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Sehlstedt, Maria
Publications (10 of 14) Show all publications
Gouveia-Figueira, S. C., Karimpour, M., Bosson, J. A., Blomberg, A., Unosson, J., Sehlstedt, M., . . . Nording, M. L. (2018). Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust. Analytica Chimica Acta, 1018, 62-69
Open this publication in new window or tab >>Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust
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2018 (English)In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, p. 62-69Article in journal (Refereed) Published
Abstract [en]

Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Oxylipin, Endocannabinoid, Eicosanoid, Mass spectrometry, Rapeseed methyl ester, Inflammation
National Category
Occupational Health and Environmental Health Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-148622 (URN)10.1016/j.aca.2018.02.032 (DOI)000428798200008 ()29605135 (PubMedID)
Funder
Swedish Research Council, 2010-303AFA Insurance, 130320
Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2018-06-26Bibliographically approved
Pfeffer, P. E., Ho, T. R., Mann, E. H., Kelly, F. J., Sehlstedt, M., Pourazar, J., . . . Hawrylowicz, C. M. (2018). Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes. Immunology, 153(4), 502-512
Open this publication in new window or tab >>Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes
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2018 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 153, no 4, p. 502-512Article in journal (Refereed) Published
Abstract [en]

Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPM in vitro in the presence/absence of granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was then assessed by measuring T-cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon-γ (IFN-γ)-producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-γ+ cells. The secretion of tumour necrosis factor-α, interleukin-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T-cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
CD8(+) T lymphocyte, dendritic cells, granulocyte-macrophage colony-stimulating factor, granzyme, lung, particulate matter
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-146142 (URN)10.1111/imm.12852 (DOI)000426728600010 ()29044495 (PubMedID)
Available from: 2018-05-15 Created: 2018-05-15 Last updated: 2018-06-09Bibliographically approved
Muala, A., Rankin, G., Sehlstedt, M., Unosson, J., Bosson, J. A., Behndig, A., . . . Sandström, T. (2015). Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity. Particle and Fibre Toxicology, 12, Article ID 33.
Open this publication in new window or tab >>Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity
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2015 (English)In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 12, article id 33Article in journal (Refereed) Published
Abstract [en]

Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 mu g/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, < 0.05, < 0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (< 0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, < 0.05 and < 0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, < 0.05, < 0.05 and < 0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure.

Keywords
Air pollution, Biomass, Bronchoscopy, Cytotoxicity, Neutrophils, Lymphocytes, Mast cells
National Category
Environmental Sciences
Identifiers
urn:nbn:se:umu:diva-111761 (URN)10.1186/s12989-015-0111-7 (DOI)000363833500001 ()26511835 (PubMedID)2-s2.0-84945908415 (Scopus ID)
Available from: 2015-11-25 Created: 2015-11-23 Last updated: 2018-06-07Bibliographically approved
Pourazar, J., Behndig, A. F., Helleday, R., Muala, A., Rankin, G., Sehlstedt, M., . . . Bosson, J. A. (2015). Airway Inflammatory Response In Healthy Subjects Following Chamber Exposure To 100% Rme Biodiesel. Paper presented at International Conference of the American-Thoracic-Society (ATS), MAY 15-20, 2015, Denver, CO. American Journal of Respiratory and Critical Care Medicine, 191, Article ID A5252.
Open this publication in new window or tab >>Airway Inflammatory Response In Healthy Subjects Following Chamber Exposure To 100% Rme Biodiesel
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2015 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, article id A5252Article in journal, Meeting abstract (Other academic) Published
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-123483 (URN)000377582807072 ()
Conference
International Conference of the American-Thoracic-Society (ATS), MAY 15-20, 2015, Denver, CO
Available from: 2016-07-06 Created: 2016-07-04 Last updated: 2018-06-07Bibliographically approved
Muala, A., Sehlstedt, M., Bion, A., Österlund, C., Bosson, J. A., Behndig, A. F., . . . Sandström, T. (2014). Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers. Environmental health, 13(1), Article ID 16.
Open this publication in new window or tab >>Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers
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2014 (English)In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, no 1, article id 16Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.

METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.

RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.

CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.

Place, publisher, year, edition, pages
BioMed Central, 2014
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-88557 (URN)10.1186/1476-069X-13-16 (DOI)000334547200001 ()24621126 (PubMedID)
Available from: 2014-05-08 Created: 2014-05-08 Last updated: 2018-06-07Bibliographically approved
Bolling, A. K., Totlandsdal, A. I., Sallsten, G., Braun, A., Westerholm, R., Bergvall, C., . . . Herseth, J. I. (2012). Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines. Particle and Fibre Toxicology, 9, 45
Open this publication in new window or tab >>Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines
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2012 (English)In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 9, p. 45-Article in journal (Refereed) Published
Abstract [en]

Background: Exposure to particulate matter (PM) has been linked to several adverse cardiopulmonary effects, probably via biological mechanisms involving inflammation. The pro-inflammatory potential of PM depends on the particles' physical and chemical characteristics, which again depend on the emitting source. Wood combustion is a major source of ambient air pollution in Northern countries during the winter season. The overall aim of this study was therefore to investigate cellular responses to wood smoke particles (WSPs) collected from different phases of the combustion cycle, and from combustion at different temperatures. Results: WSPs from different phases of the combustion cycle induced very similar effects on pro-inflammatory mediator release, cytotoxicity and cell number, whereas WSPs from medium-temperature combustion were more cytotoxic than WSPs from high-temperature incomplete combustion. Furthermore, comparisons of effects induced by native WSPs with the corresponding organic extracts and washed particles revealed that the organic fraction was the most important determinant for the WSP-induced effects. However, the responses induced by the organic fraction could generally not be linked to the content of the measured polycyclic aromatic hydrocarbons (PAHs), suggesting that also other organic compounds were involved. Conclusion: The toxicity of WSPs seems to a large extent to be determined by stove type and combustion conditions, rather than the phase of the combustion cycle. Notably, this toxicity seems to strongly depend on the organic fraction, and it is probably associated with organic components other than the commonly measured unsubstituted PAHs.

Keywords
Particulate matter, Inflammation, Wood smoke, Combustion phase, Combustion temperature, Organic fraction
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-66809 (URN)10.1186/1743-8977-9-45 (DOI)000314264500001 ()
Available from: 2013-03-08 Created: 2013-03-05 Last updated: 2018-06-08Bibliographically approved
Sehlstedt, M. (2011). Respiratory effects of particulate matter air pollution: studies on diesel exhaust, road tunnel, subway and wood smoke exposure in human subjects. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Respiratory effects of particulate matter air pollution: studies on diesel exhaust, road tunnel, subway and wood smoke exposure in human subjects
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background:

Ambient air pollution is associated with adverse health effects, but the sources and components, which cause these effects is still incompletely understood. The aim of this thesis was to investigate the pulmonary effects of a variety of common air pollutants, including diesel exhaust, biomass smoke, and road tunnel and subway station environments. Healthy non-smoking volunteers were exposed in random order to the specific air pollutants and air/control, during intermittent exercise, followed by bronchoscopy.

Methods and results:

In study I, exposures were performed with diesel exhaust (DE) generated at transient engine load and air for 1 hour with bronchoscopy at 6 hours post-exposure. Immunohistochemical analyses of bronchial mucosal biopsies showed that DE exposure significantly increased the endothelial adhesion molecule expression of p-selectin and VCAM-1, together with increased bronchoalveolar lavage (BAL) eosinophils.

In study II, the subjects were exposed for 1 hour to DE generated during idling with bronchoscopy at 6 hours. The bronchial mucosal biopsies showed significant increases in neutrophils, mast cells and lymphocytes together with bronchial wash neutrophils. Additionally, DE exposure significantly increased the nuclear translocation of the aryl hydrocarbon receptor (AhR) and phosphorylated c-jun in the bronchial epithelium. In contrast, the phase II enzyme NAD(P)H-quinone oxidoreductase 1 (NQO1) decreased after DE.

In study III, the 2-hour exposures took place in a road tunnel with bronchoscopy 14 hours later. The road tunnel exposure significantly increased the total numbers of lymphocytes and alveolar macrophages in BAL, whereas NK cell and CD56+/T cell numbers significantly decreased. Additionally, the nuclear expression of phosphorylated c-jun in the bronchial epithelium was significantly increased after road tunnel exposure.

In study IV, the subjects were exposed to metal-rich particulate aerosol for 2 hours at a subway station with bronchial biopsy and BAL sampling at 14 hours. The subway exposure significantly increased the concentration of glutathione disulphide (GSSG) in BAL, with no airway inflammatory responses. In contrast, the number of neutrophils in the bronchial mucosa and the nuclear expression of phosphorylated c-jun in the bronchial epithelium tended to decrease after the subway exposure.

In study V, the exposure to biomass smoke lasted 3 hours. Bronchoscopy was conducted 24 hours post exposure. The investigated biomass combustion emissions resulted in a significant increase in total glutathione and reduced glutathione in BAL, without any evident acute airway inflammatory responses.

 

 

Conclusion:

The present thesis presents data from exposures of healthy subjects to a variety of common air pollutants, as compared with an air reference. Oxidative as well as bronchial mucosal and bronchoalveolar responses differed between these air pollutants, with the most pronounced airway effects seen after exposure to diesel exhaust. This may be due to differences in pulmonary deposition, physicochemical characteristics, toxicological pathways and potency. Additional studies will assist in addressing dose-response and time kinetic aspects of the airway responses.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2011. p. 110
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1394
Keywords
Airway inflammation, antioxidant, bronchoscopy, detoxification, immunohistochemistry, particulate matter
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-39568 (URN)978-91-7459-130-9 (ISBN)
Public defence
2011-02-24, E04, Byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2011-02-04 Created: 2011-02-01 Last updated: 2018-06-08Bibliographically approved
Sehlstedt, M., Behndig, A., Boman, C., Blomberg, A., Sandström, T. & Pourazar, J. (2010). Airway inflammatory response to diesel exhaust generated at urban cycle running conditions. Inhalation Toxicology, 22(14), 1144-1150
Open this publication in new window or tab >>Airway inflammatory response to diesel exhaust generated at urban cycle running conditions
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2010 (English)In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 22, no 14, p. 1144-1150Article in journal (Refereed) Published
Abstract [en]

DE generated under urban running conditions increased bronchial adhesion molecule expressions, together with the novel finding of bronchoalveolar eosinophilia, which has not been shown after exposure to DE at idling. Variations in airway inflammatory response to DE generated under diverse running condition may be related to differences in exhaust composition.

Keywords
Air pollution, adhesion molecules, airway inflammation, particulate matter.
Identifiers
urn:nbn:se:umu:diva-5164 (URN)10.3109/08958378.2010.529181 (DOI)000284889300002 ()21110774 (PubMedID)
Available from: 2006-05-11 Created: 2006-05-11 Last updated: 2018-06-09Bibliographically approved
Sehlstedt, M., Dove, R., Boman, C., Pagels, J., Swietlicki, E., Löndahl, J., . . . Blomberg, A. (2010). Antioxidant airway responses following experimental exposure to wood smoke in man. Particle and fibre toxicology, 7, 21
Open this publication in new window or tab >>Antioxidant airway responses following experimental exposure to wood smoke in man
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2010 (English)In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 7, p. 21-Article in journal (Refereed) Published
Abstract [en]

Exposure of healthy subjects to wood smoke, derived from an experimental wood pellet boiler operating under incomplete combustion conditions with PM emissions dominated by organic matter, caused an increase in mucosal symptoms and GSH in the alveolar respiratory tract lining fluids but no acute airway inflammatory responses. We contend that this response reflects a mobilisation of GSH to the air-lung interface, consistent with a protective adaptation to the investigated wood smoke exposure.

Identifiers
urn:nbn:se:umu:diva-39427 (URN)10.1186/1743-8977-7-21 (DOI)000282501800001 ()20727160 (PubMedID)
Available from: 2011-01-27 Created: 2011-01-27 Last updated: 2018-06-08Bibliographically approved
Sehlstedt, M., Andersen, G. N., Nilsson, K., Blomberg, A., Mincheva-Nilsson, L., Waldenström, A., . . . Sandström, T. (2009). Suppressed signal transduction in the bronchial epithelium of patients with systemic sclerosis. Respiratory Medicine, 103(2), 301-308
Open this publication in new window or tab >>Suppressed signal transduction in the bronchial epithelium of patients with systemic sclerosis
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2009 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 103, no 2, p. 301-308Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disorder, which frequently affects the lungs, with manifestations of interstitial lung disease (ILD) with lung fibrosis and of pulmonary hypertension. The pathogenesis remains largely unrecognised.

OBJECTIVE: The aim of this study was to elucidate the inflammation in the bronchial mucosa in patients with SSc.

SUBJECTS AND METHODS: Twenty-three subjects diagnosed with SSc participated. Twelve of the SSc patients showed signs of ILD, four were smokers and seven were treated with oral corticosteroids. Seventeen non-smoking, age- and sex-matched healthy subjects served as controls. Bronchoscopy was performed to sample endobronchial mucosal biopsies, which were immunohistochemically stained using a panel of antibodies against inflammatory markers.

RESULTS: The number of neutrophils was significantly elevated in the submucosa of SSc patients, regardless of ILD, or whether the subject was smoking or using oral corticosteroids. No up-regulation of neutrophil chemoattractants or cytokines was seen in the bronchial epithelium. The signal transduction pathways and adhesion molecule expression tended to be suppressed or unchanged in SSc patients compared with controls.

CONCLUSION: It is concluded that SSc is associated with a chronic neutrophilic inflammation in the bronchial mucosal, with signs of suppressed signal transduction, regardless of the presence of interstitial lung disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-21507 (URN)10.1016/j.rmed.2008.08.011 (DOI)18819788 (PubMedID)
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
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