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Christian S Mayer,1,* Isabella Baur,1,* Julia Storr,2 Alexander Markard,1 Ramin Khoramnia1 1Department of Ophthalmology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany; 2Department of Ophthalmology, Technical University Munich, Munich, Germany*These authors contributed equally to this workCorrespondence:Christian S MayerDepartment of Ophthalmology, University Hospital Heidelberg, University of Heidelberg, Im Neuenheimer Feld 400, Heidelberg 69120, GermanyEmail Christian.Mayer@med.uni-heidelberg.dePurpose: Patients with traumatic aniridia, aphakia and retinal complications can require silicone oil endotamponade. In the absence of compartmentalization, there is a risk of silicone oil migrating to the anterior chamber which can cause long-term complications. We report a two-step procedure in trauma cases, using sutures for silicone oil retention in primary care and subsequently prior to secondary artificial iris (AI) and intraocular lens (IOL) implantation, to achieve a reconstruction of the anterior and posterior chamber.Material and Methods: Seven patients with loss of the iris-lens-diaphragm after an ocular trauma and the need for silicone oil endotamponade underwent a primary intervention including wound closure, placement of silicone oil retention sutures and silicone oil filling. Four of those underwent secondary reconstruction with silicone oil removal and AI and IOL implantation and could be included in this retrospective observational study. All main outcome measures were evaluated after the first and after the second surgery. The main outcome measures were morphological findings, subjective impairment from glare, subjective cosmetic disfigurement, patient satisfaction and intraocular pressure (IOP) as well as best-corrected distance visual acuity and objective refraction.Results: The retention sutures could effectively prevent silicone oil migration into the anterior chamber in the first surgery. Silicone oil emulsifications in the anterior chamber were observed in one patient. In two patients, pigment deposition at the sutures was seen. Subjective impairment from glare and subjective cosmetic disfigurement could be reduced after the second surgery compared to the evaluation after the first surgery. IOP and best-corrected distance visual acuity remained stable. No eye needed silicone oil refilling after the secondary reconstruction surgery.Conclusion: Our two-step approach is viable and provides good functional and aesthetic results. We observed a high patient satisfaction.Keywords: aniridia, aphakia, trauma, open globe injury, retinal detachment

Alizé A Rogge,1 Isabel Baur,2 Gabriele Blettner,3 Ulrike Holtkamp,4 Markus Horneber,5 Patrick Jahn,6 Stefanie Joos,7 Silva Keberle,8 Anita Kettelgerdes,9 David Klemperer,10 Alfred Längler,11 Petra Voiß,12,13 Joachim Weis,14 Claudia M Witt1,15,16 1Institute for Social Medicine, Epidemiology, and Health Economics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany; 2Legal Institute, Competence Center Medicine - Ethics - Law Helvetiae, University of Zurich, Zurich, Switzerland; 3Deutsche Krebshilfe, INFONETZ KREBS, Bonn, Germany; 4German Leukemia & Lymphoma Patients‘ Association, Bonn, Germany; 5Department of Internal Medicine, Division of Oncology and Hematology, Paracelsus Medical University, Klinikum Nuremberg, Nuremberg, Germany; 6Department for Nursing Science, Institute for Health Science, Medical Faculty, Eberhard Karls University Tübingen, Tübingen, Germany; 7Institute for General Practice and Interprofessional Health Care, University Clinic Tübingen, Tübingen 72076, Germany; 8Eskamed AG, Basel, Switzerland; 9TK – Techniker Krankenkasse, Hamburg, Germany; 10Faculty of Social and Health Sciences, Ostbayerische Technische Hochschule Regensburg, Regensburg., Germany; 11Gemeinschaftskrankenhaus Herdecke, Institute of Integrative Medicine, Witten/Herdecke University, Herdecke, Germany; 12Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany; 13Gynaecological Clinic, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe, Germany; 14Department of Self-Help Research, Comprehensive Cancer Center University Clinic Freiburg, Freiburg i.Br., Germany; 15Institute for Complementary and Integrative Medicine, University of Zurich and University Hospital Zurich, Zurich, Switzerland; 16Center for Integrative Medicine, University of Maryland School of Medicine Baltimore, Baltimore, MarylandCorrespondence: Claudia M WittInstitute for Complementary and Integrative Medicine, University Hospital Zurich and University Zurich, Sonneggstrasse 6, Zurich 8091, SwitzerlandEmail claudia.witt@uzh.chPurpose: Even in cases of positive evidence for complementary medicine (CM) therapies, it is still difficult for cancer patients to identify reputable providers. The aim of this study was to develop and evaluate a criteria list to provide guidance to cancer patients seeking a reputable CM provider.Methods: The design combined a literature review, an expert consensus procedure (n=15) and an assessment from three stakeholder perspectives (patients (n=18), CM providers (n=26) and oncology physicians (n=20)).Results: A total of 30 existing CM criteria were extracted from the literature, and 12 more were added by the experts. The main challenge was to define criteria that could easily be applied by the patients. A final comprehensive list of 8 criteria guiding cancer patients to find a reputable CM provider was developed.Conclusion: Health professionals and cancer information services might find the criteria list helpful when aiming to strengthen patients’ awareness of quality-related factors associated with CM providers. The criteria developed might be helpful when standards are established for quality assurance in CM in oncology.Keywords: neoplasms, complementary medicine, patient-centered care, standards, healthcare quality assurance

Dairy farmers face various challenges in developing their businesses. The current literature identifies several constraints towards a more efficient dairy sector that relate mostly to on-farm management practices. The available studies analyze constraints mostly from the objective viewpoint of the researcher, whereas very little is known about what farmers themselves perceive to be challenging. To better understand the farmers' perspective and what they perceive to be challenging, and how these challenges differ across regions, this paper builds on a survey of 529 dairy farmers in Malawi. In the survey, respondents were asked in an open question to name their three main challenges. Based on the responses, a three-level coding scheme was elaborated. Data were then coded by two researchers to ensure reliability of coding. Codes were then used to calculate relative frequencies for the different challenges and to perform chi-square tests to check for regional differences in frequencies. Results suggest that farmers perceive low milk price and milk yield, animal health, availability of feedstock, and the costs for drugs as the main challenges. The analysis also revealed that the challenges vary strongly between the three main regions in the country--Blantyre (south), Lilongwe (central), and Mzuzu (north). The perceived challenges reflect the different production systems in the regions. In Blantyre, dairy farming is low in intensity, and farmers thus perceive inputs, in particular the availability of fodder, as well as outputs, in particular milk yields more frequently as a challenge than farmers in Lilongwe and Mzuzu. In contrast, dairy farming in Lilongwe is the most intense. Accordingly, farmers in Lilongwe perceive costs, in particular for inputs such as mash and concentrates as major constraints. Farmers in Mzuzu, which is a rather remote region, consider a lack of assistance, in particular concerning extension services significantly more challenging than the farmers in the other two regions do. Considering these insights, development work and extensions services may be able to increase outcomes in the dairy sector by targeting the regional challenges. Key words: Challenges, dairy production, smallholders, Malawi, qualitative study, regions, INTRODUCTION Dairy cattle production has the potential to contribute to the livelihood of many smallholders in Malawi through income generation, increased resilience during food crises, and by strengthening social security [...]

This commentary focuses on the challenges and possibilities that adolescents and young adults with cancer (AYA) desiring parenthood face under Swiss law. The regulation of reproductive medicine procedures is stricter in Switzerland than in some other countries. Health insurance is compulsory, but the interventions that are covered are in constant flux. Recent changes pertain to the possibilities of future AYA parenthood and keeping up to date with practical and legal ramifications is taxing even for health professionals. AYA facing treatment decisions are uniquely vulnerable and dependent on comprehensive, clear, current, and country-specific information regarding risks and options pertaining to their fertility. This commentary provides a short overview of the Swiss legal framework related to reproductive medicine, highlighting its access restrictions and prohibitions, as well as recent changes. While the importance of patient, peer, caregiver, and interest groups supporting people affected by health conditions has long been recognized in many countries, an AYA organization was only recently established in Switzerland. Such organizations are vital for providing accurate, country-specific information and support, while individualized medical guidance, informed by the most current legal framework and its consequences, remains essential in addressing AYAs' specific needs in connection with the desire to have children.

(1) Background: Laparoscopic resection for colon and rectal cancer was introduced in the early 1990s; the aim of this analysis was to show possible advantages of minimal-invasive approaches in rectal cancer surgery. (2) Methods: From 2016 to 2020, all patients undergoing open, laparoscopic or robotic-assisted rectal cancer surgery in Germany were retrospectively analyzed regarding sex distribution, conversion rates and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRGs). (3) Results: In total, 68,112 patients were analyzed, and most commonly, low anterior rectal resections with primary anastomosis ( n = 25,824) were performed with an increase of minimal-invasive procedures over the years (open: 51% to 27%; laparoscopic: 47% to 63% and robotic: 2% to 10%). In-hospital mortality rate was 2.95% ( n = 2012). In total, 4.61%, 1.77%, 1.14% and 3.95% of patients with open, laparoscopic, robotic and converted-to-open surgery died during hospital stay, respectively (open vs. laparoscopic p < 0.0001; open vs. robotic p < 0.00001; laparoscopic vs. robotic p = 0.001). Conversion rates were significantly more favorable in the robotic compared to the laparoscopic group. (11.94% vs. 2.53%; p < 0.0001). (4) Conclusion: Minimal-invasive rectal cancer surgery might have some advantages in terms of a reduced in-hospital mortality, and an improved conversion rate for the robotic approach.

Objective: Tailored approaches in gastrointestinal oncology have been more frequently introduced in past years and for patients with peritoneal metastases. This article attempts to overview the current strategies in surgical gastrointestinal oncology, with a focus on gastrointestinal peritoneal metastases., Methods: In 2019, all patients undergoing PIPAC therapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates. Furthermore, patients with chemotherapy-refractory peritoneal metastases from gastric cancer undergoing PIPAC-therapy at our institution were analyzed., Results: In 2019, 534 patients received PIPAC treatment in german hospitals. The in-hospital mortality rate was 0%. In total, 36 patients suffered from postoperative complications (8%). From April 2016 to September 2021, a total of 44 patients underwent 93 PIPAC applications at our institution. The non-access-rate was 0%. The median PRGS was two (range, 1-4). Eleven patients (44%) showed histologically stable disease, whereas six patients (24%) showed histological regression. Median survival, calculated from the date of the first PIPAC application, was 181 days (range, 43-636 days)., Conclusions: PIPAC is a safe and feasible procedure with a low in-hospital morbidity and mortality. Furthermore, PIPAC in the palliative and chemorefractory setting and is an appealing approach for patient management in the future.

Background: Invasiveness is a major factor contributing to metastasis of tumour cells. Given the broad variety and plasticity of invasion mechanisms, assessing potential metastasis-promoting effects of irradiation for specific mechanisms is important for further understanding of potential adverse effects of radiotherapy. In fibroblast-led invasion mechanisms, fibroblasts produce tracks in the extracellular matrix in which cancer cells with epithelial traits can follow. So far, the influence of irradiation on this type of invasion mechanisms has not been assessed., Methods: By matrix-embedding coculture spheroids consisting of breast cancer cells (MCF-7, BT474) and normal fibroblasts, we established a model for fibroblast-led invasion. To demonstrate applicability of this model, spheroid growth and invasion behaviour after irradiation with 5 Gy were investigated by microscopy and image analysis., Results: When not embedded, irradiation caused a significant growth delay in the spheroids. When irradiating the spheroids with 5 Gy before embedding, we find comparable maximum migration distance in fibroblast monoculture and in coculture samples as seen in unirradiated samples. Depending on the fibroblast strain, the number of invading cells remained constant or was reduced., Conclusion: In this spheroid model and with the cell lines and fibroblast strains used, irradiation does not have a major invasion-promoting effect. 3D analysis of invasiveness allows to uncouple effects on invading cell number and maximum invasion distance when assessing radiation effects., (© 2021. The Author(s).)

Nucleoli have attracted interest for their role as cellular stress sensors and as potential targets for cancer treatment. The effect of DNA double-strand breaks (DSBs) in nucleoli on rRNA transcription and nucleolar organisation appears to depend on the agent used to introduce DSBs, DSB frequency and the presence (or not) of DSBs outside the nucleoli. To address the controversy, we targeted nucleoli with carbon ions at the ion microbeam SNAKE. Localized ion irradiation with 1-100 carbon ions per point (about 0.3-30 Gy per nucleus) did not lead to overall reduced ribonucleotide incorporation in the targeted nucleolus or other nucleoli of the same cell. However, both 5-ethynyluridine incorporation and Parp1 protein levels were locally decreased at the damaged nucleolar chromatin regions marked by γH2AX, suggesting localized inhibition of rRNA transcription. This locally restricted transcriptional inhibition was not accompanied by nucleolar segregation, a structural reorganisation observed after inhibition of rRNA transcription by treatment with actinomycin D or UV irradiation. The presented data indicate that even multiple complex DSBs do not lead to a pan-nucleolar response if they affect only a subnucleolar region., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Inducible transcription and position-independent expression are critical issues after gene transfer. To gain insight into the amount of variability of transcriptional regulation due to random proviral integration, we analyzed a total of 200 C6 glioma and rat-1 fibroblast clones retrovirally infected with the conventional and reverse tet systems where a luciferase reporter gene was placed under control of a tetracycline-responsive promoter. Repressed luciferase activities differed by up to 81000-fold among individual clones. Repressed activities close to baseline levels were observed in eight clones, all of them transduced with the conventional tet system. Regulation factors ranged from less than two-fold (indicating absence of regulation), observed in 17 clones to 90-fold. Regulation was higher with the conventional tet system as compared with the reverse tet system. Our data show that even under these standardized conditions there was a very high variability in absolute expression levels and regulability between individual clones, and they suggest that homogeneous transcriptional regulation in a cellular population remains a challenge for research in biotechnology.

The association of the src homology 2 (SH2) domain-containing tyrosine phosphatase (SH-PTP2) with the activated epidermal growth factor (EGF) and platelet-derived growth factor receptors, as well as the insulin receptor substrate 1 and growth-factor-receptor-bound protein 2 and its intrinsic tyrosine phosphatase activity suggests an important role for this phosphatase in signal transduction. Previous studies have shown a positive role for SH-PTP2 in growth-factor-mediated cell signaling. We show here that SH-PTP2 can also function to negatively regulate EGF-mediated signal transduction in the human glioma cell line SNB19. We demonstrate this by showing that, in SNB19 cells, which lack the ability to proliferate in response to EGF but retain the ability to bind EGF and also activate the EGF receptor as well as allow for the association of SH-PTP2 with the phosphorylated receptor, stable overexpression of an interfering SH-PTP2 mutant can restore the ability of these cells to proliferate in response to EGF.

We studied the immunohistochemical expression of integrin alpha and beta chains in the normal and neoplastic human brain. Normal astrocytes expressed alpha 2, alpha 3, alpha 6, beta 1, and beta 4 chains in some areas facing major interstitial tissues, but they were consistently negative for the other integrins examined (alpha 4, alpha 5, alpha V, alpha L, alpha M, alpha X, beta 2, beta 3). Neoplastic astrocytes in vivo and in vitro showed increased expression of alpha 3 and beta 1, and some also of alpha 5, alpha V, beta 3, and beta 4. Neoexpression of alpha 4 and reduced levels of beta 4 were detected in glioblastoma vascular proliferations compared with normal endothelial cells. Oligodendroglioma, ependymoma, choroid plexus papilloma, pituitary adenoma, and meningioma cells showed the same integrin pattern as their normal counterparts. Adhesion assays using the astrocytoma cell lines U-138 MG and U-373 MG revealed strong attachment to collagen types I to VI and undulin, which was inhibited by antibodies to beta 1, but not by those to alpha 2, alpha 3, alpha 6, and alpha V. We conclude that astrocytomas show increased levels or neoexpression of various integrins and strong attachment to various extracellular matrix components, which appears to be almost exclusively mediated by beta 1-integrins.