of the endoscopic schedule.The aim of this opinion review is to analyze the clinical applications of CAD and artificial intelligence in colonoscopy,as it is reported in literature,addressing evidence,limitations,and future prospects.

Targeted molecular therapy (modified RIST regimen) in relapsed high risk stage Ⅳ neuroblastoma: two cases report

The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge,and currently there are no known curative salvage regimens.In this paper we investigated the effect of imatinib with rapamycin and the chemotherapeutic agents temozolomide and irinotecan.We treated two children with recurrent neuroblastoma with this so called RIST protocol.Both patients,off therapy for 15 and 31 months,respectively are well,and developing normally,without any complications.These findings suggest that a combination regimen of RIST may provide a therapeutic benefit with a favorable toxicity profile to a unfortunate subset of patients with neuroblastoma.

Electrical probing of carrier separation in InAs/InP/GaAsSb core-dualshell nanowires

We investigate the tunnel coupling between the outer p-type GaAsSb shell and the n-type InAs core in catalyst-free InAs/lnP/GaAsSb core-dualshell nanowires.We present a device fabrication protocol based on wet-etching processes on selected areas of the nanostructures that enables multiple configurations of measurements in the same nanowire-based device(i.e.shell-shell,core-core and core-shell).Low-temperature(4.2 K)transport in the shell-shell configuration in nanowires with 5 nm-thick InP barrier reveals a weak negative differential resistance.Differently,when the InP barrier thickness is increased to 10 nm,this negative differential resistance is fully quenched.The electrical resistance between the InAs core and the GaAsSb shell,measured in core-shell configuration,is significantly higher with respect to the resistance of the InAs core and of the GaAsSb shell.The field effect,applied via a back-gate,has an opposite impact on the electrical transport in the core and in the shell portions.Our results show that electron and hole free carriers populate the InAs and GaAsSb regions respectively and indicate InAs/InP/GaAsSb core-dualshell nanowires as an ideal system for the investigation of the physics of interacting electrons and holes at the nanoscale.