| 11. |
- Baudet, Aurélie, et al.
(författare)
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Small Molecule Screening of Primary Human Acute Myeloid Leukemia Using Co-culture and Multiplexed FACS Analysis
- 2022
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Ingår i: Bio-protocol. - 2331-8325. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Ex vivo culture of primary acute myeloid leukemia (AML) cells is notoriously difficult due to spontaneous differentiation and cell death, which hinders mechanistic and translational studies. To overcome this bottleneck, we have implemented a co-culture system, where the OP9-M2 stromal cells support the growth, but most notably limit the differentiation of primary AML cells, thus allowing for mechanistic studies in vitro. Additionally, the co-culture on OP9-M2 stromal is superior in preserving surface marker expression of primary (adult and pediatric) AML cells in comparison to stroma-free culture. Thus, by combining the co-culture with multicolor, high-throughput FACS, we can evaluate the effect of hundreds of small molecules on multi-parametric processes including: cell survival, stemness (leukemic stem cells), and myeloid differentiation on the primary AML cells at a single-cell level. This method streamlines the identification of potential therapeutic agents, but also facilitates combinatorial screening aiming, for instance, at dissecting the regulatory pathways in a patient-specific manner.
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| 12. |
- Bergstrand, Sara, 1978-
(författare)
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Preventing pressure ulcers by assessment of the microcirculation in tissue exposed to pressure
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to combine optical methods into a system with the ability to simultaneously measure blood flow changes at different tissue depths. The goal of such a system was to reveal vascular mechanisms relevant to pressure ulcer etiology under clinically relevant conditions and in relation to the evaluation of pressure-redistribution support surfaces.This thesis consists of four quantitative, cross-sectional studies measuring blood flow responses before, during, and after pressure exposure of the sacral tissue. Two optical methods – photoplethysmography and laser Doppler flowmetry – were combined in a newly developed system that has the ability to discriminate blood flows at different tissue depths. Studies I and II explored blood flow responses at different depths in 17 individuals. In Study I the blood flow was related to tissue thickness and tissue compression during pressure exposure of ≥ 220 mmHg. In Study II, the sacral tissue was loaded with 37.5 mmHg and 50.0 mmHg, and the variation in blood flow was measured. Studies III and IV included 42 healthy individuals < 65 years, 38 healthy individuals ≥ 65 years, and 35 patients ≥ 65 years. Study III included between-subject comparisons of blood flow and pressure between individuals in the three study groups lying in supine positions on a standard hospital mattress. Study IV added within-subject comparisons while the individual was lying on four different types of mattress. The studies explored the vascular phenomena pressure-induced vasodilation (PIV) and reactive hyperemia (RH).The most common blood flow response to tissue exposure in this thesis was PIV, although a decrease in blood flow (a lack of PIV) was observed in some individuals. The patients tended to have higher interface pressure during pressure exposure than the healthy groups but no differences in blood flow responses were seen. Our results showed that pressure levels that are normally considered to be harmless could have a significant effect on the microcirculation in different tissue structures. Differences in individual blood flow responses in terms of PIV and RH were seen, and a larger proportion of individuals lacked these responses in the deeper tissue structures compared to more superficial tissue structures.This thesis identified PIV and RH that are important vascular mechanisms for pressure ulcer development and revealed for the first time that PIV and RH are present at different depths under clinically relevant conditions. The thesis also identified a population of individuals not previously identified who lack both PIV and RH and seem to be particularly vulnerable to pressure exposure. Further, this thesis has added a new perspective to the microcirculation in pressure ulcer etiology in terms of blood flow regulation and endothelial function that are anchored in clinically relevant studies. Finally, the evaluation of pressureredistribution support surfaces in terms of mean blood flow during and after tissue exposure was shown to be unfeasible, but the assessment of PIV and RH could provide a new possibility for measuring individual physiological responses that are known to be related to pressure ulcer development.
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| 13. |
- Björck, Fredrik, et al.
(författare)
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Warfarin persistence among atrial fibrillation patients – why is treatment ended?
- 2016
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Ingår i: Cardiovascular Therapeutics. - : Wiley. - 1755-5914. ; 34:6, s. 468-474
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Tidskriftsartikel (refereegranskat)abstract
- Background and AimWarfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). Studies mainly focused on whether the proportion of warfarin persistence and discontinuationare clinically appropriate are absent. This study evaluates warfarin persistence with focus on predictors for, and reasons to, warfarin discontinuation in AF patients.MethodsFrom the national quality register AuriculA, all AF patients in Sundsvall, Sweden, on warfarin treatment on January first, 2010 were included. These 478 patients were followed until discontinuation or study-stop December 31, 2013. By going through each patient’s medical record risk factors for thromboembolism, bleeding and causes of discontinuation were obtained.ResultsProportion of warfarin persistence was 0.91 (95% confidence interval (CI) 0.89 to 0.93) after one year and 0.73 (95% CI 0.69 to 0.77) after four years. Previous intracranial bleeding, excessive alcohol use, anemia and pulmonary or peripheral emboli were each associated with over two times higher risk of discontinuation (hazard ratio (HR) 5.66, CI 2.23-14.36, HR 2.54, CI 1.48-4.37, HR 2.40, CI 1.38-4.17, and HR 2.13, CI 1.02-4.46). Among patients discontinuing, 50.5% were due to questionable causes, such as sinus rhythm (33.9%), patients demand (10.1%) and falls (8.2%). The majority (43.1%) of treatment discontinuers were changed to aspirin, while 40.4% of them were left without medical stroke prophylaxis.ConclusionsAlthough persistence to warfarin among AF patients proves higher than previously reported, there is room for improvement since half of the discontinuers have questionable reasons for treatment stop and the majority of them receive no other efficient stroke prophylaxis.
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| 14. |
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| 15. |
- Bohgard, Mats, et al.
(författare)
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Pedagogisk förändring av arbetsvetenskapskurser i några olika utbildningsprogram vid LTH
- 2003
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Ingår i: Pedagogisk inspirationskonferens LTH 27 maj 2003. - Lund : Lunds tekniska högskola, Lunds universitet. ; , s. 14-17
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Konferensbidrag (refereegranskat)abstract
- Vi har genomfört genomgripande förändringar i obligatoriska grundkurser i arbetsvetenskap. Förändringarna har genomförts som en utvecklingsprocess i vilken samtliga lärare som deltagit i kurserna har medverkat. Processen startade med konsulthjälp från Universitetspedagogiskt centrum vid Lunds universitet, fortsatte med kompetensutveckling av oss själva och följdes av några utvecklingsprojekt, varefter från grunden förändrade kurser genomfördes under fyra år. Den nya uppläggningen medförde att vi fick positiva attityder i studentenkäterna när det gällde två av kurserna i årskurs 2 i vilken medodiken genomfördes fullständigt. I en kurs, som gavs i årskurs 1 och i vilken den nya uppläggningen endast delvis genomfördes blev studentattityderna negativa.
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| 16. |
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| 17. |
- Campos-Rodriguez, Carolina, et al.
(författare)
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Enantiomeric N-substituted phthalimides with excitatory amino acids protect zebrafish larvae against PTZ-induced seizures
- 2020
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 888
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Tidskriftsartikel (refereegranskat)abstract
- Epilepsy is a chronic neurological disease with high prevalence and adverse impacts on the quality of life of patients and caregivers. Up to one-third of individuals with epilepsy do not respond to current pharmacotherapy, underscoring the importance of identifying new molecules for epilepsy control. Thalidomide, the first synthetized phthalimide, is a neuroactive molecule with anti-seizure drug properties. The phthalimide group has been studied in some N-phthaloyl amino acids due to its pharmacological properties. Here we examine enantiomers of phthaloyl aspartate (R and S) and phthaloyl glutamate (R and S) for anti-seizure effects using zebrafish as a model. The zebrafish model is rapidly growing in use as a preclinical screening tool for drug discovery in epilepsy. Pentylenetetrazol (PTZ) exposure was used to produce convulsive behavior in 7- and 10-days post-fertilization (dpf) zebrafish larvae; these ages correspond to before and after the blood-brain-barrier (BBB) is fully developed. Larvae were pre-treated for 60 min with: control, valproic acid sodium salt (SVP) 3 mM, or one of two concentrations of N-phthaloyl-R-glutamic acid (R-TGLU; 100, 316 μM) prior to PTZ addition. R-TGLU modified the locomotor phenotype and protected against PTZ in 7 and 10 dpf larvae at 316 μM, suggesting it crossed the BBB. We next tested the per se and anticonvulsant effect of the glutamate and aspartate phthalimides were tested at 237.1 and 316 μM concentration in 10dpf zebrafish. The four tested molecules produced an anticonvulsant effect at 237.1 μM concentration, however the behavioral changes that they induce suggest that they might act by different mechanisms.
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| 18. |
- Carlsson, Fredrik, 1968, et al.
(författare)
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All it takes is one: The effect of weakest-link and summation aggregation on public good provision under threshold uncertainty
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We report experimental evidence on the voluntary provision of public goods under threshold uncertainty. By explicitly comparing two prominent technologies, summation and weakest link, we show that uncertainty is particularly detrimental to threshold attainment under weakest link, where low contributions by one subject cannot be compensated by others. In contrast, threshold uncertainty does not affect contributions under summation. We demonstrate non-binding pledges as one mechanism to improve chances of threshold attainment under both technologies, yet in particular under weakest link.
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| 19. |
- Carlsson, Fredrik, 1968, et al.
(författare)
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One bad apple spoils the barrel? Public good provision under threshold uncertainty
- 2024
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Ingår i: EXPERIMENTAL ECONOMICS. - 1386-4157 .- 1573-6938. ; 27:3, s. 664-686
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Tidskriftsartikel (refereegranskat)abstract
- We report laboratory evidence on the voluntary provision of threshold public goods when the exact location of the threshold is not known. Our experimental treatments explicitly compare two prominent technologies, summation, and weakest link. Uncertainty in threshold location is particularly detrimental to threshold attainment under weakest link, where low contributions by one subject cannot be compensated by others. In contrast, threshold uncertainty does not affect contributions under summation. We demonstrate that non-binding pledges improve the chances of threshold attainment under both technologies, particularly under weakest link.
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| 20. |
- Dash, Pujarini, et al.
(författare)
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High PGD2 receptor 2 levels are associated with poor prognosis in colorectal cancer patients and induce VEGF expression in colon cancer cells and migration in a zebrafish xenograft model
- 2022
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 126:4, s. 586-597
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite intense research, the prognosis for patients with advanced colorectal cancer (CRC) remains poor. The prostaglandin D2 receptors DP1 and DP2 are explored here as potential therapeutic targets for advanced CRC. Methods: A CRC cohort was analysed to determine whether DP1 and DP2 receptor expression correlates with patient survival. Four colon cancer cell lines and a zebrafish metastasis model were used to explore how DP1/DP2 receptor expression correlates with CRC progression. Results: Analysis of the clinical CRC cohort revealed high DP2 expression in tumour tissue, whereas DP1 expression was low. High DP2 expression negatively correlated with overall survival. Other pathological indicators, such as TNM stage and metastasis, positively correlated with DP2 but not DP1 expression. In accordance, the in vitro results showed high DP2 expression in four CC-cell lines, but only one expressed DP1. DP2 stimulation resulted in increased proliferation, p-ERK1/2 and VEGF expression/secretion. DP2-stimulated cells exhibited increased migration in the zebrafish metastasis model. Conclusion: Our results support DP2 receptor expression and signalling as a therapeutic target in CRC progression based on its expression in CRC tissue correlating with poor patient survival and that it triggers proliferation, p-ERK1/2 and VEGF expression and release and increased metastatic activity in CC-cells.
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