One death and one early implant dislocation occurred. Following electromagnetic induction heating, radiographic and macroscopic changes of the implant proved successful SME activation. All osteotomies healed. In the treatment group, bending stiffness increased over time. Differences between groups were not significant. In conclusion, we demonstrated successful healing of rabbit tibia osteotomies using our novel NiTi-SMA plate. We demonstrated shape-changing SME in-vivo through transcutaneous electromagnetic induction heating. Thus, future orthopaedic implants could be modified without additional surgery.Nickel-titanium shape memory alloy (NiTi-SMA) implants might allow modulating fracture healing, changing their stiffness through alteration of both elastic modulus and cross-sectional shape by employing the shape memory effect (SME). Hypotheses: a novel NiTi-SMA plate stabilizes tibia osteotomies in rabbits. After noninvasive electromagnetic induction heating the alloy exhibits the SME and the plate changes towards higher stiffness (inverse dynamization) resulting in increased fixation stiffness and equal or better bony healing. In 14 rabbits, 1.0 mm tibia osteotomies were fixed with our experimental plate. Animals were randomised for control or induction heating at three weeks postoperatively. Repetitive X-ray imaging and in vivo measurements of bending stiffness were performed. After sacrifice at 8 weeks, macroscopic evaluation,  Besides biological factors, such as blood supply, cellular immune response, and availability of osteoinductive cytokines, fracture healing strongly depends on adequate biomechanical stimuli –3. WhilePhysiologically, fracture healing consists of several phases: haematoma formation and inflammation, progression into fibrous tissue, endochondral ossification and formation of hard callus, and remodelling of the bone . It seemFurthermore, to date, all options of adapting the stability of an internal osteosynthesis in situ have required invasive procedures, such as removing or adding bolts or screws in nail or plate osteosynthesis , 17.Nickel-titanium (NiTi) shape memory alloys (SMA) have the unique ability to return to their original shape after being deformed by warming the material over an alloy-specific temperature . NumerouMs (martensite start temperature), the monocrystalline structure of the metal changes into twinned martensite. This transformation ends by reaching the martensite finish temperature (Mf). In this state, the martensite can be mechanically deformed, whereby the maximum reversible deformation (ε), which can be applied, lies between 6 and 8%  for NiTi-SMAs [Af), the martensite converts into austenite again  by warming the implant above ing test .The present study was designed to test the hypothesis that a novel NiTi-SMA plate stabilizes tibia osteotomies in rabbits and allows for bony healing. After noninvasive electromagnetic induction heating the alloy exhibits the SME and the plate changes its configuration towards higher stiffness resulting in increased fixation stiffness of the osteosynthesis .In addition, we aimed to evaluate whether this “inverse dynamization” affects efficacy of bony healing compared to fixation with the same plate without altering its stiffness.n = 14, weight 2.90–3.02 kg) were operated after randomization for subsequent noninvasive induction heating of the implant or a control group without heat induction. Animals were caged according to the guidelines of the European Commission  and fed with 100 g of pelletized special rabbit food and a small piece of apple per day. Postoperative analgesia (Carprofen) and antibiotics (Baytril) were subcutaneously administered once per day for 10 days. Postoperatively, animals were visited daily and checked for signs of pain or infection.All operations and procedures were approved by the state veterinary administration (TV 10/170) and complied with the Animal Protection Act of Germany. Adult male New Zealand rabbits . NiTi-SMA sheets measuring 0.5 and 1.0 mm in thickness were used in a sandwich construction. Segments were cut using a cutting laser FLS 352 N  and subsequently welded together using a pulsed Nd:YAG laser system True Pulse 103 . After mechanical bevelling of the screw holes, the implants were cleaned using an ultrasonic bath.A six-hole plate was designed using CAD-software . Dimensions were chosen to match those of a regular 2.0 mm AO small animal plate (DCP) for the use in small dogs . Plates The plates were autoclaved at 121°C for 90 minutes prior to implantation and mechanically deformed to the “dog shape” configuration using a standard needle holder .The induction heating process was performed using a water-cooled generator-oscillator combination as described before  , 31. TheA control loop was integrated within the induction system for the purpose of increasing the temperature of the NiTi-SMA plates to a specified temperature. In order to determine suitable induction parameters, first warming experiments were performed in vitro . The indAll procedures were performed under general anaesthesia. Premedication was intramuscularly applied using 5 mg midazolam, 25 mg ketamine, 0.15 mg buprenorphine, and 0.1 mg glycopyrronium bromide. General anaesthesia was induced using propofol 1 mg/kg body weight and maintained with 2% isoflurane and oxygen at a flow rate of 1500 mL/min after orotracheal intubation. Baytril 2.5% 7.5 mg/kg was administered subcutaneously for prophylaxis of infection. The animal was placed in a supine position. The right hind limb was shaved, cleaned, disinfected, and draped. A 5 cm skin incision was performed and the anteromedial aspect of the tibia was exposed. The plate was provisionally fixed and holes for all screws were drilled using a 1.6 mm drill. An osteotomy was performed in the middle of the inner holes using an oscillating saw, resulting in a 1.0 mm gap. The plate was fixed with bicortical 2.0 mm screws . In addition, four 1.6 mm Kirschner wires were drilled parallel to the plate position into the tibia with two on each side of the osteotomy in order to allow for later in vivo measurements of stiffness. The wound was irrigated and closed with absorbable sutures. Kirschner wires were shortened and a sterile dressing and a soft cast were put on.Under general anaesthesia, conventional X-ray images in two planes were obtained immediately after surgery and again after 3, 4, 5, and 6 weeks. X-ray images were reviewed for signs of implant dislocation, fractures, and bone healing.μm the measurements were stopped to avoid damage of the callus [2 according to ISO9585:1990(E) and ASTM F382-99 after measurement of the exact position of the K-wires relative to the osteotomy in X-rays standardised for magnification factor .A validated 4-point-bending stiffness device was used as previously described . Under ge callus . StructuFollowing the in vivo stiffness measurement three weeks after the procedure, in animals randomized for induction heating, the right hind limb was placed in the induction device. Based on prior in vivo and in vitro experiments, the initial induction heating parameters were set to 5 seconds at a machine power of 3 kW and thereby an estimated power uptake of 40 ± 5 W , 29–31. Subsequently, postinduction in vivo stiffness measurement was done.After euthanasia of the animals six weeks postoperatively, the right and left tibiae were harvested and dissected from all soft tissue. The bone plates were removed and all bones were covered with a bandage moistened with 0.9% saline. Six native tibiae  were randomly chosen to serve as a control group.μCT scanner. The osteotomy regions of all specimens were then imaged with a μCT scanner  at 15–90 μm spatial resolutions. Three-dimensional images were calculated and the newly built bone within the osteotomy gap was analysed. The bone volumes as well as trabecular thicknesses were calculated on a Hewlett Packard AlphaStation DS25 computer .Tibiae were preserved in synthetic cylinders that fit into the The specimens then underwent a series of nondestructive four-point bending tests according to the protocol described in ISO9585:1990(E) and ASTM F382-99 using a universal materials-testing machine . All tests were carried out in coronal plane with a maximum moment of 330 Nmm at a speed of 2 mm/min. Each test was repeated a total of five times. The linear portion of the load-deformation curve was used to calculate the structural bending stiffness of the bones. Five loading cycles were performed; the first two cycles served as preconditioning of the samples and the subsequent three cycles were used for calculating average stiffness.p < 0.05. The null hypothesis was that no differences would be present between the groups (induction and control). Mann-Whitney U test was used to analyse μCT data and results from in vivo stiffness measurement. For statistical analysis of the ex vivo bending test the Kruskal-Wallis test was used to determine the similarity of the medians of the three groups.The level of significance was set at Two animals (one per group) suffered fractures distant to the osteotomy gap during implantation of the plates, which could be successfully managed with additional lag screw fixation. No other intraoperative complications occurred. One animal of the control group broke its hind leg two days postoperatively after getting stuck between two bars of the cage and was sacrificed early. There were no signs of undue pain and no signs of infection in any of the remaining animals postoperatively. One animal bit off parts of the dressing and the suture of the skin; after irrigation and wound closure, the wound healed primarily and healing was otherwise uneventful. One rabbit of the induction group died during transport to the X-ray unit after the induction heating procedure. Therefore, six animals per group remained until the end of the experiment.After sacrifice, macroscopically primary healing of the osteotomy was apparent in all remaining 12 cases. No dislocations of implants occurred. In all animals from the induction group, in the middle section of the plate the outer NiTi-SMA layer (averted from the bone) was straight, while the part facing the bone displayed only partial straightening . In animThere were no signs of implant loosening or displacement. At three weeks, callus formation and partial osseous healing (bridging of the osteotomy gap) were evident in all cases. At 6 weeks, osseous healing of the fracture was apparent in all but one case. Final X-ray images in two planes after transcutaneous induction heating showed successful transformation from dogbone to straight configuration of the plate in all cases cf. .2 at 16 ± 1 days to 0.76 ± 0.27 Nm2 at 58 ± 1 days postoperatively (p = 0.043), whereas in the control group, the average bending stiffness increased from 0.10 ± 0.11 Nm2 at 19 ± 4 days to 0.67 ± 0.79 Nm2 at 55 ± 3 days postoperatively (n.s.). Differences between both groups were not significant. Due to a technical breakdown of the measurement device, in three animals of the treatment group, the postinduction measurement was carried out one week after the induction procedure. Comparison between structural bending stiffness just before induction heating and the first measurement after revealed a mean increase of bending stiffness of the tibiae from 0.50 ± 0.44 Nm2 at 22 ± 4 days to 0.60 ± 0.31 Nm2 at 24 ± 3 days postoperatively (n.s.).In three animals , the position of the Kirschner wires prevented application of the in vivo measurement device. Full sets of measurements were, therefore, available in nine subjects (six of them induction group). In the induction group, the average structural bending stiffness increased from 0.19 ± 0.15 Nm2) of the “intact”  group (0.92 ± 0.22 Nm2). The induction group showed a mean bending structural stiffness of 85% (0.79 ± 0.17 Nm2) relative to the intact group (p = 0.11).The control osteotomy group without induction showed a mean structural bending stiffness that was 72% . Mean trabecular thickness was 0.119 ± 0.017 mm and 0.095 ± 0.010 mm, respectively (n.s.). Supplementary Figure 3 shows an example of a 3D reconstruction of the scanned area of a tibia from the induction group. Detailed information as to the μCT analysis.In this study, a novel NiTi shape memory alloy plate was used to stabilize tibiae in rabbits after osteotomy. At the time of sacrifice, bony healing was apparent macroscopically and radiologically. Induction heating in the treatment group resulted in deployment of the SME and change of configuration of the plate towards higher stiffness, shown radiologically and macroscopically after sacrifice. In vivo stiffness measurements showed high intra- and interindividual variations. Differences between groups were not significant. Bending tests following sacrifice demonstrated a trend for higher structural bending stiffness of the tibiae in the induction group relative to the control group. Differences for the volume of newly built bone at the osteotomy gap were not significant in the To our knowledge this is the first study of its kind, reporting data on the use of a new concept of internal fixation in long bones, which allows increasing fixation stiffness during the course of healing without additional surgery. As with our earlier experiments, in which small NiTi-SMA specimens beneath rats' femora were used, contactless electromagnetic induction heating proved to be efficient in raising the temperature of a much bigger implant above the austenite finish temperature . FurtherIn the past, various attempts have been made to influence bone healing by optimizing biomechanical parameters , 37–45. Several limitations of this study should be considered when drawing conclusions. As this is the first in vivo application of this new technique, we were not able to calculate the number of animals needed for an adequate sample size estimate. In this study, we used an osteotomy model to represent long-bone fracture in a small animal model. Certain inherent differences exist between fracture and osteotomy situations with respect to soft-tissue damage, cytokine release, and bony involvement. However, it has been shown that bone healing after osteotomy very closely resembles regular fracture healing .Although animals were randomized for treatment or control group, the workflow did not allow blinding of the researcher in regard to the in vivo measurement. Nor was there a feasible way to do a sham induction heating, as the effect was clearly visible in X-ray controls. In vivo stiffness measurements as performed in this study reflect the stiffness of the combination of plate, bone, and K-wires rather than the stiffness of the plate alone. However, it seems unlikely that either bone or K-wires change their stiffness between the measurements before and after the induction process, and measuring the stiffness of the whole system might even better reflect the strain distribution at the fracture site which is always a combination of fracture pattern, fixation, and load. The exact position of the K-wires relative to the position of the plate might influence the absolute measurement of stiffness; therefore, only intraindividual changes and not absolute values of stiffness can be compared , 35.Due to its limited use so far, NiTi-SMA as an implant material might raise concerns with regards to biocompatibility. However, earlier studies have not shown significant adverse effects in experimental orthopaedic applications , 53. FurμCT between both groups.To the best of our knowledge, this study reflects the first attempt to apply the idea of noninvasive inverse dynamization to an internal osteosynthesis in vivo. A novel NiTi shape memory plate was used for stabilization of an experimental tibia fracture in rabbits. Noncontact electromagnetic induction heating of the plate three weeks after the initial procedure resulted in a change of its shape towards a state of higher stiffness. Fracture healing was unimpaired and successful in all cases. However, we were unable to measure changes of in vivo implant stiffness between pre- and postinduction. Neither could we show significant differences in bending stiffness of the tibiae ex vivo or in bony structure by Nonetheless, the ability of applying the shape memory effect noninvasively might allow for adaptation of the implant depending on the individual course of fracture healing. Therefore, our findings encourage the further development of novel concepts for long-bone fracture fixation with variable stiffness, which might be used in the future to improve fracture healing and prevent or reduce nonunion.Supplementary Figure 1: Calculation of structural bending stiffness from in-vivo stiffness measurements.Supplementary Figure 2: Setup of the ex-vivo bending-test.Supplementary Figure 3: μCT 3D reconstruction of the osteotomy region of the tibia below the explanted plate  shows bony bridging of the osteotomy 42 days after surgery.Supplementary Table 1: Data from μCT analysis of rabbit tibiae after explantation.


Garment and textile (G&T) industry has been playing as a driving force for the socio-economic development of Vietnam. With the international integration process and rising challenges from the global market, there is a need to examine international competitiveness of Vietnam’s G&T industry to find out what Vietnam should focus on to enhance its position in the global market place. This paper, by using the Generalized Double Diamond Model (GDDM), analyzed international competitiveness of Vietnam’s G&T industry and compared it with China. The results showed that Vietnam was less competitive than China in all four attributes of the GDDM. The lowest competitiveness of Vietnam in comparison with China was Related and Supporting industries, followed by Factor Conditions. Therefore, the paper argued that although Vietnam should improve all of the four attributes in the long term, Vietnam must put a high priority on developing Related and Supporting Industries and then enhance Factor Conditions while maintaining its strengths over China in terms of G&T export growths and favorable business context.The online version of this article (doi:10.1186/s40064-016-1912-3) contains supplementary material, which is available to authorized users. In Vietnam, garment and textile industry (G&T) has been a key exporting industry and contributed considerably to the social and economic development. In 2014, G&T was the second biggest exporting industry and contributed 11.51 % to the total GDP of Vietnam  and the Diamond Model of Michael Porter. Vitas  used SWOThe nature of international competitiveness of an industry as stated above is its ability to compete internationally and must be assessed by comparing with the same industry in other countries. One common point of all previous papers relating to international competitiveness of Vietnam’s G&T is that although they were informative to describe the current development of this industry, they failed to measure or quantify international competitiveness of Vietnam’s G&T aggregately in indexes and therefore it is hard to position Vietnam’s international competiveness in the global marketplace. In addition, the past studies proposed a wide range of measures for Vietnam’s G&T industry but the priority measures were unclear. To fill this gap, the paper concentrates on analyzing and measuring international competitiveness of Vietnam’s G&T industry by using the GDDM. With this methodology and framework, the contribution of this paper is twofold. Firstly, the paper develops a specific framework for assessing international competitiveness of G&T industry. Secondly, this is the pioneering study adopting the GDDM to examine international competitiveness of an industry in Vietnam.In this paper, the GDDM, with the analysis of both domestic and international attributes, helps answer how internationally competitive Vietnam’s G&T is quantitatively compared to the benchmark country, China, and draw out better implications for Vietnam to improve international competitiveness of G&T industry. The paper is structured as below. After the introduction, the second part introduces the framework used while the third part explains the methodology and selection of proxies for the GDDM. In the next part, the paper presents the main results on international competitiveness of Vietnam’s G&T and the final part points out some conclusions and implications, which are essential for Vietnam’s G&T industry to enhance its international competitiveness in the future.Among the models that are adopted to explain nation or industry competitiveness, the widely used one is Michael Porter’s Diamond Model introduced firstly in Porter . AccordiIn spite of being influential and widely used, Michael Porter’s Diamond Model of competitiveness still has some severe limitations. Firstly, the Diamond Model leaves out the multinational activities such as inbound and outbound foreign direct investment (FDI) and is mainly fixed on a large home base country  inward and (2) outward FDI  the total population, (2) GDP and (3) the employment rate were used to represent the size of domestic market demand  total G&T export value and (2) growth rate of G&T export value  Cotton exports and (2) yarn exports were used to indicate how strong these industries were in the global market through its expansion into related and supporting international industries  Market share of the country in G&T global market was used for rivalry proxy and (2) the average import tariff rate representing international business context , International Trade Center, International Telecommunication Union and the United States Department of Agriculture. The latest available data for both Vietnam and China were used for each proxy. One point worth commenting is that the paper aims at assessing international competitiveness of Vietnam’s G&T industry through comparing it with China’s. Therefore, data of all proxies are not necessary to be collected for 1 year but data for a proxy must be in 1 year for both nations. This is also data selection approach used in previous literature by Moon et al. , Liu andAfter data for the above-mentioned proxies were collected, they were then translated into scores to quantify international competitiveness of G&T industry in Vietnam and the benchmark nation, China. The method of score translation used in this study was similar to the one used in Rugman and Verbeke  and SardFrom descriptive data for Vietnam and China’s G&T industries shown in Table Except for Factor Conditions, Vietnam’s G&T industry was less competitive than China’s in all domestic determinants Fig. . The reaThe domestic Firm Strategy, Structures and Rivalry of Vietnam were only about 1 % less competitive to China’s Fig. . Thanks The domestic Demand Conditions of Vietnam were far less completive than that of China Fig.  because China was superior to Vietnam in all five proxies of Related and Supporting Industries. Vietnam’s competitive value of this attribute was only equal to 34.42 % of China  2014/2015 compared to 4.4 million hectares in China because of unfavorable weather condition and restricted agricultural land. Therefore, cotton output of Vietnam reached 1.36 thousand tons, equivalent to only around 0.02 % of that of China  method, by which the Vietnamese G&T firms received orders from their partners abroad, manufactured and then sent back the final products, which would be distributed and sold by foreign partners. Or Vietnam’s G&T firms exported products to destinations as instructed by foreign partners. Therefore, marketing and distribution network of Vietnam’s G&T enterprises has been underdeveloped and relied largely on foreign distributors Bui ; Vu 2014The weak upstream and downstream industries of Vietnam together with the loose connectivity between them have also resulted in the lack of G&T clusters in Vietnam. In fact, Vietnam had only a handful number of G&T clusters with the biggest one located in the south. This cluster was the result of the co-operation between Ho Chi Minh City, Dong Nai province and Binh Duong province, contributing 56.4 % to total G&T output, 39.4 % to total export value, and 30 % to total labor in G&T industry in 2011 ; demanding needs of consumers, and preference for local brands in oversea market (Demand Conditions); G&T cluster, and educational facility related to G&T industry (Related and Supporting Industries); and the rate of added value in G&T industry  to provide better results on Vietnam’s competitiveness of G&T industry.Finally, this paper chooses China, which is a developing but much bigger than Vietnam in terms of GDP, population and area, as the benchmark country to compare with Vietnam. In order to provide multi-dimensional analysis of Vietnam’s G&T international competitiveness, identify more precisely Vietnam’s G&T international competitiveness gap with its main competitors and more importantly recommend the progress measures for Vietnam to improve its international competitiveness, the future research can take into consideration of some other comparing nations with more similar size such as Bangladesh, Turkey and Cambodia.


IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. In recent years, consistent efforts have been made to develop new non-invasive biomarkers for IgAN progression. In our previous in vitro study we found mesangial derived CXCL1 as a contributor for kidney injury, and observed higher urinary CXCL1 levels in patients with IgAN. It implied that the urinary CXCL1 might be a potential biomarker.In the present study, we enrolled 425 IgAN patients with follow-up data and detected their urinary CXCL1 levels at the time of renal biopsy, to explore the predictive value of urinary CXCL1 in IgAN progression. Urinary CXCL1 levels were measured using enzyme-linked immunosorbent assay.Urinary CXCL1 levels were associated with presently well established predictors of IgAN progression, including SBP , DBP , proteinuria , eGFR  and tubular atrophy and interstitial fibrosis . After adjusted for them, higher levels of urinary CXCL1 were independently associated with a greater risk of deterioration in renal function . Furthermore, time-dependent receiver operating characteristic (ROC) curve showed that urinary CXCL1, when combined with proteinuria and eGFR, could enhance the prognostic value of these traditional predictors for IgAN progression.The results in our present study suggested urinary CXCL1 as a new non-invasive predictor of IgAN progression. Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis (GN) worldwide , charactIn recent years, consistent efforts have been made to develop new non-invasive biomarker for acute and chronic kidney diseases. Approximately 70% of the urinary proteins are from the kidney and urinary tract, and therefore urine becomes a promising bio-sample for biomarker identification in patients with kidney disease. Recently, there are several studies devoted in urinary biomarker for IgAN, such as epidermal growth factor (EGF) , monocytWe previously reported that IgA1 complexes from IgAN patients could induce the up-regulation of chemokine (C-X-C motif) ligand 1 (CXCL1) in mesangial cells. And further in vitro experiments proved the podocyte injury effect induced by mesangial derived CXCL1. Moreover, we observed significantly higher urinary CXCL1 levels in patients with IgAN than those in healthy controls, which implied urinary CXCL1 as a potential bio-marker for IgAN . In the 2, steroids are recommended. Steroids, in combination of other immunosuppressive agents, like cyclophosphamide, mycophenolate mofetil or FK506, were appropriate for crescentic IgAN with rapid progression [The present study recruited 425 IgAN patients with regular follow-up in Peking University First Hospital. The IgAN diagnosis was based upon the presence of dominant IgA demonstration in mesangial area by immunofluorescence, and confirmed by light microscopy and electronic microscopy, as well as the lack of clinical or serological evidence of other inflammatory conditions, such as systemic lupus erythematosus, vasculitis, or Henoch–Schoenlein purpura. During follow-up, patients received the same therapy regimen that be treated according to the Kidney Disease: Improving Global Outcomes (KDIGO) Guideline. As the proteinuria>1g/d, ACE inhibitors or ARBs were provided and dosage-adjusted according to the changes of blood pressure that optimal control target of < 130/80mmHg. Proteinuria is higher than 1g for three to six months without relief, and estimated glomerular filtration rate (eGFR)>50 ml/min/1.73mgression , 11.For enrolled patients, clinical manifestations, including age, gender, blood pressure, serum creatinine and 24h urine protein excretion were collected from medical records. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation . All renIn the present study, we also enrolled 40 patients with minimal change disease (MCD), 40 patients with membranous nephropathy (MN), 40 patients with primary focal segmental glomerulosclerosis (FSGS), and 40 patients with lupus nephritis (LN) as disease controls. Moreover, 74 healthy subjects whose urinary CXCL1 were detected in our previous study were enrolled as healthy controls .The study protocol was reviewed and approved by the Ethics Committee of Peking University and written informed consent was obtained from all participants.Early morning urine samples on the day of renal biopsy from recruited 425 patients, as well as on the day of follow-up visits of 6 patients, were centrifuged immediately at 1800rpm and 4°C for 5 minutes. Then supernatants were stored at -80°C until the time of assays.Urinary CXCL1 were quantified by a standard sandwich ELISA assays using the DuoSet human CXCL1 ELISA kits , according to the manufacturer’s protocol. Urinary CXCL1 were calibrated against urine creatinine before the levels were compared.2 or need for renal replacement therapy , for the purpose of this study.At first, the correlation of urinary CXCL1 levels with clinical and pathological indicators at the time of renal biopsy were explored. And then, survival analysis was applied to evaluate whether urinary CXCL1 levels at biopsy could predict IgAN outcome. A composite end point, defined as 50% eGFR decline, ESRD or death, whichever occurred first, was used in the present study. ESRD was defined as eGFR < 15 ml/min per 1.73 mt test was used if the data was in normal distribution, and if not, Mann-Whitney or Kruskal-Wallis test was performed. Categorical variables were compared using χ2 test. Spearman’s correlation was applied for analyzing correlation. Factors correlated with urinary CXCL1 were further explored using multivariable linear regression analysis. We derived cumulative kidney survival curves using the Kaplan Meier method, and analyzed differences between curves by log-rank test.Statistical analyses were performed by SPSS software . Normally distributed quantitative variables were expressed as mean ± standard deviation. For non-normally distributed variables, we used median and interquartile range (IQR). Categorical data were summarized as absolute frequencies and percentages. For Continuous variables, independent-samples For the analysis of Cox proportional hazards models and time-dependent receiver operating characteristic (ROC) curve, survival package and suvivalROC package in R (Version number: 3.0.2) were used, respectively. Cox proportional hazards models were used to analyze the association of urinary CXCL1 levels and the composite outcome. Results were presented as hazard ratio (HR) and 95% confidence interval (CI). Urinary CXCL1 were highly skewed to the left in our patients, therefore, natural log transformation was used. Urinary CXCL1 was analyzed as a continuous variable with HRs calculated per s.d. increment of natural log–transformed CXCL1. The relationship between CXCL1 and risk of end point was examined in unadjusted and multivariable-adjusted Cox models. Additionally, time-dependent receiver operating characteristic (ROC) curve analysis was conducted to evaluate the prognostic value of CXCL1 for the composite end. Areas under the curve were calculated for CXCL1, eGFR, proteinuria. A two-tailed P-value less than 0.05 was considered statistically significant.2. The mean systolic blood pressure (SBP) was 123±15 mmHg, while diastolic blood pressure (DBP) was 79±12 mmHg. Mesangial hypercellularity (M1), endocapillary hypercellularity (E1), and segmental glomerulosclerosis (S1) were found in 79.8%, 54.8%, and 67.6% of patients, respectively. Tubular atrophy and interstitial fibrosis, 0% to 25% (T0), 26% to 50% (T1), and >50% (T2), were found in 68.1%, 21.2%, and 10.7% of patients, respectively. And the median urinary CXCL1 level was 18.29 pg/mg (IQR: 10.17–33.47 pg/mg). During the follow-up period, 408 (96.0%) patients received ACE inhibitors or ARBs therapy, 179 (42.1%) received oral corticosteroids and 119(28.0%) received other immunosuppressive agents. In total, 45 patients reached the composite end point of 50% eGFR decline (n = 32), ESRD , or death .We defined the time of renal biopsy as baseline and the characteristics of patients with IgAN (n = 425) were summarized in Urinary CXCL1 levels were significantly higher in the patients of IgAN  than those in patients of MCD , MN  and FSGS , while not significantly higher than those in LN  . The uriA cross section correlation analysis between urinary CXCL1 levels and clinical and histological manifestations of IgAN patients at the time of renal biopsy was performed. The levels of CXCL1 in IgAN patients were positively correlated with proteinuria , SBP , DBP , tubular atrophy and interstitial fibrosis , and negatively correlated with eGFR . Patients with IgAN in severe CKD stages showed higher urinary CXCL1 levels .2 vs. 92.72±26.51 ml/min/1.73m2, P<0.001), higher SBP ,higher DBP ,and more serious tubular atrophy and interstitial fibrosis (P = 0.002).We divided the patients into two groups: according to the median level of urinary CXCL1 (18.29 pg/mg), and we found that compared with CXCL1 below median group, CXCL1 upper median group have higher initial proteinuria  g/24h vs.  g/24h, P = 0.002, In order to identify the independent factors correlated with urinary CXCL1, we then applied multivariable linear regression model to our data. After adjusted for gender, age, eGFR, systolic blood pressure, diastolic blood pressure and tubular atrophy and interstitial fibrosis, proteinuria was independently associated with urinary CXCL1 levels . Patients with CXCL1 levels less than 18.29 pg/mg were classified as group A, while others (CXCL1 levels above 18.29 pg/mg) were classified as group B. During follow-up, 11 patients (5.2%) in group A reached the composite outcome compared with 34 patients (16.0%) in group B P<0.001; . Of thesKaplan-Meier survival analysis indicated that renal survival for the composite outcome was significantly lower in group B than that in group A .To evaluate the operating characteristics of urinary CXCL1 level as a prognostic value for IgAN progression, we conducted a time-dependent ROC analysis for urinary CXCL1 level in comparison with proteinuria and reciprocal of eGFR (1/eGFR) level . The areIn order to further evaluate the additive effect of urinary CXCL1 on traditional predictive markers for IgAN progression, we carried out the survival analysis by using both base model  and a new model, in which urinary CXCL1 were added (M1 = M0+CXCL1). The results showed that with addition of urinary CXCL1, the overall performance of the predictive model for IgAN progression improved (R square: M1 Vs M0: 0.182 Vs 0.164, p = 0.002, CXCL1, also known as growth-regulated oncogene-alpha, is one of the CXC chemotactic factors –16. It pOur present study is the first clinical study evaluating the prognostic significance of urinary CXCL1 level on renal survival conducted in a cohort of IgAN patients with long-term follow-up. We found that urinary CXCL1 levels were significantly higher in patients with IgAN and LN than in other GN, including MCD, MN and FSGS. Since usually accompanied with other systemic symptoms, LN can be easily differentiated from IgAN. Therefore, although urinary CXCL1 cannot be used as a fully specific biomarker for IgAN among patients with primary nephritis, those with IgAN showed significantly higher urinary CXCL1 levels. Combined with other clinical parameters, urinary CXCL1 might be used as specific biomarker set for IgAN. Of course, the establishment of the specific biomarker set for IgAN needs further exploration and validation in the future studies.In this study, we found that urinary CXCL1 levels were positively associated with 24h urinary protein excretion, SBP and tubular atrophy and interstitial fibrosis, and negatively associated with eGFR, all of which were well-established predictive markers for IgAN progression. Interestingly, when combined with baseline 1/eGFR and proteinuria, urinary CXCL1 could enhance the prognostic value over each individual clinical marker. The results were consistent with our previous finding in cross-sectional study, IgAN patients with severe clinical and pathological lesions presented with higher urinary CXCL1 levels . In the Following our identification that urinary CXCL1 level was independently associated with 24h urinary protein excretion, we further evaluated the dynamic changes of urinary CXCL1 during treatment, focused on those patients who presented with some degrees of proteinuria remission after treatment. Our observation in follow-up patients with sequential urine samples suggested that only for patients with high levels of baseline urinary CXCL1, the fluctuations of urinary CXCL1 levels were synchronized with those of proteinuria, implying that urinary CXCL1 above a certain level might participate in podocyte injury. Thereby, for those with high baseline levels, urinary CXCL1 could be served as a useful marker for not only IgAN progression, but also treatment efficacy, especially regarding proteinuria remission. However, our sequential urine samples were just available in a small proportion of patients. We presently have no chance to evaluate the correlation of proteinuria and urianry CXCL1 during follow-up in all patients, which awaiting further verification in future studies.In order to evaluate the role of urinary CXCL1 in prediction of IgAN progression, COX regression model was used in our study. We demonstrated that urinary CXCL1 could serve as an independent prognostic factor for composite end point of IgAN, even after adjustment for baseline risk factors including proteinuria, eGFR, SBP and tubular atrophy and interstitial fibrosis. This result implied extra value of urinary CXCL1 over already established risk factors for the prediction of IgAN progression. Furthermore, we evaluated the predictive value of urinary CXCL1 in IgAN progression. With addition of urinary CXCL1 onto the traditional predictive markers for IgAN, the overall performance of the predictive model for IgAN progression improved significantly, which suggested that urinary CXCL1, although not fully specific, still could be served as a valuable non-invasive biomarker in predicting IgAN progression.Regarding the underlying mechanism of CXCL1 in IgAN progression, we had little evidence, which was the limitation of our present study. CXCL1 was famous for its powerful neutrophil chemoattractant activity. However, in IgAN, the infiltrating inflammatory cells are mainly lymphocytes and monocytes, rather than neutrophils. Our previous study proved that up-regulated CXCL1, derived from mesangial cells under the challenge of pathogenic IgA1 complex, would increase podocyte death and reduce podocyte adhesion, and at last lead to podocyte loss . In accoIn conclusion, we showed that high urinary CXCL1 level is associated with severe clinical and histological findings, and poor renal prognosis in IgAN. When combined with well-established clinical risk factors, urinary CXCL1 may be a useful non-invasive biomarker for IgAN progression.


Malaria Journal.The authors of  would liIn the third paragraph of ‘Case detection and clinical outcome’ in the “Results” section of , “acute In addition, in Table 3 of the original publication , the OveWe regret these mistakes.


Bacillus amyloliquefaciens Z7. Plackett–Burman design was applied to determine the specific medium components affecting CDA activity and found that starch, chitin and MgSO4 were critical in augmenting CDA activity. These significant parameters were further optimized using Box–Behnken RSM and the optimum concentrations of starch, chitin and MgSO4 were found to be 24.4, 8.8 and 0.19 g/L, respectively. The optimum medium composition was chitin 8.8 g/L, starch 24.4 g/L, yeast extract 10g/L, MgSO4 0.19 g/L, K2HPO4 0.3 g/L and NaCl 5 g/L. Under these optimal conditions, the CDA activity of Bacillus amyloliquefaciens Z7 increased distinctly from 18.75 to 27.48 U/mL .Plackett–Burman design and Box–Behnken response surface methodology (RSM) was employed to optimize the medium components for the chitin deacetylase (CDA) activity from  Absidia coerulea,[Aspergillus nidulans,[Colletotrichum lindemuthianum ATCC56676,[Colletotrichum lindemuthianum DSM63144,[Flammulina velutipes,[Mucor rouxii,[Rhizopus circinans,[Rhizopus nigricans,[Saccharomyces brevicaulis,[Saccharomyces cerevisiae.[The enzyme chitin deacetylase (CDA) EC 3.5.1.41) is a key enzyme that catalyses the conversion of chitin to chitosan by the deacetylation of N-acetyl-D-glucosamine residues. It is a member of the carbohydrate esterase family 4, according to the CAZY database..41 is a  CDAs havr rouxii, Rhizopusircinans, Rhizopusigricans, Saccharovicaulis, and Saccrevisiae.Bacillus amyloliquefaciens strain (Z7) with high CDA activity. The high CDA activity of this strain is one of the critical factors in favour of its application, but the optimal fermentation medium has not been studied.Today, chitosan is mainly produced from chitin via chemical NaOH pyrolysis, which has some disadvantages, such as poor quality of the resulting chitosan, high energy consumption and environmental pollution. These problems could theoretically be overcome by the use of CDA-producing bacteria for chitin N-deacetylation. We have previously screened and isolated a Statistical methodologies are useful tools to study the interaction between the physiological factors that play important roles in biotechnological processes. ResponseBacillus amyloliquefaciens Z7. Taking CDA activity as the index, the medium components were optimized using Plackett–Burman design and Box–Behnken RSM.The present study focuses on improving CDA activity of Bacillus amyloliquefaciens Z7 was isolated from soil of the banks of the Xiangjiang River in Changsha City, Hunan, China. Strain Z7 was maintained in the Central South University of Forestry and Technology Strains Conservation Center at 4 °C and subcultured every four weeks.CDA activity was determined by two different assays. (1) Acetate released by the action of CDA on various chitinous substrates was determined by the enzymatic method of Bergmeyer , via thr(2) A radiometric assay, in whichThe basal medium was starch 20 g/L, yeast extract 10 g/L and NaCl 5 g/L, pH 6.5. The best carbon source, nitrogen source and inorganic salt were confirmed in our previous research.[2PO4 and MgSO4) were selected for this study, with each being represented at two levels, high (+1) and low (−1), as shown in t-test. The level of significance  was also evaluated for each factor.Plackett–Burman design is a commonly used statistical technique for medium optimization  and was 1), starch (X5) and MgSO4 (X8), were selected for steepest ascent design. The direction change and step size of the three factors were set on the basis of their effect size. Chitin and starch had a positive effect and their step size was 2 g/L; whereas MgSO4 had a negative effect and its step size was 0.05 g/L.The most important factors were found by analysing the Plackett–Burman design results. Response surface fitting is applicable to the real situation only at examining a small region. That is 4 (0.2–0.3 g/L), in Z7 fermentation medium. Starch (X1), chitin (X2) and MgSO4 (X3) were considered as independent factors, whereas the CDA activity was considered as the response. The experimental factors and levels are shown in Y is the predicted response, β0 is the intercept, β1, β2 and β3 are the linear coefficients, β11, β22 and β33 are the squared coefficients, and β12, β13 and β23 are the interaction coefficients. The analyses of the data were done using DESIGN EXPERT V8.0.Box–Behnken RSM was employed to establish the optimum levels of the three variables: addition of starch (20–25 g/L), chitin (9–11 g/L) and MgSOB. amyloliquefaciens Z7 was reported in our previous research. Chitin is the substrate of CDA and, by increasing the substrate concentration, the reaction rate will increase due to the likelihood that the number of enzyme–substrate complexes will increase. The results showed that the chitin level which gave the highest CDA activity was 10 g/L . The CDA activity increased with chitin levels from 2 to 10 g/L and decreased from 10 to 14 g/L. Therefore, the most appropriate chitin levels were found to lie in the region around 10 g/L.The influence of the carbon source, nitrogen source and inorganic salt in the fermentation medium on the activity of CDA produced by t-test are shown in 1), starch (X5) and MgSO4 (X8) concentrations were significant (P < 0.05). Based on these results, chitin, starch and MgSO4 were selected as variables and applied to optimize the medium composition by RSM.The most important three aspects of the CDA production were determined by Plackett–Burman experimental design. In 1), starch (X5) and MgSO4 (X8) were selected for steepest ascent design. The direction change and step size of these three factors were set on the basis of their effect size .As CDA from strain Z7 was strongly affected by chitin, starch and MgSO4. Through regression fitting, regression equation (Equation (2)) expressed the influence of these three factors on the response:Y is the response (CDA activity), and A, B and C are the starch, chitin and MgSO4 concentrations, respectively. The ANOVA analysis showed that Prob > F < 0.0001, indicating that the model was significant for the response (R2) was calculated to be 0.9892, which ensures a satisfactory adjustment of the quadratic model to the experimental data and indicated that 98.9% of the variability in the response could be explained by the model. The adjusted coefficient of determination (Adj R2) value of 0.9754 indicates an adequate signal. Thus, this model could be used for analysis and prediction of CDA activity.Regression analysis was then performed on the obtained data. The regression equation obtained after the analysis of variance (ANOVA) gives the level of CDA produced as a function of the initial values of chitin, starch and MgSOresponse . The coeA, C, A2, B2, C2 and the interaction item of AB were highly significant (P < 0.01), and B and BC were significant at P < 0.5. ANOVA revealed that the three factors have an effect on the CDA activity and the interactions of AB and BC were significant. The response surfaces and contour plots in Figures S2–S7  show that the CDA activity reached the highest level when starch was 24.4 g/L, chitin was 8.82 g/L and MgSO4 was 0.185 g/L. The DESIGN EXPERT V8.0 presented the maximal numerical solution with the predicted CDA activity up to 28.46 U/mL. The contour plot in Figure S3 is flat, indicating that the effects of starch and chitin on the CDA activity of strain Z7 are higher. The contour plot in Figure S5 is an ellipse, indicating that the interaction between starch and MgSO4 affects the CDA activity of strain Z7 more. The contour plot in Figure S7 is round, implying that the interaction between chitin and MgSO4 has a minimum effect on the CDA activity of strain Z7.4 0.19 g/L, K2HPO4 0.3 g/L and NaCl 5 g/L) was performed. The experiments under optimized conditions were carried out in triplicate. Under these conditions, the micro-organism produced 27.48 U/mL of CDA. The values predicted by the model were well in agreement with the results obtained for various concentrations of starch, chitin and MgSO4.To confirm the model's adequacy for predicting CDA activity, a verification experiment using the optimum medium composition . The interaction between these components was confirmed using response surface models. Therefore, it could be concluded that the existing statistical models can successfully aid the optimization of media components for increased CDA activity.In this study, Plackett–Burman design, steepest ascent design and RSM were used to investigate the main and interaction effects of independent variables important for the activity of CDA produced by


DIZZYNET, a European network for management of dizzy patients and for vertigo and balance research, was founded in October, 2014 by international experts from 13 countries all over Europe. Its structural concept, aims, and visions are presented in the supplement’s first article. The supplement documents the constitutive meeting that took place in Sonnenhausen, Bavaria last year. The other articles, which are based on expert talks presented at the meeting, reflect current developments and controversies in neuro-otology.DIZZYNET will not compete with national or international societies active in the field. It sees its central aim in collaboration and exchange among scientists, physicians, technicians, and physiotherapists working in the field of vertigo and balance disorders. Working groups have been established on basic and translational research, clinical management, clinical trials, rehabilitation, and epidemiology in order to promote multiprofessional education. The European DIZZYNET will organize yearly international master classes on treatment of vertigo and balance disorders. The concept of this master class is “Two Days of Teaching”: how to manage dizzy patients and how to conduct otoneurological research in form of lectures for all participants and hands-on courses with an occupational focus.


PLOS Computational Biology editorial team would like to express our tremendous gratitude to all those individuals who participated in the peer review process this past year at PLOS Computational Biology. As a journal that is run by and for the scientific community, we depend upon you, the community, to communicate our best work. 2015 was great year for PLOS Computational Biology; during the year, over 2,600 reviewers from around the world helped evaluate over 970 articles.The Public Library of Science (PLOS) and the PLOS Computational Biology authors. Your efforts are an important part of making the journal a highly valued Open Access resource created by and for the benefit of the scientific community.The names of our 2015 reviewers are listed in S1 Reviewer List(PDF)Click here for additional data file.


Biological Procedures Online, for their invaluable assistance with review of manuscripts for the journal in Volume 16 (2014).A peer-reviewed journal would not survive without the generous time and insightful comments of the reviewers, whose efforts often go unrecognized. Although final decisions are always editorial, they are greatly facilitated by the deeper technical knowledge, scientific insights, understanding of social consequences, and passion that reviewers bring to our deliberations. For these reasons, the Editor-in-Chief and staff of the journal warmly thank the reviewers whose comments helped to shape  Aruna AmbagalaCanadaHosam ArafateSaudi ArabiaDeb CourtCanadaMarina CretichItalyWim DhaezeUSAMarxa FigueiredoUSAChing-Hung HsuUSAChing-Hung HsuChinaYingqi HuaUSAMichael HustGermanyDavid le CouteurAustraliaBolin LiuUSALucia Manso-SilvanFranceNitish MishraUSAMauro ProvincialiItalySebastien RodrigueCanadaLucia SacchettiItalyAkinori SatoJapanMasatoshi TagawaJapanLynn ThomasonUSAShi XuUSAShaomian YaoUSA


The following scientists assisted the journal by reviewing manuscripts during the period October 1, 2013 to September 30, 2014. We greatfully acknowledge their critical evaluation and assistance in selecting articles for publication.


We compared the accuracy of NOGA endocardial mapping for delineating transmural and non-transmural infarction to the results of cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement (LE) for guiding intramyocardial reparative substance delivery using data from experimental myocardial infarction studies.Sixty domestic pigs underwent diagnostic NOGA endocardial mapping and cMRI-LE 60 days after induction of closed-chest reperfused myocardial infarction. The infarct size was determined by LE of cMRI and by delineation of the infarct core on the unipolar voltage polar map. The sizes of the transmural and non-transmural infarctions were calculated from the cMRI transmurality map using signal intensity (SI) cut-offs of>75% and>25% and from NOGA bipolar maps using bipolar voltage cut-off values of <0.8 mV and <1.9 mV. Linear regression analysis and Bland-Altman plots were used to determine correlations and systematic differences between the two images. The overlapping ratios of the transmural and non-transmural infarcted areas were calculated.Infarct size as determined by 2D NOGA unipolar voltage polar mapping correlated with the 3D cMRI-LE findings  with a mean difference of 2.82% in the left ventricular (LV) surface between the two images. Polar maps of transmural cMRI and bipolar maps of NOGA showed significant association for determining of the extent of transmural infarction  and non-transmural infarction . NOGA overestimated the transmural scar size (6.81% of the LV surface) but slightly underestimated the size of the non-transmural infarction (−3.04% of the LV surface).By combining unipolar and bipolar voltage maps, NOGA endocardial mapping is useful for accurate delineation of the targeted zone for intramyocardial therapy and is comparable to cMRI-LE. This may be useful in patients with contraindications for cMRI who require targeted intramyocardial regenerative therapy. The border zone of myocardial infarction (MI) represents myocardial areas with decreased viability and reduced wall motion capacity. Perfusion and transport of cell-death waste products, such as oxygen radicals and other metabolic substances, is impaired due to the close proximity to the non-perfused infarcted area, and this may account for the functional decline. These areas are targeted by cardiac regenerative therapies because regenerative cells delivered to these areas may survive and help restore cardiac function.Compared to intracoronary or intravenous delivery, intramyocardial delivery of regenerative drugs, genes, or cells into the border zone of chronic myocardial ischemia results in higher retention of the applied substances, which may result in more effective therapy Three-dimensional (3D) NOGA endocardial mapping and electromagnetic guided percutaneous intramyocardial therapy is the method that is currently used for real-time (on-table) assessment of myocardial viability and for delineation of the infarct and infarct border zone Here we focused on the accuracy of NOGA mapping to delineate transmural and non-transmural infarction by comparing it with cMRI-LE imaging. We investigated whether NOGA mapping is suitable for guiding intramyocardial drug or cell delivery using data from experimental myocardial infarction studies. We chose to use an animal model of closed chest reperfused MI. This is very similar to human primary percutaneous coronary intervention in acute MI, which simulates post-infarction left ventricular dysfunction.We hypothesized that real-time, on-Closed-chest reperfused acute MI was induced in 60 female farm pigs by percutaneous occlusion of the mid left anterior descending coronary artery. Sixty days later, the pigs underwent cMRI-LE images to confirm chronic myocardial infarction. Additional NOGA endocardial mapping was then performed 2±1 days later, just before the animals were euthanized, aiming to search for correlations between the two images.2 (1.6–1.8 vol%), and N2O (0.5 vol%). O2 saturation, blood pressure, and electrocardiography were monitored continuously. After an arteriotomy of the right femoral artery, a 6F introducer sheath  was inserted. Heparin (200 IU/kg) was administered followed by selective angiography of the left coronary artery tree. A balloon catheter  was advanced into the left anterior descending coronary artery (LAD). After the origin of the second major diagonal branch, the mid LAD was occluded by inflation of the balloon at 5 atmospheres for 90 minutes, followed by deflation of the balloon to allow opening of the infarct-related artery and reperfusion of the ischemia-affected myocardium. The pigs were then allowed to recover from the anesthesia.Briefly, all pigs were sedated with ketamine hydrochloride (12 mg/kg), xylazine (1 mg/kg), and atropine (0.04 mg/kg) intramuscularly. The pigs were intubated intratracheally and anesthetized with isoflurane (1.5–2.5 vol%), OThis study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Experimental Animal Care and Use Committee at the Faculty of Animal Science of the University of Kaposvar (Hungary) (Permit Numbers: 246/002/SOM2006/11/11 and 246/002/SOM2006/08/11). All procedures were performed under general anesthesia, and all efforts were made to minimize the suffering of the animals.The electromechanical maps of the pigs were obtained 62±1 days after induction of acute MI. The principles and procedures of NOGA electroanatomical mapping have been described previously At least four points were acquired in each of twelve myocardial segments. During the mapping process, simultaneous unipolar and bipolar electrocardiograms were recorded as well as the 3D location and orientation of the catheter tip of several sites within the LV cavity. The electrophysiological and mechanical data were integrated to create a color-coded 3D reconstruction of the LV chamber to facilitate assessment of the regional viability. The stability of the catheter-to-wall contact was evaluated at every location in real time, and only stable location points were accepted to create the 3D maps Using the movement of the catheter tip in the LV cavity, the end-diastolic, end-systolic volumes and global ejection fraction were calculated automatically. The average heart rate was calculated during the electroanatomical mapping procedure.ImageJ for Windows  was used to determine the relative size of the area of interest. The 3D unipolar (UPV) and bipolar (BiPV) voltages of each measuring point were displayed as two-dimensional polar maps (bull's eye format). The same discriminatory threshold values were used for all NOGA maps: <5 mV for non-viable infarcted area, 5–15 mV for infarct border zone and>15 mV for normal viability in unipolar maps and <0.8 mV for transmural, 0.8–1.9 mV for non-transmural infarction and>1.9 mV for normal myocardium in bipolar maps. These cut-off values are represented by the color-coding of the NOGA images and facilitate the identification of areas with reduced UPVs and BiPVs , Fig. 1.In order to determine the BiPV cut-off that provides the best fit to the size of transmural and non-transmural cMRI-LE areas, we also tested 0.5–1.5 mV and 1.0–2.0 mV BiPV cut-offs . The fibThe relative size of the infarct core, border areas, and normal myocardium was determined from the color-coded unipolar voltage polar map, and the sizes of the transmural and non-transmural infarction were delineated on the bipolar maps  and 5. TCardiac magnetic resonance (cMRI) images were acquired on a 1.5 T Siemens Avanto Syngo B17 clinical scanner  with a phased-array coil and a vector ECG system. Functional (dynamic) images were acquired using a retrospective ECG-gated (HR: 80–100 beats/minute), steady-state free precession (SSFP - TRUFISP sequence) technique in short-axis and long-axis sections of the heart using 1.2-ms echo time (TE), 40-ms repetition time (TR), 25 phases, 50° flip angle, 360-mm field-of-view, 8-mm slice thickness, and a 256×256 image matrix. For quantitative measurement of infarct extent and transmurality, delayed enhancement diastolic phase short-axis images were obtained after injection of 0.05 mmol/kg of contrast medium using an inversion recovery prepared gradient-echo sequence. LE images were obtained 10 minutes after gadolinium contrast agent injection.In all cases, care was taken to include the entire heart volume from the apex to the level of the great vessels, and the entire left ventricle was included in the MRI analysis. Analysis was consistently restricted to slices between the apex and the basis on which the left ventricle myocardium is seen in 360 degrees. Image analysis was performed using Segment for Windows software  The 3D infarct volume was determined both in absolute units and as a percentage of the total LV myocardium volume . The entPolar plots were derived from the infarct segmentations using segmental transmurality data. The corresponding bull's eye maps were processed to achieve the same apex, heart axis, and orientation as for NOGA maps.For these visualizations, viability data from 8 apico-basal slices and 32 wall sectors per slice were interpolated and smoothed. The linear borders of 17 segments were overlaid on the images graphically to help interpret the images using “classical” segmental nomenclature, while the interpolated data originated from 32 sections per slice. The endo- and epicardial borders were segmented, and a segmental model was fitted on the left ventricle model (32 sections per slice). Using the standard transmurality analysis feature of the Segment software , the midline was calculated for each section of the LV myocardium. The transmurality of the infarct is given as the radial projection of the segmented scar volume on the midline, summed for each section.By applying two-dimensional planimetry to the polar plots, we performed two distinct measurements of the transmurality of the infarct. The extents of the transmural or non-transmural infarct and normal areas were defined as the percentage of sectors in which the SI was>75% (infarct core), 51–75% (border zone of infarction), 25–50% , or <25%  Dynamic MR images were analyzed for myocardial wall movement and functional parameters. We carried out semi-automatic segmentation of the LV endocardial and epicardial borders while the end-diastolic volume (EDV), end-systolic volume (ESV), global LV ejection fraction (EF), and cardiac output (CO) were calculated automatically on short-axis images.The overlap ratio between the cMRI and NOGA bipolar transmurality maps was calculated as follows /For the overlap ratio of the transmural, non-transmural and the combined transmural and non-transmural  areas the following cut-off values were used:Transmurality overlap ratio: between a NOGA bipolar map area with BipV <0.8 mV and a cMRI transmurality area with SI>75%;Non-transmural areas overlap ratio: between a NOGA bipolar map area with BipV 0.8-1.9 mV and a cMRI transmurality area with SI 25–75%;Combined transmural and non-transmural  area overlap ratio: between a NOGA bipolar map area with BipV <1.9 mV and a cMRI transmurality area with SI>25%  and 5.Overlap>60% was considered good accuracy Myocardial samples were collected from transmural and non-transmural infarctions and from normal heart tissue. These were areas with bipolar voltage values <0.8 mV, from 0.8–1.9 mV, and>1.9 mV with corresponding cMRI-LE transmurality values of>75%, 50%, and <25%, respectively. The samples were stored in 4.5% buffered formalin for at least 24 h and embedded in paraffin. Sections were cut into 4- to 6-µM thick slices and stained with hematoxylin-eosin.Continuous variables are presented as mean values ± standard deviation. The correlation between NOGA- and cMRI-derived parameters  was calculated by linear regression analysis using Pearson Product Moment Correlation and Bland-Altman plots. Linear regression and Bland-Altman analysis was performed using Matlab R2010 software for Windows. During the iterative fitting of the linear function, a “least absolute residual” robust regression approach was used In order to choose the correct BiPV cut-off values for determining the transmural and non-transmural scars, all UPVs were also correlated with the corresponding BiPVs using linear regression analysis. Using a 5 mV UPV value as the cut-off for viability/non-viability, receiver operator curve (ROC) analysis was performed, and the sensitivity, specificity of different BiPV values, and the area under the curve, with 95% confidence intervals, were calculated.For all statistical analyses, a p-value <0.05 was considered statistically significant.There were no complications during the NOGA and cMRI-LE procedures that required additional medication or cardiopulmonary resuscitation.Depending on the threshold values applied to the NOGA bipolar voltage maps, the correlations between the different cut-offs of the two images were r = 0.27–0.57. The 75% MRI transmurality areas showed the best correlation with the NOGA-based areas using a cut-off of 0.76 mV, while the 60% transmurality areas correlated best with NOGA maps using a 0.87 mV threshold. The validation experiment resulted in a cut-off value of 1.3 mV for 25% transmurality. In order to exclude non-transmural ischemia, we used the usual value of 1.9 mV for normal, non-infarcted areas . NotablyThe cMRI-LE and NOGA endocardial mapping results are summarized in The NOGA endocardial maps contained a mean of 202±31 (range: 152–295) mapping points per animal, with a mapping point distribution of 16.8±5.5 points per segment of the 12-segment view. The mapping points were connected automatically if the distance between points was less than 15 mm. The mean time for the NOGA procedure was 35±9 min.The BiPV values correlated significantly with the UPV values . ROC anaThe unipolar voltage map-derived scar size (UPV<5 mV) showed a moderate association with the transmural scar size as determined by bipolar maps (BiPV<0.8 mV) . There was better concordance between the border zone of infarction (UPV 5–15 mV) and non-transmural scars (BiPV 0.8–1.9 mV) . The total size of the ischemic area showed good correlation between the two maps .There was a significant correlation  between the infarct size as determined using the NOGA unipolar voltage polar map and the size determined by cMRI-LE. The Bland-Altman plot showed that NOGA mapping resulted in a systematically higher infarct size compared to cMRI-LE, with a mean difference between the two images of 2.82±7.43% in the LV surface .Using SI>75% and NOGA BipV <0.8 mV, the correlation between the two images was r = 0.727 (p<0.001) for the size of the transmural infarction. NOGA bipolar mapping resulted in a larger transmural infarction size than did cMRI-LE, with a mean difference of 6.81±4.39%) in the LV surface.Using cut-offs for infarct transmurality of SI>60% and NOGA BipV<0.8 mV, the correlation was slightly lower , with a mean difference between the two images of 2.14%±5.62% of LV surface.Using SI = 51–75% and NOGA BipV 0.8–1.9 mV to define non-transmural infarction, the correlation between the two images was r = 0.555 (p<0.001). NOGA bipolar mapping resulted in a smaller area of non-transmural infarction, with a mean difference of 3.04±5.92% between the two images .Using SI = 31–60% and NOGA BipV 0.8–1.9 mV as cut-offs for non-transmural infarction, the correlation was slightly higher , with a mean difference between the two images of 3.23±4.56% of LV surface.The overlap ratio was 81.6±11.1% and 70.6±18.5% for delineation of the transmural and non-transmural infarction size on the cMRI and NOGA images, respectively. None of the images showed an overlapping accuracy below 60% regarding transmural infarction. Regarding non-transmurality, two of the 60 animals (3.3%) showed an overlapping ratio between 50% and 60%, which was considered moderate agreement between the two imaging methods.The overlap ratio of the combined transmural and non-transmural infarction was 70.2±12.2%.Our results indicate that NOGA electroanatomical mapping is accurate enough to guide targeted intramyocardial therapy if both unipolar and bipolar maps are used. The results of NOGA were comparable to those of cMRI-LE, regarding the extent of the transmural and non-transmural scars and viable and reduced viability myocardial areas.The main difference between the two 3D images is that different sampling methods are used to construct them. The NOGA 3D LV shape is constructed by point-to-point measurements, which is in contrast with the other 3D methods, such as cMRI-LE, which have a spatial resolution of 1.4 mm per voxel. For map construction, a 15-mm point-to-point distance was used by endocardial mapping, while an in-plane resolution of 1–2 mm with an 8-mm slice thickness was utilized for cMRI-LE analysis. Accordingly, the accuracy of the NOGA map depends mainly on the number of gathered and measured points and on the quality of the acquired points used to construct the 3D map. Difficulties in reaching some regions with the mapping catheter due to LV cavity structures such as the papillary muscles or the occurrence of ventricular arrhythmias due to touching vulnerable ischemic areas might lead to insufficient sampling, resulting in incomplete mapping. Nevertheless, unipolar voltage mapping overestimated the infarct size by just 2.82% of the entire LV endocardial surface, and bipolar mapping overestimated the transmural scar by just 6.82% of the LV. These estimates are acceptable for performing intramyocardial procedures safely and accurately. The overestimation of the infarct size and transmural scar as compared to cMRI-LE might result from the quantitative comparison of 2D NOGA polar maps and 3D cMRI-LE and 2D transmurality cMRI-LE images. According to our results, both the unipolar and bipolar voltage maps showed wider zones of interest than on cMRI, which may raise the risk of injecting reparative substances into normal myocardium. The intramyocardial injections are oriented into the non-transmural infarct or into areas with decreased viability. Different cut-offs are suggested for viability and transmurality thresholds in the literature; there are no universally agreed-upon definitions for these terms. Of course, the operators should try to make sure that the intramyocardial injections are made into the correct area, but an injection may be made into the “normal” myocardium if stronger cut-off criteria for non-normal territory are used. However, regenerative cells or other material delivered into the lane neighboring the non-transmural infarction have a good chance of being retained, being functional, and migrating or penetrating into the ischemic area, so a wider zone might result in more effective and safe treatment.The sizes of the unipolar voltage scar and border zone differed from the sizes of transmural and non-transmural infarction as determined on the bipolar maps. Although the total size of the unhealthy areas on the unipolar and bipolar polar maps showed good correlation, the size of the infarction and border area determined on the unipolar maps was systematically larger than the size of the transmural and non-transmural regions on the bipolar maps. This is not surprising, because an infarct area contains heterogeneously viable myocytes that can be apoptotic or hibernating. Accordingly, the infarct core and the border area (i.e. the extent of infarction) do not necessarily overlap the transmural and non-transmural infarction (i.e. the infarction severity) because the infarct core may include transmural and non-transmural necrotic areas.The unipolar voltage values represent a summation of the action potentials of the surrounding endocardial surface areas, while the bipolar voltage values represent the amplified difference between the tip of the unipolar electrode and the additional proximal electrode placed within the catheter. Accordingly, a non-transmural infarction with severe endocardial  necrosis may appear to be an infarct core in the unipolar map. This might explain the differences between the unipolar and bipolar NOGA maps, and between the NOGA maps and other 3D images that measure infarct size. Nevertheless, using both (uni- and bipolar) maps of the NOGA images, information about both the extent and the severity of infarction are available real-time, on-table during a procedure, in contrast to off-line images such as cMRI-LE or myocardial single photon emission computed tomography.Additionally, to set the correct and right cut-off values of the NOGA maps is of great importance. Several authors used several different cut-off values for definition of viability using the unipolar voltage maps, while the usage of bipolar maps is less common, probably due to the small range of not normal values (0–1.9 mV of interest) suggesting less precise differentiations. We have measured the transmural and non-transmural scars on the cMRI-LE image using two different SI cut-offs, because a SI between 25% and 50% suggests a false positive non-transmural infarction. When the cMRI transmurality threshold is lowered to 60% from 75% and to 31–60% from 51–75%, the size of the transmural and non-transmural infarct areas increase, and the correlations are slightly lower and higher, respectively. The SI of 30% and 60% for cut-off of non-transmural and transmural scars gave a better correlation with slight overestimation of the non-transmural scar by 3.23% of the LV. Since the endocardial injections should target non-transmural infarct areas, higher correlation between the two images in that region is desirable.The need to localize the arrhythmogenic focus for ablation during catheter-based electrophysiological procedure prompted several research groups to develop hybrid software that analyzes the 3D images of both NOGA maps and cMRI-LE. Fusion of cMRI with electroanatomical mapping of the LV proved to be successful with a registration error of 3.8±0.6 mm We did not use local linear shortening maps of the NOGA for delineating of the hibernating myocardium characterized by preserved viability and decreased segmental wall motion We are aware that there are ongoing efforts to fuse 3D NOGA endocardial maps and cardiac MRIs to determine the similarities of infarct location and extent. Although numerous percutaneous intramyocardial therapy studies are currently underway with the aim of determining the optimal injection location, currently there is no commercially available 3D MRI-NOGA fusion software. The comparisons of cMRI and NOGA polar maps published previously lack some of the refinements we used, such as comparison of the transmurality map with the bipolar map and calculation of the overlapping ratio.Unfortunately, we could not perform 3D volumetric co-registration of the compared modalities, as currently we do not have an image-processing tool with which to conduct such a comparison. The spatial correspondence was ensured by (1) similar selection of the basal and apical slice positions and (2) similar orientation of the bull's eye maps. The definition of sector orientation was based on manual selection of the right ventricular insertion point (sector 0) on the most basal MRI slice of the left ventricular myocardium. A real value of the fusion of the off-line cMRI-LE and on-table NOGA endocardial mapping would be the real-time display of the actual catheter position and location of the intramyocardial therapy on the reconstructed hybrid (cMRI and NOGA) image; which software is currently not available.We have included the NOGA-derived volumetric measurements. The similarities between the NOGA-derived and cMRI-derived end-diastolic and end-systolic volume and calculated stroke volume and ejection fraction  and 3 enThe use of 2SD method of cMRI-LE might overestimate the infarct size, as compared with the 5SD or “full width at half maximum” (FWHM) method. In our experience, it has not been the case that the 5SD method better reflects the infarct size compared to the 2SD approach, and there are data in the literature that show a higher correlation coefficient for the 2SD approach than the 5SD approach Our results demonstrate the usefulness of unipolar and bipolar maps generated using real-time electroanatomical mapping for targeted intramyocardial regenerative therapy. NOGA mapping showed good concordance with the off-line gold standard, cMRI-LE imaging. NOGA mapping may be useful in patients with contraindications for cMRI who require targeted intramyocardial regenerative therapy.


International Journal of Clinical Pediatric Dentistry is 5 years old and over this period of time has achieved the reputation of a well-managed clinical journal cited by many authors around the world. International Journal of Clinical Pediatric Dentistry is 5 years old and over this period of time has achieved the reputation of a well-managed clinical journal cited by many authors around the world. This journal is unique in providing complete, definitive and authoritative reviews on many aspects of clinical pediatric dentistry and continues to be a significant contribution to the art of this speciality. At the same time, we know that there will always be room for improvement. The Editor and the Editorial Board have worked with the outstanding publishing staff to design the journal with a very contemporary and easy to follow outlook. All figures and photographs are of high color quality and could be found in the online version of the manuscript, enabling easy access to a number of very relevant clinical conditions. To further broaden the outreach and appeal of the topics published, we try to emphasize the need for multidisciplinary approach in clinical pediatric dentistry aiming at integrating research in this field with other oral health and general health disciplines. In this way, we hope to cross many bridges that will broaden the impact of the International Journal of Clinical Pediatric Dentistry in both the basic and clinical research domains. It is important to add that the Editorial Board of the journal is international-based which provides a real international outreach. We are certain that the international expertize of our board members will keep the journal up to date in regard to the clinical and scientific significance of the topics discussed. In closing this message I would like to thank the Editor and the Board members for their continued efforts in having the International Journal of Clinical Pediatric Dentistry provide an important contribution to the art and science of pediatric dentistry.Charles LekicDDM, MSc, PhD, FRCD(C)Associate and Managing Editor


The scientific paper is one of the most visible areas of science. It is disseminating hisideas, new techniques and discoveries that the scientist, whether he is doctor,physician, biologist, engineer etc., plays his role in the expansion of knowledge andthe consequent benefit to society and may break paradigms. This process is not simple,as we know, going through a series of bottlenecks ranging from consulting the relevantliterature, research, data compilation, writing, journal's choice, where it passesthrough the sieve of the reviewers, final approval by the Editor and finallyadjustments, in minor or major ways, until its release/publication., in the case of Brazil, or the need for the articleis written in English so it can be read, and eventually cited by the greatest number ofreaders.Currently, the requirements are higher, either because postgraduate school to which theauthor is connected requires publishing studies in journals with higher impact factor(IF), depending on the CAPES criteria In choosing a journal until the speed of dissemination of knowledge on the Internet, itis important, since today's novelty turns into something "outdated" tomorrow..In The Lancet, for example, it is 95%. In journals restricted to a specific area such as theBrazilian Journal of Cardiovascular Surgery (BJCVS), the percentage is somewhat lower,but has been increasing over the years.Aware of this new scenario, scientific journals have sought to refine their acceptancecriteria and publishing articles. The Scielo has encouraged the journals that are partof its regular basis to take action accordingly. This creates a side effect, which isthe increasing rejection of studies, either in submission or during the review process.In journals from various fields, not only among the best known, the rate of rejectedmanuscripts exceeds 90%pari passu" with thebest-known journals. Our rejection rate is rising gradually. In 2013, of 186 studiesreceived, 61 were rejected (32.79%). In 2014, we received 162 manuscripts and 70 wererejected (43.21%). The average time between the submission of the study and the decisionto approve or reject fell 147 days in 2013 to 86 days in the last year  allowing its citation in the literature.Despite all our efforts to internationalize the BJCVS, it is still an eminently Brazilianjournal. In 2013, of the total number of items received, 161 were from Brazil, followedby 14 from Turkey, 4 from China, 2 from the United States, 2 from Greece, 1 fromArgentina, 1 from Colombia and 1 from the Netherlands. In 2014, 120 were from Brazil, 22from China, 11 from Turkey, 2 from Colombia, 2 from Greece and 1 from Germany, 1 fromItaly, 1 from Portugal, 1 from Serbia and 1 from Venezuela .Due to the largest number of studies received, Brazil was the country with the largestnumber of rejected manuscripts .With the adoption of English as the official language of the journal, six issues a yearand a greater increase in disclosure, we hope to receive more international qualitystudies, and also from Brazil.Without being redundant, I explain the reason to emphasize that the studies should be ofquality and international. I see this as the only way to see our IF increase because thechance of readers of BJCVS to cite our journal in other publications that also are inthe Thomson database and the Scopus increases in parallel to these parameters.http://www.redalyc.org/). Based inMexico, Redalyc has nearly 1,000 open access journals, allowing the dissemination ofscientific information.Aiming to expand our visibility, after various requirements and a long time inanother database, the Redalyc admitted us , several activities tocommemorate the 30We trust that even facing many obstacles, never interrupting the circulation, theperspective is positive for us to continue our successful track record. The journalis available on multiple platforms, is present in social networks and alwaysattentive to new technology and, of course, always trying to improve itscontent.Post-cardiotomy ECMO in pediatric and congenital heartsurgery: impact of team training and equipment in the results" (page409); "Relationship between pre-extubation positive end-expiratory pressureand oxygenation after coronary artery bypass grafting" (page 443);"Evaluation of the influence of pulmonary hypertension inultra-fast-track anesthesia technique in adult patients undergoing cardiacsurgery" (page 449); "Effects of intraoperative diltiazeminfusion on flow changes in arterial and venous grafts in coronary artery bypassgraft surgery" (page 459). I emphasize that the CME is a valuable toolfor learning and updating of knowledge and is worth 0.5 points in the BJSVC proof oftitle. We are open to suggestions and criticisms to improve the system.The following items are available for the testing of Continuing Medical Education(CME) in this issue: "My warmest regards,- BJCVS/RBCCVDomingo Braile


ESSKA is a non-profit organization that stands for quality, independence, high ethical standards and rigor.ESSKA has during the past few years experienced an exceptional growth, undergoing several important changes/improvements and consolidating its position as one of the world’s leading societies in orthopaedic sports traumatology and degenerative joint disease.ESSKA has doubled the number of members in the past two years and with its 2800 members and 26 affiliated societies ESSKA is the most important European sports traumatology association.ESSKA has during the last 10 years taken increased responsibility for research and education. The ESSKA journal; Knee Surgery Sports Traumatology Arthroscopy (KSSTA) is now more than 20 years and is increasingly popular as the clinical journal of ESSKA. But, we must remember that all clinical and patient-related research is based on basic science.Why a new Journal? Basic science is the corner-stone for the understanding of disease on which depends the delivery of high quality patient care. This is what Evidence-Based Medicine (EBM) is founded upon. Whilst Europe has a very strong position in terms of research and science, it was perceived to be lacking an outlet for its the basic reserach scientists (within the field of Orthopaedic Sports Medicine/Traumatology and degenerative joint diseases) to disseminate their findings. This gap, (in ESSKA’s view), therefore warranted the setting up of a basic science journal.A development strategy set out during a strategic planning meeting in Amsterdam 2010 by ESSKA’s Board, highlighted and addresssed (over the intervening years), the development needs of such a scientific journal, alongside with KSSTA. Following the initial preparatory work, the journal was successfully launched in December 2013 under the leadership of Henning Madry. Springer will publish the new journal with the Journals’editorial office based in Luxembourg.The new journal, entitled the Journal of Experimental Orthopaedics (JEO) shall collaborate closely with the Knee Surgery Sports Traumatology Arthroscopy journal (KSSTA), ESSKA’s clinical journal. The intention being, to build a strong publication team in order to cover the entire scientific field of sports traumatology and degenarative joint desease.This is a similar approach to that which AOSSM developed with their successful American Journal of Sports Medicine (AJSM) and now Orthopaedic Journal of Sports Medicine (OJSM). Also AANA recently added Arthroscopic Techniques to their already successful journal of Arthroscopy.As mentioned before ESSKA found the need to move in this same direction and responded with the development of the JEO. The ESSKA Board saw that the most important contribution would be to basic science within the field of orthopaedic sports traumatology and degenerative joint desease. ESSKA’s reputation stands for quality patient care through education and this new journal will reflect and build on the proud reputation of KSSTA these core values.In line with this new relationship between the KSSTA and JEO journals, the ESSKA Board has decided that KSSTA will in the future concentrate mainly on clinical topics. The Editors in Chief of both journals are fully aware that this transition will take some time and therefore it is expected that the number of experimental/basic science studies in KSSTA will reduce in number over a period of time and in the future any such studies submitted to KSSTA shall be cascaded to JEO; this being optional to authors, of course. In this manner the sister journals will be better able to cover the full spectrum of basic science and clinical studies in our field in the future.JEO will be published as an open access, online publication benefiting from fast handling of manuscripts and on completion immediate publication. JEO’s prevailing aim is to bridge the gap between basic science and the clinical field and welcomes basic science studies on all aspects of musculo-skeletal diseases.www.jeo-esska.com.We welcome the new journal and we invite you to submit your manuscripts to the JEO at;


Purpose. To report 7 cases of intraocular lens (IOL) opacification following treatment of postoperative anterior chamber fibrin with recombinant tissue plasminogen activator (rtPA) after cataract surgery. Methods. Retrospective case series of 7 eyes in 7 patients who developed IOL opacification after receiving rtPA for anterior chamber inflammatory membrane formation resulting from phacoemulsification cataract surgery. Three explanted IOLs were investigated with light microscopy, histochemical analysis, scanning electron microscopy, and X-ray spectrometry. Results. All patients underwent uncomplicated cataract surgery and posterior chamber hydrophilic IOL implantation. Anterior chamber inflammatory membranes developed between 1 and 4 weeks of surgery and were treated with intracameral rtPA. IOL opacification was noted between 4 weeks and 6 years after rtPA treatment with reduced visual acuity, and IOL exchange was carried out in 3 patients. Light microscopy evaluation revealed diffuse fine granular deposits on the anterior surface/subsurface of IOL optic that stained positive for calcium salts. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS) confirmed the presence of calcium and phosphate on the IOL. Conclusions. Intracameral rtPA, though rapidly effective in the treatment of anterior chamber inflammatory membranes following cataract surgery, may be associated with IOL opacification. Postoperative uveitis associated with inflammatory membrane formation occurs in less than 3% of cases after uneventful cataract surgery and intraocular lens (IOL) implantation . ComplicIntracameral injection of recombinant tissue plasminogen activator (rtPA), a highly potent fibrinolytic protein used for systemic thrombolysis, has been shown to successfully lyse fibrin membranes –5. ReporWe report 7 cases of IOL opacification subsequent to rtPA treatment for postoperative inflammatory membranes following uneventful phacoemulsification and hydrophilic acrylic one-piece IOL implantation (Rayner C-flex 570C and Superflex 620H). To the best of our knowledge, this is the first report of hydrophilic acrylic IOL opacification following the use of intracameral rtPA.This retrospective case series included 7 eyes of 7 patients. Three patients had type 2 diabetes and treated proliferative retinopathy, and one patient presented with phacomorphic glaucoma requiring urgent cataract surgery. Two patients had medically controlled systemic hypertension but none had abnormal albumin or serum calcium levels.All patients underwent uneventful cataract phacoemulsification and posterior chamber IOL implantation under local anaesthesia between August 2002 and September 2009. One procedure was combined with elective vitreoretinal surgery. Two percent hydroxypropylmethylcellulose (Coatel) and balanced salt solution (BSS) were used in all cases. The Rayner C-flex 570C IOL was implanted in 4 patients and the Rayner Superflex 620H was implanted in 3 patients. No remaining viscoelastic material or soft lens matter was observed at the end of all procedures. All patients received 4 hourly dexamethasone 0.1% and 6 hourly chloramphenicol eye drops postoperatively.μL of this solution was injected into the anterior chamber using an insulin syringe with a 30-gauge needle. Slit lamp examination and intraocular pressure measurement were performed 2 and 24 hours after rtPA treatment. The frequency of dexamethasone 0.1% was increased to be hourly by day, together with chloramphenicol 6 hourly and cyclopentolate 1% 8 hourly. Further reviews were scheduled at weeks 1 and 3 and at 6 months after treatment.Inflammatory membrane formation was noted within 1 week in three patients and between 2 and 4 weeks in the remaining 4 patients. Intracameral rtPA (Actilyse) was prepared under sterile conditions using 50 mg vials of rtPA diluted with 50 mL of sterile water to create a 1 mg/mL solution. 10–50 Intraocular lens exchange was performed in 3 patients. Opacified IOLs were viscodissected with sodium hyaluronate , with care taken to avoid manipulation of the opacified portion. One patient required bisection of the IOL and anterior vitrectomy due to severe adhesion between the IOL and lens capsule. Explanted IOLs were placed in a sterile container with neutral buffered formalin 10% before they were sent for laboratory analysis.Two explanted IOLs were sent to the Laboratories for Ophthalmic Devices Research, Sullivan's Island, South Carolina, USA, for light microscopy and histochemical analysis. Another IOL was sent for light microscopy, scanning electron microscopy, and X-ray spectrometry at the International Vision Correction Research Centre, Department of Ophthalmology, University of Heidelberg, Germany.Detailed techniques for preparation and staining of explanted IOLs for calcium have been described elsewhere . BrieflyMacroscopic and microscopic findings on all explanted IOLs were highly comparable. On macroscopic examination, fine granular whitish opacities were observed in the central part of all explanted IOL optics . Light mCross-sectional SEM of opacified IOL showed crystalline deposits distributed close to the surface of the IOL . AnalysiIOL opacification is an infrequent complication after uneventful cataract surgery, resulting in symptoms of visual loss or glare, necessitating IOL exchange in some cases. To our knowledge, this is the first report of IOL opacification due to calcification following the use of rtPA for postoperative fibrinous membranes after cataract surgery.A number of cases of IOL opacification have previously been reported; almost all were involving hydrophilic acrylic IOLs from various manufacturers –15. It iIOL calcification has been associated with systemic disease, intraocular surgery, inflammation, or drug administration , 16–18. In our series, all cases had postoperative inflammatory membranes that were successfully treated with rtPA. In our unit, rtPA was more commonly used in phakic patients with fibrinous uveitis. We are not aware of any other pseudophakic patients who had received intracameral rtPA injections. Thus it would be suggested that intracameral rtPA injection is an absolute risk factor for IOL opacification. In response to our findings, we stopped further usage of intracameral rtPA in cases of postoperative inflammatory membrane formation, and we have not observed any cases of IOL opacification since. These cases were also reported to the Medicines & Healthcare Products Regulatory Agency in the United Kingdom.We hypothesise that rtPA contributes to IOL opacification through its action on aqueous calcium-phosphate homeostasis and possible disruption of the blood-aqueous barrier (BAB). Intracameral rtPA lyses fibrinous inflammatory membranes and in doing so releases sequestered calcium from the fibrinous matrix. It also introduces phosphate ions contained in its buffer solution, which may potentiate abnormal calcium precipitation. A case report of band keratopathy formation after rtPA injection lends support to our hypothesis . Recent Similar to air injection in DSAEK graft rebubbling , rtPA inμg) in all except 2 cases [We have considered alternative hypotheses for our findings. Although intraocular inflammation could be solely responsible for IOL opacification, it fails to explain the strong association between IOL opacification and the use of rtPA. The dosages of rtPA used in our patients were within the range reported by previous authors 3–25 5 μg in a 2 cases , 24. It Another possible cause could be the IOLs we used in these patients. Cases of IOL opacification occurred during a period when our unit exclusively used Rayner IOLs. C-flex and Superflex differ in the size of the optic  and the range of diopter power , but they are both hydrophilic acrylic one-piece monofocal IOLs. However, there was no evidence of any manufacturing defects on the explanted IOLs in our histopathological analysis. Opacification of hydrophilic acrylic lenses from other manufacturers has also been previously reported. Therefore, we do not believe our findings are IOL-specific phenomenon.This study highlights that intracameral injection of rtPA for the treatment of postoperative inflammatory membranes could lead to IOL opacification requiring IOL exchange. The limitations of this study were its retrospective nature and the small number of cases involved. The intraocular effects of rtPA may be more extensive than previously thought, and further laboratory investigations on this are needed. Caution should be exercised in using rtPA to treat inflammatory membranes following intraocular surgery, especially in the presence of hydrophilic IOLs.