Varicella zoster virus and influenza vaccine antibody titres in patients from MAGNIFY-MS who were treated with cladribine tablets for highly active relapsing multiple sclerosis

Lette

Microsurgical third ventriculocisternostomy as an alternative to ETV: report of two cases

OBJECTIVE: To describe a microsurgical alternative to endoscopic third ventriculocisternostomy. METHODS: Two children with shunt-dependent hydrocephalus and multiple shunt revisions were considered candidates for third ventriculocisternostomy (TVS). Because of slit ventricles, an endoscopic approach was not possible and, therefore, both patients received a microsurgical TVS by a supraorbital approach. RESULTS: In both cases, microsurgical TVS was successful and the patients became shunt free. CONCLUSION: Microsurgical TVS by a supraorbital craniotomy is a viable alternative to endoscopic TVS in selected cases

rst Transcriptional Activity Influences kirre mRNA Concentration in the Drosophila Pupal Retina during the Final Steps of Ommatidial Patterning

Background: Drosophila retinal architecture is laid down between 24-48 hours after puparium formation, when some of the still uncommitted interommatidial cells (IOCs) are recruited to become secondary and tertiary pigment cells while the remaining ones undergo apoptosis. This choice between survival and death requires the product of the roughest (rst) gene, an immunoglobulin superfamily transmembrane glycoprotein involved in a wide range of developmental processes. Both temporal misexpression of Rst and truncation of the protein intracytoplasmic domain, lead to severe defects in which IOCs either remain mostly undifferentiated and die late and erratically or, instead, differentiate into extra pigment cells. Intriguingly, mutants not expressing wild type protein often have normal or very mild rough eyes. Methodology/Principal Findings: By using quantitative real time PCR to examine rst transcriptional dynamics in the pupal retina, both in wild type and mutant alleles we showed that tightly regulated temporal changes in rst transcriptional rate underlie its proper function during the final steps of eye patterning. Furthermore we demonstrated that the unexpected wild type eye phenotype of mutants with low or no rst expression correlates with an upregulation in the mRNA levels of the rst paralogue kin-of-irre (kirre), which seems able to substitute for rst function in this process, similarly to their role in myoblast fusion. This compensatory upregulation of kirre mRNA levels could be directly induced in wild type pupa upon RNAi-mediated silencing of rst, indicating that expression of both genes is also coordinately regulated in physiological conditions. Conclusions/Significance: These findings suggest a general mechanism by which rst and kirre expression could be fine tuned to optimize their redundant roles during development and provide a clearer picture of how the specification of survival and apoptotic fates by differential cell adhesion during the final steps of retinal morphogenesis in insects are controlled at the transcriptional level

Unravelling the microbial fitness and the acquired co-resistances towards environmental extremes of vancomycin resistant enterococci

The World Health Organization listed vancomycin-resistant enterococci (VRE) within high priority on the global list of antibiotic resistant bacteria, which prioritizes the development and research of novel antibiotics. As a cause of endemic hospital outbreaks worldwide, VRE emerged as nosocomial pathogens, which can cause severe infections like bacteremia. One representative is vancomycinresistant Enterococcus faecium, an opportunistic pathogen that is part of the human intestinal microbiota but can be life threatening for immunosuppressed patients. Weakened immune functions are also a health issue for astronauts exposed to various stressors on long-term space missions. Therefore, VRE can become a threat whether on earth or in space. To prevent VRE infections and guarantee the health of the crew members it is important to understand the influence of microgravity on the development of antibiotic resistances. To investigate changes in the antibiotic resistance behavior due to microgravity, clinical VRE isolates were tested in their antibiotic resistances under simulated microgravity. As a result, the majority of the VRE isolates showed no change in their susceptibility to 22 different antibiotics or growth-inhibiting compounds after simulated microgravity. The unchanged resistance behavior stresses importance under both conditions and allows for similar containment and therapy strategies in the healthcare environment and in spaceflight. To estimate the risk of VRE and their role in an already existing pandemic of drug resistant infections it is essential to investigate VRE fitness and narrow down methods against the arising challenge of antibiotic resistant bacteria. Therefore, analysis of multi-stress factors of VRE and research of coresistance towards environmental extremes and space conditions will be implemented to improve the understanding how to fight drug resistant bacteria and, therefore, minimize healthcare-associated infections worldwide

Unraveling the resilience of vancomycin resistant E. faecium through long-term desiccation and novel decontamination methods

The World Health Organization (WHO) listed vancomycin-resistant enterococci (VRE) within high priority on the global list of antibiotic resistant bacteria, emphasizing the need for the development and research of new antibiotics. One representative is vancomycin-resistant Enterococcus (E.) faecium, an opportunistic pathogen that is part of the human intestinal flora but can be life threatening for immunosuppressed patients. As a cause of endemic hospital outbreaks worldwide, VRE emerged as nosocomial pathogens which can trigger bacteremia and endocarditis. Moreover, as vancomycin is the treatment of choice for these infections, therapy is limited. Here we tested the survival and metabolic activity after several months of desiccation of five representative E. faecium isolates. Additionally, novel and effective decontamination methods against these isolates were investigated. Therefore, the antimicrobial effect of blue light (408 nm) and copper coatings was determined. To estimate the risk of VRE and their role in an already existing pandemic of drug resistant infections it is essential to investigate VRE fitness and narrow down methods against the arising challenge of antibiotic resistant bacteria

Unraveling the microbial fitness and the acquired co-resistances towards environmental extremes of vancomycin

Vancomycin resistant Enterococcus (E.) faecium (VRE) is a healthcare associated nosocomial pathogen causing serious diseases in immunocompromised patients. As previously shown, immune functions of astronauts during spaceflight are also dysregulated and, moreover, the treatment options are limited during long-term missions. Thus, the question arises how tolerant VRE against desiccation and which decontamination methods are efficient against opportunistic bacteria. Which is highly relevant for spaceflight and clinical environments. Therefore, the microbial fitness of clinical isolates after four months of desiccation was determined, which were recovering to 100% metabolic activity again. As a potential decontamination method against VRE, the antimicrobial effect of copper coatings was tested. Here copper coatings showed different efficiency against VRE depending on their resistance to copper and vancomycin. Moreover, five E. faecium isolates were sequenced with Illumina for further genomic analysis and antibiotic resistance genes in addition to the characterization of a co-resistant isolate to vancomycin and copper. To prevent VRE infections and guarantee health of the crewmembers for future long-term space missions, it is essential to improve the understanding about the tenacity of VRE and gain knowledge about the adaptations to environmental stressors. Therefore, analysis of multi-stress factors of VRE and research of co-resistance towards environmental extremes and space conditions will be implemented to improve the understanding how to fight drug resistant bacteria

Impact of simulated microgravity on antibiotic resistance, biofilm formation and desiccation tolerance of vancomycin resistant Enterococcus faecium

Vancomycin resistant Enterococcus (E.) faecium (VRE) is a healthcare associated nosocomial pathogen causing serious diseases in immunocompromised patients. As previously shown, immune functions of astronauts during spaceflight are also dysregulated and, moreover, the treatment options are limited during long-term missions. Thus, the question arises how opportunistic and gastrointestinal bacteria, like VRE, may change regarding their resistance behavior to antibiotics, desiccation tolerance and biofilm formation under the loss of gravity. Therefore, we tested the change in antibiotic susceptibility of vancomycin susceptible (VSE, n=20), vancomycin resistant (VRE, n=17) and vancomycin-variable (VVE-B, n=5) E. faecium isolates to 22 different antibiotics, after incubation in simulated microgravity (sim. µg, by clinorotation) and as a control after seven days of incubation at 1 x g. Additionally, the clinical isolates were characterized regarding their biofilm formation and tolerance to desiccation after sim. µg. Three isolates increased in their minimal inhibitory concentration (MIC) to Vancomycin, Daptomycin and Fosfomycin after sim. µg. Whereas one isolate decreased in MIC to Oxacillin after sim. µg. Furthermore, we found four isolates which showed significant increase in biofilm formation and in total nine isolates that were more tolerant to desiccation after incubation under sim. µg. To prevent VRE infections and guarantee health of the crewmembers for future longterm space missions, it is essential to improve the understanding about the tenacity of VRE and gain knowledge about the influence of microgravity on the resistance behavior to different stressors. In this study sim. µg was generated by using a 2D Clinostat, which is a functional simulation and differs from real microgravity. Nevertheless, these first insights show how VRE are able to adapt in their resistance behavior and change due to spaceflight analog conditions like sim. µg