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Article: Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro.

Tuukkanen, J / Väänänen, H K

1986 Volume 38, Issue 2, Page(s) 123–125

Abstract: ... of gastric parietal cell membrane H+-K+-ATPase. It is now demonstrated that similar concentrations of omeprazole ...

Abstract	Omeprazole has been previously shown to block gastric acid secretion by specific inhibition of gastric parietal cell membrane H+-K+-ATPase. It is now demonstrated that similar concentrations of omeprazole will inhibit PGE2- and PTH-stimulated 45Ca++ release from prelabelled neonatal mouse calvariae without affecting the viability of cultured calvaria explants.
MeSH term(s)	Adenosine Triphosphatases/antagonists & inhibitors ; Animals ; Benzimidazoles/pharmacology ; Bone Resorption/drug effects ; Calcium/metabolism ; H(+)-K(+)-Exchanging ATPase ; In Vitro Techniques ; Mice ; Omeprazole ; Osteoclasts/drug effects ; Osteoclasts/metabolism
Chemical Substances	Benzimidazoles ; Adenosine Triphosphatases (EC 3.6.1.-) ; H(+)-K(+)-Exchanging ATPase (EC 3.6.3.10) ; Omeprazole (KG60484QX9) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	1986-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	304266-2
ISSN	1432-0827 ; 0171-967X ; 0944-0747 ; 0008-0594
ISSN (online)	1432-0827
ISSN	0171-967X ; 0944-0747 ; 0008-0594
DOI	10.1007/bf02556841
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Zs.A 317: Show issues

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Article ; Online: 3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort.

Grassi, Lorenzo / Väänänen, Sami P / Jehpsson, Lars / Ljunggren, Östen / Rosengren, Björn E / Karlsson, Magnus K / Isaksson, Hanna

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2023 Volume 38, Issue 9, Page(s) 1258–1267

Abstract: Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models ... ...

Abstract	Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
MeSH term(s)	Male ; Humans ; Absorptiometry, Photon/methods ; Finite Element Analysis ; Osteoporotic Fractures/diagnostic imaging ; Osteoporotic Fractures/epidemiology ; Sweden/epidemiology ; Hip Fractures/diagnostic imaging ; Hip Fractures/epidemiology ; Bone Density
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4878
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Article: Anthropogenic bottom-up and top-down impacts on boreal breeding waterbirds.

Holopainen, Sari / Jaatinen, Kim / Laaksonen, Toni / Lindén, Andreas / Nummi, Petri / Piha, Markus / Pöysä, Hannu / Toivanen, Tero / Väänänen, Veli-Matti / Alhainen, Mikko / Lehikoinen, Aleksi

Ecology and evolution

2024 Volume 14, Issue 3, Page(s) e11136

Abstract: Wetland habitats are changing under multiple anthropogenic pressures. Nutrient leakage and pollution modify physico-chemical state of wetlands and affect the ecosystem through bottom-up processes, while alien predators affect the ecosystems in a top-down ...

Abstract	Wetland habitats are changing under multiple anthropogenic pressures. Nutrient leakage and pollution modify physico-chemical state of wetlands and affect the ecosystem through bottom-up processes, while alien predators affect the ecosystems in a top-down manner. Boreal wetlands are important breeding areas for several waterbird species, the abundances of which potentially reflect both bottom-up and top-down ecosystem processes. Here, we use long-term national monitoring data gathered from c. 130 waterbird breeding sites in Finland from the 1980s to the 2020s. We hypothesised that the physico-chemical state of the waters and increasing alien predator abundance both play a role in steering the waterbird population trends. We set out to test this hypothesis by relating population changes of 17 waterbird species to changes in water chemistry and to regional alien predator indices while allowing species-specific effects to vary with foraging niche (dabblers, invertivore divers, piscivorous divers, herbivores), nesting site, female mass and habitat (oligotrophic, eutrophic). We found niche and nesting site-specific, habitat-dependent changes in waterbird numbers. While the associations with higher phosphorus levels and browning water were in overall positive at the oligotrophic lakes, the numbers of invertivore and piscivore diving ducks were most strongly negatively associated with higher phosphorus levels and browning water at the eutrophic lakes. Furthermore, increased pH levels benefitted piscivores. Invertivore diving duck species nesting on the wetlands had declined most on sites with high alien predator indices. Large herbivorous species and species preferring oligotrophic lakes seem to be successful. We conclude that the large-scale breeding waterbird decline in Finland is closely connected to both bottom-up and top-down processes, where negative associations are emphasised especially at eutrophic lakes. Niche-, nest site- and habitat-specific management actions are required to conserve declining waterbird populations. Managing wetlands on catchments level together with alien predator control may provide important approaches to future wetland management.
Language	English
Publishing date	2024-03-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2635675-2
ISSN	2045-7758
ISSN	2045-7758
DOI	10.1002/ece3.11136
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Article ; Online: Effects of β-blockers on ventricular repolarization documented by 24-hour electrocardiography in long QT syndrome type 2.

Koponen, Mikael / Marjamaa, Annukka / Väänänen, Heikki / Tuiskula, Annukka M / Kontula, Kimmo / Swan, Heikki / Viitasalo, Matti

Heart rhythm

2022 Volume 19, Issue 9, Page(s) 1491–1498

Abstract: Background: Long QT syndrome (LQTS) is an inherited arrhythmia disorder characterized by ventricular repolarization abnormalities and a risk of sudden cardiac death. The electrophysiological components generating the high risk of arrhythmias in LQTS are ...

Abstract	Background: Long QT syndrome (LQTS) is an inherited arrhythmia disorder characterized by ventricular repolarization abnormalities and a risk of sudden cardiac death. The electrophysiological components generating the high risk of arrhythmias in LQTS are prolonged repolarization, increased dispersion of repolarization, and early afterdepolarizations, which are clinically estimated as QT interval, T-wave peak to T-wave end (TPE) interval, and T2/T1-wave amplitude ratio, respectively. In experimental LQTS type 2 (LQT2) models, β-blockers decrease dispersion of repolarization and prevent early afterdepolarizations. In clinical studies in patients with LQT2 , β-blockers are more effective against exercise-induced than arousal-induced cardiac events. Objectives: The aim of the study was to investigate the effects of β-blocker therapy on repolarization properties in LQT2. Methods: QT and TPE intervals and maximal T2/T1-wave amplitude ratios recorded by 24-hour electrocardiograms before and during β-blocker therapy were evaluated in 25 patients with LQT2. Results: β-Blocker therapy decreased the maximal T2/T1-wave amplitude ratio from 2.9 ± 1.1 to 1.8 ± 0.7 (P < .001), but did not change the pause-induced T2/T1-wave amplitude ratio. Under medication, abrupt maximal TPE intervals were shorter at heart rates of ≥75 beats/min and maximal QT intervals were shorter at a heart rate of 100 beats/min. Conclusion: β-Blockers stabilize ventricular repolarization in LQT2 by reducing electrocardiographic early afterdepolarizations and by reducing abrupt prolongation of electrocardiographic dispersion of repolarization and ventricular repolarization duration at elevated heart rates. The effect of β-blockers on pause-induced electrocardiographic early afterdepolarizations is weak. The findings provide electrocardiographic explanation for the protective effects of β-blockers against exercise-induced cardiac events in LQT2.
MeSH term(s)	Adrenergic beta-Antagonists/pharmacology ; Adrenergic beta-Antagonists/therapeutic use ; Arrhythmias, Cardiac/drug therapy ; Electrocardiography ; Electrocardiography, Ambulatory ; Heart Rate ; Humans ; Long QT Syndrome/diagnosis ; Long QT Syndrome/drug therapy
Chemical Substances	Adrenergic beta-Antagonists
Language	English
Publishing date	2022-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2022.04.028
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Zs.A 6278: Show issues

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Article ; Online: Removal of proteinase K resistant αSyn species does not correlate with cell survival in a virus vector-based Parkinson's disease mouse model.

Eteläinen, Tony S / Kilpeläinen, Tommi P / Ignatius, Adele / Auno, Samuli / De Lorenzo, Francesca / Uhari-Väänänen, Johanna K / Julku, Ulrika H / Myöhänen, Timo T

Neuropharmacology

2022 Volume 218, Page(s) 109213

Abstract: ... significantly proteinase K-resistant αSyn oligomers and oxidative damage related to αSyn aggregation ...

Abstract	Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neurons and accumulation of α-synuclein (αSyn) as Lewy bodies. Currently, there is no disease-modifying therapy available for PD. We have shown that a small molecular inhibitor for prolyl oligopeptidase (PREP), KYP-2047, relieves αSyn-induced toxicity in various PD models by inducing autophagy and preventing αSyn aggregation. In this study, we wanted to study the effects of PREP inhibition on different αSyn species by using cell culture and in vivo models. We used Neuro2A cells with transient αSyn overexpression and oxidative stress or proteasomal inhibition-induced αSyn aggregation to assess the effect of KYP-2047 on soluble αSyn oligomers and on cell viability. Here, the levels of soluble αSyn were measured by using ELISA, and the impact of KYP-2047 was compared to anle138b, nilotinib and deferiprone. To evaluate the effect of KYP-2047 on αSyn fibrillization in vivo, we used unilateral nigral AAV1/2-A53T-αSyn mouse model, where the KYP-2047 treatment was initiated two- or four-weeks post injection. KYP-2047 and anle138b protected cells from αSyn toxicity but interestingly, KYP-2047 did not reduce soluble αSyn oligomers. In AAV-A53T-αSyn mouse model, KYP-2047 reduced significantly proteinase K-resistant αSyn oligomers and oxidative damage related to αSyn aggregation. However, the KYP-2047 treatment that was initiated at the time of symptom onset, failed to protect the nigrostriatal dopaminergic neurons. Our results emphasize the importance of whole αSyn aggregation process in the pathology of PD and raise an important question about the forms of αSyn that are reasonable targets for PD drug therapy.
MeSH term(s)	Animals ; Cell Survival ; Disease Models, Animal ; Endopeptidase K ; Mice ; Parkinson Disease/drug therapy ; Prolyl Oligopeptidases ; alpha-Synuclein
Chemical Substances	alpha-Synuclein ; Prolyl Oligopeptidases (EC 3.4.21.26) ; Endopeptidase K (EC 3.4.21.64)
Language	English
Publishing date	2022-08-12
Publishing country	England
Document type	Journal Article
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2022.109213
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Ui I Zs.242: Show issues

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Article ; Online: Invasive species control with apex predators: increasing presence of wolves is associated with reduced occurrence of the alien raccoon dog

Selonen, V. / Brommer, J. E. / Holopainen, S. / Kauhala, K. / Krüger, H. / Poutanen, J. / Väänänen, V.-M. / Laaksonen, T.

Biol Invasions. 2022 Nov., v. 24, no. 11 p.3461-3474

2022

Abstract: The role of an alien predator in the community depends on its interaction with native predators. The absence of apex predators may facilitate outbreaks of invasive mesopredators, but the effect of apex predators may vary between species and environments. ...

Abstract	The role of an alien predator in the community depends on its interaction with native predators. The absence of apex predators may facilitate outbreaks of invasive mesopredators, but the effect of apex predators may vary between species and environments. We analysed the occurrence of a common invasive mesopredator in Europe, the raccoon dog (Nyctereutes procyonoides), and native mesopredators, the red fox and the Eurasian badger, in camera-trap data from Finland. The observations in cameras were analysed in relation to the presence of apex predators in the landscape (grey wolf and Eurasian lynx), human density, and habitat. We observed negative effect of increasing presence of wolves and lynxes on the occurrence of raccoon dogs. This effect appeared clear compared to the effects of habitat and human density. The effect of lynxes on raccoon dogs was clearer in areas with short growth season. For the occurrence of badgers, the presence of wolves had a weak negative effect and the presence of lynxes had a positive effect. For the occurrence of red foxes, wolves had a positive effect when agricultural fields were sparse in the landscape and lynxes had no effect. We also observed that the invasive raccoon dog currently appears to be the most common mesopredator within the study area. We conclude that the effect of apex predators on mesopredators depends on the environment and, in our case, was more suppressive on the alien mesopredator than on the native mesopredators. Thus, apex predators can play an important role in controlling invasive mesopredators.
Keywords	Lynx lynx ; Meles meles ; Nyctereutes procyonoides ; Procyon lotor ; Vulpes vulpes ; cameras ; habitats ; humans ; invasive species ; landscapes ; mesopredators ; wolves ; Finland
Language	English
Dates of publication	2022-11
Size	p. 3461-3474.
Publishing place	Springer International Publishing
Document type	Article ; Online
ZDB-ID	1438729-3
ISSN	1573-1464 ; 1387-3547
ISSN (online)	1573-1464
ISSN	1387-3547
DOI	10.1007/s10530-022-02850-2
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A prolyl oligopeptidase inhibitor reduces tau pathology in cellular models and in mice with tauopathy.

Eteläinen, Tony S / Silva, M Catarina / Uhari-Väänänen, Johanna K / De Lorenzo, Francesca / Jäntti, Maria H / Cui, Hengjing / Chavero-Pieres, Marta / Kilpeläinen, Tommi / Mechtler, Christina / Svarcbahs, Reinis / Seppälä, Erin / Savinainen, Juha R / Puris, Elena / Fricker, Gert / Gynther, Mikko / Julku, Ulrika H / Huttunen, Henri J / Haggarty, Stephen J / Myöhänen, Timo T

Science translational medicine

2023 Volume 15, Issue 691, Page(s) eabq2915

Abstract: Tauopathies are neurodegenerative diseases that are characterized by accumulation of hyperphosphorylated tau protein, higher-order aggregates, and tau filaments. Protein phosphatase 2A (PP2A) is a major tau dephosphorylating phosphatase, and a decrease ... ...

Abstract	Tauopathies are neurodegenerative diseases that are characterized by accumulation of hyperphosphorylated tau protein, higher-order aggregates, and tau filaments. Protein phosphatase 2A (PP2A) is a major tau dephosphorylating phosphatase, and a decrease in its activity has been demonstrated in tauopathies, including Alzheimer's disease. Prolyl oligopeptidase is a serine protease that is associated with neurodegeneration, and its inhibition normalizes PP2A activity without toxicity under pathological conditions. Here, we assessed whether prolyl oligopeptidase inhibition could protect against tau-mediated toxicity in cellular models in vitro and in the PS19 transgenic mouse model of tauopathy carrying the human tau-P301S mutation. We show that inhibition of prolyl oligopeptidase with the inhibitor KYP-2047 reduced tau aggregation in tau-transfected HEK-293 cells and N2A cells as well as in human iPSC-derived neurons carrying either the P301L or tau-A152T mutation. Treatment with KYP-2047 resulted in increased PP2A activity and activation of autophagic flux in HEK-293 cells and N2A cells and in patient-derived iNeurons, as indicated by changes in autophagosome and autophagy receptor markers; this contributed to clearance of insoluble tau. Furthermore, treatment of PS19 transgenic mice for 1 month with KYP-2047 reduced tau burden in the brain and cerebrospinal fluid and slowed cognitive decline according to several behavioral tests. In addition, a reduction in an oxidative stress marker was seen in mouse brains after KYP-2047 treatment. This study suggests that inhibition of prolyl oligopeptidase could help to ameliorate tau-dependent neurodegeneration.
MeSH term(s)	Mice ; Humans ; Animals ; Prolyl Oligopeptidases ; HEK293 Cells ; Tauopathies/metabolism ; tau Proteins/metabolism ; Mice, Transgenic ; Serine Endopeptidases/metabolism ; Enzyme Inhibitors ; Disease Models, Animal
Chemical Substances	Prolyl Oligopeptidases (EC 3.4.21.26) ; tau Proteins ; Serine Endopeptidases (EC 3.4.21.-) ; Enzyme Inhibitors
Language	English
Publishing date	2023-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abq2915
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Zs.A 6941: Show issues

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Article ; Online: Comparative whole-genome transcriptome analysis in renal cell populations reveals high tissue specificity of MAPK/ERK targets in embryonic kidney.

Kurtzeborn, Kristen / Kwon, Hyuk Nam / Iaroshenko, Vladislav / Faisal, Imrul / Ambrož, Martin / Jin, Xing / Qureshi, Talha / Kupari, Jussi / Ihermann-Hella, Anneliis / Väänänen, Juho / Tyynismaa, Henna / Boušová, Iva / Park, Sunghyouk / Kuure, Satu

BMC biology

2022 Volume 20, Issue 1, Page(s) 112

Abstract: Background: MAPK/ERK signaling is a well-known mediator of extracellular stimuli controlling intracellular responses to growth factors and mechanical cues. The critical requirement of MAPK/ERK signaling for embryonic stem cell maintenance is ... ...

Abstract	Background: MAPK/ERK signaling is a well-known mediator of extracellular stimuli controlling intracellular responses to growth factors and mechanical cues. The critical requirement of MAPK/ERK signaling for embryonic stem cell maintenance is demonstrated, but specific functions in progenitor regulation during embryonic development, and in particular kidney development remain largely unexplored. We previously demonstrated MAPK/ERK signaling as a key regulator of kidney growth through branching morphogenesis and normal nephrogenesis where it also regulates progenitor expansion. Here, we performed RNA sequencing-based whole-genome expression analysis to identify transcriptional MAPK/ERK targets in two distinct renal populations: the ureteric bud epithelium and the nephron progenitors. Results: Our analysis revealed a large number (5053) of differentially expressed genes (DEGs) in nephron progenitors and significantly less (1004) in ureteric bud epithelium, reflecting likely heterogenicity of cell types. The data analysis identified high tissue-specificity, as only a fraction (362) of MAPK/ERK targets are shared between the two tissues. Tissue-specific MAPK/ERK targets participate in the regulation of mitochondrial energy metabolism in nephron progenitors, which fail to maintain normal mitochondria numbers in the MAPK/ERK-deficient tissue. In the ureteric bud epithelium, a dramatic decline in progenitor-specific gene expression was detected with a simultaneous increase in differentiation-associated genes, which was not observed in nephron progenitors. Our experiments in the genetic model of MAPK/ERK deficiency provide evidence that MAPK/ERK signaling in the ureteric bud maintains epithelial cells in an undifferentiated state. Interestingly, the transcriptional targets shared between the two tissues studied are over-represented by histone genes, suggesting that MAPK/ERK signaling regulates cell cycle progression and stem cell maintenance through chromosome condensation and nucleosome assembly. Conclusions: Using tissue-specific MAPK/ERK inactivation and RNA sequencing in combination with experimentation in embryonic kidneys, we demonstrate here that MAPK/ERK signaling maintains ureteric bud tip cells, suggesting a regulatory role in collecting duct progenitors. We additionally deliver new mechanistic information on how MAPK/ERK signaling regulates progenitor maintenance through its effects on chromatin accessibility and energy metabolism.
MeSH term(s)	Epithelial Cells ; Female ; Gene Expression Profiling ; Humans ; Kidney/metabolism ; Nephrons/metabolism ; Organ Specificity ; Pregnancy
Language	English
Publishing date	2022-05-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/s12915-022-01309-z
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Article ; Online: Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB.

Bicak, Mesude / Wang, Xing / Gao, Xiaoni / Xu, Xing / Väänänen, Riina-Minna / Taimen, Pekka / Lilja, Hans / Pettersson, Kim / Klein, Robert J

Human molecular genetics

2020 Volume 29, Issue 10, Page(s) 1581–1591

Abstract: How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 ...

Abstract	How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis.
MeSH term(s)	Alleles ; CRISPR-Cas Systems ; Cell Line, Tumor ; Gene Editing ; Gene Expression Regulation/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide/genetics ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Prostatic Secretory Proteins/genetics ; Quantitative Trait Loci/genetics ; RNA, Long Noncoding/genetics ; RNA, Untranslated/genetics
Chemical Substances	Prostatic Secretory Proteins ; RNA, Long Noncoding ; RNA, Untranslated ; beta-microseminoprotein
Language	English
Publishing date	2020-02-20
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddaa026
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Zs.A 3469: Show issues

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Article ; Online: Clinical Contrast-Enhanced Computed Tomography With Semi-Automatic Segmentation Provides Feasible Input for Computational Models of the Knee Joint.

Myller, Katariina A H / Korhonen, Rami K / Töyräs, Juha / Tanska, Petri / Väänänen, Sami P / Jurvelin, Jukka S / Saarakkala, Simo / Mononen, Mika E

Journal of biomechanical engineering

2019 Volume 142, Issue 5

Abstract: Computational models can provide information on joint function and risk of tissue failure related to progression of osteoarthritis (OA). Currently, the joint geometries utilized in modeling are primarily obtained via manual segmentation, which is time- ... ...

Abstract	Computational models can provide information on joint function and risk of tissue failure related to progression of osteoarthritis (OA). Currently, the joint geometries utilized in modeling are primarily obtained via manual segmentation, which is time-consuming and hence impractical for direct clinical application. The aim of this study was to evaluate the applicability of a previously developed semi-automatic method for segmenting tibial and femoral cartilage to serve as input geometry for finite element (FE) models. Knee joints from seven volunteers were first imaged using a clinical computed tomography (CT) with contrast enhancement and then segmented with semi-automatic and manual methods. In both segmentations, knee joint models with fibril-reinforced poroviscoelastic (FRPVE) properties were generated and the mechanical responses of articular cartilage were computed during physiologically relevant loading. The mean differences in the absolute values of maximum principal stress, maximum principal strain, and fibril strain between the models generated from semi-automatic and manual segmentations were <1 MPa, <0.72% and <0.40%, respectively. Furthermore, contact areas, contact forces, average pore pressures, and average maximum principal strains were not statistically different between the models (p >0.05). This semi-automatic method speeded up the segmentation process by over 90% and there were only negligible differences in the results provided by the models utilizing either manual or semi-automatic segmentations. Thus, the presented CT imaging-based segmentation method represents a novel tool for application in FE modeling in the clinic when a physician needs to evaluate knee joint function.
MeSH term(s)	Adult ; Cartilage, Articular ; Computer Simulation ; Finite Element Analysis ; Humans ; Knee Joint ; Tibia ; Tomography, X-Ray Computed
Language	English
Publishing date	2019-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	243094-0
ISSN	1528-8951 ; 0148-0731
ISSN (online)	1528-8951
ISSN	0148-0731
DOI	10.1115/1.4045279
Database	MEDical Literature Analysis and Retrieval System OnLINE

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