Repression of Flagella Is a Common Trait in Field Isolates of Salmonella enterica Serovar Dublin and Is Associated with Invasive Human Infections

The nontyphoidal Salmonella enterica serovar Dublin is adapted to cattle but infrequently infects humans, very often resulting in invasive infections with high levels of morbidity and mortality. A Salmonella-induced intestinal acute inflammatory response is postulated as a mechanism to prevent bacterial dissemination to systemic sites. In S. enterica serovar Typhimurium, flagella contribute to this response by providing motility and FliC-mediated activation of pattern recognition receptors. In this study, we found 4 Salmonella enterica isolates, with the antigenic formula 9,12:−:−, that, based on fliC sequence and multilocus sequence type (MLST) analyses, are aflagellate S. Dublin isolates. Interestingly, all were obtained from human bloodstream infections. Thus, we investigated the potential role of flagella in the unusual invasiveness exhibited by S. Dublin in humans by analyzing flagellation and proinflammatory properties of a collection of 10 S. Dublin human clinical isolates. We found that 4 of 7 blood isolates were aflagellate due to significantly reduced levels of fliC expression, whereas all 3 isolates from other sources were flagellated. Lack of flagella correlated with a reduced ability of triggering interleukin-8 (IL-8) and CCL20 chemokine expression in human intestinal Caco-2 cells and with reduced early inflammation in the ceca of streptomycin-pretreated C57/BL6 mice. These results indicate that flagella contribute to the host intestinal inflammatory response to Salmonella serovar Dublin and suggest that their absence may contribute to its systemic dissemination through dampening of the gut immune response. Analysis of FliC production in a collection of cattle isolates indicated that the aflagellate phenotype is widely distributed in field isolates of S. Dublin.     

Dispersion of γ-Alumina Nano-Sized Spherical Particles in a Calamitic Liquid Crystal. Study and Optimization of the Confinement Effects

We report an experimental study on confined systems formed by butyloxybenzylidene octylaniline liquid crystal (4O.8) + γ-alumina nanoparticles. The effects of the confinement in the thermal and dielectric properties of the liquid crystal under different densities of nanoparticles is analyzed by means of high resolution Modulated Differential Scanning Calorimetry (MDSC) and broadband dielectric spectroscopy. First, a drastic depression of the N-I and SmA-N transition temperatures is observed with confinement, the more concentration of nanoparticles the deeper this depression is, driving the nematic range closer to the room temperature. An interesting experimental law is found for both transition temperatures. Second, the change in shape of the heat capacity peaks is quantified by means of the full width half maximum (FWHM). Third, the confinement does not noticeably affect the molecular dynamics. Finally, the combination of nanoparticles and the external applied electric field tends to favor the alignment of the molecules in metallic cells. All these results indicate that the confinement of liquid crystals by means of γ-alumina nanoparticles could be optimum for liquid crystal-based electrooptic devices.     

Functional and structural adaptations in the pancreatic α-cell and changes in glucagon signaling during protein malnutrition

Chronic malnutrition leads to multiple changes in β-cell function and peripheral insulin actions to adapt glucose homeostasis to these restricted conditions. However, despite glucose homeostasis also depends on glucagon effects, the role of α-cells in malnutrition is largely unknown. Here, we studied α-cell function and hepatic glucagon signaling in mice fed with low-protein (LP) or normal-protein diet for 8 wk after weaning. Using confocal microscopy, we found that inhibition of Ca2? signaling by glucose was impaired in α-cells of LP mice. Consistent with these findings, the ability of glucose to inhibit glucagon release in isolated islets was also diminished in LP mice. This altered secretion was not related with changes in either glucagon gene expression or glucagon content. A morphometric analysis showed that α-cell mass was significantly increased in malnourished animals, aspect that was probably related with their enhanced plasma glucagon levels. When we analyzed the hepatic function, we observed that the phosphorylation of protein kinase A and cAMP response-binding element protein in response to fasting or exogenous glucagon was impaired in LP mice. Additionally, the up-regulated gene expression in response to fasting observed in the hepatic glucagon receptor as well as several key hepatic enzymes, such as peroxisome proliferator-activated receptor γ, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase, was altered in malnourished animals. Finally, liver glycogen mobilization in response to fasting and the ability of exogenous glucagon to raise plasma glucose levels were lower in LP mice. Therefore, chronic protein malnutrition leads to several alterations in both the α-cell function and hepatic glucagon signaling.     

Laser Therapy as an Effective Method for Implant Surface Decontamination: A Histomorphometric Study in Rats

Background: To the best of the authors’ knowledge, a standard protocol for treating peri‐implantitis is not yet established. Methods: A total of 150 titanium disks with smooth or rough surfaces contaminated with microbial biofilm were implanted subcutaneously in rats after undergoing one of three treatments: 1) low‐intensity laser (LIL); 2) antimicrobial photodynamic therapy (aPDT); or 3) toluidine blue O (TBO). Sterile and contaminated disks served as negative (NC) and positive (C) control groups, respectively. After days 7, 28, and 84, tissue inflammation was evaluated microscopically by measuring the density of collagen fibers (degree of fibrosis) and concentration of polymorphonuclear neutrophils. Results: Surface texture did not affect the degree of inflammation, but the area of reactive tissue was significantly greater for rough implants (2.6 ± 3.7 × 10⁶ µm²) than for smooth ones (1.9 ± 2.6 × 10⁶ µm²; P = 0.0377). Group C presented the lowest and group NC presented the highest degree of fibrosis with significance only after day 7; these groups had the highest and lowest scores, respectively, for degree of inflammation. Group C showed the largest area of reactive tissue (9.11 ± 2.10 × 10⁶ µm²), but it was not significantly larger than group LIL (P = 0.3031) and group TBO (P = 0.1333). Group aPDT showed the smallest area (4.34 ± 1.49 × 10⁶ µm²) of reactive tissue among the treatment groups. After day 28, groups LIL, aPDT, TBO, and C resembled group NC in all the studied parameters. Conclusion: Group aPDT showed more favorable results in parameter area of reactive tissue than the other methods after day 7, but over longer time periods all methods produced outcomes equivalent to sterile implants.     

Post‐transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.