| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Razavi, H., et al.
(författare)
-
Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study
- 2017
-
Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 2:5, s. 325-336
-
Tidskriftsartikel (refereegranskat)abstract
- Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000-3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0.64% (95% UI 0.41-0.74). We estimated that 1 180 000 (95% UI 1 003 000-1 357 000) people were diagnosed with viraemia (36.4%), 150 000 (12 000-180 000) were treated (4.6% of the total infected population or 12.7% of the diagnosed population), 133 000 (106 000-160 000) were cured (4.1%), and 57 900 (43 900-67 300) were newly infected (1.8%) in 2015. Additionally, 30 400 (26 600-42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Carravetta, V., et al.
(författare)
-
PH-dependent X-ray Photoelectron Chemical Shifts and Surface Distribution of Cysteine in Aqueous Solution
- 2019
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 123:17, s. 3776-3785
-
Tidskriftsartikel (refereegranskat)abstract
- The distribution and protonation states of amino acids in water droplets are of considerable concern in studies on the formation of clouds in the atmosphere as well as in many biological contexts. In the present work we use the amino acid cysteine as a prototypical example and explore the protonation states of this molecule in aqueous solution, which are strongly affected by the acidity of the environment and also can show different distributions between surface and bulk. We use a combination of X-ray photoelectron chemical shift measurements, density functional theory calculations of the shifts, and reactive force field molecular dynamics simulations of the underlying structural dynamics. We explore how the photoelectron spectra distinctly reflect the different protonation states that are generated by variation of the solution acidity and how the distribution of these protonation states can differ between bulk and surface regions. At specific pH values, we find that the distribution of the cysteine species at the surface is quite different from that in bulk, in particular, for the appearance in the surface region of species which do not exist in bulk. Some ramifications of this finding are discussed.
|
|
| 9. |
|
|
| 10. |
- de Souza Marinho, Thatiany, et al.
(författare)
-
Rosuvastatin limits the activation of hepatic stellate cells in diet-induced obese mice
- 2017
-
Ingår i: Hepatology Research. - : WILEY. - 1386-6346 .- 1872-034X. ; 47:9, s. 928-940
-
Tidskriftsartikel (refereegranskat)abstract
- Aim The aim of this study was to investigate the effects of rosuvastatin in a model of diet-induced obesity and non-alcoholic fatty liver disease, with attention to the activation of hepatic stellate cells (HSCs). Method Male C57BL/6 mice received a control diet (C; 10% energy as lipids) or a high-fat diet (HF; 50% energy as lipids) for 12 weeks, followed by 7 weeks of treatment. Group CR received control diet + rosuvastatin; group HFR received high-fat diet + rosuvastatin. Results The HF group showed higher insulin, total cholesterol, triacylglycerol, and leptin levels than the C group, all of which were significantly diminished by rosuvastatin in the HFR group. The HF group had greater steatosis and activated HSCs than the C group, whereas rosuvastatin diminished the steatosis (less 21%, P amp;lt; 0.001) and significantly inhibited the activation of the HSCs in the HFR group compared to the HF group. The sterol regulatory element-binding protein-1 and the peroxisome proliferator-activated receptor (PPAR)-gamma protein expressions were increased in HF animals and reduced after treatment in the HFR group. By contrast, low PPAR-alpha and carnitine palmitoyltransferase-1 expressions were found in the HF group, and were restored by rosuvastatin treatment in the HFR group. Conclusion Rosuvastatin mitigated hepatic steatosis by modulating PPAR balance, favoring PPAR-alpha over PPAR-gamma downstream effects. The effects were accompanied by a diminishing of insulin resistance, the anti-inflammatory adipokine profile, and HSC activation, avoiding non-alcoholic fatty liver disease progression and non-alcoholic steatohepatitis onset in this model.
|
|
