| 1. |
- Bousquet, J., et al.
(författare)
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Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
- 2017
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
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Tidskriftsartikel (refereegranskat)abstract
- The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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| 2. |
- Duong, M., et al.
(författare)
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Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV 1 (PURE): an international, community-based cohort study
- 2019
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Ingår i: The Lancet Global Health. - 2214-109X. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: The associations between the extent of forced expiratory volume in 1 s (FEV 1 ) impairment and mortality, incident cardiovascular disease, and respiratory hospitalisations are unclear, and how these associations might vary across populations is unknown. Methods: In this international, community-based cohort study, we prospectively enrolled adults aged 35–70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV 1 . FEV 1 values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV 1 value (FEV 1 %). FEV 1 % was categorised as no impairment (FEV 1 % ≥0 SD from country-specific mean), mild impairment (FEV 1 % <0 SD to −1 SD), moderate impairment (FEV 1 % <–1 SD to −2 SDs), and severe impairment (FEV 1 % <–2 SDs [ie, clinically abnormal range]). Follow-up was done every 3 years to collect information on mortality, cardiovascular disease outcomes (including myocardial infarction, stroke, sudden death, or congestive heart failure), and respiratory hospitalisations (from chronic obstructive pulmonary disease, asthma, pneumonia, tuberculosis, or other pulmonary conditions). Fully adjusted hazard ratios (HRs) were calculated by multilevel Cox regression. Findings: Among 126 359 adults with acceptable spirometry data available, during a median 7·8 years (IQR 5·6–9·5) of follow-up, 5488 (4·3%) deaths, 5734 (4·5%) cardiovascular disease events, and 1948 (1·5%) respiratory hospitalisation events occurred. Relative to the no impairment group, mild to severe FEV 1 % impairments were associated with graded increases in mortality (HR 1·27 [95% CI 1·18–1·36] for mild, 1·74 [1·60–1·90] for moderate, and 2·54 [2·26–2·86] for severe impairment), cardiovascular disease (1·18 [1·10–1·26], 1·39 [1·28–1·51], 2·02 [1·75–2·32]), and respiratory hospitalisation (1·39 [1·24–1·56], 2·02 [1·75–2·32], 2·97 [2·45–3·60]), and this pattern persisted in subgroup analyses considering country income level and various baseline risk factors. Population-attributable risk for mortality (adjusted for age, sex, and country income) from mildly to moderately reduced FEV 1 % (24·7% [22·2–27·2]) was larger than that from severely reduced FEV 1 % (3·7% [2·1–5·2]) and from tobacco use (19·7% [17·2–22·3]), previous cardiovascular disease (5·5% [4·5–6·5]), and hypertension (17·1% [14·6–19·6]). Population-attributable risk for cardiovascular disease from mildly to moderately reduced FEV 1 was 17·3% (14·8–19·7), second only to the contribution of hypertension (30·1% [27·6–32·5]). Interpretation: FEV 1 is an independent and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation, even across the clinically normal range (mild to moderate impairment). Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline, Novartis, and King Pharma. Additional funders are listed in the appendix. © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
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| 3. |
- O'Byrne, P., et al.
(författare)
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Asthma progression and mortality: the role of inhaled corticosteroids
- 2019
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 54:1
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Tidskriftsartikel (refereegranskat)abstract
- Overall, asthma mortality rates have declined dramatically in the last 30 years, due to improved diagnosis and to better treatment, particularly in the 1990s following the more widespread use of inhaled corticosteroids (ICSs). The impact of ICS on other long-term outcomes, such as lung function decline, is less certain, in part because the factors associated with these outcomes are incompletely understood. The purpose of this review is to evaluate the effect of pharmacological interventions, particularly ICS, on asthma progression and mortality. Furthermore, we review the potential mechanisms of action of pharmacotherapy on asthma progression and mortality, the effects of ICS on long-term changes in lung function, and the role of ICS in various asthma phenotypes. Overall, there is compelling evidence of the value of ICS in improving asthma control, as measured by improved symptoms, pulmonary function and reduced exacerbations. There is, however, less convincing evidence that ICS prevents the decline in pulmonary function that occurs in some, although not all, patients with asthma. Severe exacerbations are associated with a more rapid decline in pulmonary function, and by reducing the risk of severe exacerbations, it is likely that ICS will, at least partially, prevent this decline. Studies using administrative databases also support an important role for ICS in reducing asthma mortality, but the fact that asthma mortality is, fortunately, an uncommon event makes it highly improbable that this will be demonstrated in prospective trials.
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| 4. |
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| 5. |
- Marinho, Catarina M., et al.
(författare)
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The σB-dependent regulatory sRNA Rli47 represses isoleucine biosynthesis in Listeria monocytogenes through a direct interaction with the ilvA transcript
- 2019
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Ingår i: RNA Biology. - : Taylor & Francis. - 1547-6286 .- 1555-8584. ; 16:10, s. 1424-1437
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Tidskriftsartikel (refereegranskat)abstract
- The facultative intracellular pathogen Listeria monocytogenes can persist and grow in a diverse range of environmental conditions, both outside and within its mammalian host. The alternative sigma factor Sigma B (sigma(B)) plays an important role in this adaptability and is critical for the transition into the host. While some of the functions of the sigma(B) regulon in facilitating this transition are understood the role of sigma(B)-dependent small regulatory RNAs (sRNAs) remain poorly characterized. In this study, we focused on elucidating the function of Rli47, a sigma(B)-dependent sRNA that is highly induced in the intestine and in macrophages. Using a combination of in silico and in vivo approaches, a binding interaction was predicted with the Shine-Dalgarno region of the ilvA mRNA, which encodes threonine deaminase, an enzyme required for branched-chain amino acid biosynthesis. Both ilvA transcript levels and threonine deaminase activity were increased in a deletion mutant lacking the rli47 gene. The Delta rli47 mutant displayed a shorter growth lag in isoleucine-depleted growth media relative to the wild-type, and a similar phenotype was also observed in a mutant lacking sigma(B). The impact of the Delta rli47 on the global transcription profile of the cell was investigated using RNA-seq, and a significant role for Rli47 in modulating amino acid metabolism was uncovered. Taken together, the data point to a model where Rli47 is responsible for specifically repressing isoleucine biosynthesis as a way to restrict growth under harsh conditions, potentially contributing to the survival of L. monocytogenes in niches both outside and within the mammalian host.
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