Cryptosporidium-alkueläimen diagnostiikka ja esiintyminen vasikoilla

Kaikki Cryptosporidium-sukuun kuuluvat alkueläimet ovat solunsisäisiä parasiitteja, jotka voivat infektoida yli 150 nisäkäslajin lisäksi myös lintuja, matelijoita, sammakkoeläimiä ja kaloja. Kryptosporideja esiintyy kaikkialla maailmassa. Tutkituin Cryptosporidium-laji on Cryptosporidium parvum, joka on varsinkin nuorten vasikoiden parasiitti. Muita naudoilla esiintyviä kryptosporidilajeja ovat Cryptosporidium bovis, Cryptosporidium ryanae ja Cryptosporidium andersoni. Kryptosporidioosiksi kutsutaan Cryptosporidium-alkueläimen aiheuttamaa tautia, jonka tyypillisin oire on itsestään rajoittuva lievä ripuli. Kryptosporidioosi diagnosoidaan etsimällä Cryptosporidium-alkueläimen ookystamuotoja ulostenäytteistä. Yleisimmin käytössä oleva menetelmä on joko värjättyjen tai värjäämättömien näytteiden mikroskopointi. Cryptospordium-alkueläimiä voidaan tutkia suoraan ulostenäytteistä, mutta yleensä näytteet konsentroidaan ennen varsinaista diagnosointia. Konsentrointimenetelmillä pyritään kasvattamaan ulostenäytteiden ookystien määrää suhteessa näytetilavuuteen, jolloin niiden havaitseminen helpottuu. Konsentrointi tapahtuu käyttämällä apuna erilaisia sentrifugointi- ja flotaatiomenetelmiä sekä tietyn tiheyden omaavia suola- tai sokeriliuoksia. Kryptosporideille on viime vuosina kehitetty myös useita polymeraasiketjureaktioon (PCR) perustuvia molekylaarisia tunnistusmenetelmiä. Tutkimuksen tarkoituksena oli verrata keskenään Cryptosporidium-alkueläinten diagnostiikassa käytettäviä analyysimenetelmiä sekä kartoittaa kryptosporidien esiintymistä vasikoilla. Ulostenäytteet kerättiin vasikoiden kolmivaihekasvattamosta, jossa vasikat olivat keskimäärin alle kuukauden ikäisiä. 64 näytettä sisälsivät riittävästi ulostetta, jotta ne voitiin hyväksyä tutkimukseen. Tutkimuksen kokeellisessa osassa tarkasteltiin kolmea yleisimmin käytössä olevaa kryptosporidien konsentrointimenetelmää, jotka olivat natriumkloridiflotaatio, sokeriflotaatio ja formaliini-etyyliasetaattimenetelmä. Cryptosporidium-ookystien havaitsemiseen konsentroiduista ulostenäytteistä käytettiin sekä Ziehl-Neelsen värjäysmenetelmää että polymeraasiketjureaktiota (PCR). Kahdeksan kryptosporidien suhteen positiivista ulostenäytettä tyypitettiin DNA-sekvensoinnin avulla, jotta saatiin tietoa Suomessa esiintyvien Cryptosporidium-lajien prevalensseista. Analysoiduista 64 ulostenäytteestä 19 (29,7 %) oli PCR-menetelmällä kryptosporidien suhteen positiivisia. DNA-sekvensointiin valituista kahdeksasta näytteestä seitsemän oli genotyypiltään C. bovis ja yksi C. ryanae. Verratuista Cryptosporidium-alkueläinten diagnostiikassa käytettävistä menetelmistä Ziehl-Neelsen värjäys sopii varsinkin kliinisten näytteiden analysointiin, jotka sisältävät paljon ookystia. PCR-menetelmää kannattaa käyttää näytteille, joiden ookystamäärä on vähäinen tai joiden parasitologinen status halutaan selvittää laji- tai genotyyppitasolle asti. Tämän tutkimuksen perusteella kryptosporidien diagnostiikassa käytettävistä konsentrointimenetelmistä toimivin on natriumkloridiflotaatio, ja se voidaan ongelmitta yhdistää joko PCR-menetelmään tai Ziehl-Neelsen-värjäykseen

Katsaus suomalaisen yrittäjyyskasvatustutkimuksen nykytilaan ja tulevaisuuden suuntiin

In this review article, we examine the current state of Finnish entrepreneurship education research and the directions of the future. Our goal is to find out to what extent and what kind of research Finnish entrepreneurship education researchers have carried out and published in major Finnish and international research publications (journals) during 2015–2020. As a research method, we have applied an integrative literature review and qualitative content analysis of 26 research articles. The results of the review show that in recent years Finnish entrepreneurship education researchers have focused on the same thematic themes as their international peer scholars with the main focus of research being on entrepreneurial learning issues. In addition to this, also issues and factors related to entrepreneurial teaching are examined and the institutional level, effecting on both learning and teaching, is opened up. In this respect, Finnish entrepreneurship education research seems to follow much the same paths as international entrepreneurship education research, particularly European and Nordic streams of it. However, Finnish entrepreneurship education research also seems to have its specific characteristics. As the Finnish-language studies published in Finland shows, the dialogue between entrepreneurship and education is more robust, and there is a stronger focus on educational policy. A more critical approach to entrepreneurship education has also been applied compared to international entrepreneurship education research.Tarkastelemme tässä katsausartikkelissa suomalaisen yrittäjyyskasvatustutkimuksen nykytilaa ja tulevaisuuden suuntia. Tavoitteenamme on selvittää missä määrin ja minkälaista tutkimusta suomalaiset yrittäjyyskasvatustutkijat ovat tehneet ja julkaisseet merkittävissä kotimaisissa ja kansainvälisissä tutkimusjulkaisuissa (journals) vuosien 2015–2020 aikana. Tutkimusmenetelmänä olemme soveltaneet integroivaa kirjallisuuskatsausta ja artikkelien analyysimenetelmänä on käytetty laadullista sisällönanalyysiä. Tulokset osoittavat, että tarkasteltavana ajanjaksona suomalaisten yrittäjyyskasvatustutkijoiden mielenkiinnon kohteena on ollut erityisesti yrittäjämäinen oppiminen ja siihen liittyvät kysymykset. Tämän ohella on tarkasteltu myös yrittäjämäiseen opettajuuteen liittyviä tekijöitä sekä avattu institutionaalisen tason vaikutuksia niin oppimiseen kuin opettamiseenkin. Suomalainen yrittäjyyskasvatustutkimus näyttäisi noudattelevan niin temaattisesti kuin myös metodologisesti pitkälti samoja polkuja kansainvälisen, etenkin eurooppalaisen ja pohjoismaisen yrittäjyyskasvatustutkimuksen kanssa. Suomalaiselle yrittäjyyskasvatustutkimukselle on kuitenkin tunnistettavissa myös erityispiirteitä. Etenkin kotimaassa julkaistussa suomenkielisessä tutkimuksessa näkyy yrittäjyyden ja kasvatuksen tiivis vuoropuhelu, voimakkaampi koulutuspoliittinen näkemys ja myös yrittäjyyskasvatukselle kriittisempi ote kansainväliseen yrittäjyyskasvatustutkimukseen verrattuna

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

Genetic Risk Score for Intracranial Aneurysms : Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10-3per year [95% CI, -6.49×10-3to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.Peer reviewe

FinnGen provides genetic insights from a well-phenotyped isolated population

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.Peer reviewe

FinnGen provides genetic insights from a well-phenotyped isolated population.

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10-11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants

Sleep apnoea is a risk factor for severe COVID-19

Background Obstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if OSA is an independent risk factor for COVID-19 infection or for severe COVID-19.Methods OSA diagnosis and COVID-19 infection were extracted from the hospital discharge, causes of death and infectious diseases registries in individuals who participated in the FinnGen study (n=260 405). Severe COVID-19 was defined as COVID-19 requiring hospitalisation. Multivariate logistic regression model was used to examine association. Comorbidities for either COVID-19 or OSA were selected as covariates. We performed a meta-analysis with previous studies.Results We identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10−5, OR-adjusted=2.93 (95% CI 1.02 to 8.39), p-adjusted=0.045). OSA was not associated with the risk of contracting COVID-19 (p=0.25). A meta-analysis of OSA and severe COVID-19 showed association across 15 835 COVID-19 positive controls, and n=1294 patients with OSA with severe COVID-19 (OR=2.37 (95% 1.14 to 4.95), p=0.021).Conclusion Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19