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Background Several factors may decrease the accuracy of quantitative PET myocardial perfusion imaging (MPI). It is therefore essential to ensure that myocardial blood flow (MBF) values are reproducible and accurate, and to design systematic protocols to achieve this. Until now, no systematic phantom protocols have been available to assess the technical factors affecting measurement accuracy and reproducibility in MPI. Materials and methods We implemented a standard measurement protocol, which applies a flow phantom in order to compare image-derived flow values with respect to a ground truth flow value with [ 15 O]H 2 O MPI performed on both a Discovery MI (DMI-20, GE Healthcare) and a Biograph Vision 600 (Vision-600, Siemens Healthineers) system. Both systems have automatic [ 15 O]H 2 O radio water generators (Hidex Oy) individually installed, allowing us to also study the differences occurring due to two different bolus delivery systems. To investigate the technical factors contributing to the modelled flow values, we extracted the [ 15 O]H 2 O bolus profiles, the flow values from the kinetic modeling (Qin and Qout), and finally calculated their differences between test-retest measurements on both systems. Results The measurements performed on the DMI-20 system produced Qin and Qout values corresponging to each other as well as to the reference flow value across all test-retest measurements. The repeatability differences on DMI-20 were 2.1% ± 2.6% and 3.3% ± 4.1% for Qin and Qout , respectively. On Vision-600 they were 10% ± 8.4% and 11% ± 10% for Qin and Qout , respectively. The measurements performed on the Vision-600 system showed more variation between Qin and Qout values across test-retest measurements and exceeded 15% difference in 7/24 of the measurements. Conclusions A preliminary protocol for measuring the accuracy and reproducibility of flow values in [ 15 O]H 2 O MPI between digital PET/CT systems was assessed. The test-retest reproducibility falls below 15% in majority of the measurements conducted between two individual injector systems and two digital PET/CT systems. This study highlights the importance of implementing a standardized bolus injection and delivery protocol and importance of assessing technical factors affecting flow value reproducibility, which should be carefully investigated in a multi-center setting.

To successfully implement the UN’s Sustainable Development Goals (SDGs), we must encourage all citizens to work together to enable a good life not only for us now but future generations too. In this article, we present an experiment carried out in autumn 2020 on a smart aeroponic garden. The goal of the experiment was to learn more about aeroponic cultivation and IoT technology and to acquire the know-how that would enable the participants to influence the environmental burden of food production. Our experiment showed that technology could also be used to introduce sustainable development themes to reach those target groups whose attention could not be attracted through other methods.

Several factors may decrease the accuracy of quantitative PET myocardial perfusion imaging (MPI). It is therefore essential to ensure that myocardial blood flow (MBF) values are reproducible and accurate, and to design systematic protocols to achieve this. Until now, no systematic phantom protocols have been available to assess the technical factors affecting measurement accuracy and reproducibility in MPI. We implemented a standard measurement protocol, which applies a flow phantom in order to compare image-derived flow values with respect to a ground truth flow value with [ O]H O MPI performed on both a Discovery MI (DMI-20, GE Healthcare) and a Biograph Vision 600 (Vision-600, Siemens Healthineers) system. Both systems have automatic [ O]H O radio water generators (Hidex Oy) individually installed, allowing us to also study the differences occurring due to two different bolus delivery systems. To investigate the technical factors contributing to the modelled flow values, we extracted the [ O]H O bolus profiles, the flow values from the kinetic modeling (Qin and Qout), and finally calculated their differences between test-retest measurements on both systems. The measurements performed on the DMI-20 system produced Qin and Qout values corresponging to each other as well as to the reference flow value across all test-retest measurements. The repeatability differences on DMI-20 were 2.1% ± 2.6% and 3.3% ± 4.1% for Qin and Qout, respectively. On Vision-600 they were 10% ± 8.4% and 11% ± 10% for Qin and Qout, respectively. The measurements performed on the Vision-600 system showed more variation between Qin and Qout values across test-retest measurements and exceeded 15% difference in 7/24 of the measurements. A preliminary protocol for measuring the accuracy and reproducibility of flow values in [ O]H O MPI between digital PET/CT systems was assessed. The test-retest reproducibility falls below 15% in majority of the measurements conducted between two individual injector systems and two digital PET/CT systems. This study highlights the importance of implementing a standardized bolus injection and delivery protocol and importance of assessing technical factors affecting flow value reproducibility, which should be carefully investigated in a multi-center setting.

Several factors may decrease the accuracy of quantitative PET myocardial perfusion imaging (MPI). It is therefore essential to ensure that myocardial blood flow (MBF) values are reproducible and accurate, and to design systematic protocols to achieve this. Until now, no systematic phantom protocols have been available to assess the technical factors affecting measurement accuracy and reproducibility in MPI.BACKGROUNDSeveral factors may decrease the accuracy of quantitative PET myocardial perfusion imaging (MPI). It is therefore essential to ensure that myocardial blood flow (MBF) values are reproducible and accurate, and to design systematic protocols to achieve this. Until now, no systematic phantom protocols have been available to assess the technical factors affecting measurement accuracy and reproducibility in MPI.We implemented a standard measurement protocol, which applies a flow phantom in order to compare image-derived flow values with respect to a ground truth flow value with [15O]H2O MPI performed on both a Discovery MI (DMI-20, GE Healthcare) and a Biograph Vision 600 (Vision-600, Siemens Healthineers) system. Both systems have automatic [15O]H2O radio water generators (Hidex Oy) individually installed, allowing us to also study the differences occurring due to two different bolus delivery systems. To investigate the technical factors contributing to the modelled flow values, we extracted the [15O]H2O bolus profiles, the flow values from the kinetic modeling (Qin and Qout), and finally calculated their differences between test-retest measurements on both systems.MATERIALS AND METHODSWe implemented a standard measurement protocol, which applies a flow phantom in order to compare image-derived flow values with respect to a ground truth flow value with [15O]H2O MPI performed on both a Discovery MI (DMI-20, GE Healthcare) and a Biograph Vision 600 (Vision-600, Siemens Healthineers) system. Both systems have automatic [15O]H2O radio water generators (Hidex Oy) individually installed, allowing us to also study the differences occurring due to two different bolus delivery systems. To investigate the technical factors contributing to the modelled flow values, we extracted the [15O]H2O bolus profiles, the flow values from the kinetic modeling (Qin and Qout), and finally calculated their differences between test-retest measurements on both systems.The measurements performed on the DMI-20 system produced Qin and Qout values corresponging to each other as well as to the reference flow value across all test-retest measurements. The repeatability differences on DMI-20 were 2.1% ± 2.6% and 3.3% ± 4.1% for Qin and Qout, respectively. On Vision-600 they were 10% ± 8.4% and 11% ± 10% for Qin and Qout, respectively. The measurements performed on the Vision-600 system showed more variation between Qin and Qout values across test-retest measurements and exceeded 15% difference in 7/24 of the measurements.RESULTSThe measurements performed on the DMI-20 system produced Qin and Qout values corresponging to each other as well as to the reference flow value across all test-retest measurements. The repeatability differences on DMI-20 were 2.1% ± 2.6% and 3.3% ± 4.1% for Qin and Qout, respectively. On Vision-600 they were 10% ± 8.4% and 11% ± 10% for Qin and Qout, respectively. The measurements performed on the Vision-600 system showed more variation between Qin and Qout values across test-retest measurements and exceeded 15% difference in 7/24 of the measurements.A preliminary protocol for measuring the accuracy and reproducibility of flow values in [15O]H2O MPI between digital PET/CT systems was assessed. The test-retest reproducibility falls below 15% in majority of the measurements conducted between two individual injector systems and two digital PET/CT systems. This study highlights the importance of implementing a standardized bolus injection and delivery protocol and importance of assessing technical factors affecting flow value reproducibility, which should be carefully investigated in a multi-center setting.CONCLUSIONSA preliminary protocol for measuring the accuracy and reproducibility of flow values in [15O]H2O MPI between digital PET/CT systems was assessed. The test-retest reproducibility falls below 15% in majority of the measurements conducted between two individual injector systems and two digital PET/CT systems. This study highlights the importance of implementing a standardized bolus injection and delivery protocol and importance of assessing technical factors affecting flow value reproducibility, which should be carefully investigated in a multi-center setting.

This chapter describes the significance of ABC transporters in human placenta for the exposure of the fetus to xenobiotics. Many xenobiotics go through the placenta very easily by passive diffusion. Passive diffusion is the most common mechanism of transfer and depends on the chemical characteristics of compounds, such as molecular weight, lipid solubility, binding to proteins and the degree of ionization. The first part of this chapter details the structure, function and polymorphisms of human efflux ABC transporters. The experimental models used to study placental transfer processes in vitro include placental perfusion, cultured placental tissue explants or isolated villous trees, primary cell cultures, immortalized or cancer cell lines, placental membrane vesicles and cloned transporters. These studies give an idea how the compounds reach the fetus and increase understanding of the significance of transplacental transport in vivo. Because animal studies, especially transporter knockout mice, have given valuable data about the significance of the role of transporters in fetal exposure and fetotoxicity, some of those data are also included. Since ABC transporters take part in important functions in body, it is no wonder that genetic polymorphisms of the transporters are known or suspected to be linked to diseases of many organs. Studies on gene knockout transgenic mice have clearly shown the importance of placental transporters in the protection against toxic insult to the fetus.

Oncogenic transcription factor Myc deregulates the cell cycle and simultaneously reprograms cellular metabolism to meet the biosynthetic and bioenergetic needs of proliferation. Myc also sensitizes cells to mitochondria-dependent apoptosis. Although metabolic reprogramming has been circumstantially connected to vulnerability to apoptosis, the connecting molecular pathways have remained poorly defined. Here, we show that Myc-induced altered glutamine metabolism involves ATP depletion and activation of the energy sensor AMP-activated protein kinase (AMPK), which induces stabilizing phosphorylation of p53 at Ser15. Under influence of Myc, AMPK-stabilized tumor suppressor protein p53 accumulates in the mitochondria and interacts with the protein complex comprised of B-cell lymphoma 2 (Bcl-2) antagonist/killer (BAK) and Bcl2-like 1 (Bcl-xL). Mitochondrial p53 induces conformational activation of proapoptotic Bak without disrupting the Bak–Bcl-x L interaction. Further liberation of Bak specifically from the p53-activated Bak–Bcl-x L complex leads to spontaneous oligomerization of Bak and apoptosis. Thus, Myc-induced metabolic changes are coupled via AMPK and phospho-p53 to the mitochondrial apoptosis effector Bak, demonstrating a cell-intrinsic mechanism to counteract uncontrolled proliferation.

Selector transcription factors (TFs) control choices of alternative cellular fates during development. The ventral rhombomere 1 of the embryonic mouse ( Mus musculus ) brainstem produces neuronal precursors that can differentiate into either inhibitory GABAergic or excitatory glutamatergic neurons important for the control of behaviour. TFs Tal1 , Gata2 , and Gata3 are required for adopting the GABAergic neuronal identity and inhibiting the glutamatergic identity. Here, we asked how these selector TFs are activated and how they control the identity of the developing brainstem neurons. We addressed these questions by analysing chromatin accessibility at putative gene regulatory elements active during GABAergic and glutamatergic neuron lineage bifurcation, combined with studies of TF expression and DNA binding. Our results show that the Tal1 , Gata2 , and Gata3 genes are activated by highly similar mechanisms, with connections to regional patterning, neurogenic cell cycle exit and general course of neuronal differentiation. After activation, Tal1 , Gata2 , and Gata3 are linked by auto- and cross-regulation as well as regulatory interactions with TFs of the glutamatergic branch. Predicted targets of these selector TFs include genes expressed in GABAergic neurons, glutamatergic neurons, or both. Unlike genes specific to the glutamatergic branch, the genes expressed in GABAergic neurons appear to be under combinatorial control of Tal1 , Gata2 , and Gata3 . Understanding gene regulatory interactions affecting the anterior brainstem GABAergic and glutamatergic neuron differentiation may give genetic and mechanistic insights into neurodevelopmental traits and disorders.

Selector transcription factors (TFs) control choices of alternative cellular fates during development. The ventral rhombomere 1 of the embryonic mouse ( Mus musculus ) brainstem produces neuronal precursors that can differentiate into either inhibitory GABAergic or excitatory glutamatergic neurons important for the control of behaviour. TFs Tal1 , Gata2 , and Gata3 are required for adopting the GABAergic neuronal identity and inhibiting the glutamatergic identity. Here, we asked how these selector TFs are activated and how they control the identity of the developing brainstem neurons. We addressed these questions by analysing chromatin accessibility at putative gene regulatory elements active during GABAergic and glutamatergic neuron lineage bifurcation, combined with studies of TF expression and DNA binding. Our results show that the Tal1 , Gata2 , and Gata3 genes are activated by highly similar mechanisms, with connections to regional patterning, neurogenic cell cycle exit and general course of neuronal differentiation. After activation, Tal1 , Gata2 , and Gata3 are linked by auto- and cross-regulation as well as regulatory interactions with TFs of the glutamatergic branch. Predicted targets of these selector TFs include genes expressed in GABAergic neurons, glutamatergic neurons, or both. Unlike genes specific to the glutamatergic branch, the genes expressed in GABAergic neurons appear to be under combinatorial control of Tal1 , Gata2 , and Gata3 . Understanding gene regulatory interactions affecting the anterior brainstem GABAergic and glutamatergic neuron differentiation may give genetic and mechanistic insights into neurodevelopmental traits and disorders.

Genomic prediction of antipsychotic dose and polypharmacy has been difficult, mainly due to limited access to large cohorts with genetic and drug prescription data. In this proof of principle study, we investigated if genetic liability for schizophrenia is associated with high dose requirements of antipsychotics and antipsychotic polypharmacy, using real-world registry and biobank data from five independent Nordic cohorts of a total of N = 21,572 individuals with psychotic disorders (schizophrenia, bipolar disorder, and other psychosis). Within regression models, a polygenic risk score (PRS) for schizophrenia was studied in relation to standardized antipsychotic dose as well as antipsychotic polypharmacy, defined based on longitudinal prescription registry data as well as health records and self-reported data. Meta-analyses across the five cohorts showed that PRS for schizophrenia was significantly positively associated with prescribed (standardized) antipsychotic dose (beta(SE) = 0.0435(0.009), p = 0.0006) and antipsychotic polypharmacy defined as taking ≥2 antipsychotics (OR = 1.10, CI = 1.05-1.21, p = 0.0073). The direction of effect was similar in all five independent cohorts. These findings indicate that genotypes may aid clinically relevant decisions on individual patients´ antipsychotic treatment. Further, the findings illustrate how real-world data have the potential to generate results needed for future precision medicine approaches in psychiatry.

Aim: We compared fresh and in vitro expanded human Tregs for their CTLA4 splicing isoform expression. Methods: The CD4+CD25+CD127low/-phenotype was used for sorting Tregs and mRNA levels were measured with relative qRT-PCR. Results: In fresh Tregs the level of soluble CTLA4 (sCTLA4) was half of that of full-length CTLA4, whereas in expanded cells sCTLA4 level was tenfold lower. The most striking change took place early on: sCTLA4 expression decreased significantly when cells were simply kept in culture. Conclusion: In the in vitro expanded Tregs, the splicing of CTLA4 is affected. Our findings can be significant for clinical cell manufacturing. First, even minimal processing of cells may impact the functional molecules. Second, Treg expansion yields more potent CTLA4 receptor bearing cells.