Targeting a Newly Established Spontaneous Feline Fibrosarcoma Cell Line by Gene Transfer

Fibrosarcoma is a deadly disease in cats and is significantly more often located at classical vaccine injections sites. More rare forms of spontaneous non-vaccination site (NSV) fibrosarcomas have been described and have been found associated to genetic alterations. Purpose of this study was to compare the efficacy of adenoviral gene transfer in NVS fibrosarcoma. We isolated and characterized a NVS fibrosarcoma cell line (Cocca-6A) from a spontaneous fibrosarcoma that occurred in a domestic calico cat. The feline cells were karyotyped and their chromosome number was counted using a Giemsa staining. Adenoviral gene transfer was verified by western blot analysis. Flow cytometry assay and Annexin-V were used to study cell-cycle changes and cell death of transduced cells. Cocca-6A fibrosarcoma cells were morphologically and cytogenetically characterized. Giemsa block staining of metaphase spreads of the Cocca-6A cells showed deletion of one of the E1 chromosomes, where feline p53 maps. Semi-quantitative PCR demonstrated reduction of p53 genomic DNA in the Cocca-6A cells. Adenoviral gene transfer determined a remarkable effect on the viability and growth of the Cocca-6A cells following single transduction with adenoviruses carrying Mda-7/IL-24 or IFN-γ or various combination of RB/p105, Ras-DN, IFN-γ, and Mda-7 gene transfer. Therapy for feline fibrosarcomas is often insufficient for long lasting tumor eradication. More gene transfer studies should be conducted in order to understand if these viral vectors could be applicable regardless the origin (spontaneous vs. vaccine induced) of feline fibrosarcomas

Diagnosis and treatment of Chronic Constipation and Obstructed Defecation (part II: treatment)

The second part of the Consensus Statement of the Italian Association of Hospital Gastroenterologists and Italian Society of Colo-Rectal Surgery reports on the treatment of chronic constipation and obstructed defecation. There is no evidence that increasing fluid intake and physical activity can relieve the symptoms of chronic constipation. Patients with normal-transit constipation should increase their fibre intake through their diet or with commercial fibre. Osmotic laxatives may be effective in patients who do not respond to fibre supplements. Stimulant laxatives should be reserved for patients who do not respond to osmotic laxatives. Controlled trials have shown that serotoninergic enterokinetic agents, such as prucalopride, and prosecretory agents, such as lubiprostone, are effective in the treatment of patients with chronic constipation. Surgery is sometimes necessary. Total colectomy with ileorectostomy may be considered in patients with slow-transit constipation and inertia coli who are resistant to medical therapy and who do not have defecatory disorders, generalised motility disorders or psychological disorders. Randomised controlled trials have established the efficacy of rehabilitative treatment in dys-synergic defecation. Many surgical procedures may be used to treat obstructed defecation in patients with acquired anatomical defects, but none is considered to be the gold standard. Surgery should be reserved for selected patients with an impaired quality of life. Obstructed defecation is often associated with pelvic organ prolapse. Surgery with the placement of prostheses is replacing fascial surgery in the treatment of pelvic organ prolapse, but the efficacy and safety of such procedures have not yet been established

Diagnosis and treatment of Chronic Constipation and Obstructed Defecation (part II: treatment)

The second part of the Consensus Statement of the Italian Association of Hospital Gastroenterologists and Italian Society of Colo-Rectal Surgery reports on the treatment of chronic constipation and obstructed defecation. There is no evidence that increasing fluid intake and physical activity can relieve the symptoms of chronic constipation. Patients with normal-transit constipation should increase their fibre intake through their diet or with commercial fibre. Osmotic laxatives may be effective in patients who do not respond to fibre supplements. Stimulant laxatives should be reserved for patients who do not respond to osmotic laxatives. Controlled trials have shown that serotoninergic enterokinetic agents, such as prucalopride, and prosecretory agents, such as lubiprostone, are effective in the treatment of patients with chronic constipation. Surgery is sometimes necessary. Total colectomy with ileorectostomy may be considered in patients with slow-transit constipation and inertia coli who are resistant to medical therapy and who do not have defecatory disorders, generalised motility disorders or psychological disorders. Randomised controlled trials have established the efficacy of rehabilitative treatment in dys-synergic defecation. Many surgical procedures may be used to treat obstructed defecation in patients with acquired anatomical defects, but none is considered to be the gold standard. Surgery should be reserved for selected patients with an impaired quality of life. Obstructed defecation is often associated with pelvic organ prolapse. Surgery with the placement of prostheses is replacing fascial surgery in the treatment of pelvic organ prolapse, but the efficacy and safety of such procedures have not yet been established

High risk gaming is associated with frequent substance use: an exploratory survey among young adults

Introduction: internet gaming disorder (IGD) is an emerging conditions within the field of behavioural addictions. IGD has been demonstrated to be highly comorbid with many other mental health disorders. Among these, substance use has been associated with IGD, and there are underlying similarities between behavioural addictions and substance use disorders (SUDs). The aims of the present study were (i) to investigate the association between high risk gaming and substance use among young adults drawn from the general Italian population; (ii) to explore the psychopathological correlates of high risk gaming. Methods: lifetime substance use, type of substances consumed, and frequency of use were investigated through an online survey in a sample of 913 adults aged 18-40 years. High risk gaming was assessed using the ten-item Internet Gaming Disorder Test (IGDT-10). Psychopathology was assessed using the Revised 90-item Symptom Checklist (SCL-90-R). Results: high risk gaming prevalence rate was 4.4%. High risk gamers scored higher on all dimensions of psychopathology, confirming the association between high risk gaming and psychiatric distress. Regarding substance use, high risk gamers were more commonly polysubstance users and more commonly made use of psychodysleptic substances. High risk gamers were more commonly frequent substance users, and 32.5% of high risk gamers used or had used psychoactive substances often or everyday throughout their lives. Discussion and conclusion: The findings are in line with the concept of a common neurobiological vulnerability for both gaming and substance use. There is the need for more research to examine the phenomenology of gaming and its interplay with substance use to help develop effective interventions and prevention strategies

Fecal and mucosal microbiota profiling in irritable bowel syndrome and inflammatory bowel disease

An imbalance in the bacterial species resulting in the loss of intestinal homeostasis has been described in inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). In this prospective study, we investigated whether IBD and IBS patients exhibit specific changes in richness and distribution of fecal and mucosal-associated microbiota. Additionally, we assessed potential 16S rRNA gene amplicons biomarkers for IBD, IBS, and controls (CTRLs) by comparison of taxonomic composition. The relative abundance of bacteria, at phylum and genus/species levels, and the bacterial diversity were determined through 16S rRNA sequence-based fecal and mucosal microbiota analysis. Linear discriminant analysis effect size (LEfSe) was used for biomarker discovery associated to IBD and IBS as compared to CTRLs. In fecal and mucosal samples, the microbiota richness was characterized by a microbial diversity reduction, going from CTRLs to IBS to IBD. β-diversity analysis showed a clear separation between IBD and CTRLs and between IBD and IBS with no significant separation between IBS and CTRLs. β-diversity showed a clear separation between mucosa and stool samples in all the groups. In IBD, there was no difference between inflamed and not inflamed mucosa. Based upon the LEfSe data, the Anaerostipes and Ruminococcaceae were identified as the most differentially abundant bacterial taxa in CTRLs. Erysipelotrichi was identified as potential biomarker for IBS, while Gammaproteobacteria, Enterococcus, and Enterococcaceae for IBD. This study provides an overview of the alterations of microbiota and may aid in identifying potential 16S rRNA gene amplicons mucosal biomarkers for IBD and IBS

MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. Methods: A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). Results: OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P <= 0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. Conclusions: MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients