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- Eron, Joseph J., et al.
(author)
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Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
- 2019
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In: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 170
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Journal article (peer-reviewed)abstract
- © 2019 The Authors Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
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- Pastur, G. J. M., et al.
(author)
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Landscape Variables Influence over Active Restoration Strategies of Nothofagus Forests Degraded by Invasive Castor canadensis in Tierra del Fuego
- 2021
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In: Sustainability. - : MDPI AG. - 2071-1050. ; 13:14
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Journal article (peer-reviewed)abstract
- North American beavers (Castor canadensis) are responsible for the major changes in the Tierra del Fuego Archipelago, altering riparian forests for the long-term. Passive restoration of the areas affected was ineffective in the medium-term (up to 20 years), being necessary active strategies. Plantations in abandoned ponds were made with Nothofagus pumilio and N. antarctica tree species across Tierra del Fuego island (Argentina). In the first experiment, we analysed the influence of biotic and abiotic factors in three micro-habitats in the impacted areas: front and tail of ponds, and cut not-flooded forest areas. Five-years-old N. pumilio seedlings had 39% survival in front, 21% in tails, and 46% in cut areas at year-3 of the restoration experiments, being negatively influenced by plant cover and soil moisture. Lower growth was recorded during year-1 (0.7-0.9 cm yr(-1)), but increased on time (1.9 cm yr(-1) front, 1.6 cm yr(-1) tail, 4.3 cm yr(-1) cut areas). A second experiment explores the alternative to substitute the tree species to face the harder conditions of the impact and climate change. For this, we conducted a new plantation at four locations across the main bioclimatic zones, where 10-40 cm N. antarctica plants attained 17% survival in meadows (front and tail) and 30% in cut areas, being higher with larger than smaller plants (25% vs. 18%), and where they are mainly influenced by rainfall (4% in sites 400 mm yr(-1)). The main damage was detected in the above-ground biomass due to dryness, but root survival allowed the emergence of new shoots in the following growing season. It is necessary to monitor different Nothofagus species across natural environments in the landscape to determine the feasibility and effectiveness of different strategies in restoration plans, considering the selection of climate-resilient tree species.
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| 6. |
- Lindqvist, Daniel, et al.
(author)
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Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress.
- 2014
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In: Brain Behavior and Immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 42:Jun 12, s. 81-88
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Journal article (peer-reviewed)abstract
- Chronic inflammation may be involved in combat-related post-traumatic stress disorder (PTSD) and may help explain comorbid physical diseases. However, the extent to which combat exposure per se, depression, or early life trauma, all of which are associated with combat PTSD, may confound the relationship between PTSD and inflammation is unclear.
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| 7. |
- Bersani, Francesco S, et al.
(author)
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Association of dimensional psychological health measures with telomere length in male war veterans.
- 2016
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In: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 190, s. 537-542
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Journal article (peer-reviewed)abstract
- Several psychiatric disorders may be characterized by peripheral telomere shortening. However, it is unclear whether telomere shortening is associated with these psychiatric disorders per se or, rather, with underlying dimensional parameters that are often, but not necessarily, associated with them. We explored the association between dimensional psychopathological measures and telomere length (TL) in granulocytes among veterans independent of psychiatric diagnosis.
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- Lazaridis, Iosif, et al.
(author)
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Ancient human genomes suggest three ancestral populations for present-day Europeans
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 409-
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Journal article (peer-reviewed)abstract
- We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
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- Mellon, Synthia H., et al.
(author)
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Metabolomic analysis of male combat veterans with post traumatic stress disorder
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
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Journal article (peer-reviewed)abstract
- Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We sought to identify metabolites that are altered in male combat veterans with PTSD. In this case-control study, we compared metabolomic profiles from age-matched male combat trauma-exposed veterans from the Iraq and Afghanistan conflicts with PTSD (n = 52) and without PTSD (n = 51) (‘Discovery group’). An additional group of 31 PTSD-positive and 31 PTSD-negative male combat-exposed veterans was used for validation of these findings (‘Test group’). Plasma metabolite profiles were measured in all subjects using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified key differences between PTSD subjects and controls in pathways related to glycolysis and fatty acid uptake and metabolism in the initial ‘Discovery group’, consistent with mitochondrial alterations or dysfunction, which were also confirmed in the ‘Test group’. Other pathways related to urea cycle and amino acid metabolism were different between PTSD subjects and controls in the ‘Discovery’ but not in the smaller ‘Test’ group. These metabolic differences were not explained by comorbid major depression, body mass index, blood glucose, hemoglobin A1c, smoking, or use of analgesics, antidepressants, statins, or anti-inflammatories. These data show replicable, wide-ranging changes in the metabolic profile of combat-exposed males with PTSD, with a suggestion of mitochondrial alterations or dysfunction, that may contribute to the behavioral and somatic phenotypes associated with this disease.
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