2,329 research outputs found

    Targeting Drp1 and mitochondrial fission for therapeutic immune modulation

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    Mitochondria are dynamic organelles whose processes of fusion and fission are tightly regulated by specialized proteins, known as mitochondria-shaping proteins. Among them, Drp1 is the main pro-fission protein and its activity is tightly regulated to ensure a strict control over mitochondria shape according to the cell needs. In the recent years, mitochondrial dynamics emerged as a new player in the regulation of fundamental processes during T cell life. Indeed, the morphology of mitochondria directly regulates T cell differentiation, this by affecting the engagment of alternative metabolic routes upon activation. Further, Drp1-dependent mitochondrial fission sustains both T cell clonal expansion and T cell migration and invasivness. By this review, we aim at discussing the most recent findings about the roles played by the Drp1-dependent mitochondrial fission in T cells, and at highlighting how its pharmacological modulation could open the way to future therapeutic approaches to modulate T cell response

    Trust your back : classification-based care for low back pain in primary care

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    Abstract Low back pain (LBP), mostly a non-specific symptom, is a leading cause of years lived with disability: multiple biological, psychological, social and lifestyle factors lead to pain-related disability and use of healthcare. Evidence-based care for LBP comprises active treatments that address biopsychosocial factors and focus on improving functioning, self-management, education, and advice to stay active, also at work. The STarT Back Tool (SBT) and the Örebro Musculoskeletal Pain Screening Questionnaire Short Form (ÖMPSQ-SF) were created to enable easy and systematic identification of predictive psychosocial and symptom-related factors. The patient education booklet was designed to support evidence-based care and reduce inappropriate imaging. The study aim was to evaluate the concordance of the SBT and ÖMPSQ-SF and the accumulation of psychiatric, psychological, lifestyle, and social risk factors in the high-risk groups of both questionnaires among population with LBP. We also aimed to translate and validate the patient education booklet. We separately assessed the effectiveness of the patient education booklet and the classification-based approach to LBP care in primary care and compared it to that of usual care. SBT and ÖMPSQ-SF were compared in a population-based study using the Northern Finland Birth Cohort 1966. The preliminary evaluation of the patient education booklet was obtained using web-based questionnaires. A cluster randomised study evaluated the effectiveness of the patient education booklet, and a Benchmarking Controlled Trial evaluated the effectiveness of a classification-based approach to LBP care in primary care. Individual psychological and social risk factors accumulated among the high-risk groups of the SBT and the ÖMPSQ-SF. The education booklet helped patients understand their pain, encouraged them to be physically active, decreased imaging and the number of LBP-related sick leave days. Although classification-based care did not seem to influence physical functioning in the long term, pain was alleviated more quickly, and the use of healthcare services and number of back-related sick leave days decreased in the intervention group. A combination of education for healthcare professionals, classification-based care using the SBT, and systematic use of the patient education booklet seems to bring value to LBP care in primary healthcare. Original papers Simula, A. S., Ruokolainen, O., Oura, P., Lausmaa, M., Holopainen, R., Paukkunen, M., Auvinen, J., Linton, S. J., Hill, J. C., & Karppinen, J. (2020). Association of STarT Back Tool and the short form of the Örebro Musculoskeletal Pain Screening Questionnaire with multidimensional risk factors. Scientific Reports, 10(1), 290. https://doi.org/10.1038/s41598-019-57105-3 https://doi.org/10.1038/s41598-019-57105-3 Self-archived version Simula, A. S., Jenkins, H. J., Holopainen, R., Oura, P., Korniloff, K., Häkkinen, A., Takala, E.-P., Hancock, M. J., & Karppinen, J. (2019). Transcultural adaption and preliminary evaluation of “understanding low back pain” patient education booklet. BMC Health Services Research, 19(1), 1010. https://doi.org/10.1186/s12913-019-4854-y https://doi.org/10.1186/s12913-019-4854-y Self-archived version Simula, A. S., Jenkins, H. J., Hancock, M. J., Malmivaara, A., Booth, N., & Karppinen, J. (2021). Patient education booklet to support evidence-based low back pain care in primary care – a cluster randomized controlled trial. BMC Family Practice, 22(1), 178. https://doi.org/10.1186/s12875-021-01529-2 https://doi.org/10.1186/s12875-021-01529-2 Self-archived version Simula, A. S., Malmivaara, A., Booth, N., & Karppinen, J. (2020). A classification-based approach to low back pain in primary care – protocol for a benchmarking controlled trial. BMC Family Practice, 21(1), 61. https://doi.org/10.1186/s12875-020-01135-8 https://doi.org/10.1186/s12875-020-01135-8 Self-archived version Simula, A. S., Malmivaara, A., Booth, N., & Karppinen, J. (2024). Effectiveness of a classification-based approach to low back pain in primary care – a benchmarking controlled trial. Journal of Rehabilitation Medicine, 56, jrm28321. https://doi.org/10.2340/jrm.v56.28321 https://doi.org/10.2340/jrm.v56.28321 Self-archived version Tiivistelmä Alaselkäkipu on yleisin haittaa aiheuttava vaiva, enimmäkseen epäspesifi oire, jossa monet biologiset, psykologiset, sosiaaliset ja elintapatekijät vaikuttavat kipuun liittyvään haittaan ja terveyspalveluiden käyttöön. Näyttöön perustuva alaselkäkivun hoito on aktiivista ja huomioi biopsykososiaaliset tekijät. Hoidon keskiössä on toimintakyvyn parantaminen, omahoito, ohjaus ja neuvonta sekä ohje pysyä aktiivisena työ mukaan lukien. STarT-selkäkysely (SBT) ja Örebro-kipukysely (ÖMPSQ-SF) on kehitetty auttamaan ennustavien psykososiaalisten ja oireeseen liittyvien tekijöiden tunnistamisessa. Uusi potilasopas on kehitetty tukemaan näyttöön perustuvaa hoitoa ja vähentämään tarpeetonta kuvantamista. Tavoitteemme oli arvioida SBT ja ÖMPSQ-SF yhdenmukaisuutta sekä psykiatristen, psykologisten, elintapaan liittyvien ja sosiaalisten riskitekijöiden kasautumista molempien kyselyiden korkeaan riskiryhmään alaselkäkipuisessa väestössä. Tavoitteena oli myös kääntää ja validoida uusi potilasopas suomeksi. Lisäksi arvioimme erikseen potilasoppaan vaikuttavuutta ja luokitteluun perustuvan hoitomallin vaikuttavuutta alaselkäkipupotilaiden hoidossa perusterveydenhuollossa. SBT ja ÖMPSQ-SF vertailtiin väestöaineistossa käyttäen Pohjois-Suomen syntymäkohortti 1966 aineistoa. Alustava arvio potilasoppaasta tehtiin nettikyselyillä. Ryvässatunnaistetussa asetelmassa tutkittiin potilasoppaan vaikuttavuutta ja vertaiskontrolloidussa asetelmassa luokitteluun perustuvan hoitomallin jalkauttamisen vaikuttavuutta alaselkäkivun hoidossa perusterveydenhuollossa. Yksilölliset psykologiset ja sosiaaliset riskitekijät kasautuivat SBT ja ÖMPSQ-SF korkean riskin ryhmiin. Potilasopas auttoi potilaita ymmärtämään heidän kipuansa, rohkaisi heitä olemaan fyysisesti aktiivisia ja vähensi alaselän kuvantamistutkimuksia sekä sairauslomapäiviä. Vaikka luokitteluun perustuva hoitomalli ei vaikuttanut fyysiseen toimintakykyyn pitkällä aikavälillä, kipuoireet näyttivät paranevan nopeammin, terveyspalvelujen käyttö oli vähäisempää ja selkäkipuun liittyvien sairaslomapäivien määrä oli pienempi interventioryhmässä. Yhdessä terveydenhuollon ammattilaisten koulutus, luokitteluun perustuva alaselkäkipupotilaiden hoito STarT-selkäkyselyä käyttäen ja systemaattinen potilasoppaan käyttö näytti edistävän alaselkäkipupotilaiden hoitoa perusterveydenhuollossa. Osajulkaisut Simula, A. S., Ruokolainen, O., Oura, P., Lausmaa, M., Holopainen, R., Paukkunen, M., Auvinen, J., Linton, S. J., Hill, J. C., & Karppinen, J. (2020). Association of STarT Back Tool and the short form of the Örebro Musculoskeletal Pain Screening Questionnaire with multidimensional risk factors. Scientific Reports, 10(1), 290. https://doi.org/10.1038/s41598-019-57105-3 https://doi.org/10.1038/s41598-019-57105-3 Rinnakkaistallennettu versio Simula, A. S., Jenkins, H. J., Holopainen, R., Oura, P., Korniloff, K., Häkkinen, A., Takala, E.-P., Hancock, M. J., & Karppinen, J. (2019). Transcultural adaption and preliminary evaluation of “understanding low back pain” patient education booklet. BMC Health Services Research, 19(1), 1010. https://doi.org/10.1186/s12913-019-4854-y https://doi.org/10.1186/s12913-019-4854-y Rinnakkaistallennettu versio Simula, A. S., Jenkins, H. J., Hancock, M. J., Malmivaara, A., Booth, N., & Karppinen, J. (2021). Patient education booklet to support evidence-based low back pain care in primary care – a cluster randomized controlled trial. BMC Family Practice, 22(1), 178. https://doi.org/10.1186/s12875-021-01529-2 https://doi.org/10.1186/s12875-021-01529-2 Rinnakkaistallennettu versio Simula, A. S., Malmivaara, A., Booth, N., & Karppinen, J. (2020). A classification-based approach to low back pain in primary care – protocol for a benchmarking controlled trial. BMC Family Practice, 21(1), 61. https://doi.org/10.1186/s12875-020-01135-8 https://doi.org/10.1186/s12875-020-01135-8 Rinnakkaistallennettu versio Simula, A. S., Malmivaara, A., Booth, N., & Karppinen, J. (2024). Effectiveness of a classification-based approach to low back pain in primary care – a benchmarking controlled trial. Journal of Rehabilitation Medicine, 56, jrm28321. https://doi.org/10.2340/jrm.v56.28321 https://doi.org/10.2340/jrm.v56.28321 Rinnakkaistallennettu versio Academic dissertation to be presented with the assent of the Doctoral Programme Committee of Health and Biosciences of the University of Oulu for public defence in MKS Auditorium (Mikkeli), on 13 December 2024, at 12 noonAbstract Low back pain (LBP), mostly a non-specific symptom, is a leading cause of years lived with disability: multiple biological, psychological, social and lifestyle factors lead to pain-related disability and use of healthcare. Evidence-based care for LBP comprises active treatments that address biopsychosocial factors and focus on improving functioning, self-management, education, and advice to stay active, also at work. The STarT Back Tool (SBT) and the Örebro Musculoskeletal Pain Screening Questionnaire Short Form (ÖMPSQ-SF) were created to enable easy and systematic identification of predictive psychosocial and symptom-related factors. The patient education booklet was designed to support evidence-based care and reduce inappropriate imaging. The study aim was to evaluate the concordance of the SBT and ÖMPSQ-SF and the accumulation of psychiatric, psychological, lifestyle, and social risk factors in the high-risk groups of both questionnaires among population with LBP. We also aimed to translate and validate the patient education booklet. We separately assessed the effectiveness of the patient education booklet and the classification-based approach to LBP care in primary care and compared it to that of usual care. SBT and ÖMPSQ-SF were compared in a population-based study using the Northern Finland Birth Cohort 1966. The preliminary evaluation of the patient education booklet was obtained using web-based questionnaires. A cluster randomised study evaluated the effectiveness of the patient education booklet, and a Benchmarking Controlled Trial evaluated the effectiveness of a classification-based approach to LBP care in primary care. Individual psychological and social risk factors accumulated among the high-risk groups of the SBT and the ÖMPSQ-SF. The education booklet helped patients understand their pain, encouraged them to be physically active, decreased imaging and the number of LBP-related sick leave days. Although classification-based care did not seem to influence physical functioning in the long term, pain was alleviated more quickly, and the use of healthcare services and number of back-related sick leave days decreased in the intervention group. A combination of education for healthcare professionals, classification-based care using the SBT, and systematic use of the patient education booklet seems to bring value to LBP care in primary healthcare.Tiivistelmä Alaselkäkipu on yleisin haittaa aiheuttava vaiva, enimmäkseen epäspesifi oire, jossa monet biologiset, psykologiset, sosiaaliset ja elintapatekijät vaikuttavat kipuun liittyvään haittaan ja terveyspalveluiden käyttöön. Näyttöön perustuva alaselkäkivun hoito on aktiivista ja huomioi biopsykososiaaliset tekijät. Hoidon keskiössä on toimintakyvyn parantaminen, omahoito, ohjaus ja neuvonta sekä ohje pysyä aktiivisena työ mukaan lukien. STarT-selkäkysely (SBT) ja Örebro-kipukysely (ÖMPSQ-SF) on kehitetty auttamaan ennustavien psykososiaalisten ja oireeseen liittyvien tekijöiden tunnistamisessa. Uusi potilasopas on kehitetty tukemaan näyttöön perustuvaa hoitoa ja vähentämään tarpeetonta kuvantamista. Tavoitteemme oli arvioida SBT ja ÖMPSQ-SF yhdenmukaisuutta sekä psykiatristen, psykologisten, elintapaan liittyvien ja sosiaalisten riskitekijöiden kasautumista molempien kyselyiden korkeaan riskiryhmään alaselkäkipuisessa väestössä. Tavoitteena oli myös kääntää ja validoida uusi potilasopas suomeksi. Lisäksi arvioimme erikseen potilasoppaan vaikuttavuutta ja luokitteluun perustuvan hoitomallin vaikuttavuutta alaselkäkipupotilaiden hoidossa perusterveydenhuollossa. SBT ja ÖMPSQ-SF vertailtiin väestöaineistossa käyttäen Pohjois-Suomen syntymäkohortti 1966 aineistoa. Alustava arvio potilasoppaasta tehtiin nettikyselyillä. Ryvässatunnaistetussa asetelmassa tutkittiin potilasoppaan vaikuttavuutta ja vertaiskontrolloidussa asetelmassa luokitteluun perustuvan hoitomallin jalkauttamisen vaikuttavuutta alaselkäkivun hoidossa perusterveydenhuollossa. Yksilölliset psykologiset ja sosiaaliset riskitekijät kasautuivat SBT ja ÖMPSQ-SF korkean riskin ryhmiin. Potilasopas auttoi potilaita ymmärtämään heidän kipuansa, rohkaisi heitä olemaan fyysisesti aktiivisia ja vähensi alaselän kuvantamistutkimuksia sekä sairauslomapäiviä. Vaikka luokitteluun perustuva hoitomalli ei vaikuttanut fyysiseen toimintakykyyn pitkällä aikavälillä, kipuoireet näyttivät paranevan nopeammin, terveyspalvelujen käyttö oli vähäisempää ja selkäkipuun liittyvien sairaslomapäivien määrä oli pienempi interventioryhmässä. Yhdessä terveydenhuollon ammattilaisten koulutus, luokitteluun perustuva alaselkäkipupotilaiden hoito STarT-selkäkyselyä käyttäen ja systemaattinen potilasoppaan käyttö näytti edistävän alaselkäkipupotilaiden hoitoa perusterveydenhuollossa

    An?lise e Simula??o de Filtros de Microfita Utilizando o M?todo FDTD

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    Esta Disserta??o descreve a aplica??o do m?todo das Diferen?as Finitas no Dom?nio do Tempo (FDTD ? Finite Difference Time Domain) para a an?lise de filtros fabricados em linhas de microfita para a faixa de micro-ondas. O m?todo FDTD 3-D, desenvolvido em linguagem C, implementa condi??es de contorno com o uso da t?cnica PML (Perfect Matched Layer), permitindo a determina??o num?rica dos campos eletromagn?ticos com uma menor interfer?ncia das reflex?es indesej?veis nos limites da malha FDTD. A fim de comparar os resultados obtidos com o m?todo FDTD, o software comercial Ansoft DesignerTM tamb?m ? usado para simula??o dos filtros abordados. Cinco prot?tipos foram constru?dos e caracterizados experimentalmente com o uso de um analisador de redes vetorial, Agilent N5230A. Estes resultados num?ricos e experimentais s?o usados para a compara??o do m?todo FDTD 3-D desenvolvido. O m?todo FDTD foi aplicado para an?lise de um filtro passa-baixa em linha de microfita, de filtros DGS (Defected Ground Structure) unit?rios e peri?dicos e de um filtro spur-line. Os resultados de simula??o foram concordantes com os experimentos realizados com um erro m?ximo de 4,8% para os filtros abordados. Atrav?s de varia??es na malha FDTD, uma an?lise de desempenho do m?todo FDTD foi realizada em termos de precis?o e esfor?o computacional

    The carboxyterminal peptide of chorionic gonadotropin facilitates activation of the marmoset LH receptor

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    Luteinizing hormone (LH) and chorionic gonadotropin (CG) are heterodimeric glycoprotein hormones acting on the luteinizing hormone receptor (LHR). In the LHR, which is genomically encoded by eleven exons, exon 10 encodes for the hinge region and its elimination impairs LH action, while CG maintains normal activity. The two gonadotropins differ in the carboxyterminal peptide (CTP) present in CG but absent in LH. Since the marmoset monkey (Callithrix jacchus) LHR naturally lacks exon 10 (LHR type II), we generated two recombinant marmoset gonadotropin preparations, one consisting of the wild type CG and one of truncated CG lacking the CTP (CG (-CTP)). After calibration in a mouse Leydig cell bioassay against the WHO LH80/522 standard, the ED (50) of the CG preparation on a COS7 cell line permanently expressing the marmoset LHR was 4.25 +/- 0.21 IU/L (n = 3). Stimulation of the COS7 cell line with equipotent concentrations of CG and CG (-CTP) resulted in significantly different formation of cAMP (two-way ANOVA, p < 0.001). In particular, cAMP production stimulated by CG (-CTP) was 3 - 4 times lower compared to CG at the saturating CG concentration (8 IU/L). We conclude, supplementing one current model of LHR activation, that exon 10 might play a permissive role in releasing the constraint of the receptor upon hormone binding, resulting in receptor activation. We speculate that, when exon 10 is lacking, the CTP can overcome its absence and facilitates the opening of the receptor, resulting in normal activation.T. Müller, J. Gromoll, A. P. Simula, R. Norman, R. Sandhowe-Klaverkamp, M. Simon

    The new forest policy in Finland

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    In a presentation made to the Agriculture Academy of France in April 2014, Mr. Simula described the new Finnish forestry policy against the backdrop of developments experienced by Finnish forestry sector in the last few decades. To complete this documented overview, a table comparing the Finnish situation with the French situation —which is less different than generally assumed— is providedDans la note présentée à l’Académie d’agriculture de France en avril 2014, M. Simula décrit la nouvelle politique forestière finlandaise en la replaçant devant les évolutions récentes que la Finlande forestière a connues depuis quelques décennies. Un tableau de comparaison avec la situation française, qui n’est pas si différente qu’on pourrait le penser, complète ce panorama document

    Masses, decay constants and HQE matrix elements of pseudoscalar and vector heavy-light mesons in LQCD

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    We present a precise lattice computation of masses and decay constants of pseudoscalar and vector heavy-light mesons with m l = m u/d, m s and m h in the range (m c, ∼ 3m c). We employ the ETMC gauge configurations with both N f = 2 and N f = 2 + 1 + 1 dynamical quarks and the ETMC ratio method to reach the b-quark mass. In the case of the vector decay constants an unusual quenching effect of the strange quark is observed. Specific masses combinations are then analyzed in terms of the Heavy Quark Expansion (HQE) to extract matrix elements up to dimension-6, including , and and with a good precision. These parameters play a crucial role in the inclusive determination of the V ub and V cb matrix elements

    Vortices in dilute Bose-Einstein condensates

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    Bose-Einstein condensation, first predicted by Bose and Einstein in 1924, was finally realized in dilute, weakly interacting gases of alkali atoms in 1995. A few years later, quantized vortices - intimately related to the phenomenon of superfluidity - were created and observed in these novel quantum many-body systems. In this Thesis, vortices in dilute atomic Bose-Einstein condensates are studied theoretically and computationally using microscopic mean-field theory formalisms. Special emphasis is on the structure and the stability of vortices at finite temperatures. The formation of quantized circulation in Bose-Einstein condensates is investigated, as well as multiply quantized vorticity and the adiabaticity of the precessing motion of a vortex. This research strongly relies on numerically solving the Gross-Pitaevskii equation for the macroscopic condensate wavefunction and the coupled Bogoliubov equations and their variants for the collective quasiparticle excitation eigenmodes. The computed elementary excitation spectra are used, for instance, in determining the local stability of various condensate states. The vortex formation process is studied at finite temperatures in terms of the surface modes of the condensate providing the Landau critical velocities for the breakdown of superfluidity. Free energy calculations are used for determining the thermodynamic equilibrium states. Singly quantized, axisymmetric vortex states are found to be locally energetically stable even in the zero-temperature limit within the self-consistent finite-temperature approximations. This would imply for the vortex a precession direction opposite to that observed in the experiment. Adiabatic approximation of quantum mechanics is formulated for Bose-Einstein condensed systems and is applied to a case of a moving vortex line. The experimentally observed precessing motion of the vortex is found to be nonadiabatic. A method to create stable multiply quantized vortices using an additional pinning potential is presented. The computed critical trap rotation frequencies for vortex nucleation at finite temperatures are in agreement with experiments and the predictions of zero-temperature field theories.reviewe

    Leading isospin-breaking corrections to meson masses on the lattice

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    We present a study of the isospin-breaking (IB) corrections to pseudoscalar (PS) meson masses using the gauge configurations produced by the ETM Collaboration with Nf = 2+1+1 dynamical quarks at three lattice spacings varying from 0.089 to 0.062 fm. Our method is based on a combined expansion of the path integral in powers of the small parameters m d-m u/ΛQCD and αem, where m f is the renormalized quark mass and αem the renormalized fine structure constant. We obtain results for the pion, kaon and Dmeson mass splitting; for the Dashen's theorem violation parameters ∈ γ(MM, 2 GeV), ∈ π 0 ∈ K 0(MS, 2 GeV) for the light quark masses m d-m uMS̄,2GeV,m u/m dMS̄,2GeV; for the flavour symmetry breaking parameters R(MS, 2 GeV) and Q(MS, 2 GeV) and for the strong IB effects on the kaon decay constants. © The Authors, published by EDP Sciences, 2018
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