| 1. |
- Ericsson, Hans, et al.
(författare)
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The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food
- 2012
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 98:3, s. 436-444
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
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| 3. |
- Mu, Yabing, et al.
(författare)
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TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer
- 2011
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Ingår i: Nature Communications. - London : Macmillan Publishers Limited. - 2041-1723. ; 2:330
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Sotak, Matus, et al.
(författare)
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Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity.
- 2021
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Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 267
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery.We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls.Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before Roux-en-Y gastric bypass (RYGB) were lower than in lean individuals, but substantially upregulated 6 months post-RYGB.Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.
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| 5. |
- Spante, Maria, 1967-, et al.
(författare)
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Unlock the rigidity and design for flexibility
- 2010
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Ingår i: US-China Education Review. - : David Publishing Company. - 1548-6613. ; 7:11, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports findings from a project implementing the VL (virtual labs) site featuringflash-based animations developed at Stanford University. The main conclusion in this paper stresses the need todesign for flexibility and adaptability of interactive media to better suit the specific situation teachers encounter intheir everyday work, in order to allow them to build their own audiovisual presentation kits based on variousavailable resources. Ambitious but rigid visualization products might otherwise end up not being used at all.
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| 6. |
- Tardocchi, M., et al.
(författare)
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Modeling of neutron emission spectroscopy in JET discharges with fast tritons from (T)D ion cyclotron heating
- 2006
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 77:12
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of fast ion populations is one of the diagnostic capabilities provided by neutron emission spectroscopy (NES). NES measurements were carried out during JET trace tritium campaign with the magnetic proton recoil neutron spectrometer. A favorable plasma scenario is (T)D where the resulting 14 MeV neutron yield is dominated by suprathermal emission from energetic tritons accelerated by radio frequency at their fundamental cyclotron frequency. Information on the triton distribution function has been derived from NES data with a simple model based on two components referred to as bulk (B) and high energy (HE). The HE component is based on strongly anisotropic tritium distribution that can be used for routine best-fit analysis to provide tail temperature values (T-HE). This article addresses to what extent the T-HE values are model dependent by comparing the model above with a two-temperature (bi-) Maxwellian model featuring parallel and perpendicular temperatures. The bi-Maxwellian model is strongly anisotropic and frequently used for radio frequency theory.
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| 7. |
- Aengerud, Karin Hellstroem, et al.
(författare)
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Symptoms of Acute Myocardial Infarction as Described in Calls to Tele-Nurses and in Questionnaires A Mixed-Methods Study
- 2023
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Ingår i: Journal of Cardiovascular Nursing. - : LIPPINCOTT WILLIAMS & WILKINS. - 0889-4655 .- 1550-5049. ; 38:2, s. 150-157
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatient-reported symptoms of acute myocardial infarction (MI) may be affected by recall bias depending on when and where symptoms are assessed.AimThe aim of this study was to gain an understanding of patients symptom description in more detail before and within 24 hours after a confirmed MI diagnosis.MethodsA convergent parallel mixed-methods design was used to examine symptoms described in calls between the tele-nurse and the patient compared with symptoms selected by the patient from a questionnaire less than 24 hours after hospital admission. Quantitative and qualitative data were analyzed separately and then merged into a final interpretation.ResultsThirty patients (median age, 67.5 years; 20 men) were included. Chest pain was the most commonly reported symptom in questionnaires (24/30). Likewise, in 19 of 30 calls, chest pain was the first complaint mentioned, usually described together with the symptom onset. Expressions used to describe symptom quality were pain, pressure, discomfort, ache, cramp, tension, and soreness. Associated symptoms commonly described were pain or numbness in the arms, cold sweat, dyspnea, weakness, and nausea. Bodily sensations, such as feeling unwell or weak, were also described. Fear and tiredness were described in calls significantly less often than reported in questionnaires (P = .01 and P = .02), whereas "other" symptoms were more often mentioned in calls compared with answers given in the questionnaire (P = .02). Some symptoms expressed in the calls were not listed in the questionnaire, which expands the understanding of acute MI symptoms. The results showed no major inconsistencies between datasets.ConclusionPatients MI symptom descriptions in tele-calls and those reported in questionnaires after diagnosis are comparable and convergent.
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| 8. |
- Alm, Fredrik, 1983-, et al.
(författare)
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Adherence to Swedish guidelines for pain treatment in relation to pediatric tonsil surgery : A survey of the multidisciplinary team
- 2017
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Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier. - 0165-5876 .- 1872-8464. ; 101, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- Background: 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 tonsilloperation.se, were developed and implemented in 2013.Objectives 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.Method: 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.Results: 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 tonsilloperation.se to provide information to the patients and their caregivers.Conclusion: 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.
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| 9. |
- Andersson Sundén, Erik, et al.
(författare)
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Evaluation of neutron spectrometer techniques for ITER using synthetic data
- 2013
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 701, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- A neutron spectrometer at ITER is expected to provide estimates of plasma parameters such as ion temperature, Ti, fuel ion ratio, nt/nd, and Qthermal/Qtot, with 10-20% precision at a time resolution, Δt, 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 Ti 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 Δt in the determination of Ti varies in time scales from ms (for the magnetic and thin-foil proton recoil) to s (for gamma discriminating organic scintillator).
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| 10. |
- Andersson Sundén, Erik, et al.
(författare)
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Instrumentation for neutron emission spectrometry in use at JET
- 2010
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 623:2, s. 681-685
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Tidskriftsartikel (refereegranskat)abstract
- The present contribution discusses two neutron spectrometers: the time-of-flight spectrometer (TOFOR) and the magnetic proton recoil spectrometer (MPRu). TOFOR uses fast plastic scintillators equipped with digital time-stamping electronics to register the time of each eligible scintillation event. The time trace for each detector is acquired practically dead-time free. The detectors of the MPRu are of phoswich type and each detector is connected to a digital transient recorder card that stores the full waveform for an event. By using phoswich detectors, pulse-shape discrimination techniques can be applied offline to distinguish signal events from background. A future upgrade of TOFOR could be digital “hybrid” cards, which store correlated time and waveform information. This information can be used to decrease the background level in the ttof spectrum, thereby increasing the operating range.
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