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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Hernández-Alvarez, María Isabel, et al.
(author)
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Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease
- 2019
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In: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 177:4, s. 881-895.e17
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Journal article (peer-reviewed)abstract
- Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
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| 3. |
- Julià, Mireia, et al.
(author)
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Employment and Labor Market Results of the SOPHIE Project : Concepts, Analyses, and Policies
- 2017
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In: International Journal of Health Services. - : SAGE Publications. - 0020-7314 .- 1541-4469. ; 47:1, s. 18-39
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Journal article (peer-reviewed)abstract
- This article reports evidence gained by the SOPHIE Project regarding employment and labor market-related policies. In the first step, quality of employment and of precarious and informal employment in Europe were conceptualized and defined. Based on these definitions, we analyzed changes in the prevalence and population distribution of key health-affecting characteristics of employment and work between times of economic prosperity and economic crisis in Europe and investigated their impact on health outcomes. Additionally, we examined the effects of several employment and labor market-related policies on factors affecting health equity, including a specific analysis concerning work-related gender equity policies and case studies in different European countries. Our findings show that there is a need to standardize definitions and indicators of (the quality of) employment conditions and improve information systems. This is challenging given the important differences between and within European countries. In our results, low quality of employment and precarious employment is associated with poor mental health. In order to protect the well-being of workers and reduce work-related health inequalities, policies leading to precarious working and employment conditions need to be suspended. Instead, efforts should be made to improve the security and quality of employment for all workers.
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| 5. |
- Ryan, Charles J, et al.
(author)
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Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302) : final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study
- 2015
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In: The Lancet Oncology. - 1474-5488. ; 16:2, s. 60-152
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Journal article (peer-reviewed)abstract
- BACKGROUND: Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies.METHODS: In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198.FINDINGS: At a median follow-up of 49.2 months (IQR 47.0-51.8), 741 (96%) of the prespecified 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34.7 months [95% CI 32.7-36.8] vs 30.3 months [28.7-33.3]; hazard ratio 0.81 [95% CI 0.70-0.93]; p=0.0033). The most common grade 3-4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [<1%]), and hypertension (25 [5%] vs 17 [3%]).INTERPRETATION: In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.FUNDING: Janssen Research & Development.
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| 6. |
- Valle, Xavier, et al.
(author)
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Muscle Injuries in Sports: A New Evidence-Informed and Expert Consensus-Based Classification with Clinical Application.
- 2017
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In: Sports medicine (Auckland, N.Z.). - : Springer Science and Business Media LLC. - 1179-2035 .- 0112-1642. ; 47:7, s. 1241-1253
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Journal article (peer-reviewed)abstract
- Muscle injuries are among the most common injuries in sport and continue to be a major concern because of training and competition time loss, challenging decision making regarding treatment and return to sport, and a relatively high recurrence rate. An adequate classification of muscle injury is essential for a full understanding of the injury and to optimize its management and return-to-play process. The ongoing failure to establish a classification system with broad acceptance has resulted from factors such as limited clinical applicability, and the inclusion of subjective findings and ambiguous terminology. The purpose of this article was to describe a classification system for muscle injuries with easy clinical application, adequate grouping of injuries with similar functional impairment, and potential prognostic value. This evidence-informed and expert consensus-based classification system for muscle injuries is based on a four-letter initialism system: MLG-R, respectively referring to the mechanism of injury (M), location of injury (L), grading of severity (G), and number of muscle re-injuries (R). The goal of the classification is to enhance communication between healthcare and sports-related professionals and facilitate rehabilitation and return-to-play decision making.
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