Rich microbial and depolymerising diversity in Antarctic krill gut.

With almost a quadrillion individuals, the Antarctic krill processes five million tons of organic carbon every day during austral summer. This high carbon flux requires a broad range of hydrolytic enzymes to decompose the diverse food-derived biopolymers. While krill itself possesses numerous such enzymes, it is unclear, to what extent the endogenous microbiota contribute to the hydrolytic potential of the gut environment. Here we applied amplicon sequencing, shotgun metagenomics, cultivation, and physiological assays to characterize the krill gut microbiota. The broad bacterial diversity (273 families, 919 genera, and 2,309 species) also included a complex potentially anaerobic sub-community. Plate-based assays with 198 isolated pure cultures revealed widespread capacities to utilize lipids (e.g., tributyrin), followed by proteins (casein) and to a lesser extent by polysaccharides (e.g., alginate and chitin). While most isolates affiliated with the genera Pseudoalteromonas and Psychrobacter, also Rubritalea spp. (Verrucomicrobia) were observed. The krill gut microbiota growing on marine broth agar plates possess 13,012 predicted hydrolyses; 15-fold more than previously predicted from a transcriptome-proteome compendium of krill. Cultivation-independent and -dependent approaches indicated members of the families Flavobacteriaceae and Pseudoalteromonadaceae to dominate the capacities for lipid/protein hydrolysis and to provide a plethora of carbohydrate-active enzymes, sulfatases, and laminarin- or porphyrin-depolymerizing hydrolases. Notably, also the potential to hydrolyze plastics such as polyethylene terephthalate and polylactatide was observed, affiliating mostly with Moraxellaceae. Overall, this study shows extensive microbial diversity in the krill gut, and suggests that the microbiota likely play a significant role in the nutrient acquisition of the krill by enriching its hydrolytic enzyme repertoire.IMPORTANCEThe Antarctic krill (Euphausia superba) is a keystone species of the Antarctic marine food web, connecting the productivity of phyto- and zooplankton with the nutrition of the higher trophic levels. Accordingly, krill significantly contributes to biomass turnover, requiring the decomposition of seasonally varying plankton-derived biopolymers. This study highlights the likely role of the krill gut microbiota in this ecosystem function by revealing the great number of diverse hydrolases that microbes contribute to the krill gut environment. The here resolved repertoire of hydrolytic enzymes could contribute to the overall nutritional resilience of krill and to the general organic matter cycling under changing environmental conditions in the Antarctic sea water. Furthermore, the krill gut microbiome could serve as a valuable resource of cold-adapted hydrolytic enzymes for diverse biotechnological applications.

Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Low-dose naltrexone is used to treat fibromyalgia despite minimal evidence for its efficacy. This trial aimed to investigate whether 12-week treatment with 6 mg low-dose naltrexone was superior to placebo for reducing pain in women with fibromyalgia. METHODS: We did a single-centre, randomised, double-blind, placebo-controlled trial in Denmark. We enrolled women aged 18-64 years who were diagnosed with fibromyalgia. Participants were randomly assigned 1:1 to receive low-dose naltrexone (6 mg) or an identical-appearing placebo, using a computerised algorithm with no stratifications applied. Participants, investigators, outcome assessors, and statistical analysts were all masked to treatment allocation. The primary outcome was change in pain intensity on an 11-point numeric rating scale from baseline to week 12, in the intention-to-treat population. Safety was assessed in participants in the intention-to-treat population who received at least one dose of their allocated intervention. This trial was registered with ClincalTrials.gov (NCT04270877) and EudraCT (2019-000702-30). FINDINGS: We screened 158 participants for eligibility from Jan 6, 2021, to Dec 27, 2022, and 99 patients were randomly assigned to low-dose naltrexone (n=49) or placebo (n=50). The mean age was 50·6 years (SD 8·8), one (1%) of 99 participants was Arctic Asian and 98 (99%) were White. No participants were lost to follow-up. The mean change in pain intensity was -1·3 points (95% CI -1·7 to -0·8) in the low-dose naltrexone group and -0·9 (-1·4 to -0·5) in the placebo group, corresponding to a between-group difference of -0·34 (-0·95 to 0·27; p=0·27, Cohen's d 0·23). Discontinuations due to adverse events were four (8%) of 49 in the low-dose naltrexone group and three (6%) of 50 in the placebo group. 41 (84%) of 49 patients in the low-dose naltrexone group had an adverse event versus 43 (86%) of 50 in the placebo group. One serious adverse event occurred in the placebo group and no deaths occurred. INTERPRETATION: This study did not show that treatment with low-dose naltrexone was superior to placebo in relieving pain. Our results indicate that low-dose naltrexone might improve memory problems associated with fibromyalgia, and we suggest that future trials investigate this further. FUNDING: The Danish Rheumatism Association, Odense University Hospital, Danielsen's Foundation, and the Oak Foundation.

Current Therapeutic Approaches for Graves' Orbitopathy - are Targeted Therapies the Future? / Aktuelle Therapieansätze der endokrinen Orbitopathie ­ sind die zielgerichteten Therapien die Zukunft?

Graves' orbitopathy is an autoimmune disease of the orbit that most frequently occurs with Graves' hyperthyroidism. The occurrence of autoantibodies directed against the TSH receptor (TRAb) is of central importance for the diagnosis and pathogenesis. These autoantibodies are mostly stimulating, and induce uncontrolled hyperthyroidism and tissue remodelling in the orbit and more or less pronounced inflammation. Consequently, patients suffer to a variable extent from periocular swelling, exophthalmos, and fibrosis of the eye muscles and thus restrictive motility impairment with double vision. In recent decades, therapeutic approaches have mainly comprised immunosuppressive treatments and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production. With the recognition that TRAb also activates an important growth factor receptor, IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed. Teprotumumab (an inhibitory IGF1R antibody) has already been approved in the USA and the therapeutic effects are enormous, especially with regard to the reduction of exophthalmos. Side effects are to be considered, especially hyperglycaemia and hearing loss. It is not yet clear whether the autoimmune reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced by anti-IGF1R inhibiting agents. Recurrences after therapy show that the inhibition of antibody development must be included in the therapeutic concept, especially in severe cases.

Rat cytomegalovirus efficiently replicates in dendritic cells and induces changes in their transcriptional profile.

Dendritic cells (DC) play a crucial role in generating and maintaining antiviral immunity. While DC are implicated in the antiviral defense by inducing T cell responses, they can also become infected by Cytomegalovirus (CMV). CMV is not only highly species-specific but also specialized in evading immune protection, and this specialization is in part due to characteristic genes encoded by a given virus. Here, we investigated whether rat CMV can infect XCR1+ DC and if infection of DC alters expression of cell surface markers and migration behavior. We demonstrate that wild-type RCMV and a mutant virus lacking the γ-chemokine ligand xcl1 (Δvxcl1 RCMV) infect splenic rat DC ex vivo and identify viral assembly compartments. Replication-competent RCMV reduced XCR1 and MHCII surface expression. Further, gene expression of infected DC was analyzed by bulk RNA-sequencing (RNA-Seq). RCMV infection reverted a state of DC activation that was induced by DC cultivation. On the functional level, we observed impaired chemotactic activity of infected XCR1+ DC compared to mock-treated cells. We therefore speculate that as a result of RCMV infection, DC exhibit diminished XCR1 expression and are thereby blocked from the lymphocyte crosstalk.

PANGAEA - Data Publisher for Earth & Environmental Science.

The information system PANGAEA provides targeted support for research data management as well as long-term data archiving and publication. PANGAEA is operated as an open access library for archiving, publishing, and distributing georeferenced data from earth and environmental sciences. It focuses on observational and experimental data. Citability, comprehensive metadata descriptions, interoperability of data and metadata, a high degree of structural and semantic harmonization of the data inventory as well as the commitment of the hosting institutions ensures the long-term usability of archived data. PANGAEA is a pioneer of FAIR and open data infrastructures to enable data intensive science and an integral component of national and international science and technology activities. This paper provides an overview of the recent organisational, structural, and technological advancements in developing and operating the information system.

First virological and pathological study of Göttingen Minipigs with Dippity Pig Syndrome (DPS).

Dippity Pig Syndrome (DPS) is a well-known but rare complex of clinical signs affecting minipigs, which has not been thoroughly investigated yet. Clinically affected animals show acute appearance of red, exudating lesions across the spine. The lesions are painful, evidenced by arching of the back (dipping), and the onset of clinical signs is generally sudden. In order to understand the pathogenesis, histological and virological investigations were performed in affected and unaffected Göttingen Minipigs (GöMPs). The following DNA viruses were screened for using PCR-based methods: Porcine cytomegalovirus (PCMV), which is a porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses (PLHV-1, PLHV-2, PLHV-3), porcine circoviruses (PCV1, PCV2, PCV3, PCV4), porcine parvovirus 1 (PPV1), and Torque Teno sus viruses (TTSuV1, TTSuV2). Screening was also performed for integrated porcine endogenous retroviruses (PERV-A, PERV-B, PERV-C) and recombinant PERV-A/C and their expression as well as for the RNA viruses hepatitis E virus (HEV) and SARS-CoV-2. Eight clinically affected and one unaffected GöMPs were analyzed. Additional unaffected minipigs had been analyzed in the past. The analyzed GöMPs contained PERV-A and PERV-B integrated in the genome, which are present in all pigs and PERV-C, which is present in most, but not all pigs. In one affected GöMPs recombinant PERV-A/C was detected in blood. In this animal a very high expression of PERV mRNA was observed. PCMV/PRV was found in three affected animals, PCV1 was found in three animals with DPS and in the unaffected minipig, and PCV3 was detected in two animals with DPS and in the unaffected minipig. Most importantly, in one animal only PLHV-3 was detected. It was found in the affected and unaffected skin, and in other organs. Unfortunately, PLHV-3 could not be studied in all other affected minipigs. None of the other viruses were detected and using electron microscopy, no virus particles were found in the affected skin. No porcine virus RNA with exception of PERV and astrovirus RNA were detected in the affected skin by next generation sequencing. This data identified some virus infections in GöMPs with DPS and assign a special role to PLHV-3. Since PCMV/PRV, PCV1, PCV3 and PLHV-3 were also found in unaffected animals, a multifactorial cause of DPS is suggested. However, elimination of the viruses from GöMPs may prevent DPS.

[Graves' orbitopathy: Current concepts for medical treatment]. / Endokrine Orbitopathie: Aktueller Stand der medikamentösen Therapie.

BACKGROUND: The therapy of severe manifestations of Graves' orbitopathy (GO) is still a challenge and requires good interdisciplinary cooperation. It is especially important to use stage-adapted anti-inflammatory therapy to avoid irreversible damage. MATERIAL AND METHODS: Discussion of the latest results of multicentre randomised therapy studies on anti-inflammatory treatments for Graves' orbitopathy, as well as new therapeutic concepts. RESULTS: Mild cases of GO can be treated with only selenium supplementation and a watchful waiting strategy. In the moderate-to-severe active form of GO, primary therapy consists of i. v. steroids (cumulative 4-5 g) in combination with orbital irradiation in patients with impaired motility. In patients with insufficient therapeutic response after 6 weeks, treatment should be switched to other immunosuppressive agents. In severe sight-threatening disease, bony orbital decompression is usually necessary. As basic research has improved our understanding of the underlying pathophysiology of GO, it has been possible to develop targeted therapies for GO. Teprotumumab, an IGF-1 receptor antibody, was effective in treating GO patients in a phase III trial and should soon be awarded approval for Europe. CONCLUSION: The current therapy concept for Graves' orbitopathy is as follows: first anti-inflammatory therapy then surgical correction of the permanent defects. This may soon be modified, due to the use of targeted therapies.

Participatory research: a Priority Setting Partnership for chronic musculoskeletal pain in Denmark.

OBJECTIVES: Patient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to establish research priorities for chronic musculoskeletal (MSK) pain by engaging with people living with chronic MSK pain, relatives to people living with chronic MSK pain, healthcare professionals (HCP), and researchers working with chronic MSK pain. METHODS: This JLA-PSP included a nation-wide survey in Denmark, an interim prioritisation, and an online consensus building workshop. The information gained from this was the basis for developing the final list of specific research priorities within chronic MSK pain. RESULTS: In the initial survey, 1010 respondents (91% people living with chronic MSK pain/relatives, 9% HCPs/researchers) submitted 3121 potential questions. These were summarised into 19 main themes and 36 sub-themes. In the interim prioritisation exercise, 51% people living with pain/relatives and 49% HCPs/researchers reduced the list to 33 research questions prior to the final priority setting workshop. 23 participants attended the online workshop (12 people/relatives, 10 HCPs, and 1 researcher) who reached consensus for the most important research priorities after two rounds of discussion of each question. CONCLUSIONS: This study identified several specific research questions generated by people living with chronic MSK pain, relatives, HCPs, and researchers. The stakeholders proposed prioritization of the healthcare system's ability to support patients, focus on developing coherent pathways between sectors and education for both patients and HCP. These research questions can form the basis for future studies, funders, and be used to align research with end-users' priorities.

Factors influencing the immune response over 15 months after SARS-CoV-2 infection: A longitudinal population-wide study in the Faroe Islands.

BACKGROUND: The durability of SARS-CoV-2 antibody response and the resulting immunity to COVID-19 is unclear. OBJECTIVES: To investigate long-term humoral immunity to SARS-CoV-2. METHODS: In this nationwide, longitudinal study, we determined antibody response in 411 patients aged 0-93 years from two waves of infections (March to December 2020) contributing 1063 blood samples. Each individual had blood drawn on 4-5 occasions 1-15 months after disease onset. We measured total anti-SARS-CoV-2 receptor-binding domain (RBD) antibody using a qualitative RBD sandwich ELISA, IgM, IgG and IgA levels using an quantitative in-house ELISA-based assay  and neutralizing antibodies (NAbs) using an in-house ELISA-based pseudoneutralizing assay. IgG subclasses were analyzed in a subset of samples by ELISA-based assay. We used nonlinear models to study the durability of SARS-CoV-2 antibody responses and its influence over time. RESULTS: After 15 months, 94% still had detectable circulating antibodies, mainly the IgG isotype, and 92% had detectable NAbs. The distribution of IgG antibodies varied significantly over time, characterized by a biphasic pattern with an initial decline followed by a plateau after approximately 7 months. However, the NAbs remained relatively stable throughout the period. The strength of the antibody response was influenced by smoking and hospitalization, with lower IgG levels in smokers and higher levels in hospitalized individuals. Antibody stability over time was mainly associated with male sex and older age with higher initial levels but more marked decrease. CONCLUSIONS: The humoral immune response to SARS-CoV-2 infection varies depending on behavioral factors and disease severity, and antibody stability over 15 months was associated with sex and age.

The left upper lobe challenge in video-assisted thoracoscopic surgery-use of a composite score to improve the assessment of simulated lobectomy.

AIM: The aim of this study is to develop a reliable composite score based on simulator metrics to assess competency in virtual reality video-assisted thoracoscopic surgery lobectomy and explore the benefits of combining it with expert rater assessments. METHODS: Standardized objective assessments (time, bleeding, economy of movement) and subjective expert rater assessments from 2 previous studies were combined. A linear mixed model including experience level, lobe and the number of previous simulated procedures was applied for the repeated measurements. Reliability for each of the 4 assessments was calculated using Cronbach's alpha. The Nelder-Mead numerical optimization algorithm was used for optimal weighting of scores. A pass-fail standard for the composite score was determined using the contrasting groups' method. RESULTS: In total, 123 virtual reality video-assisted thoracoscopic surgery lobectomies were included. Across the 4 different assessments, there were significant effects (P < 0.01) of experience, lobe, and simulator experience, but not for simulator attempts on bleeding (P = 0.98). The left upper lobe was significantly more difficult compared to other lobes (P = 0.02). A maximum reliability of 0.92 could be achieved by combining the standardized simulator metrics with standardized expert rater scores. The pass/fail level for the composite score when including 1 expert rater was 0.33. CONCLUSIONS: Combining simulator metrics with 1 or 2 raters increases reliability and can serve as a more objective method for assessing surgical trainees. The composite score may be used to implement a standardized and feasible simulation-based mastery training program in video-assisted thoracoscopic surgery lobectomy.

Transcriptome-proteome compendium of the Antarctic krill (Euphausia superba): Metabolic potential and repertoire of hydrolytic enzymes.

The Antarctic krill (Euphausia superba Dana) is a keystone species in the Southern Ocean that uses an arsenal of hydrolases for biomacromolecule decomposition to effectively digest its omnivorous diet. The present study builds on a hybrid-assembled transcriptome (13,671 ORFs) combined with comprehensive proteome profiling. The analysis of individual krill compartments allowed detection of significantly more different proteins compared to that of the entire animal (1464 vs. 294 proteins). The nearby krill sampling stations in the Bransfield Strait (Antarctic Peninsula) yielded rather uniform proteome datasets. Proteins related to energy production and lipid degradation were particularly abundant in the abdomen, agreeing with the high energy demand of muscle tissue. A total of 378 different biomacromolecule hydrolysing enzymes were detected, including 250 proteases, 99 CAZymes, 14 nucleases and 15 lipases. The large repertoire in proteases is in accord with the protein-rich diet affiliated with E. superba's omnivorous lifestyle and complex biology. The richness in chitin-degrading enzymes allows not only digestion of zooplankton diet, but also the utilisation of the discharged exoskeleton after moulting.

Clinical characteristics of the Omicron variant - results from a Nationwide Symptoms Survey in the Faroe Islands.

OBJECTIVES: Omicron appears to lead to a milder illness for patients compared with previous COVID-19 variants. However, not all infected with Omicron would describe their illness as mild. In this study, we investigate the experienced severity and symptoms of the Omicron variant. METHODS: We conducted a nationwide cross-sectional study, including 5036 individuals of all ages, consisting of reverse transcription-polymerase chain reaction confirmed SARS-CoV-2 cases from 1 January to 31 January 2022 (n = 4506) and a control group without SARS-COV-2 infection in December 2021 or January 2022 (n = 530). Omicron was dominant during this period. Cases were asked about their acute symptoms and answered a web-based questionnaire 10-30 days after their positive test while controls were asked about symptoms during the past week. RESULTS: Among cases, 97% reported at least one symptom during the acute phase compared with 79% of controls. Just over half the cases assessed their illness as asymptomatic or mild, whereas 46% assessed their illness as moderate or severe. Children reported fewer symptoms and less severe illnesses than adults (P <0.001). The largest risk differences (RDs) between adult cases and controls due to symptoms were observed for fever (RD = 60.6%, confidence interval [CI] 57.4-63.6), fatigue (RD = 49.6%, CI 44.1-54.7), and chills (RD = 48.8%, CI 43.8-53.2). CONCLUSION: Most of those infected with Omicron experience symptoms, and the Omicron variant appears to lead to less severe disease. However, this does not mean that all the infected experience an Omicron infection as mild. The unprecedented rate of Omicron infections worldwide leads to urgent questions about the rate of long COVID after Omicron infections.

Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity.

Intestinal microbiota dysbiosis can initiate overgrowth of commensal Candida species - a major predisposing factor for disseminated candidiasis. Commensal bacteria such as Lactobacillus rhamnosus can antagonize Candida albicans pathogenicity. Here, we investigate the interplay between C. albicans, L. rhamnosus, and intestinal epithelial cells by integrating transcriptional and metabolic profiling, and reverse genetics. Untargeted metabolomics and in silico modelling indicate that intestinal epithelial cells foster bacterial growth metabolically, leading to bacterial production of antivirulence compounds. In addition, bacterial growth modifies the metabolic environment, including removal of C. albicans' favoured nutrient sources. This is accompanied by transcriptional and metabolic changes in C. albicans, including altered expression of virulence-related genes. Our results indicate that intestinal colonization with bacteria can antagonize C. albicans by reshaping the metabolic environment, forcing metabolic adaptations that reduce fungal pathogenicity.

Assessing VATS competence based on simulated lobectomies of all five lung lobes.

OBJECTIVES: To determine the number of procedures and expert raters necessary to provide a reliable assessment of competence in Video-Assisted Thoracoscopic Surgery (VATS) lobectomy. METHODS: Three randomly selected VATS lobectomies were performed on a virtual reality simulator by participants with varying experience in VATS. Video recordings of the procedures were independently rated by three blinded VATS experts using a modified VATS lobectomy assessment tool (VATSAT). The unitary framework of validity was used to describe validity evidence, and generalizability theory was used to explore the reliability of different assessment options. RESULTS: Forty-one participants (22 novices, 10 intermediates, and 9 experienced) performed a total of 123 lobectomies. Internal consistency reliability, inter-rater reliability, and test-retest reliability were 0.94, 0.85, and 0.90, respectively. Generalizability theory found that a minimum of two procedures and four raters or three procedures and three raters were needed to ensure the overall reliability of 0.8. ANOVA showed significant differences in test scores between the three groups (P < 0.001). A pass/fail level of 19 out of 25 points was established using the contrasting groups' standard setting method, leaving one false positive (one novice passed) and zero false negatives (all experienced passed). CONCLUSION: We demonstrated validity evidence for a VR simulator test with different lung lobes, and a credible pass/fail level was identified. Our results can be used to implement a standardized mastery learning training program for trainees in VATS lobectomies that ensures that everyone reaches basic competency before performing supervised operations on patients.

Ultrastructural examination of lung "cryobiopsies" from a series of fatal COVID-19 cases hardly revealed infected cells.

Ultrastructural analysis of autopsy samples from COVID-19 patients usually suffers from significant structural impairment possibly caused by the rather long latency between death of the patient and an appropriate sample fixation. To improve structural preservation of the tissue, we obtained samples from ventilated patients using a trans-bronchial "cryobiopsy" within 30 min after their death and fixed them immediately for electron microscopy. Samples of six COVID-19 patients with a documented histopathology were systematically investigated by thin section electron microscopy. The different samples and areas inspected revealed the ultrastructural correlates of the different phases of diffuse alveolar damage, including detachment of the alveolar epithelium, hyperplasia of type 2 cells, exudates, and accumulation of extracellular material, such as the hyaline membranes and fibrin. Macrophages and neutrophilic granulocytes were regularly detected. Structural integrity of endothelium was intact in regions where the alveolar epithelium was already detached. Aggregates of erythrocytes, leukocytes with fibrin, and thrombocytes were not observed. Coronavirus particles were only found in and around very few cells in one of the six patient samples. The type and origin of these cells could not be assessed although the overall structural preservation of the samples allowed the identification of pulmonary cell types. Hence, the observed alveolar damage is not associated with virus presence or structural impairment due to ongoing replication at later stages of the disease in fatal cases, which implies that the lung damage in these patients is at least propagated by alternative mechanisms, perhaps, an inappropriate immune or stress response.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

INTRODUCTION: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. METHODS AND ANALYSIS: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. ETHICS AND DISSEMINATION: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www. CLINICALTRIALS: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: NCT04095676.

Omicron Outbreak at a Private Gathering in the Faroe Islands, Infecting 21 of 33 Triple-Vaccinated Healthcare Workers.

There are concerns that the severe acute respiratory syndrome coronavirus 2 Omicron variant evades immune responses due to an unusually high number of mutations on the spike protein. Here, we report a superspreading event of Omicron infections among 21 of 33 triple-vaccinated healthcare workers who attended a private gathering.

Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs.

BACKGROUND: Porcine endogenous retroviruses (PERVs) can infect human cells and pose a risk for xenotransplantation when pig cells, tissues or organs are transplanted to human recipients. Xenotransplantation holds great promise to overcome the shortage of human donor organs after solving the problems of rejection, functionality and virus safety. We recently described the transmission of a human-tropic recombinant PERV-A/C, designated PERV-F, from peripheral blood mononuclear cells (PBMCs) of a Göttingen Minipig (GöMP) to human 293 cells (Krüger et al., in Viruses 12(1):38, 2019). The goal of this study was to characterize PERV-F in more detail and to analyze the probability of virus isolation from other animals. METHODS: The recombination site in the envelope (env) gene, the long terminal repeats (LTR), the proteins and the morphology of the recombinant PERV-F were characterized by polymerase chain reaction (PCR), sequencing, Western blot analysis, immunofluorescence, and transmissible electron microscopy. Mitogen-stimulated PBMCs from 47 additional pigs, including 17 new GöMP, were co-cultured with highly susceptible human 293 T cells, and the PERV-A/C prevalence and PERV transmission was analyzed by PCR. RESULTS: PERV-F, isolated from a GöMP, is an infectious human-tropic PERV-A/C virus with a novel type of recombination in the env gene. The length of the LTR of PERV-F increased after passaging on human cells. In a few minipigs, but not in German landrace pigs, PERV-A/C were found. There was no transmission of human-tropic PERV-A/C from additional 47 pigs, including 17 GöMP, to human cells. CONCLUSION: These data show that human-tropic recombinant PERV-A/C proviruses can only be found in a very small number of minipigs, but not in other pigs, and that their isolation as infectious virus able to replicate on human cells is an extremely rare event, even when using highly susceptible 293 cells.

Effects of shared mental models in teams performing video-assisted thoracoscopic surgery lobectomy.

BACKGROUND: Important non-technical skills enable operating teams to establish shared mental models (SMMs). The importance of SMMs in regards to surgical performance and peri-operative outcomes remains to be investigated. The aim of this study was to explore whether shared mental models (SMMs) of team resources and the current situation, respectively, were predictive of technical skills, duration of surgery, and amount of intra-operative bleeding in video-assisted thoracoscopic surgery (VATS). METHODS: A prospective multi-center observational study was conducted at four tertiary academic hospitals during VATS lobectomy procedures. Data included pre-operative and post-operative questionnaires answered by each of the six team members to measure the SMMs; thoracoscopic video recordings assessed using the previously validated VATS lobectomy Assessment Tool (VATSAT); surgery-related time stamps; and amount (volume) of intra-operative bleeding. Linear regression analyses were conducted to adjust for confounders. RESULTS: Fifty-eight lobectomy procedures were included. Median (interquartile range) VATSAT score was 33.3 (scale 8-40) duration of surgery 101 min (88-123), and amount of intra-operative bleeding 100 ml (20-150). The mean (± SD) of teams' SMMs of the current situation was 20 (± 5). They were not predictive of the surgeons' technical skills, but every one point increase in SMM score significantly predicted a 1 min 52 s decrease in duration of surgery and an 11% decrease in amount of bleeding. The SMMs of team resources were not predictive of any outcomes. CONCLUSION: VATS teams' superior SMMs of the current situation related to significantly shorter duration of surgery and decreased intra-operative bleeding, indicating an effect on team performance and patient care. TRIAL REGISTRATION: NCT02999113 at http://www. CLINICALTRIALS: gov .

[Graves' orbitopathy]. / Endokrine Orbitopathie.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune orbital disease which is mostly associated with Graves' disease and requires good interdisciplinary cooperation. To minimize irreversible damages a stage-adapted anti-inflammatory therapy is of great importance. MATERIAL AND METHODS: Discussion of the latest results of new findings of the pathogenesis, randomized controlled trials on anti-inflammatory treatments for Graves' orbitopathy and novel therapeutic concepts. RESULTS: In all patients with GO achieving euthyroidism, as well as cessation of smoking is very important to avoid prolongated diseases. Mild cases of GO can be treated with selenium supplementation and artificial tears. The moderate-to-severe, active form of GO requires primarily i. v. steroids in combination with orbital irradiation in case of impaired motility. In patients with insufficient therapeutic response after 6 weeks, treatment should be switched to other immunosuppressive agents. In severe sight-threatening cases even high-dose i. v. steroid treatments are often ineffective and bony orbital decompression is necessary. As latest research data have improved our understanding of the pathophysiology of GO, targeted therapies have been developed for GO. Teprotumumab, an IGF-1 receptor antibody, was shown effective in treating GO patients in a phase III trial and should soon be awarded approval for Europe. Inactive patients, who suffer from disturbing exophthalmos should be also treated with bony decompression before eye muscle or lid surgery. CONCLUSION: The current concept for Graves' orbitopathy is as follows: first anti-inflammatory therapy then surgical correction of the permanent defects. This might be modified in the future, due to the promising effects of targeted therapies.