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Background: Ulcerative colitis (UC) is a progressive disorder that elevates the risk of colon cancer development through a colitis-dysplasia-carcinoma sequence. Gene expression profiling of colitis-associated lesions obtained from patients with varied extents of UC can be mined to define molecular panels associated with colon cancer development., Methods: Differential gene expression profiles of 3 UC clinical subtypes and healthy controls were developed for the GSE47908 microarray data set of healthy controls, left-sided colitis, pancolitis, and colitis-associated dysplasia (CAD) using limma R., Results: A gene ontology enrichment analysis of differentially expressed genes (DEGs) revealed a shift in the transcriptome landscape as UC progressed from left-sided colitis to pancolitis to CAD, from being immune-centric to being cytoskeleton-dependent. Hippo signaling (via Yes-associated protein [YAP]) and Ephrin receptor signaling were the top canonical pathways progressively altered in concert with the pathogenic progression of UC. A molecular interaction network analysis of DEGs in left-sided colitis, pancolitis, and CAD revealed 1 pairwise line, or edge, that was topologically important to the network structure. This edge was found to be highly enriched in actin-based processes, and death-associated protein kinase 3 (DAPK3) was a critical member and sole protein kinase member of this network. Death-associated protein kinase 3 is a regulator of actin-cytoskeleton reorganization that controls proliferation and apoptosis. Differential correlation analyses revealed a negative correlation for DAPK3-YAP in healthy controls that flipped to positive in left-sided colitis. With UC progression to CAD, the DAPK3-YAP correlation grew progressively more positive., Conclusion: In summary, DAPK3 was identified as a candidate gene involved in UC progression to dysplasia., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18., Methods: In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis., Results: Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota., Conclusions: Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Background: Recovery of dialysis-independent renal function in long-term dialysis patients has not been studied extensively. The aim of this study was to investigate the effect of dialysis modality on the likelihood, timing and durability of recovery of dialysis-independent renal function., Methods: The study reviewed all patients in Australia and New Zealand who commenced dialysis for treatment of end-stage renal disease (ESRD) between 1963 and 2006. Dialysis modality was assigned at 90 days. A supplementary analysis was also conducted using a contemporary cohort that included data on comorbidities, smoking and eGFR at dialysis onset., Results: During the study period, 15 912 individuals received peritoneal dialysis (PD) and 23 658 received haemodialysis (HD). Renal recovery occurred in 176 (1.1%) PD and 244 (1.0%) HD patients. Using multivariate Cox proportional hazards regression analyses, dialysis modality was not independently predictive of time to renal recovery (HR 0.92, 95% CI 0.76-1.13, P = 0.4). Recovery was significantly more likely in patients with higher baseline eGFR, with no hypertension or peripheral vascular disease, and with certain causes of kidney failure (autoimmune renal disease, haemolytic uraemic syndrome, interstitial nephritis, obstructive uropathy, paraproteinaemia and renovascular nephrosclerosis). Recovery was less likely in Maori/Pacific Islanders and polycystic kidney disease. Among patients who recovered, 328 (78%) subsequently experienced renal death, mostly within the first year. The duration of renal recovery was not associated with initial dialysis modality (OR 0.82, 95% CI 0.50- 1.32)., Conclusions: Dialysis modality is not associated with the likelihood, timing or durability of spontaneous recovery of dialysis-independent renal function in patients thought to have ESRD.

Aims: Current US regulations (40 CFR 503) for 'Class A' biosolids (treated sewage sludge) requires use of multiple-tube fermentation techniques for fecal coliform or multiple tube enrichment techniques for Salmonella spp. followed by isolation and biochemical and serologic confirmation. The technical difficulties and the time required to complete the procedure for enumeration of Salmonellae in biosolids and sludges has limited the use of this assay. This study was conducted to determine if a commercially available molecular probe system could be used to isolate and enumerate Salmonella spp. in biosolids or sludges in less time than cultural techniques with biochemical confirmation., Methods and Results: Several types of treated and untreated municipal sludges were assayed for Salmonellae using a cultural technique with biochemical and serologic confirmation and a DNA probe diagnostic test kit. The results indicate that the molecular probe and the conventional fermentation tube technique yielded equivalent results. Interestingly, the probe technique yielded results within 52 h following initiation of sample analysis compared with the conventional fermentation tube technique with confirmation which required approx. 120 h., Conclusions: These results suggest that the molecular probe system used for this work may be used to determine the presence or absence of Salmonella spp. in biosolids within a relatively short time frame., Significance and Impact of the Study: The ease of using the DNA probe test kit, along with its ability to produce results in less than half the time of conventional culture techniques, suggests that this assay is useful for determining the presence or absence of Salmonellae in biosolids samples.

We describe an isothermal gas-liquid chromatographic procedure developed for measuring procaine and chloroprocaine in plasma. The unchanged drug is extracted into toluene from alkalinized plasma, together with an internal standard. The solvent is removed, the residue redissolved in methanol, and aliquots are injected into a 91.5-cm gas-liquid chromatographic column containing 3% OV-210. Sensitivity of detection is in the nanogram range.

We describe an isothermal gas-liquid chromatographic procedure developed for measuring thiamylal and thiopental in plasma. The unchanged drug is extracted into ethyl acetate from acidified plasma, together with an internal standard. The solvent is removed, the residue methylated, aliquots, diluted with benzene, are injected into a 183-cm gas-liquid chromatographic column containing 3% OV-17. Sensitivity of detection is in the nanogram to picogram range.

Internal fistula formation is a rare complication of pancreatic abscess or pseudocyst; a fairly extensive search of the literature has produced only 47 cases. Common factors in the aetiology, presentation and management are discussed, and a further case is reported which demonstrates many features of this unusual condition.