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  • Hansson, Sara F., et al. (författare)
  • Secretagogin is increased in plasma from type 2 diabetes patients and potentially reflects stress and islet dysfunction
  • 2018
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Beta cell dysfunction accompanies and drives the progression of type 2 diabetes mellitus (T2D), but there are few clinical biomarkers available to assess islet cell stress in humans. Secretagogin, a protein enriched in pancreatic islets, demonstrates protective effects on beta cell function in animals. However, its potential as a circulating biomarker released from human beta cells and islets has not been studied. In this study primary human islets, beta cells and plasma samples were used to explore secretion and expression of secretagogin in relation to the T2D pathology. Secretagogin was abundantly and specifically expressed and secreted from human islets. Furthermore, T2D patients had an elevated plasma level of secretagogin compared with matched healthy controls, which was confirmed in plasma of diabetic mice transplanted with human islets. Additionally, the plasma secretagogin level of the human cohort had an inverse correlation to clinical assessments of beta cell function. To explore the mechanism of secretagogin release in vitro, human beta cells (EndoC-[beta H1) were exposed to elevated glucose or cellular stress-inducing agents. Secretagogin was not released in parallel with glucose stimulated insulin release, but was markedly elevated in response to endoplasmic reticulum stressors and cytokines. These findings indicate that secretagogin is a potential novel biomarker, reflecting stress and islet cell dysfunction in T2D patients.</p>
  • Ericsson, Hans, et al. (författare)
  • The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food
  • 2012
  • Ingår i: Diabetes Research and Clinical Practice. - Elsevier. - 0168-8227 .- 1872-8227. ; 98:3, s. 436-444
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Aims: To investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1 day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM). less thanbrgreater than less thanbrgreater thanMethods: This was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180 mg) or placebo in the fasted or fed states (both n = 8). In Part B, patients (n = 8) received placebo and a total dose of AZD6370 180 mg given in one, two or four divided doses. Plasma glucose, insulin and C-peptide changes versus placebo were assessed. less thanbrgreater than less thanbrgreater thanResults: AZD6370 provided dose-dependent reductions in plasma glucose of up to 30% versus placebo in both fasted and fed patients (p andlt; 0.001 at 60 and 180 mg doses). Insulin secretion increased with dose, but absolute increases were relatively small in the fasted versus fed state (0-4 h). Dosing AZD6370 twice or four-times over 1 day gave a smoother 24-h glucose profile than single-dose. AZD6370 was rapidly absorbed. Pharmacokinetics of AZD6370 were dose-independent and unaffected by food. AZD6370 was generally well tolerated. less thanbrgreater than less thanbrgreater thanConclusions: AZD6370 produced dose-dependent glucose reductions and increased glucose-stimulated insulin secretion in patients with T2DM.</p>
  • Mu, Yabing, et al. (författare)
  • TRAF6 ubiquitinates TGF beta type I receptor to promote its cleavage and nuclear translocation in cancer
  • 2011
  • Ingår i: Nature Communications. - London : Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 2:330, s. 11
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Transforming growth factor beta (TGF beta) is a pluripotent cytokine promoting epithelial cell plasticity during morphogenesis and tumour progression. TGF beta binding to type II and type I serine/threonine kinase receptors (T beta RII and T beta RI) causes activation of different intracellular signaling pathways. T beta RI is associated with the ubiquitin ligase tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). Here we show that TGF beta, via TRAF6, causes Lys63-linked polyubiquitination of T beta RI, promoting cleavage of T beta RI by TNF-alpha converting enzyme (TACE), in a PKC zeta-dependent manner. The liberated intracellular domain (ICD) of T beta RI associates with the transcriptional regulator p300 to activate genes involved in tumour cell invasiveness, such as Snail and MMP2. Moreover, TGF beta-induced invasion of cancer cells is TACE- and PKC zeta-dependent and the T beta RI ICD is localized in the nuclei of different kinds of tumour cells in tissue sections. Thus, our data reveal a specific role for T beta RI in TGF beta mediated tumour invasion.</p>
  • Mu, Yabing, et al. (författare)
  • TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer
  • 2011
  • Ingår i: Nature Communications. - Macmillan Publishers Limited. - 2041-1723 .- 2041-1723. ; 2:330
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Transforming growth factor β (TGFβ) is a pluripotent cytokine promoting epithelial cell plasticity during morphogenesis and tumour progression. TGFβ binding to type II and type I serine/threonine kinase receptors (TβRII and TβRI) causes activation of different intracellular signaling pathways. TβRI is associated with the ubiquitin ligase tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). Here we show that TGFβ, via TRAF6, causes Lys63-linked polyubiquitination of TβRI, promoting cleavage of TβRI by TNF-alpha converting enzyme (TACE), in a PKCζ-dependent manner. The liberated intracellular domain (ICD) of TβRI associates with the transcriptional regulator p300 to activate genes involved in tumour cell invasiveness, such as Snail and MMP2. Moreover, TGFβ-induced invasion of cancer cells is TACE- and PKCζ- dependent and the TβRI ICD is localized in the nuclei of different kinds of tumour cells in tissue sections. Thus, our data reveal a specific role for TβRI in TGFβ mediated tumour invasion.</p>
  • Spante, Maria, 1967-, et al. (författare)
  • Unlock the rigidity and design for flexibility
  • 2010
  • Ingår i: US-China Education Review. - David Publishing Company. - 1548-6613. ; 7:11, s. 44-52
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>This paper reports findings from a project implementing the VL (virtual labs) site featuring</p><p>flash-based animations developed at Stanford University. The main conclusion in this paper stresses the need to</p><p>design for flexibility and adaptability of interactive media to better suit the specific situation teachers encounter in</p><p>their everyday work, in order to allow them to build their own audiovisual presentation kits based on various</p><p>available resources. Ambitious but rigid visualization products might otherwise end up not being used at all. </p>
  • Alm, Fredrik, 1983-, et al. (författare)
  • Adherence to Swedish guidelines for pain treatment in relation to pediatric tonsil surgery : A survey of the multidisciplinary team
  • 2017
  • Ingår i: Effective postoperative pain management in children after tonsil surgery: barriers and possible solutions. - Elsevier.
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background:</strong> Pain management in children after tonsil surgery is essential, and optimal pain treatment has been discussed for many years. Data from the National Tonsil Register in Sweden (NTRS) and a national mapping system have demonstrated the need for national pain treatment guidelines for pediatric tonsil surgery. As a result, Swedish national guidelines, together with updated patient information on the website <em>tonsilloperation.se</em>, were developed and implemented in 2013.</p><p><strong>Objectives </strong>The objective of this study was to evaluate the professionals’ opinions of and adherence to pain treatment guidelines for pediatric tonsil surgery patients in a two-year follow-up.</p><p><strong>Method:</strong> This descriptive cross-sectional study was based on data from an inter-professional questionnaire, which was validated by an expert group using a content validity index (S-CVI 0.93). The questionnaire was sent to all Swedish ear, nose and throat (ENT) departments (n=49) that the NTRS identified as performing tonsil surgery on children younger than 18 years of age. In each clinic, we asked for responses from staff in each of the following professions: ENT physicians, anesthesia physicians, registered nurse anesthetists, and registered nurses in the ENT departments.</p><p><strong>Results</strong>: Respondents from 48 ENT departments participated, and 139/163 (85%) completed questionnaires were returned. The guidelines were reported as being clear, ensuring patient safety and providing optimal pharmacological treatment. Treatment was given according to the guidelines: Half of the departments gave pre- or intraoperative treatment with clonidine, betamethasone and high-dose paracetamol (acetaminophen). A multimodal pain approach (paracetamol and COX inhibitors) after hospital discharge was prescribed by all departments after tonsillectomy and, more extensively, after tonsillotomy. One-third of the departments prescribed paracetamol with a higher normal dose for the first three postoperative days. Half of the departments prescribed rescue analgesics, clonidine or opioids after tonsillectomy. None of the departments prescribed codeine or tramadol, drugs that are discouraged in the guidelines. The majority of the departments used the website <em>tonsilloperation.se</em> to provide information to the patients and their caregivers.</p><p><strong>Conclusio</strong>n: The respondents' opinions of and the ENT departments adherence to the Swedish national guidelines were considered to be good. The national implementation process in Sweden has impacted the manner in which ENT departments treat pain after tonsil surgery.</p>
  • Alm, Fredrik, 1983-, et al. (författare)
  • Adherence to Swedish Guidelines for Pain Treatment in Tonsil Surgery in Pediatric Patients
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • <p><strong>Objective:</strong> As shown by data from the National Tonsil Surgery Register in Sweden, tonsil surgery often causes severe pain that lasts for many days. The register data demonstrate the necessity for better evidence-based pain treatment guidelines for tonsil surgery. The guidelines, introduced in 2013, consist of both pharmacological and non-pharmacological recommendations. In the guidelines, a multimodal analgesic approach and combination of analgesics are recommended to provide effective pain treatment with limited side effects. Two national multi-professional education days on pain, pharmacology and the guidelines were offered. Web-based information about pharmacological treatment (www.tonsililloperation.se) was designed for patients and next-of-kin. The current aims were to describe adherence to the Swedish guidelines for pain treatment in tonsil surgery in pediatric patients &lt; 18 years</p><p><strong>Method: </strong>An inter-professional questionnaire was developed, including questions linked to the relevant guidelines. The questions came from a national mapping before the guidelines were designed. The items were discussed by an expert group, and content validity was evaluated using the content validity index.ENT-and anesthesia physicians and nurses from all 50 ENT clinics in Sweden were enrolled.</p><p><strong>Results: </strong>Most clinics had received the guidelines, but there was a discrepancy between the professions. More than half had perused the literature review performed before the guidelines were designed, and attended themulti-professional education day. Pre- and perioperative treatment usually included paracetamol, clonidine and betamethasone. A multimodal pain approach after discharge from hospital (tonsillectomy and tonsillotomy) was used, combining paracetamol with cox-inhibitors. Most clinics used paracetamol, with a higher dose for the first 3 days (healthy children and acceptable nutrition), and a reduced dose from day 4.In case of inadequate analgesia after tonsillectomy, oral clonidine or opioids were used. Several clinics followed the recommendation to use clonidine as first choice and secondly an opioid. No respondents prescribed codeine compared to 80% at the mapping before the guidelines were designed. The guidelines were experienced as clear, safe and sufficient. The web-based information was used by most of the clinics to improve quality of care and provide facilitating tools for patients, relatives and caregivers.</p><p><strong>Conclusion:</strong> Swedish guidelines for tonsil surgery provide practical evidence-based pain treatment recommendations. To achieve a change, multi-professional education is necessary. This needs to be repeated for a wider spread.</p><p>Future research should include evaluation through pain diaries and questionnaires to next-of-kin and children. There should be matching of data from the quality registers at each clinic, with pain variables such as unplanned health care contacts due to pain, number of days with analgesics, and return to normal diet</p>
  • Andersson Sundén, Erik, et al. (författare)
  • Evaluation of neutron spectrometer techniques for ITER using synthetic data
  • 2013
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A : Accelerators, Spectrometers, Detectors and Associated Equipment. - 0168-9002 .- 1872-9576. ; 701, s. 62-71
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>A neutron spectrometer at ITER is expected to provide estimates of plasma parameters such as ion temperature, <em>T</em><sub>i</sub>, fuel ion ratio, <em>n</em><sub>t</sub>/<em>n</em><sub>d</sub>, and <em>Q</em><sub>thermal</sub><em>/Q</em><sub>tot</sub>, with 10-20% precision at a time resolution, <em>Δt</em>, of at least 100 ms. The present paper describes a method for evaluating different neutron spectroscopy techniques based on their instrumental response functions and synthetic measurement data. We include five different neutron spectrometric techniques with realistic response functions, based on simulations and measurements where available. The techniques are magnetic proton recoil, thin-foil proton recoil, gamma discriminating organic scintillator, diamond and time-of-flight. The reference position and line of sight of a high resolution neutron spectrometer on ITER are used in the study. ITER plasma conditions are simulated for realistic operating scenarios. The ITER conditions evaluated are beam and radio frequency heated and thermal deuterium-tritium plasmas. Results are given for each technique in terms of the estimated time resolution at which the parameter determination can be made within the required precision (here 10% for <em>T</em><sub>i</sub> and the relative intensities of NB and RF emission components). It is shown that under the assumptions made, the thin-foil techniques out-perform the other spectroscopy techniques in practically all measurement situations. For thermal conditions, the range of achieved <em>Δt</em> in the determination of <em>T</em><sub>i</sub> varies in time scales from ms (for the magnetic and thin-foil proton recoil) to s (for gamma discriminating organic scintillator).</p>
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