The response regulator OmpR is involved in numerous adaptive responses to environmental challenges. The role that OmpR plays in swarming behavior and swarm-cell differentiation in the symbiotic-pathogenic bacterium Xenorhabdus nematophila was examined in this study. Swarming began 4 h sooner in an ompR mutant strain than in wild-type cells. Precocious swarming was correlated with elevated expression of fliC, early flagellation, and cell elongation. The level of flhDC mRNA was elevated during the early period of swarming in the ompR strain relative to the level in the wild type. These findings show that OmpR is involved in the temporal regulation of flhDC expression and flagellum production and demonstrate that this response regulator plays a role in the swarming behavior of X. nematophila.Xenorhabdus nematophila is a motile gram-negative bacterium belonging to the Proteus clade of the Enterobacteriaceae family (9, 10). Its life cycle is characterized by a symbiotic association with a soil nematode and by pathogenic interactions with different insect hosts. X. nematophila persists in the specialized gut sac of the entomopathogenic nematode Steinernema carpocapsae (10,20). As X. nematophila transitions from the symbiotic stage in the nematode to the pathogenic stage, it must adapt to the hemocoel environment and the innate immune system of the insect. The regulatory pathways involved in adaptation to the insect hemocoel are not well understood. Bacterial adaptation to different environmental conditions involves two-component signal transduction pathways consisting of histidine kinase sensors and response regulators (22, 23). Histidine kinases sense environmental signals, undergo autophosphorylation, and subsequently transfer a phosphate group to a cognate response regulator. Sensor kinases can also possess phosphatase activity that stimulates the dephosphorylation of the cognate response regulator. In addition, response regulators can be phosphorylated by low-molecular-weight phosphodonors such as acetyl phosphate (21, 31). Modulation of the phosphorylated state of the response regulator controls the expression of the target genes.The OmpR-EnvZ two-component system has been studied extensively in Escherichia coli and Salmonella. The response regulator OmpR is involved in regulating numerous cell functions, including the expression of ompF and ompC porin genes, motility, biofilm formation, adaptation to acidic conditions, and virulence (2,18,23,25,26,30). In E. coli and Salmonella enterica serovar Typhimurium, ompF is expressed under lowosmolarity conditions, while ompF is repressed and ompC expression increases under high-osmolarity conditions. In contrast, expression of opnP, the ompF homolog of X. nematophila, requires OmpR, but OpnP is not osmoregulated (5,11,28). A shift to high-osmolarity conditions does not reduce OpnP production or affect the production of other outer membrane proteins (11). An ompC homolog has not been identified in X. nematophila, and inactivation of ompR does not affect the production of...

Epidermal squamous cell carcinoma is an extremely common type of cancer. Early tumors can be successfully treated by surgery, but recurrent disease is aggressive and resistant to therapy. Cisplatin is often used as a treatment, but the outcome is rarely satisfactory. For this reason new strategies are required. Sulforaphane is a diet‐derived cancer prevention agent that is effective in suppressing tumor growth in animal models of skin cancer. We monitored the efficacy of sulforaphane and cisplatin as a combined therapy for squamous cell carcinoma. Both agents suppress cell proliferation, growth of cancer stem cell spheroids, matrigel invasion and migration of SCC‐13 and HaCaT cells, and combination treatment is more efficient. In addition, SCC‐13 cell derived cancer stem cells are more responsive to these agents than non‐stem cancer cells. Both agents suppress tumor formation, but enhanced suppression is observed with combined treatment. Moreover, both agents reduce the number of tumor‐resident cancer stem cells. SFN treatment of cultured cells or tumors increases apoptosis and p21Cip1 level, and both agents increase tumor apoptosis. We suggest that combined therapy with sulforaphane and cisplatin is efficient in suppressing tumor formation and may be a treatment option for advanced epidermal squamous cell carcinoma.

Alvimopan is a μ-opioid receptor antagonist used in the post-operative period to decrease rates of post-operative ileus (POI) following radical cystectomy (RC) and thereby shorten length of stay (LOS). Naloxegol is a much less expensive drug of the same class that has yet to be studied for prevention of POI in the peri-operative period. The purpose of the current study is to evaluate the differences in LOS and development of POI in patients post-RC who take alvimopan versus those who take naloxegol, with the hope that drug efficacy can be evaluated against the significant difference in cost burden between the two drugs. The study population included all adult patients between 18–89 years of age with bladder cancer undergoing radical cystectomy with urostomy at University of Colorado Hospital. Those patients who received usual post-operative care as well as either alvimopan or naloxegol between September 2011 and December 2017 were selected for analysis. Patients who did not take either medication or were switched from one drug to the other were excluded from the study. A zero-truncated binomial regression analysis was used to analyze differences in length of stay in patients who received alvimopan versus those who received naloxegol. Additionally, the incidence of post-operative ileus was compared between treatment groups. 130 patients who underwent RC and received either alvimopan or naloxegol were included in the study: 75 (58%) received alvimopan and 55 (42%) received naloxegol. Baseline characteristics were similar between treatment groups. There was no significant difference in the length of stay between patients who received alvimopan and patients who received naloxegol after adjusting for age, sex, BMI, length of surgical time, or stage of disease (p = 0.41). There was no significant between the two drugs for development of POI (p = 0.85). Development of POI was significantly associated with a longer LOS (p = 0.007). The analysis showed that naloxegol was comparable to alvimopan when it came to length of hospital stay following RC. Therefore, naloxegol may be offered as a less expensive, effective alternative to alvimopan.

No abstract

Introduction: Bowel obstruction is a rare but well reported complication of blunt abdominal trauma (BAT). Obstruction is most often seen acutely caused by bowel wall hematomas and chronically as a result of post-traumatic strictures. Here, we present a novel case of BAT causing a subacute obstructing bowel wall hematoma. Case Report: A healthy, 32-year-old male presented to our emergency department with three days of nausea and vomiting. Chart review revealed he had been seen two weeks prior after a high-speed motor vehicle collision. During that initial visit, the patient had a benign abdominal exam and was discharged without imaging. On this return visit, the patient was found to have a large, obstructing colonic hematoma. Conclusion: Because emergency physicians care for patients in both the acute and subacute phases of trauma, clinicians should recognize the more subtle sequelae of BAT.