Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl 4 -induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B hi F4/80 int Ly-6C lo macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter-diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C hi monocytes, a common origin with profibrotic Ly-6C hi macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C lo subset, compared with Ly-6C hi macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process.

Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics.

Emergency cholecystectomy is less costly and more effective than delayed cholecystectomy. This approach is likely to be beneficial to patients in terms of improved health outcomes and to the healthcare provider owing to the reduced costs.

BackgroundPostoperative pulmonary complications (PPC) are an under-reported but major cause of perioperative morbidity and mortality. The aim of this prospective, contemporary, multicentre cohort study of unselected patients undergoing major elective abdominal surgery was to determine the incidence and effects of PPC.MethodsData on all major elective abdominal operations performed over a 2-week period in December 2014 were collected in six hospitals. The primary outcome measure of PPC at 7 days was used. Univariate and multivariate analyses were performed to investigate how different factors were associated with PPC and the effects of such complications.ResultsTwo hundred sixty-eight major elective abdominal operations were performed, and the internal validation showed that the data set was 99 % accurate. Thirty-two (11.9 %) PPC were reported at 7 days. PPC was more common in patients with a history of chronic obstructive pulmonary disease compared to those with no history (26.7 vs. 10.2 %, p < 0.001). PPC was not associated with other patient factors (e.g. age, gender, body mass index or other comorbidities), type/method of operation or postoperative analgesia. The risk of PPC appeared to increase with every additional minute of operating time independent of other factors (odds ratio 1.01 (95 % confidence intervals 1.00–1.02), p = 0.007). PPC significantly increase the length of hospital stay (10 vs. 3 days). Attendance to the emergency department within 30 days (27.3 vs. 10.6 %), 30-day readmission (21.7 vs. 9.9 %) and 30-day mortality (12.5 vs. 0.0 %) was higher in those with PPC.ConclusionsPPC are common and have profound effects on outcomes. Strategies need to be considered to reduce PPC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13741-016-0037-0) contains supplementary material, which is available to authorized users.

Patients with similar characteristics presenting to different hospitals with acute gallbladder pathology do not receive comparable care.

The reversible photocontrol of an enzyme governing blood coagulation is demonstrated. The thrombin binding aptamer (TBA), was rendered photochromic by modification with two anthracene groups. Lighttriggered anthracene photodimerisation distorts its structure, inhibiting binding of the enzyme thrombin, which in turn triggers catalysis and the resulting clotting process.External control of biomolecule function is important for regulating biological processes that are relevant to various therapeutic and diagnostic applications. Photoregulation is a popular method of control due to the high level of specificity gained without the use of additional chemical reagents, 1 with photoswitchable groups allowing properties to be controlled in a reversible manner. As part of ongoing interest in this area, there are now a number of examples of different photoactive groups used for photocontrollable catalysis. 1a,2,3 Here, through the use of a photoswitchable DNA aptamer that displays anthracene photochromism, we demonstrate a new way of using light to reversibly control a catalytic process.Human a-thrombin, an enzyme from the family of serine proteases, is a key biological protein involved in the process of blood coagulation at the site of a blood vessel injury. 4 It has two anion binding exosites, one of which (exosite I) binds fibrinogen. During the formation of a blood clot, thrombin catalyses the production of insoluble fibrin polymers from soluble fibrinogen monomers. DNA aptamers, short single stranded oligonucleotides generated synthetically to bind proteins and small molecules, are widely used for a range of applications linked to diagnostics and therapy. 5 The thrombin binding aptamer or TBA (Fig. 1) is a 15-mer that adopts an anti-parallel G-quadruplex (G4) tertiary structure in the presence of K + ions and binds to thrombin at exosite I, the fibrinogen binding site. 6,7 The resulting complex competitively inhibits the binding of the enzyme to fibrinogen, thereby inhibiting the process of blood coagulation. This has led to the consideration of TBA and related compounds as treatments for medical conditions linked to blood clotting disorders. 5d However the use of anticoagulants, including traditional ones (e.g. heparin or warfarin), can often result in other healthcare risks. 8 For example, the reduction in systemic clotting capability could mean that wound healing is compromised at injury sites away from where anticoagulation is required. A dynamic system in which anticoagulation could be deactivated locally using an orthogonal and external source, and more quickly than the body's clearance systems, could provide an effective solution to such an issue.Previous examples exploring this idea using TBA derivatives 2d, f,7b have included azobenzene 2d and nitrophenyl 2f systems in which the application of light was found to alter clotting times. Anthracene photochromism is known to be particularly effective in photoregulatory processes within supramolecular systems as its reversible photodimerisation reaction can induce s...

A novel DNA sensing method based on LD spectroscopy and using bionanoparticle scaffolds is described, as demonstrated by the rapid detection of DNA strands associated with bacterial and viral pathogens.

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