815 results on '"Korhonen M"'
Search Results
302. Void Growth as a Function of Residual Stress Level in Thin, Narrow Aluminum Lines.
- Author
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Korhonen, M. A., Børgesen, P., Paszkiet, C. A., Lee, J. K., and Li, Che-Yu
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- 1991
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303. Mechanisms of Inelastic Deformation and Stress Relaxation in Thin Metallizations Bonded to Hard Substrates.
- Author
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Korhonen, M. A., Brørgesen, P., and Li, Che-Yu
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- 1991
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304. The Formation and Morphology of Stress Induced Voids in Thin Narrow Aluminum Lines.
- Author
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Paszkiet, C. A., Korhonen, M. A., and Li, Che-Yu
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- 1990
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305. Measurement of Stress Relaxation in Thin Aluminum Metallizations by Continuous Indentation and X-Ray Techniques.
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Korhonen, M. A., LaFontaine, W. R., Paszkiet, C. A., Black, R. D., and Li, Che-Yu
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- 1990
- Full Text
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306. X-Ray Stress Studies of Passivated and Unpassivated Narrow Aluminum Metallizations.
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Paszkiet, C. A., Korhonen, M. A., and Li, Che-Yu
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- 1990
- Full Text
- View/download PDF
307. Micromechanical Testing of Electronic Packaging Components and Materials.
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Li, C.-Y., Yost, B., Korhonen, M. A., and Dion, J.
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- 1993
- Full Text
- View/download PDF
308. Mechanical Properties of Plated Copper.
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Korhonen, M. A., Brown, D. D., Li, C.-Y., and Steinwall, J. E.
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- 1993
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309. Stress and current induced voiding in passivated metal lines
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Borgesen, P., Korhonen, M. A., and Li, C.-Y.
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- 1992
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310. Assessing the impact of dabigatran and warfarin on health-related quality of life: Results from an RE-LY sub-study.
- Author
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Monz, B.U., Connolly, S.J., Korhonen, M., Noack, H., and Pooley, J.
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WARFARIN , *ANTICOAGULANTS , *ATRIAL fibrillation treatment , *STROKE prevention , *VITAMIN K , *QUALITY of life , *HEALTH outcome assessment , *VITAMIN therapy - Abstract
Abstract: Background: Anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent strokes. Vitamin K antagonists, such as warfarin, are associated with numerous practical limitations – frequent anticoagulation monitoring, lifestyle and dietary restrictions – that complicate patient management and may impact health-related quality of life (HRQoL). This study derived HRQoL estimates for AF patients receiving warfarin or dabigatran etexilate (dabigatran), a new oral anticoagulant not requiring anticoagulation monitoring, during one year of stable treatment, i.e. in the absence of outcome events, such as strokes or major bleedings. Methods: Changes in HRQoL over time and between treatments were assessed using the EQ-5D (utility and Visual Analogue Scale (VAS) scores) at baseline, 3 and 12months in a sub-group of 1435 patients participating in the RE-LY trial. RE-LY was a phase III study that compared the safety and efficacy of warfarin, dabigatran 150mg bid and dabigatran 110mg bid for stroke prevention in patients with AF. Results: Utilities ranged from 0.805 (dabigatran 150mg bid) to 0.811 (dabigatran 110mg bid) at baseline, and did not change over the one year observation period. No differences between the dabigatran groups and warfarin were statistically significant except for the dabigatran 150mg bid group at 3months. Similarly, none of the within-group or between-group differences in VAS scores were statistically significant. Conclusions: Over the course of one year, all anticoagulated patients without outcome events (e.g. strokes or major bleedings) had stable HRQoL. Scores between dabigatran and warfarin were comparable, which was unexpected given the known complexities of warfarin treatment. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
311. The effect of current density, stripe length, stripe width, and temperature on resistance saturation during electromigration testing.
- Author
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Filippi, R. G., Wachnik, R. A., Eng, C.-P., Chidambarrao, D., Wang, P.-C., White, J. F., Korhonen, M. A., Shaw, T. M., Rosenberg, R., and Sullivan, T. D.
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ELECTRODIFFUSION , *SCANNING electron microscopes - Abstract
Resistance saturation as a function of current density, stripe length, stripe width, and temperature is investigated for a two-level structure with Ti/AlCu/Ti/TiN stripes and interlevel W stud vias. A simple model based on first principles is presented, which relates the maximum fractional resistance change to the current density and stripe length. Experimental results for stripe lengths of 30, 50, 70, and 100 μm are in good agreement with the model predictions. Estimated void sizes based on the resistance saturation data are consistent with the actual void sizes determined from scanning electron microscopy analysis. A weak temperature dependence is found for 0.33 μm-wide samples in the range 170–250°C, while a strong width dependence is observed between 0.33 and 1.50 μm- wide samples. The width dependence is qualitatively explained in terms of a relaxed bulk modulus that depends on the aspect ratio of the interconnect lines. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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312. Grounding Employability in Both Agency and Collective Identity: An Emancipatory Agenda for Higher Education
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Kahn, Peter, Lundgren‐Resenterra, Mariangela, Siivonen, P, Isopahkala-Bouret, U, Tomlinson, M, Korhonen, M, and Haltia, N
- Abstract
Debates on graduate employability are presently dominated by a focus on labour market outcomes that are framed on an individualistic basis. Such a focus is evident not only when attention falls on the skills and experience of individual graduates, but also when analysis highlights the impact of social differences on individual positioning in the labour market. This chapter presents the argument that work itself is determined in fundamental ways on collective considerations. It argues, furthermore, that if graduate employability were to be understood as the capacity of a graduate to exercise agency in ways that contribute to collective agendas within workplaces, then there would be enhanced potential for universities and workplaces to address challenges that matter to society, including those that relate to such concerns as decent work, sustainability and equity. In considering the nature of contributions to collective agendas, the account explores how collective identity underpins both primary and corporate agency within workplaces, drawing on the realist social theory of Margaret Archer.
- Published
- 2023
313. Automated image analysis detects aging in clinical-grade mesenchymal stromal cell cultures.
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Oja, S., Komulainen, P., Penttilä, A., Nystedt, J., and Korhonen, M.
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COMPUTER-assisted image analysis (Medicine) , *COMPUTER-aided diagnosis , *DIAGNOSTIC imaging , *MESENCHYMAL stem cells , *STROMAL cells - Abstract
Background: Senescent cells are undesirable in cell therapy products due to reduced therapeutic activity and risk of aberrant cellular effects, and methods for assessing senescence are needed. Early-passage mesenchymal stromal cells (MSCs) are known to be small and spindle-shaped but become enlarged upon cell aging. Indeed, cell morphology is routinely evaluated during MSC production using subjective methods. We have therefore explored the possibility of utilizing automated imaging-based analysis of cell morphology in clinical cell manufacturing. Methods: An imaging system was adopted for analyzing changes in cell morphology of bone marrow-derived MSCs during long-term culture. Cells taken from the cultures at the desired passages were plated at low density for imaging, representing morphological changes observed in the clinical-grade cultures. The manifestations of aging and onset of senescence were monitored by population doubling numbers, expression of p16INK4a and p21Cip1/Waf1, β-galactosidase activity, and telomeric terminal restriction fragment analysis. Results: Cell area was the most statistically significant and practical parameter for describing morphological changes, correlating with biochemical senescence markers. MSCs from passages 1 (p1) and 3 (p3) were remarkably uniform in size, with cell areas between 1800 and 2500 μm². At p5 the cells began to enlarge resulting in a 4.8-fold increase at p6-9 as compared to p1. The expression of p16INK4a and activity of β-galactosidase had a strong correlation with the increase in cell area, whereas the expression of p21Cip1/Waf1 reached its maximum at the onset of growth arrest and subsequently decreased. Mean telomere length shortened at an apparently constant rate during culture, from 8.2 ± 0.3 kbp at p1, reaching 6.08 ± 0.6 kbp at senescence. Conclusions: Imaging analysis of cell morphology is a useful tool for evaluating aging in cell cultures throughout the lifespan of MSCs. Our findings suggest that imaging analysis can reproducibly detect aging-related changes in cell morphology in MSC cultures. These findings suggest that cell morphology is still a supreme measure of cell quality and may be utilized to develop new noninvasive imaging-based methods to screen and quantitate aging in clinical-grade cell cultures. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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314. Medical surveillance for occupational asthma--how are cases detected?
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Suojalehto, H., Karvala, K., Haramo, J., Korhonen, M., Saarinen, M., and Lindström, I.
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OCCUPATIONAL asthma , *PUBLIC health surveillance , *SPIROMETRY , *INDUSTRIAL hygiene , *RESPIRATORY diseases , *DIAGNOSIS - Abstract
Background: In Finland, medical surveillance, including spirometry, is periodically performed for workers who are exposed to agents capable of causing occupational asthma (OA). Although it has been shown that surveillance can detect OA at an early stage, few studies have assessed its benefits or the role of surveillance spirometry. Aims: To assess the role of surveillance and spirometry in detecting OA and to evaluate the quality of spirometry. Methods: We retrospectively reviewed the medical files of patients in health surveillance programmes who were diagnosed with sensitizer-induced OA at the Finnish Institute of Occupational Health in 2012-14. We collected information on work exposure, respiratory symptoms, healthcare visits that initiated the diagnostic process, first spirometry and other diagnostic tests. Results: Sixty files were reviewed. Medical surveillance detected 11 cases (18%) and 49 cases (82%) were detected at doctors' appointments that were not related to surveillance. The median delay from the onset of asthma symptoms to diagnosis was 2.2 years. Delay did not differ between these groups. No cases were detected on the basis of abnormal spirometry without respiratory symptoms. However, five patients (8%) initially reported solely work-related rhinitis symptoms. Spirometry was normal in half of the cases and quality criteria were fulfilled in 86% of the tests. Conclusions: Fewer than one in five OA cases were detected through medical surveillance. Investigations were initiated by respiratory symptoms. No asymptomatic worker was referred because of abnormal spirometry. Our results highlight the importance of work-related nasal symptoms in detecting OA. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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315. Antidepressant use and work-related injuries.
- Author
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Kouvonen, A., Vahtera, J., Pentti, J., Korhonen, M. J., Oksanen, T., Salo, P., Virtanen, M., and Kivimäki, M.
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WORK-related injuries risk factors , *ANTIDEPRESSANTS , *CONFIDENCE intervals , *EPIDEMIOLOGY , *SEROTONIN uptake inhibitors , *WOUNDS & injuries , *TREATMENT duration , *ELECTRONIC health records , *ODDS ratio - Abstract
BackgroundAdverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use.MethodAntidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design).ResultsIn 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10–1.48). This was also the case among those who had used only selective serotonin reuptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08–1.83).ConclusionsAntidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury. [ABSTRACT FROM PUBLISHER]
- Published
- 2016
- Full Text
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316. Towards a global system of vigilance and surveillance in unrelated donors of haematopoietic progenitor cells for transplantation.
- Author
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Shaw, B E, Chapman, J, Fechter, M, Foeken, L, Greinix, H, Hwang, W, Phillips-Johnson, L, Korhonen, M, Lindberg, B, Navarro, W H, and Szer, J
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PROGENITOR cells , *BONE marrow transplantation , *HEALTH care reform , *TRANSPLANTATION of organs, tissues, etc. , *ORGAN donation - Abstract
Safety of living donors is critical to the success of blood, tissue and organ transplantation. Structured and robust vigilance and surveillance systems exist as part of some national entities, but historically no global systems are in place to ensure conformity, harmonisation and the recognition of rare adverse events (AEs). The World Health Assembly has recently resolved to require AE/reaction (AE/R) reporting both nationally and globally. The World Marrow Donor Association (WMDA) is an international organisation promoting the safety of unrelated donors and progenitor cell products for use in haematopoietic progenitor cell (HPC) transplantation. To address this issue, we established a system for collecting, collating, analysing, distributing and reacting to serious adverse events and reactions (SAE/R) in unrelated HPC donors. The WMDA successfully instituted this reporting system with 203 SAE/R reported in 2011. The committee generated two rapid reports, reacting to specific SAE/R, resulting in practice changing policies. The system has a robust governance structure, formal feedback to the WMDA membership and transparent information flows to other agencies, specialist physicians and transplant programs and the general public. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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317. Collection, processing and testing of bone, corneas, umbilical cord blood and haematopoietic stem cells by European Blood Alliance members.
- Author
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Närhi, M., Natri, O., Desbois, I., Kinggaard Holm, D., Galea, G., Aranko, K., Korhonen, M., and Nordstrom, K.
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QUESTIONNAIRES , *BONES , *CORNEA , *CORD blood , *STEM cells , *ACQUISITION of data - Abstract
Background and Objectives A questionnaire study was carried out in collaboration with the European Blood Alliance ( EBA) Tissues and Cells ( T& C) working group. The aim was to assess the level of involvement and commonality of processes on the procurement, testing and storage of bone, corneas, umbilical cord blood ( UCB) and haematopoietic stem cells ( HSC) in order to identify different practices and to explore whether recommendations can be made for harmonization. Materials and Methods An online questionnaire was used for data collection in 2011, and 43 replies were received covering 71 product answers from 13 countries. Results and conclusions Estimated percentages of tissue and cell banking covered by EBA member blood banks as a proportion of all collections of each individual country varied markedly. There were also major differences in the amounts of products collected and discarded and in proportions tissues provided for grafting. However, discarding of certain collections also reflects the practice of increasing the likelihood of the very best units being used for transplantation. Harmonization of possible practices should focus on matching supply with demand and on identifying the most efficient operators. This could allow for the development of practices for minimizing unnecessary collections. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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318. Donor selection and release criteria of cellular therapy products.
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Eichler, H., Schrezenmeier, H., Schallmoser, K., Strunk, D., Nystedt, J., Kaartinen, T., Korhonen, M., Fleury‐Cappellesso, S., Sensebé, L., Bönig, H., Rebulla, P., Giordano, R., Lecchi, L., Takanashi, M., Watt, S. M., Austin, E. B., Guttridge, M., McLaughlin, L. S., Panzer, S., and Reesink, H. W.
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CELLULAR therapy , *QUALITY control - Abstract
The article provides answers to the questions related to cellular therapy (CT) products including kind of CT products, selection of living donors and how quality control testing of the final CT product is performed.
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- 2013
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319. Quality controls of cryopreserved haematopoietic progenitor cells (peripheral blood, cord blood, bone marrow).
- Author
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Rosskopf, K., Ragg, S. J., Worel, N., Grommé, M., Preijers, F. W. M. B., Braakman, E., Schuurhuis, G. J., van Riet, I., Wendel, S., Fontão-Wendel, R., Lazar, A., Goldman, M., Halpenny, M., Giulivi, A., Letcher, B., McGann, L., Korhonen, M., Arvola, A., Humpe, A., and Buwitt-Beckmann, U.
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STANDARDIZATION , *BLOOD transfusion , *CRYOPRESERVATION of organs, tissues, etc. , *HEMATOPOIETIC stem cells , *QUALITY control , *BLOOD products - Abstract
The article discusses the issue concerning the standardization for the processing of cryopreserved hematopoietic progenitor cells. It notes that the quality controls applied after freezing-thawing varies among transfusion centers. Moreover, it suggests that the participation of institutions in external proficiency testing, as well as through individual validation studies to establish their specifications for release can address the interlaboratory discrepancies.
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- 2011
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320. Infrainguinal percutaneous transluminal angioplasty or bypass surgery in patients aged 80 years and older with critical leg ischaemia.
- Author
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Arvela, E., Venermo, M., Söderström, M., Korhonen, M., Halmesmäki, K., Albäck, A., Lepäntalo, M., and Biancari, F.
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TRANSLUMINAL angioplasty , *CORONARY artery bypass , *ISCHEMIA , *LEG surgery , *ARTERIAL catheterization - Abstract
Angioplasty first suggested [ABSTRACT FROM AUTHOR]
- Published
- 2011
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321. Effects of dietary salt restriction with or without cilazapril on office and ambulatory blood pressure
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Rauramaa, R., Korhonen, M., Litmanen, H., Niskanen, L., and Uusitupa, M.
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- 1994
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322. Risk drinking behavior among psychotropic drug users in an aging Finnish population: The FinDrink study
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Ilomaki, Jenni, Korhonen, M, Enlund, H, Hartzema, AG, and Kauhanen, J
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Aging ,Alcohol consumption ,Concomitant use ,FinDrink study ,Population study ,Psychotropic drugs - Published
- 2008
323. South Pacific Englishes – Unity and diversity in the usage of the present perfect
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Biewer, Carolin, University of Zurich, Nevalainen, T, Taavitsainen, I, Pahta, P, Korhonen, M, and Biewer, Carolin
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10097 English Department ,820 English & Old English literatures - Published
- 2008
324. External environmental costs of power production
- Author
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Hongisto, Mikko, Järvinen, Pekka, Pingoud, Kim, Thun, R., and Korhonen, M.
- Published
- 1999
325. Influence of therapy exposures on specific late morbidities, prescription drug purchases, and mortality in aging male survivors of childhood cancer: A registry-based study.
- Author
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Koskela M, Korhonen M, Haavisto A, and Jahnukainen K
- Abstract
Childhood cancer treatments predispose to late health problems and premature death. Our aim was to use national registry data to study associations between cancer therapy exposures and late health outcomes in aging male childhood cancer survivors (CCS). The study comprised 200 male CCS (survival ≥5 years) treated with conventional cancer therapy at a single institution in 1964-2000 and 1000 matched population controls. Analyses involved registry-based data on prescription drug purchases, reimbursements for chronic conditions, hospital admissions, and deaths that occurred ≥5 years after the cancer diagnosis. Mean age of CCS was 45.4 years. Compared to population controls, CCS had a higher risk for hospital admissions due to cardiovascular diseases and late mortality, both of which increased after age 40 years. CCS also had a higher risk for purchases of antihypertensives and lipid-lowering drugs within the last year of the study. Heart radiation ≥10 Gy was associated with hospitalizations due to cardiovascular diseases (HR 4.14, 95%CI 1.81-9.48), purchases of antihypertensives (OR 3.05, 95%CI 1.32-7.36), and purchases of lipid-lowering drugs (OR 2.93, 95%CI 1.08-7.73). Testosterone deficiency developed typically during pediatric follow-up, and it was associated with testicular radiation ≥20 Gy (HR 41.2, 95%CI 15.4-110) but not with alkylating agents. Of patients treated with testicular radiation ≥20 Gy, 91% had purchased testosterone within the last year. Reassuringly, CCS had no excess risk for purchases of opioids, anxiolytics, antiepileptics, or antidepressants. These findings emphasize the need for risk-based follow-up. Middle-aged male CCS are at an increased risk of premature cardiovascular morbidity and excess mortality., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2024
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326. Automated and closed clinical-grade manufacturing protocol produces potent NK cells against neuroblastoma cells and AML blasts.
- Author
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Jahan F, Penna L, Luostarinen A, Veltman L, Hongisto H, Lähteenmäki K, Müller S, Ylä-Herttuala S, Korhonen M, Vettenranta K, Laitinen A, Salmenniemi U, and Kerkelä E
- Subjects
- Humans, Cell Line, Tumor, Cytotoxicity, Immunologic, Interleukin-15 metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, Interleukin-2 metabolism, Leukapheresis methods, Cytokines metabolism, Killer Cells, Natural immunology, Neuroblastoma pathology, Neuroblastoma immunology, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute therapy
- Abstract
Natural killer (NK) cells are a promising allogeneic immunotherapy option due to their natural ability to kill tumor cells, and due to their apparent safety. This study describes the development of a GMP-compliant manufacturing protocol for the local production of functionally potent NK cells tailored for high-risk acute myeloid leukemia (AML) and neuroblastoma (NBL) patients. Moreover, the quality control strategy and considerations for product batch specifications in early clinical development are described. The protocol is based on the CliniMACS Prodigy platform and Natural Killer Cell Transduction (NKCT) (Miltenyi Biotec). NK cells are isolated from leukapheresis through CD3 depletion and CD56 enrichment, followed by a 12-hour activation with IL-2 and IL-15 cytokines. Three CliniMACS Prodigy processes demonstrated the feasibility and consistency of the modified NKCT process. A three-step process without expansion, however, compromised the NK cell yield. T cells were depleted effectively, indicating excellent safety of the product. Characterization of the NK cells before and after cytokine activation revealed a notable increase in the expression of activation markers, particularly CD69, consistent with enhanced functionality. Intriguingly, the NK cells exhibited increased killing efficacy against patient-derived CD33 + AML blasts and NBL cells in vitro, suggesting a potential therapeutic benefit in AML and NBL., (© 2024. The Author(s).)
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- 2024
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327. Alcohol use-associated alterations in the circulating metabolite profile in the general population and in individuals with major depressive disorder.
- Author
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Kärkkäinen O, Tolmunen T, Kivimäki P, Kurkinen K, Ali-Sisto T, Mäntyselkä P, Valkonen-Korhonen M, Koivumaa-Honkanen H, Honkalampi K, Ruusunen A, Velagapudi V, and Lehto SM
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Cohort Studies, Metabolome drug effects, Chromatography, Liquid, Depressive Disorder, Major blood, Hippurates blood, Alcohol Drinking blood
- Abstract
Our aim was to evaluate whether alcohol use is associated with changes in the circulating metabolite profile similar to those present in persons with depression. If so, these findings could partially explain the link between alcohol use and depression. We applied a targeted liquid chromatography mass spectrometry method to evaluate correlates between concentrations of 86 circulating metabolites and self-reported alcohol use in a cohort of the non-depressed general population (GP) (n = 247) and a cohort of individuals with major depressive disorder (MDD) (n = 99). Alcohol use was associated with alterations in circulating concentrations of metabolites in both cohorts. Our main finding was that self-reported alcohol use was negatively correlated with serum concentrations of hippuric acid in the GP cohort. In the GP cohort, consumption of six or more doses per week was associated with low hippuric acid concentrations, similar to those observed in the MDD cohort, but in these individuals it was regardless of their level of alcohol use. Reduced serum concentrations of hippuric acid suggest that already-moderate alcohol use is associated with depression-like changes in the serum levels of metabolites associated with gut microbiota and liver function; this may be one possible molecular level link between alcohol use and depression., Competing Interests: Declaration of competing interest OK is a co-founder of Afekta Technologies Ltd., a company providing metabolomics analysis services (not used in the present study). All other authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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328. Longitudinal trends in testicular volume z scores from puberty to adulthood, sperm quality, and paternity outcomes after childhood cancer.
- Author
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Korhonen M, Jahnukainen K, and Koskela M
- Abstract
Background: Childhood cancer therapy may cause subfertility. This study correlated cancer therapy exposures with testicular volumes from puberty to adulthood, spermatogenesis, and paternity outcomes in adulthood., Methods: The study population comprised 255 male childhood cancer survivors (CCS) (survival ≥5 years, diagnosed in 1964-2000 at the Helsinki Children's Hospital) whose testicular volume was measured at ages 12 years (n = 38), 14 years (n = 57), 16 years (n = 63), 18 years (n = 105), and in adulthood (n = 43; median age, 27 years). Testicular volumes were converted to age-specific z scores. In addition, 92 CCS provided semen sample in adulthood (median age, 25.2 years); and paternity was evaluated through national register data (mean age at assessment, 37.6 years; n = 252)., Results: Compared with age-specific reference values, CCS generally exhibited low testicular volume z scores at ages 12-18 years. Testicular volume z scores in CCS treated exclusively with chemotherapy returned to the reference range in adulthood. In contrast, patients exposed to testicular radiation ≥1 gray (Gy) (median dose, 12 Gy) showed no late recovery in testicular size. Testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥12 g/m
2 were identified as risk factors for azoospermia in adulthood. Patients exposed to testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥4 g/m2 had lower paternity rates., Conclusions: Testicular volume growth after prolonged follow-up suggests a potential late recovery of spermatogenesis in CCS treated exclusively with chemotherapy. However, alkylating agents increased the risk of having prolonged azoospermia and nonpaternity. High-dose testicular radiation causes long-term depletion of spermatogonia and was the strongest risk factor for azoospermia and nonpaternity., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)- Published
- 2024
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329. Value of Pharmacogenetic Testing Assessed with Real-World Drug Utilization and Genotype Data.
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Litonius K, Kulla N, Falkenbach P, Kristiansson K, Tarkiainen EK, Ukkola-Vuoti L, Cajanus K, Korhonen M, Khan S, Sistonen J, Orpana A, Lindstedt M, Nyrönen T, Perola M, Turpeinen M, Kytö V, Tornio A, and Niemi M
- Abstract
Implementation of pharmacogenetic testing in clinical care has been slow and with few exceptions is hindered by the lack of real-world evidence on how to best target testing. In this retrospective register-based study, we analyzed a nationwide cohort of 1,425,000 patients discharged from internal medicine or surgical wards and a cohort of 2,178 university hospital patients for purchases and prescriptions of pharmacogenetically actionable drugs. Pharmacogenetic variants were obtained from whole genome genotype data for a subset (n = 930) of the university hospital patients. We investigated factors associated with receiving pharmacogenetically actionable drugs and developed a literature-based cost-benefit model for pre-emptive pharmacogenetic panel testing. In a 2-year follow-up, 60.4% of the patients in the nationwide cohort purchased at least one pharmacogenetically actionable drug, most commonly ibuprofen (25.0%) and codeine (19.4%). Of the genotyped subset, 98.8% carried at least one actionable pharmacogenetic genotype and 23.3% had at least one actionable gene-drug pair. Patients suffering from musculoskeletal or cardiovascular diseases were more prone to receive pharmacogenetically actionable drugs during inpatient episode. The cost-benefit model included frequently dispensed drugs in the university hospital cohort, comprising ondansetron (19.4%), simvastatin (7.4%), clopidogrel (5.0%), warfarin (5.1%), (es)citalopram (5.3%), and azathioprine (0.5%). For untargeted pre-emptive pharmacogenetic testing of all university hospital patients, the model indicated saving €17.49 in direct healthcare system costs per patient in 2 years without accounting for the cost of the test itself. Therefore, it might be reasonable to target pre-emptive pharmacogenetic testing to patient groups most likely to receive pharmacogenetically actionable drugs., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2024
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330. Productivity costs of schizophrenia spectrum and other psychotic disorders by friction cost and human capital methods: The Northern Finland Birth Cohort 1966.
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Majuri T, Nerg I, Huikari S, Rissanen I, Jääskeläinen E, Miettunen J, and Korhonen M
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- Humans, Finland epidemiology, Male, Female, Middle Aged, Adult, Adolescent, Cohort Studies, Young Adult, Employment statistics & numerical data, Retirement economics, Registries, Schizophrenia economics, Schizophrenia epidemiology, Psychotic Disorders economics, Psychotic Disorders epidemiology, Cost of Illness, Efficiency
- Abstract
Purpose: Psychotic disorders are associated with substantial productivity costs; however no previous studies have compared these between schizophrenia spectrum (SSD) and other psychotic disorders (OP). The human capital method (HCM) and the friction cost method (FCM) are the two most common approaches to assess productivity costs. The HCM focuses on employees' perspectives on the costs, whereas the FCM demonstrates employers' perspectives. Studies comparing these methods when estimating the productivity costs of psychoses are lacking., Methods: Utilizing the Northern Finland Birth Cohort 1966 with linkages to national registers, we compared the adjusted productivity costs of SSD (n = 216) and OP (n = 217). The productivity costs were estimated from ages 18 to 53 including projections to statutory retirement age using the FCM and HCM., Results: When estimated via the HCM, productivity losses were higher for SSD (€193,940) than for OP (€163,080). However, when assessed using the FCM, costs were significantly lower for SSD (€2,720) than for OP (€4,430). Productivity costs varied by sex and various clinical and occupational factors., Conclusion: This study highlights how productivity costs vary by psychosis diagnosis. These differences should be noted when planning interventions. The low FCM estimates indicate the need of interventions before or during the early phases of psychoses. From a societal perspective, interventions are needed, particularly for those with highest HCM productivity losses, such as males with SSD. Besides psychiatric services, the roles of social services, employment agencies and occupational health care should be considered when helping individuals with psychoses to working life., (© 2024. The Author(s).)
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- 2024
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331. Effects of ambient air pollution from shipping on mortality: A systematic review.
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Kiihamäki SP, Korhonen M, Kukkonen J, Shiue I, and Jaakkola JJK
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- Humans, Environmental Exposure statistics & numerical data, Ships, Mortality, Particulate Matter analysis, Air Pollution statistics & numerical data, Air Pollutants analysis
- Abstract
Background: Shipping contributes to air pollution causing adverse health effects. We conducted for the first time a systematic review on the health and economic impacts of ambient air pollution from shipping emissions., Methods: We performed a systematic search in PubMed, Web of Science, EBSCO (Medline), and Scopus of all time up to December 2023. We then inter-compared semi-quantitatively the results of the included eligible studies., Results: We identified 23 eligible studies, 22 applying health impact assessment, and 1 using epidemiological methods. These studies used different methods for the evaluation of emissions, dispersion, and exposure, and for the exposure-mortality risk functions for exposure to shipping emissions for 1-2 years. The estimated excess global all-cause mortality from six studies ranged between 1 and 5 deaths per 100,000 person-years. However, the heterogeneity of the methods and critical gaps in the reporting seriously limited the synthesis of the evidence on health and economic effects of shipping emissions. Sufficient spatial and temporal resolutions in both dispersion and exposure modeling, as well as presentation of uncertainties is needed. Health impact assessment should present the results with all the main risk functions and population attributable risks, and the magnitude of the effect should be expressed in excess number per a given person-time or per population size. Economic effects should also cover work productivity, mental well-being, and cognitive functions., Conclusions: We recommend that future studies should properly evaluate and report the uncertainty ranges and the confidence limits of the results. Rigorous studies are needed on multipollutant exposures, exposures from various source categories, and exposures attributed to various particulate matter measures. Studies should report the health impact measures in a format that facilitates straightforward inter-study comparisons. Further research should also specifically report the used grid spacings and resolutions and evaluate whether these are optimal for the task., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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332. Mothers' and their children's emotional and behavioral symptom trajectories and subsequent maternal adjustment: Twenty-seven years of motherhood.
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Luoma I, Korhonen M, Salmelin RK, Siirtola A, Mäntymaa M, Valkonen-Korhonen M, and Puura K
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- Humans, Female, Adult, Adolescent, Child, Finland, Longitudinal Studies, Child, Preschool, Pregnancy, Mother-Child Relations, Depression psychology, Male, Behavioral Symptoms psychology, Depression, Postpartum psychology, Depression, Postpartum diagnosis, Child Behavior Disorders psychology, Child Behavior Disorders diagnosis, Mothers psychology, Adaptation, Psychological
- Abstract
Background: This study aims to describe maternal depressive symptoms (MDS) trajectories in a longitudinal study extending from pregnancy to 27 years after the birth of the firstborn child. We also explored the associations of both MDS trajectories and child internalizing and externalizing problem trajectories with maternal adjustment (adaptive functioning, emotional and behavioral problems)., Methods: The population-based study was conducted in Tampere, Finland, and the sample comprised 356 first-time mothers. MDS were screened with the Edinburgh Postnatal Depression Scale during pregnancy, first week after delivery, 2 and 6 months postnatally, and when the child was 4-5, 8-9, 16-17, and 26-27 years of age. The internalizing and externalizing problems of the children were assessed with the Child Behavior Checklist when the child was 4-5, 8-9, and 16-17 years of age. Maternal adaptive functioning and internalizing and externalizing problems were assessed with the Adult Self Report at 26-27 years after the birth of the first child. Complete follow-up data were available for 168 mothers., Results: We describe a three-group trajectory model of MDS (High Stable, Low Stable, Very Low). Elevated depressive symptom patterns were associated with less optimal maternal outcomes regarding both adaptive and problem dimensions. The child's internalizing and externalizing problem trajectories were associated with maternal internalizing and externalizing problems but not with maternal adaptive functioning., Limitations: Maternal and child measures were based on maternal reports only., Conclusions: The interconnectedness of the well-being of the mother and child should be noted in health and mental health services for adults and children., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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333. Superspreading of SARS-CoV-2 at a choir rehearsal in Finland-A computational fluid dynamics view on aerosol transmission and patient interviews.
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Tuhkuri Matvejeff A, Laitinen A, Korhonen M, Oksanen LM, Geneid A, Sanmark E, and Vuorinen V
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- Humans, Finland epidemiology, Male, Hydrodynamics, Female, Adult, Middle Aged, Computer Simulation, COVID-19 transmission, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 virology, SARS-CoV-2, Aerosols
- Abstract
Introduction: COVID-19 pandemic has highlighted the role of aerosol transmission and the importance of superspreading events. We analyzed a choir rehearsal in November 2020, where all participants, except one who had recently earlier recovered from COVID-19, were infected. We explore the risk factors for severe disease in this event and model the aerosol dispersion in the rehearsal room., Materials and Methods: Characteristics of participants were collected by interviews and supplemented with patient records. A computational simulation of aerosol distribution in the rehearsal room and the efficacy of potential safety measures was conducted using the Large-Eddy Simulation approach. Infection risk was studied by analyzing quanta emission and exposure with the Wells-Riley equation., Results: The simulation showed that airborne transmission likely explains this mass contagion event. Every singer was exposed to the virus in only 5 min from the beginning of the rehearsal, and maximum concentration levels were reached at 20 min the concentration levels started to approach a steady state after 20 min. Although concentration differences existed in the room, risk levels near (1 m) and far (5 m) from the aerosol source were similar for certain singers. Modeling indicated infection risk levels of 70-100% after one hour; the risk would have been considerably reduced by wearing high-filtration respirators. Age and pre-existing comorbidities predicted more severe disease. The high incidence of illness may be partly attributed to the relatively high median age of individuals. Additionally, those admitted to the hospital had multiple underlying health conditions that predispose them to more severe disease., Conclusions: Airborne transmission and indoor space can explain this mass exposure event. High-filtration respirators could have prevented some infections. The importance of safety distances diminishes the longer the indoor event. The concept of safety distance is challenging, as our study suggests that long range airborne transmission may occur in indoor events with extended duration. We encourage informing the public, especially persons at risk, of safety measures during epidemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tuhkuri Matvejeff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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334. Associations of Symptoms of ADHD and Oppositional Defiant Disorder (ODD) in Adolescence With Occupational Outcomes and Incomes in Adulthood.
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Seppä S, Huikari S, Korhonen M, Nordström T, Hurtig T, and Halt AH
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- Adolescent, Adult, Female, Humans, Male, Cohort Studies, Employment statistics & numerical data, Finland epidemiology, Sick Leave statistics & numerical data, Young Adult, Attention Deficit Disorder with Hyperactivity epidemiology, Income statistics & numerical data, Oppositional Defiant Disorder epidemiology, Unemployment statistics & numerical data
- Abstract
Objective: The purpose of this study was to examine the associations of ADHD and ODD symptoms in adolescence with occupational outcomes and incomes in adulthood within the Northern Finland Birth Cohort 1986 (NFBC1986)., Method: ADHD symptoms were evaluated at ages 15 to 16 years using the Strengths and Weaknesses of ADHD symptoms and Normal Behaviors (SWAN) scale. ODD symptoms were assessed using a 7-point scale, like the SWAN assessment., Results: Symptoms of ADHD and ADHD + ODD were associated with elevated rates of unemployment, increased sick days, and lower annual incomes compared to controls for both sexes. Symptoms of ODD were associated with higher unemployment and more sick days for males, although these associations did not reach statistical significance in their association with annual incomes., Conclusion: Symptoms of ADHD were associated with adverse occupational outcomes and lower incomes. Furthermore, symptoms of ODD were associated with occupational outcomes but not with incomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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335. Productivity costs of lifelong smoking-the Northern Finland Birth Cohort 1966 study.
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Rissanen I, Nerg I, Oura P, Huikari S, and Korhonen M
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- Humans, Finland epidemiology, Female, Male, Middle Aged, Adult, Birth Cohort, Young Adult, Cost of Illness, Adolescent, Cohort Studies, Smoking epidemiology, Smoking economics, Efficiency
- Abstract
Background: Smoking is one of the leading causes of impaired health and mortality. Loss of paid and unpaid work and replacements due to morbidity and mortality result in productivity costs. Our aim was to investigate the productivity costs of lifelong smoking trajectories and cumulative exposure using advanced human capital method (HCM) and friction cost method (FCM)., Methods: Within the Northern Finland Birth Cohort 1966 (NFBC1966), 10 650 persons were followed from antenatal period to age 55 years. The life course of smoking behaviour was assessed with trajectory modelling and cumulative exposure with pack-years. Productivity costs were estimated with advanced HCM and FCM models by using detailed, national register-based data on care, disability, mortality, education, taxation, occupation and labour market. A two-part regression model was used to predict productivity costs associated with lifelong smoking and cumulative exposure., Results: Of the six distinct smoking trajectories, lifetime smokers had the highest productivity costs followed by late starters, late adult quitters, young adult quitters and youth smokers. Never-smokers had the lowest productivity costs. The higher the number of pack-years, the higher the productivity costs. Uniform patterns were found in both men and women and when estimated with HCM and FCM. The findings were independent of other health behaviours., Conclusions: Cumulative exposure to smoking is more crucial to productivity costs than starting or ending age of smoking. This suggests that the harmful effects of smoking depend on dose and duration of smoking and are irrespective of age when smoking occurred., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)
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- 2024
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336. Occupational health patients' parallel use of primary- and secondary-care services and linkage to work disability: A follow-up study in Finland.
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Reho T, Atkins S, Korhonen M, Siukola A, Viljamaa M, Sumanen M, Uitti J, and Sauni R
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- Female, Humans, Follow-Up Studies, Finland, Secondary Care, Pensions, Sick Leave, Sweden epidemiology, Occupational Health, Disabled Persons
- Abstract
Aims: This study aimed to investigate occupational health (OH) primary-care patients' use of other health-care services and whether parallel use affects their likelihood to have sickness absences (SA) or disability pensions (DP)., Methods: Primary-care services in Finland are provided through three parallel health-care sectors, all available to the working population: public, private and OH sectors. Patients may also be referred to secondary care. This follow-up study combines real-world medical record data containing SA data from a nationwide OH provider with health-care attendance data from public and private primary-care sectors and public secondary care, sociodemographic data and DP decisions. Patients between 18 and 68 years of age who used OH primary care at least once during the study years 2014-2016 were included. The total study population comprised 59,650 patients. Odds ratios were used to analyse association between parallel service use and SA or DP., Results: Females and patients with a lower educational level were more likely to use services in other health-care sectors in addition to OH than others. Those patients who used any other health-care sector in addition to OH primary care had an increased likelihood of having long SA or receiving DP., Conclusions: OH primary-care patients using the services of several health-care sectors in parallel have an increased likelihood of receiving disability benefits - either SA or DP. There is need for care coordination to ensure adequate measures for work-ability support., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
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- 2024
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337. Solanidine is a sensitive and specific dietary biomarker for CYP2D6 activity.
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Kiiski JI, Neuvonen M, Kurkela M, Hirvensalo P, Hämäläinen K, Tarkiainen EK, Sistonen J, Korhonen M, Khan S, Orpana A, Filppula AM, Lehtonen M, and Niemi M
- Subjects
- Humans, Paroxetine pharmacology, Biomarkers, Genotype, Cytochrome P-450 CYP2D6 genetics, Genome-Wide Association Study, Diosgenin
- Abstract
Background: Individual assessment of CYP enzyme activities can be challenging. Recently, the potato alkaloid solanidine was suggested as a biomarker for CYP2D6 activity. Here, we aimed to characterize the sensitivity and specificity of solanidine as a CYP2D6 biomarker among Finnish volunteers with known CYP2D6 genotypes., Results: Using non-targeted metabolomics analysis, we identified 9152 metabolite features in the fasting plasma samples of 356 healthy volunteers. Machine learning models suggested strong association between CYP2D6 genotype-based phenotype classes with a metabolite feature identified as solanidine. Plasma solanidine concentration was 1887% higher in genetically poor CYP2D6 metabolizers (gPM) (n = 9; 95% confidence interval 755%, 4515%; P = 1.88 × 10
-11 ), 74% higher in intermediate CYP2D6 metabolizers (gIM) (n = 89; 27%, 138%; P = 6.40 × 10-4 ), and 35% lower in ultrarapid CYP2D6 metabolizers (gUM) (n = 20; 64%, - 17%; P = 0.151) than in genetically normal CYP2D6 metabolizers (gNM; n = 196). The solanidine metabolites m/z 444 and 430 to solanidine concentration ratios showed even stronger associations with CYP2D6 phenotypes. Furthermore, the areas under the receiver operating characteristic and precision-recall curves for these metabolic ratios showed equal or better performances for identifying the gPM, gIM, and gUM phenotype groups than the other metabolites, their ratios to solanidine, or solanidine alone. In vitro studies with human recombinant CYP enzymes showed that solanidine was metabolized mainly by CYP2D6, with a minor contribution from CYP3A4/5. In human liver microsomes, the CYP2D6 inhibitor paroxetine nearly completely (95%) inhibited the metabolism of solanidine. In a genome-wide association study, several variants near the CYP2D6 gene associated with plasma solanidine metabolite ratios., Conclusions: These results are in line with earlier studies and further indicate that solanidine and its metabolites are sensitive and specific biomarkers for measuring CYP2D6 activity. Since potato consumption is common worldwide, this biomarker could be useful for evaluating CYP2D6-mediated drug-drug interactions and to improve prediction of CYP2D6 activity in addition to genotyping., (© 2024. The Author(s).)- Published
- 2024
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338. The use of dental anxiety management techniques during one-session treatment: a study on five video-recorded patient cases.
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Kurki P, Korhonen M, Honkalampi K, Lahti S, and Suominen AL
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- Adult, Humans, Dentist-Patient Relations, Attitude of Health Personnel, Dental Anxiety therapy, Dental Anxiety psychology, Dentists psychology
- Abstract
Objective: The aim was to examine what kinds of dental anxiety management techniques dentists use in the context of one-session treatment., Material and Methods: The data consisted of videotaped treatment sessions for five dentally anxious adults. The treatment was conducted by two experienced dentists without formal training in the treatment of dentally anxious patients or behavioral management techniques. Theory-driven qualitative content analysis, based on the anxiety management classification of Milgrom et al. was used to identify and classify the techniques used during the treatments., Results: Altogether, diverse categories of dental anxiety management techniques were identified under the main themes of enhancing trust and control and psychological management. Techniques that fell into enhancing trust and control included the categories of 'building a trustful relationship', 'informational control', and 'behavioral control'. These techniques were used consistently throughout the sessions. Additionally, psychological management techniques were identified and classified as 'behavioral strategies: relaxing the body' and 'cognitive strategies: relaxing the mind', which were regularly used in specific situations., Conclusion: The results indicate that a variety of dental anxiety management techniques were used during one-session treatments. The findings provide valuable insights for dentists in managing their patients with dental anxiety and improving their overall treatment experience.
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- 2024
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339. Therapeutic exposures and pubertal testicular dysfunction are associated with adulthood milestones and paternity after childhood cancer.
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Korhonen M, Tainio J, Koskela M, Madanat-Harjuoja LM, and Jahnukainen K
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- Child, Humans, Male, Infant, Newborn, Infant, Child, Preschool, Adolescent, Cross-Sectional Studies, Paternity, Semen, Testis, Testosterone, Follicle Stimulating Hormone, Luteinizing Hormone, Neoplasms drug therapy
- Abstract
Background: Childhood cancer therapy may cause long-term effects. This cross-sectional study evaluated adulthood milestones in male childhood cancer survivors (CCS)., Methods: The study population comprised 252 male CCS with 6 to 42 years of survival diagnosed at the Children's Hospital in Helsinki (1964-2000) at the age of 0 to 17 years. Sex-, age-, and area of residence-matched population controls were randomly selected from the Finnish national registries. Data on moving away from the parental home, marital status, offspring, and adoption in CCS were compared with the population controls. We analyzed the influence of chemotherapy and radiation exposures and testicular dysfunction (ever nontestosterone-substituted serum follicle stimulating hormone >15 IU/L, luteinizing hormone >15 IU/L, testosterone <2 ng/mL (5 nmol/L), need of testosterone replacement therapy, or testicular volume <12 mL at the end of puberty) during pubertal maturation on long-term social outcomes., Results: CCS moved away from their parental home as frequently as population controls (97.8% vs. 98.5%, p = .45). CCS were less likely to marry or live in a registered relationship (46.4% vs. 57.5%, p < .001), especially when diagnosed at a young age (<4 years). Among those married, the probability of divorce was similar between CCS and population controls (27.4% vs. 23.8%, p = .41). Survivors were less likely to sire a child (38.5% vs. 59.1%, p < .001) and more likely to adopt (2% vs. 0.4%, p = .015). Lower probability of paternity was associated with hematopoietic stem cell therapy, testicular radiation dose >6 Gy, pubertal signs of testicular dysfunction (nontestosterone-substituted serum follicle stimulating hormone >15 IU/L, luteinizing hormone >15 IU/L, testosterone <2 ng/mL (5 nmol/L), or need of testosterone replacement therapy during puberty, or testicular volume <12 mL at the end of puberty) or azoospermia after puberty., Conclusions: This study emphasizes the value of pubertal monitoring of testicular function to estimate future probability of paternity. If no signs of dysfunction occurred during pubertal follow-up, paternity was comparable to population controls. Testicular radiation dose >6 Gy appeared to be the strongest risk factor for decreased paternity., Plain Language Summary: Treatment with intensive therapies, including hematopoietic stem cell therapy, testicular radiation dose >6 Gy, and signs of testicular dysfunction, during puberty are important risk factors for lower rates of fertility. Intensive therapies and testicular dysfunction itself do not similarly hamper psychosocial milestones in adulthood; cancer diagnosis at a very young age (<4 years) lower the probability of marriage. This study accentuates the importance of monitoring of pubertal development, emphasizing on testicular function, not only sperm analysis, to estimate future fertility among male childhood cancer survivors., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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- 2023
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340. The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials.
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Mikola T, Marx W, Lane MM, Hockey M, Loughman A, Rajapolvi S, Rocks T, O'Neil A, Mischoulon D, Valkonen-Korhonen M, Lehto SM, and Ruusunen A
- Subjects
- Adult, Humans, Randomized Controlled Trials as Topic, Vitamin D therapeutic use, Vitamins therapeutic use, Depression drug therapy, Dietary Supplements
- Abstract
Neurosteroid and immunological actions of vitamin D may regulate depression-linked physiology. Meta-analyses investigating the effect of vitamin D on depression have been inconsistent. This meta-analysis investigated the efficacy of vitamin D in reducing depressive symptoms among adults in randomized placebo-controlled trials (RCT). General and clinical populations, and studies of ill individuals with systemic diseases were included. Light therapy, co-supplementation (except calcium) and bipolar disorder were exclusionary. Databases Medline, PsycINFO, CINAHL and The Cochrane Library were searched to identify relevant articles in English published before April 2022. Cochrane risk-of-bias tool (RoB 2) and GRADE were used to appraise studies. Forty-one RCTs ( n = 53,235) were included. Analyses based on random-effects models were performed with the Comprehensive Meta-analysis Software. Results for main outcome ( n = 53,235) revealed a positive effect of vitamin D on depressive symptoms (Hedges' g = -0.317, 95% CI [-0.405, -0.230], p < 0.001, I
2 = 88.16%; GRADE: very low certainty). RoB assessment was concerning in most studies. Notwithstanding high heterogeneity, vitamin D supplementation ≥ 2,000 IU/day appears to reduce depressive symptoms. Future research should investigate possible benefits of augmenting standard treatments with vitamin D in clinical depression. PROSPERO registration number: CRD42020149760. Funding: Finnish Medical Foundation, grant 4120 and Juho Vainio Foundation, grant 202100353.- Published
- 2023
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341. Individualizing the burnout problem: Health professionals' discourses of burnout and recovery in the context of rehabilitation.
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Korhonen M and Komulainen K
- Subjects
- Female, Humans, Health Personnel psychology, Workplace psychology, Aging, Burnout, Psychological, Mental Disorders
- Abstract
This discourse analytical study explores how health professionals (HPs) construct burnout as a form of mental distress in the context of Finnish burnout rehabilitation framed with a particular rehabilitation ethos. Burnout is a fuzzy concept and lacks a disease status. Therefore, it calls for context-specific definition and justification. By highlighting the socially and interactionally produced character of categories of mental distress, the study investigates the kinds of discourses HPs use to formulate "the problem" and its solutions, and how people dealing with burnout are categorized in these discourses. The data consists of field notes from the observation of group discussion sessions in two 1-year burnout rehabilitation courses. As a result of the analysis, five partly overlapping discourses were identified: psychological, evolutionary, healthy lifestyle, biomedical, and welfare. Within these discourses, people who experience burnout were categorized as over-conscientious employees, "good girls," "primitive people," self-responsible rehabilitees, patients, and (aging) employees with social and legal rights. Burnout rehabilitation and HPs' views reproduce a cultural and clinical discourse around burnout in which work-related problems are treated as individual-level problems and individuals are responsibilized for the management of mental distress. Based on the results, it is concluded that the hybrid type of interventions that attempt to influence both individual- and work-related problems behind burnout would help to prevent people dealing with burnout from being over-responsibilized for solving problems at the workplace.
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- 2023
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342. The association between chronotype and wages at mid-age.
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Conlin A, Nerg I, Ala-Mursula L, Räihä T, and Korhonen M
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- Humans, Male, Middle Aged, Follow-Up Studies, Sleep, Salaries and Fringe Benefits, Surveys and Questionnaires, Circadian Rhythm, Chronotype
- Abstract
Sleep has been shown to affect economic outcomes, including wages. The mechanisms by which sleep affects wages remain unclear. We examine the relationship between chronotype - morning larks, evening owls - and wages at mid-age. We propose a novel model relating chronotype to wages in consideration of human, social, and health capital constructs. Empirically, we explore the effects of chronotype mediated through life course choices, such as work experience, trust, and health behaviour. The data come from the 46-year-old follow-up study of the Northern Finland Birth Cohort (1966) and from registers of the Finnish Tax Administration. We find evening chronotype to have a significant indirect negative effect on wages, which occurs through accumulating less work experience and through poor health outcomes. The effect is largest for male workers, with a total indirect effect on average wages of - 4%. We also provide evidence that chronotype has a long-term association with wages between 29 and 50 years of age. We conclude that evening-type workers are less suited to typical working hours and accumulate less human, social and health capital which in turn negatively affects their wages. Our findings are of great socio-economic importance because evening chronotypes make up a significant part of the population., Competing Interests: Declarations of interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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343. ATMP-classified, scalable, autologous cell spray for the treatment of skin wounds and assessment of its effects on wound healing clinically and on a molecular level.
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Nuutila K, Katayama S, Laitinen A, Siltanen A, Patrikoski M, Valtonen J, Kankainen M, Kerkelä E, Kaartinen T, Juteau S, Korhonen M, Vuola J, and Kankuri E
- Subjects
- Humans, Transplantation, Autologous, Wound Healing, Skin pathology, Skin Transplantation adverse effects, Burns pathology, Soft Tissue Injuries surgery
- Abstract
Background: Autologous split-thickness skin grafts (STSGs) are the standard of care for closure of deep and large burns. However, perforation and extensive fishnet-like expansion of the grafts to achieve greater area wound coverage can lead to treatment failures or esthetically poor healing outcomes and scarring. The purpose of this study was to validate an autologous advanced therapy medicinal product (ATMP)-compliant skin cell suspension and evaluate its efficacy to promote epithelialization., Methods: Cells isolated from a piece of STSG according to ATMP classification requirements were sprayed onto 20 patients during a single operation in a validation study. Comparative evaluation of treatment efficacy was carried out using side-by-side skin graft donor site wounds that were standardized in depth. Firstly, we characterized wound healing transcriptomes at 14 and 21 days from serial wound biopsies in seven patients. Then, side-by-side wounds in four patients were treated with or without the skin cells. The wounds were photographed, clinical outcomes assessed, and the treatment and control wound transcriptomes at 14 days were compared to the untreated wounds' healing transcriptomes., Results: The average cell yield after isolation from the STSG was 2.4 × 10
6 cells/cm2 with 96 % viability. The product contained mainly keratinocytes and their precursors but also other skin cells such as fibroblasts were present. As compared to vehicle-treated donor site wounds, the wounds treated with cells demonstrated improved epithelialization by both direct comparison and machine learning analysis of the transcriptomes., Conclusions: We showed that rapid and scalable ATMP-classified processing of skin cells is feasible, and application of the skin cells effectively promotes healing and epithelization of donor site wounds., Competing Interests: Conflict of interest The views expressed in this article are those of the authors and do not reflect the official policy or position of the U.S. Army Medical Department, Department of the Army, DOD, or the U.S. Government. All the authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
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344. Rhabdomyolysis during concomitant ticagrelor and rosuvastatin: A breast cancer resistance protein-mediated drug interaction?
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Lehtisalo M, Kiander W, Filppula AM, Deng F, Kidron H, Korhonen M, Sinkko J, Koivula K, and Niemi M
- Subjects
- United States, Humans, Female, Rosuvastatin Calcium adverse effects, Rosuvastatin Calcium pharmacokinetics, Ticagrelor adverse effects, ATP Binding Cassette Transporter, Subfamily G, Member 2, Neoplasm Proteins metabolism, Drug Interactions, Organic Anion Transporters metabolism, Rhabdomyolysis chemically induced, Breast Neoplasms drug therapy
- Abstract
We present 3 patients diagnosed with rhabdomyolysis 1-6 months after the initiation of concomitant rosuvastatin and ticagrelor medication. A literature review and Food and Drug Administration adverse event reporting system revealed >40 reports of rhabdomyolysis during concomitant ticagrelor and rosuvastatin, including 3 with a fatal outcome. We show that ticagrelor inhibits breast cancer resistance protein-, organic anion transporting polypeptide (OATP) 1B1-, 1B3- and 2B1-mediated transport of rosuvastatin in vitro with half-maximal unbound inhibitory concentrations of 0.36, 4.13, 7.5 and 3.26 μM, respectively. A static drug interaction model predicted that ticagrelor may inhibit intestinal breast cancer resistance protein and thus increase rosuvastatin plasma exposure 2.1-fold, whereas the OATP-mediated hepatic uptake of rosuvastatin should not be inhibited due to relatively low portal ticagrelor concentrations. Taken together, concomitant use of ticagrelor with rosuvastatin may increase the systemic exposure to rosuvastatin and the risk of rosuvastatin-induced rhabdomyolysis. Further studies are warranted to investigate the potential pharmacokinetic interaction between ticagrelor and rosuvastatin in humans., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
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- 2023
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345. The effectiveness of a diagnostic interview and modified one-session treatment for dental anxiety in primary dental care-A pilot study.
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Kurki P, Korhonen M, Honkalampi K, and Suominen AL
- Subjects
- Adult, Humans, Pilot Projects, Surveys and Questionnaires, Psychometrics, Dental Care, Dental Anxiety, Fear
- Abstract
Aims: To investigate the effectiveness of a cognitive-behavioral intervention that included either a diagnostic interview (DI) or a DI combined with modified one-session treatment (M-OST) for dental anxiety among adults in a primary care setting., Methods and Results: Nineteen participants were assigned to either a DI before conventional dental treatment (group T1) or DI and M-OST (group T2). The severity of dental anxiety was measured with three self-reported measures before and after the intervention: the Modified Dental Anxiety Scale (MDAS), the Index of Dental Anxiety and Fear (IDAF-4C), and the Visual Analogue Scale-Anxiety (VAS-A). Dental care attendance was enquired in a 1-year follow-up. The scores for all three scales decreased among both study groups, with the largest decrease recorded in treatment group T1 assessed with the VAS-A. A higher dental anxiety score measured before the intervention associated most significantly with a higher dental anxiety score after the intervention. At the 1-year follow-up, 82% of participants in T1 and 67% in T2 had visited a dentist., Conclusion: A DI alone and combined with M-OST is potentially effective in reducing dental anxiety and in supporting the engagement of adult patients with dental treatment in primary dental care., (© 2022 The Authors. Special Care in Dentistry published by Special Care Dentistry Association and Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
346. Using the Jurkat reporter T cell line for evaluating the functionality of novel chimeric antigen receptors.
- Author
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Jahan F, Koski J, Schenkwein D, Ylä-Herttuala S, Göös H, Huuskonen S, Varjosalo M, Maliniemi P, Leitner J, Steinberger P, Bühring HJ, Vettenranta K, and Korhonen M
- Abstract
Background: T cells that are genetically modified with chimeric antigen receptor (CAR) hold promise for immunotherapy of cancer. Currently, there are intense efforts to improve the safety and efficacy of CAR T cell therapies against liquid and solid tumors. Earlier we designed a novel CAR backbone (FiCAR) where the spacer is derived from immunoglobulin (Ig) -like domains of the signal-regulatory protein alpha (SIRPα). However, the analysis of novel CAR using primary T cells is slow and laborious. Methods: To explore the versatility of the CAR backbone, we designed a set of variant FiCARs with different spacer lengths and targeting antigens. To expedite the analysis of the novel CARs, we transduced the FiCAR genes using lentiviruses into Jurkat reporter T cells carrying fluorescent reporter genes. The expression of fluorescent markers in response to FiCAR engagement with targets was analyzed by flow cytometry, and cytotoxicity was evaluated using killing assays. Furthermore, the killing mechanisms that are employed by FiCAR-equipped Jurkat T cells were investigated by flow cytometry, and the intracellular pathways involved in signaling by FiCAR were analyzed by phosphoproteomic analysis using mass spectrometry. Results: Seven different CARs were designed and transduced into Jurkat reporter cells. We show that the SIRPα derived FiCARs can be detected by flow cytometry using the SE12B6A4 antibody recognizing SIRPα. Furthermore, FiCAR engagement leads to robust activation of NFκβ and NFAT signaling, as demonstrated by the expression of the fluorescent reporter genes. Interestingly, the Jurkat reporter system also revealed tonic signaling by a HER-2 targeting FiCAR. FiCAR-equipped Jurkat T cells were cytotoxic in cocultures with target cells and target cell engagement lead to an upregulation of CD107a on the Jurkat reporter T cell surface. Phosphoproteomic analyses confirmed signal transduction via the intracellular CD28/CD3ζ sequences upon the interaction of the FiCAR1 with its antigen. In addition, downstream signaling of CD3ζ/ZAP70- SLP-76-PLCγ, PI3K-AKT-NFκB pathways and activation of NFAT and AP-1 were observed. Conclusion: We conclude that the FiCAR backbone can be shortened and lengthened at will by engineering it with one to three SIRPα derived Ig-like domains, and the FiCARs are functional when equipped with different single chain variable fragment target binding domains. The Jurkat reporter system expedites the analysis of novel CARs as to their expression, signaling function, evaluation of tonic signaling issues and cytotoxic activity., Competing Interests: KJ and KM are inventors in the patent application in the field of chimeric antigen receptors and received research funding from Orion Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jahan, Koski, Schenkwein, Ylä-Herttuala, Göös, Huuskonen, Varjosalo, Maliniemi, Leitner, Steinberger, Bühring, Vettenranta and Korhonen.)
- Published
- 2023
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- View/download PDF
347. The Individual-Level Productivity Costs of Physical Inactivity.
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Kari JT, Nerg I, Huikari S, Leinonen AM, Nurkkala M, Farrahi V, Korpelainen R, and Korhonen M
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- Humans, Leisure Activities, Self Report, Employment, Sedentary Behavior, Exercise
- Abstract
Purpose: This study estimated the long-term individual-level productivity costs of physical inactivity., Methods: The data were drawn from the Northern Finland Birth Cohort 1966, to which the productivity cost variables (sick leaves and disability pensions) from Finnish registries were linked. Individuals ( N = 6261) were categorized into physical activity groups based on their level of physical activity, which was measured in three ways: 1) self-reported leisure-time moderate- to vigorous-intensity physical activity (MVPA) at 46 yr old, 2) longitudinal self-reported leisure-time MVPA at 31-46 yr old, and 3) accelerometer-measured overall MVPA at 46 yr old. The human capital approach was applied to calculate the observed costs (years 2012-2020) and the expected costs (years 2012-2031)., Results: The results showed that the average individual-level productivity costs were higher among physically inactive compared with the costs among physically active. The results were consistent regardless of the measurement type of physical activity or the period used. On average, the observed long-term productivity costs among physically inactive individuals were €1900 higher based on self-reported MVPA, €1800 higher based on longitudinal MVPA, and €4300 higher based on accelerometer-measured MVPA compared with the corresponding productivity costs among physically active individuals. The corresponding difference in the expected costs was €2800, €1200, and €8700, respectively., Conclusions: The results provide evidence that productivity costs differ according to an individual's level of physical activity. Therefore, investments in physical activity may decrease not only the direct healthcare costs but also the indirect productivity costs paid by the employee, the employer, and the government., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)
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- 2023
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348. Serum levels of carnosine may be associated with the duration of MDD episodes.
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Ali-Sisto T, Tolmunen T, Kraav SL, Mäntyselkä P, Valkonen-Korhonen M, Honkalampi K, Ruusunen A, Velagapudi V, and Lehto SM
- Subjects
- Humans, Histidine blood, Carnosine blood, Depressive Disorder, Major
- Abstract
Background: Major depressive disorder (MDD) is a recurrent disorder that incurs a high societal burden. However, the etiology of MDD remains unclear. The functioning of several systems associated with the etiopathogenesis of MDD, such as inflammatory and stress systems, is partially modulated by the dipeptide carnosine., Methods: The study comprised 99 MDD patients and 253 non-depressed controls aged 20-71 years. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of carnosine and its constituent, histidine. We compared these metabolites in three different settings: 1) MDD patients vs. non-depressed controls and 2) remitted vs. non-remitted MDD patients, as well as 3) changes in the metabolite levels during the follow-up period within a) the remitted group and b) the non-remitted group. In addition, we assessed the possible effect of medications on the measured metabolites., Results: We observed higher serum levels of carnosine in the MDD group compared to the control group at baseline (OR = 1.895, 95%CI = 1.223-2.937, p = 0.004). Elevated serum levels of carnosine were also associated with a longer duration of the depressive episode (Z = 0.406, p = 0.001). However, the use of any antipsychotic medication (n = 36) was associated with lowered carnosine levels (p = 0.010 for use vs. non-use). At the follow-up, remitted and non-remitted participants displayed no significant differences in their carnosine levels (Z = -0.14, p = 0.891) or histidine (Z = -1.39 p = 0.164)., Conclusions: An increase in circulating carnosine may characterize depressive episodes and may represent a protective homeostatic reaction against MDD-related oxidative stress and inflammation., Competing Interests: Conflict of Interest None declared., (Copyright © 2022. Published by Elsevier B.V.)
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- 2023
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349. Novel modular chimeric antigen receptor spacer for T cells derived from signal regulatory protein alpha Ig-like domains.
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Koski J, Jahan F, Luostarinen A, Schenkwein D, Ylä-Herttuala S, Göös H, Monzo H, Ojala PM, Maliniemi P, and Korhonen M
- Abstract
Background: T cells equipped with chimeric antigen receptors (CAR) have shown remarkable efficacy in targeting B lineage malignancies. Improvement of the CAR structure is needed, however, with a view to developing flexibly modifiable spacers that are inert in interactions with unwanted cells. Specifically, binding to cells carrying receptors for IgG's crystallizable fragment (FcR), that recognize IgG-derived domains in CARs is to be avoided. Methods: Two novel CARs targeting the CD19 antigen where the IgG1-CH2 and -CH3 domains were replaced with Ig-like domains from signal-regulatory protein α (SIRPα) were designed in silico . An IgG1-based CAR and a CAR lacking both SIRPα and IgG1 domains were used as comparators. The phenotype and memory phenotype of the expanded cells were analyzed by flow cytometry, and CAR T cell activation and cytotoxic efficacy were assessed in co-culture experiments in response to CD19
+ target cells. Unwanted interactions with FcR-expressing myeloid cells were interrogated in co-culture assays with THP-1 monocytic cells. Results: T cells carrying the novel SIRPα-based CARs enacted potent in vitro cytotoxicity against CD19 positive B-lineage leukemia cells, comparable to traditional IgG1-based CAR T cells. Co-culture of IgG1-based CAR T cells with FcR-expressing THP-1 monocytic cells led to prominent cell surface expression of CD69 on T cells together with production of Interleukin (IL)-2 and Interferon-γ, and production of IL-1β, indicating activation of the T cells and monocytes, respectively. Longer co-culture led to killing of the monocytes. No signs of T cell nor monocyte activation were detected in co-cultures of SIRPα-based CAR T cells with THP-1 cells. Arming T cells with the SIRPα-based CARs favored differentiation towards CD4+ phenotype during expansion, while the effects on memory phenotype of the T cells were equivalent between the SIRPα- and IgG1-based CARs. In a pilot experiment, T cells modified with one of the SIRPα-based CARs showed dose dependent leukemia cell control. Conclusion: The novel SIRPα based spacers offer a suitable backbone for developing chimeric antigen receptors that evade the off-target binding to FcR while the cells retain a favorable memory phenotype and efficient cytotoxicity, establishing a promising candidate for future in vivo and clinical testing., Competing Interests: PMO and HM have performed CRO work for Orion Corporation Finland to develop FiCAR 1 based CAR T cell therapies. MK and JK are inventors of a CAR structure-related patent. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Koski, Jahan, Luostarinen, Schenkwein, Ylä-Herttuala, Göös, Monzo, Ojala, Maliniemi and Korhonen.)- Published
- 2022
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350. Fear, isolation and the importance of support: A qualitative study of parents' experiences of feeding a child born with esophageal atresia.
- Author
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Wallace V, Honkalampi K, and Korhonen M
- Subjects
- Child, Humans, Parents psychology, Family, Qualitative Research, Fear, Esophageal Atresia psychology
- Abstract
Objective: Feeding and swallowing difficulties in children are increasing due to improved survival rates of children with complex medical conditions. Despite being common complications of esophageal atresia (EA), EA related feeding difficulties have received little attention in research. Establishing positive feeding interactions and practices are important for child health and development, and for parental and child mental health. The current study aimed to investigate the parental experiences of feeding a child born with EA., Methods: An international online survey was developed and disseminated to parents of children born with EA, aged 0-12 years, in collaboration with a patient charity for EA. Reflexive Thematic Analysis was used to analyze the qualitative survey responses., Results: 176 participants were included in the qualitative sample from a larger international online survey study, chosen by a process of selective coding. Three themes were constructed during the analysis: 1) Anxiety, trauma and loss; 2) Isolated and unsupported; and 3) Supported. The results indicated that parents of children born with EA experienced significant anxiety related to their child's swallowing and feeding difficulties and traumatic experiences during feeding, and that these led to parents feeling a sense of loss and sadness. It was also found that support, or a lack of support, within parents' social environment might mediate parental experiences of child's feeding difficulties., Conclusions: This study highlighted the importance of support for parents of children born with EA, and suggested a need for improved guidance for feeding and swallowing difficulties., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
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