| 1. |
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| 2. |
- Hänzelmann, Sonja, et al.
(författare)
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Thrombin stimulates insulin secretion via protease-activated receptor-3.
- 2015
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Ingår i: Islets. - : Informa UK Limited. - 1938-2022 .- 1938-2014. ; 7:4, s. 1118195-1118195
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Tidskriftsartikel (refereegranskat)abstract
- The disease mechanisms underlying type 2 diabetes (T2D) remain poorly defined. Here we aimed to explore the pathophysiology of T2D by analyzing gene co-expression networks in human islets. Using partial correlation networks we identified a group of co-expressed genes ('module') including F2RL2 that was associated with glycated hemoglobin. F2Rl2 is a G-protein-coupled receptor (GPCR) that encodes protease-activated receptor-3 (PAR3). PAR3 is cleaved by thrombin, which exposes a 6-amino acid sequence that acts as a 'tethered ligand' to regulate cellular signaling. We have characterized the effect of PAR3 activation on insulin secretion by static insulin secretion measurements, capacitance measurements, studies of diabetic animal models and patient samples. We demonstrate that thrombin stimulates insulin secretion, an effect that was prevented by an antibody that blocks the thrombin cleavage site of PAR3. Treatment with a peptide corresponding to the PAR3 tethered ligand stimulated islet insulin secretion and single β-cell exocytosis by a mechanism that involves activation of phospholipase C and Ca(2+) release from intracellular stores. Moreover, we observed that the expression of tissue factor, which regulates thrombin generation, was increased in human islets from T2D donors and associated with enhanced β-cell exocytosis. Finally, we demonstrate that thrombin generation potential in patients with T2D was associated with increased fasting insulin and insulinogenic index. The findings provide a previously unrecognized link between hypercoagulability and hyperinsulinemia and suggest that reducing thrombin activity or blocking PAR3 cleavage could potentially counteract the exaggerated insulin secretion that drives insulin resistance and β-cell exhaustion in T2D.
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| 3. |
- Krizhanovskii, Camilla, et al.
(författare)
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EndoC-beta H1 cells display increased sensitivity to sodium palmitate when cultured in DMEM/F12 medium
- 2017
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Ingår i: Islets. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 9:3, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Aims - Human pancreatic islets are known to die in response to the free fatty acid of sodium palmitate when cultured in vitro. This is in contrast to EndoC-beta H1 cells, which in our hands are not sensitive to the cell death-inducing effects sodium palmitate, making these cells seemingly unsuitable for lipotoxicity studies. However, the EndoC-beta H1 cells are routinely cultured in a nutrient mixture based on Dulbecco's Modified Eagle Medium (DMEM), which may not be the optimal choice for studies dealing with lipotoxicity. The aim of the present investigation was to define culture conditions that render EndoC-beta H1 cells sensitive to toxic effects of sodium palmitate. Methods - EndoC-beta H1 cells were cultured at standard conditions in either DMEM or DMEM/F12 culture medium. Cell death was analyzed using propidium iodide staining and flow cytometry. Insulin release and content was quantified using a human insulin ELISA. Results - We presently observe that substitution of DMEM for a DMEM/Ham's F12 mixture (50%/50% vol/vol) renders the cells sensitive to the apoptotic effects of sodium palmitate and sodium palmitate + high glucose leading to an increased cell death. Supplementation of the DMEM culture medium with linoleic acid partially mimicked the effect of DMEM/F12. Culture of EndoC-beta H1 cells in DMEM/F12 resulted also in increased proliferation, ROS production and insulin contents, but markers for metabolic stress, autophagy or amyloid deposits were unaffected. Conclusions - The culture conditions for EndoC-beta H1 cells can be modified so these cells display signs of lipotoxicity in response to sodium palmitate.
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| 4. |
- Lundberg, Marcus, et al.
(författare)
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Expression profiles of stress-related genes in islets from donors with progressively impaired glucose metabolism
- 2018
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Ingår i: Islets. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 10:2, s. 69-79
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Tidskriftsartikel (refereegranskat)abstract
- It is currently unknown how the islet transcriptional pattern changes as glucose metabolism deteriorates and progresses to fulminant type 2 diabetes (T2D). In this study, we hypothesized that islets from donors with elevated HbA1c levels, but not yet diagnosed with T2D, would show signs of cell stress on a transcriptional level. Laser capture microdissection and qPCR arrays including 330 genes related to mitochondria, oxidative stress, or the unfolded protein response were used to extract and analyze islets from organ donors with HbA1c <5.5% (37mmol/mol), elevated HbA1c (6.0-6.5% (42-48mmol/mol)), high HbA1c (>6.5% (48mmol/mol)) or established T2D. Principal component analysis and hierarchical clustering based on the expression of all 330 genes displayed no obvious separation of the four different donor groups, indicating that the inter-donor variations were larger than the differences between groups. However, 44 genes were differentially expressed (P < 0.05, false discovery rate <30%) between islets from donors with HbA1c <5.5% (37mmol/mol) compared with islets from T2D subjects. Twelve genes were differentially expressed compared to control islets in both donors with established T2D and donors with elevated HbA1c (6.0-6.5% (42-48mmol/mol)). Overexpressed genes were related mainly to the unfolded protein response, whereas underexpressed genes were related to mitochondria. Our data on transcriptional changes in human islets retrieved by LCM from high-quality biopsies, as pre-diabetes progresses to established T2D, increase our understanding on how islet stress contributes to the disease development.
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| 5. |
- Stenwall, Anton, et al.
(författare)
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Characterization of host defense molecules in the human pancreas
- 2019
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Ingår i: Islets. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 11:4, s. 89-101
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota can play a role in pancreatitis and, likely, in the development of type 1 diabetes (T1D). Anti-microbial peptides and secretory proteins are important mediators of the innate immune response against bacteria but their expression in the human pancreas is not fully known. In this study, immunohistochemistry was used to analyze the expression of seven anti-microbial peptides (Defensin alpha 1, alpha 4, beta 1-4 and Cathelicidin) and two secretory proteins with known antimicrobial properties (REG3A and GP2) in pancreatic and duodenal biopsies from 10 non-diabetic organ donors and one organ donor that died at onset of T1D. Immunohistochemical data was compared with previously published whole-transcriptome data sets. Seven (Defensin alpha 1, beta 2, beta 3, alpha 4, GP2, Cathelicidin, and REG3A) host defense molecules showed positive staining patterns in most non-diabetic organ donors, whereas two (Defensin beta 1 and beta 4) were negative in all non-diabetic donors. Two molecules (Defensin alpha 1 and GP2) were restricted to the exocrine pancreas whereas two (Defensin beta 3, alpha 4) were only expressed in islet tissue. Cathelicidin, beta 2, and REG3A were expressed in both islets and exocrine tissue. The donor that died at onset of T1D had generally less positivity for the host defense molecules, but, notably, this pancreas was the only one where defensin beta 1 was found. Neither donor age, immune-cell infiltration, nor duodenal expression correlated to the pancreatic expression of host defense molecules. In conclusion, these findings could have important implications for the inflammatory processes in diabetes and pancreatitis as we find several host defense molecules expressed by the pancreatic tissue.
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| 6. |
- Taneera, Jalal, et al.
(författare)
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RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells
- 2019
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Ingår i: Islets. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 11:1, s. 10-20
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA 1c levels as well as insulin secretory capacity in isolated human islets were evaluated. The impact of RORB and RORC expression on insulin secretion in INS-1 (832/13) cells was validated as well. While RORA was the highest expressed gene among the three RORs in human islet cells, RORC was the highest expressed in INS-1 cells (832/13) and while RORB was the lowest expressed gene in human islet cells, RORA was the highest expressed in INS-1 cells (832/13). The expression of RORB and RORC was significantly lower in diabetic/hyperglycemic donors as compared with non-diabetic counterparts. Furthermore, while the expression of RORB correlated positively with insulin secretion and negatively with HbA 1c , that of RORC correlated negatively with HbA 1c . The expression pattern of RORA did not correlate with either of the two parameters. siRNA silencing of RORB or RORC in INS-1 (832/13) cells resulted in a significant downregulation of insulin mRNA expression and insulin secretion. These findings suggest that RORB and RORC are part of the molecular cascade that regulates insulin secretion in pancreatic β cells; and insight that provides for further work on the potential therapeutic utility of RORB and RORC genes in β cell dysfunction in type 2 diabetes.
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| 7. |
- Ekwall, Daniel, 1974-, et al.
(författare)
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Theft of pharmaceuticals during transport in Europe
- 2015
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Ingår i: Journal of Transportation Security. - : Springer Science and Business Media LLC. - 1938-7741 .- 1938-775X. ; 9:1, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this paper is to identify and describe the scale of cargo theft inthe European pharmaceutical supply chain in 2014. The study is based on a systemtheoreticalapproach which emphasises a holistic rather than atomistic view. Theresearch in this paper is deductive and descriptive in its nature and aims to present acurrent description of theft of pharmaceuticals in a European perspective. This paper’shypotheses on cargo theft have been developed from theories of criminology, forapplicable use, to strengthen the scientific field of logistics. A survey was conductedin autumn 2014 whereby the respondents were asked to provide their opinions inrelation to eleven questions. The survey was sent out to all major players in theEuropean pharmaceutical sector – manufacturers and logistics providers specializingin pharmaceuticals. The survey captured more or less 80 % of the European pharmaceuticalmanufacturers' market share.We found that the current threats against Europeanpharmaceutical transport are small in relative occurrence terms (relatively few attacks ona yearly basis compared to other product categories) but on an impact basis thefts ofpharmaceuticals place as one of the top targets (value wise) for criminals. This researchsupports other sources that the current geographical hot spot for these thefts in Europe isin Italy. The top risks are rated as either robbery or theft from vehicle at unsecure parkingareas. These two different modi operandi can be divided into one frequency relatedthreat (theft from unsecure parking) and one impact related risk (robbery).
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| 8. |
- Gentile, Michael
(författare)
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West oriented in the East-oriented Donbas : a political stratigraphy of geopolitical identity in Luhansk, Ukraine
- 2015
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Ingår i: Post-Soviet Affairs. - 1060-586X .- 1938-2855. ; 31:3, s. 201-223
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Tidskriftsartikel (refereegranskat)abstract
- Building on data from a survey (n = 4000) conducted in the eastern Ukrainian city of Luhansk in late 2013, this article explores the link between national identity and foreign policy preferences in the Donbas, suggesting that they are increasingly conflated in distinct geopolitical identities. Descriptive statistics and multinomial logistic regression are used to compare the characteristics of pro-West and uncertain individuals with those of the pro-Russian/Soviet individuals, with preferences on North Atlantic Treaty Organization (NATO) and European Union (EU) accession underlying this distinction. The results show that geopolitical identities in Luhansk have a complex political stratigraphy that includes demographic, socioeconomic, cultural, and attitudinal components. The pro-West constituency is younger, not Russian but often including members of other ethnic groups, well educated, more tolerant toward sexual minorities, generally more satisfied with life, and it also speaks better English. Conversely, those with pro-Russia/Soviet geopolitical identities are older, Russian, low educated, less fluent in English, intolerant, and unsatisfied with their lives. Uncertainty is more randomly distributed among social groups, indicating different underlying causes related to the source of the respondents’ uncertainty.
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| 9. |
- Steinthorsdottir, Margret, et al.
(författare)
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EVIDENCE FOR INSECT AND ANNELID ACTIVITY ACROSS THE TRIASSIC-JURASSIC TRANSITION OF EAST GREENLAND
- 2015
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Ingår i: Palaios. - : Society for Sedimentary Geology. - 0883-1351 .- 1938-5323. ; 30:8, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- During a study of macroflora from the Astartekloft locality in Jameson Land, East Greenland, endophytic insect ovipositions (egg traces) belonging to ichnogenus Paleoovoidus were recorded for the first time in ginkgoalean (Ginkgoites, Sphenobaiera, and Baiera) fossil leaves across the Triassic-Jurassic (Tr-J) transition (ca. 200 Ma). The ovipositions may have been produced by insects in the order Odonata (dragonflies and damselflies) and are relatively more abundant before than after the Tr-J transition, possibly reflecting changes in plant-insect association. Fossil clitellate annelid (leech) cocoons were also discovered in a macerated sample from a single bed within the Tr-J transition. The cocoons belong to two species: Dictyothylakos pesslerae and Pilothylakos pilosus, extending the range of the latter genus from the Early Cretaceous to the Early Jurassic. This new evidence suggests that the ecosystem and food webs were profoundly affected by the environmental degradation surrounding the end-Triassic event (ETE), which was marked by faunal mass extinctions and floral turnover. Invertebrate ichno- and body fossils may add significantly to paleoenvironmental information provided by plant fossil assemblages, and therefore a protocol for recording evidence of invertebrate activity in paleobotanical research is suggested, including analyzing a standardized number of specimens for fossil traces and bulk maceration for discovery of invertebrate body fossils. More well-designed studies on Mesozoic plant-invertebrate associations are needed and will provide deeper knowledge about the structure and evolution of complex ecosystems.
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| 10. |
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| 11. |
- Wästlund, Erik, 1969-, et al.
(författare)
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Evaluating gaze-driven power wheelchair with navigation support for persons with disabilities
- 2015
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Ingår i: Journal of rehabilitation research and development. - 0748-7711 .- 1938-1352. ; 52:7, s. 815-826
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Tidskriftsartikel (refereegranskat)abstract
- This article describes a novel add-on for powered wheelchairs that is composed of a gaze-driven control system and a navigation support system. The add-on was tested by three users. All of the users were individuals with severe disabilities and no possibility of moving independently. The system is an add-on to a standard power wheelchair and can be customized for different levels of support according to the cognitive level, motor control, perceptual skills, and specific needs of the user. The primary aim of this study was to test the functionality and safety of the system in the user's home environment. The secondary aim was to evaluate whether access to a gaze-driven powered wheelchair with navigation support is perceived as meaningful in terms of independence and participation. The results show that the system has the potential to provide safe, independent indoor mobility and that the users perceive doing so as fun, meaningful, and a way to reduce dependency on others. Independent mobility has numerous benefits in addition to psychological and emotional well-being. By observing users' actions, caregivers and healthcare professionals can assess the individual's capabilities, which was not previously possible. Rehabilitation can be better adapted to the individual's specific needs, and driving a wheelchair independently can be a valuable, motivating training tool.
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| 12. |
- Schindler, Karin, et al.
(författare)
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To eat or not to eat? Indicators for reduced food intake in 91,245 patients hospitalized on nutritionDays 2006-2014 in 56 countries worldwide : a descriptive analysis
- 2016
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Ingår i: American Journal of Clinical Nutrition. - Bethesda, USA : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 104:5, s. 1393-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inadequate nutrition during hospitalization is strongly associated with poor patient outcome, but ensuring adequate food intake is not a priority in clinical routine worldwide. This lack of priority results in inadequate and unbalanced food intake in patients and huge amounts of wasted food.Objectives: We evaluate the main factors that are associated with reduced meal intake in hospitalized patients and the differences between geographical regions.Design: We conducted a descriptive analysis of data from 9 consecutive, annual, and cross-sectional nutritionDay samples (2006-2014) in a total of 91,245 adult patients in 6668 wards in 2584 hospitals in 56 countries. A general estimation equation methodology was used to develop a model for meal intake, and P-value thresholding was used for model selection.Results: The proportion of patients who ate a full meal varied widely (24.7-61.5%) across world regions. The factors that were most strongly associated with reduced food intake on nutritionDay were reduced intake during the previous week (OR: 0.20; 95% CI: 0.17, 0.22), confinement to bed (OR: 0.49; 95% CI: 0.44, 0.55), female sex (OR: 0.53; 95% CI: 0.5, 0.56), younger age (OR: 0.74; 95% CI: 0.64, 0.85) and older age (OR: 0.80; 95% CI: 0.74; 0.88), and low body mass index (OR: 0.84; 95% CI: 0.79, 0.90). The pattern of associated factors was homogenous across world regions.Conclusions: A set of factors that are associated with full meal intake was identified and is applicable to patients hospitalized in any region of the world. Thus, the likelihood for reduced food intake is easily estimated through access to patient characteristics, independent of world regions, and enables the easy personalization of food provision. This trial was registered at clinicaltrials.gov as NCT02820246.
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| 13. |
- Gustavsson, Bengt, 1947, et al.
(författare)
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A Review of the Evolution of Systemic Chemotherapy in the Management of Colorectal Cancer.
- 2015
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Ingår i: Clinical colorectal cancer. - : Elsevier BV. - 1938-0674 .- 1533-0028. ; 14:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Herein we present a historical review of the development of systemic chemotherapy for colorectal cancer (CRC) in the metastatic and adjuvant treatment settings. We describe the discovery of 5-fluorouracil (5-FU) by Heidelberger and colleagues in 1957, the potentiation of 5-FU cytotoxicity by the reduced folate leucovorin, and the advent of novel cytotoxic agents, including the topoisomerase I inhibitor irinotecan, the platinum-containing agent oxaliplatin, and the 5-FU prodrug capecitabine. The combination therapies, FOLFOX (5-FU/leucovorin and oxaliplatin) and FOLFIRI (5-FU/leucovorin and irinotecan), have become established as efficacious cytotoxic regimens for the treatment of metastatic CRC, resulting in overall survival times of approximately 2 years. When used as adjuvant therapy, FOLFOX also improves survival and is now the gold standard of care in this setting. Biological agents have been discovered that enhance the effect of cytotoxic therapy, including bevacizumab (a humanized monoclonal antibody that targets vascular endothelial growth factor, a central regulator of angiogenesis) and cetuximab/panitumumab (monoclonal antibodies directed against the epidermal growth factor receptor). Despite the ongoing development of novel antitumor agents and therapeutic principles as we enter the era of personalized cancer medicine, systemic chemotherapy involving infusional 5-FU/leucovorin continues to be the cornerstone of treatment for patients with CRC.
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| 14. |
- Nearchou, Andreas, et al.
(författare)
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Acquired Hypothyroidism as a Predictive Marker of Outcome in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors : A Literature-Based Meta-Analysis
- 2015
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Ingår i: Clinical Genitourinary Cancer. - : Elsevier BV. - 1558-7673 .- 1938-0682. ; 13:4, s. 280-286
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Forskningsöversikt (refereegranskat)abstract
- Hypothyroidism in patients with metastatic renal cell carcinoma (mRCC) during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. Furthermore, the potential role of hypothyroidism as predictive marker of outcome has been studied but with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for progression-free (PFS) and overall survival (OS) in patients with mRCC during TKI therapy. We searched PubMed and the electronic abstract databases of the major international congresses' proceedings to identify all eligible studies that reported a correlation between the development of hypothyroidism during TKI treatment and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis. Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism during sunitinib therapy and unaffected patients (HR, 0.82; 95% CI, 0.59-1.13; P = .22; 6 studies; 250 patients). The HR for OS was 0.52 (95% CI, 0.31-0.87; P = .01) for patients who developed hypothyroidism during sunitinib therapy compared with patients who did not (4 studies; 147 patients). The development of hypothyroidism during TKI therapy is not clearly shown to be predictive of efficacy in patients with mRCC. The observed advantage in OS for the patients with acquired hypothyroidism should be interpreted with caution.
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| 15. |
- Gama, Fábio, 1980-
(författare)
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Managing collaborative ideation : The role of formal and informal appropriability mechanisms
- 2019
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Ingår i: The International Entrepreneurship and Management Journal. - New York, NY : Springer. - 1554-7191 .- 1555-1938. ; 15:1, s. 97-118
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Tidskriftsartikel (refereegranskat)abstract
- Collaborative ideation is a key practice for innovation. Implementing suitable appropriability mechanisms during this collaborative ideation is a necessary yet difficult task. This difficulty owes to a high level of uncertainty and low level of codification because partners work on loosely defined concepts that may change during the collaboration. Firms can employ several appropriability mechanisms to protect their knowledge. Examples include patents, copyright, legal agreements, document management, lead time, secrecy and complexity. However, the best time to apply each mechanism remains unclear, and few empirical studies have explored this issue. This study is based on exploratory case studies of three manufacturing firms. The goal is to identify which appropriability mechanisms are pertinent at each phase of collaborative ideation and how they influence the effectiveness of protection. The results of the analysis lead to the development of a model describing the managerial practices that influence the effectiveness of protection. The results also lead to a set of research propositions to define when each appropriability mechanism is most likely to be used. Overall, this research contributes to the discussion of how to integrate formal and informal appropriability mechanisms for safe collaborative ideation. The paper concludes by discussing theoretical and managerial implications as well as directions for future research.
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| 16. |
- Foka, Anna, 1981-, et al.
(författare)
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Introduction to the DHQ Special Issue : Digital Technology in the Study of the Past
- 2018
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Ingår i: Digital Humanities Quarterly. - Boston : Alliance for Digital Humanities Organisations. - 1938-4122. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Digital technology is transforming the assemblage and dissemination of historical information. Museums, libraries, archives, and universities increasingly modify their digital research infrastructures in order to make data open and available (see [Crane, Seales, and Terras 2009]; [Smithies 2014]; [Terras, Nyhan, and Vanhoutte 2013]; cf [Foka et al. 2017]). The imminent assessment and representation of historical data has admittedly challenged the boundaries of historical knowledge and generated new research questions [Drucker 2013] [Nygren, Foka, and Buckland 2014] #nygren2016 [Westin 2014] #westin2015[Chapman, Foka, and Westin 2016] [Foka and Arvidsson 2016]. The process of reconstructing, visualizing and rendering historical data has equally developed together with technology [Westin, Foka, and Chapman 2018]. This is the case in both academic and heritage contexts and in less immediately obvious popular uses, such as the increasingly significant presence and use of history within video games [Chapman 2016]. Regardless of specific context, as this collection of articles shows, the process of digitally capturing and representing historical data is often analogous to and determined by the digital platform used.
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| 17. |
- Roslin, Tomas
(författare)
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Spatiotemporal snowmelt patterns within a high Arctic landscape, with implications for flora and fauna
- 2018
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Ingår i: Arctic, Antarctic, and Alpine Research. - : Informa UK Limited. - 1523-0430 .- 1938-4246. ; 50
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Tidskriftsartikel (refereegranskat)abstract
- Snow conditions are important drivers of the distribution and phenology of Arctic flora and fauna, but the extent and effects of local variation in snowmelt are still inadequately studied. We analyze snowmelt patterns within the Zackenberg valley in northeast Greenland. Drawing on landscape-level snowmelt dates and meteorological data from a central climate station, we model snowmelt trends during 1998-2014. We then use time-lapse photographs to examine consistency in spatiotemporal snowmelt patterns during 2006-2014. Finally, we use monitoring data on arthropods and plants for 1998-2014 to investigate how snowmelt date affects the phenology of Arctic organisms. Despite large interannual variation in snowmelt timing, we find consistency in the relative order of snowmelt among sites within the landscape. With a slight overall advancement in snowmelt during the study period, early melting locations have advanced more than late-melting ones. Individual organism groups differ greatly in how their phenology shifts with snowmelt, with much variance attributable to variation in life history and diet. Overall, we note that local variation in snowmelt patterns may drive important ecological processes, and that more attention should be paid to variability within landscapes. Areas optimal for a given taxon vary between years, thereby creating spatial structure in a seemingly uniform landscape.
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| 18. |
- Saeidi, Alireza, et al.
(författare)
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Functional role of mucosal-associated invariant T cells in HIV infection
- 2016
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Ingår i: Journal of Leukocyte Biology. - : FEDERATION AMER SOC EXP BIOL. - 0741-5400 .- 1938-3673. ; 100:2, s. 305-314
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Forskningsöversikt (refereegranskat)abstract
- MAIT cells represent an evolutionarily conserved, MR1-restricted, innate-like cell subset that express high levels of CD161; have a canonical semi-invariant TCR iV alpha 7.2; and may have an important role in mucosal immunity against various bacterial and fungal pathogens. Mature MAIT cells are CD161(hi)PLZF(hi)IL-18R alpha(+)iV alpha 7.2(+)gamma delta-CD3(+)CD8(+) T cells and occur in the peripheral blood, liver, and mucosa of humans. MAIT cells are activated by a metabolic precursor of riboflavin synthesis presented by MR1 and, therefore, respond to many bacteria and some fungi. Despite their broad antibacterial properties, their functional role in persistent viral infections is poorly understood. Although there is an increasing line of evidence portraying the depletion of MAIT cells in HIV disease, the magnitude and the potential mechanisms underlying such depletion remain unclear. Recent studies suggest that MAIT cells are vulnerable to immune exhaustion as a consequence of HIV and hepatitis C virus infections and HIV/tuberculosis coinfections. HIV infection also appears to cause functional depletion of MAIT cells resulting from abnormal expression of T-bet and EOMES, and effective ART is unable to completely salvage functional MAIT cell loss. Depletion and exhaustion of peripheral MAIT cells may affect mucosal immunity and could increase susceptibility to opportunistic infections during HIV infection. Here, we review some of the important mechanisms associated with depletion and functional loss of MAIT cells and also suggest potential immunotherapeutic strategies to restore MAIT cell functions, including the use of IL-7 to restore effector functions in HIV disease.
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| 19. |
- Han, Hedong, et al.
(författare)
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Utilization of Palliative Care for Patients Undergoing Hematopoietic Stem Cell Transplantation During Hospitalization : A Population-Based National Study
- 2019
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Ingår i: The American Journal of Hospice and Palliative Medicine. - : Sage Publications. - 1049-9091 .- 1938-2715. ; 36:10, s. 900-906
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients undergoing hematopoietic stem cell transplantation (HSCT) have substantial physical and psychological symptoms. This study aimed to investigate the utilization of palliative care (PC) in patients undergoing HSCT during hospitalization.METHODS: The 2008-2014 National Inpatient Sample was queried for eligible participants. Demographics, hospital characteristics, comorbidities, posttransplantation complications, and inpatient procedures were compared between patients with and without PC. Multivariate logistic regression was performed to identify predictors associated with PC use.RESULTS: Among 21 458 patients undergoing HSCT during hospitalization, 278 (1.30%) received PC. The rate of PC use has significantly increased from 0.64% in 2008 to 1.95% in 2014. Patients receiving PC had more co-comorbidities, posttransplantation complications, inpatient procedures, and were more likely to carry a diagnosis of leukemia. In allogeneic HSCT, large bed size (odds ratio [OR] =2.80; 95% confidence interval [CI]: 1.17-6.70), stem cell source from cord blood (OR = 1.93; 95% CI: 1.15-3.24), and graft-versus-host disease (OR = 2.04; 95% CI: 1.36-3.06) were predictors of PC use. In a subset analysis of 783 patients who died during hospitalization, 166 (21.20%) received PC. Among the decedents, Hispanic race had lower odds of PC use (OR = 0.20; 95% CI: 0.05-0.82) in allogeneic HSCT and women had higher odds of PC (OR = 2.70; 95% CI: 1.35-5.41) in autologous HSCT.CONCLUSIONS: The rate of PC use has significantly increased among patients undergoing HSCT during hospitalization from 2008 to 2014 but still remains very low. Further investigation is warranted to verify and better understand the barriers toward PC use for HSCT patients.
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| 20. |
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| 21. |
- Dolan, Kathleen, et al.
(författare)
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Blaming Women or Blaming the System? Public Perceptions of Women's Underrepresentation in Elected Office
- 2018
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Ingår i: Political Research Quarterly. - : SAGE Publications. - 1938-274X .- 1065-9129. ; 71:3, s. 668-680
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Tidskriftsartikel (refereegranskat)abstract
- While scholars understand some of the reasons for the underrepresentation of women in elected office in the United States, we know almost nothing about what the public sees as the explanation for this reality. We also know relatively little about the degree to which people see women’s underrepresentation as a problem. Drawing on blame attribution theories, we examine whether people believe that there are systematic or individual explanations for the number of women in elected office. As blame explanations often influence positions on outcomes, we also test whether these explanations are related to people’s attitudes toward women in office and their vote choice behaviors in U.S. House races with women candidates present. Using data from a 2014 Cooperative Congressional Election Study (CCES) survey, we find differences among people in the blame explanations they make. These explanations are significantly related to attitudes about women in office but do not influence vote choice decisions when women run for office.
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| 22. |
- Foka, Anna, 1981-, et al.
(författare)
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Experiential Analogies : A Sonic Digital Ekphrasis as a Digital Humanities Project
- 2016
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Ingår i: Digital Humanities Quarterly. - Boston : Alliance Digital Humanities Organizations. - 1938-4122. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Humanistic uses of digital technologies have opened up new ways to think about, communicate, and discuss historical research. The common use of digital tools to visually represent ancient cultures and sites, however, has also introduced new issues. For example, critics have argued that digital visualisations, largely synonymous with reconstruction in 3D models, often attempt to represent a photorealistic-artificial vision of the past, and may often prove to be a way to communicate history to a large(r) audience [Forte and Siliotti 1997]. Against this backdrop, this article will discuss precisely how technology may help immerse researchers into historically situated life, and radically advance historical research. Adding to related criticisms of ocularcentric traditions of knowledge production, we contribute to this stream of research by arguing that contemporary visual representations of the past often concentrate on visual representations and seemingly maintain antiquity as a sanitised historio-cultural ideal [Westin 2012] [Tziovas 2014]. More specifically, this article seeks to demonstrate the potential of digital humanities to move beyond mere representations on screen and to mobilize other senses (specifically sound) as a historically situated component for research. For this purpose, we focus on the abstract principles and overall methodology for a recreation of the experience of sounds in the Roman amphitheatre.
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| 23. |
- Arnemo, Jon
(författare)
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Metal Deposition of Copper and Lead Bullets in Moose Harvested in Fennoscandia
- 2017
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Ingår i: Wildlife Society Bulletin. - : Wiley. - 0091-7648 .- 1938-5463. ; 41, s. 98-106
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Tidskriftsartikel (refereegranskat)abstract
- Fragments from bullets used for moose (Alces alces) hunting contaminate meat, gut piles, and offal and expose humans and scavengers to lead and copper. We sampled bullets (n = 1,655) retrieved from harvested moose in Fennoscandia (Finland, Sweden, and Norway) to measure loss of lead and copper. Concordant questionnaires (n = 5,255) supplied ballistic information to complete this task. Hunters preferred lead-based bullets (90%) to copper bullets (10%). Three caliber classes were preferred: 7.62mm(69%), 9.3mm(12%), and 6.5mm(12%). Bullets passed completely through calves (76%) more frequently compared to yearlings (63%) or adults (47%). Metal deposition per bullet type (bonded lead core, lead core, and copper) did not vary among moose age classes (calves, yearlings, and adults). Average metal loss per bullet type was 3.0g, 2.6g, and 0.5g for lead-core, bonded lead-core, and copper bullets, respectively. This corresponded to 18-26, 10-25, and 0-15% metal loss for lead-core, bonded lead-core, and copper bullets, respectively. Based on the harvest of 166,000 moose in Fennoscandia during the 2013/2014 hunting season, we estimated that lead-based bullets deposited 690 kg of lead in moose carcasses, compared with 21 kg of copper from copper bullets. Bone impact increased, whereas longer shooting distances decreased, lead loss from lead-based bullets. These factors did not influence loss of copper from copper bullets. In conclusion, a significant amount of toxic lead from lead-based bullets is deposited in the tissue of harvested moose, which may affect the health of humans and scavengers that ingest it. By switching to copper bullets, Fennoscandian hunters can eliminate a significant source of lead exposure in humans and scavengers. (C) 2017 The Wildlife Society.
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| 24. |
- Wesslen, C, et al.
(författare)
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Contemporary Management and Outcome After Lower Extremity Fasciotomy in Non-Trauma-Related Vascular Surgery
- 2018
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Ingår i: Vascular and endovascular surgery. - : SAGE Publications. - 1938-9116 .- 1538-5744. ; 52:7, s. 493-497
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Tidskriftsartikel (refereegranskat)abstract
- Acute compartment syndrome (ACS) is a challenging and recognized complication to vascular surgery revascularization. The aim of this study was to investigate the current epidemiology, management, and early outcomes of fasciotomy in vascular surgery. Methods: Retrospective cohort study of all patients undergoing lower extremity fasciotomy at a single university center between January 2008 and December 2014. Patient demographics, operative techniques, and outcomes were analyzed. Results: The cohort (n = 113 limbs; 107 patients; 48% women; mean age was 74 (12) years [range, 50-97 years]) included 81 (72%) limbs undergoing revascularization for acute limb ischemia, 7 (6.2%) limbs related to acute aortic disease, and 23 (20%) limbs undergoing elective vascular surgery. Five patients underwent bilateral lower extremity fasciotomy. In all, 64 (57%) limbs had signs of ACS and underwent a therapeutic fasciotomy, while 49 (43%) fasciotomies were prophylactic. There were 20 (18%) fasciotomies performed after endovascular interventions. A 4-compartment fasciotomy was performed in 82% (n = 93) of limbs with a double incision technique. Split thickness skin graft was required in 11% (12/112) and vacuum-assisted closure treatment in 11% (12/111). The mean length of stay in hospital was 11 (9) days. Most common complication was lower extremity nerve deficit 32% (33/104) followed by wound infection 30% (32/108). At 30-day follow-up, amputation rate was 13% (14/107 limbs) and mortality 23% (25/107 patients). In the multivariate logistic regression analysis, prophylactic fasciotomy was associated with amputation (odds ratio: 28.9; 95% confidence interval: 1.96-425; P = .014). Conclusion: Acute compartment syndrome is primarily related to acute ischemic conditions but occurs after both aortic or elective vascular procedures and endovascular treatments. There are significant complications related to lower extremity fasciotomy in vascular surgery.
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| 25. |
- Lehmann, U., et al.
(författare)
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Efficacy of fish intake on vitamin D status: a meta-analysis of randomized controlled trials
- 2015
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 102:4, s. 837-847
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is well known that fish is the major natural source of vitamin D in the diet; therefore, this meta-analysis investigated the influence of fish consumption in randomized controlled trials (RCTs) on serum 25-hydroxyvitamin D [25(OH)D] concentrations. Objective: A literature search was carried out in Medline, Embase, Web of Science, and the Cochrane Library (up to February 2014) for RCTs that investigated the effect of fish consumption on 25(OH)D concentrations in comparison to other dietary interventions. Results: Seven articles and 2 unpublished study data sets with 640 subjects and 14 study groups met the inclusion criteria and were included in this meta-analysis. Compared with controls, the consumption of fish increased 25(OH)D concentrations, on average, by 4.4 nmol/L (95% CI: 1.7, 7.1 nmol/L; P < 0.0001, I-2 = 25%; 9 studies). The type of the fish also played a key role: the consumption of fatty fish resulted in a mean difference of 6.8 nmol/L (95% CI: 3.7, 9.9 nmol/L; P < 0.0001, I-2 = 0%; 7 study groups), whereas for lean fish the mean difference was 1.9 nmol/L (95% CI: -2.3, 6.0 nmol/L; P < 0.38, I-2 = 37%; 7 study groups). Short-term studies (4-8 wk) showed a mean difference of 3.8 nmol/L (95% CI: 0.6, 6.9 nmol/L; P < 0.02, I-2 = 38%; 10 study groups), whereas in long-term studies (similar to 6 mo) the mean difference was 8.3 nmol/L (95% CI: 2.1, 14.5 nmol/L; P < 0.009, I-2 = 0%; 4 study groups). Conclusion: As the major food source of vitamin D, fish consumption increases concentrations of 25(OH)D, although recommended fish intakes cannot optimize vitamin D status.
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| 26. |
- Nystrom, C. D., et al.
(författare)
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Mobile-based intervention intended to stop obesity in preschool-aged children: the MINISTOP randomized controlled trial
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 105:6, s. 1327-1335
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Tidskriftsartikel (refereegranskat)abstract
- Background: Traditional obesity prevention programs are time-and cost-intensive. Mobile phone technology has been successful in changing behaviors and managing weight; however, to our knowledge, its potential in young children has yet to be examined. Objective: We assessed the effectiveness of a mobile health (mHealth) obesity prevention program on body fat, dietary habits, and physical activity in healthy Swedish children aged 4.5 y. Design: From 2014 to 2015, 315 children were randomly assigned to an intervention or control group. Parents in the intervention group received a 6-mo mHealth program. The primary outcome was fat mass index (FMI), whereas the secondary outcomes were intakes of fruits, vegetables, candy, and sweetened beverages and time spent sedentary and in moderate-to-vigorous physical activity. Composite scores for the primary and secondary outcomes were computed. Results: No statistically significant intervention effect was observed for FMI between the intervention and control group (mean +/- SD: -0.23 +/- 0.56 compared with -0.20 +/- 0.49 kg/m(2)). However, the intervention group increased their mean composite score from baseline to follow-up, whereas the control group did not (+ 0.36 +/- 1.47 compared with -0.06 +/- 1.33 units; P = 0.021). This improvement was more pronounced among the children with an FMI above the median (4.11 kg/m(2)) (P = 0.019). The odds of increasing the composite score for the 6 dietary and physical activity behaviors were 99% higher for the intervention group than the control group (P = 0.008). Conclusions: This mHealth obesity prevention study in preschool-aged children found no difference between the intervention and control group for FMI. However, the intervention group showed a considerably higher postintervention composite score (a secondary outcome) than the control group, especially in children with a higher FMI. Further studies targeting specific obesity classes within preschool-aged children are warranted.
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| 27. |
- Tärnqvist, J., et al.
(författare)
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On-scene and final assessments and their interrelationship among patients who use the EMS on multiple occasions
- 2017
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Ingår i: Prehospital and Disaster Medicine. - : Cambridge University Press. - 1049-023X .- 1945-1938. ; 32:5, s. 528-535
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The use of Emergency Medical Services (EMS) is increasing. A number of patients call repeatedly for EMS. Early studies of frequent callers show that they form a heterogenous group. Problem: There is a lack of research on frequent EMS callers. There is furthermore a lack of knowledge about characteristics and the prehospital assessment of the patients who call for EMS on several occasions. Finally, there is a general lack of knowledge with regard to the association between the prehospital assessment by health care providers and the final diagnosis. Method: Patients in Skaraborg in Western Sweden, who used the EMS at least four times in 2014, were included, excluding transport between hospitals. Information on the prehospital assessment on-scene and the final diagnosis was collected from the EMS and hospital case records. Results: In all, 339 individual patients who used the EMS on 1,855 occasions were included, accounting for five percent of all missions. Fifty percent were women. The age range was 10-98 years, but more than 50.0% were in the age range of 70-89 years. The most common emergency signs and symptoms (ESS) codes on the scene were dyspnea, chest pain, and abdominal pain. The most common final diagnosis was chronic obstructive pulmonary disease (eight percent). Thirteen percent of all cases had a final diagnosis defined as a potentially life-threatening condition. Among these, 22.0% of prehospital assessments were retrospectively judged as potentially inappropriate. Forty-nine percent had a defined final diagnosis not fulfilling the criteria for a potentially life-threatening condition. Among these cases, 30.0% of prehospital assessments were retrospectively judged as potentially inappropriate. Conclusion:: Among patients who used EMS on multiple occasions, the most common symptoms on-scene were dyspnea, chest pain, and abdominal pain. The most common final diagnosis was chronic obstructive pulmonary disease. In 13.0%, the final diagnosis of a potentially life-threatening condition was indicated. In a minority of these cases, the assessment on-scene was judged as potentially inappropriate.
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