Serological survey in the Finnish human population implies human-to-human transmission of Ljungan virus or antigenically related viruses

Ljungan virus (LV) is a picornavirus related to human parechoviruses (HPeV). The virus has been found in bank voles (Myodes glareolus) and several other rodent species, and suggested to have zoonotic potential. Thus far, seroepidemiological data on LV infections in humans are scarce. In this study, we aimed to characterize the demographic and geographical distribution of LV-reactive antibodies in Finland, and to investigate its occurrence in patients suspected of having a rodent-borne disease, nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV). Using an immunofluorescence assay (LV strain 145SLG), we screened human sera (n = 1378) and found LV-reactive antibodies in 36% of samples. The probability of possessing LV-reactive antibodies peaked at age of 14 years, suggesting that most infections occur in childhood. The prevalence of LV-reactive antibodies was significantly higher in the urbanized area surrounding Helsinki than in more rural Central Finland. These findings are uncharacteristic of a rodent-borne pathogen, and therefore we consider human-to-human transmission of one or several Ljungan-like viruses as a likely cause for most of the observed antibody responses.Peer reviewe

Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >= 2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.Peer reviewe

Specialist laboratory networks as preparedness and response tool - The emerging viral diseases-expert laboratory network and the chikungunya outbreak, Thailand, 2019

We illustrate the potential for specialist laboratory networks to be used as preparedness and response tool through rapid collection and sharing of data. Here, the Emerging Viral Diseases-Expert Laboratory Network (EVD-LabNet) and a laboratory assessment of chikungunya virus (CHIKV) in returning European travellers related to an ongoing outbreak in Thailand was used for this purpose. EVD-LabNet rapidly collected data on laboratory requests, diagnosed CHIKV imported cases and sequences generated, and shared among its members and with the European Centre for Disease Prevention and Control. Data across the network showed an increase in CHIKV imported cases during 1 October 2018-30 April 2019 vs the same period in 2018 (172 vs 50), particularly an increase in cases known to be related to travel to Thailand (72 vs 1). Moreover, EVD-LabNet showed that strains were imported from Thailand that cluster with strains of the ECSA-IOL E1 A226 variant emerging in Pakistan in 2016 and involved in the 2017 outbreaks in Italy. CHIKV diagnostic requests increased by 23.6% between the two periods. The impact of using EVD-LabNet or similar networks as preparedness and response tool could be improved by standardisation of the collection, quality and mining of data in routine laboratory management systems

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

National MEDigi project:systematic implementation of digitalization to undergraduate medical and dental education in Finland

Abstract MEDigi is a nationwide Finnish project that aims to develop and implement digital teaching, learning and assessment solutions and to provide possibilities for national harmonization of undergraduate medical and dental education in Finland. The MEDigi project will investigate the options and feasibility of a common national digital online platform and produce digital content and solutions for medical education. Furthermore, tools and support system for digital pedagogy training will be created to ensure that the teaching staff will achieve and retain appropriate digipedagogical skills. The project aims also to increase the competence related to the digital tools used in clinical practice (eHealth, digital health) of physicians and dentists. Furthermore, academic research will be carried out on various aspects of the project. All the universities in Finland that offer the Licentiate Degree in Medicine and Dentist programmes are involved: Universities of Eastern Finland, Helsinki, Oulu, Tampere and Turku. The project is coordinated by the University of Oulu. The project is carried out in close collaboration with the Finnish Medical Society Duodecim and the Finnish Dental Society Apollonia. The project lifespan is until the end of May 2021. MEDigi project is financed by the Finnish Ministry of Culture and Education and its total budget is over 4 million euros

Normaalipaineisen hydrokefaluksen kliininen kuva, diagnostiset tutkimukset ja hoito

Abstract Acute hydrocephalus is a life-threatening emergency. Primary diagnosis and suspected shunt malfunction requires immediate CT or MR imaging and neurosurgical consultation. Normal pressure hydrocephalus (NPH) is a chronic degenerative disease but requires prompt diagnosis and treatment due to progressive nature. Recent studies indicate apparent specific disease mechanisms of idiopathic NPH including potential genetic risk factors. CSF shunt may significantly improve gait, urinary incontinence and cognitive symptoms in selected patients. Noteworthy, iNPH seems to progress frequently despite of shunt emphasizing the need for active follow-up. Recognition and appropriate treatment of potential comorbid neurodegenerative diseases like vascular dementia and Alzheimer’s disease are needed in case of cognitive deterioration.Tiivistelmä Akuutti hydrokefalia on henkeä uhkaava tila kaikenikäisillä. Mikäli sunttiriippuvaisella potilaalla epäillään suntin toimintahäiriötä, on pään TT (tai MK) tehtävä viipymättä ja tarvitessa konsultoitava päivystävää neurokirurgista yksikköä välittömästi. Normaalipaineinen hydrokefalia (NPH) on harvoin päivystyksellinen ongelma, mutta tauti on selkeästi etenevä ja hoidon viivästyminen heikentää ennustetta. Tuoreet tutkimukset avaavat idiopaattisen NPH-taudin (iNPH) etiologiaa ja patofysiologisia mekanismeja sekä ennustetta. Osalla potilaista likvorisuntti voi merkittävästi lievittää oireita, erityisesti liikkumisvaikeuksia mutta myös inkontinenssia ja tiedonkäsittelyn ongelmia. Suntista huolimatta tauti pyrkii vuosien myötä etenemään, korostaen seurannan merkitystä. iNPH potilailla on usein myös samanaikainen vaskulaarinen kognitiivinen heikkenemä, Alzheimerin tauti tai muu aivorappeumasairaus, joka on myös diagnosoitava ja hoidettava

Cerebrospinal fluid and MRI biomarkers in neurodegenerative diseases:a retrospective memory clinic-based study

Abstract Background: Cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers of neurodegenerative diseases are relatively sensitive and specific in highly curated research cohorts, but proper validation for clinical use is mostly missing. Objective: We studied these biomarkers in a novel memory clinic cohort with a variety of different neurodegenerative diseases. Methods: This study consisted of 191 patients with subjective or objective cognitive impairment who underwent neurological, CSF biomarker (Aβ42, p-tau, and tau) and T1-weighted MRI examinations at Kuopio University Hospital. We assessed CSF and imaging biomarkers, including structural MRI focused on volumetric and cortical thickness analyses, across groups stratified based on different clinical diagnoses, including Alzheimer’s disease (AD), frontotemporal dementia, dementia with Lewy bodies, Parkinson’s disease, vascular dementia, and mild cognitive impairment (MCI), and subjects with no evidence of neurodegenerative disease underlying the cognitive symptoms. Imaging biomarkers were also studied by profiling subjects according to the novel amyloid, tau, and, neurodegeneration (AT(N)) classification. Results: Numerous imaging variables differed by clinical diagnosis, including hippocampal, amygdalar and inferior lateral ventricular volumes and entorhinal, lingual, inferior parietal and isthmus cingulate cortical thicknesses, at a false discovery rate (FDR)-corrected threshold for significance (analysis of covariance; p < 0.005). In volumetric comparisons by AT(N) profile, hippocampal volume significantly differed (p < 0.001) between patients with normal AD biomarkers and patients with amyloid pathology. Conclusion: Our analysis suggests that CSF and MRI biomarkers function well also in clinical practice across multiple clinical diagnostic groups in addition to AD, MCI, and cognitively normal groups

Serum neurofilament light chain in FTLD:association with C9orf72, clinical phenotype, and prognosis

Abstract Objective: The aim of the present study was to compare the levels of serum neurofilament light chain (sNfL) in frontotemporal lobar degeneration (FTLD) patients of different clinical subtypes (bvFTD, PPA, and FTLD‐MND) and with or without the C9orf72 repeat expansion, and to correlate sNfL levels to disease progression, assessed by the brain atrophy rate and survival time. Methods: The sNfL levels were determined from 78 FTLD patients (C9orf72 repeat expansion carriers [n = 26] and non‐carriers [n = 52]) with Single Molecule Array (SIMOA). The progression of brain atrophy was evaluated using repeated T1‐weighted MRI scans and the survival time from medical records. Results: In the total FTLD cohort, sNfL levels were significantly higher in C9orf72 repeat expansion carriers compared to non‐carriers. Considering clinical phenotypes, sNfL levels were higher in the C9orf72 repeat expansion carriers than in the non‐carriers in bvFTD and PPA groups. Furthermore, sNfL levels were the highest in the FTLD‐MND group (median 105 pg/mL) and the lowest in the bvFTD group (median 27 pg/mL). Higher sNfL levels significantly correlated with frontal cortical atrophy rate and subcortical grey matter atrophy rate. The higher sNfL levels also associated with shorter survival time. Interpretation: Our results indicate that the C9orf72 repeat expansion carriers show elevated sNFL levels compared to non‐carriers and that the levels differ among different clinical phenotypes of FTLD. Higher sNfL levels correlated with a shorter survival time and cortical and subcortical atrophy rates. Thus, sNfL could prove as a potential prognostic biomarker in FTLD

A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics

Background. Primary diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is based on detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates. Methods. We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), Si and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, Middle East respiratory syndrome (MERS), and 4 low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA, and IgM EIA results. Results. The sensitivity of EIA for detecting immune response in COVID-19 patients (n = 101) was 77% in the acute phase and 100% in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. Si and RBD-based EIA results had a strong correlation with microneutralization test results. Conclusions. The data indicate a combination of SARS-CoV-2 Si or RBD and N proteins and analysis of IgG and IgA immunoglobulin classes in sera provide an excellent basis for specific and sensitive serological diagnostics of COVID-19.Peer reviewe