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- Kiviniemi, T., et al.
(författare)
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A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery––LAA-CLOSURE trial protocol
- 2021
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 237, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation. © 2021 The Author(s)
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| 18. |
- Airaksinen, Anu J., et al.
(författare)
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Massive Online Open Course „Essential Radiochemistry for Society“
- 2023
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Ingår i: Chemicke Listy. - 1213-7103 .- 0009-2770. ; 117:11, s. 708-713
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Tidskriftsartikel (refereegranskat)abstract
- The massive open online course "Essential radio-chemistry for society" represents a modern form of education. Due to its attractive design, varied content and inter-active nature, it has the potential to appeal to various inter-est groups. Thematically, the course is divided into five weeks: Radiochemistry for the environment, health, indus-try, nuclear energy and society. In addition to radiochem-istry and nuclear chemistry, which are the basis of the course, direct connections can be found to biology, phys-ics, ecology, art and culture. The course is comprehensive; a participant can study only selected chapters or the entire course independently. Recommendations and tips for ef-fectively using the course in classes have been compiled for teachers and lecturers.
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| 19. |
- Kurko, TAT, et al.
(författare)
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Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - a systematic review of register-based studies
- 2015
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 1778-3585. ; 30:8, s. 1037-1047
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNumerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. Despite this, long-term BZD use remains a controversial subject in clinical patient care with “for and against” debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD.MethodsSystematic review of register-based studies on long-term BZD use published in 1994–2014.ResultsFourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as “long-term” varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13–36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31–64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found.ConclusionsLong-term BZD use is common and a clinical reality. Uniform definitions for “long-term”, which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use.
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- Negrin, Maddalena, et al.
(författare)
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A MOOC in Nuclear- and Radio-Chemistry: from the design to the feedback
- 2023
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Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - : Springer Science and Business Media LLC. - 0236-5731 .- 1588-2780. ; 332:5, s. 1549-1555
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the loss of expertise in the nuclear- and radio-chemistry (NRC) is becoming an issue of concern, because of few engaging curricula and career prospects. To counteract this trend, the Massive Open Online Course “Essential Radiochemistry for Society” has been developed with the intent of letting young students in scientific matters discover all the benefits of NRC to society and improving their awareness of these disciplines. The MOOC development process as well as the feedbacks collected in the first MOOC editions are analyzed by highlighting strong points and weakness of the followed strategy.
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- Rivera, C, et al.
(författare)
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BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion
- 2002
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 159:5, s. 747-752
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Tidskriftsartikel (refereegranskat)abstract
- Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl- regulation, which can lead to a suppression of fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases neuronal excitability through a conjunction of mechanisms that include regulation of the efficacy of GABAergic transmission. Here, we show that exposure of rat hippocampal slice cultures and acute slices to exogenous BDNF or neurotrophin-4 produces a TrkB-mediated fall in the neuron-specific K+-Cl- cotransporter KCC2 mRNA and protein, as well as a consequent impairment in neuronal Cl- extrusion capacity. After kindling-induced seizures in vivo, the expression of KCC2 is down-regulated in the mouse hippocampus with a spatio-temporal profile complementary to the up-regulation of TrkB and BDNF. The present data demonstrate a novel mechanism whereby BDNF/TrkB signaling suppresses chloride-dependent fast GABAergic inhibition, which most likely contributes to the well-known role of TrkB-activated signaling cascades in the induction and establishment of epileptic activity.
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| 27. |
- Vermeulen, Roel, et al.
(författare)
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Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma : univariate and functionally informed multivariate analyses
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:6, s. 1335-1347
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Tidskriftsartikel (refereegranskat)abstract
- Recent prospective studies have shown that dysregulation of the immune system may precede the development of B‐cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case–control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01–15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor‐2 (FGF‐2 p = 7.2 × 10−4) and transforming growth factor alpha (TGF‐α, p = 6.5 × 10−5) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF‐2 (p = 7.8 × 10−7), TGF‐α (p = 4.08 × 10−5), fractalkine (p = 1.12 × 10−3), monocyte chemotactic protein‐3 (p = 1.36 × 10−4), macrophage inflammatory protein 1‐alpha (p = 4.6 × 10−4) and vascular endothelial growth factor (p = 4.23 × 10−5). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case‐only analyses showed that Granulocyte‐macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth‐factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL.
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| 28. |
- Wolfensberger, Saskia P, et al.
(författare)
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Quantification of the neurokinin 1 receptor ligand [¹¹C]R116301
- 2011
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Ingår i: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 32:10, s. 896-902
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Recently, it was shown that, in the human brain, a specific NK1 receptor-related signal was obtained with the novel radioligand, [¹¹C]R116301, using positron emission tomography. The purpose of this study was to evaluate various methods for quantifying specific [¹¹C]R116301 binding.METHODS:Two dynamic 90-min [¹¹C]R116301 scans, separated by 5 h, were performed in 11 healthy volunteers. In three patients, the second scan was performed after an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no intervention was performed (test-retest). Whole striatum was used as the tissue of interest, as it has the highest density of NK1 receptors. Cerebellum was used as the reference tissue.RESULTS:Reference tissue models were stable with the simplified reference tissue model (SRTM) performing best. Average (± standard deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all (first) baseline scans was 0.64±0.31 (n=11), which reduced to -0.01±0.03 (n=3) after aprepitant administration. Test-retest results showed low variability (14.0±10.7%) and excellent reliability, as indicated by the intraclass correlation coefficient (0.93). The ratio of standardized uptake values of striatum and cerebellum minus 1, an approximation of BP(ND), showed very low variability (6.2±3.1%) with excellent reliability (intraclass correlation coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R²=0.96).CONCLUSION:SRTM is the model of choice for quantifying [¹¹C]R116301 binding. Semiquantitative tissue ratios hold promise for routine clinical applications.
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| 33. |
- Airaksinen, P J, et al.
(författare)
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Visual field and retinal nerve fibre layer in early glaucoma after optic disc haemorrhage
- 1983
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Ingår i: Acta Ophthalmologica. - : Wiley. - 0001-639X .- 1755-375X. ; 61:2, s. 94-186
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Tidskriftsartikel (refereegranskat)abstract
- Computerized visual field testing with the Competer automatic perimeter including automatic profile perimetry revealed early glaucomatous field loss in 9 of 10 eyes with photographically demonstrable retinal nerve fibre layer (RNFL) defects after optic disc haemorrhages despite the fact than conventional routine perimetry had failed to do so. In 7 of these cases the Competer central pattern test was abnormal; in 2 cases field defects could be shown only when automatic high-resolution static profile perimetry was performed and directed according to the information present in wide-angle RNFL photographs. A field defect was also found in one of five eyes with no photographic RNFL changes. Visual field defects seem to occur in a higher proportion of cases with RNFL defects than was previously thought, but they can be very subtle and hard to find. There are, however, cases where in spite of the presence of an indisputable RNFL defect no visual field defects can be shown even with painstaking technique and conversely field defects may be present without RNFL defects. Automatic perimetry and RNFL photography complement each other in early detection and quantitation of glaucomatous damage.
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| 34. |
- Berger, Eloise, et al.
(författare)
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Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma : Findings from two prospective cohorts
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and Β-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = -1.28, p = 0.012), and, to lesser, extent with BC (β = -0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.
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- Chatziioannou, Aristotelis, et al.
(författare)
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Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.
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- Moghadam, Saeed Montazeri, et al.
(författare)
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An automated bedside measure for monitoring neonatal cortical activity : a supervised deep learning-based electroencephalogram classifier with external cohort validation
- 2022
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Ingår i: The Lancet Digital Health. - : Elsevier. - 2589-7500. ; 4:12, s. E884-E892
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Tidskriftsartikel (refereegranskat)abstract
- Background Electroencephalogram (EEG) monitoring is recommended as routine in newborn neurocritical care to facilitate early therapeutic decisions and outcome predictions. EEG's larger-scale implementation is, however, hindered by the shortage of expertise needed for the interpretation of spontaneous cortical activity, the EEG background. We developed an automated algorithm that transforms EEG recordings to quantified interpretations of EEG background and provides simple intuitive visualisations in patient monitors. Methods In this method-development and proof-of-concept study, we collected visually classified EEGs from infants recovering from birth asphyxia or stroke. We used unsupervised learning methods to explore latent EEG characteristics, which guided the supervised training of a deep learning-based classifier. We assessed the classifier performance using cross-validation and an external validation dataset. We constructed a novel measure of cortical function, brain state of the newborn (BSN), from the novel EEG background classifier and a previously published sleep-state classifier. We estimated clinical utility of the BSN by identification of two key items in newborn brain monitoring, the onset of continuous cortical activity and sleep-wake cycling, compared with the visual interpretation of the raw EEG signal and the amplitude-integrated (aEEG) trend. Findings We collected 2561 h of EEG from 39 infants (gestational age 35 center dot 0-42 center dot 1 weeks; postnatal age 0-7 days). The external validation dataset included 105 h of EEG from 31 full-term infants. The overall accuracy of the EEG background classifier was 92% in the whole cohort (95% CI 91-96; range 85-100 for individual infants). BSN trend values were closely related to the onset of continuous EEG activity or sleep-wake cycling, and BSN levels showed robust difference between aEEG categories. The temporal evolution of the BSN trends showed early diverging trajectories in infants with severely abnormal outcomes. Interpretation The BSN trend can be implemented in bedside patient monitors as an EEG interpretation that is intuitive, transparent, and clinically explainable. A quantitative trend measure of brain function might harmonise practices across medical centres, enable wider use of brain monitoring in neurocritical care, and might facilitate clinical intervention trials. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.
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| 47. |
- Nakigudde, J., et al.
(författare)
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An exploratory study on the feasibility and appropriateness of family psychoeducation for postpartum women with psychosis in Uganda
- 2013
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Ingår i: BMC Psychiatry. - 1471-244X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: We explored how family psychoeducation could be made culturally sensitive for postpartum mothers with psychotic illness in a Ugandan setting.Methods: A qualitative multi-method approach using an already existing family psychoeducation Tool Kit was adapted to incorporate lay perceptions related to psychotic illness in the postpartum period in this Ugandan setting. The participants consisted of postpartum women with psychotic illness, caregivers/family members, psychiatric nurses and psychologists. A modified version of a family psychoeducation programme for postpartum women with psychosis was formulated and pilot-tested.Results: Modifications in the standard family psychoeducation programme were both in the process and content of family psychoeducation. Under process, effective communication, cultural background, appropriate dress, involving only one family member, low literacy, and flexibility in timekeeping were raised. The theme of content yielded the incorporation of lay perceptions of mental illness, family planning, income generating, and an emphasis of premorbid and morbid personalities of the patients.Conclusion: The basic principles and assumptions underlying psychoeducation remained the same. Changes made in the process and content of family psychoeducation reflected the social, cultural and gender reality of the population. © 2013 Nakigudde et al.; licensee BioMed Central Ltd.
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