1. |
- Fridlund, Bengt, et al.
(author)
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Essentials of Nursing Care in Randomized Controlled Trials of Nurse-Led Interventions in Somatic Care : A Systematic Review
- 2014
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In: Open Journal of Nursing. - Irvine : Scientific Research Publishing. - 2162-5336 .- 2162-5344. ; 4:3, s. 181-197
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Research review (peer-reviewed)abstract
- Background: Nursing practice has to contribute to evidence pointing out why there is a need for more nurse-designed randomized control trials (RCTs) focusing on evidence-based practice (EBP). How far this EBP has progressed in different health aspects is usually established by systematic reviews of RCTs. Nurse-led RCTs exist but no study has addressed the essentials of nursing care. Aim: The aim was therefore to determine the essentials of nurses’ interventions by means of nurse-led RCTs in somatic care focusing on the stated context, goals, content, strategies as well as the nurse’s role related to effectiveness. Methods: A systematic review was realized according to Cochrane review assumptions to identify, appraise and synthesize all empirical evidence meeting pre-specified eligibility criteria. The PRISMA statement guided the data extraction process (n = 55) from PubMed and CINAHL. Results: Of the RCTs in somatic care, 71% showed a positive effectiveness of nurse-led interventions, of which the nurse had a significant role with regard to being the main responsible in 67% of the studies. Also, 47% of the RCTs presented a theoretical standpoint related to the nurse-led interventions and most prominent were international evidence-based guidelines. Goals were found to have either a patient-centered or a professional-centered ambition. Strategies were based on patient-directed initiatives, nurse-patient-directed initiatives or nurse-directed initiatives, while contents were built upon either a patient-nurse interaction or a nursing management plan. Conclusions: This review underlines the necessity of a holistic view of a person, as nurse-led RCTs comprising a patient-centered ambition, patient-directed initiative and patient-nurse interaction plan showed beneficial nursing care effectiveness, particularly if theory-based. In a nurse-led RCT, a basic theoretical perspective is advantageous as well as to elucidate the role of the nurse in relation to the estimated effects.
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3. |
- Ali, Mina, et al.
(author)
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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1649-
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Journal article (peer-reviewed)abstract
- Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
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4. |
- Amisten, Stefan, et al.
(author)
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Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriersof the Thr-87 variant of the ATP receptor P2Y11.
- 2007
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In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 28:1, s. 13-18
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Journal article (peer-reviewed)abstract
- Aims Extracellular ATP acting on the P2Y(11) receptor regulates inflammatory cells. We hypothesized that polymorphisms in the receptor could influence the risk of acute myocardial infarction (AMI). Methods and results In the Malmo diet and cancer AMI case-control study (n = 3732) the P2Y(11) gene Thr-87 polymorphism was present in 19.8% of the controls and 22.9% in AMI patients (OR 1.21; P = 0.03). Stronger associations were found in patients with family history (FH) of AMI, 1.32; early-onset (EO) AMI, 1.43; or EO AMI combined with FH, 1.50; supporting a genetic mechanism. The Thr-87 homozygotes had an even greater risk of AMI, 1.94 (P = 0.04); and 2.48 in the EO AMI subgroup, suggesting a genetic dosage effect. In the cardiovascular risk factor group (n = 6055), 21.3% carried the Thr-87 allele. C-reactive protein was elevated in Thr-87 carriers: 1.6 mg/L vs. 1.3 mg/L (P = 0.001). No difference was seen for blood pressure, lipids, body mass index, smoking, or diabetes mellitus. Conclusion The common Ala-87-Thr polymorphism of the P2Y(11) receptor is associated with AMI and increased levels of C-reactive protein. We hypothesize that an inflammatory mechanism might be involved. The P2Y(11) receptor is a promising new drug target in the prevention of AMI.
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5. |
- Balogh, Johanna, et al.
(author)
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Phospholipase C and cAMP-dependent positive inotropic effects of ATP in mouse cardiomyocytes via P2Y(11)-like receptors.
- 2005
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In: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 1095-8584 .- 0022-2828. ; 39:2, s. 223-230
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Journal article (peer-reviewed)abstract
- ATP is released as a cotransmitter together with catecholamines from sympathetic nerves. In the heart ATP has been shown to cause a pronounced positive inotropic effect and may also act in synergy with β-adrenergic agonists to augment cardiomyocyte contractility. The aim of the present study was to investigate the inotropic effects mediated by purinergic P2 receptors using isolated mouse cardiomyocytes. Stable adenine nucleotide analogs were used and the agonist rank order for adenine nucleotide stimulation of the mouse cardiomyocytes was AR-C67085 > ATPγS > 2-MeSATP >>> 2-MeSADP = 0, that fits the agonist profile of the P2Y11 receptor. ATPγS induced a positive inotropic response in single mouse cardiomyocytes. The response was similar to that for the β1 receptor agonist isoproterenol. The most potent response was obtained using AR-C67085, a P2Y11 receptor agonist. This agonist also potentiated contractions in isolated trabecular preparations. The adenylyl cyclase blocker (SQ22563) and phospholipase C (PLC) blocker (U73122) demonstrated that both pathways were required for the inotropic response of AR-C67085. A cAMP enzyme immunoassay confirmed that AR-C67085 increased cAMP in the cardiomyocytes. These findings are in agreement with the P2Y11 receptor, coupled both to activation of IP3 and cAMP, being a major receptor for ATP induced inotropy. Analyzing cardiomyocytes from desmin deficient mice, Des–/–, with a congenital cardiomyopathy, we found a lower sensitivity to AR-C67085, suggesting a down-regulation of P2Y11 receptor function in heart failure. The prominent action of the P2Y11 receptor in controling cardiomyocyte contractility and possible alterations in its function during cardiomyopathy may suggest this receptor as a potential therapeutic target. It is possible that agonists for the P2Y11 receptor could be used to improve cardiac output in patients with circulatory shock and that P2Y11 receptor antagonist could be beneficial in patients with congestive heart failure (CHF).
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6. |
- Bergdahl, Andreas, et al.
(author)
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Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry.
- 2005
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In: American Journal of Physiology: Cell Physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 288:4, s. 872-880
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Journal article (peer-reviewed)abstract
- Loss of the smooth muscle contractile phenotype is critical in atherosclerosis and in restenosis after angioplasty, but its early signals are incompletely understood. In this study, we have explored the role of transient receptor potential canonical (TRPC) proteins, which have been suggested to mediate store-operated Ca2+ entry (SOCE). Contractility of rat cerebral arteries in organ culture is preserved for several days, whereas SOCE is increased. In correlation with this increase is that nifedipine-insensitive whole cell current, activated by depletion of intracellular Ca2+ stores, was increased by 50% in cells isolated from arteries cultured for 3 days. TRPC1 and TRPC6 mRNA were more than fivefold increased in cells isolated after organ culture, whereas TRPC3 was decreased. Immunofluorescent staining and/or Western blotting of arteries and isolated cells showed upregulation of TRPC1 and TRPC6 proteins during organ culture. In intact arteries, TRPC4 expression correlated with the amount of endothelium present. Ca2+ addition after store depletion caused a contraction in cultured, but not in freshly dissected, arteries. A polyclonal TRPC1 antibody directed against an extracellular epitope inhibited this contraction by approximately 50%. To investigate the basis of the TRPC upregulation and assess its possible clinical significance, segments of human internal mammary artery were organ cultured for 24 h and then exposed to balloon dilatation in vitro, followed by further culturing for up to 48 h. After dilatation, TRPC1 and TRPC6 mRNA were progressively increased compared with undilated control segments. The results of this study indicate that vascular injury enhances plasticity in TRPC expression, that TRPC expression correlates with cellular Ca2+ handling, and that TRPC1 is a subunit of upregulated store-operated Ca2+ channels.
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7. |
- Braun, Oscar, et al.
(author)
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Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y(1) and the P2Y (12) receptor and is correlated with protein expression of P2Y (12).
- 2007
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In: Purinergic Signalling. - : Springer Science and Business Media LLC. - 1573-9546 .- 1573-9538. ; 3:3, s. 195-201
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Journal article (peer-reviewed)abstract
- Two ADP receptors have been identified on human platelets: P2Y(1) and P2Y(12). The P2Y(12) receptor blocker clopidogrel is widely used to reduce the risks in acute coronary syndromes, but, currently, there is no P2Y(1) blocker in clinical use. Evidence for variable responses to clopidogrel has been described in several reports. The mechanistic explanation for this phenomenon is not fully understood. The aim of this study was to examine mechanisms responsible for variability of 2MeS-ADP, a stable ADP analogue, induced platelet reactivity in clopidogrel-treated patients. Platelet reactivity was assessed by flow cytometry measurements of P-selectin (CD62P) and activated GpIIb/IIIa complex (PAC-1). Residual 2MeS-ADP activation via the P2Y(12) and P2Y(1) receptors was determined by co-incubation with the selective antagonists AR-C69931 and MRS2179 in vitro. P2Y(1) and P2Y(12) receptor expression on both RNA and protein level were determined, as well as the P2Y(12) H1 or H2 haplotypes. Our data suggest that the residual platelet activation of 2MeS-ADP after clopidogrel treatment is partly due to an inadequate antagonistic effect of clopidogrel on the P2Y(12) receptor and partly due to activation of the P2Y(1) receptor, which is unaffected by clopidogrel. Moreover, a correlation between increased P2Y(12) protein expression on platelets and decreased response to clopidogrel was noticed, r(2)=0.43 (P<0.05). No correlation was found between P2Y(12) mRNA levels and clopidogrel resistance, indicating post-transcriptional mechanisms. To achieve additional ADP inhibition in platelets, antagonists directed at the P2Y(1) receptor could be more promising than the development of more potent P2Y(12) receptor antagonists.
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8. |
- Ekvall-Hansson, Eva, et al.
(author)
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Satisfaction with rehabilitation in relation to self-perceived quality of life and function among patients with stroke - a 12 month follow-up.
- 2013
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In: Scandinavian Journal of Caring Sciences. - : Wiley. - 1471-6712 .- 0283-9318. ; 27:2, s. 373-379
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Journal article (peer-reviewed)abstract
- Scand J Caring Sci; 2012 Satisfaction with rehabilitation in relation to self-perceived quality of life and function among patients with stroke - a 12 month follow-up Background and Purpose: Stroke causes complex disability and function, and perceived quality of life has been shown to correlate with satisfaction with care as well as with life in general among stroke patients. The aim of this study was to study the relation of satisfaction with how rehabilitation was provided with self-perceived quality of life, self-perceived function and rehabilitation received, 12 months after the incidence. Method: The subjects were assessed 12 months after the onset of stroke. The Barthel index was used to measure function, and the EuroQol-5D to measure quality of life. To measure satisfaction with how rehabilitation was provided, a questionnaire from the Swedish Stroke Register was used. Results: Two hundred and eighty-three patients participated in the follow-up, 137 women and 146 men, aged between 42 and 95 years (mean age 75.2, SD 11.8). For the majority of patients rehabilitation was initiated at in-hospital care (directly after onset). One hundred and sixty-eight patients considered that rehabilitation was well provided for. Sixty-six regarded that the rehabilitation was only partly provided for and 35 that it was not provided for at all. High value on Barthel Index was associated with satisfaction with how rehabilitation was provided for (OR 2.81). Also, rehabilitation on three or more levels was negatively associated with satisfaction with rehabilitation provision (OR 0.24) and so was being male (OR 0.49). Conclusion: In this study, patients with higher values on Barthel Index were more satisfied with how rehabilitation was provided for. However, male patients and patients who received rehabilitation on three or more levels of care were less satisfied. Given the assumption that patients with more severe dysfunction after stroke are being rehabilitated on more levels, this might imply that it is not the amount of rehabilitation that gives satisfaction but the patients self-perceived function after rehabilitation.
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9. |
- Fridlund, Bengt, et al.
(author)
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Essentials of teamcare in randomized controlled trials of multidisciplinary or interdisciplinary interventions in somatic care : A systematic review
- 2015
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In: Open Journal of Nursing. - : Scientific Research Publishing. - 2162-5336 .- 2162-5344. ; 5:12, s. 1089-1101
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Research review (peer-reviewed)abstract
- Background: Teamcare should, like all patient care, also contribute to evidence-based practice (EBP). Randomized controlled trials (RCTs) focusing on teamcare have been performed but no study has addressed its essentials. How far this EBP has progressed in different health aspects is generally established in systematic reviews of RCTs.Aim: The aim is to determine the essentials of teamcare including the nurse profession in RCTs of multi- or interdisciplinary interventions in somatic care focusing on the stated context, goals, strategies, content as well as effectiveness of quality of care.Methods: A systematic review was performed according to Cochrane review assumptions to identify, appraise and synthesize all empirical evidence meeting pre-specified eligibility criteria. The PRISMA statement guided the data selection process of 27 articles from PubMed and CINAHL.Results: Eighty-five percent of RCTs in somatic care showed a positive effectiveness of teamcare interventions, of which interdisciplinary ones showed a greater effectiveness compared with the multidisciplinary approach (100% vs 76%). Also theory-based RCTs presented higher positive effectiveness (85%) compared with non-theory-based RCTs (79%). The RCTs with positive effectiveness showed greater levels for professional-centered ambition in terms of goals and for team-directed initiatives in terms of strategy, and a significantly higher level for patient-team interaction plans in terms of content was shown.Conclusions: Teamcare RCTs are still grounded in the multidisciplinary approach having a professional-centered ambition while interdisciplinary approaches especially those that are theory-based appear to be essential with regard to positive effectiveness and preferable when person-centered careis applied.
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10. |
- Jonsson, Stefan, et al.
(author)
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Identification of sequence variants influencing immunoglobulin levels
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
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Journal article (peer-reviewed)abstract
- Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
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