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Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene-sequence-similarity-based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseudomonas was observed including the production of several new NPs derived from previously uncharacterized non-ribosomal peptide synthetases (NRPS). This easyPACId approach (easy Promoter Activated Compound Identification) facilitates NP identification due to low interference from other NPs. Moreover, it allows direct bioactivity testing of supernatants containing secreted NPs, without laborious purification.
Background: Recently, public and political interest has focused on people living with rare diseases and their health concerns. Due to the large number of different types of rare diseases and the sizable number of patients, taking action to improve the life of those affected is gaining importance. In 2013, the federal government of Germany adopted a national action plan for rare diseases, including the call to establish a central information portal on rare diseases (Zentrales Informationsportal über seltene Erkrankungen, ZIPSE).
Objective: The objective of this study, therefore, was to conduct scientific research on how such a portal must be designed to meet the needs of patients, their families, and medical professionals, and to provide high-quality information for information seekers.
Methods: We chose a 3-step procedure to develop a needs-based prototype of a central information portal. In the first step, we determined the information needs of patients with rare diseases, their relatives, and health care professionals by means of qualitative interviews and their content-analytical evaluation. On the basis of this, we developed the basic structure of the portal. In the second step, we identified quality criteria for websites on rare diseases to ensure that the information linked with ZIPSE meets the quality demands. Therefore, we gathered existing criteria catalogs and discussed them in an expert workshop. In the third step, we implemented and tested the developed prototypical information portal.
Results: A portal page was configured and made accessible on the Web. The structure of ZIPSE was based on the findings from 108 qualitative interviews with patients, their relatives, and health care professionals, through which numerous information needs were identified. We placed particularly important areas of information, such as symptoms, therapy, research, and advisory services, on the start page. Moreover, we defined 13 quality criteria, referring to factors such as author information, creation date, and privacy, enabling links with high-quality information. Moreover, 19 users tested all the developed routines based on usability and comprehensibility. Subsequently, we improved the visual presentation of search results and other important search functions.
Conclusions: The implemented information portal, ZIPSE, provides high-quality information on rare diseases from a central point of access. By integrating the targeted groups as well as different experts on medical information during the construction, the website can assure an improved search for information for users. ZIPSE can also serve as a model for other Web-based information systems in the field of rare diseases.
Registered Report Identifier: RR1-10.2196/7425.
Background: Rare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.
Methods: In total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.
Results: Out of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling—in particular, differential diagnostics—and referrals.
Conclusions: Therefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.
Purpose: There are little or no published data comparing the outcomes of ILUVIEN® (0.19 mg fluocinolone acetonide [FAc]) and OZURDEX® (0.7 mg dexamethasone [DEX]) implants in patients with diabetic macular edema (DME), and this case sought to compare their outcomes.
Methods: This case was extracted from a monocentric audit involving a pool of 25 patients (33 eyes) with DME and treated with a single FAc implant between October 2013 and December 2016. This case, a 61-year-old male with a pseudophakic lens, is from a patient that had received 4 intravitreal injections of a DEX implant prior to FAc implant and then was monitored for 3 years until re-treatment with a second FAc implant. Parameters measured included visual acuity (VA), central retinal thickness (CRT), and intraocular pressure (IOP).
Results: After the DEX implants, CRT transiently improved. In March 2014, the decision was taken to administer an FAc implant, and this led to a reduction in CRT below 300 µm (from a baseline of 748 µm), and this was sustained for 30 months. VA remained above 65 Early Treatment Diabetic Retinopathy Study letters to month 36, after which time a second FAc implant (in April 2017) was administered due to recurrence of edema and CRT decreased to below 300 µm and VA improved to 70 letters. Side effects included elevated IOP, which was effectively managed with IOP-lowering drops.
Conclusion: A single injection of FAc implant led to sustained improvements in CRT and VA that lasted for between 30 and 36 months, which is in contrast to the DEX implant where re-treatment was generally required within 6–7 months. After 36 months, re-treatment with the FAc implant again led to improved VA and CRT, and responses that were similar to those achieved with the first FAc implant.
Seit Beginn der 1990er Jahre rückt der Begriff des 'Autors' und der 'Autorschaft' wieder verstärkt in den Fokus literaturwissenschaftlicher Theoriebildung. Im Unterschied zu den subjektkritischen Konzepten der Postmoderne, insbesondere denjenigen des Poststrukturalismus, die in Roland Barthes' These vom Tod des Autors (1967) wohl am prominentesten widerhallen, gewinnt die Autorfunktion als legitime Bezugsgröße im interpretatorischen Zugriff auf den literarischen Text wieder an Bedeutung. Auch der Werkbegriff erhält infolge dieser Aufwertung des textgenerierenden Subjekts in Praxis und Theorie neue Aufmerksamkeit. Im Falle von Felicitas Hoppe wird über diesen Kontext hinaus die Betrachtung eines einzelnen Autorenwerks auch intrinsisch durch ihre Texte nahegelegt. Die inhaltliche und sprachliche Kontinuität zwischen fiktionalen und nicht-fiktionalen Texten, die enge auto-intertextuelle Verknüpfung sowie Hoppes ästhetischer Autonomieanspruch verlangen in besonderer Weise nach einer Fokussierung des autorspezifischen Werkzusammenhangs.
Im Folgenden sollen deshalb zunächst vereinzelte Aussagen zusammengeführt werden, aus denen sich ein poetologisches Kernthema ihres Schreibens erschließt: Als Kunstideal gilt Hoppe eine spezifische Verbindung von 'Realität' und 'Imagination', die letztlich auch in der oxymoronischen Selbstbezeichnung ihrer Texte als 'ehrliche Erfindung' mitschwingt, die von Literaturkritik und -wissenschaft so häufig aufgegriffen wurde. In einem zweiten Schritt wird argumentiert, dass dieses ästhetische Ideal in den literarischen Texten mehrfach bildlich dargestellt ist. Nach dieser Präzisierung der poetologischen Zielsetzung stellt sich die Frage, in welchem Verhältnis die explizit-essayistischen und implizit-fiktionalen Reflexionen zur literarischen Praxis stehen. Daran schließt die Hauptthese dieses Beitrags an: Die Bildlichkeit von Hoppes Texten lässt sich zeichentheoretisch als 'ikonisches Erzählen' spezifizieren und hier liegt eine narrative Form vor, die die angestrebte Verbindung von 'Realität' und 'Imagination' umsetzt. Auf der Basis eines vom Symbolbegriff abgegrenzten Ikonbegriffs wird argumentiert, dass in Hoppes Texten die konkrete Ebene inhärente Ähnlichkeitsbeziehungen zu einer abstrakten Ebene aufweist. Bedeutungszuschreibungen, so die Folgerung, lassen sich entsprechend dem Autonomieanspruch der Autorin, für ihre Texte weitgehend durch Abstraktions- und Analogisierungsverfahren ableiten.
Introduction: For management of complicated retinal detachments, a pars plana vitrectomy with temporary silicone oil (SO) fill is the method of choice. According to literature, the retinal redetachment rate varies between <10% and >70% with around 36% in our own group (retrospective data analysis, n = 119 eyes).
Methods: The main goal was to reduce the retinal redetachment rate. Standard operating procedures (SOPs) and evaluation protocols (EVALPs) were developed to prospectively analyse risk factors. Lab analysis of SO was performed, and the role of surgical experience was evaluated and investigated with Eyesi®.
Results: We achieved a significant reduction of the retinal redetachment rate (to 6.80%, n = 101, p = 0.002). After surgery with SO injection, neither further membrane peeling (in 16.5%) nor retinal laser coagulation (in 100%) during revision surgery had a significant effect on the reattachment rate (p = 0.167, p = 0.23), while extensive additional laser coagulation reduced visual acuity (p = 0.01). A 3-port approach had to be set up to complete SO removal. A difference in success rate depending on surgical experience was confirmed, and the performance in Eyesi correlated with that in the patients' eye.
Conclusions: A SOP- and EVALP-based management and new strategies to secure the surgical performance seem to be essential for successful surgery.
Purpose: To evaluate the efficacy of the virtual reality training simulator Eyesi to prepare surgeons for performing pars plana vitrectomies and its potential to predict the surgeons’ performance.
Methods: In a preparation phase, four participating vitreoretinal surgeons performed repeated simulator training with predefined tasks. If a surgeon was assigned to perform a vitrectomy for the management of complex retinal detachment after a surgical break of at least 60 hours it was randomly decided whether a warmup training on the simulator was required (n = 9) or not (n = 12). Performance at the simulator was measured using the built-in scoring metrics. The surgical performance was determined by two blinded observers who analyzed the video-recorded interventions. One of them repeated the analysis to check for intra-observer consistency. The surgical performance of the interventions with and without simulator training was compared. In addition, for the surgeries with simulator training, the simulator performance was compared to the performance in the operating room.
Results: Comparing each surgeon’s performance with and without warmup trainingshowed a significant effect of warmup training onto the final outcome in the operating room. For the surgeries that were preceeded by the warmup procedure, the performance at the simulator was compared with the operating room performance. We found that there is a significant relation. The governing factor of low scores in the simulator were iatrogenic retinal holes, bleedings and lens damage. Surgeons who caused minor damage in the simulation also performed well in the operating room.
Conclusions: Despite the large variation of conditions, the effect of a warmup training as well as a relation between the performance at the simulator and in the operating room was found with statistical significance. Simulator training is able to serve as a warmup to increase the average performance.
