| 1. |
- Aidoukovitch, Alexandra, et al.
(författare)
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Antimicrobial peptide LL-37 and its pro-form, hCAP18, in desquamated epithelial cells of human whole saliva
- 2020
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Ingår i: European Journal of Oral Sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 128:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- The antimicrobial peptide LL-37 is active against oral bacteria and has been demonstrated to be present in human saliva, but its distribution in different fractions of saliva is not known. LL-37 is formed from its intracellular pro-form, hCAP18, in an extracellular enzymatic reaction catalyzed by proteinase 3 and kallikrein 5. Here, we prepared cell-containing and cell-free fractions of unstimulated human whole saliva by centrifugation after depolymerization of mucins with dithiothreitol, and measured the levels of hCAP18/LL-37 in these fractions using ELISA. Cellular expression of hCAP18/LL-37 was determined by western blotting and immunocytochemistry. The ELISA analyses demonstrated that both cells and cell-free saliva contained hCAP18/LL-37. Western blot analysis of cell-pellet homogenates showed a strong band corresponding to hCAP18 at the correct molecular weight and a weak band corresponding to LL-37. Phase-contrast and light microscopy revealed that the cells consisted of desquamated epithelial cells. These cells expressed cytoplasmic immunoreactivity for hCAP18/LL-37. The peripheral part of the cytoplasm, corresponding to the plasma membrane, was particularly rich in hCAP18/LL-37 immunoreactivity. No immunoreactivity was observed after omission of the primary antibody. We conclude that desquamated epithelial cells of human whole saliva contain antimicrobial hCAP18/LL-37, suggesting that these cells may take part in the innate immune system by harboring and releasing these peptides.
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| 2. |
- Baravdish, George, 1964-, et al.
(författare)
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Generalizations of p-Laplace operator for image enhancement : Part 2
- 2020
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Ingår i: Communications on Pure and Applied Analysis. - Springfield, MO, United States : American Institute of Mathematical Sciences. - 1534-0392 .- 1553-5258. ; 19:7, s. 3477-3500
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Tidskriftsartikel (refereegranskat)abstract
- We have in a previous study introduced a novel elliptic operator Delta((p,q))u = vertical bar del u vertical bar(q) Delta(1)u + (p - 1) vertical bar del u vertical bar(p-2)Delta(infinity) u, p >= 1, q >= 0, as a generalization of the p-Laplace operator. In this paper, we establish the well-posedness of the parabolic equation u(t) =vertical bar del u vertical bar(1-q) Delta((1+q,q)), where q = q(vertical bar del u vertical bar) is continuous and has range in [0, 1], in the framework of viscosity solutions. We prove the consistency and convergence of the numerical scheme of finite differences of this parabolic equation. Numerical simulations shows the advantage of this operator applied to image enhancement.
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| 3. |
- Dahl, Sara, et al.
(författare)
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Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells
- 2020
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 69:6, s. 579-588
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The importance of human host defense peptide LL-37 in vascular innate immunity is not understood. Here, we assess the impact of LL-37 on double-stranded RNA (dsRNA) signaling in human vascular smooth muscle cells.MATERIALS AND METHODS: Cellular import of LL-37 and synthetic dsRNA (poly I:C) were investigated by immunocytochemistry and fluorescence imaging. Transcript and protein expression were determined by qPCR, ELISA and Western blot. Knockdown of TLR3 was performed by siRNA.RESULTS: LL-37 was rapidly internalized, suggesting that it has intracellular actions. Co-stimulation with poly I:C and LL-37 enhanced pro-inflammatory IL-6 and MCP-1 transcripts several fold compared to treatment with poly I:C or LL-37 alone. Poly I:C increased IL-6 and MCP-1 protein production, and this effect was potentiated by LL-37. LL-37-induced stimulation of poly I:C signaling was not associated with enhanced import of poly I:C. Treatment with poly I:C and LL-37 in combination increased expression of dsRNA receptor TLR3 compared to stimulation with poly I:C or LL-37 alone. In TLR3 knockdown cells, treatment with poly I:C and LL-37 in combination had no effect on IL-6 and MCP-1 expression, showing loss of function.CONCLUSIONS: LL-37 potentiates dsRNA-induced cytokine production through up-regulation of TLR3 expression representing a novel pro-inflammatory mechanism.
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| 4. |
- Hendrikse, Natalie M., et al.
(författare)
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Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia
- 2020
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Phenylalanine/tyrosine ammonia-lyases (PAL/TALs) have been approved by the FDA for treatment of phenylketonuria and may harbour potential for complementary treatment of hereditary tyrosinemia Type I. Herein, we explore ancestral sequence reconstruction as an enzyme engineering tool to enhance the therapeutic potential of PAL/TALs. We reconstructed putative ancestors from fungi and compared their catalytic activity and stability to two modern fungal PAL/TALs. Surprisingly, most putative ancestors could be expressed as functional tetramers in Escherichia coli and thus retained their ability to oligomerize. All ancestral enzymes displayed increased thermostability compared to both modern enzymes, however, the increase in thermostability was accompanied by a loss in catalytic turnover. One reconstructed ancestral enzyme in particular could be interesting for further drug development, as its ratio of specific activities is more favourable towards tyrosine and it is more thermostable than both modern enzymes. Moreover, long-term stability assessment showed that this variant retained substantially more activity after prolonged incubation at 25 °C and 37 °C, as well as an increased resistance to incubation at 60 °C. Both of these factors are indicative of an extended shelf-life of biopharmaceuticals. We believe that ancestral sequence reconstruction has potential for enhancing the properties of enzyme therapeutics, especially with respect to stability. This work further illustrates that resurrection of putative ancestral oligomeric proteins is feasible and provides insight into the extent of conservation of a functional oligomerization surface area from ancestor to modern enzyme.
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| 5. |
- Nilsson, Niklas, et al.
(författare)
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The economic cost and patient-reported outcomes of chronic Achilles tendon ruptures.
- 2020
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Ingår i: Journal of experimental orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- While most Achilles tendon ruptures are dramatic and diagnosed quickly, some are missed, with a risk of becoming chronic. A chronic Achilles tendon rupture is defined as a rupture that has been left untreated for more than 4 weeks. By mapping the health economic cost of chronic Achilles tendon ruptures the health-care system might be able to better distribute resources to detect these ruptures at an earlier time.All patients with a chronic Achilles tendon rupture who were treated surgically at Sahlgrenska University Hospital or Kungsbacka Hospital between 2013 and 2018 were invited to participate in the study. The patients were evaluated postoperatively using the validated Achilles tendon Total Rupture Score (ATRS). The health-care costs were assessed using clinical records. The production-loss costs were extracted from the Swedish Social Insurance Agency. The cost of chronic Achilles tendon ruptures was then compared with the cost of acute ruptures in a previous study by Westin et.al.Forty patients with a median (range) age of 66 (28-86) were included in the study. The mean total cost (± SD) for the patients with a chronic Achilles tendon rupture was 6494 EUR ± 6508, which is 1276 EUR higher than the mean total cost of acute ruptures. Patients with chronic Achilles tendon ruptures reported a mean (min-max) postoperative ATRS of 73 (14-100).Missing an Achilles tendon rupture will entail higher health-care costs compared with acute ruptures. Health-care resources can be saved if Achilles tendon ruptures are detected at an early stage.
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| 6. |
- Steingrimsson, Steinn, et al.
(författare)
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Electroencephalography-based neurofeedback as treatment for post-traumatic stress disorder: A systematic review and meta-analysis
- 2020
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Royal College of Psychiatrists. - 1778-3585. ; 63:1
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND.: Post-traumatic stress disorder (PTSD) is debilitating for patients and society. There are a number of treatment methods albeit not all patients respond to these and an interesting method using electroencephalography-based neurofeedback (EEG-NF) has become more prominent in recent years. This systematic review aimed to assess whether EEG-NF, compared with sham NF, other treatment, or no treatment, is effective for PTSD. Primary outcomes were self-harm, PTSD symptoms, level of functioning and health-related quality of life. METHODS.: Systematic literature searches for randomized controlled trials (RCTs) were conducted in six databases. Random effects meta-analysis was performed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. RESULTS.: Four RCTs were included (123 participants). Suicidal thoughts were significantly reduced after EEG-NF compared with a waiting list in a small study. PTSD symptoms were assessed in all studies with different instruments. Results were consistently in favor of EEG-NF with large effect sizes (standardized mean difference -2.30 (95% confidence interval: -4.37 to -0.24). One study reported significantly improved level of executive functioning and one study a reduction in use of psychotropic medication. Complications were scarcely reported. Certainty of evidence was assessed as very low for the four assessed outcomes. CONCLUSIONS.: Based on four RCTs, with several study limitations and imprecision, it is uncertain whether EEG-NF reduces suicidal thoughts, PTSD symptoms, medication use, or improves function. Although all studies showed promising results, further studies are needed to increase the certainty of evidence.
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| 7. |
- Svensson, Karin, et al.
(författare)
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Exchange of Modular Components Improves Success of Debridement, Antibiotics, and Implant Retention: An Observational Study of 575 Patients with Infection After Primary Total Hip Arthroplasty
- 2020
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Ingår i: JB & JS open access. - : The Journal of Bone and Joint Surgery Inc.. - 2472-7245. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Debridement, antibiotics, and implant retention (DAIR) is a surgical treatment for periprosthetic joint infection (PJI). DAIR is a desirable treatment option from an economic and patient perspective, if successful. The aim of this observational study was to compare the rates of success, defined as no additional reoperations due to PJI, between DAIR with exchange of modular components and DAIR without exchange in patients who had first-time PJI after primary total hip arthroplasty (THA).Methods: Patients with PJI at the site of a primary THA who were treated with DAIR in Sweden between January 1, 2009, and December 31, 2016, were identified in the Swedish Hip Arthroplasty Register. Supplementary questionnaires were sent to orthopaedic departments for additional variables of interest related to PJI. The primary end point was another reoperation due to PJI within 2 years after the first-time DAIR. DAIR with exchange was compared with DAIR without exchange using Kaplan-Meier survival analysis and Cox regression analysis.Results: A total of 575 patients treated with DAIR for a first-time PJI at the site of a primary THA were analyzed; 364 underwent component exchange and 211 did not. The exchange of components was associated with a lower rate of reoperations due to PJI after DAIR (28.0%) compared with non-exchange (44.1%). The Kaplan-Meier implant survival estimate for exchange was 71.4% (95% confidence interval [CI] = 66.9% to 76.3%) compared with 55.5% (95% CI = 49.1% to 62.7%) for non-exchange. With the analysis adjusted for confounders, DAIR with exchange was associated with a significantly decreased risk of another reoperation due to PJI compared with non-exchange (hazard ratio [HR] = 0.51 [95% CI = 0.38 to 0.68]).Conclusions: In patients with a first-time PJI at the site of a primary THA, DAIR with exchange of modular components was superior to non-exchange DAIR. Surgeons should strive to exchange components when they perform DAIR, but there is a need to further identify how DAIR best should be practiced and which patients benefit from it.Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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| 8. |
- Åberg, N David, 1970, et al.
(författare)
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Circulating levels of vascular endothelial growth factor and post-stroke long-term functional outcome
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:5, s. 405-14
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Vascular endothelial growth factor (VEGF) acts in angiogenesis and neuroprotection, although the beneficial effects on experimental ischemic stroke (IS) have not been replicated in clinical studies. We investigated serum VEGF (s-VEGF) in the acute stage (baseline) and 3 months post-stroke in relation to stroke severity and functional outcome. Methods The s-VEGF and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in patients enrolled in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) at the acute time-point (median 4 days, N = 492, 36% female; mean age, 57 years) and at 3 months post-stroke (N = 469). Baseline stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes (3 months and 2 years) were evaluated using the modified Rankin Scale (mRS), dichotomized into good (mRS 0-2), and poor (mRS 3-6) outcomes. Multivariable logistic regression analyses were adjusted for covariates. Results The baseline s-VEGF did not correlate with stroke severity but correlated moderately with hs-CRP (r = .17, P < .001). The baseline s-VEGF was 39.8% higher in total anterior cerebral infarctions than in lacunar cerebral infarctions. In binary logistic regression analysis, associations with 3-month functional outcome were non-significant. However, an association between the 3-month s-VEGF and poor 2-year outcome withstood adjustments for age, sex, cardiovascular covariates, and stroke severity (per 10-fold increase in s-VEGF, odds ratio [OR], 2.56, 95% confidence interval [CI] 1.12-5.82) or hs-CRP (OR 2.53, CI 1.15-5.55). Conclusions High 3-month s-VEGF is independently associated with poor 2-year functional outcome but not with 3-month outcome.
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