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During winter 2015/2016, the Arctic stratosphere was characterized by extraordinarily low temperatures in connection with a very strong polar vortex and with the occurrence of extensive polar stratospheric clouds. From mid-December 2015 until mid-March 2016, the German research aircraft HALO (High Altitude and Long-Range Research Aircraft) was deployed to probe the lowermost stratosphere in the Arctic region within the POLSTRACC (Polar Stratosphere in a Changing Climate) mission. More than 20 flights have been conducted out of Kiruna, Sweden, and Oberpfaffenhofen, Germany, covering the whole winter period. Besides total reactive nitrogen (NOy), observations of nitrous oxide, nitric acid, ozone, and water were used for this study. Total reactive nitrogen and its partitioning between the gas and particle phases are key parameters for understanding processes controlling the ozone budget in the polar winter stratosphere. The vertical redistribution of total reactive nitrogen was evaluated by using tracer–tracer correlations (NOy–N2O and NOy–O3). The trace gases are well correlated as long as the NOy distribution is controlled by its gas-phase production from N2O. Deviations of the observed NOy from this correlation indicate the influence of heterogeneous processes. In early winter no such deviations have been observed. In January, however, air masses with extensive nitrification were encountered at altitudes between 12 and 15 km. The excess NOy amounted to about 6 ppb. During several flights, along with gas-phase nitrification, indications for extensive occurrence of nitric acid containing particles at flight altitude were found. These observations support the assumption of sedimentation and subsequent evaporation of nitric acid-containing particles, leading to redistribution of total reactive nitrogen at lower altitudes. Remnants of nitrified air masses have been observed until mid-March. Between the end of February and mid-March, denitrified air masses have also been observed in connection with high potential temperatures. This indicates the downward transport of air masses that have been denitrified during the earlier winter phase. Using tracer–tracer correlations, missing total reactive nitrogen was estimated to amount to 6 ppb. Further, indications of transport and mixing of these processed air masses outside the vortex have been found, contributing to the chemical budget of the winter lowermost stratosphere. Observations within POLSTRACC, at the bottom of the vortex, reflect heterogeneous processes from the overlying Arctic winter stratosphere. The comparison of the observations with CLaMS model simulations confirm and complete the picture arising from the present measurements. The simulations confirm that the ensemble of all observations is representative of the vortex-wide vertical NOy redistribution.
Das erstmals Ende 2002 im Süden Chinas aufgetretene schwere akute respiratorische Syndrom (SARS) führte bis zum August 2003 zu insgesamt über 8000 Erkrankungen und über 700 Todesfällen. Eine von der Weltgesundheitsorganisation (WHO) ins Leben gerufene Kooperation verschiedener Laboratorien weltweit ermöglichte innerhalb von nur vier Wochen die Identifizierung des kausalen Agens, eines bislang unbekannten Coronavirus (vorläufig bezeichnet als SARS-assoziiertes Coronavirus oder SARS-CoV), welches die Koch’schen Postulate erfüllt. Der Erreger lässt sich (unter Hochsicherheitsbedingungen) gut in Zellkulturen vermehren, was weitere Studien zur Stabilität sowie die Entwicklung von antiviral wirksamen Substanzen und Impfstoffen erleichtert.
Obwohl schon rasch diagnostische Labortests, insbesondere zum Nachweis der viralen Nukleinsäure und virusspezifischer Antikörper, zur Verfügung standen, basiert die Falldefinition von SARS weiterhin auf klinisch-epidemiologischen Kriterien. In Hinblick auf die Gefahr eines (saisonalen) Wiederauftretens der Infektion müssen die verfügbaren Labormethoden dringend überprüft und weiter verbessert werden.
SARS ist ein gutes Beispiel dafür, wie schnell sich eine Infektionskrankheit über den internationalen Reiseverkehr ausbreiten kann, aber auch dafür, wie wichtig in einem solchen Falle eine gut koordinierte internationale Kooperation ist; durch Einsatz neuester, aber auch bewährter konventioneller Labormethoden und ständigen Austausch aktueller (Zwischen-)Ergebnisse sowie von Patientenproben und Reagenzien führte eine bisher einmalige Zusammenarbeit schnell zu einem Durchbruch. Dies lässt auf ähnliche Fortschritte beim Kampf gegen weitere neuartige Infektionserreger hoffen.
Background and Objectives: Proteins of the coagulation system contribute to autoimmune inflammation in patients with multiple sclerosis (MS). On blood-brain barrier (BBB) disruption, fibrinogen enters the CNS and is rapidly converted to fibrin, unfolding pleiotropic autoimmune mechanisms. Fibrin accumulation leads to subsequent proteolytic degradation that results in D-dimer generation. The primary objective of this study was to determine intrathecal levels of D-dimer in CSF as a measure of intrathecal coagulation cascade activation and to evaluate its diagnostic utility in patients with MS in contrast to healthy subjects. Key secondary objectives included analysis of CSF D-dimer in differential diagnoses of MS and its relation to routine clinical markers of disease activity.
Methods: Patients admitted for the assessment of suspected MS were prospectively recruited from October 2017 to December 2020. Blood plasma and citrated CSF samples were analyzed using a highly sensitive luminescent oxygen channeling immunoassay. Intrathecal generation of D-dimer was analyzed by adjusting for CSF/serum albumin (Qalb) and CSF/plasma D-dimer quotients (QD-dimer), and corresponding CSF fibrinogen levels were determined. Final diagnoses after full evaluation and clinical data were recorded.
Results: Of 187 patients, 113 patients received a diagnosis of MS or clinically/radiologically isolated syndrome. We found increased intrathecal CSF D-dimer generation levels (QD-dimer/Qalb-index) for patients with relapsing-remitting MS (RRMS; n = 71, median 4.7, interquartile range [IQR] 2.5–8.0) when compared with those for disease controls (n = 22, median 2.6, IQR 2.1–4.8, p = 0.031). Absolute CSF D-dimer values correlated with CSF fibrinogen levels (r = 0.463; p < 0 .001) and CSF leukocytes (r = 0.273; p = 0.003) and were elevated in MS patients with contrast enhancement (CE) compared with MS patients without CE on MRI (n = 48, median 6 ng/mL, and IQR 3–15.25 vs n = 41, median 4 ng/mL, and IQR 2–7; p = 0.026). Exploratory subgroup analyses indicated a correlation of intrathecal inflammatory activity and CSF D-dimer levels.
Discussion: D-dimer in CSF can be reliably determined and correlates with markers of CNS inflammation and CSF fibrinogen levels. Adjusted for BBB dysfunction, CSF D-dimer may allow the identification of intrathecal coagulation cascade activation in patients with MS.
Classification of Evidence: This study provides Class I evidence that CSF D-dimer levels are elevated in patients with RRMS.
DGK and DZHK position paper on genome editing: basic science applications and future perspective
(2021)
For a long time, gene editing had been a scientific concept, which was limited to a few applications. With recent developments, following the discovery of TALEN zinc-finger endonucleases and in particular the CRISPR/Cas system, gene editing has become a technique applicable in most laboratories. The current gain- and loss-of function models in basic science are revolutionary as they allow unbiased screens of unprecedented depth and complexity and rapid development of transgenic animals. Modifications of CRISPR/Cas have been developed to precisely interrogate epigenetic regulation or to visualize DNA complexes. Moreover, gene editing as a clinical treatment option is rapidly developing with first trials on the way. This article reviews the most recent progress in the field, covering expert opinions gathered during joint conferences on genome editing of the German Cardiac Society (DGK) and the German Center for Cardiovascular Research (DZHK). Particularly focusing on the translational aspect and the combination of cellular and animal applications, the authors aim to provide direction for the development of the field and the most frequent applications with their problems.
Aim: Radioiodine therapy (RIT) may trigger the development of Graves’ ophthalmopathy (GO) or exacerbate pre-existing subclinical GO. Therefore, glucocorticoid administration is recommended for patients with pre-existing GO. Aim of this study was to analyze the influence of glucocorticoid therapy with methylprednisolone on intratherapeutic effective half-life (EHL) of radioiodine-131 in patients with Graves’ disease (GD) as recent studies showed an effect for prednisolone.
Methods: In a retrospective study, 264 patients with GD who underwent RIT without any additional antithyroid medication were evaluated. Intrathyroidal EHL was determined pre- and intratherapeutically. Patients with co-existing GO (n = 43) received methylprednisolone according to a fixed scheme starting 1 day prior to RIT, patients without GO (n = 221) did not receive any protective glucocorticoid medication. The ratios of EHL during RIT and during radioiodine uptake test (RIUT) were compared.
Results: Patients receiving methylprednisolone showed a slight decrease of the mean EHL from 5.63 d (RIUT) to 5.39 d (RIT) (p > 0.05). A comparable result was obtained in patients without glucocorticoids (5.71 d (RIUT) to 5.47 d (RIT); p > 0.05). The ratios of the EHL between RIT and RIUT failed to show a significant difference between the two groups. EHL is therefore not significantly influenced by an additional protective treatment with methylprednisolone.
Conclusions: In the present study a decreased intrathyroidal EHL under glucocorticoid medication with methylprednisolone could not be detected. Therefore, co-medication with methylprednisolone in patients with GO may be preferred to avoid an intratherapeutic decrease of EHL by accompanying protective glucocorticoides.