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Allogeneic Hematopoietic Stem Cell Transplantation in ERCC6L2 Disease
No full textAbstract
The hallmark of ERCC6L2 disease (ED) is a highly penetrant progression from bone marrow failure (BMF) to erythroid-predominant, TP53-mutated myeloid malignancy with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option, but concerns exist regarding transplant-related toxicities due to the underlying DNA repair defect. This is the first study to report a systematic analysis of HSCT in ED. We conducted a retrospective multicenter study involving 45 patients with ED who underwent HSCT in 2004-2024. The primary outcomes were overall survival (OS), transplant-related toxicity, and non-relapse mortality (NRM). The 1-year and 3-year OS were 79% (95% confidence interval [CI], 66-91) and 54% (95% CI, 35-73), respectively. Prior history of excess blasts significantly predicted inferior survival (hazard ratio [HR], 6.8; 95% CI, 2.2-20.3; P<0.001), with a median survival of 12 months (95% CI, 0-24). Grade 3-5 endothelial toxicities occurred in 27% of patients and were associated with higher NRM (HR, 7.7; 95% CI, 1.5-38.8; P=0.016). The use of non-treosulfan-based myeloablative conditioning (MAC) regimens increased the risk of endothelial complications compared to reduced-intensity conditioning (RIC) (HR, 4.9; 95% CI, 1.1-22.0; P=0.040), whereas outcomes with treosulfan-based MAC were comparable to RIC. In summary, allogeneic HSCT is a viable curative strategy for ED when performed before transformation to an aggressive malignancy i.e. myelodysplasia with excess blasts or acute myeloid leukemia. However, the elevated incidence of endothelial toxicity highlights the importance of optimizing conditioning intensity and enhancing peritransplant monitoring in this population.Abstract
The hallmark of ERCC6L2 disease (ED) is a highly penetrant progression from bone marrow failure (BMF) to erythroid-predominant, TP53-mutated myeloid malignancy with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option, but concerns exist regarding transplant-related toxicities due to the underlying DNA repair defect. This is the first study to report a systematic analysis of HSCT in ED. We conducted a retrospective multicenter study involving 45 patients with ED who underwent HSCT in 2004-2024. The primary outcomes were overall survival (OS), transplant-related toxicity, and non-relapse mortality (NRM). The 1-year and 3-year OS were 79% (95% confidence interval [CI], 66-91) and 54% (95% CI, 35-73), respectively. Prior history of excess blasts significantly predicted inferior survival (hazard ratio [HR], 6.8; 95% CI, 2.2-20.3; P<0.001), with a median survival of 12 months (95% CI, 0-24). Grade 3-5 endothelial toxicities occurred in 27% of patients and were associated with higher NRM (HR, 7.7; 95% CI, 1.5-38.8; P=0.016). The use of non-treosulfan-based myeloablative conditioning (MAC) regimens increased the risk of endothelial complications compared to reduced-intensity conditioning (RIC) (HR, 4.9; 95% CI, 1.1-22.0; P=0.040), whereas outcomes with treosulfan-based MAC were comparable to RIC. In summary, allogeneic HSCT is a viable curative strategy for ED when performed before transformation to an aggressive malignancy i.e. myelodysplasia with excess blasts or acute myeloid leukemia. However, the elevated incidence of endothelial toxicity highlights the importance of optimizing conditioning intensity and enhancing peritransplant monitoring in this population
Mapping and Modelling Specific Sediment Yield and Future Soil Erosion Trends in the Jhelum Catchment, India
No full textAbstract
Soil erosion management is a crucial component of sustainable soil and water management, especially in regions where agricultural productivity is at risk and areas that are more vulnerable to the impacts of climate change, such as the Himalayan region. This study explores soil erosion dynamics in the Jhelum Catchment, India, using advanced mapping and modelling techniques to analyse and predict trends of potential soil loss from 2020 to 2090. The study integrates the RUSLE model with projected climate to assess the impact of climate change on soil erosion and rainfall erosivity. The InVEST SDR model is used to quantify sediment transport and specific sediment yield, enhancing our understanding of the hydrological processes that drive soil erosion and sediment mobilisation in the Jhelum Catchment. The RUSLE, along with advanced climate modelling, land-use data, and spatial analysis, is used in this study to predict trends in soil erosion. Climate data from the Coupled Model Intercomparison Project Phase 6 (CMIP6) is combined with data from the India Meteorological Department (IMD) to project rainfall erosivity (R). R, along with soil erodibility (K), slope length and steepness (LS), land cover (C), and support practices (P) factors, are mapped and applied in the Revised Universal Soil Loss Equation (RUSLE) model, which evaluates the potential for soil erosion. This study forecasts soil loss trends by combining climate data, land-use information, and spatial analysis from 2020 to 2090 under two scenarios [SSP245 (moderate emissions) and SSP585 (high emissions)]. Results indicate escalating soil loss, particularly in less severe areas in 2020, highlighting the dynamic threat. The mean value of soil loss for SSP245 exhibits a continuous rise from 46.17 t/ha/year in 2030 to 51.54 t/ha/year in 2090. SSP585 shows a more severe trend, peaking at 71.67 t/ha/year in 2090. The study also classifies potential soil loss into severity classes, observing a decrease in the percentage area of less severe classes over time. Soil erosion class-wise projections from 2020 to 2090, based on LULC and soil type, reveal trends across various categories of land use, including Agriculture, Forest, Built-up Areas, and Grass/Grazing Land, as well as soil types like Cambisols, Lithosols, Glaciers, and Inland Water. These results highlight the urgent need for proactive interventions, offering practical insights for sustainable land management and providing actionable guidance for strategic planning and policy development focused on sustainable agricultural practices and climate change adaptation. This novel approach integrates advanced modelling and GIS-based analysis, making it applicable to other catchments with similar climate and land-use challenges. The study's findings directly apply to informing land management strategies, making the research highly relevant and practical.Abstract
Soil erosion management is a crucial component of sustainable soil and water management, especially in regions where agricultural productivity is at risk and areas that are more vulnerable to the impacts of climate change, such as the Himalayan region. This study explores soil erosion dynamics in the Jhelum Catchment, India, using advanced mapping and modelling techniques to analyse and predict trends of potential soil loss from 2020 to 2090. The study integrates the RUSLE model with projected climate to assess the impact of climate change on soil erosion and rainfall erosivity. The InVEST SDR model is used to quantify sediment transport and specific sediment yield, enhancing our understanding of the hydrological processes that drive soil erosion and sediment mobilisation in the Jhelum Catchment. The RUSLE, along with advanced climate modelling, land-use data, and spatial analysis, is used in this study to predict trends in soil erosion. Climate data from the Coupled Model Intercomparison Project Phase 6 (CMIP6) is combined with data from the India Meteorological Department (IMD) to project rainfall erosivity (R). R, along with soil erodibility (K), slope length and steepness (LS), land cover (C), and support practices (P) factors, are mapped and applied in the Revised Universal Soil Loss Equation (RUSLE) model, which evaluates the potential for soil erosion. This study forecasts soil loss trends by combining climate data, land-use information, and spatial analysis from 2020 to 2090 under two scenarios [SSP245 (moderate emissions) and SSP585 (high emissions)]. Results indicate escalating soil loss, particularly in less severe areas in 2020, highlighting the dynamic threat. The mean value of soil loss for SSP245 exhibits a continuous rise from 46.17 t/ha/year in 2030 to 51.54 t/ha/year in 2090. SSP585 shows a more severe trend, peaking at 71.67 t/ha/year in 2090. The study also classifies potential soil loss into severity classes, observing a decrease in the percentage area of less severe classes over time. Soil erosion class-wise projections from 2020 to 2090, based on LULC and soil type, reveal trends across various categories of land use, including Agriculture, Forest, Built-up Areas, and Grass/Grazing Land, as well as soil types like Cambisols, Lithosols, Glaciers, and Inland Water. These results highlight the urgent need for proactive interventions, offering practical insights for sustainable land management and providing actionable guidance for strategic planning and policy development focused on sustainable agricultural practices and climate change adaptation. This novel approach integrates advanced modelling and GIS-based analysis, making it applicable to other catchments with similar climate and land-use challenges. The study's findings directly apply to informing land management strategies, making the research highly relevant and practical
When floods meet dispersal: Unravelling macroinvertebrate community dynamics in a large subtropical monsoonal river basin
No full textAbstract
Disentangling the mechanisms underlying community assembly is a central topic in community ecology and an important prerequisite for bioassessment. The relative importance of deterministic and stochastic processes is expected to change among organisms relying on different dispersal modes and may vary considerably through time. However, how seasonal change and dispersal modes will interplay to influence community assembly remains to be demonstrated. Here, we examined seasonal dynamics in the relative role of environmental filtering and potential dispersal pathways (overland vs. watercourse) on community assembly of aquatic macroinvertebrates in a Chinese river experiencing monsoon oscillations. We also investigated if and how community assembly processes are dependent on dispersal modes. To do this, we divided the entire metacommunity into three groups: strictly aquatic dispersers (G1), aquatic/aerial dispersers with weak dispersal ability (G2), aquatic/aerial dispersers with strong dispersal ability (G3). Our results showed strong changes in environmental conditions and community structure before, during and after the monsoon. Watercourse distances were more relevant for strictly aquatic dispersers (i.e., G1), whereas overland distances were more strongly related with taxa able to fly during their adult phase (i.e., G2 and G3). Environmental filtering was consistently predominant across seasons. Moreover, mechanisms underlying community assembly of strictly aquatic dispersers remained relatively stable among seasons. On the other hand, ecological correlates of aquatic/aerial dispersers exhibited pronounced seasonal dynamics, probably as a result of their changing dispersal abilities in the transition from larvae to adulthood. Overall, our findings suggest that the relative importance of environmental filtering and spatial processes are mediated by dispersal modes and the hydrological dynamics imposed by seasonal monsoons. Hence, we argue that incorporating the temporal aspect of intra-annual hydrological variation and considering multiple dispersal modes are crucial for unravelling the dynamic nature of community assembly and for improving river bioassessment and management.Abstract
Disentangling the mechanisms underlying community assembly is a central topic in community ecology and an important prerequisite for bioassessment. The relative importance of deterministic and stochastic processes is expected to change among organisms relying on different dispersal modes and may vary considerably through time. However, how seasonal change and dispersal modes will interplay to influence community assembly remains to be demonstrated. Here, we examined seasonal dynamics in the relative role of environmental filtering and potential dispersal pathways (overland vs. watercourse) on community assembly of aquatic macroinvertebrates in a Chinese river experiencing monsoon oscillations. We also investigated if and how community assembly processes are dependent on dispersal modes. To do this, we divided the entire metacommunity into three groups: strictly aquatic dispersers (G1), aquatic/aerial dispersers with weak dispersal ability (G2), aquatic/aerial dispersers with strong dispersal ability (G3). Our results showed strong changes in environmental conditions and community structure before, during and after the monsoon. Watercourse distances were more relevant for strictly aquatic dispersers (i.e., G1), whereas overland distances were more strongly related with taxa able to fly during their adult phase (i.e., G2 and G3). Environmental filtering was consistently predominant across seasons. Moreover, mechanisms underlying community assembly of strictly aquatic dispersers remained relatively stable among seasons. On the other hand, ecological correlates of aquatic/aerial dispersers exhibited pronounced seasonal dynamics, probably as a result of their changing dispersal abilities in the transition from larvae to adulthood. Overall, our findings suggest that the relative importance of environmental filtering and spatial processes are mediated by dispersal modes and the hydrological dynamics imposed by seasonal monsoons. Hence, we argue that incorporating the temporal aspect of intra-annual hydrological variation and considering multiple dispersal modes are crucial for unravelling the dynamic nature of community assembly and for improving river bioassessment and management
Planning terminology for northern minority languages: The Saami case
No full textThis chapter focuses on the development and standardization of terminology for the Saami languages. The Saami languages form a dialect continuum ranging from mid-Scandinavia to the tip of Kola Peninsula and are spoken in four countries: Norway, Sweden, Finland and Russia. This chapter relies on knowledge accumulated by the authors while working as Saami language advisers, as well as on information collected from previous research and reviews of old documents. The first official body for the standardization of Saami languages, the Saami Language Council, was created in 1971. In the 2020s, a permanent standardization body, Sámi Giellagáldu, was finally established by the three Nordic Saami parliaments. Despite its young age, initial practical hurdles and a degree of financial uncertainty, Sámi Giellagáldu has already achieved many results and proves that an international and multilingual expert body has a lot of potential to support the revitalization of indigenous minority languages.This chapter focuses on the development and standardization of terminology for the Saami languages. The Saami languages form a dialect continuum ranging from mid-Scandinavia to the tip of Kola Peninsula and are spoken in four countries: Norway, Sweden, Finland and Russia. This chapter relies on knowledge accumulated by the authors while working as Saami language advisers, as well as on information collected from previous research and reviews of old documents. The first official body for the standardization of Saami languages, the Saami Language Council, was created in 1971. In the 2020s, a permanent standardization body, Sámi Giellagáldu, was finally established by the three Nordic Saami parliaments. Despite its young age, initial practical hurdles and a degree of financial uncertainty, Sámi Giellagáldu has already achieved many results and proves that an international and multilingual expert body has a lot of potential to support the revitalization of indigenous minority languages
Protein phosphatase modulator CIP2A and non-canonical Wnt11 in cardiac remodeling and development of heart failure
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Cardiovascular diseases are the leading cause of deaths in the Western adult population. The major cardiovascular pathologies such as valve disease, hypertension and coronary artery disease, as well as the use of cardiotoxic drugs result in cardiac injury and predispose to heart failure. Despite the currently available cardiovascular therapies, the prognosis is poor for clinically manifested severe heart failure with a 5-year mortality rate of 50%. At the moment, there is no treatment that could stop or reverse the progression of heart failure. In this thesis, two potential genes connected to cardiac remodeling and heart failure were studied: Wnt11 and Cip2a.
The non-canonical Wnt11 plays a crucial role in the embryonic development of the heart, however its function after birth and in the stressed adult heart is largely unknown. In this thesis, the proliferation/maturation of cardiomyocytes in early postnatal and juvenile mice was investigated and Wnt11 deficiency was found to moderately promote hypertrophy and growth. To study the Wnt11 deficiency in cardiac stress, adult male mice were subjected to a hemodynamic pressure overload model and no effect for Wnt11 deficiency was found in cardiac remodeling, hypertrophy or fibrosis. However, based on experiments with cultured cardiomyocytes, co-operation of Wnt11 and Wnt5a under cardiac stress is likely required for an anti-hypertrophic effect.
CIP2A is a well-studied candidate for anti-cancer therapy, however its effects on the heart are unknown. Cardiomyocytes with a diminished Cip2a gene expression were investigated and CIP2A deficiency was found to suppress the stress response of cardiac cells. Next, Cip2a hypomorphic mice under hemodynamic pressure overload-induced cardiac stress were used and CIP2A deficiency was found to reduce the pathological cardiac hypertrophy and remodeling. The CIP2A deficiency also protected the heart from a stress-induced deterioration of the cardiac systolic function and the development of heart failure.
Altogether, these results demonstrated that the Wnt11-signaling alone is not sufficient to influence cardiac remodeling under stress, but together with Wnt5a, it may regulate the cardiomyocyte growth. The CIP2A deficiency reduced pathological left ventricular remodeling without exhibiting cardiotoxicity, thereby suggesting that CIP2A can be considered a potential therapeutic target for heart failure and a viable therapeutic target for cancer. Original papers Halmetoja, E., Nagy, I., Szabo, Z., Alakoski, T., Yrjölä, R., Vainio, L., Viitavaara, E., Lin, R., Rahtu‐Korpela, L., Vainio, S., Kerkelä, R., & Magga, J. (2022). Wnt11 in regulation of physiological and pathological cardiac growth. The FASEB Journal, 36(10), e22544. https://doi.org/10.1096/fj.202101856RRRR https://doi.org/10.1096/fj.202101856RRRR Self-archived version Halmetoja, E., Szabó, Z., Vainonen, J. P., Rahtu-Korpela, L., Saarimäki, S., Swan, J., Elzeneini, E., Westermarck, J., Kerkelä, R., & Magga J. (2025). CIP2A depletion is cardioprotective in mice. Manuscript in preparation. Tiivistelmä
Sydän- ja verisuonisairaudet ovat yleisin kuolinsyy länsimaissa. Sydämelle vahingolliset sairaudet kuten sydämen läppävika, verenpainetauti ja sepelvaltimotauti sekä sydäntoksisten lääkkeiden käyttö johtavat kudosvaurioihin ja lopulta jopa sydämen vajaatoimintaan. Nykylääketieteestä huolimatta sydämen vajaatoiminnan ennuste on huono; puolet sairastuneista menehtyy 5 vuoden aikana diagnoosista. Nykyisillä lääkehoidoilla ei voida pysäyttää vajaatoiminnan kehittymistä eikä parantaa taudin aiheuttamia sydänvaurioita. Tässä väitöskirjassa tutkittiin kahta sydämen uudelleenmuovautumiseen sekä vajaatoimintaan mahdollisesti liittyvää geeniä: Wnt11 ja Cip2a.
Ei-kanoninen Wnt11 on oleellinen alkion sydämenkehityksessä, mutta sen toiminta sydämessä syntymän jälkeen ja sydänsairauksissa on suurelta osin tuntematon. Tutkittaessa kardiomyosyyttien proliferaatiota/maturaatiota vastasyntyneissä ja nuorissa hiirissä havaittiin, että Wnt11:n puutos lisää hieman sydänlihassolujen kasvua. Tutkittaessa Wnt11-geenin roolia sydänsairaudessa, aikuisille hiirille aiheutettiin paineylikuormitus sydämeen, mutta Wnt11:n puutos ei vaikuttanut sydämen uudelleenmuovautumiseen, hypertrofiaan eikä fibroosiin. Sydänlihassolukokeissa kuitenkin havaittiin, että kahden ei-kanonisen Wnt-proteiinin (Wnt11 ja Wnt5a) yhteisvaikutus saattaa olla tarpeen kasvua estävän vaikutuksen saavuttamiseksi sydämen kuormituksessa.
CIP2A:ta on tutkittu laajasti syöpähoitojen kohdeproteiinina, mutta sen vaikutuksia sydämessä ei tunneta. Cip2a-geenin osalta hiljennetyissä sydänlihassoluissa CIP2A:n puute heikensi sydänsolujen stressivastetta. Cip2a-hypomorfisilla hiirillä sydämen paineylikuormitus osoitti CIP2A:n puutteen hillitsevän sydämen patologista hypertrofiaa ja uudelleenmuovautumista. Lisäksi CIP2A:n puutos suojasi sydäntä systolisen toiminnan heikkenemiseltä ja sydämen vajaatoiminnan kehittymiseltä.
Tämän väitöskirjan tulokset osoittavat, että Wnt11-geenin hiljentäminen ei ole ainoa tekijä, joka vaikuttaa sydämen uudelleenmuovautumiseen, vaan se toimii yhdessä toisen Wnt-signalointiproteiinin, kuten Wnt5a:n kanssa, sydämen hypertrofian estossa. CIP2A:n puutos ei aiheuta sydäntoksisuutta ja näyttäisi vähentävän patologista uudelleenmuovautumista. Näiden löydösten perusteella CIP2A on mahdollinen lääkekohde sekä syöpä- että sydänsairauksien, kuten sydämen vajaatoiminnan, hoidossa. Osajulkaisut Halmetoja, E., Nagy, I., Szabo, Z., Alakoski, T., Yrjölä, R., Vainio, L., Viitavaara, E., Lin, R., Rahtu‐Korpela, L., Vainio, S., Kerkelä, R., & Magga, J. (2022). Wnt11 in regulation of physiological and pathological cardiac growth. The FASEB Journal, 36(10), e22544. https://doi.org/10.1096/fj.202101856RRRR https://doi.org/10.1096/fj.202101856RRRR Rinnakkaistallennettu versio Halmetoja, E., Szabó, Z., Vainonen, J. P., Rahtu-Korpela, L., Saarimäki, S., Swan, J., Elzeneini, E., Westermarck, J., Kerkelä, R., & Magga J. (2025). CIP2A depletion is cardioprotective in mice. Manuscript in preparation. Academic dissertation to be presented with the assent of the Doctoral Programme Committee of Health and Biosciences of the University of Oulu for public defence in Auditorium F202 of the Faculty of Medicine (Aapistie 5 B), on 16 January 2026, at 12 noonAbstract
Cardiovascular diseases are the leading cause of deaths in the Western adult population. The major cardiovascular pathologies such as valve disease, hypertension and coronary artery disease, as well as the use of cardiotoxic drugs result in cardiac injury and predispose to heart failure. Despite the currently available cardiovascular therapies, the prognosis is poor for clinically manifested severe heart failure with a 5-year mortality rate of 50%. At the moment, there is no treatment that could stop or reverse the progression of heart failure. In this thesis, two potential genes connected to cardiac remodeling and heart failure were studied: Wnt11 and Cip2a.
The non-canonical Wnt11 plays a crucial role in the embryonic development of the heart, however its function after birth and in the stressed adult heart is largely unknown. In this thesis, the proliferation/maturation of cardiomyocytes in early postnatal and juvenile mice was investigated and Wnt11 deficiency was found to moderately promote hypertrophy and growth. To study the Wnt11 deficiency in cardiac stress, adult male mice were subjected to a hemodynamic pressure overload model and no effect for Wnt11 deficiency was found in cardiac remodeling, hypertrophy or fibrosis. However, based on experiments with cultured cardiomyocytes, co-operation of Wnt11 and Wnt5a under cardiac stress is likely required for an anti-hypertrophic effect.
CIP2A is a well-studied candidate for anti-cancer therapy, however its effects on the heart are unknown. Cardiomyocytes with a diminished Cip2a gene expression were investigated and CIP2A deficiency was found to suppress the stress response of cardiac cells. Next, Cip2a hypomorphic mice under hemodynamic pressure overload-induced cardiac stress were used and CIP2A deficiency was found to reduce the pathological cardiac hypertrophy and remodeling. The CIP2A deficiency also protected the heart from a stress-induced deterioration of the cardiac systolic function and the development of heart failure.
Altogether, these results demonstrated that the Wnt11-signaling alone is not sufficient to influence cardiac remodeling under stress, but together with Wnt5a, it may regulate the cardiomyocyte growth. The CIP2A deficiency reduced pathological left ventricular remodeling without exhibiting cardiotoxicity, thereby suggesting that CIP2A can be considered a potential therapeutic target for heart failure and a viable therapeutic target for cancer.Tiivistelmä
Sydän- ja verisuonisairaudet ovat yleisin kuolinsyy länsimaissa. Sydämelle vahingolliset sairaudet kuten sydämen läppävika, verenpainetauti ja sepelvaltimotauti sekä sydäntoksisten lääkkeiden käyttö johtavat kudosvaurioihin ja lopulta jopa sydämen vajaatoimintaan. Nykylääketieteestä huolimatta sydämen vajaatoiminnan ennuste on huono; puolet sairastuneista menehtyy 5 vuoden aikana diagnoosista. Nykyisillä lääkehoidoilla ei voida pysäyttää vajaatoiminnan kehittymistä eikä parantaa taudin aiheuttamia sydänvaurioita. Tässä väitöskirjassa tutkittiin kahta sydämen uudelleenmuovautumiseen sekä vajaatoimintaan mahdollisesti liittyvää geeniä: Wnt11 ja Cip2a.
Ei-kanoninen Wnt11 on oleellinen alkion sydämenkehityksessä, mutta sen toiminta sydämessä syntymän jälkeen ja sydänsairauksissa on suurelta osin tuntematon. Tutkittaessa kardiomyosyyttien proliferaatiota/maturaatiota vastasyntyneissä ja nuorissa hiirissä havaittiin, että Wnt11:n puutos lisää hieman sydänlihassolujen kasvua. Tutkittaessa Wnt11-geenin roolia sydänsairaudessa, aikuisille hiirille aiheutettiin paineylikuormitus sydämeen, mutta Wnt11:n puutos ei vaikuttanut sydämen uudelleenmuovautumiseen, hypertrofiaan eikä fibroosiin. Sydänlihassolukokeissa kuitenkin havaittiin, että kahden ei-kanonisen Wnt-proteiinin (Wnt11 ja Wnt5a) yhteisvaikutus saattaa olla tarpeen kasvua estävän vaikutuksen saavuttamiseksi sydämen kuormituksessa.
CIP2A:ta on tutkittu laajasti syöpähoitojen kohdeproteiinina, mutta sen vaikutuksia sydämessä ei tunneta. Cip2a-geenin osalta hiljennetyissä sydänlihassoluissa CIP2A:n puute heikensi sydänsolujen stressivastetta. Cip2a-hypomorfisilla hiirillä sydämen paineylikuormitus osoitti CIP2A:n puutteen hillitsevän sydämen patologista hypertrofiaa ja uudelleenmuovautumista. Lisäksi CIP2A:n puutos suojasi sydäntä systolisen toiminnan heikkenemiseltä ja sydämen vajaatoiminnan kehittymiseltä.
Tämän väitöskirjan tulokset osoittavat, että Wnt11-geenin hiljentäminen ei ole ainoa tekijä, joka vaikuttaa sydämen uudelleenmuovautumiseen, vaan se toimii yhdessä toisen Wnt-signalointiproteiinin, kuten Wnt5a:n kanssa, sydämen hypertrofian estossa. CIP2A:n puutos ei aiheuta sydäntoksisuutta ja näyttäisi vähentävän patologista uudelleenmuovautumista. Näiden löydösten perusteella CIP2A on mahdollinen lääkekohde sekä syöpä- että sydänsairauksien, kuten sydämen vajaatoiminnan, hoidossa
Paving the way for dynamic assessment through diagnostic self-assessment: A comparison of Finnish and Chinese university students
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Diagnostic assessment has traditionally been used to identify learners’ profiles of strengths and weaknesses in their language proficiency. The hypothesis in the present study was that diagnostic assessment through self-assessment focused on reading, writing, listening, spoken interaction, and spoken production could point out the specific areas students need to develop further in a compulsory English language course. The study also used a placement test to shed light on to what extent the students’ self-assessments were in line with their tested language proficiency, which may help evaluate the validity of self-assessments as a diagnostic tool in the two educational contexts covered in the study. Data were collected from 60 Finnish and 80 Chinese first-year university students. The results revealed a weak correlation between self-assessments and the test for the Chinese students but a somewhat stronger correlation for the Finnish group. Detailed analyses of the self-assessment statements reveal specific strengths and weaknesses across language skills and between the two groups. The differences in the Chinese and Finnish students’ self-assessed and tested proficiency and their responses to individual self-assessment statements suggest that the educational context needs to be considered when drawing inferences from diagnostic assessments. Finally, the placement test and self-assessments become the first step in introducing dynamic assessment in areas that need further attention later in the classroom. Thus, to complement our diagnostic assessment approach, which combines testing and self-assessment, dynamic assessment is needed to expand the diagnosis to the skills in the process of development to inform the action phase of the diagnostic cycle.Abstract
Diagnostic assessment has traditionally been used to identify learners’ profiles of strengths and weaknesses in their language proficiency. The hypothesis in the present study was that diagnostic assessment through self-assessment focused on reading, writing, listening, spoken interaction, and spoken production could point out the specific areas students need to develop further in a compulsory English language course. The study also used a placement test to shed light on to what extent the students’ self-assessments were in line with their tested language proficiency, which may help evaluate the validity of self-assessments as a diagnostic tool in the two educational contexts covered in the study. Data were collected from 60 Finnish and 80 Chinese first-year university students. The results revealed a weak correlation between self-assessments and the test for the Chinese students but a somewhat stronger correlation for the Finnish group. Detailed analyses of the self-assessment statements reveal specific strengths and weaknesses across language skills and between the two groups. The differences in the Chinese and Finnish students’ self-assessed and tested proficiency and their responses to individual self-assessment statements suggest that the educational context needs to be considered when drawing inferences from diagnostic assessments. Finally, the placement test and self-assessments become the first step in introducing dynamic assessment in areas that need further attention later in the classroom. Thus, to complement our diagnostic assessment approach, which combines testing and self-assessment, dynamic assessment is needed to expand the diagnosis to the skills in the process of development to inform the action phase of the diagnostic cycle
The effect of type 2 diabetes on the prognosis of patients with coronary artery disease
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Cardiovascular diseases (CVD) are the most common cause of death in the Western countries. Type II diabetes (T2D) at least doubles the risk of CVD such as coronary artery disease (CAD). Over 50% of mortality in diabetic patients is caused by CVD. Moreover, T2D increases the risk of chronic heart failure and cardiac death regardless of CAD. Currently, the T2D incidence is increasing rapidly due to the global obesity epidemic. Therefore, issues related to T2D and CVD are bound to have an increased impact in society in the future.
In this thesis the correlation between biomarkers of collagen synthesis and inflammation, the amount of myocardial fibrosis estimated from cardiac magnetic resonance imaging (cMRI), and diastolic properties of the left ventricle was evaluated in 63 patients (I). An impaired diastolic function correlated with the cMRI findings and the levels of biomarkers PIIINP, Gal-3 and sST2.
In studies II-IV, 1946 patients with a stable CAD with or without T2D were investigated. The value of biomarkers in the risk prediction among patients with T2D and CAD was assessed (II). During the two-year follow-up, especially elevated high-sensitivity troponin T (hs-TnT) levels were associated with an 9.9-fold (p < 0.001) increased risk of a cardiac death or hospitalisation for congestive heart failure. During the 6.3-year follow-up, elevated hs-TnT and elevated sST2 levels together led to a 6.4-fold (p < 0.001) increase in the risk of a sudden cardiac death (SCD) compared to those with normal values among all CAD patients with or without T2D (III). The risk of SCD or aborted cardiac arrest was 2.6-fold (p < 0.01) higher in the T2D patients compared to their non-diabetic counterparts (IV). There was, however, no difference in the risk for non-SCD. Hospitalisation for congestive heart failure was significantly more common among the T2D patients (p < 0.001). The annual mortality of the non-diabetic CAD patients was 0.50%, which is lower than the cardiac mortality reported in a matched general Finnish population (0.59%).
In conclusion, T2D in CAD patients results in a significantly worse prognosis. Novel risk markers such as the hs-TnT are associated with adverse events among T2D patients with CAD. These results suggest that T2D might have a direct effect on the myocardium, which results in an increased risk for heart failure and SCD. Original papers Lepojärvi, E. S., Piira, O.-P., Pääkkö, E., Lammentausta, E., Risteli, J., Miettinen, J. A., Perkiömäki, J. S., Huikuri, H. V., & Junttila, M. J. (2015). Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties. Frontiers in Physiology, 6. https://doi.org/10.3389/fphys.2015.00200 https://doi.org/10.3389/fphys.2015.00200 Lepojärvi, E. S., Piira, O.-P., Kiviniemi, A. M., Miettinen, J. A., Kenttä, T., Ukkola, O., Tulppo, M. P., Huikuri, H. V., & Junttila, M. J. (2016). Usefulness of highly sensitive troponin as a predictor of short-term outcome in patients with diabetes mellitus and stable coronary artery disease (from the artemis study). The American Journal of Cardiology, 117(4), 515–521. https://doi.org/10.1016/j.amjcard.2015.11.038 https://doi.org/10.1016/j.amjcard.2015.11.038 Lepojärvi, E. S., Huikuri, H. V., Piira, O.-P., Kiviniemi, A. M., Miettinen, J. A., Kenttä, T., Ukkola, O., Perkiömäki, J. S., Tulppo, M. P., & Junttila, M. J. (2018). Biomarkers as predictors of sudden cardiac death in coronary artery disease patients with preserved left ventricular function (ARTEMIS study). PLOS ONE, 13(9), e0203363. https://doi.org/10.1371/journal.pone.0203363 https://doi.org/10.1371/journal.pone.0203363 Self-archived version Junttila, M. J., Kiviniemi, A. M., Lepojärvi, E. S., Tulppo, M., Piira, O.-P., Kenttä, T., Perkiömäki, J. S., Ukkola, O. H., Myerburg, R. J., & Huikuri, H. V. (2018). Type 2 diabetes and coronary artery disease: Preserved ejection fraction and sudden cardiac death. Heart Rhythm, 15(10), 1450–1456. https://doi.org/10.1016/j.hrthm.2018.06.017 https://doi.org/10.1016/j.hrthm.2018.06.017 Tiivistelmä
Sydän- ja verisuonisairaudet ovat suurin yksittäinen kuolemansyy länsimaissa. Yli puolella aikuistyypin diabeetikoista (T2D) kuoleman syynä ovat sydän- ja verisuonisairaudet. Lisäksi T2D lisää riskiä sydämen vajaatoiminnan ilmaantumiselle ja sydänperäiselle äkkikuolemalle sepelvaltimotaudista riippumatta. Huomioiden T2D:n jatkuvasti lisääntyvä ilmaantuvuus, T2D tulee olemaan merkittävä yhteiskunnallinen ongelma tulevaisuudessa.
Ensimmäisessä osajulkaisussa (I) tutkittiin kollageenisynteesiä ja inflammaatiota kuvaavien biomarkkereiden, sydämen magneettikuvauksesta (cMRI) arvioidun sydänlihaksen sidekudoksen määrän ja sydämen diastoliseen toiminnan korrelaatiota 63 potilaan aineistossa. Huonompi diastolinen toiminta korreloitui sekä cMRI-löydökseen että biomarkkereista PIIINP, Gal-3 ja sST2 pitoisuuksiin.
Muissa osajulkaisuissa arvioitiin uusien riskimarkkereiden kykyä ennustaa sydäntapahtumia prospektiivisessa 1946 potilaan tapaus-verrokki-tutkimuksessa stabiilia sepelvaltimotautia sairastavilla diabeetikoilla ja ei-diabeetikoilla. Kahden vuoden seurannassa varsinkin poikkeava herkän troponiini T:n (hs-TnT) pitoisuus lisäsi diabeetikon sydänkuoleman tai vajaatoimintahospitalisaation riskiä 9.9 kertaiseksi (p < 0.001) (II). Keskimäärin 6.3 vuoden seurannassa poikkeavat hs-TnT ja sST2 tasot yhdessä nostivat sydänperäisen äkkikuoleman riskin 6.4 kertaiseksi (p < 0.001) verrattuna niihin potilaisiin, joilla arvot olivat normaalit (III). Sydänperäisen äkkikuoleman tai sydänpysähdyksen riski oli aikuistyypin diabeetikoilla 2.6 kertainen (p < 0.01) verrattuna ei-diabeetikoihin (IV). Sen sijaan muussa sydänkuolleisuudessa ei todettu eroa. Vajaatoimintahospitalisaatiot olivat myös selkeästi yleisempiä diabeetikoilla (p < 0.001). Tässä tutkimuksessa vuosittainen kuolleisuus ei-diabeetikoilla oli 0.50 %, mikä on matalampi kuin samanikäisessä yleisessä suomalaisessa väestössä (0.59 %).
Tutkimukset osoittivat että, aikuistyypin diabetes sepelvaltimotautipotilaalla huonontaa ennustetta selkeästi ei-diabeetikkoon verrattuna. Uudet riskimarkkerit, kuten hs-TnT, liittyvät huonompaan ennusteeseen sepelvaltimotautia sairastavilla T2D potilailla. Näiden tulosten perusteella vaikuttaa siltä, että aikuistyypin diabetekseen voi liittyä merkittävä riski sydänlihassairaudelle, joka voi johtaa sydämen vajaatoimintaan ja äkkikuolemaan. Osajulkaisut Lepojärvi, E. S., Piira, O.-P., Pääkkö, E., Lammentausta, E., Risteli, J., Miettinen, J. A., Perkiömäki, J. S., Huikuri, H. V., & Junttila, M. J. (2015). Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties. Frontiers in Physiology, 6. https://doi.org/10.3389/fphys.2015.00200 https://doi.org/10.3389/fphys.2015.00200 Lepojärvi, E. S., Piira, O.-P., Kiviniemi, A. M., Miettinen, J. A., Kenttä, T., Ukkola, O., Tulppo, M. P., Huikuri, H. V., & Junttila, M. J. (2016). Usefulness of highly sensitive troponin as a predictor of short-term outcome in patients with diabetes mellitus and stable coronary artery disease (from the artemis study). The American Journal of Cardiology, 117(4), 515–521. https://doi.org/10.1016/j.amjcard.2015.11.038 https://doi.org/10.1016/j.amjcard.2015.11.038 Lepojärvi, E. S., Huikuri, H. V., Piira, O.-P., Kiviniemi, A. M., Miettinen, J. A., Kenttä, T., Ukkola, O., Perkiömäki, J. S., Tulppo, M. P., & Junttila, M. J. (2018). Biomarkers as predictors of sudden cardiac death in coronary artery disease patients with preserved left ventricular function (ARTEMIS study). PLOS ONE, 13(9), e0203363. https://doi.org/10.1371/journal.pone.0203363 https://doi.org/10.1371/journal.pone.0203363 Rinnakkaistallennettu versio Junttila, M. J., Kiviniemi, A. M., Lepojärvi, E. S., Tulppo, M., Piira, O.-P., Kenttä, T., Perkiömäki, J. S., Ukkola, O. H., Myerburg, R. J., & Huikuri, H. V. (2018). Type 2 diabetes and coronary artery disease: Preserved ejection fraction and sudden cardiac death. Heart Rhythm, 15(10), 1450–1456. https://doi.org/10.1016/j.hrthm.2018.06.017 https://doi.org/10.1016/j.hrthm.2018.06.017 Academic dissertation to be presented with the assent of the Doctoral Programme Committee of Health and Biosciences of the University of Oulu for public defence in Auditorium 10 of Oulu University Hospital (Kajaanintie 50), on 23 January 2026, at 12 noonAbstract
Cardiovascular diseases (CVD) are the most common cause of death in the Western countries. Type II diabetes (T2D) at least doubles the risk of CVD such as coronary artery disease (CAD). Over 50% of mortality in diabetic patients is caused by CVD. Moreover, T2D increases the risk of chronic heart failure and cardiac death regardless of CAD. Currently, the T2D incidence is increasing rapidly due to the global obesity epidemic. Therefore, issues related to T2D and CVD are bound to have an increased impact in society in the future.
In this thesis the correlation between biomarkers of collagen synthesis and inflammation, the amount of myocardial fibrosis estimated from cardiac magnetic resonance imaging (cMRI), and diastolic properties of the left ventricle was evaluated in 63 patients (I). An impaired diastolic function correlated with the cMRI findings and the levels of biomarkers PIIINP, Gal-3 and sST2.
In studies II-IV, 1946 patients with a stable CAD with or without T2D were investigated. The value of biomarkers in the risk prediction among patients with T2D and CAD was assessed (II). During the two-year follow-up, especially elevated high-sensitivity troponin T (hs-TnT) levels were associated with an 9.9-fold (p < 0.001) increased risk of a cardiac death or hospitalisation for congestive heart failure. During the 6.3-year follow-up, elevated hs-TnT and elevated sST2 levels together led to a 6.4-fold (p < 0.001) increase in the risk of a sudden cardiac death (SCD) compared to those with normal values among all CAD patients with or without T2D (III). The risk of SCD or aborted cardiac arrest was 2.6-fold (p < 0.01) higher in the T2D patients compared to their non-diabetic counterparts (IV). There was, however, no difference in the risk for non-SCD. Hospitalisation for congestive heart failure was significantly more common among the T2D patients (p < 0.001). The annual mortality of the non-diabetic CAD patients was 0.50%, which is lower than the cardiac mortality reported in a matched general Finnish population (0.59%).
In conclusion, T2D in CAD patients results in a significantly worse prognosis. Novel risk markers such as the hs-TnT are associated with adverse events among T2D patients with CAD. These results suggest that T2D might have a direct effect on the myocardium, which results in an increased risk for heart failure and SCD.Tiivistelmä
Sydän- ja verisuonisairaudet ovat suurin yksittäinen kuolemansyy länsimaissa. Yli puolella aikuistyypin diabeetikoista (T2D) kuoleman syynä ovat sydän- ja verisuonisairaudet. Lisäksi T2D lisää riskiä sydämen vajaatoiminnan ilmaantumiselle ja sydänperäiselle äkkikuolemalle sepelvaltimotaudista riippumatta. Huomioiden T2D:n jatkuvasti lisääntyvä ilmaantuvuus, T2D tulee olemaan merkittävä yhteiskunnallinen ongelma tulevaisuudessa.
Ensimmäisessä osajulkaisussa (I) tutkittiin kollageenisynteesiä ja inflammaatiota kuvaavien biomarkkereiden, sydämen magneettikuvauksesta (cMRI) arvioidun sydänlihaksen sidekudoksen määrän ja sydämen diastoliseen toiminnan korrelaatiota 63 potilaan aineistossa. Huonompi diastolinen toiminta korreloitui sekä cMRI-löydökseen että biomarkkereista PIIINP, Gal-3 ja sST2 pitoisuuksiin.
Muissa osajulkaisuissa arvioitiin uusien riskimarkkereiden kykyä ennustaa sydäntapahtumia prospektiivisessa 1946 potilaan tapaus-verrokki-tutkimuksessa stabiilia sepelvaltimotautia sairastavilla diabeetikoilla ja ei-diabeetikoilla. Kahden vuoden seurannassa varsinkin poikkeava herkän troponiini T:n (hs-TnT) pitoisuus lisäsi diabeetikon sydänkuoleman tai vajaatoimintahospitalisaation riskiä 9.9 kertaiseksi (p < 0.001) (II). Keskimäärin 6.3 vuoden seurannassa poikkeavat hs-TnT ja sST2 tasot yhdessä nostivat sydänperäisen äkkikuoleman riskin 6.4 kertaiseksi (p < 0.001) verrattuna niihin potilaisiin, joilla arvot olivat normaalit (III). Sydänperäisen äkkikuoleman tai sydänpysähdyksen riski oli aikuistyypin diabeetikoilla 2.6 kertainen (p < 0.01) verrattuna ei-diabeetikoihin (IV). Sen sijaan muussa sydänkuolleisuudessa ei todettu eroa. Vajaatoimintahospitalisaatiot olivat myös selkeästi yleisempiä diabeetikoilla (p < 0.001). Tässä tutkimuksessa vuosittainen kuolleisuus ei-diabeetikoilla oli 0.50 %, mikä on matalampi kuin samanikäisessä yleisessä suomalaisessa väestössä (0.59 %).
Tutkimukset osoittivat että, aikuistyypin diabetes sepelvaltimotautipotilaalla huonontaa ennustetta selkeästi ei-diabeetikkoon verrattuna. Uudet riskimarkkerit, kuten hs-TnT, liittyvät huonompaan ennusteeseen sepelvaltimotautia sairastavilla T2D potilailla. Näiden tulosten perusteella vaikuttaa siltä, että aikuistyypin diabetekseen voi liittyä merkittävä riski sydänlihassairaudelle, joka voi johtaa sydämen vajaatoimintaan ja äkkikuolemaan
Early-life antibiotics, gut microbiota, and later health in children
No full textAbstract
Children are commonly exposed to antibiotics in utero, at birth, and during childhood. The most common reason for antibiotic exposure during vaginal birth is intrapartum antibiotic prophylaxis (IAP), administered for Group B Streptococcus (GBS)-colonized mothers to prevent severe neonatal early-onset GBS infections, such as sepsis and meningitis. Early-life antibiotic exposure has been put forth as a cause of short-term alterations in children’s gut microbiota, which in turn may be associated with autoimmune diseases, allergic diseases, and weight gain. Research concerning the potential long-term effects of perinatal antibiotic exposure on children’s gut microbiota and later health is limited.
We explored perinatal antibiotic exposure and children’s gut microbiota composition in a prospective cohort study of 100 vaginally delivered infants. We collected fecal samples at one year of age and analyzed them using 16S ribosomal RNA gene next-generation sequencing. Perinatal antibiotic exposure was associated with alterations in the infant’s gut microbiota at 1 year of age, alterations that were greater than those of exposure to courses of antibiotics during the first year of life.
We conducted a population-based and register-based study of an estimated 40,000 vaginally delivered children born in Oulu University Hospital and Oulaskangas Hospital to explore early-life antibiotic exposure and children’s later health. Perinatal antibiotic exposure was associated with an increased risk of autoimmune disease diagnoses in childhood. We found no such association with the diagnosis of allergic diseases or obstructive airway diseases. However, perinatal antibiotic exposure was found to be associated with an increased risk of the use of obstructive airway–related medications in children. Antibiotic exposure in the first two years of life was associated with childhood overweight and obesity, whereas we found no such association with antibiotic exposure before or during pregnancy or during the perinatal period. Original papers Ainonen, S., Tejesvi, M. V., Mahmud, Md. R., Paalanne, N., Pokka, T., Li, W., Nelson, K. E., Salo, J., Renko, M., Vänni, P., Pirttilä, A. M., & Tapiainen, T. (2022). Antibiotics at birth and later antibiotic courses: Effects on gut microbiota. Pediatric Research, 91(1), 154–162. https://doi.org/10.1038/s41390-021-01494-7 https://doi.org/10.1038/s41390-021-01494-7 Self-archived version Ainonen, S., Ronkainen, E., Hakkola, M., Pokka, T., Honkila, M., Paalanne, M., Kajantie, E., Paalanne, N., & Ruuska, T. S. (2024). Risk of immune-related diseases in childhood after intrapartum antibiotic exposure. American Journal of Obstetrics and Gynecology, 231(4), 454.e1-454.e10. https://doi.org/10.1016/j.ajog.2024.02.020 https://doi.org/10.1016/j.ajog.2024.02.020 Self-archived version Ainonen, S., Paalanne, M., Ronkainen, E., Pokka, T., Honkila, M., Kajantie, E., Paalanne N., & Ruuska-Loewald T. (2025). Early-life antibiotic exposure and the risk of overweight and obesity in children. Manuscript submitted for publication. Tiivistelmä
Lapset altistuvat yleisesti mikrobilääkkeille raskauden aikana kohdussa, syntymässä ja myöhemmin lapsuudessa. Yleisin syy mikrobilääkealtistukselle alatiesynnytyksessä on synnytyksen aikainen mikrobilääkeprofylaksi. Profylaksi annetaan B-ryhmän Streptokokin (GBS) kantajaäideille estämään vastasyntyneiden vakavia varhaisia GBS infektioita, kuten sepsistä ja aivokalvontulehdusta.
Varhaisten mikrobilääkkeiden on esitetty aiheuttavan lyhytaikaisia muutoksia lasten suolen mikrobistossa, jotka puolestaan on yhdistetty mahdollisiin autoimmuunisairauksiin, allergisiin sairauksiin ja ylipainoon. Tutkimusta perinataalisten antibioottien mahdollisista pitkäaikaisvaikutuksista lasten suolen mikrobistolle ja myöhemmälle terveydelle on rajatusti.
Tutkimme perinataalista mikrobilääkealtistusta ja lasten suolen mikrobiston koostumusta prospektiivisessa 100 alateitse syntyneen lapsen kohorttitutkimuksessa. Keräsimme ulostenäytteet yhden vuoden iässä ja analysoimme ne käyttäen 16S ribosomaalista RNA-geenin uuden sukupolven sekvensointi-menetelmää. Altistuminen perinataaliselle mikrobilääkkeelle yhdistyi lasten suolen mikrobiston muutoksiin yhden vuoden iässä, ja muutokset olivat ensimmäisen elinvuoden mikrobilääkekuureja merkittävämpiä.
Selvitimme populaatio- ja rekisteripohjaisessa yli 40 000 alateitse Oulun yliopistollisessa sairaalassa ja Oulaskankaan sairaalassa syntyneen lapsen tutkimuksessa varhaisen mikrobilääkealtistuksen yhteyttä lasten myöhempään terveyteen. Perinataaliseen mikrobilääkealtistukseen liittyi suurentunut lapsuusiän autoimmuunisairauksien riski. Yhteyttä allergisiin tai ahtauttaviin ilmatiesairauksiin ei löydetty, mutta perinataalinen mikrobilääkealtistus yhdistyi suurentuneeseen riskiin käyttää ahtauttaviin ilmatiesairauksiin liittyviä lääkkeitä. Mikrobilääkealtistus ensimmäisen kahden elinvuoden aikana oli yhteydessä lapsuusiän ylipainoon ja lihavuuteen kun taas samanlaista yhteyttä mikrobilääkealtistuksella ennen raskautta, raskauden aikana tai syntymän yhteydessä ei löydetty. Osajulkaisut Ainonen, S., Tejesvi, M. V., Mahmud, Md. R., Paalanne, N., Pokka, T., Li, W., Nelson, K. E., Salo, J., Renko, M., Vänni, P., Pirttilä, A. M., & Tapiainen, T. (2022). Antibiotics at birth and later antibiotic courses: Effects on gut microbiota. Pediatric Research, 91(1), 154–162. https://doi.org/10.1038/s41390-021-01494-7 https://doi.org/10.1038/s41390-021-01494-7 Rinnakkaistallennettu versio Ainonen, S., Ronkainen, E., Hakkola, M., Pokka, T., Honkila, M., Paalanne, M., Kajantie, E., Paalanne, N., & Ruuska, T. S. (2024). Risk of immune-related diseases in childhood after intrapartum antibiotic exposure. American Journal of Obstetrics and Gynecology, 231(4), 454.e1-454.e10. https://doi.org/10.1016/j.ajog.2024.02.020 https://doi.org/10.1016/j.ajog.2024.02.020 Rinnakkaistallennettu versio Ainonen, S., Paalanne, M., Ronkainen, E., Pokka, T., Honkila, M., Kajantie, E., Paalanne N., & Ruuska-Loewald T. (2025). Early-life antibiotic exposure and the risk of overweight and obesity in children. Manuscript submitted for publication. Academic dissertation to be presented with the assent of the Doctoral Programme Committee of Health and Biosciences of the University of Oulu for public defence in Auditorium F202 of the Faculty of Medicine (Aapistie 5 B), on 6 February 2026, at 12 noonAbstract
Children are commonly exposed to antibiotics in utero, at birth, and during childhood. The most common reason for antibiotic exposure during vaginal birth is intrapartum antibiotic prophylaxis (IAP), administered for Group B Streptococcus (GBS)-colonized mothers to prevent severe neonatal early-onset GBS infections, such as sepsis and meningitis. Early-life antibiotic exposure has been put forth as a cause of short-term alterations in children’s gut microbiota, which in turn may be associated with autoimmune diseases, allergic diseases, and weight gain. Research concerning the potential long-term effects of perinatal antibiotic exposure on children’s gut microbiota and later health is limited.
We explored perinatal antibiotic exposure and children’s gut microbiota composition in a prospective cohort study of 100 vaginally delivered infants. We collected fecal samples at one year of age and analyzed them using 16S ribosomal RNA gene next-generation sequencing. Perinatal antibiotic exposure was associated with alterations in the infant’s gut microbiota at 1 year of age, alterations that were greater than those of exposure to courses of antibiotics during the first year of life.
We conducted a population-based and register-based study of an estimated 40,000 vaginally delivered children born in Oulu University Hospital and Oulaskangas Hospital to explore early-life antibiotic exposure and children’s later health. Perinatal antibiotic exposure was associated with an increased risk of autoimmune disease diagnoses in childhood. We found no such association with the diagnosis of allergic diseases or obstructive airway diseases. However, perinatal antibiotic exposure was found to be associated with an increased risk of the use of obstructive airway–related medications in children. Antibiotic exposure in the first two years of life was associated with childhood overweight and obesity, whereas we found no such association with antibiotic exposure before or during pregnancy or during the perinatal period.Tiivistelmä
Lapset altistuvat yleisesti mikrobilääkkeille raskauden aikana kohdussa, syntymässä ja myöhemmin lapsuudessa. Yleisin syy mikrobilääkealtistukselle alatiesynnytyksessä on synnytyksen aikainen mikrobilääkeprofylaksi. Profylaksi annetaan B-ryhmän Streptokokin (GBS) kantajaäideille estämään vastasyntyneiden vakavia varhaisia GBS infektioita, kuten sepsistä ja aivokalvontulehdusta.
Varhaisten mikrobilääkkeiden on esitetty aiheuttavan lyhytaikaisia muutoksia lasten suolen mikrobistossa, jotka puolestaan on yhdistetty mahdollisiin autoimmuunisairauksiin, allergisiin sairauksiin ja ylipainoon. Tutkimusta perinataalisten antibioottien mahdollisista pitkäaikaisvaikutuksista lasten suolen mikrobistolle ja myöhemmälle terveydelle on rajatusti.
Tutkimme perinataalista mikrobilääkealtistusta ja lasten suolen mikrobiston koostumusta prospektiivisessa 100 alateitse syntyneen lapsen kohorttitutkimuksessa. Keräsimme ulostenäytteet yhden vuoden iässä ja analysoimme ne käyttäen 16S ribosomaalista RNA-geenin uuden sukupolven sekvensointi-menetelmää. Altistuminen perinataaliselle mikrobilääkkeelle yhdistyi lasten suolen mikrobiston muutoksiin yhden vuoden iässä, ja muutokset olivat ensimmäisen elinvuoden mikrobilääkekuureja merkittävämpiä.
Selvitimme populaatio- ja rekisteripohjaisessa yli 40 000 alateitse Oulun yliopistollisessa sairaalassa ja Oulaskankaan sairaalassa syntyneen lapsen tutkimuksessa varhaisen mikrobilääkealtistuksen yhteyttä lasten myöhempään terveyteen. Perinataaliseen mikrobilääkealtistukseen liittyi suurentunut lapsuusiän autoimmuunisairauksien riski. Yhteyttä allergisiin tai ahtauttaviin ilmatiesairauksiin ei löydetty, mutta perinataalinen mikrobilääkealtistus yhdistyi suurentuneeseen riskiin käyttää ahtauttaviin ilmatiesairauksiin liittyviä lääkkeitä. Mikrobilääkealtistus ensimmäisen kahden elinvuoden aikana oli yhteydessä lapsuusiän ylipainoon ja lihavuuteen kun taas samanlaista yhteyttä mikrobilääkealtistuksella ennen raskautta, raskauden aikana tai syntymän yhteydessä ei löydetty
The study of animal personality as a part of mammalian species conservation
No full textEläinten suojelun tärkeys korostuu kuudennesta sukupuuttoaallosta puhuttaessa, sillä monissa uhanalaisissa ekosysteemeissä eläimet ovat tärkeä, jopa kantava osa. Uhanalaisten lajien suojelua on harjoitettu jo pitkään, mutta suojelutapoja ei ole vuosien saatossa juuri kehitetty. Edelleen vallalla on käsitys, jonka mukaan yksi suojelun tapa sopisi kaikille tietyn lajin yksilöille. Persoonallisuuden tutkimuksen myötä on kuitenkin paljastunut, että harvemmin näin on.
Eläinten yksilöllinen persoonallisuus rakentuu persoonallisuuden piirteistä, jotka voidaan käsittää kaikkien eläimen osoittamien käytösten “yhteenvetoina”. Persoonallisuuden piirteiden yhdistymänä puolestaan syntyy yksilön yleinen persoonallisuus. Sekä piirteet että yleinen persoonallisuus vaihtelevat lajin yksilöiden välillä. Eläinten persoonallisuuden olemassaolo on tiedostettu jo lähes sadan vuoden ajan, mutta pitkään sitä pidettiin vain ns. ylimääräisenä taustahälynä. Tutkimusta onkin alettu tekemään enemmän vasta viime vuosikymmeninä.
Persoonallisuutta voidaan tutkia eläintarhaolosuhteissa, sekä eläinten luonnollisessa elinympäristössä esimerkiksi järjestämällä ympäristöä muokkaavia koetilanteita. Tällaisia voivat olla esimerkiksi avoin kenttä, jossa nimensäkin mukaan on avoin alue, jolla liikkuvan eläimen liikkeitä mitataan ja niiden perusteella voidaan määritellä esimerkiksi eläimen ujoutta tai rohkeutta.
Kun eläimelle on testien myötä määritetty tiettyjä persoonallisuuden piirteitä ja sitä myötä kokonainen persoonallisuus, on sen käyttäytymistä tulevaisuudessa, esimerkiksi suojelutoimien yhteydessä helpompi ennustaa.
Persoonallisuuden vaihtelu tuo mukanaan monia ekologisia ja evolutiivisia vaikutuksia. Nykyään niistä tiedetään jo paljon, ja se mahdollistaa paremman suojelutoimien suunnittelun, sekä tarkemman tulevaisuuden uhkien ennakoinnin. Näistä puolestaan on apua esimerkiksi siirtoistutuksessa, joka on yleinen suojelun tapa. Siinä muodostetaan villeistä tai vangituista yksilöistä uusi populaatio, joka siirretään uudelle alueelle. Populaation toivotaan tietysti menestyvän uudella alueella ja avain menestykseen saattaakin löytyä persoonallisuuden piirteistä.
Tutkimusala on vielä kovin nuori. Haasteita löytyy yhtä jos toista ja monet asiat ovat vielä pitkälti hämärän peitossa, mainittakoon esimerkkeinä persoonallisuuden plastisuus (mukautuvuus) ja persoonallisuuden piirteiden linkitysten ekologiset yhteisvaikutukset. Eläinten persoonallisuuden maailmassa on siispä vielä paljon löydettävää