Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass

Objectives Cardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6). Materials and methods The role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model. Results In the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB). Conclusion CPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflammatory response to cardiac surgery may be manipulated to improve clinical outcomes

Controls on plant functional surface cover types along a precipitation gradient in the Negev Desert of Israel

We studied the controls on functional surface cover types in four catchments along a semi-arid to arid precipitation gradient in the northern Negev Desert of Israel. First, we selected four functional types, based on their unique water use and redistribution functionality: shrubs, Asphodelus ramosus, other herbaceous plants and surface crusts. We estimated percentage of surface covered by these functional types and by bedrock outcrops and loose surface stones. Additionally data was collected on soil depth, relative elevation, insolation, slope, curvature, and overlain with surface cover maps. Relations between functional types and landscape structure variables were analyzed with descriptive statistics. The landscape structure variables bedrock, relative elevation, soil depth and surface stones explained most of the cover variance in the catchments. In catchments with many bedrock outcrops, functional types were best explained by the landscape structure variables. In catchments with homogeneous soils reaching beyond the root zone, the biological interactions between functional types were more important. Along the precipitation gradient the explanatory power of the biological variables decreased with decreasing precipitation, while the explanatory power of landscape structure variables appeared unrelated. Only in homogeneous semi-arid catchments regular vegetation patterns can develop, in arid and heterogeneous catchments irregular patterns dominate

Shrub mound formation and stability on semi-arid slopes in the Northern Negev Desert of Israel: A field and simulation study

In semi-arid areas vegetation is scarce and often dominated by individual shrubs on raised mounds. The processes of formation of these mounds are diverse and still debated. Often, shrub mound formation is directly related to the formation of vegetation patterns, thereby assuming that shrub mound formation is driven by biological interactions. We hypothesize that water-related erosion and sedimentation are also important drivers of shrub mound formation in the Northern Negev Desert of Israel. We test this hypothesis by combining field observations with model simulations. We studied shrub mounds in the semi-arid catchment of Sayeret Shaked in the Northern Negev Desert (200 mm annual precipitation). Height and diameter of shrub-canopy and shrub mounds were measured and micro-morphological techniques were used to reconstruct the formation of the shrub mounds. We used landscape evolution model LAPSUS to simulate shrub mound formation at short (single precipitation event) and longer (100 years) timescales at different slope angles. Both field and model results indicate that shrub mounds in Sayeret Shaked are at least partly formed by redeposition of eroded material below the shrubs, and by erosion and lowering of the surrounding crust. Additional model simulations suggest that mounds are formed most under low shrub density and large shrub-canopy diameter. Shrub mound formation increases with slope. In dryer and wetter climates than the studied 200 mm rainfall semi-arid climate zone, shrub mound formation is less likel

New developments in the standardization of total prostate-specific antigen

Objective : Analytical evaluation of the calibration of three recently launched assays for the measurement of total prostate-specific antigen, i.e., IMx Total PSA (Abbott), Elecsys PSA (Roche), and IMMULITE 3rd Generation PSA (DPC). Design and methods : For accuracy assessment two reference materials were applied namely, Stanford 90:10 PSA Calibrator and Certified Reference Material 613 Prostate-Specific Antigen. Dilutions of these preparations were analyzed with all assays. In addition, clinical specimens from known prostate cancer or benign prostate hyperplasia patients and samples taken from an ongoing prostate cancer screening study were used for comparison. Results : Application of the Stanford Calibrator revealed results well within 10% of the calculated values for all assays. Regarding the CRM Calibrator only the IMx Total PSA proved to approach the line of identity. The IMMULITE results differed about 40% and the Elecsys about 18% from the calculated values. The comparison with clinical specimens showed statistically different results for the combination IMMULITE-IMx and for IMMULITE-Elecsys. The regression lines for both collections were: y(IMx) = 0.86x (IMMULITE) + 0.12 (n = 104, r = 0.970, S(y/x) = 0.883 μg/L) and y(Elecsys) = 0.98x(IMMULITE) + 0.38 (n = 97, r = 0.976, S(y/x) = 0.733 μg/L). In the lower measuring range (PSA < 5.0 μg/L) as measured with the screening samples (n = 43), these differences were less pronounced. Conclusion : In analytical sense a difference was found for both reference preparations in the assays studied. Clinically, despite improvements in methodology, results for total prostate-specific antigen are still not interchangeable. The possible consequences need to be elaborated

Impact of standardized computed tomographic angiography for minimally invasive mitral and tricuspid valve surgery

Background!#!Femoral cannulation for extracorporeal circulation (ECC) is a standard procedure for minimally invasive cardiac surgery (MICS) of the atrio-ventricular valves. Vascular pathologies may cause serious complications. Preoperative computed tomography-angiography (CT-A) of the aorta, axillary and iliac arteries was implemented at our department.!##!Methods!#!Between July 2017 and December 2018 all MICS were retrospectively reviewed (n = 143), and divided into 3 groups.!##!Results!#!In patients without CT (n = 45, 31.5%) ECC was applied via femoral arteries (91.1% right, 8.9% left). Vascular related complications (dissection, stroke, coronary and visceral ischemia, related in-hospital death) occurred in 3 patients (6.7%). In patients with non-contrast CT (n = 35, 24.5%) only femoral cannulation was applied (94.3% right) with complications in 4 patients (11.4%). CT-angiography (n = 63, 44.1%) identified 12 patients (19.0%) with vulnerable plaques, 7 patients (11.1%) with kinking of iliac vessels, 41 patients (65.1%) with multiple calcified plaques and 5 patients (7.9%) with small femoral artery diameter (d ≤ 6 mm). In 7 patients (11.1%) pathologic findings led to alternative cannulation via right axillary artery, additional 4 patients (6.3%) were cannulated via left femoral artery. Only 2 patients (3.2%) suffered from complications.!##!Conclusions!#!CT-A identifies vascular pathologies otherwise undetectable in routine preoperative preparation. A standardized imaging protocol may help to customize the operative strategy