Two-Step Nanoscale Approach for Well-Defined Complex Alkanethiol Films on Au Surfaces.

Controlling the molecular organization of organic self-assembled monolayers (SAM) is of utmost importance in nanotechnology, molecular electronics, and surface science. Here we propose two well-differentiated approaches, double printing based on microcontact printing (µ-cp) and molecular backfilling adsorption, to produce complex alkanethiol films. The resulting films on model Au surfaces were characterized by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and contact angle measurements. Double printing alkanethiols results in clear coexisting regions where no molecular displacement is observed, highlighting the slow diffusion rates of long alkanethiols and large attractive interaction between long alkyl chains. Exposing a single-print µ-cp Au substrate to an additional alkanethiol solution yields the formation of differently ordered domain boundaries with different thickness and micrometer lateral size. The high order is a result of enhanced molecular mobility and restructuring during solution backfilling. The formed molecular assemblies constitute an excellent testing ground for nanoscale phenomena that strongly depend on the nanoscale geometrical and chemical features of the surface such as designed functionality or corrosion initiation and inhibition.

Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series.

Treatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post-treatment, demonstrated improvements in individuals' mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP).

Uncertainties in Monte Carlo-based absorbed dose calculations for an experimental benchmark.

There is a need to verify the accuracy of general purpose Monte Carlo codes like EGSnrc, which are commonly employed for investigations of dosimetric problems in radiation therapy. A number of experimental benchmarks have been published to compare calculated values of absorbed dose to experimentally determined values. However, there is a lack of absolute benchmarks, i.e. benchmarks without involved normalization which may cause some quantities to be cancelled. Therefore, at the Physikalisch-Technische Bundesanstalt a benchmark experiment was performed, which aimed at the absolute verification of radiation transport calculations for dosimetry in radiation therapy. A thimble-type ionization chamber in a solid phantom was irradiated by high-energy bremsstrahlung and the mean absorbed dose in the sensitive volume was measured per incident electron of the target. The characteristics of the accelerator and experimental setup were precisely determined and the results of a corresponding Monte Carlo simulation with EGSnrc are presented within this study. For a meaningful comparison, an analysis of the uncertainty of the Monte Carlo simulation is necessary. In this study uncertainties with regard to the simulation geometry, the radiation source, transport options of the Monte Carlo code and specific interaction cross sections are investigated, applying the general methodology of the Guide to the expression of uncertainty in measurement. Besides studying the general influence of changes in transport options of the EGSnrc code, uncertainties are analyzed by estimating the sensitivity coefficients of various input quantities in a first step. Secondly, standard uncertainties are assigned to each quantity which are known from the experiment, e.g. uncertainties for geometric dimensions. Data for more fundamental quantities such as photon cross sections and the I-value of electron stopping powers are taken from literature. The significant uncertainty contributions are identified as the energy of the radiation source and the underlying photon cross sections as well as the I-value of media involved in the simulation. The combined standard uncertainty of the Monte Carlo calculation yields 0.78% as a conservative estimation. The result of the calculation is close to the experimental result and with each combined standard uncertainty <1%, the accuracy of EGSnrc is confirmed. The setup and methodology of this study can be employed to benchmark other Monte Carlo codes for the calculation of absorbed dose in radiotherapy.

Localized dealloying corrosion mediated by self-assembled monolayers used as an inhibitor system.

The structure and chemistry of thiol or selenol self-assembled organic monolayers have been frequently addressed due to the unique opportunities in functionalization of materials. Such organic films can also act as effective inhibition layers to mitigate oxidation or corrosion. Cu-Au alloy substrates covered by self-assembled monolayers show a different dealloying mechanism compared to bare surfaces. The organic surface layer inhibits dealloying of noble metal alloys by a suppression of surface diffusion at lower potentials but at higher applied potentials dealloying proceeds in localized regions due to passivity breakdown. We present an in situ atomic force microscopy study of a patterned thiol layer applied on Cu-Au alloy surfaces and further explore approaches to change the local composition of the surface layers by exchange of molecules. The pattern for the in situ experiment has been applied by micro-contact printing. This allows the study of corrosion protection with its dependence on different molecule densities at different sites. Low-density thiol areas surrounding the high-density patterns are completely protected and initiation of dealloying proceeds only along the areas with the lowest inhibitor concentration. Dealloying patterns are highly influenced and controlled by molecular thiol to selenol exchange and are also affected by introducing structural defects such as scratches or polishing defects.

The effect of psychotherapy for depression on improvements in social functioning: a meta-analysis.

BACKGROUND: Patients with depression often report impairments in social functioning. From a patient perspective, improvements in social functioning might be an important outcome in psychotherapy for depression. Therefore, it is important to examine the effects of psychotherapy on social functioning in patients with depression. METHOD: We conducted a meta-analysis on studies of psychotherapy for depression that reported results for social functioning at post-treatment. Only studies that compared psychotherapy to a control condition were included (31 studies with 2956 patients). RESULTS: The effect size of psychotherapy on social functioning was small to moderate, before [Hedges' g = 0.46, 95% confidence interval (CI) 0.32-0.60] and after adjusting for publication bias (g = 0.40, 95% CI 0.25-0.55). Univariate moderator analyses revealed that studies using care as usual as a control group versus other control groups yielded lower effect sizes, whereas studies conducted in the USA versus other countries and studies that used clinician-rated instruments versus self-report yielded higher effect sizes. Higher quality studies yielded lower effect sizes whereas the number of treatment sessions and the effect size of depressive symptoms were positively related to the effect size of social functioning. When controlling for these and additional characteristics simultaneously in multivariate meta-regression, the effect size of depressive symptoms, treatment format and number of sessions were significant predictors. The effect size of social functioning remained marginally significant, indicating that improvements in social functioning are not fully explained by improvements in depressive symptoms. CONCLUSIONS: Psychotherapy for depression results in small to moderate improvements in social functioning. These improvements are strongly associated with, but not fully explained by, improvements in depressive symptoms.

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways.

Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.

Element-resolved corrosion analysis of stainless-type glass-forming steels.

Ultrathin passive films effectively prevent the chemical attack of stainless steel grades in corrosive environments; their stability depends on the interplay between structure and chemistry of the constituents iron, chromium, and molybdenum (Fe-Cr-Mo). Carbon (C), and eventually boron (B), are also important constituents of steels, although in small quantities. In particular, nanoscale inhomogeneities along the surface can have an impact on material failure but are still poorly understood. Addressing a stainless-type glass-forming Fe50Cr15Mo14C15B6 alloy and using a combination of complementary high-resolution analytical techniques, we relate near-atomistic insights into increasingly inhomogeneous nanostructures with time- and element-resolved dissolution behavior. The progressive elemental partitioning on the nanoscale determines the degree of passivation. A detrimental transition from Cr-controlled passivity to Mo-controlled breakdown is dissected atom by atom, demonstrating the importance of nanoscale knowledge for understanding corrosion.

The risk of polyomavirus-associated graft nephropathy is increased by a combined suppression of CD8 and CD4 cell-dependent immune effects.

Polyomavirus-associated graft nephropathy (PAN) has emerged as a significant risk factor for kidney graft loss. We analyzed intracellular cytokine responses for possible protective versus permissive immunologic effects on BK-virus replication. One hundred five renal transplant patients included in a prospective single-center study were randomized to receive cyclosporine mycophenolate mofetil (MMF) (CM: n = 31), tacrolimus (Tac)/MMF (TM: n = 32) or Tac/MMF with conversion to everolimus (TErl; n = 32). Ten patients were not randomized (NR) due to contraindications to MMF. The immunosuppressive therapy was monitored pre- and posttransplantation at 4, 12, and 24 months using triple fluorescence flow cytometry for intracellular interleukin (Il)-2 Il-4 and interferon (IFN)-γ production in phorbol myristate acetate- and lipopolysaccharide- stimulated lymphocyte cultures. BK viremia screening was performed by reverse-transcriptase polymerase chain reaction testing on days 0, 14, 30, 60, 90, 120, 180, 270, 360, and 720. Seven of 105 (6.7%) patients developed biopsy-proven PAN (CM: n = 1, TM: n = 3, TErl: n = 2, NR: n = 1), among whom 4 lost their grafts (TM: n = 1, TErl: n = 2, NR: n = 1). Twenty-one of 105 (20.0%) patients had documented BK viremia. BK viremia which preceded PAN in all cases, was significantly associated with TM immunosuppression: 4/31 (12.9%) CM: 11/32 (34.4%) TM; 5/32 (15.6%) TErl, and 1/10 (10.0%) NR patients (P = .034). BK-viremic patients showed significantly diminished CD8(+) T-cell Il-2 production at 120 days (P = .011) and 1 year posttransplantation (P = .014) compared with non-BK-viremic patients. Patients with PAN displayed significantly lower CD4(+) T-cell Il-4 responses at 1 and 2 years after transplantation (1 year: P = .007; 2 years: P = .001) with diminished IFN-γ responses at 1 year after transplantation (P = .011). Our analysis showed the incidence of BK viremia to be increased among patients with defective cytotoxic CD8(+) T-cell -dependent immune reactivity. Recipients who progressed from BK viremia to overt PAN showed an additional immunologic defect in CD4(+) T-cell function. Patients on a Tac- plus MMF-based immunosuppression were at higher risk to develop BK viremia.

Prevalence of flat lesions in a large screening population and their role in colonoscopy quality improvement.

BACKGROUND AND STUDY AIMS: Flat lesions pose new challenges for endoscopists, but the importance of detecting them is still controversial. Most screening studies do not survey macroscopic polyp morphology. The aims were to evaluate the percentage of flat polyp findings in a large asymptomatic adult screening population (n = 52 521), to assess the impact of shape and size on malignant transformation, and to assess the role of flat lesions regarding quality assurance in colorectal cancer prevention. MATERIAL AND METHODS: Retrospective analysis of screening colonoscopies performed between 2007 and 2011 according to the Austrian "Quality management for colon cancer prevention" program. RESULTS: 17 771 patients with polyps were included in the study. Patients with flat polyps represented 24.2 % (n = 4293), 62.4 % (n = 11 097) were classified as having sessile and 13.4 % (n = 2381) as pedunculated polyps. Among those with flat polyps 51.4 % had adenomas (n = 2207). High grade dysplasia (HGD) was found in 2.1 % (n = 47) of flat adenomas, in 1.5 % (n = 89) of sessile adenomas and 4.7 % (n = 92) of pedunculated adenomas (P < 0.0001. The risk for containing HGD was 1.0 % for flat lesions ≤ 10 mm in size compared with 10.3 % for lesions > 10 mm, and 1.0 % for polypoid lesions ≤ 10 mm compared with 9.3 % for lesions > 10 mm (P < 0.0001). Multivariable logistic regression showed that polyp size (P < 0.0001) but not polyp shape (P = 0.438) is an independent predictor for HGD. Adenoma detection rate (ADR) correlated weakly with the flat polyp detection rate (Pearson r = 0.24). CONCLUSION: Malignant potential of polyps is mostly affected by size but not by shape. Since flat polyp detection rate only correlates poorly with ADR we do not recommend its incorporation in quality assured screening colonoscopy.

One hundred six live kidney donors in a single German transplantation center: renal, physical, and psychological follow-up.

OBJECTIVE: The objective of this study was to analyze the psychological and physical status as well as renal outcomes of 106 live kidney donors between 1993 and 2003. METHODS: We performed general and nephrological examinations, including measurements of creatinine clearance (ClCr), proteinuria, and 24-hour blood pressure monitoring. We evaluated the psychological and general health situation using the standardized SF-36 questionnaire. RESULTS: We evaluated 69/106 (65%) live kidney donors at 5.3 ± 0.4 years after donation. The reason for the 37 drop-outs were unknown current address (n = 21), refusal of study participation (n = 14), and death due to accident and suicide (n = 2). In the 69 donors renal function was well preserved: serum creatinine 1.3 ± 0.0 mg/dL; ClCr 81 ± 2 mL/min; postdonation to predonation ClCr ratio 0.73 ± 0.02; and proteinuria 104 ± 11 mg/d. None of the donors experienced renal failure, although 36/69 (52%) patients have developed de novo hypertension. Compared with normotensive donors, the hypertensive subgroup was significantly older at the time of donation (50.7 ± 1.4 vs 46.4 ± 1.6 years; P = .010) and had a longer interval since donation (6.4 ± 0.2 vs 3.9 ± 0.1 years; P = .001). SF-36 questionnaire results in live kidney donors showed higher scores regarding physical (54.3 ± 0.8 vs 49.3 ± 0.1; P = .048) and psychological health (53.8 ± 0.6 vs 50.7 ± 0.1; P = .043) compared with the average German population. CONCLUSION: Our cohort of live kidney donors showed good renal outcomes and superior SF-36 scores in both physical and psychological health compared with the German population. The risk of de novo hypertension increased with age and time after donation. Blood pressure screening should be regularly performed especially in the long term after donation.

Impact of pretransplant intravenous immunoglobulin administration on anti-AB0 antibody levels in AB0-incompatible living donor kidney transplantation.

BACKGROUND: From March 2007 to July 2010, we performed 14 AB0-incompatible (AB0i) living kidney transplantations using donor blood group-specific immunoadsorption (IA), anti-CD20 monoclonal antibody, and intravenous immunoglobulin (IVIG) pretreatment. METHODS: To analyze the effect of a presumed anti-donor blood group-specific antibody transfer by IVIG administration (0.5 g/kg; 5.4 ± 0.9 days pretransplant), we assessed AB0i antibody titers in different IVIG preparations and evaluated their impact on patient AB0i antibody titers. RESULTS: AB0i antibody IgG titers before treatment ranged from 8 to 1024. We performed 6.9 ± 1.1 IA procedures pretransplant to reach AB0i antibody titers ≤4, which enabled successful transplantation in all pretreated patients. Their mean serum creatinine at discharge was 1.5 ± 0.1 mg/dL. IVIG preparations differed profoundly in their AB0i antibody titers: The lowest titers were observed in Sandoglobulin preparations (1-8) compared with Intratect (2-128), Octagam (4-32) and Gamunex (2-512). Usually, administration of the IVIG preparation containing the lowest isoagglutinin titer resulted in low AB0i antibody titer increments in patient sera: Sandoglobulin, 2 titer steps (n = 2), 1 titer step (n = 1), and 0 titer steps (n = 5). In contrast, Octagam showed 0 titer steps (n = 2) and Intratect, 0 titer steps (n = 3). However, after Gamunex administration, the AB0i antibody titer of 8 and the AB0i antibody titer rose 3 titer steps (16 to 128; n = 1), which could not be explained by passive transfer of isoagglutinin alone. CONCLUSION: Our data showed that the choice of IVIG preparation with the lowest AB0i antibody levels is a time- and cost-sparing step in the pretreatment of AB0i living donor kidney recipients. Posttransplant, a high isoagglutinin content within the IVIG preparation has the potential to induce antibody-mediated rejection.

Postoperative bleeding after AB0-incompatible living donor kidney transplantation.

BACKGROUND: Since 2007, we have performed 14 AB0-incompatible (AB0i) living kidney transplantations to increase the number of living kidney transplantations. METHODS: To prevent clotting, donor kidneys were perfused with an HTK/heparin solution with heparin washed out immediately pretransplantation. However, in 4/14 recipients, significant postoperative diffuse hemorrhage occurred with the need for surgical intervention in 3 patients. To analyze the cause of postoperative diffuse bleeding, sequentially before and after opening the graft anastomosis, we prospectively performed coagulation studies: partial thromboplastin time (PTT), thrombin time, thromboplastin time, fibrinogen, antithrombin, D-dimers, plasminogen, and thrombelastography. RESULTS: We found no clotting disturbances owing to blood group-specific immunoadsorption. However, 3/4 patients with bleeding complications showed elevated PTT values even 2 hours after opening the anastomosis, which was proven to be a heparin effect by in vitro application of heparinase. Hyperfibrinolysis and disturbances of platelet aggregation were not detected. Because of these results, we lowered the heparin dose administered after donor nephrectomy from initially 10,000-20,000 to 4000 IU resulting in significantly lower PTT values at 2 hours (34.6 ± 4.5 s among patients 6-14 vs 69.0 ± 16.3 s among patients 1-5; P = .012). There were no further bleeding complications. Lowering the heparin dosage had no impact on graft function: serum creatinine at discharge of 1.5 ± 0.1 versus 1.6 ± 0.2 mg/dL. CONCLUSION: Our data indicated that postoperative hemorrhage after AB0i kidney transplantation was associated with the amount of heparin used for graft perfusion after donor nephrectomy. The use of antifibrinolytic agents may be harmful; no hyperfibrinolysis takes place in the AB0i transplant setting.

[Antibiotic prophylaxis in gastrointestinal endoscopy--recommendations of the Austrian Society of Gastroenterology and Hepatology]. / Antibiotikaprophylaxe in der gastrointestinalen Endoskopie--Empfehlungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

The recommendations of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) for antibiotic prophylaxis in gastrointestinal endoscopy of the year 2002 have been updated in accord with the recently published guidelines of the American Society of Gastrointestinal Endoscopy (ASGE) and the American Heart Association (AHA). Antibiotic prophylaxis for any endoscopic intervention to prevent infectious endocarditis is no longer necessary. Moreover, the prophylactic use of antibiotics for ERCP without biliary obstruction and ERCP with obstruction and a likelihood of complete drainage is no longer recommended. For ERCP with obstruction and anticipated incomplete drainage, a full course of antibiotics should be administered to prevent cholangitis. For the prevention of local infections antibiotics are useful prior to endoscopic puncturing, contrasting or drainage of cystic lesions as well as just before application of a PEG tube. In cirrhotic patients with GI bleeding antibiotic prophylaxis should be started as early as possible and be administered for several days.

New-onset diabetes mellitus after renal transplantation.

BACKGROUND: New-onset diabetes mellitus after organ transplantation (PTDM) significantly impairs patient and organ survival. Published rates of PTDM range from 2% to 54%, depending on the definition. OBJECTIVES: To analyze incidence of PTDM after renal transplantation according to recent guidelines and to evaluate implementation of a prospective standardized screening protocol. PATIENTS AND METHODS: Data for all consecutive patients who underwent transplantation from 2000 to 2006 were analyzed retrospectively for PTDM. In a prospective pilot trial all candidates for living related donor transplantation underwent a 75-g oral glucose tolerance test at evaluation prior to renal transplantation and at 3, 6, and 12 months thereafter. RESULTS: Data for 181 out of 271 consecutive patients were analyzed. Of these patients, 36 (19.9%) developed PTDM. Age, body mass index, pretransplantation fasting glucose concentration, and number of HLA mismatches were significant predictive risk factors. Posttransplantation diabetes mellitus occurred more frequently in patients receiving a cadaver organ compared with a living donor organ and in those receiving tacrolimus therapy vs cyclosporine therapy. Preliminary results demonstrated a 55.5% incidence of PTDM at 3 months in patients who received a living donor organ, much higher than expected. CONCLUSIONS: With an incidence of approximately 20%, PTDM is a frequent complication of transplantation. Prospective screening using oral glucose tolerance testing is a more sensitive method for detection of impaired glucose metabolism and PTDM. Relevance and therapeutic consequences must be determined in large-scale prospective studies.

Tacrolimus intoxication resolved by gastrointestinal bleeding: case report.

Tacrolimus is a potent immunosuppressive agent widely used in renal and liver transplantations. Its potential side effects due to overdosing are variable. Most commonly toxic tacrolimus blood levels affect the central and peripheral nervous systems. Once absorbed, tacrolimus binds to plasma proteins and accumulates within erythrocytes. Current treatment strategies to overcome acute intoxications focus on the induction of hepatic cytochrome P450 enzymes to accelerate tacrolimus degradation. We report the case of a 69-year-old renal transplant recipient presenting with acute liver failure, septic shock, and tacrolimus intoxication. The intoxication was resolved by massive gastrointestinal bleeding and subsequent transfusion of packed erythrocytes. We concluded that exchange blood transfusions offer an alternative therapeutic approach for patients with severe liver function impairment and tacrolimus intoxication.

Immunoglobulin induction therapy in renal transplant recipients: Effects on immunoglobulin and regulatory antibody levels.

We have previously shown that high pretransplant regulatory autoantibodies are associated with better kidney graft outcome. To analyze the effect of intravenous immunoglobulin (IVIG) induction therapy on these regulatory antibodies, we performed a prospective randomized study in 50 renal transplant recipients who were randomly assigned to receive 7 x 10 g IVIG or 7 x 10 g IV albumin infusions. Basic immunosuppressive therapy consisted of tacrolimus/azathioprine (n = 24) and tacrolimus/mycophenolate mofetil (n = 26), respectively. ELISA was used to assess IgG-/IgA-anti-Fab, -anti-F(ab)2 and -anti-hinge regulatory antibodies. IVIG induction therapy resulted in upregulation of serum IgG and IgA levels within the first 20 days posttransplant (P = .001, IgG; P = .04, IgA), so that a significant IgG deficiency was found only in non-IVIG patients (day 10: IgG <6 g/L: 7/25 (28%) non-IVIG versus 0/25 IVIG patients; P = .005). As the IVIG charges contained all of the regulatory antibodies tested, intravenous administration of these antibodies explain the elevated IgG- and IgA-anti-F(ab)2 antibody levels found in IVIG compared to non-IVIG patients on day 10 (P = .005 and P = .04, respectively). Our data indicated that IVIG induction prevented severe IgG deficiency in the early posttransplant period but had no impact on severe infectious complications. IVIG induction enhanced immunoregulatory antibody levels early posttransplant, which might provide graft protective effects.

Post-transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens.

Immunological monitoring for chronic allograft nephropathy (CAN) is of great potential interest. We assessed serum soluble CD30 (sCD30) together with in vitro Th2-type responses (IL-4, IL-10, CD4 helper activity) and neopterin in a prospective study of 84 renal transplant recipients with 2-year follow-up. Patients were randomized to CsA/Aza, CsA/MMF and Tacr/Aza, respectively, to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin. ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 (p = 0.003 at 4 months) and sustained upregulation of neopterin (corrected for graft function (Neo/CR) p = 0.005 at 2 years). Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1-year sCD30, which was positively related to Neo/CR (p = 0.007 and 0.01, respectively; logistic regression). Importantly, increased 1-year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years (p = 0.02 and p < 0.0005, respectively) and evidence of CAN (p < 0.0005). High 1-year sCD30 could not be attributed to enhanced Th2-type responses and was not associated with HLA antibody formation. Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN. Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin.

Initial corrosion observed on the atomic scale.

Corrosion destroys more than three per cent of the world's GDP. Recently, the electrochemical decomposition of metal alloys has been more productively harnessed to produce porous materials with diverse technological potential. High-resolution insight into structure formation during electrocorrosion is a prerequisite for an atomistic understanding and control of such electrochemical surface processes. Here we report atomic-scale observations of the initial stages of corrosion of a Cu3Au111 single crystal alloy within a sulphuric acid solution. We monitor, by in situ X-ray diffraction with picometre-scale resolution, the structure and chemical composition of the electrolyte/alloy interface as the material decomposes. We reveal the microscopic structural changes associated with a general passivation phenomenon of which the origin has been hitherto unclear. We observe the formation of a gold-enriched single-crystal layer that is two to three monolayers thick, and has an unexpected inverted (CBA-) stacking sequence. At higher potentials, we find that this protective passivation layer dewets and pure gold islands are formed; such structures form the templates for the growth of nanoporous metals. Our experiments are carried out on a model single-crystal system. However, the insights should equally apply within a crystalline grain of an associated polycrystalline electrode fabricated from many other alloys exhibiting a large difference in the standard potential of their constituents, such as stainless steel (see ref. 5 for example) or alloys used for marine applications, such as CuZn or CuAl.

Dendritic cell deficiency in the blood of kidney transplant patients on long-term immunosuppression: results of a prospective matched-cohort study.

Evidence from in vitro studies suggests that immunosuppressive drugs interfere with key functions of dendritic cells (DCs), but the in vivo relevance of these findings is elusive. We prospectively analyzed the major DC precursor subsets in the blood of kidney transplant recipients on long-term immunosuppression (> or =1 year). A total of 87 patients were compared to 87 age- and sex-matched controls. Total DC numbers and the precursor subsets, myeloid type 1 DCs, myeloid type 2 DCs (mDC1, mDC2) and plasmacytoid DCs (pDCs) were identified by four color flow cytometry. Long-term immunosuppression was associated with significant reduction of all major DC subsets in comparison to healthy controls (mDC1 p < 0.001; mDC2 p < 0.0001; two-tailed Mann-Whitney U-test) with the strongest negative impact on pDCs (p < 0.00001). In contrast, total leukocyte numbers were not significantly affected. Analysis of the relative impact of different agents revealed a significant impact of prednisolone on pDCs (p = 0.009) and mDCs2 (p = 0.006). The functional relevance of pDC deficiency was confirmed independently by Interferon-alpha analysis after Toll-like receptor 7 (p < or = 0.001) and 9 (p < 0.05) stimulation. These results indicate for the first time a profound negative impact of long-term immunosuppression on major DC subsets in kidney transplant recipients. DC deficiency may have important implications with respect to viral infections and tumor development.

sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil.

High pretransplantation sCD30 levels have been shown to be associated with lower 5-year kidney graft survival in mainly Cyclosporine A (CsA)-treated recipients (Collaborative Transplant Study database). To analyze the effect of different immunosupressive regimens (CsA/Azathioprine [Aza], CsA/Mycophenolate Mofetil [MMF], Tacrolimus [Tacr]/Aza) on sCD30, we assessed serum sCD30 and neopterin together with in vitro cytokine responses in a prospective randomized study of 84 renal transplant recipients before, 4 months, and 1 year after transplantation. Panel-reactive antibody (PRA) formation, HLA matching, ATG induction therapy, and acute rejections had no impact on sCD30 levels, whereas cytomegalovirus (CMV) infections induced an up-regulation of sCD30 4 months posttransplantation (P = .003). Whereas MMF showed no effect on sCD30 compared with Aza therapy, we found a significant impact of Tacr versus CsA treatment (1-year sCD30 > or = 60 U/mL: 14/42 (33%), CsA; 1/38 (3%), Tacr; P < .0005). Chronic rejection 2 years posttransplantation was associated with elevated 1-year sCD30 (P = .001) and neopterin levels (P = .006). Our data indicate that the Th2 activation marker sCD30 provides a risk factor for chronic rejection independent of classical immunological risk factors and may be down-regulated using Tacr treatment.