Review on tissue repair and M1‐like to M2a‐like macrophages, exhibiting important differences from in vitro phenotypes.
Mp are crucial for tissue repair and regeneration but can also contribute to ...tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best‐characterized in vitro phenotypes are a proinflammatory “M1” phenotype, produced by exposure to IFN‐γ and TNF‐α, and an anti‐inflammatory “M2a” phenotype, produced by IL‐4 or IL‐13. M2a Mp are frequently termed “wound healing” Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro‐defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a‐associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1‐ and M2‐associated markers may be expressed simultaneously by actual tissue‐repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.
Macrophages are essential for the efficient healing of numerous tissues, and they contribute to impaired healing and fibrosis. Tissue repair proceeds through overlapping phases of inflammation, ...proliferation, and remodeling, and macrophages are present throughout this progression. Macrophages exhibit transitions in phenotype and function as tissue repair progresses, although the precise factors regulating these transitions remain poorly defined. In efficiently healing injuries, macrophages present during a given stage of repair appear to orchestrate transition into the next phase and, in turn, can promote debridement of the injury site, cell proliferation and angiogenesis, collagen deposition, and matrix remodeling. However, dysregulated macrophage function can contribute to failure to heal or fibrosis in several pathological situations. This review will address current knowledge of the origins and functions of macrophages during the progression of tissue repair, with emphasis on skin and skeletal muscle. Dysregulation of macrophages in disease states and therapies targeting macrophage activation to promote tissue repair are also discussed.
Temporal changes for intestinal resections for Crohn's disease (CD) are controversial. We validated administrative database codes for CD diagnosis and surgery in hospitalized patients and then ...evaluated temporal trends in CD surgical resection rates.
First, we validated International Classification of Disease (ICD)-10-CM coding for CD diagnosis in hospitalized patients and Canadian Classification of Health Intervention coding for surgical resections. Second, we used these validated codes to conduct population-based surveillance between fiscal years 2002 and 2010 to identify adult CD patients undergoing intestinal resection (n=981). Annual surgical rate was calculated by dividing incident surgeries by estimated CD prevalence. Time trend analysis was performed and annual percent change (APC) with 95% confidence intervals (CI) in surgical resection rates were calculated using a generalized linear model assuming a Poisson distribution.
In the validation cohort, 101/104 (97.1%) patients undergoing surgery and 191/200 (95.5%) patients admitted without surgery were confirmed to have CD on chart review. Among the 116 administrative database codes for surgical resection, 97.4% were confirmed intestinal resections on chart review. From 2002 to 2010, the overall CD surgical resection rate was 3.8 resections per 100 person-years. During the study period, rate of surgery decreased by 3.5% per year (95% CI: -1.1%, -5.8%), driven by decreasing emergent operations (-10.1% per year (95% CI: -13.4%, -6.7%)) whereas elective surgeries increased by 3.7% per year (95% CI: 0.1%, 7.3%).
Overall surgical resection rates in CD are decreasing, but a paradigm shift has occurred whereby elective operations are now more commonly performed than emergent surgeries.
Sputum culture is an insensitive method for the diagnosis of pulmonary aspergillosis. Growth of the organism allows identification of the causative species and susceptibility testing, both of which ...can inform treatment choices. The current practice is to culture an aliquot of diluted sputum. We assessed the value of culturing large volumes of unprocessed sputum, a method that we have termed high-volume culture (HVC).
Specimens were processed by conventional culture (using an aliquot of homogenized, diluted sputum on Sabouraud agar at 37°C and 45°C for up to 5 days) and HVC (using undiluted sputum on Sabouraud agar at 30°C for up to 14 days). A separate specimen was tested by quantitative real-time PCR. Antifungal susceptibility testing was performed by the EUCAST standard.
We obtained sputum specimens from 229 individuals with the following conditions: chronic pulmonary aspergillosis (66.8%, 153/229), allergic bronchopulmonary aspergillosis (25.3%, 58/229) and Aspergillus bronchitis (7.9%, 18/229). Individuals with invasive pulmonary aspergillosis were not included. The positivity rate of conventional culture was 15.7% (36/229, 95% CI 11.6%–21.0%) and that of HVC was 54.2% (124/229, 95% CI 47.7%–60.5%) (p < 0.001). The higher positivity rate of HVC was demonstrated regardless of administration of antifungal treatment. Quantitive real-time PCR had an overall positivity rate of 49.2% (65/132, 95% CI 40.9%–57.7%), comparable to that of HVC.
Detection of Aspergillus spp. in sputum is greatly enhanced by HVC. HVC allows for detection of azole-resistant isolates that would have been missed by conventional culture. This method can be performed in any microbiology laboratory without the need for additional equipment.
•A full-scale moving bed biofilm reactor (MBBR) was operated for 5 years.•MBBR was fed with wastewater containing cyanides, aniline and very high salinity.•Mean cyanide removal efficiency ranged from ...75% to 99%.•Aniline removal efficiency reached more than 85%.•The MBBR was capable to fulfil the requirements of Czech Water and Waste Acts.
Treatment of industrial wastewaters is usually difficult due to large variations in their composition, high organic matter content and presence of poorly biodegradable compounds. This paper describes operational experience with the first full-scale application of a moving bed biofilm reactor (MBBR) in the Czech Republic. The MBBR treats industrial wastewater from the Lučební závody Draslovka a.s. (Kolín) chemical plant in the Czech Republic, and particularly that from production of diphenylguanidine. The wastewater is characterised by a high content of cyanides and aniline, very high salinity, diphenylguanidine and phenylurea residues, and considerable fluctuations in concentrations as well as temperature during the year.
Long-term (5-years) MBBR operation has demonstrated that, following initial stabilisation and implementation of additional pretreatment, the system is capable of treating such hardly biodegradable industrial wastewater with high removal efficiency, with mean cyanide removal efficiency ranging from 75% to 99%. Aniline removal efficiency also reached more than 85%, while diphenylguanidine, phenylurea and N,N-diphenylurea removal was almost quantitative.
To understand shapes and movements of cells undergoing lamellipodial motility, we systematically explore minimal free-boundary models of actin-myosin contractility consisting of the force-balance and ...myosin transport equations. The models account for isotropic contraction proportional to myosin density, viscous stresses in the actin network, and constant-strength viscous-like adhesion. The contraction generates a spatially graded centripetal actin flow, which in turn reinforces the contraction via myosin redistribution and causes retraction of the lamellipodial boundary. Actin protrusion at the boundary counters the retraction, and the balance of the protrusion and retraction shapes the lamellipodium. The model analysis shows that initiation of motility critically depends on three dimensionless parameter combinations, which represent myosin-dependent contractility, a characteristic viscosity-adhesion length, and a rate of actin protrusion. When the contractility is sufficiently strong, cells break symmetry and move steadily along either straight or circular trajectories, and the motile behavior is sensitive to conditions at the cell boundary. Scanning of a model parameter space shows that the contractile mechanism of motility supports robust cell turning in conditions where short viscosity-adhesion lengths and fast protrusion cause an accumulation of myosin in a small region at the cell rear, destabilizing the axial symmetry of a moving cell.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ultrasound is accurate in the detection of Crohn's disease. Our aim was to identify ultrasound parameters contributing to inflammatory disease activity, develop a simple score, and validate this ...score prospectively.
This study comprised 2 single-center investigations. The first was a retrospective study on a population that had received colonoscopies (as a gold-standard diagnostic) within 60 days of ultrasound. The second was a prospective study on 2 populations: patients requiring induction with adalimumab and patients on adalimumab maintenance therapy. Ultrasound and endoscopy were preformed within 14 days in both prospective groups. The endoscopy results were graded with the Simple Endoscopic Score and the Rutgeerts score and compared with 5 ultrasound parameters. We used a proportional odds model to determine which ultrasound parameters correlated significantly with the endoscopy results. We then developed a predictive ultrasound score for disease activity, plotted the receiver operating characteristic curves, and undertook prospective validation of the score.
We evaluated 160 patients retrospectively to compare ultrasound and colonoscopy. Two of 5 parameters were found to correlate significantly with disease activity: bowel wall thickness (P = <0.0001) and color Doppler signal (P = 0.0292). We developed a score that uses weighted variables. The area under the corresponding receiver operating characteristic curve was 0.8658.
A simple ultrasonographic score that accurately identifies Crohn's disease activity has been developed and validated. Ultrasound may be a surrogate for endoscopy to guide disease management, but future studies should be conducted to establish interrater variability.
Hybrid deterministic-stochastic methods provide an efficient alternative to a fully stochastic treatment of models which include components with disparate levels of stochasticity. However, ...general-purpose hybrid solvers for spatially resolved simulations of reaction-diffusion systems are not widely available. Here we describe fundamentals of a general-purpose spatial hybrid method. The method generates realizations of a spatially inhomogeneous hybrid system by appropriately integrating capabilities of a deterministic partial differential equation solver with a popular particle-based stochastic simulator, Smoldyn. Rigorous validation of the algorithm is detailed, using a simple model of calcium 'sparks' as a testbed. The solver is then applied to a deterministic-stochastic model of spontaneous emergence of cell polarity. The approach is general enough to be implemented within biologist-friendly software frameworks such as Virtual Cell.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Treatment targets of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) have evolved over the last decade. Goals of therapy consisting of symptom control and steroid ...sparing have shifted to control of disease activity with endoscopic remission being an important endpoint. Unfortunately, this requires ileocolonoscopy, an invasive procedure. Biomarkers C-reactive protein (CRP) and fecal calprotectin (FCP) have emerged as surrogates for endoscopic remission and disease activity, but also have limitations. Despite this evolution, we must not lose sight that CD involves transmural inflammation, not fully appreciated with ileocolonoscopy. Therefore, transmural assessment of disease activity by cross-sectional imaging, in particular with magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS), is vital to fully understand disease control. Bowel-wall thickness (BWT) is the cornerstone in assessment of transmural inflammation and BWT normalization, with or without bloodflow normalization, the key element demonstrating resolution of transmural inflammation, namely transmural healing (TH) or transmural remission (TR). In small studies, achievement of TR has been associated with improved long-term clinical outcomes, including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. This review will focus on the existing literature investigating the concept of TR or residual transmural disease and its relation to other existing treatment targets. Current data suggest that TR may be the next logical step in the evolution of treatment targets.
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