Browsing by Subject "STRAIN"

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  • Kivimäki, Mika; Walker, Keenan A.; Pentti, Jaana; Nyberg, Solja; Mars, Nina; Vahtera, Jussi; Suominen, Sakari B.; Lallukka, Tea; Rahkonen, Ossi; Pietiläinen, Olli; Koskinen, Aki; Vaananen, Ari; Kalsi, Jatinderpal K.; Goldberg, Marcel; Zins, Marie; Alfredsson, Lars; Westerholm, Peter J. M.; Knutsson, Anders; Theorell, Tores; Ervasti, Jenni; Oksanen, Tuula; Sipilä, Pyry N.; Tabak, Adam G.; Ferrie, Jane E.; Williams, Stephen A.; Livingston, Gill; Gottesman, Rebecca F.; Singh-Manoux, Archana; Zetterberg, Henrik; Lindbohm, Joni (2021)
    OBJECTIVES To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association. DESIGN Multicohort study with three sets of analyses. SETTING United Kingdom, Europe, and the United States. PARTICIPANTS Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies. MAIN OUTCOME MEASURES Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations. RESULTS During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I2=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted r3 -0.34, P(0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted r3 -0.33, P(0.001), and peptidyl-glycine alpha-amidating monooxygenase (AMD, fully adjusted r3 -0.32, P(0.001). These proteins were associated with increased dementia risk, with the fully adjusted hazard ratio per 1 SD being 1.16 (95% confidence interval 1.05 to 1.28) for SLIT2, 1.13 (1.00 to 1.27) for CHSTC, and 1.04 (0.97 to 1.13) for AMD. CONCLUSIONS The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings that
  • Virtanen, Jenni; Aaltonen, Kirsi; Vapalahti, Olli; Sironen, Tarja (2020)
    Aleutian disease (AD), caused by Aleutian mink disease virus (AMDV), causes significant welfare problems to mink, and financial losses to the farmers. As there is no vaccine or treatment available, reliable diagnostics is important for disease control. Here, we set up a probe-based real-time PCR (NS1-probe-PCR) to detect all strains of AMDV. PCR was validated and compared to two other real-time PCR methods (pan-AMDV- and pan-AMDO-PCR) currently used for AMDV diagnostics in Finland. The NS1-probe-PCR had a similar detection limit of 20 copies/reaction based on plasmid dilution series, and similar or better diagnostic sensitivity, when evaluated using spleen samples from mink, and stool samples from mink and foxes. None of the three PCR tests cross-reacted with other parvoviruses. The NS1-probe-PCR also showed a significantly higher specificity than the pan-AMDO-PCR with spleen samples and the best specificity with stool samples. Furthermore, it produced the results more rapidly than the other two PCRs making it a promising tool for both diagnostic and research purposes.
  • Wallin, Anna; Pylvas, Laura; Nokelainen, Petri (2020)
    In this article, we explore workers' stories about digitalization of work and professional development. The data (101 stories) were collected from 81 Finnish government workers through the method of empathy-based stories (MEBS). MEBS is a qualitative data collection method in which participants write short imaginary texts based on an introductory script (frame story) designed by the researcher. In this study, participants were presented with two frame stories in which they were asked to imagine why digitalization had either supported or hindered professional development. The stories were analyzed inductively using qualitative thematic analysis. The findings illustrate the double-edged nature of digitalization, as it may both support and hinder professional development and learning by changing work tasks, work practices and knowledge development and management. Overall, the stories revealed that the participants perceived that digitalization may support professional development and learning, especially by providing opportunities for job control in terms of flexibility, and new ways for knowledge development and management. Keywords
  • Turunen, Elina; Hiilamo, Heikki (2014)
  • Nava, Michele M.; Miroshnikova, Yekaterina A.; Biggs, Leah C.; Whitefield, Daniel B.; Metge, Franziska; Boucas, Jorge; Vihinen, Helena; Jokitalo, Eija; Li, Xinping; García Arcos, Juan Manuel; Hoffmann, Bernd; Merkel, Rudolf; Niessen, Carien M.; Dahl, Kris Noel; Wickström, Sara A. (2020)
    Summary Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high-amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.
  • Pimentel, Andre C.; Beraldo, Camila S.; Cogni, Rodrigo (2021)
    Host shifts, when a cross-species transmission of a pathogen can lead to successful infections, are the main cause of emerging infectious diseases, such as COVID-19. A complex challenge faced by the scientific community is to address the factors that determine whether the cross-species transmissions will result in spillover or sustained onwards infections. Here we review recent literature and present a perspective on current approaches we are using to understand the mechanisms underlying host shifts. We highlight the usefulness of the interactions between Drosophila species and viruses as an ideal study model. Additionally, we discuss how cross-infection experiments - when pathogens from a natural reservoir are intentionally injected in novel host species-can test the effect cross-species transmissions may have on the fitness of virus and host, and how the host phylogeny may influence this response. We also discuss experiments evaluating how cooccurrence with other viruses or the presence of the endosymbiont bacteria Wolbachia may affect the performance of new viruses in a novel host. Finally, we discuss the need of surveys of virus diversity in natural populations using next-generation sequencing technologies. In the long term, these approaches can contribute to a better understanding of the basic biology of host shifts.
  • Kuusio, Hannamaria; Lamsa, Riikka; Aalto, Anna-Mari; Manderbacka, Kristiina; Keskimaki, Ilmo; Elovainio, Marko (2014)
  • Thorlacius, Elin M.; Wåhlander, Håkan; Ojala, Tiina; Ylänen, Kaisa; Keski-Nisula, Juho; Synnergren, Mats; Romlin, Birgitta S.; Ricksten, Sven-Erik; Castellheim, Albert (2020)
    Objective : We aimed to determine the differential effects of intra-operative administration of milrinone versus levosimendan on myocardial function after pediatric cardiac surgery. Transthoracic echocardiography was employed for myocardial function evaluation, utilizing biventricular longitudinal strain with two-dimensional speckle tracking echocardiography in addition to conventional echocardiographic variables. Design : A secondary analysis of a randomized, prospective, double-blinded clinical drug trial Setting : Two pediatric tertiary university hospitals Participants : Infants between 1-12 months of age diagnosed with ventricular septal defect, complete atrioventricular septal defect, or tetralogy of Fallot who were scheduled for corrective surgery with cardiopulmonary bypass. Interventions : The patients were randomized to receive an infusion of milrinone or levosimendan at the start of cardiopulmonary bypass and for 26 consecutive hours. Measurements and main results : Biventricular longitudinal strain and conventional echocardiographic variables were measured preoperatively, on the first postoperative morning and prior to hospital discharge. The association between perioperative parameters and postoperative myocardial function was also investigated. Images were analyzed for left ventricular (n=67) and right ventricular (n=44) function. The day after surgery, left ventricular longitudinal strain was deteriorated in both the milrinone and levosimendan groups; 33% and 39%, respectively. The difference was not significant. The corresponding deterioration in right ventricular longitudinal strain was 42% and 50% (non-significant difference). For both groups, biventricular longitudinal strain approached their preoperative values at hospital discharge. Preoperative N-terminal pro-brain natriuretic peptide could predict the left ventricular strain on postoperative day one (p=0.014). Conclusions : Levosimendan was comparable to milrinone for left and right ventricular inotropic support in pediatric cardiac surgery.
  • Tuohinen, Suvi Sirkku; Skytta, Tanja; Poutanen, Tuija; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka (2017)
    Radiotherapy (RT) to the thoracic region increases late cardiovascular morbidity and mortality. The impact of breast cancer laterality on cardiac function is largely unknown. The aim of this prospective study was to compare RT-induced changes in left-sided and right-sided breast cancer patients using speckle tracking echocardiography (STE). Sixty eligible patients with left-sided breast cancer and 20 with right-sided breast cancer without chemotherapy were evaluated prospectively before and early after RT. A comprehensive echocardiographic examination included three dimensional measurements and STE of the left ventricle (LV). The global longitudinal strain (GLS) was reduced from -18.3 +/- 3.1 to -17.2 +/- 3.3% (p = 0.003) after RT in patients with left-sided breast cancer. Similarly, regional analysis showed a reduction in the apical strain from -18.7 +/- 5.3 to -16.7 +/- 4.9% (p = 0.002) and an increase in basal values from -21.6 +/- 5.0 to -23.3 +/- 4.9% (p = 0.024). Patients with right-sided breast cancer showed deterioration in basal anterior strain segments from -26.3 +/- 7.6 to -18.8 +/- 8.9% (p <0.001) and in pulsed tissue Doppler by 0.825 [0.365, 1.710] cm/s (p <0.001). In multivariable analysis, the use of aromatase inhibitor (beta = -2.002, p = 0.001) and decreased LV diastolic volume (beta = -0.070, p = 0.025) were independently associated with the decrease in GLS. RT caused no changes in conventional LV systolic measurements. RT induced regional changes corresponded to the RT fields. Patients with left-sided breast cancer experienced apical impact and global decline, whereas patients with right-sided breast cancer showed basal changes. The regional differences in cardiac impact warrant different methods in screening and in the follow-up of patients with left-sided versus right-sided breast cancer.
  • Lehmonen, Lauri; Jalanko, Mikko; Tarkiainen, Mika; Kaasalainen, Touko; Kuusisto, Johanna; Lauerma, Kirsi-Maria Susanna; Savolainen, Sauli (2020)
    Background Left ventricle rotation and torsion are fundamental components of myocardial function, and several software packages have been developed for analysis of these components. The purpose of this study was to compare the suitability of two software packages with different technical principles for analysis of rotation and torsion of the left ventricle during systole. Methods A group of hypertrophic cardiomyopathy (HCM) patients (N = 14, age 43 +/- 11 years), mutation carriers without hypertrophy (N = 10, age 34 +/- 13 years), and healthy relatives (N = 12, age 43 +/- 17 years) underwent a cardiovascular magnetic resonance examination, including spatial modulation of magnetization tagging sequences in basal and apical planes of the left ventricle. The tagging images were analyzed offline using a harmonic phase image analysis method with Gabor filtering and a non-rigid registration-based free-form deformation technique. Left-ventricle rotation and torsion scores were obtained from end-diastole to end-systole with both software. Results Analysis was successful in all cases with both software applications. End-systolic torsion values between the study groups were not statistically different with either software. End-systolic apical rotation, end-systolic basal rotation, and end-systolic torsion were consistently higher when analyzed with non-rigid registration than with harmonic phase-based analysis (p <0.0001). End-systolic rotation and torsion values had significant correlations between the two software (p <0.0001), most significant in the apical plane. Conclusions When comparing absolute values of rotation and torsion between different individuals, software-specific reference values are required. Harmonic phase flow with Gabor filtering and non-rigid registration-based methods can both be used reliably in the analysis of systolic rotation and torsion patterns of the left ventricle.
  • Soglia, Francesca; Petracci, Massimiliano; Puolanne, Eero (2020)
    The present study aims to measure the sarcomere lengths in normal broiler muscles and in non-lesion sites of breast muscles focally affected by Wooden Breast (WB). For this purpose, twenty Pectoralis major muscles (10 unaffected and 10 WB-focally affected cases) were sampled and used to measure sarcomere length by laser diffraction method. When compared with their unaffected counterpart, WB cases exhibited 13% longer sarcomeres (1.91 vs. 1.69 mu m; p <.001) measured within the non-lesioned site of the muscle. Although it is not simple to draw conclusions about the lesion properties based on the non-lesion area, but as the fibres are bound to each other, it may be reasonable to anticipate that the hardened consistency observed in WB is not ascribable to a more intense contraction of the sarcomeres. In addition, considering the current knowledge concerning this condition, it might be assumed that the longer sarcomeres observed in WB are not triggering the development of this condition but are rather a consequence of the profound alteration in the muscular structure resulting from it. Indeed, despite the outstanding improvements in the live and slaughtering traits, the selection programmes carried out in the past years have resulted in a reduced capillarization and impaired oxygen supply to the Pectoralis major of fast-growing hybrids thus affecting the physiology of its constituting fibres as well as maybe impairing their ability to synthetise new sarcomeres. This may result in a skeletal muscle injury, which would ultimately lead to necrosis and fibrosis.
  • Scaramuzzo, Gaetano; Broche, Ludovic; Pellegrini, Mariangela; Porra, Liisa; Derosa, Savino; Tannoia, Angela Principia; Marzullo, Andrea; Borges, Joao Batista; Bayat, Sam; Bravin, Alberto; Larsson, Anders; Perchiazzi, Gaetano (2019)
    Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH(2)O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 +/- 2.0 at PEEP 12 to 7.6 +/- 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 +/- 52 at PEEP 12 to 146.4 +/- 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.
  • Kontturi, Antti; Santiago, Begona; Tebruegge, Marc; von Both, Ulrich; Salo, Eeva; Ritz, Nicole (2016)
    Background: Recent reports indicate an ongoing BCG shortage that may influence immunisation practice. This study aimed to determine current availability of BCG vaccine across Europe, and implications on immunisation practices and policies in Europe. Methods: Web-based survey among Paediatric Tuberculosis Network European Trials Group (ptbnet) members, between May and October 2015. Results: Twenty individuals from 13 European countries participated. Ongoing shortages were reported in eight countries routinely using BCG (8/11, 73%). As a consequence of the shortage, BCG was not given as completely unavailable in some countries (2/8, 25%), was given only whenever available (1/8,13%), or only in certain regions of the country (1/8, 13%). Strategies reported to reduce loss of immunisation were administration to selected high-risk individuals (2/8, 25%), or cohorting vaccinees on specific days to maximise the use of multi-dose vials (3/8, 38%). Authorities in two countries each were considering a change of manufacturer/supplier (2/8, 25%). Conclusions: The BCG shortage in Europe leads to significant changes in immunisation policies including changes of BCG vaccine strain and manufacturer. In addition, infants and children eligible for immunisation are at risk of not receiving BCG. To ensure necessary BCG immunisations, collaboration between national health agencies and vaccine manufacturers is crucial. (C) 2016 Elsevier Ltd. All rights reserved.
  • Houlahan, Kathleen E.; Prokopec, Stephenie D.; Sun, Ren X.; Moffat, Ivy D.; Lindén, Jere; Lensu, Sanna; Okey, Allan B.; Pohjanvirta, Raimo; Boutros, Paul C. (2015)
    Polychlorinated dibenzodioxins are environmental contaminants commonly produced as a by-product of industrial processes. The most potent of these, 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD), is highly lipophilic, leading to bioaccumulation. White adipose tissue (WAT) is a major site for energy storage, and is one of the organs in which TCDD accumulates. In laboratory animals, exposure to TCDD causes numerous metabolic abnormalities, including a wasting syndrome. We therefore investigated the molecular effects of TCDD exposure on WAT by profiling the transcriptomic response of WAT to 100 mu g/kg of TCDD at 1 or 4 days in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. A comparative analysis was conducted simultaneously in identically treated TCDD-resistant Han/Wistar (Kuopio; H/W) rats one day after exposure to the same dose. We sought to identify transcriptomic changes coinciding with the onset of toxicity, while gaining additional insight into later responses. More transcriptional responses to TCDD were observed at 4 days than at I day post-exposure, suggesting WAT shows mostly secondary responses. Two classic AHR-regulated genes, Cyp1a1 and Nqo1, were significantly induced by TCDD in both strains, while several genes involved in the immune response, including Ms4a7 and Fl1a1 were altered in L-E rats alone. We compared genes affected by TCDD in rat WAT and human adipose cells, and observed little overlap. Interestingly, very few genes involved in lipid metabolism exhibited altered expression levels despite the pronounced lipid mobilization from peripheral fat pads by TCDD in L-E rats. Of these genes, the lipolysis-associated Lpin1 was induced slightly over 2-fold in L-E rat WAT on day 4. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.
  • Hanson, Linda L. Magnusson; Westerlund, Hugo; Goldberg, Marcel; Zins, Marie; Vahtera, Jussi; Rod, Naja Hulvej; Stenholm, Sari; Steptoe, Andrew; Kivimaki, Mika (2017)
    Work stress is a risk factor for cardio-metabolic diseases, but few large-scale studies have examined the clinical profile of individuals with work stress. To address this limitation, we conducted a cross-sectional study including 43,593 working adults from a French population-based sample aged 18-72 years (the CONSTANCES cohort). According to the Effort-Reward Imbalance model, work stress was defined as an imbalance between perceived high efforts and low rewards at work. A standardized health examination included measures of anthropometry, lung function, blood pressure and standard blood-based biomarkers. Linear regression analyses before and after multivariable adjustment for age, socioeconomic status, depressive symptoms, health-related behaviours, and chronic conditions showed that work stress was associated with higher BMI, waist circumference, waist-hip ratio, alanine transaminase, white blood cell count and lower high-density lipoprotein cholesterol in men, and with higher BMI and white blood cell count in women (differences 0.03-0.06 standard deviations, P <0.05 between individuals with and without work stress). No robust associations were observed with lung function, haemoglobin, creatinine, glucose levels or resting blood pressure measures. This indicates that work stress is associated altered metabolic profile, increased systemic inflammation, and, in men, poorer liver function, which is a marker of high alcohol consumption.