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Respiratory viruses are known to be the most frequent causative mediators of lung infections in humans, bearing significant impact on the host cell signaling machinery due to their host-dependency for efficient replication. Certain cellular functions are actively induced by respiratory viruses for their own benefit. This includes metabolic pathways such as glycolysis, fatty acid synthesis (FAS) and the tricarboxylic acid (TCA) cycle, among others, which are modified during viral infections. Here, we summarize the current knowledge of metabolic pathway modifications mediated by the acute respiratory viruses respiratory syncytial virus (RSV), rhinovirus (RV), influenza virus (IV), parainfluenza virus (PIV), coronavirus (CoV) and adenovirus (AdV), and highlight potential targets and compounds for therapeutic approaches.

Severe influenza virus (IV) infections still represent a major challenge to public health. To combat IV infections, vaccines and antiviral compounds are available. However, vaccine efficacies vary with very limited to no protection against newly emerging zoonotic IV introductions. In addition, the development of resistant virus variants against currently available antivirals can be rapidly detected, in consequence demanding the design of novel antiviral strategies. Virus supportive cellular signaling cascades, such as the NF-κB pathway, have been identified to be promising antiviral targets against IV in in vitro and in vivo studies and clinical trials. While administration of NF-κB pathway inhibiting agents, such as LASAG results in decreased IV replication, it remained unclear whether blocking of NF-κB might sensitize cells to secondary bacterial infections, which often come along with viral infections. Thus, we examined IV and Staphylococcus aureus growth during LASAG treatment. Interestingly, our data reveal that the presence of LASAG during superinfection still leads to reduced IV titers. Furthermore, the inhibition of the NF-κB pathway resulted in decreased intracellular Staphylococcus aureus loads within epithelial cells, indicating a dependency on the pathway for bacterial uptake. Unfortunately, so far it is not entirely clear if this phenomenon might be a drawback in bacterial clearance during infection.

Influenza virus (IV) infections are considered to cause severe diseases of the respiratory tract. Beyond mild symptoms, the infection can lead to respiratory distress syndrome and multiple organ failure. Occurrence of resistant seasonal and pandemic strains against the currently licensed antiviral medications points to the urgent need for new and amply available anti-influenza drugs. Interestingly, the virus-supportive function of the cellular phosphatidylinositol 3-kinase (PI3K) suggests that this signaling module may be a potential target for antiviral intervention. In the sense of repurposing existing drugs for new indications, we used Pictilisib, a known PI3K inhibitor to investigate its effect on IV infection, in mono-cell-culture studies as well as in a human chip model. Our results indicate that Pictilisib is a potent inhibitor of IV propagation already at early stages of infection. In a murine model of IV pneumonia, the in vitro key findings were verified, showing reduced viral titers as well as inflammatory response in the lung after delivery of Pictilisib. Our data identified Pictilisib as a promising drug candidate for anti-IV therapies that warrant further studying. These results further led to the conclusion that the repurposing of previously approved substances represents a cost-effective and efficient way for development of novel antiviral strategies.

Human beings are exposed to microorganisms every day. Among those, diverse commensals and potential pathogens including Staphylococcus aureus (S. aureus) compose a significant part of the respiratory tract microbiota. Remarkably, bacterial colonization is supposed to affect the outcome of viral respiratory tract infections, including those caused by influenza viruses (IV). Since 30% of the world’s population is already colonized with S. aureus that can develop metabolically inactive dormant phenotypes and seasonal IV circulate every year, super-infections are likely to occur. Although IV and S. aureus super-infections are widely described in the literature, the interactions of these pathogens with each other and the host cell are only scarcely understood. Especially, the effect of quasi-dormant bacterial subpopulations on IV infections is barely investigated. In the present study, we aimed to investigate the impact of S. aureus small colony variants on the cell intrinsic immune response during a subsequent IV infection in vitro. In fact, we observed a significant impact on the regulation of pro-inflammatory factors, contributing to a synergistic effect on cell intrinsic innate immune response and induction of harmful cell death. Interestingly, the cytopathic effect, which was observed in presence of both pathogens, was not due to an increased pathogen load.

Influenza virus is a well-known respiratory pathogen, which still leads to many severe pulmonary infections in the human population every year. Morbidity and mortality rates are further increased if virus infection coincides with co-infections or superinfections caused by bacteria such as Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus). This enhanced pathogenicity is due to complex interactions between the different pathogens and the host and its immune system and is mainly governed by altered intracellular signaling processes. In this review, we summarize the recent findings regarding the innate and adaptive immune responses during co-infection with influenza virus and S. pneumoniae or S. aureus, describing the signaling pathways involved and how these interactions influence disease outcomes.

OBJECTIVE. Our aim in this study was to investigate the relationship between (a) the manual abilities of children with cerebral palsy (CP), assessed with the Manual Ability Classification System (MACS) in a school rehabilitation setting, and (b) the children’s performance of self-care activities at home, assessed with the Pediatric Evaluation of Disability Inventory (PEDI). In addition, we assessed the interobserver reliability of the MACS. METHOD. Sixty-one children with CP were included (mean age = 10.3 yr, range = 5–14). The MACS was classified by 2 independent raters. The PEDI was scored in a structured interview. RESULTS. The Spearman correlation coefficient between the MACS and the self-care domain of the PEDI Caregiver Assistance Scale was high and statistically significant (r = .72). The interobserver reliability of the MACS was good (weighted κ = .86). CONCLUSION. The MACS is a reliable instrument in a school environment and is related to the performance of daily life self-care activities at home.

Plasma transferred arc (PTA) welded coatings are used to improve surface properties of mechanical parts. Advantages are the high reliability of the process and the low dilution of substrate and coating material. Processing of surfaces by PTA welding is restricted at the time to flat horizontal position. Furthermore, industry is interested in the development of strategies for coating with PTA in constraint position as complex three-dimensional (3D) parts could be then easily processed as well. Under commercial aspects, the process design can be optimized to increase process efficiency and to reduce heat input during the welding process. Process optimization involves the determination of guidelines for PTA welding in constraint positions as well. Modeling the process gives an alternative to reduce the experimental effort to optimize the welding process. Results of simulation studies of the PTA welding process are given in the present work. It will be shown that coating conditions can be optimized by varying plasma gas flow, heat input and heat flow, process speed, or powder injection with regard to welding in constraint positions. The defined controlling of the PTA welding allows modification of process management with less experimental effort and to develop coating strategies for processing in different positions. In experimental investigations, the developed coating strategies are confirmed by producing PTA coatings in constraint position as well as complex 3D parts.

Nowadays, wire-arc spraying of chromium steel has gained an important market share for corrosion and wear protection applications. However, detailed studies are the basis for further process optimization. In order to optimize the process parameters and to evaluate the effects of the spray parameters DoE-based experiments had been carried out with high-speed camera shoots. In this article, the effects of spray current, voltage, and atomizing gas pressure on the particle jet properties, mean particle velocity and mean particle temperature and plume width on X46Cr13 wire are presented using an online process monitoring device. Moreover, the properties of the coatings concerning the morphology, composition and phase formation were subject of the investigations using SEM, EDX, and XRD-analysis. These deep investigations allow a defined verification of the influence of process parameters on spray plume and coating properties and are the basis for further process optimization.

We present a case of presumed central anticholinergic syndrome due to a drug administration error. A 35-year-old woman was slow to emerge from anaesthesia for laparoscopic biliary surgery. Postoperative neurological and metabolic abnormalities were later diagnosed as central anticholinergic syndrome. Only after resolution of the clinical problems did the drug error origin of the syndrome become apparent. It was realized that hyoscine hydrobromide (scopolamine) had been inadvertently administered intraoperatively for biliary relaxation, instead of hyoscine butylbromide. This case report describes central anticholinergic syndrome and highlights potential problems involved for anaesthetists administering drugs they do not commonly use.

To investigate areas of consensus and disagreement among Dutch physiatrists concerning prescription of therapeutic footwear for the neuropathic foot and to develop a research agenda. Forty participants were physiatrists and experts in the field of orthopedic shoe techniques. Four postal Delphi rounds were followed by a final plenary session. Forty of the 44 invited experts participated in all postal Delphi rounds, with an overall response of 100%. They achieved consensus on the following. 1. (Dutch) Terminology for two sets of domains and dimensions for the various features of the neuropathic foot and for the shoe characteristics. 2. Application of specific shoe components: insole, shaft, outsole, tongue, and heel. In most features of the neuropathic foot, shaft and outsole domains were linked in the flexibility dimension. 3. Shoe prescriptions for various features of the neuropathic foot in at least four technical domains. Experts disagreed on application of rocker bar and shaft height. In a final conference, 31 experts agreed on a prioritized research agenda. An intensive Delphi process yielded consensus on terminology, and determined areas of consensus and disagreement for future research for the various features of the neuropathic foot and the shoe characteristics.