[Consensus recommendations on regional interdisciplinary standardization of MRI diagnostics for multiple sclerosis in the metropolitan area of Essen]. / Konsensusempfehlungen zur regionalen fächerübergreifenden Standardisierung der MRT-Diagnostik bei Multipler Sklerose im Großraum Essen.

Magnetic resonance imaging (MRI) is of exceptional importance in the diagnostics and monitoring of multiple sclerosis (MS); however, a close interdisciplinary cooperation between neurologists in private practice, (neuro)radiological practices, hospitals or specialized MS centers is only rarely established. In particular, there is a lack of standardized MRI protocols for image acquisition as well as established quality parameters, which guarantee the comparability of MRI records; however, this is a fundamental prerequisite for an effective application of MRI in the treatment of MS patients, e.g., for making the diagnosis or treatment monitoring. To address these challenges a group of neurologists and (neuro)radiologists developed a consensus proposal for standardization of image acquisition, interpretation and transmission of results and for improvement in interdisciplinary cooperation. This pilot project in the metropolitan area of Essen used a modified Delphi process and was based on the most up to date scientific knowledge. The recommendation takes the medical, economic, temporal and practical aspects of MRI in MS into consideration. The model of interdisciplinary cooperation between radiologists and neurologists with the aim of a regional standardization of MRI could serve as an example for other regions of Germany in order to optimize MRI for MS.

COVID-19-Related Burden and Risk Perception in Individuals with Chronic Inflammatory Demyelinating Polyneuropathy and Multifocal Motor Neuropathy: A Cross-Sectional Study.

INTRODUCTION: This study investigated the mental health burden of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN) during the COVID-19 pandemic in comparison to matched healthy controls. METHODS: The cross-sectional study included 59 patients with a diagnosis of either CIDP or MMN and 59 propensity score matched healthy controls. All participants completed a survey including demographics, distress (distress thermometer), depressive symptoms (PHQ-2), generalized anxiety (GAD-7), COVID-19-related fear, and risk perception. Additionally, patients with CIDP or MMN were asked about the frequency and type of infections since treatment initiation. RESULTS: Patients with either CIDP or MMN reported experiencing reduced frequency or no differences in infection frequency since immune medication was initiated. Regarding COVID-19, patients with CIDP or MMN rated their risk of infection similar to healthy controls, while they expected a higher probability of the occurrence of symptoms, severe course, and dying of COVID-19. They reported increased depressive symptoms, generalized anxiety, and COVID-19-related fear in comparison to healthy controls. CONCLUSION: Despite their personal experience of reduced frequency of infection since immune medication was initiated, patients with CIDP or MMN reported increased risk perception and prevalence of depressive symptoms, generalized anxiety, and COVID-19-related fear in comparison to healthy controls. This highlights the need for evidence-driven strategies to protect the mental health of this vulnerable group.

Teriflunomide provides protective properties after oxygen-glucose-deprivation in hippocampal and cerebellar slice cultures.

One of the major challenges in emergency medicine is out-of-hospital cardiac arrest (OHCA). Every year, about 53-62/100 000 people worldwide suffer an out-of-hospital cardiac arrest with serious consequences, whereas persistent brain injury is a major cause of morbidity and mortality of those surviving a cardiac arrest. Today, only few and insufficient strategies are known to limit neurological damage of ischemia and reperfusion injury. The aim of the present study was to investigate whether teriflunomide, an approved drug for treatment of relapsing-remitting-multiple-sclerosis, exerts a protective effect on brain cells in an in vitro model of ischemia. Therefore, organotypic slice cultures from rat hippocampus and cerebellum were exposed to oxygen-glucose-deprivation and subsequently treated with teriflunomide. The administration of teriflunomide in the reperfusion time on both hippocampal and cerebellar slice cultures significantly decreased the amount of detectable propidium iodide signal compared with an untreated culture, indicating that more cells survive after oxygen-glucose-deprivation. However, hippocampal slice cultures showed a higher vulnerability to ischemic conditions and a more sensitive response to teriflunomide compared with cerebellar slice cultures. Our study suggests that teriflunomide, applied as a post-treatment after an oxygen-glucose-deprivation, has a protective effect on hippocampal and cerebellar cells in organotypic slice cultures of rats. All procedures were conducted under established standards of the German federal state of North Rhine Westphalia, in accordance with the European Communities Council Directive 2010/63/EU on the protection of animals used for scientific purposes.

Ectopic expression of Snord115 in choroid plexus interferes with editing but not splicing of 5-Ht2c receptor pre-mRNA in mice.

Serotonin 5-HT2C receptor is a G-protein coupled excitatory receptor that regulates several biochemical pathways and has been implicated in obesity, mental state, sleep cycles, autism, neuropsychiatric disorders and neurodegenerative diseases. The activity of 5-HT2CR is regulated via alternative splicing and A to I editing of exon Vb of its pre-mRNA. Snord115 is a small nucleolar RNA that is expressed in mouse neurons and displays an 18-nucleotide base complementary to exon Vb of 5-HT2CR pre-mRNA. For almost two decades this putative guide element of Snord115 has wandered like a ghost through the literature in attempts to elucidate the biological significance of this complementarity. In mice, Snord115 is expressed in neurons and absent in the choroid plexus where, in contrast, 5-Ht2cr mRNA is highly abundant. Here we report the analysis of 5-Ht2cr pre-mRNA posttranscriptional processing via RNA deep sequencing in a mouse model that ectopically expresses Snord115 in the choroid plexus. In contrast to previous reports, our analysis demonstrated that Snord115 does not control alternative splicing of 5-Ht2cr pre-mRNA in vivo. We identified a modest, yet statistically significant reduction of 5-Ht2cr pre-mRNA A to I editing at the major A, B, C and D sites. We suggest that Snord115 and exon Vb of 5Ht2cr pre-mRNA form a double-stranded structure that is subject to ADAR-mediated A to I editing. To the best of our knowledge, this is the first comprehensive Snord115 gain-of-function analysis based on in vivo mouse models.

Capable and credible? Challenging nutrition science.

Nutrition science has enriched our understanding of how to stay healthy by producing valuable knowledge about the interaction of nutrients, food, and the human body. Nutrition science also has raised societal awareness about the links between food consumption and well-being, and provided the basis for food regulations and dietary guidelines. Its collaborative and interdisciplinary research has accomplished much, scientifically and socially. Despite this, nutrition science appears to be in crisis and is currently confronted with a public reluctance to trust nutritional insights. Though deflating trust is a general phenomenon surrounding the scientific community, its impact on nutrition science is particularly strong because of the crucial role of nutrition in everyone's daily life. We, a Dutch collective of nutritionists, medical doctors, philosophers and sociologists of science ( http://www.nutritionintransition.nl ), have diagnosed that nutrition science is meeting inherent boundaries. This hampers conceptual and methodological progress and the translation of novel insights into societal benefit and trust. In other words, nutrition science is facing limitations to its capability and credibility, impeding its societal value. We take up the challenge to halt the threatening erosion of nutrition science's capability and credibility, and explore a way forward. We analyse limitations to capability and credibility, then argue that nutrition science is caught in a vicious circle, and end by offering some suggestions to transcend the limitations and escape the current deadlock. We invite nutritional experts as well as scholars from adjacent disciplines to engage in the discussion.

Lifestyle Vaccines and Public Health: Exploring Policy Options for a Vaccine to Stop Smoking.

Experimental vaccines are being developed for the treatment of 'unhealthy lifestyles' and associated chronic illnesses. Policymakers and other stakeholders will have to deal with the ethical issues that this innovation path raises: are there morally justified reasons to integrate these innovative biotechnologies in future health policies? Should public money be invested in further research? Focusing on the case of an experimental nicotine vaccine, this article explores the ethical aspects of 'lifestyle vaccines' for public health. Based on findings from a qualitative study into a vaccine for smoking cessation, the article articulates possible value conflicts related to nicotine vaccination as an intervention in tobacco control. The 'vaccinization' of lifestyle disease piggybacks on the achievements of classic vaccines. Contrary to expectations of simplicity and success, quitting smoking with a vaccine requires a complex supportive network. Social justice and public trust may become important ethical challenges when deciding whether to use further public funds for research or whether to implement these innovative vaccines in the future.

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice.

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5'HPRT-LoxP-Neo(R) cassette (5'LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScr(p-/m5'LoxP)), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScr(p-/m5'LoxP) mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScr(p-/m5'LoxP) mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases.

Vaccination against smoking: an annotated agenda for debate. A review of scientific journals, 2001-13.

BACKGROUND AND AIMS: The ongoing development of novel nicotine vaccines makes it urgent to identify the normative questions around this innovative health technology against smoking. METHODS: A qualitative thematic analysis of peer-reviewed papers on nicotine vaccination published between 2001 and 2013. RESULTS: In the scientific discourse, nicotine vaccination is presented in a neurobiological frame as a potent concept for (long-term) smoking cessation. Nicotine vaccination is also considered a hypothetical strategy to prevent nicotine addiction in minors. Ethical assessments are conducted for the use of nicotine vaccination in public health and clinical medicine. Whereas vaccination for primary prevention is usually associated with public health, the hypothetical case of nicotine prevention in minors is also assessed for individualized protection. Therapeutic and preventive applications are given uneven attention: the classic goal of vaccination (primary prevention in minors) receives methodical consideration and invokes lively debate. The unprecedented use of vaccination, namely smoking cessation, is left largely unattended in the ethical analyses. CONCLUSIONS: While health innovations such as nicotine vaccination need broad reflection to guide decisions on their further development and possible future implementations, only a small part of the ethical and social issues of this innovative technology has been discussed. For a debate to come into existence, a 'neurobio-psycho-socio-cultural' frame of smoking and quitting appears fruitful. Important topics for reflection are the human activities and social processes in a vaccine-supported quit attempt, next to respect for individuals, possible harms and questions of (global) justice and research ethics.

Constructing a trial as a personal lifestyle change project: participants' experiences in a clinical study for nicotine vaccination.

The purpose of this study was to gain insight into the experiences and dynamics of the involvement of research participants in a randomized clinical trial for nicotine vaccination. Participants received an experimental nicotine vaccine or a placebo, in addition to quit smoking medication and counseling. The longitudinal design of this qualitative study allowed us to follow people from their first visit to the trial location until the unblinding of their treatment with either verum or placebo vaccine. The empirical data consisted of 49 semi-structured, in-depth interviews, field notes and memos, and trial documents collected in the Netherlands between 2010 and 2012. Participants' expectations and experiences of the innovative nicotine vaccine were characterized by ambivalence: Although they complied with the research design, throughout the study they tinkered with discourses, objects, and activities to make them serve their individual goals. They made the concepts of nicotine vaccination and placebo treatment meaningful for quitting, reshaped the meaning of research tests and obligatory visits to serve their own personal goals, and introduced a new element into the trial by creating space to discuss problems that might endanger the quit attempt. In short, the participants constructed the clinical study for nicotine vaccination as their own personal lifestyle change project.