Journal articles on the topic 'Bochetel'

En 1506, Érasme est le premier à traduire en latin des tragédies grecques entières, en l’occurrence deux tragédies d’Euripide, Hécube et Iphigénie à Aulis. S’il adopte pour l’Hécube une traduction vers à vers, il opte dans l’Iphigénie pour une traduction plus détaillée en veillant à produire dans la langue cible les effets de l’original. Dans son ouvrage sur L’Hécube d’Euripide en France, Bruno Garnier a montré comment la traduction latine d’Érasme a influencé la première traduction française de l’Hécube, attribuée à Guillaume Bochetel (1544). Cet article est consacré aux premières traductions de l’Iphigénie à Aulis et, en particulier, à celle de Thomas Sébillet qui se mesure à Érasme pour démontrer, contre Joachim Du Bellay, la capacité d’une traduction poétique à illustrer la langue française. In 1506, Erasmus was the first person to translate complete Greek tragedies into Latin, in this case two tragedies by Euripides, Hecuba and Iphigenia at Aulis. Though he used a verse by verse translation for Hecuba, he opted in Iphigenia for a more detailed translation, taking care to reproduce in the target language the effects of the original. In his work on Euripides’ Hecuba in France, Bruno Garnier has shown how the Latin translation of Erasmus influenced the first French translation of Hecuba, attributed to Guillaume Bochetel (1544). This article addresses the first translations of Iphigenia at Aulis and in particular that of Thomas Sébillet. He pitted himself against Erasmus to demonstrate, contrary to Joachim Du Bellay, the capacity of a poetic translation to exemplify the French language.

The subject of the paper is the history of Mathematics at the Krakow University of Technology since 1945 up to 2015. It presents profiles of the most famous mathematicians in the history of the Krakow University of Technology (M. Krzyżański, J. Bochenek, F. Barański, I. Łojczyk-Królikiewicz) and some information about their scientific achievements.

Este trabalho analisa o discurso sobre o político (BOCHETT, et. al, 2017) a fim de verificar representações para Michel Temer em textos que opinam sobre o seu discurso em homenagem ao Dia Internacional da Mulher. Como resultado, foram verificadas três representações para o então Presidente: como machista, que aparece como a principal e perpassa os cinco textos, e como retrógrado e inimigo das mulheres.

Este trabalho objetiva investigar como os candidatos à presidência da República do Brasil constroem representações, avaliações e imaginários acerca de si mesmos, do Brasil e dos brasileiros em um excerto do último debate televisivo presidencial de 2018. O aparato teórico-metodológico é a Linguística Sistêmico-Funcional (HALLIDAY; MATTHIESSEN, 2014), especificamente os sistemas de transitividade e de avaliatividade, além da concepção de discurso político de Wodak (2009) e Bochett et al. (2017). Evidenciamos uma predominância do imaginário de mudança, em que a maioria dos candidatos se vê como agente perseverante e capaz dessa transformação, e apenas um deles indica o povo como fator importante dessa questão.

The article presents the main stages of the A.M. Bochever’s biography, a known specialist in special bibliography and library science, who worked in the Central Scientific Agricultural Library (CSAL) for 27 years and 19 years of that period he held the position of the director. A.M. Bochever acted as an author and editor of different bibliographic textbooks. He published above 100 works; in particular he was a co-author of a textbook on agricultural bibliography “Literature on Agriculture”. He made a substantial contribution to the theory of library science and bibliography, as well as the establishment and development of the CSAL. The A.M. Bochever’s views are presented with respect to bibliography and its place in the society, the problems of a library, the separation of functions of a library and scientific and technical information bodies, the role of coordination and cooperation in the activity of agricultural libraries. He regarded bibliography as a basis for all types of scientific and technical information, emphasized its social and cultural role. He proposed to consider the bibliography of agricultural literature as an independent branch of general bibliography. He promoted creating in the CSAL of a bibliographical information system comprising alert (an initiator of creation), recommendatory, retrospective and current bibliography. In the 1960s he organized in the CSAL the Centralized Bibliographical Information (CBI): the distribution of a ready catalog card which was both the centralized catalogization of publications on agriculture, as well as the current bibliographical information. He advocated for coordination of the work of libraries and their cooperation in library service. The A.M. Bochever’s ideas were reflected in series of industry-wide methodical documents, including “Regulation on the Unified System of Scientific Technical Information of the USSR State Agriculture Committee”.

Artykuł jest poświęcony omówieniu semantyki leksemu kołacz w polszczyźnie. Dane pozyskane z podstawowych słowników rejestrujących leksykę historyczną i współczesną, ogólną i dialektalną pozwalają zaobserwować dość dużą różnorodność znaczeniową tego wyrazu. Okazuje się bowiem, że odnosi się on do przeróżnych wyrobów piekarniczych. Przede wszystkim to rodzaj ciasta, zwykle okrągłego i płaskiego (czasem podłużnego), z mąki pszennej, podawanego na ogół na uroczystościach (weselach, świętach). Oprócz tego kołacz to też ‘bochenek’, ‘bułka’, a nawet ‘każdy wyrób piekarniczy z mąki pszennej’ czy inne rodzaje ciast. Pełna definicja osobnego znaczenia, notowanego w języku ogólnym i gwarach, brzmi następująco: ‘wyciśnięte nasiona oleiste, najczęściej zbite w kształcie okrągłego placka, stanowiącedobrą paszę dla bydła i nierogacizny; makuch’ (SJPD, t. III, s. 833). Ponadto kołacz odnotowano w znaczeniach specjalistycznych – flisackim: ‘okrągłe z chlub [wici dębowych] robione wiązanie, 6 cali średnicy mające, używane w bieganiu, czyli kręceniu wici’ (SWil, t. I, s. 510) oraz górniczym: ‘napiwek dawany górnikom’ (SW, t. II, s. 407; zwany też kołaczne). Wydaje się, że taki przegląd służy lepszemu rozumieniu kołacza, funkcjonującego w ograniczonym zakresie we współczesnej polszczyźnie oraz lepszemu rozumieniu licznychzwiązków wyrazowych (frazeologizmów i przysłów) pozostających przede wszystkim w historycznych zasobach polszczyzny.

Celem pracy było określenie wpływu dodatku preparatów enzymatycznych oraz czasu i warunków przechowywania na fizykochemiczne właściwości pieczywa mieszanego wytworzonego na zakwasie. Badaniom poddano chleb pszenno-żytni bez udziału preparatów (kontrolny) oraz chleb z dodatkiem preparatów Finizyme i G-Zyme w ilościach 10 i 30 mg/900 g (bochenek). Chleby sporządzono zgodnie z recepturą na zakwasie, wypieczono w piecu przeznaczonym do wypieku chleba i przechowywano w warunkach zamrażalniczych przez 14 dni. W chlebach świeżych po siedmiu i czternastu dniach przechowywania wykonano analizy zawartości wody, objętości (chleb świeży), kwasowości, zawartości skrobi opornej i twardości miękiszu chleba. Wykonano także ocenę sensoryczną pieczywa. W czasie zamrażalniczego przechowywania zaobserwowano zmniejszenie zawartości wody (o 1 ÷ 12 %) i wzrost kwasowości, który w przypadku pieczywa z dodatkiem preparatów enzymatycznych przyczynił się do większego przyrostu ilości skrobi opornej (RS) w porównaniu z chlebem kontrolnym. Dodatek enzymów wpłynął znacząco na objętość chleba i na poprawę jego wyglądu zewnętrznego, co spowodowało, że został wyżej oceniony pod względem cech sensorycznych. Twardość chleba uległa zwiększeniu w trakcie dwóch tygodni jego przechowywania w stanie głębokiego zamrożenia. Większe zmiany wartości tego parametru stwierdzono w chlebie kontrolnym, natomiast dodatek preparatów enzymatycznych ograniczył w pewnym stopniu szybkość twardnienia miękiszu. Wprowadzenie do receptury chleba na zakwasie preparatów enzymatycznych należy więc uznać za korzystne z uwagi na wzrost objętości bochenków, ograniczenie ich twardnienia podczas zamrażalniczego przechowywania oraz zwiększenie zawartości skrobi RS – czynnika o charakterze prozdrowotnym.

✓ During the past 10 years, 125 operations for acoustic nerve tumors were performed on 114 patients at the authors' institution using a modified extended middle cranial fossa approach. This approach is based on a combination of King and Morrison's translabyrinthine-transtentorial approach and on the extended approach through the middle cranial fossa described by Bochenek and Kukwa. There were two hospital deaths (operative mortality 1.6%). In 102 operations on the initial tumor, total removal was performed in 89 cases (87%), and in 71 (80%) of these the facial nerve was anatomically preserved. Intracranial end-to-end anastomosis was performed on five of the 18 sacrificed facial nerves; a facial-hypoglossal anastomosis was carried out in the remaining 13 patients and in five (7%) of the 71 patients whose anatomically preserved facial nerve functioned poorly. In seven (39%) of the 18 patients in whom an attempt to preserve hearing was made, postoperative hearing was saved. In 23 operations on 17 patients for recurrent tumors, most of which had previously been removed subtotally via the suboccipital approach, total removal was accomplished in 13 (57% of the 23 reoperations and 76% of the 17 patients). At reoperation, the facial nerve was preserved in six (55%) of the 11 patients in whom the facial nerve had not been sacrificed. Postoperative leakage of cerebrospinal fluid occurred in 11 cases (8.8%), with rhinorrhea in 10 cases and otorrhea in one. Five of the fistulas were corrected by surgery and the rest healed spontaneously. Other complications were not significant.

The article analyses a project directed to Ukrainian students in Polish primary schools, financed by UNICEF. The project consisted of two parts. The first one is the examination of children's psychological and pedagogical needs. It was carried out with the use of the Questionnaire of Disorders in the Realization of Social Roles, among 96 students studying in IV – VIII classes of primary schools. This questionnaire serves as a screening test for the research sample. Test results show that the average and high level of disorders in the role of a peer is experienced by 30% of students, while the sense of peer rejection at the same levels is shown by as many as 35% of the respondents. The main study is an examination of the effectiveness of multimedia art therapy program in improving peer relations of Ukrainian students. The aim of this part was to support building peer relationships among studied children and provide them with the necessary emotional support. 57 students participated in a 10 group art workshops using multimedia. The theoretical concept of this project was based on Expressive Therapy (Malchodi & Bochenek, 2014). To determine the effectiveness of art therapy, qualitative methods were used: subjective scales and descriptive scales, as well as observations of the creative process, statements and reflections of students during and after the project. The results underscored a noticeable improvement in the students' self-perceptions, with reported enhancements in feelings of connection, self-worth, and self-approval. Additionally, an increase in communication skills, positive peer interactions, and social acceptance was observed.

Les discussions terminologiques à propos des différents éléments dont s’occupe la phraséologie (Thun ; Pilz ; Gläser) ont été abandonnées depuis des années. Et pourtant, la question est loin d’être résolue au niveau non seulement de la dénomination de ces éléments, mais aussi de celui de leur propre nature. En effet, il continue d’exister une profusion de termes selon les cadres théoriques de tout un chacun (expressions figées, phrasèmes, phraséologismes, unités phraséologiques, etc.). Or, face à cette profusion de dénominations et de typologies, le nom du domaine en question n’a eu qu’un seul concurrent depuis que Bally (vol. I) l’a proposé : celui d’idiomatologie (Guiraud), avec sa variante idiomatik en allemand (Burger et Jaksche), et sa traduction idiomatology en anglais (Makkai ; Kavka et Zybert ; Kavka « Compounding » ). Ce constat nous pousse à aller à la recherche d’une explication qui aille au-delà du seul sort aléatoire des mots dans leur consolidation, en retraçant l’histoire de cette concurrence, toute courte qu’elle ait pu être, pour essayer de comprendre les raisons du choix terminologique de Bally et comment ce choix est arrivé à s’imposer. Nous le ferons à travers la comparaison des termes phraséologie et idiotismes et leur coapparition dans deux ouvrages du XIXe siècle (Dupont et Bochet et al.). Cela pourra certainement nous éclairer sur le partage des spécialistes d’aujourd’hui, divisés entre une conception large ou étroite du domaine, avec des typologies plus ou moins inclusives. Mais ce sera surtout l’occasion de réconcilier la phraséologie et l’idiomatologie en tant que domaines complémentaires l’un de l’autre .

Flow cytometry is the only reliable and relatively fast method allowing separation of live X and Y spermatozoa for sex regulation. Many thousands of animals of different mammalian species have been born after insemination with sexed semen during the past 20 years. Nevertheless, the question is still open: does the bull sperm sexing technology affect chromatin structure? A case of serious chromatin damage after sexing stallion semen was reported previously (Bochenek et al. 2006 Havemeyer Foundation Monograph Series No. 18, 13 –14). The aim of this work was to examine the effect of the sexing procedure and different UV laser powers on bull sperm chromatin structure. The ejaculates of 28 bulls (one ejaculate/bull) were used in the study. Each ejaculate was divided into 5 groups: (1) control, unprocessed; (2) sorted strictly according to XY Inc. protocol (Schenk et al. 1999 Theriogenology 52, 1375 –1391); (3) as group 2, but without the Red Food dye staining used for dead spermatozoa discrimination; (4) as group 2, but with double UV laser power (300 mW); and (5) as group 3, but with double UV laser power (300 mW). Sperm sorting was performed with a MoFLoSX flow cytometer at speeds of 3000 –5000 cells/s. Sorted fractions of X and Y spermatozoa were mixed again and stored for 24 h at 15 °C. A sperm chromatin structure assay (SCSA) was performed twice on each sorted sample, immediately after sorting and after 24 h. The chromatin of control samples was examined according to the same time schedule. The percentage of spermatozoa with damaged chromatin was calculated (COMP α-t) as well as standard deviation of the α-t parameter (SD α-t). The latter parameter, although less intuitive, is considered as even more precise than COMP α-t in chromatin investigations. The mean percentage of spermatozoa with abnormal chromatin was 1.12% (SD = 0.47) for control samples. The highest level of chromatin abnormality was noted for the 300 mW group with no dead cell discrimination (Red Food staining): 1.29% (SD = 1.05). After 24 h of storage, the mean level of chromatin abnormality increased to 1.97% (SD = 0.96) in control samples whereas that in all sorted samples was lower: from 1.06% (SD = 0.4) to 1.16% (SD = 0.62) in the 150 mW/non-Red Food-stained and the 300 mW/Red Food-stained groups, respectively. This difference appeared to be statistically significant (t; P ≤ 0.05). Interestingly, the percentage of abnormal spermatozoa decreased slightly after 24 h of storage in the 300 mW/Red Food-stained and the 300 mW/non-Red Food-stained groups ( –0.13% and –0.08%, respectively). Calculation of the SD α-t parameter showed statistically significant differences in chromatin abnormality between the control group vs. the 300 mW/non-Red Food-stained group immediately after sorting and the control group vs. the 150 mW/Red Food-stained group after 24 h of storage. In conclusion, although the statistically significant increase of chromatin damage was found after sexing in some investigated groups, it seems that the level of this abnormality is far too low to affect sexed semen fertility.

Hemophilia A arises from mutations in the F8 gene, affecting ~ 1/5000 males. Treatment options include frequent intravenous factor and subcutaneous non-factor therapies. While these approaches have been widely used, they have significant limitations, such as breakthrough bleeds and joint disease due to suboptimal adherence, non-ideal factor kinetics, inhibitor generation, (Weyand, Blood 2018) as well as risk of thrombotic events and coagulation test interference with newer non-factor therapies. (Peters, Nat Rev Drug Discov 2018) Alternative modalities such as cell therapies with genetically modified, ready-made human cells are being investigated. To avoid a cytotoxic immune response by the host, allogeneic cells either need to be physically shielded and/or the host immunosuppressed. Various biomaterials, e.g. hydrogels, could serve as the physical barrier that prevents host immune cells from accessing the allogeneic cells, avoiding the need for immunosuppression altogether. However, the host can still activate a foreign body response (FBR), targeting the biomaterial, which significantly limits cell survival and durability of cell therapies. (Anderson, Semin Immunol 2008) We have successfully identified a library of proprietary small molecules, which when conjugated to alginate used to create encapsulating spheres, limit the FBR (Bochenek, Nat Biomed Eng 2018). In addition, we further reduced the FBR using two-compartment design, 1.5 mm diameter spheres, in which the cells are encapsulated in an inner compartment surrounded by an outer, acellular compartment. Using this innovative technology, we aimed to create a novel product that will deliver long-term, sustained human coagulation factor VIII (hFVIII) in vivo. First, we selected a human epithelial cell line with optimal properties for encapsulation within the spheres; considerations included safety, contact inhibition and longevity. We genetically modified this cell line using a non-viral vector and an optimized the coding sequence for a B-domain deleted hFVIII to create a proprietary engineered cell line that constitutively expresses high levels of this protein. Second, we optimized the inner compartment matrix by modulating cell density/sphere and by the addition of a novel modified alginate; these changes maximized cell viability and protein production in vivo. Finally, we further optimized the acellular outer compartment with a proprietary mixture of small-molecule-modified and unmodified alginates. The resulting SIG-001 product candidate consists of two-compartment, 1.5 mm spheres encapsulating hFVIII-expressing human cells. The spheres are sufficiently porous to allow gasses, nutrients, and secreted proteins to freely diffuse, while limiting FBR and prohibiting cell contact with the host's tissues including immune cells. Our in vitro studies demonstrated similar secretion of hFVIII protein by non-encapsulated and encapsulated engineered cells, along with viability of the same cell line after encapsulation. Several doses of SIG-001 were administered intraperitoneally to mice. Stable hFVIII production and good cell viability was shown for spheres retrieved after long-term placement in immunocompromised mice (up to 6 months). Furthermore, our data showed dose-responsive hFVIII activity and efficacious correction of the bleeding phenotype in immunocompetent Hemophilia A mice (Carmona, ISTH 2019). In conclusion, SIG-001 can deliver sustained therapeutic plasma levels of hFVIII in vivo. Our technology could eliminate the need for regular factor injections, lowering the patient burden and providing consistent factor levels without the peaks and troughs observed with factor and non-factor therapies. It also has the potential for expanded use in pediatric patients, and allows for re-dosing if needed. Additionally, there is no concern about the pre-existing antibodies to viral capsids which limit eligibility for gene therapies. We aim to use our technology platform to develop a new category of medicines for severe chronic diseases including rare blood disorders such as Hemophilia A, and to advance their development into clinical testing. Disclosures Carmona: Sigilon Therapeutics: Employment. Barney:Sigilon Therapeutics: Employment. Sewell:Sigilon Therapeutics: Employment. Newman:Sigilon Therapeutics: Employment. Carroll:Sigilon Therapeutics: Employment. Beauregard:Sigilon Therapeutics: Employment. Huang:Sigilon Therapeutics: Employment. Heidebrecht:Sigilon Therapeutics: Employment. Corzo:Sigilon Therapeutics: Employment. Moller:Sigilon Therapeutics: Employment. Smith:Sigilon Therapeutics: Employment. Peritt:Sigilon Therapeutics: Employment. Vivaldi:Sigilon Therapeutics: Employment.

Hemophilia A (HA) arises from pathogenic variants in the F8 gene, affecting ~ 1/5000 males. Current factor replacement therapies have limitations, including treatment burden, kinetics (peaks/troughs), morbidity and mortality from breakthrough bleeds, including chronic joint disease, inhibitor development, as well as risk of thrombotic events and coagulation test interference with novel non-factor therapies. Cell therapies with genetically modified human cells expressing hFVIII have been tested as a new potential therapeutic approach. To avoid host cytotoxic immune response, allogeneic cells either need to be physically shielded and/or the host immunosuppressed. Various biomaterials, which can provide a physical barrier from the host immune cells, activate a foreign body response, resulting in pericapsular fibrotic overgrowth (PFO) that significantly limits efficacy and durability of these cell-based therapies. Sigilon utilized a library of proprietary small molecules that avoid PFO when conjugated to alginate biomaterials (Bochenek Nat Biomed Eng 2018) to create a modular, cell-based platform with potential for utilization across a range of chronic diseases, including rare blood disorders. The platform consists of genetically modified allogeneic human cells engineered to produce the therapeutic protein of interest, encapsulated in a two-compartment sphere which supports the function of cells (inner compartment) and shields the cells from the host's immune system and PFO (outer layer) (Barney ASGCT 2020). SIG-001 is a buffered suspension of 1.5 mm alginate spheres encapsulating hFVIII-expressing human cells. SIG-001 can produce functionally active hFVIII in a dose-dependent manner, correct the bleeding phenotype in HA mice, and produce sustained long-lasting hFVIII levels in NSG mice sacrificed at 6 months (Carmona ASH 2019). In preparation for entry into the clinic, SIG-001 was evaluated in mice and non-human primates (NHP). The studies showed no concerning signals in the safety/toxicology profile of SIG-001 (Carmona ISTH 2020). The first-in-human phase 1/2 trial in HA (SIG-001-121, EudraCT 2019-004210-33) will assess the safety, tolerability and preliminary efficacy of SIG-001. This multi-center, open-label study with sequential, dose escalating cohorts, will enroll up to 18 participants (pts), including up to 3 initial pts per cohort and 3 additional pts if cohort expansion is warranted at any dose. A sentinel pt in each cohort will receive a single administration of SIG-001 and be evaluated for at least 4 weeks prior to enrollment of subsequent pts. The next dose level will be initiated following safety review of all pts from the previous dose level(s). The study will include adult males (≥18), with severe or moderately-severe HA (≤2% FVIII activity) who have had ≥150 exposure days to FVIII product(s). The key exclusion criteria include pts with current or past history of FVIII inhibitors. SIG-001 will be administered into the peritoneal cavity using a short laparoscopic procedure, and pts will be followed for 5 years after SIG-001 administration. Primary endpoint of the study is safety, including clinically significant changes in vital signs, clinical laboratory tests, and treatment emergent adverse events compared to baseline. Secondary endpoints include FVIII one-stage and chromogenic activity levels, FVIII inhibitor titers, annualized bleeding rate, and annualized FVIII concentrate use. Exploratory endpoints include QoL metrics, and joint health and physical activity assessments. Results will be analyzed using descriptive statistics. The study will be conducted at sites located in the UK, US and Germany. In conclusion, Sigilon has developed an innovative, modular, scalable, cell-based platform of candidate products for the treatment of chronic diseases, including rare bleeding disorders. The platform was designed to overcome the significant challenges of allogeneic cell therapy, namely immune rejection and PFO. SIG-001 produces hFVIII with in vitro and in vivo functionality. SIG-001-121, first-in-human clinical trial of SIG-001 in HA, is targeted to open in 2020. Disclosures Shapiro: Agios: Research Funding; BioMarin: Research Funding; Bioverativ: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Catalyst BioSciences: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Research Funding; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Glover Blood Therapeutics: Research Funding; Kedrion Biopharma: Research Funding; Novartis: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; OPKO: Research Funding; Octapharma: Research Funding; Pfizer: Research Funding; ProMetic Bio Therapeutics: Consultancy, Research Funding; Sangamo: Research Funding; Sigilon: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees. Konkle:Sigilon: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BioMarin: Consultancy; Takeda: Research Funding; Spark: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; CSL Behring: Consultancy; Uniquire: Research Funding; Roche: Consultancy; Baxalta: Research Funding. Croteau:Bayer: Consultancy; Genentech: Consultancy; Pfizer: Consultancy; Novo Nordisk: Research Funding; CSL-Behring: Consultancy; Spark Therapeutics: Research Funding; ATHN: Research Funding; Sigilon Therapeutics: Consultancy; National Hemophilia Foundation: Honoraria; Hemophilia Federation of America: Honoraria. Miesbach:Ablynx: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aventis: Consultancy; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Freeline: Consultancy, Membership on an entity's Board of Directors or advisory committees; LEO: Consultancy, Membership on an entity's Board of Directors or advisory committees; LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sigilon: Consultancy; UniQure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees. Mihova:Sigilon Therapeutics: Current Employment. Rangarajan:Takeda: Other: Conference support, Speakers Bureau; Grifols: Speakers Bureau; Roche: Speakers Bureau; Reliance Life Sciences: Other: Conference support; Sangamo: Research Funding. Pasi:Roche: Honoraria, Other; Sobi: Consultancy, Honoraria, Other; Tremeau: Research Funding; Pfizer: Other; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Alnylam (Sanofi): Other: Personal fees and nonfinancial support ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; ApcinteX: Consultancy, Other: Personal fees ; uniQure: Other: Grants and nonfinancial support , Research Funding; BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; Sigilon: Research Funding.

While the definition of high-dose corticosteroids depends on the indication, it is typically defined as greater than 15–20 mg for greater than 2–4 weeks. Corticosteroids have a variety of indications such as autoimmune, gastrointestinal, rheumatologic, respiratory, and hematologic conditions and after organ or hematopoietic stem cell transplantation. They can predispose these patients to infections such as pneumococcal pneumonia, Pneumocystis jirovecii (carinii) pneumonia (PJP), hepatitis B reactivation, active tuberculosis, and disseminated strongyloides infection. This article outlines ways to modify these risks in these patients. Prophylaxis is of utmost importance to those at risk for PJP with trimethoprim/sulfamethoxazole, lamivudine for those at risk of hepatitis B reactivation, isoniazid (INH) for latent tuberculosis and ivermectin for those with positive strongyloides serology. Equally important in mitigating disease risk is the appropriate timing of vaccines to elicit an adequate immune response as well as offering additional vaccines such as the pneumococcal vaccine.RésuméLa notion de dose élevée de corticostéroïdes varie selon les indications, mais elle est généralement définie comme correspondant à plus de 15‑20 mg sur une période de plus de deux à quatre semaines. Les corticostéroïdes sont indiqués dans nombre de conditions auto‑immunes, gastro-intestinales, rhumatologiques, respiratoires et hématologiques, ainsi qu’à la suite d’une transplantation d’organe ou de cellules souches hématopoïétiques. Ils peuvent toutefois prédisposer les patients à diverses infections comme la pneumonie pneumococcique et la pneumonie à Pneumocystis jirovecii (carinii) ou PCP, à une réactivation de l’hépatite B, à une tuberculose active et à une strongyloïdose disséminée. Le présent article passe en revue différentes façons de réduire ces risques chez les patients concernés. Voici des mesures de prophylaxie qui s’avèrent être de la plus haute importance pour les personnes à risque : le triméthoprime ou le sulfaméthoxazole pour celles à risque de PCP; la lamivudine pour celles à risque de réactivation de l’hépatite B; l’isoniazide (INH) dans les cas de tuberculose latente; et l’ivermectine pour les personnes montrant une sérologie positive aux strongyloïdes. De plus, pour réduire le risque de maladie, un calendrier de vaccination approprié est tout aussi important, en vue de susciter une réponse immunitaire adéquate et de pouvoir offrir d’autres vaccins comme le vaccin antipneumococcique.Corticosteroids were first used in clinical practice in 1949 for rheumatoid arthritis.1 The number of patients on high-dose corticosteroids is not well known but the use of corticosteroids is becoming increasingly common for a number of indications: An estimated 1% of the general population in the UK is treated with corticosteroids, and this rate increases with age to almost 2.5% in those aged 70–79. 4“High-dose corticosteroids” as a risk factor for infections is typically defined as greater than 15–20 mg of prednisone (or its’ equivalent) for greater than 2–4 weeks, although this definition does vary slightly depending on the infection considered. Notably, this definition is different from the standard definition of high-dose corticosteroids for treatment purposes used in the literature – which is usually defined as greater than 30 mg but less than 100 mg/day – as this dose results in almost complete cytosolic receptor saturation. 2Corticosteroids are used commonly for their anti-inflammatory effects in many conditions with an element of autoimmune disease. The mechanism is to induce transient lymphocytopenia by altering lymphocyte circulation, inducing lymphocyte death and inhibiting cytokines to prevent T-cell activation.3 For example, they are used to induce remission in inflammatory bowel disease (IBD) or to maintain symptom control in rheumatologic diseases like polymyalgia rheumatica. They are also used to prevent organ rejection in solid organ transplantation. Other indications include autoimmune hepatitis, other rheumatologic diseases such as rheumatoid arthritis, systemic lupus erythematous, vasculitis, respiratory conditions such as interstitial lung disease, sarcoidosis, hematologic disorders such as lymphoma, leukemia, idiopathic thrombocytopenic purpura, hemolytic anemia), endocrine disorders like Graves disease to prevent opthalmopathy and other conditions like multiple sclerosis.The relative risk of bacterial infections was found to be 5-fold higher in IBD patients on corticosteroids alone, 4-fold higher for other infections like strongyloides and tuberculosis, and only 1.5 fold higher for viral infections.5 However, the absolute individual risk of infectious complications from corticosteroid use remains fairly small. Nevertheless, the burden is significant at a population level due to the high frequency of corticosteroid use. 4 Thus, most practitioners eventually come across these complications during their career.VaccinationsOne of the first considerations in patients on high-dose corticosteroids is the timing of the administration of vaccines to be given to these patients. Immunizations with inactivated vaccines can be given up to 2 weeks before high-dose corticosteroids are initiated, whereas live vaccines need to be given 4 weeks before the high-dose corticosteroids are begun. If the vaccines cannot be given prior to the start of a corticosteroid treatment, both live and inactivated vaccines must wait for 4 weeks after the steroids are completed to elicit an adequate immune response and prevent infectious complications with live vaccines.6Equally important to the timing of the vaccines, patients on high-dose corticosteroids (defined as anyone receiving ³ 20 mg/day for 14 days or more) should receive additional vaccines. A single dose of an inactivated pneumococcal conjugate vaccine (Prevnar), at least one year after any previous dose of pneumococcal vaccine polyvalent (Pneumovax), followed by a single dose of Pneumovax 8 weeks later with a booster of Pneumovax 5 years later is recommended for those on high-dose corticosteroids.7,8 Pneumocystis jiroveci infectionThe following patient groups are considered to be at higher risk forPneumocystis jiroveci pneumonia (PJP; formerly known as Pneumocystis carinii pneumonia [PCP])if exposed to prednisone at doses as low as 20 mg/day for at least 4 weeks9: patients with an underlying immunosuppressive disorder (including autologous HSCT and malignancy), or those with chronic obstructive pulmonary disease and interstitial lung disease secondary to polymyositis/dermatomyositis. Also, patients receiving the same dose of prednisone plus TNF-alpha inhibitors, cyclophosphamide, methotrexate, or temsirolimus should also receive PJP prophylaxis. The first-line agent for prophylaxis is trimethoprim/sulfamethoxazole 80/400 mg (single strength) daily or 160/800 mg (double strength) three times per week (e.g., Monday/Wednesday/Friday). While adverse events are rare on such low doses, thrombocytopenia is possible given that this is an idiosyncractic reaction but pancytopenia is usually observed at much higher (i.e., treatment) doses. Also possible are hyperkalemia, increased serum creatinine and aseptic meningitis. A more rare but devastating adverse event is Stevens-Johnson syndrome. A second line agent for PJP prophylaxis is dapsone but this requires glucose-6-phosphate dehydrogenase (G6PD) testing first, as those who are deficient in this erythrocytic enzyme show a two-fold higher predisposition to dapsone-induced hemolytic anemia. Other alternatives for PJP prophylaxis are atovaquone 1500 mg daily, but this is a costly option, or inhaled pentamidine via a nebulizer at 300 mg every month. Correct administration of inhaled pentamidine is crucial and due to the route of administration, disseminated PCP disease is still possible. 9 Hepatitis B ReactivationFurthermore, patients on corticosteroids of at least 20 mg/day for at least 4 weeks, have an 11–20% chance of reactivation if they are hepatitis B surface Ag carriers. An inactive carrier is hepatitis B surface antigen positive for greater than 6 months without detectable hepatitis B e antigen (HbeAg), presence of anti-hepatitis B e antibodies (anti-Hbe), and undetectable or low levels of hepatitis B DNA, repeatedly normal ALT levels, and no or minimal liver fibrosis. Inactive carriers comprise the largest group of chronic hepatitis B infected individuals with an estimated 250 million people worldwide and can convert to active disease under such immunosuppression.Therefore, it is prudent to prescribe hepatitis B prophylaxis to these patients although no high-level evidence supporting this approach is available.11 Lamivudine is considered first choice for these patients if they do not otherwise meet treatment criteria for hepatitis B. Tenofovir is considered first line in areas highly prevalent for resistance to lamivudine, which tends to occur with prolonged lamivudine exposure. For example, lamivudine resistance develops in up to 90% of HBV-HIV co-infected individuals after 4 years of lamivudine therapy.12.In the setting of isolated anti-Hb-core antibody positivity, prophylaxis is not recommendedgiven that the rate of reactivation is less than 1%.10 Instead, patients should have serial measurements of liver function, hepatitis B serology and hepatitis B DNA every 1–3 months during the period of immunosuppressive treatment and if there is any elevation in these markers, antiviral prophylaxis or treatment (depending on the results) should be offered.So, when assessing patients for the need for PCP or hepatitis B prophylaxis, both the intended duration as well as the dose of the corticosteroids need to be considered.Strongyloides stercoralis InfectionStrongyloides stercoralis can persist for several decades and can reactivate with glucocorticoid exposure causing a severe and sometimes fatal disseminated infection. Strongyloides infection can be asymptomatic and can be acquired walking barefoot on soil in the developing world.13 Strongyloides serology is therefore recommended for refugees from low-income countries in Southeast Asia and Africa where strongyloides is endemic before starting high-dose corticosteroid treatement.14 If positive, patients should be treated with 2 doses of ivermectin to prevent the development of hyperinfection. TuberculosisPatients with latent tuberculosis on higher dose and/or longer duration of glucocorticoid use are also at risk of conversion to active disease. A one-step tuberculin skin test (TST) ³ 5 mm is considered positive when a patient is on prednisone doses ³ 15 mg/day for one month or more. First-line treatment for latent tuberculosis is isoniazid over 9 months. Patients should begin therapy ideally at least 4 weeks before starting such immunosuppression to prevent conversion to active disease.15,16. If this is not possible, the recommendation is to start isoniazid and the corticosteroids at the same time. ConclusionsSerious and potentially fatal infections are just one of the many potential complications of being on high-dose corticosteroids for a long period of time – others include diabetes, hypertension, psychosis, osteoporosis, adrenal insufficiency and the development of cushingoid features.17 Infectious diseases that are either latent or inactive may reactivate under high-dose corticosteroids including tuberculosis, pneumocystis jirovecii pneumonia, Strongyloides stercoralis, and hepatitis B. Screening and treatment for such conditions prior to starting high-dose corticosteroids, or at least once the corticosteroids are started, can prevent these complications. Furthermore, the timing of both inactivated and live vaccines is crucial for the patients’ ability to mount an appropriate immune response and to avoid complications from live vaccines. Finally, patients on high-dose corticosteroids are at higher risk for illnesses that may require additional vaccinations not otherwise given to such individuals – for example the pneumococcal vaccine.DisclosureThere are no conflicts of interest for either author on this manuscript. References1. Zoorob RJ and Cender D. A different look at corticosteroids. American Family Physician. 1998 Aug 1; 58(2): 443-450. 2. Buttgereit F, Da Silva JAP, Boers M et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002; 61: 718-722. 3.Hall BM and Hodgkinson SJ. Corticosteroids in autoimmune diseases. Aust Prescr 1999; 22: 9-11. 4. T.P. van Staa, H.G. Leufkens, L. Abenhaim, B. Begaud, B. Zhang, C. Cooper. Use of oral corticosteroids in the United Kingdom. QJM. 2000 Feb; 93(2): 105–111. 5. Paul Brassard, Alain Bitton, Alain Suissa, Liliya Sinyavskaya, Valerie Patenaude and Samy Suissa. 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