Hepatitis A in Switzerland : an analysis of 29 years of surveillance data and contemporary challenges

Hepatitis A (HA) incidence declined in most European countries in the past decades. We analysed HA notification data for Switzerland of 29 years looking for disease- and notification system-related factors possibly contributing to observed trends.; Notification data were descriptively analysed using five time intervals (1988-1993, 1994-1999, 2000-2005, 2006-2011, 2012-2016); and notification rates were calculated.; From 1988 to 2016, the HA notification rate decreased from 9.5 to 0.5 per 100'000 population in Switzerland. Median age and the proportion of hospitalised cases increased over time. In the 1988-1993-time period, intravenous drug use was the most frequently mentioned risk exposure while consumption of contaminated food/beverages was most frequently mentioned in the 2012-2016-time period.; Notification data does not allow reliably identifying current risk groups (e.g. travellers) due to low case numbers, limited availability and reliability of information. It is important to document changes in the surveillance system for later analyses and interpretation of long-term trends. Population susceptibility likely increases underlining the importance of continued and continuous surveillance and prevention efforts despite decreasing case numbers. Operational research is recommended to further investigate observed trends of HA and to enhance the abilities for decision making from Swiss HA surveillance data

Women in cardiology: past, present and future

In 2018, the Swiss Society of Cardiology celebrated its70thyear. Is this also a celebration for the achievement ofwomen in cardiology? Yes and no

A tradition and an epidemic: determinants of the campylobacteriosis winter peak in Switzerland

Campylobacteriosis is the most frequently reported food borne infection in Switzerland. We investigated determinants of infections and illness experience in wintertime. A case-control study was conducted in Switzerland between December 2012 and February 2013. Cases were recruited among laboratory-confirmed campylobacteriosis patients. Population-based controls were matched according to age group, sex and canton of residence. We determined risk factors associated with campylobacteriosis, and help seeking behaviour and illness perception. The multivariable analysis identified two factors associated with an increased risk for campylobacteriosis: consumption of meat fondue (matched odds ratio [mOR] 4.0, 95% confidence interval [CI] 2.3-7.1) and travelling abroad (mOR 2.7, 95% CI 1.1-6.4). Univariable analysis among meat fondue consumers revealed chicken as the type of meat with the highest risk of disease (mOR 3.8, 95% CI 1.1-13.5). Most frequently reported signs and symptoms among patients were diarrhoea (98%), abdominal pain (81%), fever (66%), nausea (44%) and vomiting (34%). The median perceived disease severity was 8 on a 1-to-10 rating scale. Patients reported a median duration of illness of 7days and 14% were hospitalised. Meat fondues, mostly "Fondue chinoise”, traditionally consumed during the festive season in Switzerland, are the major driver of the epidemic campylobacteriosis peak in wintertime. At these meals, individual handling and consumption of chicken meat may play an important role in disease transmission. Laboratory-confirmed patients are severely ill and hospitalisation rate is considerable. Public health measures such as decontamination of chicken meat and improved food handling behaviour at the individual level are urgently needed

Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome

Purpose: Early after [18F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [18F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [18F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. Methods: Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0-60 min) [18F]PI-2620 PET imaging. Regional perfusion (0.5-2.5 min p.i.) and tau load (20-40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value - 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). Results: Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale (R = 0.402; p = 0.0012) and activities of daily living (R = - 0.431; p = 0.0005). Conclusion: [18F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression

The EC-Earth3 Earth system model for the Coupled Model Intercomparison Project 6

The Earth system model EC-Earth3 for contributions to CMIP6 is documented here, with its flexible coupling framework, major model configurations, a methodology for ensuring the simulations are comparable across different high-performance computing (HPC) systems, and with the physical performance of base configurations over the historical period. The variety of possible configurations and sub-models reflects the broad interests in the EC-Earth community. EC-Earth3 key performance metrics demonstrate physical behavior and biases well within the frame known from recent CMIP models. With improved physical and dynamic features, new Earth system model (ESM) components, community tools, and largely improved physical performance compared to the CMIP5 version, EC-Earth3 represents a clear step forward for the only European community ESM. We demonstrate here that EC-Earth3 is suited for a range of tasks in CMIP6 and beyond.Peer reviewe

Organosulfates as Tracers for Secondary Organic Aerosol (SOA) Formation from 2-Methyl-3-Buten-2-ol (MBO) in the Atmosphere

2-Methyl-3-buten-2-ol (MBO) is an important biogenic volatile organic compound (BVOC) emitted by pine trees and a potential precursor of atmospheric secondary organic aerosol (SOA) in forested regions. In the present study, hydroxyl radical (OH)-initiated oxidation of MBO was examined in smog chambers under varied initial nitric oxide (NO) and aerosol acidity levels. Results indicate measurable SOA from MBO under low-NO conditions. Moreover, increasing aerosol acidity was found to enhance MBO SOA. Chemical characterization of laboratory-generated MBO SOA reveals that an organosulfate species (C5H12O6S, MW 200) formed and was substantially enhanced with elevated aerosol acidity. Ambient fine aerosol (PM2.5) samples collected from the BEARPEX campaign during 2007 and 2009, as well as from the BEACHON-RoMBAS campaign during 2011, were also analyzed. The MBO-derived organosulfate characterized from laboratory-generated aerosol was observed in PM2.5 collected from these campaigns, demonstrating that it is a molecular tracer for MBO-initiated SOA in the atmosphere. Furthermore, mass concentrations of the MBO-derived organosulfate are well correlated with MBO mixing ratio, temperature, and acidity in the field campaigns. Importantly, this compound accounted for an average of 0.25% and as high as 1% of the total organic aerosol mass during BEARPEX 2009. An epoxide intermediate generated under low-NO conditions is tentatively proposed to produce MBO SOA

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity