Temperature-dependent 2D-3D growth transition of ultra-thin Pt films deposited by PLD

During the growth of metal thin films on dielectric substrates at a given deposition temperature T, the film's morphology is conditioned by the magnitude and asymmetry of up- and downhill diffusion. Any severe change of this mechanism leads to a growth instability, which induces an alteration of the thin film morphology. In order to study this mechanism, ultra-thin Pt films were deposited via pulsed laser deposition (PLD) onto yttria-stabilized-zirconia single crystals at different deposition temperatures. The morphological evolution of Pt thin films has been investigated by means of scanning electron microscopy (SEM), atomic force microscopy (AFM) and standard image analysis techniques. The experimentally obtained morphologies are compared to simulated thin film structures resulting from a two-dimensional kinetic Monte Carlo (KMC) approach. Two main observations have been made: i) Thin Pt films deposited onto zirconia undergo a growth transition from two-dimensional to three-dimensional growth at T > 573 K. The growth transition and related morphological changes are a function of the deposition temperature. ii) A critical cluster size of i\ast = 4 in combination with an asymmetric Ehrlich-Schwoebel (ES) barrier favoring the uphill diffusion of atoms allows for a computational reproduction of the experimentally obtained film morphologies.Comment: 7 pages, 6 figures, 1 tabl

The Risk of Severe Infections Following Rituximab Administration in Patients With Autoimmune Kidney Diseases: Austrian ABCDE Registry Analysis.

OBJECTIVE: To characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX). METHODS: We conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between "nephrotic" and "nephritic" indications. The primary outcome was the incidence of SI within 12 months after the first RTX application. RESULTS: A total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI. CONCLUSIONS: After RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI

Identifizierung inhibitorischer Peptide gegen die Toxine von Clostridium difficile aus humanem Hämofiltrat

Clostridium (C.) difficile assoziierte Durchfallerkrankungen haben in der vergangenen Dekade einen besorgniserregenden epidemiologischen Wandel durchlaufen. Die zunehmende Inzidenz und die erhöhte Mortalität werden unter anderem mit dem Auftreten neuer, hypervirulenter Stämme assoziiert, die durch eine erhöhte Produktion der beiden Hauptvirulenzfaktoren Toxin A und Toxin B, sowie durch die zusätzliche Bildung eines dritten Toxins, der Clostridium difficile Transferase (CDT), gekennzeichnet sind. Antibiotikatherapien gelten als Hauptauslöser der Erkrankung, sind zugleich aber auch der aktuelle therapeutische Goldstandard. Metronidazol und Vancomycin stellen zwar wirksame Mittel gegen C. difficile dar, beeinflussen jedoch nicht die krankheitsauslösenden Toxine, welche zum Zeitpunkt der Erkrankung bereits im Darmlumen vorliegen. Anhand von Vergiftungsversuchen mit Toxin A und CDT auf epithelialen Zellreihen konnten im Screening einer Peptidbank drei Peptidfraktionen (E3F10, E5F18 und E7F16) mit Hemmwirkung gegen die beiden Toxine identifiziert werden. Vergiftungen konnten unter Inkubation der hemmenden Peptidfraktionen nicht verhindert, jedoch mitunter erheblich verzögert werden. Am Beispiel der Peptidfraktion E6F18 und dem binären Toxin CDT wurden weitere Auftrennungszyklen sowie Versuche zur Analyse der Hemmwirkung durchgeführt. Adverse Eigeneffekte im Sinne einer durch die Peptidlösung ausgelösten Zytotoxizität konnten auf Vero-Zellen ausgeschlossen werden. Unter Einbuße der ursprünglichen Hemmstärke konnte der Hemmeffekt von E6F18 über drei rechromatographische Auftrennungszyklen weiterverfolgt und die Isolation einzelner Peptide mit Hemmwirkung unter anderem gegen CDT ermöglicht werden. Versuche zur Analyse des Hemmmechanismus von E6F18 liefern starke Hinweise auf eine Hemmung der frühen Schritte der Toxinprozessierung. Eine Interaktion mit einer der beiden Toxinkomponenten, dem Toxinrezeptor oder der Porenbildung wären denkbare Angriffspunkte. Ob der unspezifische Hemmeffekt von E6F18 auf ein einzelnes Peptid zurückzuführen ist oder das komplexe Gesamtbild vielmehr durch einen Synergismus unterschiedlicher Peptide zu erklären ist, bleibt vorerst offen

Eosinophilia and Kidney Disease: More than Just an Incidental Finding?

Peripheral blood eosinophilia (PBE), defined as 500 eosinophils or above per microliter (µL) blood, is a condition that is not uncommon but often neglected in the management of patients with chronic kidney disease (CKD), acute kidney injury (AKI), or patients on renal replacement therapy (RRT). The nature of PBE in the context of kidney diseases is predominantly secondary or reactive and has to be distinguished from primary eosinophilic disorders. Nonetheless, the finding of persistent PBE can be a useful clue for the differential diagnosis of underdiagnosed entities and overlapping syndromes, such as eosinophilic granulomatosis with polyangiitis (EGPA), IgG4-related disease (IgG4-RD), acute interstitial nephritis (AIN), or the hypereosinophilic syndrome (HES). For patients on RRT, PBE may be an indicator for bio-incompatibility of the dialysis material, acute allograft rejection, or Strongyloides hyperinfection. In a subset of patients with EGPA, eosinophils might even be the driving force in disease pathogenesis. This improved understanding is already being used to facilitate novel therapeutic options. Mepolizumab has been licensed for the management of EGPA and is applied with the aim to abrogate the underlying immunologic process by blocking interleukin-5. The current article provides an overview of different renal pathologies that are associated with PBE. Further scientific effort is required to understand the exact role and function of eosinophils in these disorders which may pave the way to improved interdisciplinary management of such patients

Edema-like symptoms are common in ultra-distance cyclists and driven by overdrinking, use of analgesics and female sex - a study of 919 athletes.

BACKGROUND: Ultra-endurance cyclists regularly report various extents of bodily decline during long-distance bicycle rides, including potential kidney function-related symptoms such as swelling of body parts and urine changes. This study aimed to assess the prevalence of these symptoms in a representative cohort of ultra-endurance cyclists and shed light on potential predictors related to the ride, the rider and the rider's behavior. METHODS: Between November 26 and December 14, 2020, 1350 people participated in an online survey investigating potential kidney-related symptoms of ultra-distance cycling. Frequency and severity of edema-like ("swelling") symptoms and perceived changes in urine output, concentration and quality were associated with ride-related factors, demographic parameters and rider behavior-related variables. RESULTS: A total of 919 participants met the predefined inclusion criteria. The majority (N = 603, 65.6%) stated that they suffered from at least one potential kidney function-related symptom, out of which 498 (54.2%) stated one or more edema-like ("swelling") symptoms. In correlational and multiple regression analyses, female sex, intake of analgesics and drinking strategies correlated with swelling symptoms. Further analyses indicated that drinking due to thirst and/or drinking adapted to ambient sweating and temperature negatively correlated with swelling symptoms, whereas "drinking as much as possible" enhanced these. Intake of analgesics was moderately positively correlated with swelling symptoms. CONCLUSIONS: According to our survey, edema-like symptoms occur in the majority of ultra-distance cyclists and female sex, drinking strategy and intake of analgesic drugs are major predictors thereof. Studies are needed to investigate the underlying pathophysiological processes of such symptoms

Refractory lupus nephritis: When, why and how to treat.

Refractory lupus nephritis indicates an inadequate response to lupus nephritis therapy. It implies persisting or worsening disease activity despite therapy, but the definition is complicated by the parameters of response, proteinuria and renal function, that do not discriminate clearly between activity and irreversible damage. Understanding the causes of refractory disease and developing treatment strategies is important because these patients are more likely to develop poor outcomes, especially end stage renal disease. This review explores current concepts and definitions of refractory disease and summarises treatment approaches that have been used in observational cohort studies and case series. We highlight the importance of optimising adherence to the prescribed immunosuppressive and supportive measures and avoidance of diagnostic delay. Treatment options include higher dose glucocorticoid, switching between cyclophosphamide and mycophenolate acid derivates, or addition of rituximab, the latter potentially in combination with belimumab. Less evidence supports extracorporeal treatment (plasma exchange or immunoadsorption), calcineurin inhibitors (cyclosporine A or tacrolimus), intravenous immunoglobulin and stem cell transplantation. Improvements in understanding what refractory disease is and how definitions can be integrated into treatment pathways has the potential to enhance lupus nephritis outcomes

Preparation and characterization of calibration standards for bone density determination by micro-computed tomography

Phantoms for the calibration of local bone mineral densities by micro-computed tomography (?CT), consisting of lithium tetraborate (Li(2)B(4)O(7)) with increasing concentrations of hydroxyapatite [HAp, Ca(10)(PO(4))(6)(OH)(2)] have been prepared and characterized for homogeneity. Large-scale homogeneity and concentration of HAp in the phantom materials was determined using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), while homogeneity on the micrometer scale was assessed through ?CT. A series of standards was prepared by fusion of pure HAp with Li(2)B(4)O(7) in a concentration range between 0.12 and 0.74 g cm(-3). Furthermore, pressed and sintered pellets of pure HAp were prepared to extend the calibration range towards densities of up to 3.05 g cm(-3). A linear calibration curve was constructed using all individual standard materials and the slope of the curve was in good agreement with calculated absorption coefficients at the effective energy of the ?CT scanne

Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?

Contains fulltext : 226142.pdf (Publisher’s version ) (Open Access

Impact of familiarity with the format of the exam on performance in the OSCE of undergraduate medical students – an interventional study

Abstract Background Assessments, such as summative structured examinations, aim to verify whether students have acquired the necessary competencies. It is important to familiarize students with the examination format prior to the assessment to ensure that true competency is measured. However, it is unclear whether students can demonstrate their true potential or possibly perform less effectively due to the unfamiliar examination format. Hence, we questioned whether a 10-min active familiarization in the form of simulation improved medical students´ OSCE performance. Next, we wanted to elucidate whether the effect depends on whether the familiarization procedure is active or passive. Methods We implemented an intervention consisting of a 10-min active simulation to prepare the students for the OSCE setting. We compared the impact of this intervention on performance to no intervention in 5th-year medical students (n = 1284) from 2018 until 2022. Recently, a passive lecture, in which the OSCE setting is explained without active participation of the students, was introduced as a comparator group. Students who participated in neither the intervention nor the passive lecture group formed the control group. The OSCE performance between the groups and the impact of gender was assessed using X2, nonparametric tests and regression analysis (total n = 362). Results We found that active familiarization of students (n = 188) yields significantly better performance compared to the passive comparator (Cohen´s d = 0.857, p < 0.001, n = 52) and control group (Cohen´s d = 0.473, p < 0.001, n = 122). In multivariate regression analysis, active intervention remained the only significant variable with a 2.945-fold increase in the probability of passing the exam (p = 0.018). Conclusions A short 10-min active intervention to familiarize students with the OSCE setting significantly improved student performance. We suggest that curricula should include simulations on the exam setting in addition to courses that increase knowledge or skills to mitigate the negative effect of nonfamiliarity with the OSCE exam setting on the students

Additional file 1 of Impact of familiarity with the format of the exam on performance in the OSCE of undergraduate medical students – an interventional study

Additional file 1: Supplemental Table 1. OSCE subspecialties and main checklist items