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Additional file 1. Figures.

Additional file 2. Questionnaire of the online survey among health-care staff and extract of the questionnaire for caregivers (English translation).

Additional file 1. SARS-CoV-2 diagnostic test procedures.

Additional file 2. Additional tables.

Additional file 3. Results of survey on the perception of infection control measures by hospital staff, stratified by profession.

Introduction: Head and neck cancer patients often suffer from physical and cognitive impairments after cancer treatment. During rehabilitation, exercise therapy can improve physical function and quality of life (QoL). Surveys demonstrated patients’ preference for home training with low- to moderate-intensity. This study was conducted in order to develope a suitable home-based training program. Therefore, the feasibility and effects of a low- to moderate-intensity exercise intervention on physical functions and QoL were evaluated. Methods: Training was conducted as supervised group training and consisted of mobilization, coordination, resistance, stretching, and relaxation exercises. The intervention lasted 12 weeks with 2 training sessions per week. Feasibility, attendance rate, physical function (eg, range of motion, 6-minute walk test [6MWT]), and QoL (eg, EORTC QLQ-30) were analyzed. Results: Ten out of 12 participants completed the intervention (83%) with an average attendance rate of 83%. Participants showed significant improvements in selected physical functions. For example, head rotation increased by 11.2° (P = .042), walking distance in the 6MWT increased by an average of 43.3 m (P = .010), and the global QoL scale improved by 8.2 points (P = .059). Additionally, there were positive changes in the physical function scale (P = .008), cognitive function scale (P = .015), and social function scale (P = .031) of the EORTC QLQ-30. Conclusion: Data indicate that the exercise program was feasible and had positive effects on physical function and QoL. Future research will analyze the effects of a home-based exercise program on physical function and QoL in a large-scale study.

We previously showed that in mice infected with Leishmania major type I interferons (IFNs) initiate the innate immune response to the parasite at day 1 and 2 of infection. Here, we investigated which type I IFN subtypes are expressed during the first 8 weeks of L. major infection and whether type I IFNs are essential for a protective immune response and clinical cure of the disease. In self-healing C57BL/6 mice infected with a high dose of L. major, IFN-α4, IFN-α5, IFN-α11, IFN-α13, and IFN-β mRNA were most prominently regulated during the course of infection. In C57BL/6 mice deficient for IFN-β or the IFN-α/β-receptor chain 1 (IFNAR1), development of skin lesions and parasite loads in skin, draining lymph node, and spleen was indistinguishable from wild-type (WT) mice. In line with the clinical findings, C57BL/6 IFN-β−/−, IFNAR1−/−, and WT mice exhibited similar mRNA expression levels of IFN-γ, interleukin (IL)-4, IL-12, IL-13, inducible nitric oxide synthase, and arginase 1 during the acute and late phase of the infection. Also, myeloid dendritic cells from WT and IFNAR1−/− mice produced comparable amounts of IL-12p40/p70 protein upon exposure to L. major in vitro. In non-healing BALB/c WT mice, the mRNAs of IFN-α subtypes (α2, α4, α5, α6, and α9) were rapidly induced after high-dose L. major infection. However, genetic deletion of IFNAR1 or IFN-β did not alter the progressive course of infection seen in WT BALB/c mice. Finally, we tested whether type I IFNs and/or IL-12 are required for the prophylactic effect of CpG-oligodesoxynucleotides (ODN) in BALB/c mice. Local and systemic administration of CpG-ODN 1668 protected WT and IFN-β−/− mice equally well from progressive leishmaniasis. By contrast, the protective effect of CpG-ODN 1668 was lost in BALB/c IFNAR1−/− (despite a sustained suppression of IL-4) and in BALB/c IL-12p35−/− mice. From these data, we conclude that IFN-β and IFNAR1 signaling are dispensable for a curative immune response to L. major in C57BL/6 mice and irrelevant for disease development in BALB/c mice, whereas IL-12 and IFN-α subtypes are essential for the disease prevention by CpG-ODNs in this mouse strain.

16S rRNA based maximum-likelihood tree of the P. putida group isolates and reference strains. The numbers displayed at the nodes are bootstrap values. The scale bar represents the expected number of changes per site. (PDF 456Â kb)

Overview of P. putida assembly statistics and genome coverage based on the assembly obtained for the a5 assembler. (DOCX 17Â kb)

Overview of predicted plasmid harbouring a bla VIM gene and the characteristics of the genetic bla VIM environment. (DOCX 31Â kb)

Core genome maximum-likelihood phylogeny of 17 blaVIM-2 positive P. aeruginosa strains isolated from patients (n = 7, “P” as first letter) and water-related environmental sources (n = 10, “E” as first letter). All isolates are genetically highly similar. An outgroup strain (blaIMP-8 positive P. aeruginosa [29]) was introduced to ensure a proper visualisation of the strains’ sequence similarity and relatedness. The scale bar represents the expected number of changes per site. *P21 was also colonized with two different P. putida strains P21A and P21B. (PDF 295 kb)

Workflow of the study design and strain inclusion criteria. (PDF 151Â kb)

Overview of P. aeruginosa assembly statistics and genome coverage based on the assembly obtained for the a5 assembler. (DOCX 14Â kb)

Summary of epidemiological data of the P. putida isolates from the different NGS clusters. (DOCX 18Â kb)

Overview of the closest related type strains based on the average nucleotide identity (ANI). (DOCX 16Â kb)

Summary An intracellular approach for monitoring protein production in Staphylococcus aureus is described. mCherry, fused to the dodecapeptide Tip, was capable of inducing tetracycline repressor (TetR). Time‐ and concentration‐dependent production of mCherry could be correlated to TetR‐controlled GFPmut2 activity. This approach can potentially be extended to native S. aureus proteins.

The early systemic production of interferon (IFN)-αβ is an essential component of the antiviral host defense mechanisms, but is also thought to contribute to the toxic side effects accompanying gene therapy with adenoviral vectors. Here we investigated the IFN-αβ response to human adenoviruses (Ads) in mice. By comparing the responses of normal, myeloid (m)DC- and plasmacytoid (p)DC-depleted mice and by measuring IFN-αβ mRNA expression in different organs and cells types, we show that in vivo, Ads elicit strong and rapid IFN-αβ production, almost exclusively in splenic mDCs. Using knockout mice, various strains of Ads (wild type, mutant and UV-inactivated) and MAP kinase inhibitors, we demonstrate that the Ad-induced IFN-αβ response does not require Toll-like receptors (TLR), known cytosolic sensors of RNA (RIG-I/MDA-5) and DNA (DAI) recognition and interferon regulatory factor (IRF)-3, but is dependent on viral endosomal escape, signaling via the MAP kinase SAPK/JNK and IRF-7. Furthermore, we show that Ads induce IFN-αβ and IL-6 in vivo by distinct pathways and confirm that IFN-αβ positively regulates the IL-6 response. Finally, by measuring TNF-α responses to LPS in Ad-infected wild type and IFN-αβR−/− mice, we show that IFN-αβ is the key mediator of Ad-induced hypersensitivity to LPS. These findings indicate that, like endosomal TLR signaling in pDCs, TLR-independent virus recognition in splenic mDCs can also produce a robust early IFN-αβ response, which is responsible for the bulk of IFN-αβ production induced by adenovirus in vivo. The signaling requirements are different from known TLR-dependent or cytosolic IFN-αβ induction mechanisms and suggest a novel cytosolic viral induction pathway. The hypersensitivity to components of the microbial flora and invading pathogens may in part explain the toxic side effects of adenoviral gene therapy and contribute to the pathogenesis of adenoviral disease., Author Summary Adenoviruses (Ads) are important pathogens and promising vectors for gene therapy applications. In the course of adenoviral infections innate immune responses are activated, which can be beneficial for the antiviral host defense but also detrimental if activated in a deregulated manner. Type I IFNs are crucial for the innate immune control of various viral infections in the mammalian host. So far, the early, systemic release of IFN-αβ during viral infections has been attributed to specialized immune cells, the plasmacytoid dendritic cells. Here, in a mouse infection model, we show that wild type Ads, as well as adenoviral vectors, elicit rapid IFN-αβ production almost exclusively in another cell population, the splenic myeloid dendritic cells. This IFN-αβ storm depends on viral escape from endosomes to the cytosol and the requirements of the response are suggestive of a novel viral induction pathway. Furthermore, we show that virus induced IFN-αβ is the key mediator of Ad-induced hypersensitivity to the cytokine-inducing and toxic activity of lipopolysaccharide, a common constituent of Gram-negative bacteria. Since these bacteria comprise several commensals and pathogens, enhanced susceptibility to lipopolysaccharide may contribute to toxic reactions observed during adenoviral gene therapy and to the clinical symptoms of adenoviral diseases.