| 1. |
- in''t Veld, Rianne M. H. A. Huis, et al.
(författare)
-
A scenario guideline for designing new teletreatments: a multidisciplinary approach
- 2010
-
Ingår i: JOURNAL OF TELEMEDICINE AND TELECARE. - : SAGE Publications. - 1357-633X .- 1758-1109. ; 16:6, s. 302-307
-
Tidskriftsartikel (refereegranskat)abstract
- Lack of user acceptance of telemedicine services is an important barrier to deployment and stresses the need for involving users, i.e. medical professionals. However, the involvement of users in the service development process of telemedicine services is difficult because of (a) the knowledge gap between the expertise of medical and technical experts; (b) the language gap, i.e. the use of different terminologies between the medical and the technical professions; and (c) the methodological gap in applying requirement methods to multidisciplinary scientific matters. We have developed a guideline in which the medical and technical domains meet. The guideline can be used to develop a scenario from which requirements can be elicited. In a retrospective analysis of a myofeedback-based teletreatment service, the technically-oriented People-Activities-Context-Technology (PACT) framework and medically-oriented principles of evidence-based medicine were incorporated into a guideline. The guideline was developed to construct the content of a scenario which describes the new teletreatment service. This allows the different stakeholders to come together and develop the service. Our approach provides an arena for different stakeholders to take part in the early stages of the design process. This should increase the chance of user acceptance and thus adoption of the service being developed.
|
|
| 2. |
|
|
| 3. |
- Zdzalik, M., et al.
(författare)
-
Prevalence of genes encoding extracellular proteases in Staphylococcus aureus - important targets triggering immune response in vivo
- 2012
-
Ingår i: Fems Immunology and Medical Microbiology. - 0928-8244. ; 66:2, s. 220-229
-
Tidskriftsartikel (refereegranskat)abstract
- Proteases of Staphylococcus aureus have long been considered to function as important virulence factors, although direct evidence of the role of particular enzymes remains incomplete and elusive. Here, we sought to provide a collective view of the prevalence of extracellular protease genes in genomes of commensal and pathogenic strains of S.aureus and their expression in the course of human and mouse infection. Data on V8 protease, staphopains A and B, aureolysin, and the recently described and poorly characterized group of six Spl proteases are provided. A phylogenetically diverse collection of 167 clinical isolates was analyzed, resulting in the comprehensive genetic survey of the prevalence of protease-encoding genes. No correlation between identified gene patterns with specific infections was established. Humoral response against the proteases of interest was examined in the sera derived from human patients and from a model mouse infection. The analysis suggests that at least some, if not all, tested proteases are expressed and secreted during the course of infection. Overall, the results presented in this study support the hypothesis that the secretory proteases as a group may contribute to the virulence of S.aureus.
|
|
| 4. |
- Brisslert, Mikael, 1974, et al.
(författare)
-
S100A4 regulates the Src-tyrosine kinase dependent differentiation of Th17 cells in rheumatoid arthritis
- 2014
-
Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1842:11, s. 2049-2059
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the role of S100A4, a calcium-binding regulator of nonmuscle myosin assembly, for T-cell responses in rheumatoid arthritis. Methods: Arthritis was induced in the methylated bovine serum albumin (mBSA)-immunized mice lacking the entire S100A4 protein (S100A4KO) and in wild-type counterparts treated with short hairpin ribonucleic acid (shRNA)-lentiviral constructs targeting S100A4 (S100A4-shRNA). The severity of arthritis was evaluated morphologically. T-cell subsets were characterized by the expression of master transcription factors, and functionally by proliferation activity and cytokine production. The activity of the Scr-kinases Fyn and Lck was assessed by the autophosphorylation of C-terminal thyrosine and by the phosphorylation of the CD5 cytodomain. The interaction between S100A4 and the CD5 cytodomain was analysed by nuclear magnetic resonance spectrophotometry. Results: S100A4-deficient mice (S100A4KO and S100A4-shRNA) had significantly alleviated morphological signs of arthritis and joint damage. Leukocyte infiltrates in the arthritic joints of S100A4-deficient mice accumulated Foxp3(+) Treg cells, while the number of ROR gamma t(+) and (pTyr705)STAT3(+) cells was reduced. S100A4-deficient mice had a limited formation of Th17-cells with low retinoic acid orphan receptor gamma t (ROR gamma t) mRNA and IL17 production in T-cell cultures. S100A4-deficient mice had a low expression and activity of T-cell receptor (TCR) inhibitor CD5 and low (pTyr705)STAT3 (signal transducer and activator of transcription 3), which led to increased (pTyr352)ZAP-70 (theta-chain associated protein kinase of 70 kDa), lymphocyte proliferation and production of IL2. In vitro experiments showed that S100A4 directly binds Lck and Fyn and reciprocally regulates their kinase activity towards the CD5 cytodomain. Spectrometry demonstrates an interaction between the CD5 cytodomain and EF2-binding sites of S100A4. Conclusion: The present. study demonstrates that S100A4 plays an important part in the pathogenesis of arthritis. It controls CD5-dependent differentiation of Th17 cells by regulating the activity of the Src-family kinases Lck and Fyn. (C) 2014 Elsevier B.V. All rights reserved.
|
|
| 5. |
- Calander, Ann-Marie, 1957, et al.
(författare)
-
Impact of staphylococcal protease expression on the outcome of infectious arthritis
- 2004
-
Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 202-6
-
Tidskriftsartikel (refereegranskat)abstract
- The exoproteases of Staphylococcus aureus have been proposed as virulence factors during S. aureus infections. To investigate this, we used the wild-type S. aureus strain 8325-4 and its mutants devoid of aureolysin, serine protease, and cysteine protease, respectively, in a well-established model of septic arthritis in mice. The inactivation of the exoprotease genes did not affect the frequency or the severity of joint disease. We conclude that in the model of haematogenously spread staphylococcal arthritis, the bacterial proteases studied do not act as virulence factors.
|
|
| 6. |
- Kenny, John G, et al.
(författare)
-
The Staphylococcus aureus response to unsaturated long chain free fatty acids: survival mechanisms and virulence implications.
- 2009
-
Ingår i: PLoS ONE. ; 4:2
-
Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the sigma(B) and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids.
|
|
| 7. |
- Pizzolla, A., et al.
(författare)
-
Reactive Oxygen Species Produced by the NADPH Oxidase 2 Complex in Monocytes Protect Mice from Bacterial Infections
- 2012
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 188:10, s. 5003-5011
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent life-threatening bacterial and fungal infections. CGD results from defective production of reactive oxygen species by phagocytes caused by mutations in genes encoding the NADPH oxidase 2 (NOX2) complex subunits. Mice with a spontaneous mutation in Ncf1, which encodes the NCF1 (p47(Phox)) subunit of NOX2, have defective phagocyte NOX2 activity. These mice occasionally develop local spontaneous infections by Staphylococcus xylosus or by the common CGD pathogen Staphylococcus aureus. Ncf1 mutant mice were more susceptible to systemic challenge with these bacteria than were wild-type mice. Transgenic Ncf1 mutant mice harboring the wild-type Ncf1 gene under the human CD68 promoter (MN+ mice) gained the expression of NCF1 and functional NOX2 activity specifically in monocytes/macrophages, although minimal NOX2 activity was also detected in some CD11b(+)Ly6G(+) cells defined as neutrophils. MN+ mice did not develop spontaneous infection and were more resistant to administered staphylococcal infections compared with MN- mice. Most strikingly, MN+ mice survived after being administered Burkholderia cepacia, an opportunistic pathogen in CGD patients, whereas MN- mice died. Thus, monocyte/macrophage expression of functional NCF1 protected against spontaneous and administered bacterial infections. The Journal of Immunology, 2012, 188: 5003-5011.
|
|
| 8. |
- Vinnars, Marie-Therese, et al.
(författare)
-
Treatments for hyperemesis gravidarum: A systematic review
- 2024
-
Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 103:1, s. 13-29
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionHyperemesis gravidarum affects 0.3%-3% of pregnant women each year and is the leading cause of hospitalization in early pregnancy. Previous systematic reviews of available treatments have found a lack of consistent evidence, and few studies of high quality. Since 2016, no systematic review has been conducted and an up-to date review is requested. In a recent James Lind Alliance collaboration, it was clear that research on effective treatments is a high priority for both patients and clinicians.Material and methodsSearches without time limits were performed in the AMED, CINAHL, Cochrane Library, EMBASE, Medline, PsycINFO, and Scopus databases until June 26, 2023. Studies published before October 1, 2014 were identified from the review by O'Donnell et al., 2016. Selection criteria were randomized clinical trials and non-randomized studies of interventions comparing treatment of hyperemesis gravidarum with another treatment or placebo. Outcome variables included were: degree of nausea; vomiting; inability to tolerate oral fluids or food; hospital treatment; health-related quality of life, small-for-gestational-age infant; and preterm birth. Abstracts and full texts were screened, and risk of bias of the studies was assessed independently by two authors. Synthesis without meta-analysis was performed, and certainty of evidence was assessed using the GRADE approach. PROSPERO (CRD42022303150).ResultsTwenty treatments were included in 25 studies with low or moderate risk of bias. The certainty of evidence was very low for all treatments except for acupressure in addition to standard care, which showed a possible moderate decrease in nausea and vomiting, with low certainty of evidence.ConclusionsSeveral scientific knowledge gaps were identified. Studies on treatments for hyperemesis gravidarum are few, and the certainty of evidence for different treatments is either low or very low. To establish more robust evidence, it is essential to use validated scoring systems, the recently established diagnostic criteria, clear descriptions and measurements of core outcomes and to perform larger studies. The certainty of evidence according to GRADE (The Grading of Recommendations Assessment, Development and Evaluation) was very low for all treatments of hyperemesis gravidarum except for acupressure in addition to standard care, which showed a possible moderate decrease in nausea and vomiting, with low certainty of evidence.image
|
|
