Interplay between the QseC and QseE Bacterial Adrenergic Sensor Kinases in Salmonella enterica Serovar Typhimurium Pathogenesis

The bacterial adrenergic sensor kinases QseC and QseE respond to epinephrine and/or norepinephrine to initiate a complex phosphorelay regulatory cascade that modulates virulence gene expression in several pathogens. We have previously shown that QseC activates virulence gene expression in Salmonella enterica serovar Typhimurium. Here we report the role of QseE in S. Typhimurium pathogenesis as well as the interplay between these two histidine sensor kinases in gene regulation. An S. Typhimurium qseE mutant is hampered in the invasion of epithelial cells and intramacrophage replication. The ΔqseC strain is highly attenuated for intramacrophage survival but has only a minor defect in invasion. However, the ΔqseEC strain has only a slight attenuation in invasion, mirroring the ΔqseC strain, and has an intermediary intramacrophage replication defect in comparison to the ΔqseE and ΔqseC strains. The expressions of the sipA and sopB genes, involved in the invasion of epithelial cells, are activated by epinephrine via QseE. The expression levels of these genes are still decreased in the ΔqseEC double mutant, albeit to a lesser extent, congruent with the invasion phenotype of this mutant. The expression level of the sifA gene, important for intramacrophage replication, is decreased in the qseE mutant and the ΔqseEC double mutant grown in vitro. However, as previously reported by us, the epinephrine-dependent activation of this gene occurs via QseC. In the systemic model of S. Typhimurium infection of BALB/c mice, the qseC and qseE mutants are highly attenuated, while the double mutant has an intermediary phenotype. Altogether, these data suggest that both adrenergic sensors play an important role in modulating several aspects of S. Typhimurium pathogenesis.     

Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination

Human cytomegalovirus (HCMV) encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs). These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28^YFP expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAG^YFP in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28^YFP protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28^YFP is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the ΔUS28 virus (TB40/E-FLAG^YFP) generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAG^YFP (ΔUS28) displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus.     

Use of cyanoacrylate in the coaptation of edges of surgical wounds

Cyanoacrylate has been used in several fields of different surgical specialties as an adhesive for closure of gingival flaps and in mucous and cutaneous lacerations. One of its advantages is that it has an excellent immunological response. In view of aesthetic needs, cyanoacrylate has been applied with satisfactory results, when compared with sutures. It presents better coaptation of edges of cutaneous and mucosal lesions, smaller residual scars, and biocompatibility. However, it is limited to areas of little tissue tension. This work attempts to provide a literature review with the aim of revealing the advantages of using tissue adhesives, especially cyanoacrylates, in wound coaptation in comparison with conventional methods.     

Teaching advanced operation of an iPod-based speech-generating device to two students with autism spectrum disorders

We evaluated a program for teaching two adolescents with autism spectrum disorders (ASD) to perform more advanced operations on an iPod-based speech-generating device (SGD). The effects of the teaching program were evaluated in a multiprobe multiple baseline across participants design that included two intervention phases. The first intervention focused on teaching the students to navigate between two screen pages and complete a multi-step response sequence to request preferred stimuli. The second intervention aimed to teach the students to turn on and unlock the device prior to navigating to the correct screen pages. Teaching procedures included response prompting, prompt fading, and differential reinforcement. Results showed that both interventions were effective in teaching the respective operations. Learning advanced operation of the iPod-based SGD could be seen as one way to promote greater independence in using such devices for multi-step communication.     

Complications hépatobiliaires associées à l’insuffisance intestinale chez l’adulte et l’enfant

The treatment of chronic intestinal failure, of which the main cause is the short bowel syndrome, is based on parenteral nutrition. Intestinal failure-associated liver disease, which may worsen toward cirrhosis, is the most threatening intestinal failure-associated complication. Risk factors for intestinal failure-associated liver disease are related to parenteral nutrition modalities and to the underlying disease. Bowel rest and short bowel syndrome are risk factors for biliary lithiasis. Steatosis is mainly secondary to nutritional factors (excess of glucose and/or lipids, continuous parenteral nutrition). The main risk factors of cholestasis are intestinal resection, intestinal bacterial overgrowth, excess of long-chain polyunsaturated ω6 fatty acids and phytosterols from some lipid emulsions. Liver chronic inflammation, another risk factor for intestinal failure-associated liver disease, is related to recurrent infections, bacterial or toxinic translocation, high intake of long-chain polyunsaturated ω6 fatty acids as precursors of inflammatory mediators. Fibrosis, secondary to any lesions, could progress toward cirrhosis with portal hypertension and liver failure. In such condition, the only life-saving treatment is a combined liver-intestinal transplantation. The prevention is based on the identification of patients with high risk of complicated liver disease, and on the optimal management of both underlying disease and parenteral nutrition. Routine surveillance is based on biological markers of variable sensitivity and specificity, and ultrasonography. Liver biopsy is required to diagnose fibrosis, especially prior to decide for an isolated intestinal transplantation or combined intestine-liver transplantation.     

Evaluation of the validity of the Bolton Index using cone-beam computed tomography (CBCT)

Aims: To evaluate the reliability and reproducibility of calculating the Bolton Index using cone-beam computed tomography (CBCT), and to compare this with measurements obtained using the 2D Digital Method. Material and Methods: Traditional study models were obtained from 50 patients, which were then digitized in order to be able to measure them using the Digital Method. Likewise, CBCTs of those same patients were undertaken using the Dental Picasso Master 3D® and the images obtained were then analysed using the InVivoDental programme. Results: By determining the regression lines for both measurement methods, as well as the difference between both of their values, the two methods are shown to be comparable, despite the fact that the measurements analysed presented statistically significant differences. Conclusions: The three-dimensional models obtained from the CBCT are as accurate and reproducible as the digital models obtained from the plaster study casts for calculating the Bolton Index. The differences existing between both methods were clinically acceptable. Key words:Tooth-size, digital models, bolton index, CBCT.