| 1. |
- Athlin, Simon, 1971-, et al.
(författare)
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Management of community-acquired pneumonia in immunocompetent adults : updated Swedish guidelines 2017
- 2018
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 50:4, s. 247-272
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Forskningsöversikt (refereegranskat)abstract
- Based on expert group work, Swedish recommendations for the management of community-acquired pneumonia in adults are here updated. The management of sepsis-induced hypotension is addressed in detail, including monitoring and parenteral therapy. The importance of respiratory support in cases of acute respiratory failure is emphasized. Treatment with high-flow oxygen and non-invasive ventilation is recommended. The use of statins or steroids in general therapy is not found to be fully supported by evidence. In the management of pleural infection, new data show favourable effects of tissue plasminogen activator and deoxyribonuclease installation. Detailed recommendations for the vaccination of risk groups are afforded.
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| 2. |
- Ayoglu, Burcu, et al.
(författare)
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Systematic antibody and antigen-based proteomic profiling with microarrays
- 2011
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Ingår i: EXPERT REVIEW OF MOLECULAR DIAGNOSTICS. - 1473-7159. ; 11:2, s. 219-234
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Forskningsöversikt (refereegranskat)abstract
- Current approaches within affinity-based proteomics are driven both by the accessibility and availability of antigens and capture reagents, and by suitable multiplexed technologies onto which these are implemented. By combining planar microarrays and other multiparallel systems with sets of reagents, possibilities to discover new and unpredicted protein disease associations, either via directed hypothesis-driven or via undirected hypothesis-generating target selection, can be created. In the following stages, the discoveries made during these screening phases have to be verified for potential clinical relevance based on both technical and biological aspects. The use of affinity tools throughout discovery and verification has the potential to streamline the introduction of new markers, as transition into clinically required assay formats appears straightforward. In this article, we summarize some of the current building blocks within array-and affinity-based proteomic profiling with a focus on body fluids, by giving a perspective on how current and upcoming developments in this bioscience could enable a path of pursuit for biomarker discovery.
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| 3. |
- Baijnath, Sooraj, et al.
(författare)
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Advances in spatial mass spectrometry enable in-depth neuropharmacodynamics
- 2022
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier. - 0165-6147 .- 1873-3735. ; 43:9, s. 740-753
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Forskningsöversikt (refereegranskat)abstract
- Mass spectrometry imaging (MSI) is a powerful technique that combines the abil-ity of microscopy to provide spatial information about multiple molecular species with the specificity of mass spectrometry (MS) for unlabeled mapping of analytes in diverse biological tissues. Initial pharmacological applications focused on drug distributions in different organs, including the compartmentalized brain. However, recent technological advances in instrumentation, software, and chemical tools have allowed its use in quantitative spatial omics. It now enables visualization of distributions of diverse molecules at high lateral resolution in studies of the pharmacokinetic and neuropharmacodynamic effects of drugs on functional biomolecules. Therefore, it has become a versatile technique with a multitude of applications that have transformed neuropharmacological re-search and enabled research into brain physiology at unprecedented resolution, as described in this review.
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| 4. |
- Bauer, Fredric, et al.
(författare)
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Plastics and climate change breaking carbon lock-ins through three mitigation pathways
- 2022
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:4, s. 361-376
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Forskningsöversikt (refereegranskat)abstract
- The plastic industry is dependent on fossil fuels in various ways that result in strong “carbon lock-in” throughout the value chain and large and growing CO2 emissions. The industry must decarbonize to reach global net-zero pledges. Although a few initiatives have been launched, they primarily focus on plastic waste. Current research has investigated mitigation potential on different parts of the plastic value chain but remains in silos. Here, we review carbon lock-ins throughout the plastic value chain and identify possible mitigation pathways for each stage of the plastic life cycle. We show how lock-ins are stubbornly entrenched across the domains of production, markets, waste management, industry organization, and governance. Overcoming these carbon lock-ins and achieving zero-carbon targets for the sector by 2050 will require thorough systemic change to how plastics are produced, used, and recycled, including promotion of demand reduction strategies, bio-based feedstocks, and circular economy principles. Strict governance structures, enforceable regulation, and a new proactive and inclusive vision for the low-carbon transition are equally important.
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| 5. |
- Berglund, Lisa, et al.
(författare)
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A genecentric Human Protein Atlas for expression profiles based on antibodies
- 2008
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 7:10, s. 2019-2027
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Forskningsöversikt (refereegranskat)abstract
- An attractive path forward in proteomics is to experimentally annotate the human protein complement of the genome in a genecentric manner. Using antibodies, it might be possible to design protein-specific probes for a representative protein from every protein-coding gene and to subsequently use the antibodies for systematical analysis of cellular distribution and subcellular localization of proteins in normal and disease tissues. A new version (4.0) of the Human Protein Atlas has been developed in a genecentric manner with the inclusion of all human genes and splice variants predicted from genome efforts together with a visualization of each protein with characteristics such as predicted membrane regions, signal peptide, and protein domains and new plots showing the uniqueness (sequence similarity) of every fraction of each protein toward all other human proteins. The new version is based on tissue profiles generated from 6120 antibodies with more than five million immunohistochemistry-based images covering 5067 human genes, corresponding to approximately 25% of the human genome. Version 4.0 includes a putative list of members in various protein classes, both functional classes, such as kinases, transcription factors, G-protein-coupled receptors, etc., and project-related classes, such as candidate genes for cancer or cardiovascular diseases. The exact antigen sequence for the internally generated antibodies has also been released together with a visualization of the application-specific validation performed for each antibody, including a protein array assay, Western blot analysis, immunohistochemistry, and, for a large fraction, immunofluorescence-based confocal microscopy. New search functionalities have been added to allow complex queries regarding protein expression profiles, protein classes, and chromosome location. The new version of the protein atlas thus is a resource for many areas of biomedical research, including protein science and biomarker discovery.
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| 6. |
- Błaszkowska, Magdalena, et al.
(författare)
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Subclinical macroangiopathic target organ damage in type 1 diabetes mellitus patients
- 2020
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 29:6, s. 344-356
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Forskningsöversikt (refereegranskat)abstract
- Purpose: We have summarized key studies regarding the assessment of subclinical macroangiopathic target organ damage (TOD) in type 1 diabetes mellitus (T1DM). Results: Although chronic complications resulting from hyperglycemia, in particular macroangiopathies, are still the first cause of death in T1DM, there has been growing recognition of the role of hypoglycemia in cardiovascular morbidity and mortality. Subclinical TOD diagnosis ensures early implementation of the complex management aiming at either partial reversal of these complications or at least its downturn. To better identify patients with early TODs, several non-invasive diagnostic techniques are employed, including the ultrasonographic assessment of the intima-media thickness (IMT), computed tomography (CT) for coronary artery calcium (CAC) scores, and pulse wave velocity (PWV) measurement for arterial stiffness evaluation. Various studies reported that T1DM patients present an increased IMT. An increasing IMT fairly correlates with the cardiovascular (CV) events risk even after the adjustment to age, diabetes duration, quality of glucose control as well as the presence of hypertension, and chronic complications. Another, well established marker of the organ damage–CAC score is recommended by ACC/AHA guidelines to assess the overall CV risk in T1DM. Also, the arterial stiffness evaluation with PWV may further improve CV risk prediction, which has been reported in multiple studies including the Framingham Heart Study. Conclusions: There is shortage of data from prospective studies which could confirm the benefits of early treatment initiation based on the presence of the subclinical organ damage in T1DM. Most evidence comes from T2DM trials, where effective preventive measures were identified i.e.: smoking cessation, reasonable blood glucose control, efficacious hypertension treatment, and dyslipidemia management, as well as renoprotection. There is still a field for further research to see if routine assessment of asymptomatic vascular damage and early implementation of aggressive treatment would reduce mortality excess from CVD in T1DM.
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| 7. |
- Cobice, D. F., et al.
(författare)
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Future technology insight : mass spectrometry imaging as a tool in drug research and development
- 2015
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 172:13, s. 3266-3283
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Forskningsöversikt (refereegranskat)abstract
- In pharmaceutical research, understanding the biodistribution, accumulation and metabolism of drugs in tissue plays a key role during drug discovery and development. In particular, information regarding pharmacokinetics, pharmacodynamics and transport properties of compounds in tissues is crucial during early screening. Historically, the abundance and distribution of drugs have been assessed by well-established techniques such as quantitative whole-body autoradiography (WBA) or tissue homogenization with LC/MS analysis. However, WBA does not distinguish active drug from its metabolites and LC/MS, while highly sensitive, does not report spatial distribution. Mass spectrometry imaging (MSI) can discriminate drug and its metabolites and endogenous compounds, while simultaneously reporting their distribution. MSI data are influencing drug development and currently used in investigational studies in areas such as compound toxicity. In in vivo studies MSI results may soon be used to support new drug regulatory applications, although clinical trial MSI data will take longer to be validated for incorporation into submissions. We review the current and future applications of MSI, focussing on applications for drug discovery and development, with examples to highlight the impact of this promising technique in early drug screening. Recent sample preparation and analysis methods that enable effective MSI, including quantitative analysis of drugs from tissue sections will be summarized and key aspects of methodological protocols to increase the effectiveness of MSI analysis for previously undetectable targets addressed. These examples highlight how MSI has become a powerful tool in drug research and development and offers great potential in streamlining the drug discovery process.
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| 8. |
- Falk Delgado, Anna, et al.
(författare)
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Diagnostic value of alternative techniques to gadolinium-based contrast agents in MR neuroimaging : a comprehensive overview
- 2019
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Ingår i: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 10:1
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Forskningsöversikt (refereegranskat)abstract
- Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017.This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging.Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke.In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.
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| 9. |
- Fredolini, Claudia, et al.
(författare)
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Immunocapture strategies in translational proteomics
- 2016
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Ingår i: Expert Review of Proteomics. - : Taylor & Francis. - 1478-9450 .- 1744-8387. ; 13:1, s. 83-98
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Forskningsöversikt (refereegranskat)abstract
- Aiming at clinical studies of human diseases, antibody-assisted assays have been applied to biomarker discovery and toward a streamlined translation from patient profiling to assays supporting personalized treatments. In recent years, integrated strategies to couple and combine antibodies with mass spectrometry-based proteomic efforts have emerged, allowing for novel possibilities in basic and clinical research. Described in this review are some of the field's current and emerging immunocapture approaches from an affinity proteomics perspective. Discussed are some of their advantages, pitfalls and opportunities for the next phase in clinical and translational proteomics.
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| 10. |
- Fuks, Kateryna B., et al.
(författare)
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Arterial blood pressure and long-term exposure to traffic-related air pollution : an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 122:9, s. 896-905
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Long-term exposure to air pollution is hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country-specific. OBJECTIVES: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. METHODS: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated with BP lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. RESULTS: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in non-medicated participants (0.35 mmHg [95% CI: 0.02-0.68] and 0.22 mmHg [95% CI: 0.04-0.40] per 4,000,000 vehicles × m/day, respectively). The estimated odds ratio for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled air pollutants and BP were not clearly associated. CONCLUSIONS: In this first comprehensive meta-analysis of European population-based cohorts we observed a weak positive association of high residential traffic exposure with BP in non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent.
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