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| 2. |
- Bousquet, J, et al.
(författare)
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Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
- 2012
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
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Tidskriftsartikel (refereegranskat)abstract
- Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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| 3. |
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| 4. |
- Custovic, A., et al.
(författare)
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EAACI position statement on asthma exacerbations and severe asthma
- 2013
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Ingår i: Allergy. - : Wiley. - 0105-4538. ; 68:12, s. 1520-1531
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Tidskriftsartikel (refereegranskat)abstract
- Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.
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| 6. |
- Makela, K. T., et al.
(författare)
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Countrywise results of total hip replacement An analysis of 438,733 hips based on the Nordic Arthroplasty Register Association database
- 2014
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 85:2, s. 107-116
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose An earlier Nordic Arthroplasty Register Association (NARA) report on 280,201 total hip replacements (THRs) based on data from 1995-2006, from Sweden, Norway, and Denmark, was published in 2009. The present study assessed THR survival according to country, based on the NARA database with the Finnish data included. Material and methods 438,733 THRs performed during the period 1995-2011 in Sweden, Denmark, Norway, and Finland were included. Kaplan-Meier survival analysis was used to calculate survival probabilities with 95% confidence interval (CI). Cox multiple regression, with adjustment for age, sex, and diagnosis, was used to analyze implant survival with revision for any reason as endpoint. Results The 15-year survival, with any revision as an endpoint, for all THRs was 86% (CI: 85.7-86.9) in Denmark, 88% (CI: 87.6-88.3) in Sweden, 87% (CI: 86.4-87.4) in Norway, and 84% (CI: 82.9-84.1) in Finland. Revision risk for all THRs was less in Sweden than in the 3 other countries during the first 5 years. However, revision risk for uncemented THR was less in Denmark than in Sweden during the sixth (HR = 0.53, CI: 0.34-0.82), seventh (HR = 0.60, CI: 0.37-0.97), and ninth (HR = 0.59, CI: 0.36-0.98) year of follow-up. Interpretation The differences in THR survival rates were considerable, with inferior results in Finland. Brand-level comparison of THRs in Nordic countries will be required.
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| 9. |
- Hepojoki, J, et al.
(författare)
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Acute hantavirus infection induces galectin-3-binding protein
- 2014
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 95:Pt 11, s. 2356-2364
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Tidskriftsartikel (refereegranskat)abstract
- Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection bothin vitroandin vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Ourin vitroexperiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP alsoin vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection.
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| 12. |
- Baharudin, Zikri A., et al.
(författare)
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Comparative study on preliminary breakdown pulse trains observed in Johor, Malaysia and Florida, USA
- 2012
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Ingår i: Atmospheric research. - : Elsevier BV. - 0169-8095 .- 1873-2895. ; 117, s. 111-121
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the preliminary breakdown (PB) pulse train preceding the negative first return stroke (RS) is recorded using a broad band antenna system. These analyses were carried out in Johor Bahru, Malaysia and Florida, United States. This is a novel initiative at examining and identifying the characteristics of the PB pulse trains in the negative cloud-to-ground flashes observed in Malaysia. The arithmetic mean of the total pulse train duration is 12.3 ms and the weighted arithmetic mean of the pulse durations and interpulse intervals are 11 mu s and 152 mu s, respectively. The arithmetic mean ratio between the maximum peak amplitude of the PB pulse and the peak RS electric field was 27.8%, and the corresponding value in Florida was 29.4%. The arithmetic mean of the time duration between the most active part of the pulse train, and the RS was 57.6 ms in Malaysia and 22 ms in Florida. A qualitative comparison of our results with those obtained earlier in Sri Lanka. Sweden and Finland supports the hypothesis that the PBP/RS ratio is higher in the northern regions compared to the tropical regions. (C) 2012 Elsevier B.V. All rights reserved.
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| 13. |
- Baharudin, Zikri A., et al.
(författare)
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Negative cloud-to-ground lightning flashes in Malaysia
- 2014
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Ingår i: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 108, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- The characteristics of the negative cloud-to-ground lightning flashes in Malaysia are studied by analyzing the electric fields generated by the whole flash in nanosecond resolution. A total of 405 strokes obtained from 100 successive negative cloud-to-ground lightning flashes were analyzed, which were recorded from seven convective thunderstorms during the southwest monsoon period, i.e. from April to June 2009. It was found that the total number of interstroke intervals has an arithmetic mean value of 86 ms, a geometric mean value of 67 ms and does not depend on the return stroke order. Of the 100 negative ground flashes, 38 flashes (38%) have at least one subsequent return-stroke (SRS) whose electric field peak was greater than that of the first return-stroke (RS). Furthermore, 58 (19%) out of 305 SRS have electric field peak larger than those of the first RS. The arithmetic and geometric mean ratio between the peak electric field of the SRS and the peak electric field of the first RS are 0.7 and 0.6, respectively. The percentage of single-stroke flashes was 16% while the mean number of strokes per flash and maximum number of stroke per flash were 4 and 14, respectively.
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| 15. |
- Elo, Teresa D., et al.
(författare)
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Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice
- 2010
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Ingår i: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 12:11, s. 94-915
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Tidskriftsartikel (refereegranskat)abstract
- Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG) mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelial morphology progressing from atypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.
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| 17. |
- Mudo, Giuseppa, et al.
(författare)
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Transgenic expression and activation of PGC-1 alpha protect dopaminergic neurons in the MPTP mouse model of Parkinson's disease
- 2012
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : SPRINGER BASEL AG. - 1420-682X .- 1420-9071. ; 69:7, s. 1153-1165
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD), but little is known about the molecular mechanisms controlling these events. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. We show here that transgenic mice overexpressing PGC-1 alpha in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. PGC-1 alpha overexpression also protected against MPTP-induced striatal loss of dopamine, and mitochondria from PGC-1 alpha transgenic mice showed an increased respiratory control ratio compared with wild-type animals. To modulate PGC-1 alpha, we employed the small molecular compound, resveratrol (RSV) that protected dopaminergic neurons against the MPTP-induced cell degeneration almost to the same extent as after PGC-1 alpha overexpression. As studied in vitro, RSV activated PGC-1 alpha in dopaminergic SN4741 cells via the deacetylase SIRT1, and enhanced PGC-1 alpha gene transcription with increases in SOD2 and Trx2. Taken together, the results reveal an important function of PGC-1 alpha in dopaminergic neurons to combat oxidative stress and increase neuronal viability. RSV and other compounds acting via SIRT1/PGC-1 alpha may prove useful as neuroprotective agents in PD and possibly in other neurological disorders.
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| 20. |
- Peltoniemi, Mikko, et al.
(författare)
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Does canopy mean nitrogen concentration explain variation in canopy light use efficiency across 14 contrasting forest sites?
- 2012
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 1758-4469 .- 0829-318X. ; 32:2, s. 200-218
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Tidskriftsartikel (refereegranskat)abstract
- The maximum light use efficiency (LUE = gross primary production (GPP)/absorbed photosynthetic photon flux density (aPPFD)) of plant canopies has been reported to vary spatially and some of this variation has previously been attributed to plant species differences. The canopy nitrogen concentration [N] can potentially explain some of this spatial variation. However, the current paradigm of the N-effect on photosynthesis is largely based on the relationship between photosynthetic capacity (A(max)) and [N], i.e., the effects of [N] on photosynthesis rates appear under high PPFD. A maximum LUE-[N] relationship, if it existed, would influence photosynthesis in the whole range of PPFD. We estimated maximum LUE for 14 eddy-covariance forest sites, examined its [N] dependency and investigated how the [N]-maximum LUE dependency could be incorporated into a GPP model. In the model, maximum LUE corresponds to LUE under optimal environmental conditions before light saturation takes place (the slope of GPP vs. PPFD under low PPFD). Maximum LUE was higher in deciduous/mixed than in coniferous sites, and correlated significantly with canopy mean [N]. Correlations between maximum LUE and canopy [N] existed regardless of daily PPFD, although we expected the correlation to disappear under low PPFD when LUE was also highest. Despite these correlations, including [N] in the model of GPP only marginally decreased the root mean squared error. Our results suggest that maximum LUE correlates linearly with canopy [N], but that a larger body of data is required before we can include this relationship into a GPP model. Gross primary production will therefore positively correlate with [N] already at low PPFD, and not only at high PPFD as is suggested by the prevailing paradigm of leaf-level A(max)-[N] relationships. This finding has consequences for modelling GPP driven by temporal changes or spatial variation in canopy [N].
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