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Pouchitis is an idiopathic inflammatory disease that may occur in ileal pouches, and it can lead to ileal pouch failure. This was a single-center, randomized, double-blinded, placebo-controlled trial that assessed the effect of Lactobacillus casei ( L. casei ) DG®, a probiotic strain, on the ileal pouch mucosa to determine the crosstalk between microbiota and mucosal immune system. Fifty-two patients undergoing restorative proctocolectomy were recruited and randomly assigned to receive a daily oral supplementation of L. casei DG® ( n  = 26) or placebo ( n  = 26) for 8 weeks from the ileostomy closure (T0) to a pouch endoscopy after 8 weeks (T1) and 1 year (T2). Ileal pouch mucosa samples were collected at T0, T1, and T2. At T1, the L. casei DG ®-supplemented group showed a significant reduction of inflammatory cytokines levels compared to T0 baseline levels in the pouch mucosa, whereas in the placebo group cytokines levels resulted stable. In conclusion, probiotic manipulation of mucosal microbiota by L. casei DG ®-supplementation after stoma closure in patients who underwent restorative proctocolectomy has a beneficial impact on the ileal pouch microenvironment. Registration number: NCT03136419 (http://www.clinicaltrials.gov).

Rectal cancer treatments may impact negatively on patients' bowel and sexual functions and, in turn, on health-related quality of life. Information on the likely effects of treatment is essential in order to facilitate the care process and the adaptation of patients to their condition. Studies that report on the comparison between rectal cancer patients and the general population are a useful source of this evidence, providing elements to aid in answering questions such as 'is my life going to be the same as before?' In this article, the authors have systematically reviewed articles published in the last 6 years that report on the comparison between rectal patients' and the general population's health-related quality of life. Sixteen out of 645 articles were included. The results are summarized and critically discussed.

Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.

Neoadjuvant therapy followed by total mesorectal excision is standard of care for locally advanced rectal cancer. However, this approach has been previously shown to be associated with high rate of morbidity and it may have a negative effect on patients' reported outcomes (PROs). In order to summarize findings on the effect of the neoadjuvant approach on PROs, we systematically reviewed articles published in the last five years. Thirty-five articles met the inclusion criteria. Ten articles compared the effect of surgery with and without neoadjuvant therapy, six articles compared different neoadjuvant therapies, ten articles reported on patients who were all treated with neoadjuvant therapy, and nine articles examined the effect of neoadjuvant therapy in the analyses. The results are summarized by function investigated and critically commented.

Activated sludge process is the most widely diffused system to treat wastewater to control the discharge of pollutants into the environment. Microorganisms are responsible for the removal of organic matter, nitrogen, phosphorous and other emerging contaminants. The environmental conditions of biological reactors significantly affects the ecology of the microbial community and, therefore, the performance of the treatment process. In the last years, ozone has been used to reduce excess sludge production by wastewater treatment plants (WWTPs), whose disposal represents one of the most relevant operational costs. The ozonation process has demonstrated to be a viable method to allow a consistent reduction in excess sludge. This study was carried out in a full-scale plant treating municipal wastewater in two parallel lines, one ozonated in the digestion tank and another used as a control. Bacterial communities of samples collected from both lines of digestion thanks were then compared to assess differences related to the ozonation treatment. Data were then analysed with terminal restriction fragment length polymorphism (T-RFLP) analysis on 16S rRNA gene. Differences between bacterial communities of both treated and untreated line appeared 2 weeks after the beginning of the treatment. Results demonstrated that ozonation treatment significantly affected the activated sludge in WWTP.

Nucleotides play a crucial role to cellular functions; they can be obtained from the diet or through the nucleotide salvage pathway, however, in particular situations (occurring mainly in newborns) the metabolic demand of nucleotides exceeds the capacity of their synthesis. These molecules, are receiving attention from a nutraceutical point of view because of their potential direct role in regulating metabolism and infant body condition. Donkey's milk may be considered a good replacer for cow's milk in feeding children with severe Ig-E mediated cow's milk protein allergy, due to its high similarity with human milk. In this study, the presence of cytidine, uridine, CMP, UMP, guanosine, and adenosine, involved in numerous biochemical and physiological activities, were detected for the first time through a RP-HPLC method.

Aim: To assess the distribution of CDA activity from whole blood of 142 healthy subjects, determining its main predictors among genetic (six CDA SNPs) and physiological factors (age and gender). Moreover, we performed a kinetic study of the two CDA protein variants (Q27 and K27) determined by the rs2072671 SNP., Materials & Methods: CDA activity was assessed by HPLC. Selected CDA SNPs were genotyped by PCR-based methods. Recombinant CDA protein variants (Q27 and K27) were expressed in an Escherichia coli strain SØ5201 and kinetic assays were performed., Results: The mean value of CDA activity was 0.051 ± 0.024 mU/mg and followed a normal distribution in the study population. Carriers of the CDA*2B (-451T/-92G/-31Del/79C/435C) haplotype displayed higher CDA activity compared with the others. CDA -451G>A, -92A>G and 79A>C (K27Q) SNPs displayed significant associations with CDA activity. The best predictive model of CDA activity included the variables gender and CDA 79A>C (K27Q). Cytidine is the preferential substrate for the variant Q27., Conclusion: We suggest the analysis of both CDA activity and CDA 79A>C (K27Q) SNP in future prospective trials with cytidine analogs, alone or in combination, in order to identify the best marker to secure the administration of these anticancer therapies.

The thermal stability of human cytidine deaminase (CDA), an enzyme involved in pyrimidine metabolism was investigated. With this in view, the residues R68 and Y60, supposed to be involved in the intersubunit interactions and in the catalytic site of CDA, were mutated to glutamine and glycine, respectively. Thermal stability experiments were performed on the purified mutants by means of circular dichroism and enzymatic assays. The results obtained should be useful for designing more efficient cytidine based drugs for chemotherapy.

Increased urinary excretion of urinary trypsin inhibitor (UTI) has been reported in various inflammatory conditions and in Alzheimer's subjects, but its diagnostic potential remains to be elucidated. A reliable and specific enzyme-linked immunosorbent assay (ELISA) test for the determination of the UTI in human urine was developed. This assay was performed using 96-well microtiter plates. The plate surface is coated with an anti-UTI polyclonal antibody, the urine sample was added in a dilution range, and the detection was achieved using the enzyme-conjugated antibody. The assay was quantified by the build-up of colored product upon the addition of the substrate. Recoveries were 93%, and the intra- and inter-assay CVs were 4.25% and 21%, respectively. The ELISA showed parallelism of standard and urine samples and no significant interference by the biological matrix. The usefulness of the assay has been demonstrated by applying it to urine samples from Alzheimer's disease patients, and comparing with negative controls. UTI urinary levels are significantly increased in Alzheimer's subjects.