Influence of the Gas Atmosphere on the Composition and Phase Development of Polymer-Derived SiOC-Ceramics

Silicon oxycarbide (SiOC)‐based ceramics were synthesized by pyrolysis of a commercial polysiloxane containing MoSi2 and ceramic filler particles. The influence of different gas atmospheres on the chemical composition and on the phase formation of the filled Si–O–C ceramic during the pyrolysis process up to elevated temperatures of above 1200°C has been studied. The pyrolysis gas composition in the furnace during pyrolysis was measured with an in situ gas analyzer. Both the core and the surface of bulk samples were investigated with respect to composition in order to take the changes on the rim area of the specimens into account. The influence of hydrogen gas on the compositional gradient of the resulting ceramic material was derived from samples investigated by polarization microscopy, X‐ray diffraction (XRD), and micro‐XRD (μ‐XRD)

Mortalität, Morbidität und assoziierte Folgen perioperativer Bluttransfusionen orthopädischer Patienten mit Hüft- und Kniegelenkersatz: ein systematischer Review

In den vergangenen zehn Jahren gab es vermehrt Bedenken bezüglich potenzieller Risiken durch Transfusionen von Blutkomponenten jenseits des Risikos übertragbarer Infektionen. Hierzu wurde eine Fülle von Daten veröffentlicht, die sich mit transfusionsassoziierten Infektionen, Hämolyse, TRALI (transfusionsassoziierte akute Lungeninsuffizienz) und anderen Risiken befassen

Burden of seasonal influenza in the Swiss adult population during the 2016/2017–2018/2019 influenza seasons

Background Evidence on the burden of seasonal influenza in Switzerland is scarce, yet it is critical for the design of effective prevention and control measures. The objective of this study was to assess influenza-related resource utilization, health care expenditures and quality-adjusted life-years (QALYs) lost in Switzerland across the 2016/2017–2018/2019 influenza seasons. Methods We retrospectively analyzed multiple real-world data sources to calculate epidemiological and health outcomes, QALYs lost and direct medical costs due to influenza in the Swiss adult population. Subgroups included residents 18–49, 50–64 and 65+ years of age. The observation period was week 26, 2016, to week 25, 2019. Results Across the three seasons, we estimated seasonal averages of 203,090 (se ±26,717) GP visits for ILI 4,944 (se ± 785) influenza-attributable hospitalizations and 1,355 (se ±169) excess deaths attributable to influenza. We estimated a total loss of 8,429 (2016/2017), 11,179 (2017/2018) and 7,701 (2018/2019) QALYs due to influenza. On average, 88% of the loss in QALYs was attributed to premature deaths due to influenza. The total direct medical costs amounted to 44.4 (2016/2017), 77.3 (2017/2018) and 64.5 (2018/2019) million Euros. On average, 79.6% of the total costs arose due to hospitalizations. Conclusions In Switzerland, the burden of influenza on patients and payers is significant and particularly high in the elderly population. Policy interventions to increase vaccination rates as well as the uptake of more effective vaccines among the elderly are needed to reduce the burden of influenza

SARS-CoV-2-Infektionen und Sicherheit von Blut und Blutkomponenten

Um das Risiko einer Übertragung des Coronavirus SARS-CoV-2 durch Blutkomponenten abschätzen zu können, hat das Paul-Ehrlich-Institut gemeinsam mit drei virologischen Instituten die Labordaten von SARS-CoV-2-Infizierten ausgewertet. Lediglich in der Plasmaprobe eines schwer erkrankten Patienten konnte eine geringe Menge viraler RNA nachgewiesen werden. Bei asymptomatisch Infizierten sowie bei Personen mit weniger ausgeprägten Symptomen wurde hingegen kein SARS-CoV-2-Genom in Blutproben gefunden. Basierend auf diesen Befunden und auf Daten aus aktuellen Publikationen lässt sich somit kein Risiko einer transfusionsbedingten Übertragung von SARS-CoV-2 durch symptomfreie Infizierte erkennen

A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire

Many infections are caused by pathogens that are similar, but not identical, to previously encountered viruses, bacteria, or vaccines. In such re-infections, pathogens introduce known antigens, which are recognized by memory T cells and new antigens that activate naive T cells. How preexisting memory T cells impact the repertoire of T cells responding to new antigens is still largely unknown. We demonstrate that even a minimum epitope overlap between infections strongly increases the activation threshold and narrows the diversity of T cells recruited in response to new antigens. Thus, minimal cross-reactivity between infections can significantly impact the outcome of a subsequent immune response. Interestingly, we found that non-transferrable memory T cells are most effective in raising the activation threshold. Our findings have implications for designing vaccines and suggest that vaccines meant to target low-affinity T cells are less effective when they contain a strong CD8 T cell epitope that has previously been encountered

Attenuation of chronic antiviral T-cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts.

Lymphoid T-zone fibroblastic reticular cells (FRCs) actively promote T-cell trafficking, homeostasis, and expansion but can also attenuate excessive T-cell responses via inducible nitric oxide (NO) and constitutive prostanoid release. It remains unclear how these FRC-derived mediators dampen T-cell responses and whether this occurs in vivo. Here, we confirm that murine lymph node (LN) FRCs produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent and inflammation-independent fashion. We show that this COX2/PGE2 pathway is active during both strong and weak T-cell responses, in contrast to NO, which only comes into play during strong T-cell responses. During chronic infections in vivo, PGE2-receptor signaling in virus-specific cluster of differentiation (CD)8 cytotoxic T cells was shown by others to suppress T-cell survival and function. Using COX2flox/flox mice crossed to mice expressing Cre recombinase expression under control of the CC chemokine ligand (CCL19) promoter (CCL19cre), we now identify CCL19+ FRC as the critical source of this COX2-dependent suppressive factor, suggesting PGE2-expressing FRCs within lymphoid tissues are an interesting therapeutic target to improve T-cell-mediated pathogen control during chronic infection

Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.

Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8 T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than naïve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity

Characteristics, predictors and outcomes among 99 patients hospitalised with COVID-19 in a tertiary care centre in Switzerland: an observational analysis

AIMS OF THE STUDY To describe admission characteristics, risk factors and outcomes of patients with coronavirus disease 2019 (COVID-19) hospitalised in a tertiary care hospital in Switzerland during the early phase of the pandemic. METHODS This retrospective cohort study included adult patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) testing and hospitalised at the cantonal hospital Aarau (Switzerland) between 26 February 2020 and 30 April 2020. Our primary endpoint was severe COVID-19 progression defined as a composite of transfer to the intensive care unit (ICU) and in-hospital mortality. RESULTS A total of 99 patients (median age 67 years [interquartile range 56–76], 37% females) were included and 35% developed severe COVID-19 progression (24% needed ICU treatment, 19% died). Patients had a high burden of comorbidities with a median Charlson comorbidity index of 3 points and a high prevalence of hypertension (57%), chronic kidney disease (28%) and obesity (27%). Baseline characteristics with the highest prognostic value for the primary endpoint by means of area under the receiver operating characteristic curve were male gender (0.63) and initial laboratory values including shock markers (lactate on ambient air 0.67; lactate with O2 supply 0.70), markers of inflammation (C-reactive protein 0.72, procalcitonin 0.80) and markers of compromised oxygenation (pO2 0.75 on ambient air), whereas age and comorbidities provided little prognostic information. CONCLUSION This analysis provides insights into the first consecutively hospitalised patients with confirmed COVID-19 at a Swiss tertiary care hospital during the initial period of the pandemic. Markers of disease progression such as inflammatory markers, markers for shock and impaired respiratory function provided the most prognostic information regarding severe COVID-19 progression in our sample

Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner

Summary: Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector cells (SLECs) and memory precursor cells (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target of rapamycin complex 2 (mTORC2), regulates SLEC and MPEC commitment. Rictor deficiency favors memory formation and increases IL-2 secretion capacity without dampening effector functions. Moreover, mTORC2-deficient memory T cells mount more potent recall responses. Enhanced memory formation in the absence of mTORC2 was associated with Eomes and Tcf-1 upregulation, repression of T-bet, enhanced mitochondrial spare respiratory capacity, and fatty acid oxidation. This transcriptional and metabolic reprogramming is mainly driven by nuclear stabilization of Foxo1. Silencing of Foxo1 reversed the increased MPEC differentiation and IL-2 production and led to an impaired recall response of Rictor KO memory T cells. Therefore, mTORC2 is a critical regulator of CD8 T cell differentiation and may be an important target for immunotherapy interventions. : Zhang et al. demonstrate that mTORC2 deficiency favors CD8 T cell memory differentiation during the primary antigen-specific T cell response to Listeria infection. The effects result from higher Foxo1 transcriptional activity without dampening effector functions. They also show enhanced recall responses by mTORC2-deficient memory CD8 T cells. Keywords: Rictor, mTORC2, Foxo1, CD8 T cell, infectio