Julkaisut
2026
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Professional Stakeholders' Perspectives on Early Screening for Type 1 Diabetes in Children: A Systematic Review
Early screening for type 1 diabetes (T1D) is receiving increasing attention as presymptomatic screening initiatives and disease-modifying therapies continue to expand. However, the perspectives of professional stakeholders, who play a pivotal role in implementation, patient engagement, and health system preparedness, have not been systematically synthesised. We conducted a systematic review to examine professional views on paediatric early T1D screening. Following PRISMA guidelines, six... -
Network-level restoration of impaired memory function in early Alzheimer's disease via GluN2B modulation: insights from a hippocampal CA1-CA3 model
Memory storage and recall are essential tasks for the healthy function of the hippocampus, adversely affected by neurodegenerative diseases, such as Alzheimer's Disease (AD). Pathological levels of amyloid-β peptide (Aβ), found already in early-stage AD, can disrupt the NMDAR-dependent plasticity at hippocampal networks. Here we investigate these effects in a biophysically detailed computational model of a hippocampal CA1-CA3 network and examine potential mechanisms of functional recovery. We... -
Testing the safety of nature-based microbial exposure in atopic dermatitis patients: a randomized, placebo-controlled, double-blinded pilot trial
The biodiversity hypothesis posits that contact with microbial biodiversity is beneficial for human health, and that the loss of such contact may contribute to immune-mediated diseases such as atopy. Based on this hypothesis, we aimed to investigate whether a lotion containing a highly diverse mixture of inactivated natural microbes is a safe and feasible method to administer nature-based microbial exposure to humans, and to assess its effects on healthy and atopic skin. Participants with atopic... -
Algorithm to detect IgA deficiency during automated tissue transglutaminase antibody testing
CONCLUSIONS: RU-based screening using the EliA Celikey IgA assay could enable a sensitive, specific and low-cost strategy for identifying individuals requiring IgG-based CeD diagnostics, minimizing the need for routine S-IgA testing. -
Can metformin prolong pregnancy in preterm pre-eclampsia? Study protocol for a Nordic multicentre randomised placebo-controlled trial (PI4)
INTRODUCTION: Pre-eclampsia affects 2–8% of all pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality. A randomised trial in South Africa suggested metformin used to treat preterm pre-eclampsia (26–32 weeks’ gestation) may prolong pregnancy by 7 days compared with standard care. However, this finding was borderline significant and requires validation in higher-resource settings and in diverse populations. Here, we present a Nordic multicentre trial protocol... -
Legislative differences regarding coercive measures in mental health care for children and adolescents across European countries
To examine variations in legal and clinical practice regarding coercive measures use in child and adolescent psychiatry. A study commissioned by the European Society for Child and Adolescent Psychiatry (ESCAP) Policy Division in collaboration with ESCAP executive board. A questionnaire was distributed to representatives of 36 ESCAP member countries aiming to obtain an overview of coercive measures used, with a focus on regulation and use of mechanical and physical restraint, and seclusion. The... -
Stable Overall Volume, Shifting Structure: Nine Years of Paediatric Outpatient Prescribing and Dispensing in Finland, 2017-2025
CONCLUSION: Overall paediatric dispensation volume in Finland was broadly stable across 2017-2025, but the underlying structure changed substantially. Antibiotic stewardship gains held, central nervous system medicine use rose continuously, and the channel mix shifted toward private paediatric care for younger children. If access to private care depends on family resources, this shift may widen inequalities in children's access to prescribed medicines, although socioeconomic factors were not... -
Response to the letter to the editor by Zhou
No abstract -
Letter: Does Adherence-Selected Follow-Up Establish the Benefit-Harm Balance of Population Coeliac Disease Screening? Authors' Reply
No abstract -
Biophysically inspired mean-field model of neuronal populations driven by ion-exchange mechanisms
Whole-brain simulations are a valuable tool for gaining insight into the multiscale processes that regulate brain activity. Due to the complexity of the brain, it is impractical to include all microscopic details in a simulation. Hence, researchers often simulate the brain as a network of coupled neural masses, each described by a mean-field model. These models capture the essential features of neuronal populations while approximating most biophysical details. However, it may be important to... -
Population-scale immune multiome atlas reveals regulatory disease mechanisms
Most disease-associated genetic variants lie in non-coding regions^(1,2), yet mechanistic insights are limited by the lack of an empirical framework for characterizing the molecular consequences of regulatory variation. Single-cell molecular quantitative trait locus (QTL) mapping^(3,4) connects variants to gene regulation but lacks the power and simultaneous measurements to trace mechanisms from chromatin to expression⁵. Here we show that population-scale simultaneous profiling of chromatin... -
Cohort profile update: the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC)
PURPOSE: The Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) study was originally established between 2008 and 2011 to develop a nationwide clinical and genomic database. By enrolling women with and without pre-eclampsia (PE), alongside their partners and infants, the study aims to identify the genetic and molecular determinants of PE. This update summarises the final dataset, reviews key findings since the 2016 cohort profile, and outlines current research directions. -
Gut microbiome maturation in early childhood interacts with host genetics to predict type 1 diabetes risk
Prospective evidence linking early-life microbiome development and host genetics with type 1 diabetes (T1D) risk is limited. Here, we describe how gut microbiome maturation and host genetics influence T1D risk in the TEDDY study. We analysed 12,151 longitudinal metagenomes and host genetic data from 887 children at high genetic risk for T1D followed for up to 6 years. We identify three microbiome maturational patterns: Early Matured, Late Matured and Early Plateaued, driven primarily by... -
Response to the Critique by Banos et al. of Ruuska et al
No abstract -
Other special diets in addition to gluten-free diet are common among youth with celiac disease, but are not associated with overall well-being or treatment success
BackgroundVarious special diets have become increasingly common. However, their prevalence and significance in patients with celiac disease (CeD) who already adhere to a gluten-free diet (GFD) are unclear.AimWe studied the abovementioned aspects in youth with CeD and controls.Methods210 patients and 212 controls, all adolescents and young adults with comparable age 16-30 years, completed an anonymous survey. Variables were compared between CeD patients with and without additional dietary...
2025
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Transient receptor potential ankyrin 1 promotes the expression of interferon-stimulated antiviral genes in human A549 lung epithelial cells
Transient receptor potential ankyrin 1 (TRPA1) is an ion channel known for its chemosensory function in neurons, causing pain and neurogenic inflammation. TRPA1 is activated by many noxious compounds including some inflammatory mediators. We and others have shown that TRPA1 is also expressed in epithelial cells, but its function in the epithelial barrier remains unclear. Here, we discovered in RNA-seq studies that inhibition of TRPA1 reduced the expression of a large number of antiviral and... -
Clustering patterns in Finnish type 1 diabetes patients: a nationwide register-based study
CONCLUSIONS: These results demonstrate evidence of spatiotemporal clustering of T1DM in Finnish children, supporting the hypothesis of environmental triggers in T1DM etiology. These findings highlight the need for further research to identify the specific environmental factors and mechanisms behind the clustering. -
Impact of facility based versus home based growth monitoring and promotion programs on child nutritional status in rural Bangladesh
The delivery platform for growth monitoring and promotion (GMP) programs to improve child nutrition remains debated. This study compared the impact of facility-based plus non-governmental organization supported home-based GMP (FGMP + NGO-supported HGMP) versus facility-based GMP (FGMP) on child nutritional status in rural Bangladesh. Using a quasi-experimental design, 1,519 children aged 6-12 months were enrolled in each program and assessed at baseline and after 12 months. The primary outcome... -
Screening for Celiac Disease in Childhood: Cost-Effectiveness of Multiple Genetic and Serological Testing Approaches
CONCLUSIONS: The most cost-effective screening strategy for celiac disease was single-time untargeted serological testing at age 11. The optimal approach is affected by regional factors and may evolve with new evidence. Repeated screening may be preferable for high-risk groups and with high willingness to pay. -
Genetic liability to psoriasis predicts severe disease outcomes
CONCLUSIONS: The psoriasis susceptibility PRS demonstrates utility and may be more effective than established epidemiological factors, as a stratification tool to identify those individuals that are at greatest risk of severe disease and may benefit most from early intervention. -
Risk of Celiac Disease Before and After Nationwide Infant Rotavirus Vaccination: A Population-Based Study
CONCLUSIONS: This study did not find an association between rotavirus vaccine and the risk of early-onset celiac disease. -
High-Flow Oxygen Therapy vs. Continuous Positive Airway Pressure in Hospitalised Bronchiolitis: A Meta-Analysis
CONCLUSION: Both HFOT and CPAP were safe for treating bronchiolitis, but CPAP showed a lower risk of treatment failure. Our results can be generalized to those treated in the PICU. -
Characteristics and Long-Term Prognosis of Celiac Disease: Comparisons between Patients Diagnosed either in Childhood or Adulthood
CONCLUSION: Diagnosis in childhood compared to adulthood was associated with disease phenotype and its effects on long-term comorbidities are complex. -
Microbial associations and viruses on the risk of celiac disease (MAVRiC): a longitudinal post-hoc case-cohort study
Celiac disease etiopathogenesis requires genetic predisposition and exposure to gluten, yet these factors alone are not sufficient. Larger longitudinal studies are needed to determine the role of time-varying infections and gut microorganisms. The aim was to design a celiac disease case-cohort longitudinal study using The Environmental Determinants of Diabetes in the Young (TEDDY) study. By age 3-years, persistent tissue transglutaminase autoantibodies (tTGA), i.e., celiac disease autoimmunity... -
Adolescent health behaviors, family socioeconomic status and health as risk factors for tendon ruptures in adulthood: a longitudinal study
CONCLUSION: Frequent participation in sports clubs during adolescence increased the risk of tendon rupture in adulthood, while leisure time physical activity did not. Health compromising behaviors (smoking, alcohol use, overweight) or chronic diseases in adolescence does not seem to play a role in later tendon ruptures until middle age. -
Computational modelling of schizophrenia-associated alterations of ion-channel-encoding gene expression predicts a decrease in delta power
Schizophrenia presents with a wide range of phenotypes that can help to understand the the mechanisms of the disease. Among these, alterations in delta oscillations are especially amenable to experimental investigation, yet the mechanisms underlying these changes remain insufficiently understood. Biophysically detailed computational modeling offers a powerful approach to investigate these phenomena, as it enables multi-scale integration of genetic and electrophysiological data. In this study, we... -
Computational modelling of novelty detection in the mismatch negativity protocols and its impairments in schizophrenia
The human auditory system rapidly distinguishes between novel and familiar sounds, a process reflected in mismatch negativity (MMN), an EEG-based biomarker of auditory novelty detection. MMN is impaired in psychiatric conditions, most notably schizophrenia (SCZ), yet the neuronal mechanisms underlying this deficit remain unclear. Here, we combined computational modelling and genetic analyses to investigate how SCZ-associated cellular abnormalities affect auditory novelty detection. We developed... -
Impact of Preeclampsia Duration on Long-Term Cardiovascular Disease Risk
CONCLUSIONS: Long-term CVD risk before age 55 is estimated to increase 1% to 2% per day from preeclampsia diagnosis to delivery. Women with preeclampsia might benefit from early delivery. -
The prevalence of prediabetes is high and has rapidly increased, independent of the degree of obesity, in Finnish children with overweight or obesity
CONCLUSIONS: Prediabetes was decidedly prevalent in pediatric patients with obesity and was associated particularly with steatotic liver disease. Its prevalence increased steeply over time, independent of the degree of obesity. -
A clinical practice guide to transform care and save newborn lives with kangaroo mother care
No abstract
2024
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Risk of childhood brain tumors after exposure to CT radiation: A nationwide population-based case-control study in Finland
In this nationwide population-based case-control study, we assessed the risk of childhood brain tumors following exposure to radiation from CT. Brain tumors diagnosed in Finland during 1990-2016 were identified by the Finnish Cancer Registry. For each case, three age- and sex-matched controls were sampled from the Population Information System. The study population was linked to a CT dataset encompassing pediatric CTs performed in Finland during 1975-2011. We implemented a 5-year lag period and... -
Prevalence and risk factors of curable sexually transmitted and reproductive tract infections and malaria co-infection among pregnant women at antenatal care booking in Kenya, Malawi and Tanzania: a cross-sectional study of randomised controlled trial data
CONCLUSIONS: Of women infected with malaria, 49.0% also had a curable STI/RTI and one in five women with at least one STI/RTI were co-infected with more than one STI/RTI. Current antenatal interventions that address malaria and curable STIs/RTIs remain suboptimal. New approaches to preventing and managing these infections in pregnancy are urgently needed. -
Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis
BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. -
Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis
BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. -
Early maladaptive schemas, depression and anxiety in adolescent psychiatric out-patients
CONCLUSIONS: Various EMS domains were associated with depressive and anxiety symptoms among adolescent out-patients. Further studies are needed on the effect of EMSs on the treatment outcomes for depression and anxiety. -
Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia
Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to... -
Novel loci and biomedical consequences of iron homoeostasis variation
Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression,... -
Patient perceptions of the Finnish guidelines enabling coeliac disease diagnosis without biopsies in adults
CONCLUSIONS: The non-invasive approach resulted in de-centralized diagnosis and easier patient-experienced diagnostic process of coeliac disease, but was associated with increased risk for persistent symptoms and stress due to gluten-free diet. These results highlight the significance of appropriate patient guidance and support regardless of the diagnostic strategy. -
Inherited infertility: Mapping loci associated with impaired female reproduction
Female infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15%-30% of affected individuals. In our large genome-wide association study (GWAS) of 22,849 women with infertility and 198,989 control individuals from the Finnish population cohort FinnGen, we unveil a landscape of genetic factors associated with the disorder. Our recessive analysis identified a... -
Association between adolescent lifestyle factors and high-energy traumas in early adulthood: A longitudinal study
CONCLUSION: Smoking, monthly drunkenness, self-reported chronic diseases in adolescence, and low educational level in adulthood increased the risk of high-energy traumas during the mean follow-up of 27-years. Frequent physical activity and overweight in adolescence did not predict the occurrence of high-energy traumas. Intervention programs should also focus on the long-term consequences of these risk factors. -
Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations
Given that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs, the genetic basis of LDH has received relatively little research. Our aim is to increase understanding of the genetic factors influencing LDH. We perform a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results. In the meta-analysis, we identify 41... -
Looking back at the TEDDY study: lessons and future directions
The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years)... -
Perinatal and neonatal outcomes in gestational diabetes: The importance of the number of abnormal values in an oral glucose tolerance test
CONCLUSIONS: The risk of adverse perinatal and neonatal outcomes is significantly higher in women with two or more abnormal OGTT values than in those with one abnormal value. -
Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures
Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life... -
Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial
CONCLUSIONS AND RELEVANCE: Although LEN-IE did not meet prespecified statistical significance for improved PFS vs IE, this study demonstrates the importance of international collaboration and randomized clinical trials in patients with relapsed or refractory osteosarcoma and may inform future trial design.
2023
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Risk of childhood brain tumors after exposure to CT radiation: A nationwide population-based case-control study in Finland
In this nationwide population-based case-control study, we assessed the risk of childhood brain tumors following exposure to radiation from CT. Brain tumors diagnosed in Finland during 1990-2016 were identified by the Finnish Cancer Registry. For each case, three age- and sex-matched controls were sampled from the Population Information System. The study population was linked to a CT dataset encompassing pediatric CTs performed in Finland during 1975-2011. We implemented a 5-year lag period and... -
Prevalence and risk factors of curable sexually transmitted and reproductive tract infections and malaria co-infection among pregnant women at antenatal care booking in Kenya, Malawi and Tanzania: a cross-sectional study of randomised controlled trial data
CONCLUSIONS: Of women infected with malaria, 49.0% also had a curable STI/RTI and one in five women with at least one STI/RTI were co-infected with more than one STI/RTI. Current antenatal interventions that address malaria and curable STIs/RTIs remain suboptimal. New approaches to preventing and managing these infections in pregnancy are urgently needed. -
Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis
BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. -
Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis
BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. -
Early maladaptive schemas, depression and anxiety in adolescent psychiatric out-patients
CONCLUSIONS: Various EMS domains were associated with depressive and anxiety symptoms among adolescent out-patients. Further studies are needed on the effect of EMSs on the treatment outcomes for depression and anxiety. -
Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia
Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to... -
Novel loci and biomedical consequences of iron homoeostasis variation
Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression,... -
Patient perceptions of the Finnish guidelines enabling coeliac disease diagnosis without biopsies in adults
CONCLUSIONS: The non-invasive approach resulted in de-centralized diagnosis and easier patient-experienced diagnostic process of coeliac disease, but was associated with increased risk for persistent symptoms and stress due to gluten-free diet. These results highlight the significance of appropriate patient guidance and support regardless of the diagnostic strategy. -
Inherited infertility: Mapping loci associated with impaired female reproduction
Female infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15%-30% of affected individuals. In our large genome-wide association study (GWAS) of 22,849 women with infertility and 198,989 control individuals from the Finnish population cohort FinnGen, we unveil a landscape of genetic factors associated with the disorder. Our recessive analysis identified a... -
Association between adolescent lifestyle factors and high-energy traumas in early adulthood: A longitudinal study
CONCLUSION: Smoking, monthly drunkenness, self-reported chronic diseases in adolescence, and low educational level in adulthood increased the risk of high-energy traumas during the mean follow-up of 27-years. Frequent physical activity and overweight in adolescence did not predict the occurrence of high-energy traumas. Intervention programs should also focus on the long-term consequences of these risk factors. -
Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations
Given that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs, the genetic basis of LDH has received relatively little research. Our aim is to increase understanding of the genetic factors influencing LDH. We perform a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results. In the meta-analysis, we identify 41... -
Looking back at the TEDDY study: lessons and future directions
The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years)... -
Perinatal and neonatal outcomes in gestational diabetes: The importance of the number of abnormal values in an oral glucose tolerance test
CONCLUSIONS: The risk of adverse perinatal and neonatal outcomes is significantly higher in women with two or more abnormal OGTT values than in those with one abnormal value. -
Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures
Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life... -
Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial
CONCLUSIONS AND RELEVANCE: Although LEN-IE did not meet prespecified statistical significance for improved PFS vs IE, this study demonstrates the importance of international collaboration and randomized clinical trials in patients with relapsed or refractory osteosarcoma and may inform future trial design.
2022
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Prolonged grief, post-traumatic stress, and functional impairment in parents and siblings 8 years after the 2011 Utøya terror attack
Background: Research on bereavement after terrorism is limited and primarily aiming on short-term consequences.Objective: To better understand the long-term health consequences of terrorism, we studied bereaved parents and siblings eight years after the Utøya terrorist attack in Norway. We examined the participants' symptom levels of prolonged grief (PG) and post-traumatic stress (PTS), as well as their psychosocial functioning and employment status.Method: Bereaved parents (n = 88) and siblings... -
Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
CONCLUSION: BP-PRS is strongly associated with hypertensive disorders of pregnancy. Our current observations suggest that the BP-PRS could capture the genetic architecture of preeclampsia better than the current PE-PRSs. These findings also emphasize the common pathways in the development of all BP disorders. The clinical utility of a BP-PRS for preeclampsia prediction warrants further investigation. -
Optimized detection of homologous recombination deficiency improves the prediction of clinical outcomes in cancer
Homologous recombination DNA-repair deficiency (HRD) is a common driver of genomic instability and confers a therapeutic vulnerability in cancer. The accurate detection of somatic allelic imbalances (AIs) has been limited by methods focused on BRCA1/2 mutations and using mixtures of cancer types. Using pan-cancer data, we revealed distinct patterns of AIs in high-grade serous ovarian cancer (HGSC). We used machine learning and statistics to generate improved criteria to identify HRD in HGSC... -
Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing... -
Antibiotic prescriptions for child sinusitis varied between specialties after Finnish guidelines were updated in 2018
CONCLUSION: Antibiotics were prescribed for about 40% of acute sinusitis visits by Finnish children from 2014-2019. Specialities differed with regard to prescribing rates and whether they followed the guidelines. -
Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism
The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 year of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes associated with diet-related... -
Impact of Cultivation and Origin on the Fruit Microbiome of Apples and Blueberries and Implications for the Exposome
Vegetables and fruits are a crucial part of the planetary health diet, directly affecting human health and the gut microbiome. The objective of our study was to understand the variability of the fruit (apple and blueberry) microbiome in the frame of the exposome concept. The study covered two fruit-bearing woody species, apple and blueberry, two countries of origin (Austria and Finland), and two fruit production methods (naturally grown and horticultural). Microbial abundance, diversity, and... -
Effects of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries: an individual participant data meta-analysis of 2 198 655 pregnancies
BACKGROUND: Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions. -
Clinical and sonographic improvement of developmental dysplasia of the hip: analysis of 948 patients
CONCLUSION: Female sex and positive family history might be independent risk factors for slower recovery in DDH before 6 months of age. These children might need special attention in their follow-up plans and abduction treatment. -
Associations of low sex hormone-binding globulin and androgen excess in early pregnancy with fasting and post-prandial hyperglycaemia, gestational diabetes, and its severity
CONCLUSIONS: Lower SHBG levels were associated especially with early-onset GDM, higher fasting glucose and insulin treatment, whereas androgen excess was associated with higher post-prandial glucose values. Thus, a low SHBG level may reflect the degree of existing insulin resistance, while androgen excess might impair post-prandial insulin secretion. -
Association of concomitant autoimmunity with the disease features and long-term treatment and health outcomes in Celiac disease
CONCLUSIONS: Co-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support. -
A Chronic Disease in Adolescence and Selection to an Educational Path-A Longitudinal Study
Chronic disease may affect adolescents' educational success. We study whether adolescents with a somatic chronic condition have lower school performance, lower odds for academic education, and a delayed start of upper-secondary studies. Seventh graders and ninth graders in the Helsinki Metropolitan Region, Finland, were invited to participate in a school survey in 2011 and 2014, respectively. The respondents (2011, N = 8960; 2014, N = 7394) were followed using a national application registry... -
Serum 25-hydroxyvitamin D and fatty acids in relation to the risk of microbial infections in children: The TRIGR Divia study
CONCLUSIONS: In young children with increased susceptibility to type 1 diabetes, long-chain n-3 PUFAs may influence the risk of viral infections and immune response against the infections. However, this association may depend on the type of virus suggesting virus-specific effects. -
Subarachnoid Hemorrhage During Pregnancy and Puerperium: A Population-Based Study
CONCLUSIONS: The incidence of pSAH has not changed substantially over time in Finland. The majority of pSAH cases were aneurysmal and women with aneurysm had considerable mortality and morbidity. Counseling of pregnant women about smoking cessation and monitoring of blood pressure and symptoms of pre-eclampsia are important interventions to prevent pSAH. -
Facilitating conditions for staff's confidence to enforce school tobacco policies: qualitative analysis from seven European cities
CONCLUSIONS: Our study stresses the need to implement strategies at multiple levels to strengthen staff's confidence for STP enforcement. To support staff's legitimacy for enforcement, we suggest reinforcing structures and practices that facilitate consistency in STP enforcement; to support staff's ability for constructive interaction with STP violators, we suggest strengthening staff's social and emotional learning; and to support staff's experience of collegial support, we suggest reinforcing...
2021
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Letter to the Editor for the article "20-year follow-up study of celiac patients identified in a mass school screening: compliance to gluten-free diet and autoimmunity"
No abstract -
Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells
Enteroviruses, particularly the group B coxsackieviruses (CVBs), have been associated with the development of type 1 diabetes. Several CVB serotypes establish chronic infections in human cells in vivo and in vitro. However, the mechanisms leading to enterovirus persistency and, possibly, beta cell autoimmunity are not fully understood. We established a carrier-state-type persistent infection model in human pancreatic cell line PANC-1 using two distinct CVB1 strains and profiled the... -
Assessment of Food and Waterborne Viral Outbreaks by Using Field Epidemiologic, Modern Laboratory and Statistical Methods-Lessons Learnt from Seven Major Norovirus Outbreaks in Finland
Seven major food- and waterborne norovirus outbreaks in Western Finland during 2014-2018 were re-analysed. The aim was to assess the effectiveness of outbreak investigation tools and evaluate the Kaplan criteria. We summarised epidemiological and microbiological findings from seven outbreaks. To evaluate the Kaplan criteria, a one-stage meta-analysis of data from seven cohort studies was performed. The case was defined as a person attending an implicated function with diarrhoea, vomiting or two... -
Primary Site of Coxsackievirus B Replication in the Small Intestines: No Proof of Peyer's Patches Involvement
CONCLUSIONS: Virus was present in the epithelial cells but not in GCs of the PPs of the murine SIs. Our results do not support the hypothesis of EV replication in the PP especially in the GCs. -
Characteristics of preeclampsia in donor cell gestations
Pregnancies conceived through donor oocytes or sperm show increased risk for preeclampsia. We studied this issue in a preeclampsia case-control cohort (n = 2778), and found overrepresentation of donor cell gestations among women with preeclampsia (14/1627, 0.86%; OR 1.81; 95% CI: 1.07-3.08; P = 0.025) compared to the population data. Moreover, we observed excess of male births from donor cell pregnancies (male-to-female ratio 2.5 vs. 0.97; OR 2.57; 95% CI 1.02-6.36; P = 0.043). Maternal age... -
Effect of Community-Initiated Kangaroo Mother Care on Fecal Biomarkers of Gut Function in Low Birth Weight Infants in North India: A Randomized Clinical Trial
This individually randomized trial was conducted to estimate the effect of promoting community-initiated Kangaroo Mother Care (ciKMC) in low birth weight (LBW) infants on gut inflammation and permeability. Participants included 200 stable LBW infants (weighing 1,500-2,250 g) in North India enrolled between May and October 2017. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding through home visits. The mothers in the intervention... -
Cough and cold medicine prescription rates can be significantly reduced by active intervention
CONCLUSION: The study showed that a nationwide systematic intervention to change cough medicine prescription practices is feasible and requires only modest financial investments. -
Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial
CONCLUSIONS AND RELEVANCE: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery... -
Parents' Participation in School Health Examinations for Their Adolescent Children in Finland
Engaging parents in school health examinations can promote adolescents' well-being. We examined parents' participation in universal school health examinations in Finland reported by adolescents in school surveys (14 to 16-year-olds, N = 58,232). Further we studied variation between service providers and schools, and student and school-level factors in participation. National data were analyzed using multilevel logistic regression models. Less than half of the adolescents reported parents'... -
Dissecting the contribution of single nucleotide polymorphisms in <em>CCR9</em> and <em>CCL25</em> genomic regions to the celiac disease phenotype
CONCLUSIONS: We conclude that SNPs in the region of CCR9 and CCL25 with predicted functional effect or exonic localization likely contribute only modestly to various celiac disease phenotypes. -
The Way of Distance Teaching Is Related to Adolescent Students' Health and Loneliness during the School Closure in Finland
The COVID-19 pandemic enforced countries to close schools and rapidly transfer to distance teaching without preparation. Little is known about how different distance teaching practices influenced students' wellbeing. We studied this during the period of school closures in Finland. Wellbeing was measured by health complaints and perceived loneliness, and distance learning was measured in terms of structure and dialogue of teaching, functioning of internet and digital equipment, difficulty of... -
Effect of inactivated nature-derived microbial composition on mouse immune system
CONCLUSIONS: These results provide insights on the effect of biodiversity on murine immune system in sterile environment. Subjecting mice to soil-based plant and microbe structures appears to elicit immune response that could be beneficial, for example, in type 2 inflammation-related diseases, that is, allergic diseases. -
Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health
We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032... -
Modular literature review: a novel systematic search and review method to support priority setting in health policy and practice
CONCLUSIONS: The Modular Review preserves principles that have traditionally been important to systematic reviews but can address multiple research questions simultaneously. The result is an accessible, reliable answer to the question of "what works?". Thus, it is a well-suited literature review method to support prioritisation, decisions and planning to implement an agenda for health improvement. -
Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
Significant progress has been made in elucidating genetic risk factors influencing Type 1 diabetes (T1D); however, features other than genetic variants that initiate and/or accelerate islet autoimmunity that lead to the development of clinical T1D remain largely unknown. We hypothesized that genetic and environmental risk factors can both contribute to T1D through dynamic alterations of molecular interactions in physiologic networks. To test this hypothesis, we utilized longitudinal blood...
2020
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Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life
Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T... -
Enterovirus Infections Are Associated With the Development of Celiac Disease in a Birth Cohort Study
Enterovirus and adenovirus infections have been linked to the development of celiac disease. We evaluated this association in children who developed biopsy-proven celiac disease (N = 41) during prospective observation starting from birth, and in control children (N = 53) matched for the calendar time of birth, sex, and HLA-DQ genotype. Enterovirus and adenovirus infections were diagnosed by seroconversions in virus antibodies in longitudinally collected sera using EIA. Enterovirus infections... -
Normative and negative sexual experiences of transgender identifying adolescents in the community
CONCLUSIONS: Transgender identifying adolescents presented neither with delayed nor with excessively advanced sexual experiences. However, transgender youth seem to be more susceptible to subjection to sexual coercion and, unexpectedly, dating violence perpetration than their cisgender peers. However, these associations may in fact relate more closely to depression, a prevalent phenomenon among trans youth, than transgender identity itself. -
Changes in cannabis use according to socioeconomic status among Finnish adolescents from 2000 to 2015
CONCLUSIONS: Although the overall changes in the prevalence of adolescent cannabis use were modest, cannabis use increased markedly among adolescents with the most socioeconomic adversities. Socioeconomic adversities should be considered in the prevention of adolescent cannabis use. -
Transgender Identity Is Associated With Bullying Involvement Among Finnish Adolescents
CONCLUSION: Transgender identity, especially non-binary identity, is associated with both being bullied and perpetrating bullying even when a range of variables including internal stress and involvement in bullying in the opposite role are taken into account. This suggests that bullying during adolescence may serve as a mechanism of maintaining heteronormativity. -
Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso
CONCLUSIONS: In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. -
Effects of <em>In Vivo</em> Gluten Challenge on PBMC Gene Expression Profiles in Diet Treated Celiac Disease
The pathological mechanisms that lead to the onset and reactivation of celiac disease (CD) remain largely unknown. While gluten free diet (GFD) improves the intestinal damage and associated clinical symptoms in majority of cases, it falls short of providing full recovery. Additionally, late or misdiagnosis is also common as CD presents with a wide range of symptoms. Clear understanding of CD pathogenesis is thus critical to address both diagnostic and treatment concerns. We aimed to study the... -
A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders
CONCLUSIONS: These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders. -
Trends of computed tomography use among children in Finland
CONCLUSIONS: The frequency of pediatric CTs in Finland started to decrease after 2002. Apart from chest and orthopedic CTs, the utilization of pediatric CT imaging declined in recent years, most likely explained by improved awareness of medical radiation risks and reliance on alternative modalities such as MRI and ultrasound. -
Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis
CONCLUSION: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. -
Influence of HLA-DQ2.5 Dose on Clinical Picture of Unrelated Celiac Disease Patients
The clinical phenotype of celiac disease varies considerably among patients and the dosage of HLA-DQ2.5 alleles has been suggested to be a contributing factor. We investigated whether HLA-DQ2.5 allele dosage is associated with distinct clinical parameters at the time of diagnosis and with patients' response to a gluten-free diet. The final cohort included 605 carefully phenotyped non-related Finnish celiac disease patients grouped as having 0, 1 or 2 copies of HLA-DQ2.5. Clinical data at the... -
The role of polygenic risk and susceptibility genes in breast cancer over the course of life
Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer,... -
Alcohol-related mortality and all-cause mortality following bereavement in two successive generations
CONCLUSIONS: These findings emphasise the role of bereavement, particularly resulting from the death of an offspring, on alcohol-related and all-cause mortality and therefore inequalities in mortality. Furthermore, the findings highlighting the need for alcohol abuse intervention and emotional support for bereaved persons following the death of an offspring. -
Detection of Viral -RNA and +RNA Strands in Enterovirus-Infected Cells and Tissues
The current methods to study the distribution and dynamics of viral RNA molecules inside infected cells are not ideal, as electron microscopy and immunohistochemistry can only detect mature virions, and quantitative real-time PCR does not reveal localized distribution of RNAs. We demonstrated here the branched DNA in situ hybridization (bDNA ISH) technology to study both the amount and location of the emerging -RNA and +RNA during acute and persistent enterovirus infections. According to our... -
Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial
BACKGROUND: Dabigatran etexilate is a direct oral anticoagulant with potential to overcome the limitations of standard of care in children with venous thromboembolism. The aims of this clinical trial were to study the appropriateness of a paediatric dabigatran dosing algorithm, and the efficacy and safety of dabigatran dosed according to that algorithm versus standard of care in treating children with venous thromboembolism.