Variable velocity encoding in a three‐dimensional,three‐directional phase contrast sequence: Evaluation in phantom and volunteers

Purpose:

To evaluate accuracy and noise properties of a novel time‐resolved, three‐dimensional, three‐directional phase contrast sequence with variable velocity encoding (denoted 4D‐vPC) on a 3 Tesla MR system, and to investigate potential benefits and limitations of variable velocity encoding with respect to depicting blood flow patterns.

Materials and Methods:

A 4D PC‐MRI sequence was modified to allow variable velocity encoding (VENC) over the cardiac cycle in all three velocity directions independently. 4D‐PC sequences with constant and variable VENC were compared in a rotating phantom with respect to measured velocities and noise levels. Additionally, comparison of flow patterns in the ascending aorta was performed in six healthy volunteers.

Results:

Phantom measurements showed a linear relationship between velocity noise and velocity encoding. 4D‐vPC MRI presented lower noise levels than 4D‐PC both in phantom and in volunteer measurements, in agreement with theory. Volunteer comparisons revealed more consistent and detailed flow patterns in early diastole for the variable VENC sequences.

Conclusion:

Variable velocity encoding offers reduced noise levels compared with sequences with constant velocity encoding by optimizing the velocity‐to‐noise ratio (VNR) to the hemodynamic properties of the imaged area. Increased VNR ratios could be beneficial for blood flow visualizations of pathology in the cardiac cycle. J. Magn. Reson. Imaging 2012; 36:1450–1459. © 2012 Wiley Periodicals, Inc.     

The application of evidence-based measures to reduce surgical site infections during orthopedic surgery - report of a single-center experience in Sweden

ABSTRACT: BACKGROUND: Current knowledge suggests that, by applying evidence-based measures relating to the correct use of prophylactic antibiotics, perioperative normothermia, urinary tract catheterization and hand hygiene, important contributions can be made to reducing the risk of postoperative infections and device-related infections. The aim of this study was to explore and describe the application of intraoperative evidence-based measures, designed to reduce the risk of infection. In addition, we aimed to investigate whether the type of surgery, i.e. total joint arthroplasty compared with tibia and femur/hip fracture surgery, affected the use of protective measures. METHOD: Data on the clinical application of evidence-based measures were collected structurally on site during 69 consecutively included operations involving fracture surgery (n = 35) and total joint arthroplasties (n = 34) using a pre-tested observation form. For observations in relation to hand disinfection, a modified version of the World Health Organization hand hygiene observation method was used. RESULTS: In all, only 29 patients (49%) of 59 received prophylaxis within the recommended time span. The differences in the timing of prophylactic antibiotics between total joint arthroplasty and fracture surgery were significant, i.e. a more accurate timing was implemented in patients undergoing total joint arthroplasty (p = 0.02). Eighteen (53%) of the patients undergoing total joint arthroplasty were actively treated with a forced-air warming system. The corresponding number for fracture surgery was 12 (34%) (p = 0.04).Observations of 254 opportunities for hand hygiene revealed an overall adherence rate of 10.3% to hand disinfection guidelines. CONCLUSIONS: The results showed that the utilization of evidence-based measures to reduce infections in clinical practice is not sufficient and there are unjustifiable differences in care depending on the type of surgery. The poor adherence to hand hygiene precautions in the operating room is a serious problem for patient safety and further studies should focus on resolving this problem. The WHO Safe Surgery checklist "time out" worked as an important reminder, but is not per se a guarantee of safety; it is the way we act in response to mistakes or lapses that finally matters.     

GSK-3 inhibition by an orally active small molecule increases bone mass in rats

Glycogen synthase kinase 3β (GSK-3β) actions are central in the canonical Wnt pathway, important in many biological processes and a potential drug target for treating several diseases. It is appreciated that a balanced Wnt canonical signaling is crucial for the maintenance of normal bone mass. In this study we investigated the effects of a potent orally active GSK-3 inhibitor, AZD2858, on bone mass in rats. Treatment (1 μM) of human osteoblast cells with AZD2858 in vitro increased β-catenin levels after a short period of time. In rats, oral AZD2858 treatment caused a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect at a dose of 20 mg/kg once daily (total BMC: 172% of control; p<0.001). A small but significant effect was also seen at cortical sites (total BMC: 111% of control; p<0.001). Biomechanical testing demonstrated an increase in both vertebral compression strength at a dose of 20 mg/kg once daily (Load at failure: 370% of control, p<0.001) and diaphyseal strength of femora subjected to a three point bending test (Load at failure: 115% of control; p<0.01). Furthermore, histomorphometry showed a dramatic increase in bone formation indices, and serum markers of both bone formation (Osteocalcin, 146% of control; p<0.001) and resorption (CTX, 189% of control; p<0.001) were elevated. Our conclusion is that a GSK-3 inhibitor drug may prove effective as an anabolic strategy in the treatment of diseases characterized by low bone mass, since AZD2858 has extensive bone building effects at predominantly trabecular sites.     

Ammonia binding to the oxygen-evolving complex of photosystem II identifies the solvent-exchangeable oxygen bridge (μ-oxo) of the manganese tetramer

The assignment of the two substrate water sites of the tetra-manganese penta-oxygen calcium (Mn₄O₅Ca) cluster of photosystem II is essential for the elucidation of the mechanism of biological O-O bond formation and the subsequent design of bio-inspired water-splitting catalysts. We recently demonstrated using pulsed EPR spectroscopy that one of the five oxygen bridges (μ-oxo) exchanges unusually rapidly with bulk water and is thus a likely candidate for one of the substrates. Ammonia, a water analog, was previously shown to bind to the Mn₄O₅Ca cluster, potentially displacing a water/substrate ligand [Britt RD, et al. (1989) J Am Chem Soc 111(10):3522–3532]. Here we show by a combination of EPR and time-resolved membrane inlet mass spectrometry that the binding of ammonia perturbs the exchangeable μ-oxo bridge without drastically altering the binding/exchange kinetics of the two substrates. In combination with broken-symmetry density functional theory, our results show that (i) the exchangable μ-oxo bridge is O5 {using the labeling of the current crystal structure [Umena Y, et al. (2011) Nature 473(7345):55–60]}; (ii) ammonia displaces a water ligand to the outer manganese (Mn_A4-W1); and (iii) as W1 is trans to O5, ammonia binding elongates the Mn_A4-O5 bond, leading to the perturbation of the μ-oxo bridge resonance and to a small change in the water exchange rates. These experimental results support O-O bond formation between O5 and possibly an oxyl radical as proposed by Siegbahn and exclude W1 as the second substrate water.     

Endoscopic retrograde cholangiopancreatography with rendezvous cannulation reduces pancreatic injury

AIM:To examine whether rendezvous endoscopic retrograde cholangiopancreatography(ERCP)is associated with less pancreatic damage,measured as leakage of proenzymes,than conventional ERCP.METHODS:Patients(n=122)with symptomatic gallstone disease,intact papilla and no ongoing inflammation,were prospectively enrolled in this case-controldesigned study.Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones(CBDS),rendezvous ERCP was performed intraoperatively(n=40).Patients with a negative cholangiogram constituted the control group(n=41).Another 41 patients with CBDS,not subjected to surgery,underwent conventional ERCP.Pancreatic proenzymes,procarboxypeptidase B and trypsinogen-2 levels in plasma,were analysed at 0,4,8 and 24 h.The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay.Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer’s reagents.All samples were blinded at analysis.RESULTS:Post ERCP pancreatitis(PEP)occurred in3/41(7%)of the patients cannulated with conventional ERCP and none in the rendezvous group.Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4-and 8-h samples(P=0.0015;P=0.03),procarboxypeptidase B in the4-and 8-h samples(P<0.0001;P<0.0001)and trypsinogen-2 in the 24-hour samples(P=0.03).No differences in these markers were observed in patients treated with rendezvous cannulation technique compared with patients that underwent cholecystectomy alone(control group).Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification.CONCLUSION:Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique.Thus,laparo-endoscopic technique can be recom     

Oxidized Dietary Oil,High in Omega-3 and Omega-6 Polyunsaturated Fatty Acids,Induces Antioxidant Responses in a Human Intestinal HT29 Cell Line

When oxidized, dietary oils generate products which have the potential to cause adverse effects on human health. The objective of the study was to investigate whether lipid oxidation products in an oxidized dietary oil can be taken up in intestinal cells, induce antioxidant stress responses and potentially be harmful. The in vitro cell model HT29 was exposed to camelina oil with different extents of oxidation, or only 4-hydroxy-2-hexenal (HHE) or 4-hydroxy-2-nonenal (HNE). The cellular content of HHE increased with an increasing extent of oxidation of the camelina oil added to the cell’s growth media, whereas HNE did not show a similar trend. Deuterated HHE was taken up by the HT29 cells, with 140 µM HHE metabolized within 0.5–1 h. The low oxidation degree of the camelina oil increased the gene expression of antioxidant markers (GPX, ATF6, XBP1). The increase in the gene expression of SOD at medium oxidation levels of the oil might indicate different regulation mechanisms. Highly oxidized camelina oil and a low concentration of HHE, over time, induced SOD and catalase enzyme activity in HT29 cells. Oxidized camelina oil contains multiple oxidation products which can be responsible for the intracellular responses observed in HT29 cells, while HHE and HNE in combination with other oxidation products induce antioxidant defence responses.     

Plasma Concentrations of Short-Chain Fatty Acids in Active and Recovered Anorexia Nervosa

Anorexia nervosa (AN) is one of the most lethal psychiatric disorders. To date, we lack adequate knowledge about the (neuro)biological mechanisms of this disorder to inform evidence-based pharmacological treatment. Gut dysbiosis is a trending topic in mental health, including AN. Communication between the gut microbiota and the brain is partly mediated by metabolites produced by the gut microbiota such as short-chain fatty acids (SCFA). Previous research has suggested a role of SCFA in weight regulation (e.g., correlations between specific SCFA-producing bacteria and BMI have been demonstrated). Moreover, fecal SCFA concentrations are reported to be altered in active AN. However, data concerning SCFA concentrations in individuals who have recovered from AN are limited. In the present study, we analyzed and compared the plasma concentrations of seven SCFA (acetic-, butyric-, formic-, isobutyric-, isovaleric-, propionic-, and succinic acid) in females with active AN (n = 109), recovered from AN (AN-REC, n = 108), and healthy-weight age-matched controls (CTRL, n = 110), and explored correlations between SCFA concentrations and BMI. Significantly lower plasma concentrations of butyric, isobutyric-, and isovaleric acid were detected in AN as well as AN-REC compared with CTRL. We also show significant correlations between plasma concentrations of SCFA and BMI. These results encourage studies evaluating whether interventions directed toward altering gut microbiota and SCFA could support weight restoration in AN.