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Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed "original antigenic sin." The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.

BACKGROUND The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

Der im Jahre 2003 eingeführte Kurs zur Erlangung der Fähigkeit ein Praxislabor zu führen (FAPL-Kurs) ist heute bestens etabliert. Pro Jahr werden bis zu 480 Ärzte und Ärztinnen ausgebildet. Das Führen eines Praxislabors erfordert viel Fachwissen, von der Entnahme und der Vorbehandlung der Proben (Präanalytik), zur Durchführung des Testes (Analytik) bis hin zur Interpretation (Postanalytik) inkl. der Statistik. Zudem müssen die gesetzlichen Anforderungen bekannt sein und eingehalten werden. So muss die Labortätigkeit der Mitarbeiterinnen laufend geschult und überwacht werden. Diese Inhalte sind weder im Lehrplan des Medizinstudiums noch in der Ausbildung zum Facharzt entsprechend abgedeckt. Der Kurs verfolgt das Ziel, diese Inhalte verdichtet zu vermitteln, um die Dignität des Arztes für die Verrechnung von Laborleistungen vorzubereiten. Der FAPL-Kurs erfreut sich zunehmender Nachfrage. Die Teilnehmerzahlen sind in den vergangenen Jahren kontinuierlich angestiegen. Die erlangten Fähigkeiten werden als sinnvoll und für die Praxis relevant empfunden.

BACKGROUND Patients presenting very early after chest pain onset may provide a diagnostic challenge even when using a high-sensitivity cardiac troponin (hs-cTnT). We hypothesized that in these patients the incremental value of copeptin in the early diagnosis of acute myocardial infarction (AMI) may be substantial. METHODS We aimed to investigate the incremental value of copeptin in a pre-specified subgroup analysis of patients presenting with suspected AMI to the emergency department within 2 hours of symptom onset in a multicenter study. Copeptin was measured in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis using all available clinical informations, including high-sensitivity cardiac troponin T (hs-cTnT). RESULTS Overall, 2000 patients were enrolled, of whom 519 (26%) arrived within 2 hours of symptom onset. Of these, 102 patients (20%) had an AMI. The additional use of copeptin did not increase diagnostic accuracy as quantified by the area under the receiver-operating characteristic curve (AUC) of hs-cTnT (0.87 (95% confidence interval (CI): 0.83-0.90) for hs-cTnT alone to 0.86 (95% CI: 0.82-0.90) for the combination; p = NS). Copeptin (using 9 pmol/L as a cut-off) increased the negative predictive value (NPV) of hs-cTnT (using 14 ng/L as a cut-off) alone from 93% (95% CI: 90-95%) to 96% (95% CI: 93-98%). The NPV for the combination of hs-cTnT and copeptin was lower in patients arriving in the first 2 hours than in those arriving after 2 hours: 96% (95% CI: 93-98%) versus 99% (95% CI: 99-100%), respectively. CONCLUSIONS The additional use of copeptin on top of hs-cTnT seems to lead to a small increase in NPV, but no increase in AUC. Routine use of copeptin in early presenters does not seem warranted.

Reference values are generally used to allow a decision on whether a laboratory value is in the normal range or if it mirrors a pathological process. This decision is especially difficult to take, when the pathological process is just starting and the values are relatively close to the normal range. Particularly in this phase, the decision is extremely important. Harris and later on Fraser have realized that there are two variables that contribute to the credibility and significance of a measured analyte. 1. The imprecision of the measurement itself. These values have become relatively low in recent years: they amount to values between 1 and 5 %. 2. The within person biological variability, which can be 100 % or more. Both variables combined yield the "reference change value" (RCV) to define the minimal significant difference between two measurements at different time points. When using this concept, differences between two measurements can be detected before the normal range is exceeded. For any given patient the reference values of a population is actually not of primary concern. It is important to know that his personal data exceed his personal normal range, which is dependent on RCV. For many analytes in clinical chemistry and hematology the use of RCV rather than the normal range as reference improves the decision making process in a clinical setting.Eigentlich wollen wir ja meist nicht wissen, wo ein Labormesswert unseres Patienten in Bezug auf den Normbereich liegt, welcher ja aufgrund des Polymorphismus der Bevölkerung eine recht große Streuung aufweist. Was uns interessiert, ist im Grunde genommen, ob sich der Messwert beim jetzt kranken Patienten vom Wert des früheren Gesunden unterscheidet. Wir kennen das aus der Pädiatrie mit den Wachstumskurven. Das Interessante ist nicht, ob das Kind groß oder klein ist, sondern ob sich ein Knick in der Kurve gebildet hat. Da wir aber in der Regel leider keinen Ausgangswert des Patienten haben, greifen wir als Ersatz auf den Normbereich zurück und verpassen dabei die „Knicks“, die bereits innerhalb des Normbereichs stattfinden. Idealerweise hätten wir eine „Lebenskurve“ der Laborwerte eines Patienten, was ja ein Teil des Nutzens des lebenslangen Gesundheits-/Krankheits-Dossiers wäre. Die Frage, mit welcher wir uns hier beschäftigen wollen, ist, welcher Messunterschied, beziehungsweise welcher „Knick“ bereits signifikant ist. Die Signifikanz einer Änderung hängt von zwei Faktoren ab: Die Messungenauigkeit und die biologische Variabilität. Erstere wird mit zunehmend verbesserter Messtechnologie immer kleiner, letztere ist konstant und oft erstaunlich hoch. Beide zusammen können im Reference Change Value (RCV) zusammengefasst werden. Anhand von mehreren klinisch chemischen Analysen wird der Stellenwert des RCV aufgezeigt.

In Switzerland a general practitioner as well as a specialist needs a qualification to be entitled to do laboratory tests in their private offices and take advantage of health insurance funding. This qualification is reached by accomplishing the so called FAPL-course (FAPL = Fähigkeitsausweis Praxislabor). The course was introduced in 2003 and is expanding year by year. Up to 480 practitioners are thus educated per year, mostly in Luzern for the German speaking region, but also in Lausanne for the French speaking and in Locarno for the Italian speaking participants. Managing a laboratory in a medical office requires a wide knowledge concerning preanalytics including the correct sampling of body fluids, analytical techniques, the correct use and the limits of testing procedures. Furthermore postanalytical interpretations imply a good understanding of statistics. In addition legal regulations have to be respected. These topics are partially communicated using an e-learning platform and partially in a two day practical course.Der im Jahre 2003 eingeführte Kurs zur Erlangung der Fähigkeit ein Praxislabor zu führen (FAPL-Kurs) ist heute bestens etabliert. Pro Jahr werden bis zu 480 Ärzte und Ärztinnen ausgebildet. Das Führen eines Praxislabors erfordert viel Fachwissen, von der Entnahme und der Vorbehandlung der Proben (Präanalytik), zur Durchführung des Testes (Analytik) bis hin zur Interpretation (Postanalytik) inkl. der Statistik. Zudem müssen die gesetzlichen Anforderungen bekannt sein und eingehalten werden. So muss die Labortätigkeit der Mitarbeiterinnen laufend geschult und überwacht werden. Diese Inhalte sind weder im Lehrplan des Medizinstudiums noch in der Ausbildung zum Facharzt entsprechend abgedeckt. Der Kurs verfolgt das Ziel, diese Inhalte verdichtet zu vermitteln, um die Dignität des Arztes für die Verrechnung von Laborleistungen vorzubereiten. Der FAPL-Kurs erfreut sich zunehmender Nachfrage. Die Teilnehmerzahlen sind in den vergangenen Jahren kontinuierlich angestiegen. Die erlangten Fähigkeiten werden als sinnvoll und für die Praxis relevant empfunden.

A proprietary concentrate from Sambucus nigra L.--in its diluted preparation as part of a hypocaloric diet available in Switzerland--had no impact on urinary pH, urinary hydrogen ion concentrations or 24 h excretion and thus did not influence the solubility of stone-inducing ions.

Background Home (HBPM) and ambulatory (ABPM) blood pressure measurements have their advantages and disadvantages in diagnosing and managing hypertension. We studied HBPMs and ABPMs in volunteers taking part in a survey. Methods Of 366 respondents, 270 provided a total of 5997 triplicate HBPMs ( Part 1 ); 175 also provided data on ABPMs, of which the measurements obtained between 6 am and 10 pm were used in this study (Part 2 ). Results Part 1 , When all 5997 triplicate HPPMs were considered, 1st readings tended to be significantly higher than those of the 2nd and 3rd for both, systolic and diastolic pressures, but when the consideration was restricted to the very first triplicate of each of the 270 subjects, this was true only for systolic HBPM. Part 2 , The ABPMs tended to have a wider range than the corresponding HBPMs, and to be distributed towards higher values. Of the non-parametric indices of (ABPM - corresponding HBPM), (First Quartile, Median, Third Quartile and Maximim) all but the minima had positive values. Conclusions In triplicate HBPMs, the first measurement is usually but not always the highest. Increasing the number of triplicates provided by each subject increases the chance of discriminating between measurements in the triplicates. ABPMs tended to be higher than the corresponding HBPMs.

A proprietary concentrate from Sambucus nigra L. – in its diluted preparation as part of a hypocaloric diet available in Switzerland – had no impact on urinary pH, urinary hydrogen ion concentrations or 24 h excretion and thus did not influence the solubility of stone-inducing ions. Copyright © 2008 John Wiley & Sons, Ltd.

Cycloheximide, an inhibitor of protein synthesis on cytoplasmic ribosomes in eukaryotes, is shown to shift the phase of the circadian rhythm in stimulated bioluminescence in the marine dinoflagellate Gonyaulax polyedra . Kinetic analysis of the phase changes shows that this effect may be subdivided into two distinctly different and well-separated parts. The first (early) phase change occurs with 15-min exposure to cycloheximide and is saturated at low concentrations (≈10 nM). The second (late) phase changes requires about 150 min of exposure to cycloheximide and is saturated at 0.36 μM cycloheximide. Twenty-times-higher concentrations cause no further phase changes. The magnitudes of both early and late phase changes depend on the time of day when the cells are exposed to cycloheximide. Early phase changes vary from 5 hr advance at circadian time (CT) 20 to 1 hr delay at CT 12; late phase changes are larger, the maximal advance being 12 hr at CT 16 and the greatest delay, 10 hr at CT 14. It is proposed that the early phase changes are caused by alterations in the ion distribution across membranes as a consequence of the permeation of cycloheximide. Late phase changes may be the result of inhibition of protein synthesis. The phase response curve for the late phase change is identical to that obtained with saturating light pulses in otherwise constant darkness in Gonyaulax . Maximal phase changes drive the clock into the part of the circadian cycle between CTs 4 and 9. Perturbations in this part of the circadian cycle are without effect on phase. Incubation of Gonyaulax with cycloheximide for a critical duration at a critical time induces arhythmicity, but longer exposures to the inhibitor at the same time do not. This observation suggests the existence of a singularity in the circadian clock of Gonyaulax .

The total RNA in stationary phase cultures of the dinoflagellate,Gonyaulax polyedra, in continuous light showed a well-defined circadian rhythm, as measured by the fluorescence of cells stained with acridine orange. The maximum RNA was found at CT 18 and was followed by a sharp drop in RNA content. The rhythm in RNA content could be phase-shifted by light in the same way as the rhythm in bioluminescence. Ribosomal RNA synthesis, as measured by the incorporation of32P into extracted RNA, was also rhythmic. New RNAs appeared at CT 18, as shown by acrylamide/agarose gel electrophoresis. Three to four hours later these RNAs had disappeared. These findings suggest a role of transcription in the expression of circadian rhythmicity inGonyaulax.