Search

Audiological use of the 40 Hz-ASSR (auditory steady state responses) could be valuable for objectively estimating the frequency-specific threshold in adults undergoing an expertise examination for medicolegal and/or compensation purposes. The present prospective study was set up to clarify the relationship between the thresholds obtained by cortical evoked response audiometry (CERA) and by 40 Hz-ASSR, in the same ears, within a large homogeneous sample of 164 subjects (328 ears) with NIHL and well documented exposure to noise. All these subjects claimed financial compensation for occupational NIHL, and there was a suspicion of exaggeration of the reported NIHLs. ASSR thresholds show a good correlation with the CERA thresholds. However, a systematic shift is noticed, ASSR thresholds being on average (1–2 – 3 kHz) 4.38 dB lower (i.e. showing less hearing loss) than CERA thresholds. Moreover, the binaural multiple ASSR technique allows a considerable time gain when compared to the CERA.

Continuous erythropoietin receptor activator (CERA) is a third-generation erythropoiesis-stimulating agent that was developed for the treatment of anemia. However, misuse of CERA for doping in endurance sports has been reported. Previous studies have shown blood as the matrix of choice for the detection of CERA, due to its high molecular weight. The use of dried blood spots (DBSs) for anti-doping purposes constitutes a complementary approach to the standard urine and venous blood matrices and could facilitate sample collection and increase the number of blood samples available for analysis due to reduced costs of sample collection and transport. Here, we investigated whether CERA could be indirectly detected in extracts of single DBSs using an erythropoietin-specific immunoassay that is capable of providing results within approximately two hours. Reconstituted DBS samples were prepared from mixtures of red blood cell pellets and serum samples. The samples were collected in a previous clinical study in which six healthy volunteers were injected with a single, 200 μg dose of CERA. Using a commercially available ELISA kit, CERA was detected in the DBSs with a detection window of up to 20 days post-injection. Furthermore, in order to demonstrate the fitness-for-purpose, three authentic doping control serum samples, which were identified as containing CERA were analyzed by the presented methodological approach on DBS. The testing procedure described here could be used as a fast and cost-effective method for the detection of CERA abuse in sport.

Two identical backpacks were treated on two occasions to be exhibited alongside at the Lisbon Military Museum. Although both backpacks are the model 1859, the treatment procedures related to the painted canvas were approached differently. The distortions and losses of canvas on the first treated backpack were easily addressed with an ultrasonic humidifier and the insertion of new canvas. Regarding the surface coating, it was consolidated with BEVA® 371, and the inserted canvas was filled with a pigmented wax paste described in a book from the late 19th century. The second backpack was in far worse condition, which, when compared with archive record, seemed likely that it was exhibited for a long period in a damp environment. There were also traces of an organic coating distinct from the original coating. These conditions resulted in a stiffer backpack, with more losses of canvas and surface coating. As a result, the distortions could not be removed, new fabric could not be properly inserted, and the consolidation of the surface coating had to be addressed in a different way. For these motives, the goal of treatment of the second treated backpack was cut short for a more realistic goal, but resulted in a good outcome, nonetheles., Dos mochilas idénticas fueron tratadas en diferentes ocasiones para exhibirse juntas en el Museo Militar de Lisboa. Aunque ambas mochilas son del modelo 1859, los procedimientos de tratamiento relacionados con el lienzo pintado se abordaron de manera diferente. Las distorsiones y pérdidas de lienzo en la primera mochila tratada se abordaron fácilmente con un humidificador ultrasónico y la inserción de un nuevo lienzo. El revestimiento de la superficie se consolidó con BEVA® 371, y el lienzo insertado se rellenó con una pasta de cera pigmentada, descrita en un libro del final del siglo XIX. La segunda mochila estaba en condiciones mucho peores, lo que, en comparación con la evidencia de archivo, parecía probable que se exhibiera durante un largo período en un ambiente húmedo. También había rastros de un revestimiento orgánico distinto del revestimiento original. Estas dos condiciones dieron como resultado una mochila más rígida, con más pérdidas de lienzo y revestimiento superficial. Como resultado, las distorsiones no se pudieron eliminar, el nuevo lienzo no se pudo insertar correctamente y la consolidación del revestimiento de la superficie tuvo que abordarse de una manera diferente. Por estos motivos, el objetivo del tratamiento de la segunda mochila tratada se truncó para un objetivo más realista, sin embargo resultó en un buen término., Duas mochilas idênticas foram tratadas em ocasiões diferentes para serem expostas em conjunto no Museu Militar de Lisboa. Embora ambas as mochilas sejam do modelo 1859, os procedimentos de tratamento relacionados com a tela pintada foram abordados de forma diferente. As distorções e as perdas de tela na primeira mochila tratada foram facilmente resolvidas com um humidificador ultrassónico e a inserção de nova tela. O revestimento da superfície foi consolidado com BEVA® 371, e a nova tela inserida foi preenchida com uma pasta de cera pigmentada, descrita num livro do final do século XIX. A segunda mochila estava em muito pior estado, o que, quando comparada com evidências de arquivo, parecia provável que tenha sido exibida por um longo período num ambiente húmido. Também havia vestígios de uma camada orgânica distinta do revestimento original. Essas duas condições resultaram numa mochila mais rígida, com mais perdas de tela e do revestimento da superfície. Como resultado, as distorções não puderam ser eliminadas, a nova tela não pôde ser devidamente inserida, e a consolidação do revestimento da superfície teve de ser abordada de outra forma. Por essas razões, o objetivo do tratamento da segunda mochila tratada foi reduzido para um objetivo mais realista, porém resultou num bom termo.

International audience; Objectives Patient's perception analysis appears recently in numerous studies. Conjoint analysis has been used extensively by market researchers for studying how people value the characteristics of products and services. This technique was used in a clinical study to describe perceptions and preferences of anaemic patients suffering from chronic kidney disease not on dialysis (CKDnd), regarding erythropoietin stimulating agents (ESA). Methods PERCEPOLIS was a French multicenter prospective non-interventional study designed to describe the relative importance of ESA attributes according to CKDnD patients. Patients fulfilled questionnaires using an electronic device (digital tablet) at baseline and after 6 months under continuous erythropoietin receptor activator (CERA) treatment. Choice-based conjoint (CBC) questionnaires were developed with multiple components: 7 ESA attributes (2 or 3 levels per attribute), 2 partial profiles per task (2 out of the 7 attributes), and 7 tasks per questionnaire. Analyses were performed according to previous ESA treatment or not. Results From 789 analyzed patients, 433 non ESA-naive patients were more than 80% to declare treatment efficacy as the most important expectative in ESA choice process (direct question) but CBC analyses revealed that frequency of injections was more crucial (relative mean weight: ∼30% versus ∼20% for efficacy). Pain at injection site and haemoglobin not exceeding the recommended target were confirmed as important criteria for patients (relative mean weights: ∼15%). No new or unexplained safety signals were noted. Conclusions Using CBC design for the first time in a non-interventional ESA study with an electronic Patient Reported Outcome (ePRO) in an elderly population, these data showed that monthly injections and treatment efficacy were key patients’ expectations relative to ESAs. CERA efficacy to maintain stable haemoglobin within the recommended range was confirmed in real-life conditions.

Wax effigies, fully dressed life-size models of human figures, have been constructed since the medieval times. The construction materials of historical effigies differ to the contemporary ones, yet the construction process of the wax parts has more or less remained unchanged over the centuries. This paper starts with the history, construction materials and manufacture techniques of wax effigies. The inseparable relation of the wax effigies and their costumes is explained, and the characteristics and deterioration agents of their most important construction materials are presented in order to understand their needs for preservation, with emphasis on wax and fabrics. The aim of this paper is to suggest preventive conservation guidelines for wax effigies, with proposals for appropriate environmental conditions during display and storage, and suggestions for proper handling, storage and transportation. Advice for disaster preparedness and actions in cases of emergency situations is also provided. Received: 2020-1-28Revised: 2020-6-16Accepted: 2020-6-30Online: 2020-8-19Publication: 2021-2-10, As efígies de cera, modelos de figuras humanas completamente vestidas em tamanho real, foram criadas desde os tempos medievais. Os materiais de produção de efígies históricas diferem dos contemporâneos, mas o processo de produção dos componentes de cera manteve-se mais ou menos inalterado ao longo dos séculos. Este artigo começa com a história, materiais e técnicas de produção de efígies de cera. Explica-se a relação inseparável das efígies de cera e os seus trajes, apresentam-se as características e os agentes de deterioração de seus materiais de produção mais importantes, de modo a compreender as suas necessidades de preservação, com ênfase na cera e nos tecidos. O objetivo deste artigo é sugerir procedimentos de conservação preventiva para efígies de cera, com propostas de condições ambientais adequadas durante a exposição e armazenamento, e sugestões para manuseamento, armazenamento e transporte adequados. São também fornecidos conselhos para a preparação para desastres e ações em casos de situações de emergência. Recebido: 2020-1-28Revisto: 2020-6-16Aceite: 2020-6-30Online: 2020-8-19Publicação: 2021-2-10

Lipids are key ingredients in the human diet. Because of the manipulation and modification of lipids in the food industry, the amount of trans and saturated fat has been substantially increasing in industrialized products. At the same time, the number of studies demonstrating the harmful effects of these foods on human health has increased. Organogels arise as a promising alternative for replacing trans and saturated fat in processed foods. Among the main challenges of preparing an organogel is the difficulty of finding compatible and viable structuring agents in the food industry. Waxes have been studied for this purpose and are one of the most promising organogelators. This article brings a bibliographical review on the recent studies regarding the use of waxes as structuring agents for edible vegetable oils. Los lípidos son ingredientes clave en la dieta humana. Debido a la manipulación y modificación de estos lípidos en la industria alimentaria, la cantidad de grasas trans y las saturadas ha aumentado sustancialmente en los productos industrializados. Al mismo tiempo, ha aumentado la cantidad de estudios que demuestran los efectos nocivos de estos alimentos en la salud humana. Los organogeles surgen como una alternativa prometedora para reemplazar las grasas trans y las saturadas en los alimentos procesados. Entre los principales desafíos de preparar un organogel está la dificultad de encontrar agentes estructurantes compatibles y viables en la industria alimentaria. Las ceras se han estudiado para este propósito y son uno de los organogeladores más prometedores. Este artículo presenta una revisión bibliográfica de los estudios recientes sobre el uso de ceras como agentes estructurantes para aceites vegetales comestibles.

Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing myofibroblasts can originate from different sources and different mechanisms are involved in the activation process of the myofibroblasts in the fibrotic kidney. In this study, 16-week-old db/db mice, a model for type 2 DN, were treated for two weeks with continuous erythropoietin receptor activator (CERA), a synthetic erythropoietin variant with possible non-hematopoietic, tissue-protective effects. Non-diabetic and diabetic mice treated with placebo were used as controls. The effects of CERA on tubulointerstitial fibrosis (TIF) as well as on the generation of the matrix-producing myofibroblasts were evaluated by morphological, immunohistochemical, and molecular biological methods. The placebo-treated diabetic mice showed significant signs of beginning renal TIF (shown by picrosirius red staining; increased connective tissue growth factor (CTGF), fibronectin and collagen I deposition; upregulated KIM1 expression) together with an increased number of interstitial myofibroblasts (shown by different mesenchymal markers), while kidneys from diabetic mice treated with CERA revealed less TIF and fewer myofibroblasts. The mechanisms, in which CERA acts as an anti-fibrotic agent/drug, seem to be multifaceted: first, CERA inhibits the generation of matrix-producing myofibroblasts and second, CERA increases the ability for tissue repair. Many of these CERA effects can be explained by the finding that CERA inhibits the renal expression of the cytokine TGF-β1.

BACKGROUND Erythropoiesis-stimulating agents (ESAs) are the mainstay of anemia therapy. Continuous erythropoietin receptor activator (CERA) is a highly effective, long-acting ESA developed for once-monthly dosing. A multitude of clinical studies has evaluated the safety and efficiency of this treatment option for patients with renal anemia. In times of permanent financial pressure on health care systems, the cost-effectiveness of CERA should be of particular importance for payers and clinicians. OBJECTIVE To critically analyze, from the nephrologists' point of view, the published literature focusing on the cost-effectiveness of CERA for anemia treatment. METHODS The detailed literature search covered electronic databases including MEDLINE, PubMed, and Embase, as well as international conference abstract databases. RESULTS Peer-reviewed literature analyzing the definite cost-effectiveness of CERA is scarce, and most of the available data originate from conference abstracts. Identified data are restricted to the treatment of anemia due to chronic kidney disease. Although the majority of studies suggest a considerable cost advantage for CERA, the published literature cannot easily be compared. While time and motion studies clearly indicate that a switch to CERA could minimize health care staff time in dialysis units, the results of studies comparing direct costs are more ambivalent, potentially reflecting the differences between health care systems and variability between centers. CONCLUSION Analyzed data are predominantly insufficient; they miss clear evidence and have to thus be interpreted with great caution. In this day and age of financial restraints, results from well-designed, head-to-head studies with clearly defined endpoints have to prove whether CERA therapy can achieve cost savings without compromising anemia management.

Stimulation of erythropoiesis by the third-generation erythropoietin drug, continuous erythropoietin receptor activator (CERA), a pegylated derivative of epoetin-β, has provided valuable therapeutic benefits to patients suffering from renal anemia, but has also rapidly found application as an illicit performance-enhancing strategy in endurance sports. We present here a novel method for selective determination of CERA in serum, based on polyethylene glycol precipitation, followed by a commercial homogeneous immunoassay. The developed method was highly discriminating between serum samples from CERA-treated patients and control subjects, as the covalently linked polyethylene glycol chain in CERA strongly enhanced the solubility of the protein in a polyethylene glycol-containing medium. Intravenous administration of CERA could be detected for several weeks in the majority of subjects tested. This assay outperforms the currently available CERA detection methods in terms of simplicity, convenience, cost, and throughput, making it ideal as a screening tool for doping control.

Background: We investigated the efficacy, safety and tolerability of once-monthly administration of C.E.R.A. in erythropoiesis stimulating agents (ESAs) naive predialysis patients with CKD for anemia treatment, Study Design: Single arm, open label study., Methods: A total of 75 patients (mean (SD) age was 52.8 (16.4) years, 76.0% were female) were included in this study conducted between 12 August 2008 and 30 October 2009 in 9 centers across Turkey. The mean change in Hb concentration (g/dL) between baseline (week 0) and the efficacy evaluation period (EEP) was the primary efficacy parameter evaluated in three consecutive periods including a dose titration period (DTP; with initial 1.2 mu g/kg dose of C.E.R.A., subcutaneously, 28 weeks), EEP (8 weeks) and a long-term safety period (16 weeks)., Results: Our analysis revealed an improvement in Hb levels from baseline value of 9.4 (0.4) g/dL to time adjusted average level of 11.4 (0.7) g/dL in EEP in the per protocol (PP) population and from 9.3 (0.5) g/dL to 11.1 (1.0) g/dL in intent-to-treat (ITT) population. Mean (SD) change in Hb levels from baseline to EEP was 2.0 (0.7) g/dl in the PP population (primary endpoint) and 1.7 (1.1) g/dL in the ITT population. The percentage of patients whose Hb concentrations remained within the target range of 10.0-12.0 g/dL throughout the EEP was 43.9% (95% CI: 28.5-60.3%) in the PP population and 38.7% (95% CI: 27.6% to 50.6%) in the ITP population. A total of 206 adverse events (AE) were reported in 77.0% of patients with hypertension (20%) as the most frequent AE., Conclusion: Once-monthly subcutaneous C.E.R.A. administration is effective and safe in the treatment of anemia in pre-dialysis patients with CKD, who are not currently treated with ESAs.

Anemia is a common complication of chronic kidney disease (CKD), with erythropoietin deficiency being the major contributing factor. The availability of erythropoiesis-stimulating agents (ESAs) has been a seminal advance in the treatment of anemia related to chronic kidney disease. Over the course of the last decade and a half, newer generations of ESAs have become available. The first-generation ESAs or epoetins have a relatively shorter half-life and have traditionally been administered up to 3 times per week intravenously or subcutaneously to maintain adequate hemoglobin (Hb) levels. At the turn of the century, darbepoetin alfa, a hyperglycosylated form, became available for clinical use. It conferred greater metabolic stability in vivo owing to two additional N-linked carbohydrate chains attached to the protein backbone and has a half-life 3 times longer than that of epoetin (Macdougall et al 1999). Recently developed and undergoing phase III clinical trials is the third-generation ESA, Continuous Erythropoiesis Receptor Activator (CERA), which has a methoxy-polyethylene glycol polymer chain integrated and has a longer elimination half-life than the first- and second-generation ESAs. Its receptor binding characteristics also differ from those of previous ESAs. Its major advantage is that extended dosing intervals are possible in the management of anemia related to erythropoietin deficiency.

la correction et la stabilité du taux d'hémoglobine est un objectif majeur du traitement de l'anémie chez les hémodialysés chroniques. Toutefois, la cible d'hémoglobine > 11g/dl fixée par les recommandations demeure difficile à atteindre dans notre contexte. Le but de cette étude est d'évaluer la réponse au traitement par CERA (continuous erythropoietin receptor activator) chez une population d'hémodialysés chroniques naïfs de tout traitement par agent stimulant de l'érythropoïèse et étudier les différents facteurs associés à une mauvaise réponse au traitement. Il s'agit une étude prospective mono centrique faite au sein d'une population d' hémodialysés chroniques. Ont été inclus les patients en hémodialyse depuis plus de 12 mois, naïfs de tout traitement par agent stimulant de l'érythropoïèse (ASE) et ayant un taux d'hémoglobine(Hb) < 10g/dl. L'administration régulière de la CERA et l'ajustement des doses ont été faits selon les recommandations. L'évaluation de la réponse, en fin de traitement, a porté sur l'atteinte ou non d'un taux d'hémoglobine cible > 11g/dl. Sur 87 patients en hémodialyse périodique, 22 (25,3%) sont naïfs de tout traitement par ASE. Il s'agit de 13 hommes et 9 femmes avec un âge moyen de 46 ± 19 ans et une ancienneté en hémodialyse de 67 ± 59 mois. Le taux initial d'hémoglobine est de 7,8 ± 1,3 g/dl. Au bout de 4 mois de traitement régulier par la CERA, le taux final d'Hb est de 10,9 ± 2,1g/dl et 63,6% des patients ont atteint la cible d'Hb > 11g/dl. La dose moyenne de CERA à la fin de l'étude est de 0,89 ± 0,35 µg/kg/15j. L'analyse des facteurs prédictifs montre que la réponse finale dépend du taux d'Hb initial (p=0,002).En effet, quand le taux d'Hb initial est > 8 g/dl, le taux de réponse est de 88% vs 46% lorsque le taux d'Hb < 8g/dl (p

Background: The intake of erythropoietins as performance-enhancing drugs is banned in sport. The current method for their detection is based on advanced electrophoretic techniques (IEF-PAGE and SDS-PAGE/sarcosyl-PAGE) with double-blotting and chemiluminescence detection, requiring at least 2.5 days to be completed. Methodology & Results: The proposed procedure, based on vacuum-driven blotting technology, drastically reduces the time necessary to complete the analysis, while still fulfilling the criteria of the World Anti-Doping Agency. Validation was carried out on urine samples spiked with different recombinant erythropoietins, as well as on urine samples obtained following controlled excretion studies and on anonymized urine samples from antidoping tests. Conclusion: The proposed approach, allowing a faster turnaround time, could be very advantageous on the occasion of major sport international events (i.e., Olympic Games).

Background/Aims: Finding the lowest effective dose of erythropoietin-stimulating agents is critical in the management of renal anemia. We evaluated the efficacy of converting darbepoetin to CERA at doses lower than those usually recommended. Methods: We selected consecutive non-dialysis chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week in absence of iron deficiency, recent blood transfusion, bleeding, neoplasia, myocardial infarction/stroke in the last 3 months. Darbepoetin ≤20 µg/week was shifted to CERA 75 µg/month, while darbepoetin 21–40 µg/week to CERA 100 µg/month. Primary endpoint was the change in hemoglobin (Hb goal, 11–13 g/dl) at month 3, 6, 9 and 12. Results: Studied patients (n = 37) were aged 70 ± 13 years and GFR was 30 ± 12 ml/min/1.73 m2; prevalence of males, diabetes and prior cardiovascular disease was 43, 45 and 40%, respectively. Before switching, efficacy population received darbepoetin 18 ± 10 µg/week with 28 patients receiving ≤20 µg/week. Prevalence of Hb goal at baseline was 75.7% and did not change at months 3 (70.3%), 6 (70.3%), 9 (72.2%), and 12 (80.0%). CERA dose remained unchanged during the study (81 ± 11, 82 ± 16, 91 ± 30, 90 ± 54 and 88 ± 61 µg/month). Out of the 438 visits performed, CERA dose was increased in 52 (11.9%) and reduced in 36 (8.2%) visits. Blood pressure, Hb, GFR, transferrin saturation and ferritin did not change. Conclusions: In chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week, CERA can be efficaciously used at doses lower than those recommended.

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half‐life in blood and strongly suppresses hepcidin‐25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end‐stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8‐OHdG and liver‐type fatty acid–binding protein (L‐FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin‐25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67‐positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L‐FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules.