Coiled-coil irregularities of the M1 protein structure promote M1-fibrinogen interaction and influence group A Streptococcus host cell interactions and virulence

Group A Streptococcus (GAS) is a human pathogen causing a wide range of mild to severe and life-threatening diseases. The GAS M1 protein is a major virulence factor promoting GAS invasiveness and resistance to host innate immune clearance. M1 displays an irregular coiled-coil structure, including the B-repeats that bind fibrinogen. Previously, we found that B-repeat stabilisation generates an idealised version of M1 (M1*) characterised by decreased fibrinogen binding in vitro. To extend these findings based on a soluble truncated version of M1, we now studied the importance of the B-repeat coiled-coil irregularities in full length M1 and M1* expressed in live GAS and tested whether the modulation of M1-fibrinogen interactions would open up novel therapeutic approaches. We found that altering either the M1 structure on the GAS cell surface or removing its target host protein fibrinogen blunted GAS virulence. GAS expressing M1* showed an impaired ability to adhere to and to invade human endothelial cells, was more readily killed by whole blood or neutrophils and most importantly was less virulent in a murine necrotising fasciitis model. M1-mediated virulence of wild-type GAS was strictly dependent on the presence and concentration of fibrinogen complementing our finding that M1-fibrinogen interactions are crucial for GAS virulence. Consistently blocking M1-fibrinogen interactions by fragment D reduced GAS virulence in vitro and in vivo. This supports our conclusion that M1-fibrinogen interactions are crucial for GAS virulence and that interference may open up novel complementary treatment options for GAS infections caused by the leading invasive GAS strain M

Epilepsy and EEG traits in children with bilateral spastic cerebral palsy and defined cerebral lesions on MRI

Einleitung: Kinder mit bilateralen spastischen Tetraparesen weisen MR-tomographisch unterschiedliche Gehirnläsionen auf. Bei 40% dieser Kinder besteht eine Epilepsie. Ausgehend von der Hypothese, dass der Läsionstyp bestimmend für Manifestation und Prognose der Epilepsie ist, sollen in der vorliegenden Arbeit die Epilepsien von Kindern mit eindeutig definierten Läsionsmustern charakterisiert werden. Besonders sollen dabei auch bestimmte EEG-Merkmale, die so genannten „benignen fokalen Sharp Waves“, hinsichtlich ihrer Häufigkeit und prognostischen Wertigkeit untersucht werden. Patienten und Methoden: 50 Kinder mit einer kernspintomographisch definierten Hirnläsion werden in die Untersuchung eingeschlossen. Klinische Symptomatik, Epilepsie und EEG-Verlauf werden retrospektiv evaluiert. Die kernspin-tomographischen Bilder sowie die EEGs werden standardisiert verblindet nachbefundet. Ergebnisse: Kinder mit periventrikulärer Leukomalazie (PVL) haben seltener eine Epilepsie als Kinder mit cortico-subcorticalen Läsionen (CSL), Basalganglienläsionen oder Fehlbildungen. Schwere PVL-Formen bedingen signifikant häufiger eine Epilepsie als leichte Formen. Schwer verlaufende Epilepsien treten nur bei ausgeprägten Läsionsmustern auf (z.B. CSL, Fehlbildungen, schwere PVL). Bei 25 von 50 Kindern (50%) zeigen sich im EEG benigne fokale Sharp Waves. Diese kommen insbesondere bei Kindern mit PVL oder Basalganglienläsionen vor. Nicht immer besteht eine eindeutige topographische Korrelation zwischen Läsionsort und Lokalisation der benignen fokalen Sharp Waves. Kommen im EEG ausschließlich benigne fokale Sharp Waves vor, ist die Prognose einer Epilepsie gut. Schlussfolgerung: Der Läsionstyp hat eine prognostische Bedeutung für Manifestation, Art und Schweregrad einer Epilepsie. Benigne fokale Sharp Waves kommen bei bestimmten Läsionsmustern überzufällig häufig vor, so dass ein additiver Effekt von Läsion und genetischer Disposition angenommen werden kann. Möglicherweise bestimmt das Ausmaß der Läsion, ob vorwiegend läsionelle oder genetische Charakteristika den Epilepsieverlauf prägen.Introduction: Bilateral spastic cerebral palsy (CP) is associated in up to 40% with epilepsy. Pathogenetically, CP forms a heterogeneous group. Based on MRI, several patterns of lesion can be distinguished. The course of the epilepsy in these children is highly variable. Therefore, we investigated the relationship between lesion patterns and epilepsy. In addition, we wanted to characterize the EEG data in these children with special emphasis on the prognostic value of benign focal sharp waves, a genetically determined EEG trait. Patients and methods: 50 children with defined lesions on MRI were included in the study. Clinical characteristics, epilepsy and EEG data were retrospectively evaluated. MRI and EEG data were systematically reviewed by patient blinded raters. Results: Epilepsy occurred more often in children with cortico-subcortical lesions (CSL), lesions of the basal ganglia or cerebral malformations compared to children with periventricular leukomalacia (PVL). In severe PVL, the risk of epilepsy is higher than in mild forms of PVL. Overall, epilepsies with a severe course occurred only in children with severe cerebral lesions (CSL, cerebral malformations, or severe PVL). In 25 of the 50 children (50%) benign focal sharp waves were found in the EEG. They were predominantly associated with PVL or lesions of the basal ganglia. In a number of cases there was no clear topographical correlation between the site of the lesion on MRI and the location of the focal sharp waves in the EEG. Prognosis of the epilepsy was always favourable when benign focal sharp waves were the only EEG pathology during the course of the epilepsy. Conclusion: The identification of lesion patterns in children with CP has predictive value for manifestation and prognosis of the epilepsy. In addition, benign focal sharp waves in the EEG are found more often than expected indicating an additive effect of certain lesion types and an underlying genetic disposition

Losing ground at the wrong time: trends in self-reported influenza vaccination uptake in Switzerland, Swiss Health Survey 2007-2017.

OBJECTIVES We studied time trends in seasonal influenza vaccination and associations with socioeconomic and health-related determinants in Switzerland, overall and in people aged ≥65 years. DESIGN Three cross-sectional surveys. PARTICIPANTS Individuals who participated in the Swiss Health Surveys 2007, 2012 and 2017. We calculated the proportion reporting influenza vaccination in the last 12 months, and performed multivariable logistic regression analyses. RESULTS We included 51 582 individuals in this analysis. The median age was 49 years (IQR 25-64), and 27 518 were women (53.3%). The proportion of reporting a history of influenza vaccination overall was 31.9% (95% CI 31.4 to 32.4); and dropped from 34.5% in 2007 to 28.8% in 2017. The uptake of vaccination within the past 12 months was 16% in 2007 and similar in 2012 and 2017 (around 14%). In people with chronic disease, uptake dropped from 43.8% in 2007 to 37.1% in 2012 and to 31.6% in 2017 (p<0.001). In people aged ≥65 years, uptake dropped from 47.8% in 2007 to 38.5% in 2012 to 36.2% in 2017 (p<0.001). In logistic regression, self-reported vaccination coverage decreased in the 65-75 years old (adjusted OR (aOR) 0.56, 95% CI 0.48 to 0.66 between 2007 and 2012; aOR 0.89, 95% CI 0.77 to 1.03 between 2012 and 2017). Uptake was positively associated with the ≥65 age group, living in French-speaking and urban areas, history of smoking, bad self-reported health status, private/semiprivate health insurance, having a medical profession and having any underlying chronic disease. CONCLUSION Influenza vaccination coverage was low in older and chronically ill persons. Significant efforts are required in preparing for the influenza season 2020/2021 to reduce the double burden of COVID-19 and seasonal influenza. These efforts should include campaigns but also novel approaches using social media

[Communicating Prognosis and Expectations in Advanced Disease - A Balancing Act in Practice].

Communicating Prognosis and Expectations in Advanced Disease - A Balancing Act in Practice Abstract. To prepare the end of life, to plan important things, to spend the remaining time of life not only with medical treatments, but to live - these are frequently expressed wishes of people with progressive diseases. Prognostic statements are feared by professionals. At the same time, when talking about what lies ahead for those affected, professionals very often make over-optimistic promises. A broader definition of the term prognosis as well as a careful handling of expectations can help to define realistic goals together

Trends in influenza vaccination uptake in Switzerland: Swiss Health Survey 2007 and 2012.

AIMS We studied time trends in seasonal influenza vaccination and assessed associations with socioeconomic and health-related determinants in Switzerland (overall and people aged &ge;65 years). METHODS We used data from the Swiss Health Surveys of 2007 and 2012. We calculated the proportion of the population (overall and those &ge;65 years old) reporting influenza vaccination in the last 12 months, and performed multivariate logistic regression analyses, presented as adjusted odds ratios (aORs). RESULTS The average overall frequency of people reporting having been vaccinated for influenza in the previous 12 months was 15.2% (95% confidence interval [CI] 14.7&ndash;15.7); frequency decreased from 16.4% in 2007 to 14.1% in 2012 (p &lt;0.001). In elderly people (&ge;65 years) the frequency declined from 47.8 to 38.5% (p &lt;0.001). The decline was more pronounced in both the 15 to 19 age group (aOR 0.5, 95% CI 0.3&ndash;1.0) and those 65 to 75 years old (aOR 0.6, 95% CI 0.5&ndash;0.7), and in those with less education (aOR 0.6, 95% CI 0.4&ndash;0.7). Pregnant women had the lowest frequency for influenza vaccination (2.3%, 95% CI 0.6&ndash;7.9), but the frequency increased between 2007 and 2012 (aOR 4.5, 95% CI 1.0&ndash;20.5). Influenza vaccination in the last 12 months was positively associated with the &ge;65 age group, living in French-speaking and urban areas, history of smoking, bad self-reported health status, health insurance for private/semiprivate hospital stays and working in healthcare professions. CONCLUSIONS Influenza vaccination coverage was low overall and declined over time. To increase influenza vaccine uptake and reach the European target of 75% in people aged &ge;65 years, more efforts should be put into novel intervention approaches

Impact of an abrupt cooling event on interglacial methane emissions in northern peatlands

Rapid changes in atmospheric methane (CH4), temperature and precipitation are documented by Greenland ice core data both for glacial times (the so called Dansgaard-Oeschger (D-O) events) as well as for a cooling event in the early Holocene (the 8.2 kyr event). The onsets of D-O warm events are paralleled by abrupt increases in CH4 by up to 250 ppb in a few decades. Vice versa, the 8.2 kyr event is accompanied by an intermittent decrease in CH4 of about 80 ppb over 150 yr. The abrupt CH4 changes are thought to mainly originate from source emission variations in tropical and boreal wet ecosystems, but complex process oriented bottom-up model estimates of the changes in these ecosystems during rapid climate changes are still missing. Here we present simulations of CH4 emissions from northern peatlands with the LPJ-Bern dynamic global vegetation model. The model represents CH4 production and oxidation in soils and transport by ebullition, through plant aerenchyma, and by diffusion. Parameters are tuned to represent site emission data as well as inversion-based estimates of northern wetland emissions. The model is forced with climate input data from freshwater hosing experiments using the NCAR CSM1.4 climate model to simulate an abrupt cooling event. A concentration reduction of ~10 ppb is simulated per degree K change of mean northern hemispheric surface temperature in peatlands. Peatland emissions are equally sensitive to both changes in temperature and in precipitation. If simulated changes are taken as an analogy to the 8.2 kyr event, boreal peatland emissions alone could only explain 23 of the 80 ppb decline in atmospheric methane concentration. This points to a significant contribution to source changes from low latitude and tropical wetlands to this event

Bacteria Communities in Swiss Fish Farms with Recirculating Aquaculture Systems

Recirculating aquaculture systems (RAS), often used in fish farming, rely on microorganisms to maintain healthy water quality, nutrient cycling, animal welfare, and disease control. However, many daily operations in fish farms (e.g., stocking) may negatively affect the microorganisms' community composition and create a favorable environment for opportunistic pathogens. Currently, understanding microorganisms' communities within RAS is scarce, which presents an obstacle for pro-active system management. To better understand microorganism communities' spatial and temporal structure within fish farms using a RAS, we collected samples of filtered water and biofilm swabs from two different Swiss fish farms and two different locations within each farm. Water was collected from within one tank and the biofilter, while biofilm swabs were collected from the same tank's wall where the water sample was collected. DNA was extracted using the Purelink Microbial DNA Purification kit, and then each sample was prepared with three different primer pairs, 341F/805R (V3V4 region), 515F/806R (V4), 27F/534R (V1-3), and ran on the MiSeq platform (v3 600 cycles). The pilot study aimed to understand 1) how the microbiota composition changes regarding spatial and temporal scales within and between farms, 2) the primer effect on detected taxa, and 3) the difference between commonly-used 16s pipelines