| 1. |
- Abdelmagid, N., et al.
(författare)
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Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.
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| 2. |
- Ericsson, Leon, et al.
(författare)
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Generalized super-resolution 4D Flow MRI - using ensemble learning to extend across the cardiovascular system
- 2024
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Ingår i: IEEE journal of biomedical and health informatics. - 2168-2194 .- 2168-2208. ; , s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- 4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was therefore to explore the generalizability of SR 4D Flow MRI using a combination of existing super-resolution base models, novel heterogeneous training sets, and dedicated ensemble learning techniques; the latter-most being effectively used for improved domain adaption in other domains or modalities, however, with no previous exploration in the setting of 4D Flow MRI. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with the novel use of ensemble learning in the setting of advanced fullfield flow imaging extending utility across various clinical areas of interest.
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| 3. |
- Hellkvist, L., et al.
(författare)
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High dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase
- 2022
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:3, s. 883-96
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Tidskriftsartikel (refereegranskat)abstract
- Background The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. Methods Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated. Results Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. Conclusion Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.
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| 4. |
- Kerekes, Nora, 1969-, et al.
(författare)
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The associations between ADHD, pain, inflammation, and quality of life in children and adolescents-a clinical study protocol
- 2022
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9 September
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Tidskriftsartikel (refereegranskat)abstract
- New research shows that the prevalence of neurodevelopmental disorders, such as attention- deficit/hyperactivity disorder (ADHD), is increased in children and adolescents as well as in adults with chronic pain, compared to those without chronic pain. Children and adolescents with ADHD also have an increased incidence of various physical conditions associated with pain, and they more frequently suffer from inflammatory diseases. Moreover, parents of children with ADHD can often suffer from pain conditions. These epidemiological and clinical observations form the scientific basis of our study, which aims to map the relationships between ADHD, altered pain experiences/central sensitization, and inflammation in children and adolescents. We will investigate the presence of central sensitization in children and adolescents with newly diagnosed ADHD and compare it with those who have not been diagnosed with ADHD. Participants (and their biological parents) will complete surveys about their somatic health, pain experience, and quality of life. Biological samples (saliva and stool) will be collected, aiming to utilize proteome and metabolome data to discover disease mechanisms and to predict, prevent and treat them. The results from our investigation should enable an expanded understanding of the pathophysiology behind both ADHD and pain/central sensitization. Presently, there are no established protocols for addressing psychiatric symptoms when examining patients with pain conditions in a somatic care setting, nor is there any knowledge of offering patients with ADHD or other neurodevelopmental disorders adapted treatments for pain conditions. Our results, therefore, can contribute to the development of new treatment strategies for pathological pain conditions in children and adolescents with ADHD. They may also increase awareness about and provide opportunities for the treatment of attention and impulse control problems in children and adolescents with pain syndromes. © 2022 Kerekes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 5. |
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| 6. |
- Ciarimboli, Giuliano, et al.
(författare)
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Dynamic alterations of glomerular charge density in fixed rat kidneys suggest involvement of endothelial cell coat
- 2003
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Ingår i: Am J Physiol Renal Physiol.. ; 285:4
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Tidskriftsartikel (refereegranskat)abstract
- In a previous paper, we found that low ionic strength (I) reversibly reduced the glomerular charge density, suggesting increased volume of the charge-selective barrier. Because glutaraldehyde makes most structures rigid, we considered the isolated, perfusion-fixed rat kidney to be an ideal model for further analysis. The fixed kidneys were perfused with albumin solutions containing FITC-Ficoll at two different Is (I = 151 and 34 mM). At normal I, the fractional clearance () for albumin was 0.0049 (SE -0.0017, +0.0027, n = 6), whereas for neutral Ficoll35.5A of similar size was significantly higher 0.104 (SE 0.010, n = 5, P < 0.001). At low I, for albumin was 0.0030 (SE -0.0011, +0.0018, n = 6, not significant from albumin at normal I) and for Ficoll35.5A was identical to that at normal I, 0.104 (SE 0.015, n = 6, P < 0.01 compared with albumin at low I). According to a heterogeneous charged fiber model, low I reduced the fiber density from 0.056 to 0.0315, suggesting a 78% gel volume expansion. We conclude that 1) there is a significant glomerular charge barrier. 2) Solutions with low I increase the volume of the charge barrier even in kidneys fixed with glutaraldehyde. Our findings suggest that polysaccharide-rich structures, such as the endothelial cell coat, are key components in the glomerular barrier.
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| 10. |
- Hjalmarsson, Lars, 1958, et al.
(författare)
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Material degradation in implant-retained cobalt-chrome and titanium frameworks.
- 2011
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Ingår i: Journal of oral rehabilitation. - : Wiley. - 1365-2842 .- 0305-182X. ; 38:1, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to estimate in vitro material degradation in implants and cobalt-chrome or titanium frameworks, before and after exposure to artificial saliva. Four full-arch implant frameworks were fabricated according to the Cresco™ method (Astra Tech AB, Mölndal, Sweden), two in a cobalt-chrome alloy and two in commercially pure (CP) titanium. They were cut vertically, and the three central sections of each framework were used. Element leakage into an artificial saliva solution was observed with mass spectrometry. Before artificial saliva exposure, three Brånemark System(®) implants (Nobel Biocare AB, Gothenburg, Sweden) were screw-retained to cobalt-chrome sections, and three to titanium sections. The contact surfaces with the implants of the framework sections and the corresponding surfaces of six implants were examined with optical interferometry before and after exposure to artificial saliva to evaluate material degradation. Conventional descriptive statistics were used to present the mass spectrometry and interferometry data. One-way anova and Dunnett's T3 post hoc test were used to identify and study differences between the groups. To highlight changes within the groups, the Student's t-test was used. The significance level was set at 5%. There was significantly more leakage of cobalt elements than of titanium and chrome (P < 0·05). After saliva exposure and framework connection, the implants roughened (P < 0·05). The titanium frameworks were generally rougher than the cobalt-chrome frameworks, both before and after saliva exposure (P < 0·05). The findings in this study suggest active material degradation processes for both implants and framework materials.
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