In vitro diagnostika uue määruse – IVDRi – tähendus laboritele kliinikumi ühendlabori vaates

Eesti Arst 2022; 101(3):19

Longitudinal proteomic profiling reveals increased early inflammation and sustained apoptosis proteins in severe COVID-19

SARS-CoV-2 infection has a risk to develop into life-threatening COVID-19 disease. Whereas age, hypertension, and chronic inflammatory conditions are risk factors, underlying host factors and markers for disease severity, e.g. requiring intensive care unit (ICU) treatment, remain poorly defined. To this end, we longitudinally profiled blood inflammation markers, antibodies, and 101 plasma proteins of hospitalized COVID-19 patients who did or did not require ICU admission. While essentially all patients displayed SARS-CoV-2-specific antibodies and virus-neutralization capacity within 12-15 days, a rapid, mostly transient upregulation of selective inflammatory markers including IL-6, CXCL10, CXCL11, IFN gamma, IL-10, and monocyte-attracting CCL2, CCL7 and CCL8, was particularly evident in ICU patients. In addition, there was consistent and sustained upregulation of apoptosis-associated proteins CASP8, TNFSF14, HGF, and TGFB1, with HGF discriminating between ICU and non-ICU cohorts. Thus, COVID-19 is associated with a selective inflammatory milieu within which the apoptotic pathway is a cardinal feature with potential to aid risk-based patient stratification.Peer reviewe

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Päranditurism Eestis: Potentsiaal ja arenguvõimalused

Uuringu "Päranditurism Eestis: Potentsiaal ja arenguvõimalused" teostas Ettevõtluse Arenduse Sihtasutuse tellimusel 15.05.2020 - 15.03.2021 Tartu Ülikooli ajaloo ja arheoloogia instituut koostöös TÜ geograafia instituudi, Viljandi Kultuuriakadeemia ning Eesti Kirjandusmuuseumi Eesti Rahvaluule Arhiiviga. Uuring, mille eesmärk oli edendada turismi, eeskätt välisturismi Eesti maapiirkondades, kaardistas Eesti ajaloo- ja kultuuripärandit, mis võiks väliskülalistele huvi pakkuda. Määratleti pärandiliigid ja Eesti-sisesed pärandiregioonid, samuti „suured „lood“, mida võiks kasutada Eesti tutvustamiseks esmakülastajatele. Kaardistati pärandi paiknemine ja välisturistide huvid selle vastu nende päritoluriikide põhiselt, esitati soovitused konkreetsetele sihtgruppidele päranditurismi edendamiseks. Uuringu toimumist vahendas Eesti Teadusagentuur

Distinct Nuclear Organization of Telomeres and Centromeres in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Both multiple myeloma (MM) and its precursor state of monoclonal gammopathy of undetermined significance (MGUS) are characterized by an infiltration of plasma cells into the bone marrow, but the mechanisms underlying the disease progression remain poorly understood. Previous research has indicated that 3D nuclear telomeric and centromeric organization may represent important structural indicators for numerous malignancies. Here we corroborate with previously noted differences in the 3D telomeric architecture and report that modifications in the nuclear distribution of centromeres may serve as a novel structural marker with potential to distinguish MM from MGUS. Our findings improve the current characterization of the two disease stages, providing two structural indicators that may become altered in the progression of MGUS to MM

Boosting the monitoring of phytoplankton in optically complex coastal waters by combining pigment-based chemotaxonomy and in situ radiometry

Research about the occurrence and extent of the cyanobacterial blooms in the Baltic Sea is critical due to their increased magnitude and frequency. Monitoring of the blooms is complicated due to their spatially and tem- porally heterogeneous nature. For adequate assessment of the water quality, phytoplankton dynamics needs to be tracked in large areas with high monitoring frequency. The main objectives of this study were (1) to describe phytoplankton community composition by pigment-based chemotaxonomy and validate the results with mi- croscopy; (2) to improve the retrieval of information about phytoplankton community by combining remote sensing with laboratory based approaches (3) to develop a region-specific algorithm to calculate cyanobacteria biomass from reflectance spectra; (4) to detect and quantify potentially toxic bloom-forming cyanobacteria with molecular methods. In our study the reflectance-based chlorophyll a (Chl a) values overestimated the High- performance Liquid Chromatography (HPLC) values although the correlations with HPLC Chl a measurements were very strong (rp ∼ 0.8, p < 0.001). We found that 709 nm/620 nm reflectance ratio correlated strongly (rp = 0.75, p < 0.01) to cyanobacteria wet biomass in CDOM-rich Väinameri even at low cyanobacterial bio- mass levels. Correlations between pigment-based chemotaxonomy and microscopy were significant in case of cyanobacteria (rp = 0.73, p < 0.01), cryptophytes (rp = 0.71, p < 0.05) and dinoflagellates (rp = 0.64, p < 0.05).This work was supported by Estonian Ministry of Education and Research (IUT 21-02), Estonian Science Foundation (ETF9102, ETF8576), Estonian Research Council (PUTJD719), base-financed pro- ject P180023PKKH of Estonian University of Life Sciences and by Estonian Doctoral School of Earth Sciences and Ecology. We thank Dr Teele Ligi (University of Tartu) for valuable help, Simon Wright and other developers of CHEMTAX program (Australian Antarctic Division, CSIRO). The authors acknowledge CYANOCOST-COST ES 1105 for networking and sharing knowledge.This work was supported by Estonian Ministry of Education and Research (IUT 21-02), Estonian Science Foundation (ETF9102, ETF8576), Estonian Research Council (PUTJD719), base-financed pro- ject P180023PKKH of Estonian University of Life Sciences and by Estonian Doctoral School of Earth Sciences and Ecology. We thank Dr Teele Ligi (University of Tartu) for valuable help, Simon Wright and other developers of CHEMTAX program (Australian Antarctic Division, CSIRO). The authors acknowledge CYANOCOST-COST ES 1105 for networking and sharing knowledge

Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma

The prognosis of multiple myeloma (MM), an incurable B-cell malignancy, has significantly improved through the introduction of novel therapeutic modalities. Myeloma prognosis is essentially determined by cytogenetics, both at diagnosis and at disease progression. However, for a large cohort of patients, cytogenetic analysis is not always available. In addition, myeloma patients with favorable cytogenetics can display an aggressive clinical course. Therefore, it is necessary to develop additional prognostic and predictive markers for this disease to allow for patient risk stratification and personalized clinical decision-making. Genomic instability is a prominent characteristic in MM, and we have previously shown that the three-dimensional (3D) nuclear organization of telomeres is a marker of both genomic instability and genetic heterogeneity in myeloma. In this study, we compared in a longitudinal prospective study blindly the 3D telomeric profiles from bone marrow samples of 214 initially treatment-naïve patients with either monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with a minimum follow-up of 5 years. Here, we report distinctive 3D telomeric profiles correlating with disease aggressiveness and patient response to treatment in MM patients, and also distinctive 3D telomeric profiles for disease progression in smoldering multiple myeloma patients. In particular, lower average intensity (telomere length, below 13,500 arbitrary units) and increased number of telomere aggregates are associated with shorter survival and could be used as a prognostic factor to identify high-risk SMM and MM patients.Medicine, Faculty ofNon UBCMedicine, Department ofReviewedFacult