Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction

The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1^lo and F4/80^hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.     

Low dose vaccination with attenuated Francisella tularensis strain SchuS4 mutants protects against tularemia independent of the route of vaccination

Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. <100 organisms, may address this concern. Herein we describe the ability of three defined, attenuated mutants of F. tularensis SchuS4, deleted for FTT0369c, FTT1676, or FTT0369c and FTT1676, respectively, to engender protective immunity against tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia.     

Wound Edge Protectors in Open Abdominal Surgery to Reduce Surgical Site Infections: A Systematic Review and Meta-Analysis

Importance

Surgical site infections remain one of the most frequent complications following abdominal surgery and cause substantial costs, morbidity and mortality.

Objective

To assess the effectiveness of wound edge protectors in open abdominal surgery in reducing surgical site infections.

Evidence Review

A systematic literature search was conducted according to a prespecified review protocol in a variety of data-bases combined with hand-searches for randomized controlled trials on wound edge protectors in patients undergoing laparotomy. A qualitative and quantitative analysis of included trials was conducted.

Findings

We identified 16 randomized controlled trials including 3695 patients investigating wound edge protectors published between 1972 and 2014. Critical appraisal uncovered a number of methodological flaws, predominantly in the older trials. Wound edge protectors significantly reduced the rate of surgical site infections (risk ratio 0.65; 95%CI, 0.51–0.83; p = 0.0007; I² = 52%). The results were robust in a number of sensitivity analyses. A similar effect size was found in the subgroup of patients undergoing colorectal surgery (risk ratio 0.65; 95%CI, 0.44–0.97; p = 0.04; I² = 56%). Of the two common types of wound protectors double ring devices were found to exhibit a greater protective effect (risk ratio 0.29; 95%CI, 0.15–0.55) than single-ring devices (risk ratio 0.71; 95%CI, 0.54–0.92), but this might largely be due to the lower quality of available data for double-ring devices. Exploratory subgroup analyses for the degree of contamination showed a larger protective effect in contaminated cases (0.44; 95%CI, 0.28–0.67; p = 0.0002, I² = 23%) than in clean-contaminated surgeries (0.72, 95%CI, 0.57–0.91; p = 0.005; I² = 46%) and a strong effect on the reduction of superficial surgical site infections (risk ratio 0.45; 95%CI, 0.24–0.82; p = 0.001; I² = 72%).

Conclusions and Relevance

Wound edge protectors significantly reduce the rate of surgical site infections in open abdominal surgery. Further trials are needed to explore their effectiveness in different risk constellations.     

Habitat selection and spatiotemporal interactions of a reintroduced mesocarnivore

Habitat quality and quantity are key factors in evaluating the potential for success of a wildlife translocation. However, because of the difficulty or cost of evaluating these factors, habitat assessments may not include valuable information on important habitat attributes including the abundance and distribution of prey, predators, and competitors. Fishers (Pekania pennanti) are one of the most commonly reintroduced carnivores in North America, and they are a species of conservation concern in their western range. We examined the relative importance of landscape features and species interactions in determining habitat use of a reintroduced population of fishers in the southern Cascade Mountains, Washington, USA. We used detections of prey and predators at 134 remote camera stations, remotely sensed forest structure data, and telemetry locations of fishers in a resource selection function to assess the relative importance of prey, predators, and forest structure in fisher habitat selection. Fishers selected habitats based on forest conditions and activity levels of snowshoe hares (Lepus americanus), whereas bobcat (Lynx rufus) and coyote (Canis latrans) activity levels did not directly affect habitat selection. The probability of fisher use increased in older stands, close to recently disturbed stands, and in areas with intermediate levels of hare activity. Bobcat and hare activity levels were positively correlated, and fishers avoided areas with the greatest hare activity, suggesting that fishers may experience a food-safety tradeoff in the study area. Temporal activity patterns in photo detections indicate that fishers may mediate this danger by avoiding bobcats temporally. Our findings suggest that fishers in Washington prefer habitat mosaics of old and recently disturbed stands where they have greater access to resting structures and hares. Management that maintains mosaics of young and old forest across large landscapes is likely to support fisher recovery. Future reintroduction efforts would benefit from an assessment of prey and predator abundance in proposed reintroduction areas before project initiation. © 2019 The Wildlife Society.     

Potential Properties of Lactobacillus plantarum F-10 as a Bio-control Strategy for Wound Infections

In this study, Lactobacillus plantarum F-10, a promising probiotic strain isolated from fecal microbiota of healthy breastfed infant, was assessed as a bio-control strategy for wound infections. Pseudomonas aeruginosa PAO1/ATCC 27853, methicillin-resistant Staphylococcus aureus ATCC 43300, and their hospital-derived strains isolated from skin chronic wound samples were used as important skin pathogens. The cell-free extract (CFE) of the strain F-10 was shown to inhibit the growth of all pathogens tested, while no inhibition was observed when CFE was neutralized. The strain displayed no hemolysis and exhibited a strong auto-aggregating phenotype (51.48 ± 1.45%, 5 h) as well as co-aggregation. Antibiotic resistance profile was found to be safe according to the European Food Safety Authority. Biofilm formation was measured by crystal violet assay and visualized with scanning electron microscopy and confocal laser scanning microscopy. One hundred percent reduction in biofilm formation of all pathogens tested was obtained by sub-MIC value (12.5 mg/ml) of CFE following 24-h co-incubation. Inhibition of quorum sensing–controlled virulence factors (motility, protease and elastase activity, production of pyocyanin and rhamnolipid) of P. aeruginosa strains was also observed. DPPH radical scavenging activity of the CFE was determined as 88.57 ± 0.49%. In conclusion, our results suggest that L. plantarum F-10 may represent an alternative bio-control strategy against skin infections with its antimicrobial, anti-biofilm, anti-quorum sensing, and antioxidant activity.

     

Challenges to global surveillance and response to infectious disease outbreaks of international importance

This article presents a notional scheme of global surveillance and response to infectious disease outbreaks and reviews 14 international surveillance and response programs. In combination, the scheme and the programs illustrate how, in an ideal world and in the real world, infectious disease outbreaks of public health significance could be detected and contained. Notable practices and achievements of the programs are cited; these may be useful when instituting new programs or redesigning existing ones. Insufficiencies are identified in four critical areas: health infrastructure; scientific methods and concepts of operation; essential human, technical, and financial resources; and international policies. These insufficiencies challenge global surveillance of and response to infectious disease outbreaks of international importance. This article is intended to help policymakers appreciate the complexity of the problem and assess the impact and cost-effectiveness of proposed solutions. An assessment of the potential contribution of appropriate diagnostic tests to surveillance and response is included.     

Use of response surface optimization for the production of biosurfactant from Rhodococcus spp. MTCC 2574

The production of biosurfactant from Rhodococcus spp. MTCC 2574 was effectively enhanced by response surface methodology (RSM). Rhodococcus spp. MTCC 2574 was selected through screening of seven different Rhodococcus strains. The preliminary screening experiments (one-factor at a time) suggested that carbon source: mannitol, nitrogen source: yeast extract and meat peptone and inducer: n-hexadecane are the critical medium components. The concentrations of these four media components were optimized by using central composite rotatable design (CCRD) of RSM. The adequately high R2 value (0.947) and F score 19.11 indicated the statistical significance of the model. The optimum medium composition for biosurfactant production was found to contain mannitol (1.6 g/L), yeast extract (6.92 g/L), meat peptone (19.65 g/L), n-hexadecane (63.8 g/L). The crude biosurfactant was obtained from methyl tert-butyl ether extraction. The yield of biosurfactant before and after optimization was 3.2 g/L of and 10.9 g/L, respectively. Thus, RSM has increased the yield of biosurfactant to 3.4-fold. The crude biosurfactant decreased the surface tension of water from 72 mN/m to 30.8 mN/m (at 120 mg L(-1)) and achieved a critical micelle concentration (CMC) value of 120 mg L(-1).     

Déjà vu--a study of duplicate citations in Medline

MOTIVATION: Duplicate publication impacts the quality of the scientific corpus, has been difficult to detect, and studies this far have been limited in scope and size. Using text similarity searches, we were able to identify signatures of duplicate citations among a body of abstracts. RESULTS: A sample of 62,213 Medline citations was examined and a database of manually verified duplicate citations was created to study author publication behavior. We found that 0.04% of the citations with no shared authors were highly similar and are thus potential cases of plagiarism. 1.35% with shared authors were sufficiently similar to be considered a duplicate. Extrapolating, this would correspond to 3500 and 117,500 duplicate citations in total, respectively. Availability: eTBLAST, an automated citation matching tool, and Déjà vu, the duplicate citation database, are freely available at http://invention.swmed.edu/ and http://spore.swmed.edu/dejavu