Attenuated XPC expression is not associated with impaired DNA repair in bladder cancer

Bladder cancer has a high incidence with significant morbidity and mortality. Attenuated expression of the DNA damage response protein Xeroderma Pigmentosum complementation group C (XPC) has been described in bladder cancer. XPC plays an essential role as the main initiator and damage-detector in global genome nucleotide excision repair (NER) of UV-induced lesions, bulky DNA adducts and intrastrand crosslinks, such as those made by the chemotherapeutic agent Cisplatin. Hence, XPC protein might be an informative biomarker to guide personalized therapy strategies in a subset of bladder cancer cases. Therefore, we measured the XPC protein expression level and functional NER activity of 36 bladder tumors in a standardized manner. We optimized conditions for dissociation and in vitro culture of primary bladder cancer cells and confirmed attenuated XPC expression in approximately 40% of the tumors. However, NER activity was similar to co-cultured wild type cells in all but one of 36 bladder tumors. We conclude, that (i) functional NER deficiency is a relatively rare phenomenon in bladder cancer and (ii) XPC protein levels are not useful as biomarker for NER activity in these tumors

A multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and torque teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation:TTVguideIT

Background: Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. Methods: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. Discussion: The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents.</p

Eligibility for Liver Transplantation in Patients with Perihilar Cholangiocarcinoma

Background: Liver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers. Methods: Patients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT. Results: A total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3–23). Conclusion: Only 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Served straight up: Effects of verticality cues on taste evaluations and luxury perceptions

Based on the embodied cognition framework and research addressing transfer effects between visual perception and taste, the point of departure for this study is the widespread association between vertical orientation and connotations related to luxury and (economic) power. Specifically, this study tests whether vertical orientation not only affects impressions of product luxury, but also influences actual taste evaluations, including perceptions of taste strength (intensity) and taste liking. Results confirm these predictions by showing that participants in a Dutch coffee house gave higher ratings on these constructs when they were exposed to an ad display depicting vertically-oriented rather than horizontally-oriented visual cues during a coffee sample test. Findings furthermore stress the influence of design cues as opposed to more traditional product claims. Implications for marketing and design practice are discussed

Assessment of dominant factors affecting hydroisomerization on bifunctional zeolites

The hydroisomerization of n-octane in the liquid phase was investigated over beta, USY and mordenite zeolites loaded with I wt% Pt in a stirred semi-batch microautoclave. The total pressure ranged form 5 to 9 MPa and the temperature from 523 to 563 K with all initial catalyst/n-octane ratio of 7 g(catalysts)/mol(n-Cg). PtBETA was the most active catalyst at all operating conditions, followed by PtMOR and PtUSY. The isomer yields oil PtMOR were somewhat lower than oil PtBETA and PtUSY. Increasing the total pressure always resulted in a decrease in the n-octane conversion, which is indicative of so-called ideal hydroisomerization. The n-octane hydroisomerization experiments were simulated with a kinetic model based on a parallel/consecutive reaction scheme involving reversible mono- and multibranching and irreversible cracking from mono- as well as multibranched isomers. The model fitted adequately the experimental data on PtBETA and PtUSY. However, more dispersion was observed with catalyst PtMOR. The ratio of the composite rate coefficients for cracking to that for monobranching was significantly higher oil PtMOR than on PtUSY and PtBETA. The composite activation energy for monobranching was 20 kJ mol(-1) higher on USY if compared to that of mordenite and beta. These modelling results were related to pore sizes and geometry and average acid strength. (c) 2008 Elsevier B.V. All rights reserved