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- Jantti, H, et al.
(författare)
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Human PSEN1 Mutant Glia Improve Spatial Learning and Memory in Aged Mice
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:24
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Tidskriftsartikel (refereegranskat)abstract
- The PSEN1 ΔE9 mutation causes a familial form of Alzheimer’s disease (AD) by shifting the processing of amyloid precursor protein (APP) towards the generation of highly amyloidogenic Aβ42 peptide. We have previously shown that the PSEN1 ΔE9 mutation in human-induced pluripotent stem cell (iPSC)-derived astrocytes increases Aβ42 production and impairs cellular responses. Here, we injected PSEN1 ΔE9 mutant astrosphere-derived glial progenitors into newborn mice and investigated mouse behavior at the ages of 8, 12, and 16 months. While we did not find significant behavioral changes in younger mice, spatial learning and memory were paradoxically improved in 16-month-old PSEN1 ΔE9 glia-transplanted male mice as compared to age-matched isogenic control-transplanted animals. Memory improvement was associated with lower levels of soluble, but not insoluble, human Aβ42 in the mouse brain. We also found a decreased engraftment of PSEN1 ΔE9 mutant cells in the cingulate cortex and significant transcriptional changes in both human and mouse genes in the hippocampus, including the extracellular matrix-related genes. Overall, the presence of PSEN1 ΔE9 mutant glia exerted a more beneficial effect on aged mouse brain than the isogenic control human cells likely as a combination of several factors.
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- Malm, Carl Johan, et al.
(författare)
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Dual or single antiplatelet therapy after coronary surgery for acute coronary syndrome (TACSI trial): Rationale and design of an investigator-initiated, prospective, multinational, registry-based randomized clinical trial
- 2023
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 259, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investor-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG.
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- Deiktakis, Eleftherios E., et al.
(författare)
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Impact of add-back FSH on human and mouse prostate following gonadotropin ablation by GnRH antagonist treatment
- 2022
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Ingår i: Endocrine Connections. - 2049-3614. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: During androgen ablation in prostate cancer by the standard gonadotropin-releasing hormone (GnRH) agonist treatment, only luteinizing hormone (LH) is permanently suppressed while circulating follicle-stimulating hormone (FSH) rebounds. We explored direct prostatic effects of add-back FSH, after androgen ablation with GnRH antagonist, permanently suppressing both gonadotropins. Methods: The effects of recombinant human (rFSH) were examined in mice treated with vehicle (controls), GnRH antagonist degarelix (dgx), dgx + rFSH, dgx + flutamide, or dgx + rFSH + flutamide for 4 weeks. Prostates and testes size and expression of prostate-specific and/or androgen-responsive genes were measured. Additionally, 33 young men underwent dgx-treatment. Seventeen were supplemented with rFSH (weeks 1–5), and all with testosterone (weeks 4–5). Testosterone, gondotropins, prostate-specific antigen (PSA), and inhibin B were measured. Results: In dgx and dgx + flutamide treated mice, prostate weight/body weight was 91% lower than in controls, but 41 and 11%, respectively, was regained by rFSH treatment (P = 0.02). The levels of seminal vesicle secretion 6, Pbsn, Nkx3.1, beta-microseminoprotein, and inhibin b were elevated in dgx + rFSH-treated animals compared with only dgx treated (all P < 0.05). In men, serum inhibin B rose after dgx treatment but was subsequently suppressed by testosterone. rFSH add-back had no effect on PSA levels. Conclusions: These data provide novel evidence for the direct effects of FSH on prostate sizand gene expression in chemically castrated mice. However, in chemically castrated men, FSH had no effect on PSA production. Whether FSH effects on the prostate in humans also require suppression of the residual adrenal-derived androgens and/or a longer period of rFSH stimulation, remains to be explored.
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- Gremyr, Andreas, et al.
(författare)
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Using Complexity Assessment to Inform the Development and Deployment of a Digital Dashboard for Schizophrenia Care: Case Study
- 2020
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 22:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health care is becoming more complex. For an increasing number of individuals, interacting with health care means addressing more than just one illness or disorder, engaging in more than one treatment, and interacting with more than one care provider. Individuals with severe mental illnesses such as schizophrenia are disproportionately affected by this complexity. Characteristic symptoms can make it harder to establish and maintain relationships. Treatment failure is common even where there is access to effective treatments, increasing suicide risk. Knowledge of complex adaptive systems has been increasingly recognized as useful in understanding and developing health care. A complex adaptive system is a collection of interconnected agents with the freedom to act based on their own internalized rules, affecting each other. In a complex health care system, relevant feedback is crucial in enabling continuous learning and improvement on all levels. New technology has potential, but the failure rate of technology projects in health care is high, arguably due to complexity. The Nonadoption, Abandonment, and challenges to Scale-up, Spread, and Sustainability (NASSS) framework and complexity assessment tool (NASSS-CAT) have been developed specifically to help identify and manage complexity in technology-related development projects in health care. Objective: This study aimed to use a pilot version of the NASSS-CAT instrument to inform the development and deployment of a point-of-care dashboard supporting schizophrenia care in west Sweden. Specifically, we report on the complexity profile of the project, stakeholders' experiences with using NASSS-CAT, and practical implications. Methods: We used complexity assessment to structure data collection and feedback sessions with stakeholders, thereby informing an emergent approach to the development and deployment of the point-of-care dashboard. We also performed a thematic analysis, drawing on observations and documents related to stakeholders' use of the NASSS-CAT to describe their views on its usefulness. Results: Application of the NASSS framework revealed different types of complexity across multiple domains, including the condition, technology, value proposition, organizational tasks and pathways, and wider system. Stakeholders perceived the NASSS-CAT tool as useful in gaining perspective and new insights, covering areas that might otherwise have been neglected. Practical implications derived from feedback sessions with managers and developers are described. Conclusions: This case study shows how stakeholders can identify and plan to address complexities during the introduction of a technological solution. Our findings suggest that NASSS-CAT can bring participants a greater understanding of complexities in digitalization projects in general.
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- Habbouche, S., et al.
(författare)
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Comparison of the novel WEst coast System for Triage (WEST) with Rapid Emergency Triage and Treatment System (RETTS (c)): an observational pilot study
- 2022
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Ingår i: International Journal of Emergency Medicine. - : Springer Science and Business Media LLC. - 1865-1372 .- 1865-1380. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Most Swedish emergency departments (ED) use the triage system Rapid Emergency Triage and Treatment System (RETTS (c)), which over time has proven to prioritize patients to higher triage levels. When many patients are prioritized to high triage levels, challenges with identifying true high-risk patients and increased waiting time for these patients has emerged. In order to achieve a more balanced triage in relation to actual medical risk, the triage system WEst coast System for Triage (WEST) was developed, based on the South African Triage Scale (SATS). The aim of this study was to perform an initial evaluation of the novel emergency triage system WEST compared to the existing RETTS (c). Methods Both RETTS (c) and WEST are five level triage systems illustrated by colors. Nurses from each of the three adult EDs of Sahlgrenska University Hospital in Gothenburg and the ambulance service assessed and triaged 1510 patients according to RETTS (c) and immediately thereafter filled out the WEST triage form. Data from each triage report were analyzed and grouped according to the triage color, chief complaint, and outcome of each patient. Data on discharge categories and events within 72 h were also collected. Data were analyzed with descriptive statistical methods. Results In general, WEST displayed lower levels of prioritization compared to RETTS (c), with no observed impact on patients' medical outcomes. In RETTS (c) orange triage level, approximately 50% of the patients were down prioritized in WEST to yellow or green triage levels. Also, in the RETTS (c) yellow triage level, more than 55% were down prioritized to green triage level in WEST. The number of patients who experienced a serious event during the first 72 h was few. Three patients died, these were all prioritized to red triage level in RETTS (c). In WEST two of these patients were prioritized to red triage level and one to orange triage level. All these patients were admitted to hospital before deterioration. Conclusions WEST may reduce over prioritization at the ED, especially in the orange and yellow triage levels of RETTS (c), with no observed increase in medical risk. WEST can be recommended for a clinical comparative study.
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