Browsing by Subject "TRIGGERS"

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  • Ahtiainen, Laura; Mirantes, Cristina; Jahkola, Tiina; Escutenaire, Sophie; Diaconu, Iulia; Osterlund, Pamela; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli (2010)
  • Pirinen, Jani; Kuusisto, Jouni; Järvinen, Vesa; Martinez-Majander, Nicolas; Sinisalo, Juha; Pöyhönen, Pauli; Putaala, Jukka (2020)
    Background Ischaemic stroke in young individuals often remains cryptogenic. In this pilot study, we investigated, whether advanced echocardiography methods could find differences in the diastolic function between young cryptogenic stroke patients and stroke-free controls. Methods We recruited 30 cryptogenic ischaemic stroke patients aged 18-49 and 30 age- and sex-matched stroke-free controls among participants of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study (NCT01934725). We measured diastolic function parameters derived from speckle tracking strain rate, Doppler techniques and 4D volumetry. We also performed statistical analyses comparing only the highest and lowest tertile of cases and controls for each parameter. Results None of our patients or controls had diastolic dysfunction according to ASE/EACVI criteria. However, compared to stroke-free controls, the stroke patient group had lower E/A ratio of mitral inflow, lower lateral and mean e', lower A/a' ratio, lower strain rate in early diastole and lower speckle tracking-derived e/a ratio. When comparing the lowest tertiles, patients also had a lower peak filling rate by 4D volumetry, a lower peak early filling fraction (fraction of left ventricular filling during early diastole), and lower velocities in a series of the tissue Doppler-derived diastolic parameters and blood flow/tissue velocity ratios. Conclusion Our study displayed subtle differences in diastolic function between patients and stroke-free controls, which may play a role in early-onset cryptogenic stroke. The differences were clearer when the lowest tertiles were compared, suggesting that there is a subgroup of young cryptogenic stroke patients with subclinical heart disease.
  • Martinez-Majander, Nicolas; Gordin, Daniel; Joutsi-Korhonen, Lotta; Salopuro, Titta; Adeshara, Krishna; Sibolt, Gerli; Curtze, Sami; Pirinen, Jani; Liebkind, Ron; Soinne, Lauri; Sairanen, Tiina; Sinisalo, Juha; Lehto, Mika; Groop, Per-Henrik; Tatlisumak, Turgut; Putaala, Jukka (2021)
    Background The aim of this study was to assess the association between endothelial function and early-onset cryptogenic ischemic stroke (CIS), with subgroup analyses stratified by sex and age groups. Methods and Results We prospectively enrolled 136 consecutive patients aged 18 to 49 years (median age, 41 years; 44% women) with a recent CIS and 136 age- and sex-matched (+/- 5 years) stroke-free controls. Endothelial function was measured with an EndoPAT 2000 device and analyzed as tertiles of natural logarithm of reactive hyperemia index with lower values reflecting dysfunction. We used conditional logistic regression adjusting for age, education, hypertension, diabetes mellitus, dyslipidemia, current smoking, heavy drinking, obesity, and diet score to assess the independent association between endothelial function and CIS. Patients in the lowest tertile of natural logarithm of reactive hyperemia index were more often men and they more frequently had a history of dyslipidemia; they were also more often obese, had a lower diet score, and lower high-density lipoprotein cholesterol. In the entire cohort, we found no association in patients with endothelial function and CIS compared with stroke-free controls. In sex- and age-specific analyses, endothelial dysfunction was associated with CIS in men (adjusted odds ratio [OR], 3.50 for lowest versus highest natural logarithm of reactive hyperemia index tertile; 95% CI, 1.22-10.07) and in patients >= 41 years (OR, 5.78; 95% CI, 1.52-21.95). These associations remained significant when dyslipidemia was replaced with the ratio of total to high-density lipoprotein cholesterol. Conclusions Endothelial dysfunction appears to be an independent player in early-onset CIS in men and patients approaching middle age.
  • Anttila, Henrika; Pyhältö, Kirsi; Soini, Tiina; Pietarinen, Janne (2017)
    Studying to become a teacher is a highly emotional experience. Nevertheless, little is known about emotional patterns and emotional change. The aim of this study is to enhance the understanding of student teachers' academic emotions by exploring patterns of emotions experienced in emotionally loaded episodes. A total of 19 primary school student teachers were interviewed. The qualitative content analysis revealed five different emotional patterns: positive, negative, ascending, descending and changing. Most of the emotional patterns were positive or changing in nature. Yet all the emotional patterns were highly focused on studying and learning. Moreover, the patterns were experienced equally in short, medium-length and long episodes. Our study showed that emotional patterns were triggered by various task-related elements of teacher education: most commonly, fulfilled or unfilled expectations, sufficient or insufficient abilities, and experiences of social support received or not received.
  • Durgaprasad, Kavya; Roy, Merin V.; Venugopal, Anjali M.; Kareem, Abdul; Raj, Kiran; Willemsen, Viola; Mähönen, Ari Pekka; Scheres, Ben; Prasad, Kalika (2019)
    A wide variety of multicellular organisms across the kingdoms display remarkable ability to restore their tissues or organs when they suffer damage. However, the ability to repair damage is not uniformly distributed throughout body parts. Here, we unravel the elusive mechanistic basis of boundaries on organ regeneration potential using root tip resection as a model and show that the dosage of gradient-expressed PLT2 transcription factor is the underlying cause. While transient downregulation of PLT2 in distinct set of plt mutant backgrounds renders meri-stematic cells incapable of regeneration, forced expression of PLT2 acts through auto-activation to confer regeneration potential to the cells undergoing differentiation. Surprisingly, sustained exposure to nuclear PLT2, beyond a threshold, leads to reduction of regeneration potential despite giving rise to longer meristem. Our studies reveal dosage-dependent role of gradient-expressed PLT2 in root tip regeneration and uncouple the size of an organ from its regeneration potential.
  • Pirinen, Jani; Järvinen, Vesa; Martinez-Majander , Nicolas; Sinisalo, Juha; Pöyhönen, Pauli; Putaala, Jukka (2020)
    BACKGROUND: Ischemic stroke in young individuals often remains cryptogenic. Some of these strokes likely originate from the heart, and atrial fibrosis might be one of the etiological mechanisms. In this pilot study, we investigated whether advanced echocardiography findings of the left atrium (LA) of young cryptogenic stroke patients differ from those of stroke--free controls. METHODS AND RESULTS: We recruited 30 cryptogenic ischemic stroke patients aged 18 to 49 years and 30 age--and sex-matched stroke--free controls among participants of the SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study (NCT01934725). We measured basic left ventricular parameters and detailed measures of the LA, including 4--dimensional volumetry, speckle tracking epsilon, strain rate, and LA appendix orifice variation. Data were compared as continuous parameters and by tertiles. Compared with controls, stroke patients had smaller LA reservoir volumes (10.2 [interquartile range, 5.4] versus 13.2 [5.4] mL; P= 0.030) and smaller positive epsilon values (17.8 [8.5] versus 20.8 [10.1]; P= 0.023). In the tertile analysis, stroke patients had significantly lower left atrial appendage orifice variation (3.88 [0.75] versus 4.35 [0.90] mm; P=0.043), lower LA cyclic volume change (9.2 [2.8] versus 12.8 [3.5] mL; P=0.023), and lower LA contraction peak strain rate (-1.8 [0.6] versus -2.3 [0.6]; P=0.021). We found no statistically significant differences in left ventricular measures. CONCLUSIONS: This preliminary comparison suggests altered LA dynamics in young patients with cryptogenic ischemic stroke, and thus that LA wall pathology might contribute to these strokes. Our results await confirmation in a larger sample.
  • Pöyhönen, Pauli; Kuusisto, Jouni; Järvinen, Vesa; Pirinen, Jani; Räty, Heli; Lehmonen, Lauri; Paakkanen, Riitta; Martinez-Majander, Nicolas; Putaala, Jukka; Sinisalo, Juha (2020)
    Background Up to 50% of ischemic strokes in the young after thorough diagnostic work-up remain cryptogenic or associated with low-risk sources of cardioembolism such as patent foramen ovale (PFO). We studied with cardiac magnetic resonance (CMR) imaging, whether left ventricular (LV) non-compaction-a possible source for embolic stroke due to sluggish blood flow in deep intertrabecular recesses-is associated with cryptogenic strokes in the young. Methods Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is an international prospective multicenter case-control study of young adults (aged 18-49 years) presenting with an imaging-positive first-ever ischemic stroke of undetermined etiology. In this pilot substudy, 30 cases and 30 age- and sex-matched stroke-free controls were examined with CMR. Transcranial Doppler (TCD) bubble test was performed to evaluate the presence and magnitude of right-to-left shunt (RLS). Results There were no significant differences in LV volumes, masses or systolic function between cases and controls; none of the participants had non-compaction cardiomyopathy. Semi-automated assessment of LV non-compaction was highly reproducible. Non-compacted LV mass (median 14.0 [interquartile range 12.6-16.0] g/m(2)vs. 12.7 [10.4-16.6] g/m(2), p = 0.045), the ratio of non-compacted to compacted LV mass (mean 25.6 +/- 4.2% vs. 22.8 +/- 6.0%, p = 0.015) and the percentage of non-compacted LV volume (mean 17.6 +/- 2.9% vs. 15.7 +/- 3.8%, p = 0.004) were higher in cases compared to controls. In a multivariate conditional logistic regression model including non-compacted LV volume, RLS and body mass index, the percentage of non-compacted LV volume (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.10-2.18, p = 0.011) and the presence of RLS (OR 11.94, 95% CI 1.14-124.94, p = 0.038) were independently associated with cryptogenic ischemic stroke. Conclusions LV non-compaction is associated with a heightened risk of cryptogenic ischemic stroke in young adults, independent of concomitant RLS and in the absence of cardiomyopathy.
  • Lehmonen, Lauri; Putaala, Jukka; Pöyhönen, Pauli; Kuusisto, Jouni; Pirinen, Jani; Sinisalo, Juha; Järvinen, Vesa (2022)
    To elucidate underlying disease mechanisms, we compared transition of gadolinium-based contrast agent bolus in cardiac chambers in magnetic resonance imaging between young patents with cryptogenic ischemic stroke and stroke-free controls. We included 30 patients aged 18-50 years with cryptogenic ischemic stroke from the prospective Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers and Outcome (NCT01934725) study and 30 age- and gender-matched stroke-free controls. Dynamic contrast-enhanced T1-weighted first-pass perfusion images were acquired at 1.5 T and analyzed for transit time variables, area under curves, relative blood flow, and maximum and minimum enhancement rates in left atrial appendage, left atrium, and left ventricle. These data were compared with previously published left ventricular non-compaction data of the same study population. Arrival time of contrast agent bolus in superior vena cava was similar in patients and controls (6.7[2.0] vs. 7.1[2.5] cardiac cycles, P = 0.626). Arrival and peak times showed comparable characteristics in patients and controls (P > 0.535). The minimum enhancement rate of the left ventricle was lower in patients than in controls (- 28 +/- 11 vs. - 36 +/- 13 1/(cardiac cycle), P = 0.012). Area under curves, relative blood flow, and other enhancement rates showed no significant differences between patients and controls (P > 0.107). Relative blood flow of cardiac chambers correlated with non-compacted left ventricular volume ratio (P < 0.011). Our results indicate slower washout of contrast agent and blood flow stagnation in the left ventricle of young patients with cryptogenic ischemic stroke. The washout was associated with left ventricular non-compaction, suggesting conditions favoring formation of intraventricular thrombosis.
  • Takahashi, Kohta; Kanerva, Kristiina; Vanharanta, Lauri; Almeida-Souza, Leonardo; Lietha, Daniel; Olkkonen, Vesa M.; Ikonen, Elina (2021)
    Low-density lipoprotein (LDL)-cholesterol delivery from late endosomes to the plasma membrane regulates focal adhesion dynamics and cell migration, but the mechanisms controlling it are poorly characterized. Here, we employed auxin-inducible rapid degradation of oxysterol-binding protein-related protein 2 (ORP2/OSBPL2) to show that endogenous ORP2 mediates the transfer of LDL-derived cholesterol from late endosomes to focal adhesion kinase (FAK)-/integrin-positive recycling endosomes in human cells. In vitro, cholesterol enhances membrane association of FAK to PI(4,5)P-2-containing lipid bilayers. In cells, ORP2 stimulates FAK activation and PI(4,5)P-2 generation in endomembranes, enhancing cell adhesion. Moreover, ORP2 increases PI(4,5)P-2 in NPC1-containing late endosomes in a FAK-dependent manner, controlling their tubulovesicular trafficking. Together, these results provide evidence that ORP2 controls FAK activation and LDL-cholesterol plasma membrane delivery by promoting bidirectional cholesterol/PI(4,5)P-2 exchange between late and recycling endosomes.