| 1. |
- Habel, Joachim, et al.
(författare)
-
Selecting analytical tools for characterization of polymersomes in aqueous solution
- 2015
-
Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:97, s. 79924-79946
-
Forskningsöversikt (refereegranskat)abstract
- Selecting the appropriate analytical methods for characterizing the assembly and morphology of polymer-based vesicles, or polymersomes are required to reach their full potential in biotechnology. This work presents and compares 17 different techniques for their ability to adequately report size, lamellarity, elastic properties, bilayer surface charge, thickness and polarity of polybutadiene-polyethylene oxide (PB-PEO) based polymersomes. The techniques used in this study are broadly divided into scattering techniques, visualization methods, physical and electromagnetical manipulation and sorting/purification. Of the analytical methods tested, Cryo-transmission electron microscopy and atomic force microscopy (AFM) turned out to be advantageous for polymersomes with smaller diameter than 200 nm, whereas confocal microscopy is ideal for diameters >400 nm. Polymersomes in the intermediate diameter range can be characterized using freeze fracture Cryo-scanning electron microscopy (FF-Cryo-SEM) and nanoparticle tracking analysis (NTA). Small angle X-ray scattering (SAXS) provides reliable data on bilayer thickness and internal structure, Cryo-TEM on multilamellarity. Taken together, these tools are valuable for characterizing polymersomes per se but the comparative overview is also intended to serve as a starting point for selecting methods for characterizing polymersomes with encapsulated compounds or polymersomes with incorporated biomolecules (e.g. membrane proteins).
|
|
| 2. |
- Axen, Iben, et al.
(författare)
-
Misinformation, chiropractic, and the COVID-19 pandemic
- 2020
-
Ingår i: Chiropractic and Manual Therapies. - : BioMed Central (BMC). - 2045-709X. ; 28:1
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: In March 2020, the World Health Organization elevated the coronavirus disease (COVID-19) epidemic to a pandemic and called for urgent and aggressive action worldwide. Public health experts have communicated clear and emphatic strategies to prevent the spread of COVID-19. Hygiene rules and social distancing practices have been implemented by entire populations, including 'stay-at-home' orders in many countries. The long-term health and economic consequences of the COVID-19 pandemic are not yet known.Main text: During this time of crisis, some chiropractors made claims on social media that chiropractic treatment can prevent or impact COVID-19. The rationale for these claims is that spinal manipulation can impact the nervous system and thus improve immunity. These beliefs often stem from nineteenth-century chiropractic concepts. We are aware of no clinically relevant scientific evidence to support such statements. We explored the internet and social media to collect examples of misinformation from Europe, North America, Australia and New Zealand regarding the impact of chiropractic treatment on immune function. We discuss the potential harm resulting from these claims and explore the role of chiropractors, teaching institutions, accrediting agencies, and legislative bodies.Conclusions: Members of the chiropractic profession share a collective responsibility to act in the best interests of patients and public health. We hope that all chiropractic stakeholders will view the COVID-19 pandemic as a call to action to eliminate the unethical and potentially dangerous claims made by chiropractors who practise outside the boundaries of scientific evidence.
|
|
| 3. |
- Blirup, Soren, et al.
(författare)
-
Protein standardization V: value transfer. A practical protocol for the assignment of serum protein values from a Reference Material to a Target Material.
- 2008
-
Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; Sep 1, s. 1470-1479
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract We present a practical protocol for the assignment of values to serum proteins in a Target Material using a Reference Material. This protocol is based on the model of Direct Value Transfer between serum matrices and is intended to improve the value assignment of commercial calibrators using the Reference Material CRM 470 (now labeled ERM-DA 470) or similar reference materials. The procedure describes the general as well as the practical principles involved in the value assignment (with examples). The practical transfer protocol is based on multiple assays of 6 dilutions of the Reference Material and 6 dilutions of the Target Material. The transfer protocol requires several measurements a day repeated on several days, an important prerequisite being that all reconstitutions and dilutions are controlled by weighing thus reducing uncertainty in the transfer. In open systems that allow the use of the Reference Material as calibrator and the Target Material as samples, the proportionality of the two materials (the presence or absence of matrix effects) can now be directly assessed by evaluating a single regression plot. If no matrix effects are found, the regression line will pass through zero with a slope equal to the ratio of the concentrations of the two materials. In closed systems, the dedicated commercial calibrator has to be used as such; the Reference Material and the Target Material are now assayed as samples against this calibrator. Two regression plots are therefore obtained; if no matrix effects are present among the two materials and the calibrator, both the Reference and Target Materials will show zero intercepts, and the ratio of the two slopes will equal the ratio of the concentrations. Clin Chem Lab Med 2008;46.
|
|
| 4. |
- Cao, Christopher, et al.
(författare)
-
Prospective Registry On Mesothelioma Peritonei Treatment (PROMPT) : study design and rationale
- 2012
-
Ingår i: Tumori (Milano). - 0300-8916 .- 2038-2529. ; 98:1, s. 166-171
-
Tidskriftsartikel (refereegranskat)abstract
- Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive and rare form of cancer arising from the mesothelial lining of the peritoneum. Due to the latency period between asbestos exposure and disease progression, the peak in incidence of DMPM is likely to occur in the coming decade for many industrialized nations, with a multitude of industrial, medico-legal and health-related implications(1,2). Traditional therapeutic modalities such as systemic chemotherapy and radiotherapy have not been proven to be effective in the treatment of DMPM, and patients diagnosed with the disease have a life expectancy of less than 12 months(3-5). Combined treatment involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been utilized in several specialized centers around the world and has been found to be a feasible procedure with encouraging survival outcomes(6-8).
|
|
| 5. |
- Ghouse, Jonas, et al.
(författare)
-
Association of Variants Near the Bradykinin Receptor B2 Gene With Angioedema in Patients Taking ACE Inhibitors
- 2021
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 78:7, s. 696-709
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Angioedema is a rare but potentially life-threatening adverse reaction associated with angiotensinconverting enzyme (ACE) inhibitors. Identification of potential genetic factors related to this adverse event may help identify at-risk patients. OBJECTIVES The aim of this study was to identify genetic factors associated with ACE inhibitor-associated angioedema. METHODS A genomewide association study involving patients of European descent, all taking ACE inhibitors, was conducted in a discovery cohort (Copenhagen Hospital Biobank), and associations were confirmed in a replication cohort (Swedegene). Cases were defined as subjects with angioedema events and filled prescriptions for ACE inhibitors #180 days before the events. Control subjects were defined as those with continuous treatment with ACE inhibitors without any history of angioedema. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for angioedema risk using logistic mixed model regression analysis. Summary statistics from the discovery and replication cohorts were analyzed using a fixed-effects meta-analysis model. RESULTS The discovery cohort consisted of 462 cases and 53,391 ACE inhibitor-treated control subjects. The replication cohort consisted of 142 cases and 1,345 ACE inhibitor-treated control subjects. In the discovery cohort, 1 locus, residing at chromosome 14q32.2, was identified that associated with angioedema at the genomewide significance level of P <5 x 10-8. The lead variant at this locus, rs34485356, is an intergenic variant located 60 kb upstream of BDKRB2 (OR: 1.62; 95% CI: 1.38 to 1.90; P = 4.3 x 10-9). This variant was validated in our replication cohort with a similar direction and effect size (OR: 1.60; 95% CI: 1.13 to 2.25; P = 7.2 x 10-3). We found that carriers of the risk allele had significantly lower systolic (-0.46 mm Hg per T allele; 95% CI:-0.83 to-0.10; P = 0.013) and diastolic (-0.26 mm Hg per T allele; 95% CI:-0.46 to-0.05; P = 0.013) blood pressure. CONCLUSIONS In this genomewide association study involving individuals treated with ACE inhibitors, we found that common variants located in close proximity to the bradykinin receptor B2 gene were associated with increased risk for ACE inhibitor-related angioedema.
|
|
| 6. |
- Gustafsen, Camilla, et al.
(författare)
-
Heparan sulfate proteoglycans present PCSK9 to the LDL receptor
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats. Accordingly, heparan sulfate mimetics and monoclonal antibodies directed against the heparan sulfate-binding site are potent PCSK9 inhibitors. We propose that heparan sulfate proteoglycans lining the hepatocyte surface capture PCSK9 and facilitates subsequent PCSK9: LDLR complex formation. Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.
|
|
| 7. |
- Jelen, Sabina, et al.
(författare)
-
AQP9 Expression in Glioblastoma Multiforme Tumors Is Limited to a Small Population of Astrocytic Cells and CD15(+)/CalB(+) Leukocytes
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
-
Tidskriftsartikel (refereegranskat)abstract
- Aquaporin-9 (AQP9) is a membrane protein channel that is permeable to a range of small solutes, including glycerol, urea and nucleobases. Expression of AQP9 in normal brain is limited, while widespread AQP9 expression has previously been reported in human glioblastoma. However, the specific cellular expression of AQP9 in glioblastoma remains unclear. In this study, we have examined microarrays to corroborate AQP9 mRNA expression in glioma. These analyses suggested that AQP9 mRNA expression in glioblastoma is primarily explained by tumor infiltration with AQP9 expressing leukocytes. Immunolabeling confirmed that within tumor regions, AQP9 was expressed in CD15(+) and Calgranulin B+ leukocytes, but also in larger cells that morphologically resembled glioma cells. Specificity of immunoreagents was tested in recombinant cell lines, leukocyte preparations, and sections of normal human brain and liver tissue. Apparent AQP9(+) glioma cells were frequently observed in proximity to blood vessels, where brain tumor stem cells have been observed previously. A fraction of these larger AQP9 expressing cells co-expressed the differentiated astrocyte marker GFAP. AQP9 expressing glioma cells were negative for the brain tumor stem cell marker CD15, but were observed in proximity to CD15(+) glioma cells. AQP9 expression may therefore require signals of the perivascular tumor environment or alternatively it may be restricted to a population of glioma stem cell early progenitor cells.
|
|
| 8. |
- Jorgensen, Jesper Roland, et al.
(författare)
-
Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo
- 2012
-
Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 233:1, s. 172-181
-
Tidskriftsartikel (refereegranskat)abstract
- Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors. Furthermore, Cometin supports migration of neuroblasts from subventricular zone explants to the same extend as stromal cell derived factor la. Given the neurotrophic properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show that Cometin is a potent new neurotrophic factor with therapeutic potential. (C) 2011 Elsevier Inc. All rights reserved.
|
|
| 9. |
- Larsen, Anders Hostrup, et al.
(författare)
-
A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes
- 2020
-
Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:9, s. 1628-1637
-
Tidskriftsartikel (refereegranskat)abstract
- AimsThe present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes. Methods and resultsThirty-six HFrEF patients (ejection fraction 378%; median age 66years) were randomised to metformin (n = 19) or placebo (n = 17) for 3months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by C-11-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 +/- 550 mg/day) increased WMI [absolute mean difference, 1.0mmHg.mL.m(-2).10(6); 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6mL O-2.100 g(-1).min(-1); P = 0.014). Cardiac stroke work was preserved (-2J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups. ConclusionMetformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.
|
|
| 10. |
- Larsen, Signe Benzon, et al.
(författare)
-
Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort
- 2013
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 49:14, s. 3041-3048
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer. Methods and material: Case-control study nested within the Danish 'Diet, Cancer and Health' cohort of 27,179 men aged 50-64 at enrolment. PSA measured in serum collected at cohort entry in 1993-1997 was used to evaluate prostate cancer risk diagnosed up to 14 years after. We identified 911 prostate cancer cases in the Danish Cancer Registry through 31st December 2007 1:1 age-matched with cancer-free controls. Aggressive cancer was defined as >= T3 or Gleason score >= 7 or N1 or M1. Statistical analyses were based on conditional logistic regression with age as underlying time axis. Results: Total PSA and free-to-total PSA ratio at baseline were strongly associated with prostate cancer risk up to 14 years later. PSA was grouped in quintiles and free-to-total PSA ratio divided in three risk groups. The incidence rate ratio for prostate cancer was 150 (95% confidence interval, 72-310) among men with a total PSA in the highest quintile (>5.1 ng/ml) compared to the lowest (<0.80 ng/ml). The risk of aggressive cancer was highly elevated in men with a PSA level in the highest quintile. The results indicate that one-time measurement of PSA could be used in an individualised screening strategy, sparing a large proportion of men from further PSA-based screening. (C) 2013 Elsevier Ltd. All rights reserved.
|
|
