Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts

Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen

Art as a Means to Disrupt Routine Use of Space

This paper examines the publicly visible aspects of counter-terrorism activity in pedestrian spaces as mechanisms of disruption. We discuss the objectives of counter-terrorism in terms of disruption of routine for both hostile actors and general users of public spaces, categorising the desired effects as 1) triangulation of attention; 2) creation of unexpected performance; and 3) choreographing of crowd flow. We review the potential effects of these existing forms of disruption used in counter-terrorism. We then present a palette of art, advertising, architecture, and entertainment projects that offer examples of the same disruption effects of triangulation, performance and flow. We conclude by reviewing the existing support for public art in counter-terrorism policy, and build on the argument for art as an important alternative to authority. We suggest that while advocates of authority-based disruption might regard the playfulness of some art as a weakness, the unexpectedness it offers is perhaps a key strengt

Vastgoed-bv’s en bedrijfsopvolging bij schenking en vererving

In deze bijdrage gaan de auteurs in op de toepassing van de bedrijfsopvolgingsfaciliteiten terzake van de verkrijging van ab-aandelen in vennootschappen die zich bezighouden met vastgoed-exploitatie. Daarbij staat het vraagstuk rondom de kwalificatie van de werkzaamheden van vastgoed-exploitatie als onderneming centraal

Bedrijfsopvolging en vastgoed

De bedrijfsopvolgingsfaciliteiten in de Wet IB 2001 en de SW 1956 hebben tot doel om bedrijfsopvolgingen te faciliteren bij schenking of vererving. Mr. drs. O.P.M. Adriaansens en dr. A. Rozendal gaan in deze bijdrage in op de toepassing van deze faciliteiten op de schenking of vererving van onroerende zaken. Daarbij staat de kwalificatie van onroerende zaken die direct of indirect worden gehouden door een lichaam waarin de schenker of erflater een aanmerkelijk belang houdt centraal. De vraag of dergelijke onroerende zaken al dan niet kwalificeren als ondernemingsvermogen is op dit moment bijzonder actueel en leidt in de praktijk regelmatig tot discussie tussen belastingplichtigen en de fiscus. De auteurs bespreken in dit verband enkele relevante aspecten rondom de kwalificatie van vastgoedexploitatie die van belang zijn in het kader van deze discussies

Poor Correlation of Histologic Parameters Between Biopsy and Resection Specimen in Early Stage Oral Squamous Cell Carcinoma

OBJECTIVES: Infiltration depth, perineural growth (PG), vascular invasive growth (VG), and infiltrative growth (IG) are associated with regional metastases in oral squamous cell carcinomas (OSCCs). Preoperative knowledge of these parameters could facilitate the treatment planning of the neck. The aim of this study was to evaluate if the biopsy specimen correlates with the resection specimen. METHODS: In total, 149 patients with a pT1-2cN0 OSCC were included. Biopsy thickness and tumor thickness were analyzed. Occurrence of PG, VG, and IG was determined on biopsy and resection specimens and correlated with the N status and survival. Sensitivity, specificity, positive and negative predictive value, and diagnostic gain of the biopsy specimen were calculated. RESULTS: N+ patients showed PG, VG, and IG significantly more often in the resection specimen compared with N- patients (P = .02, P = .001, and P = .001, respectively). Histologic parameters in the biopsy specimens did not correlate with N status or survival. The positive diagnostic gain for biopsy specimens with PG, VG, and IG was 57%, 40%, and 19%, respectively. The negative diagnostic gain was 2%, 0%, and 22%, respectively. CONCLUSIONS: Histologic parameters in biopsy specimens do not represent the resection specimen. Determination of histologic parameters in routinely taken biopsy specimens of OSCC is not helpful in deciding whether to treat the neck

Implementation of web-based hospital specialist consultations to improve quality and expediency of general practitioners' care: a feasibility study

Contains fulltext : 204225.pdf (publisher's version ) (Open Access

Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model

Background: Both obesity and the presence of collagenolytic bacterial strains (Enterococcus faecalis) can increase the risk of anastomotic leak. The aim of this study was to determine whether mice chronically fed a high-fat Western-type diet (WD) develop anastomotic leak in association with altered microbiota, and whether this can be mitigated by a short course of standard chow diet (SD; low fat/high fibre) before surgery. Methods: Male C57BL/6 mice were assigned to either SD or an obesogenic WD for 6 weeks followed by preoperative antibiotics and colonic anastomosis. Microbiota were analysed longitudinally after operation and correlated with healing using an established anastomotic healing score. In reiterative experiments, mice fed a WD for 6 weeks were exposed to a SD for 2, 4 and 6 days before colonic surgery, and anastomotic healing and colonic microbiota analysed. Results: Compared with SD-fed mice, WD-fed mice demonstrated an increased risk of anastomotic leak, with a bloom in the abundance of Enterococcus in lumen and expelled stool (65–90 per cent for WD versus 4–15 per cent for SD; P = 0·010 for lumen, P = 0·013 for stool). Microbiota of SD-fed mice, but not those fed WD, were restored to their preoperative composition after surgery. Anastomotic healing was significantly improved when WD-fed mice were exposed to a SD diet for 2 days before antibiotics and surgery (P < 0·001). Conclusion: The adverse effects of chronic feeding of a WD on the microbiota and anastomotic healing can be prevented by a short course of SD in mice. Surgical relevance Worldwide, enhanced recovery programmes have developed into standards of care that reduce major complications after surgery, such as surgical-site infections and anastomotic leak. A complementary effort termed prehabilitation includes preoperative approaches such as smoking cessation, exercise and dietary modification. This study investigated whether a short course of dietary prehabilitation in the form of a low-fat/high-fibre composition can reverse the adverse effect of a high-fat Western-type diet on anastomotic healing in mice. Intake of a Western-type diet had a major adverse effect on both the intestinal microbiome and anastomotic healing following colonic anastomosis in mice. This could be reversed when mice received a low-fat/high-fibre diet before operation. Taken together, these data suggest that dietary modifications before major surgery can improve surgical outcomes via their effects on the intestinal microbiome