| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Adamson, R. E., et al.
(författare)
-
In Vitro Primary Cell Culture as a Physiologically Relevant Method for Preclinical Testing of Human Oncolytic Adenovirus
- 2012
-
Ingår i: Human Gene Therapy. - : Mary Ann Liebert Inc. - 1043-0342 .- 1557-7422. ; 23:2, s. 218-230
-
Tidskriftsartikel (refereegranskat)abstract
- Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.
|
|
| 6. |
|
|
| 7. |
- Evans, M, et al.
(författare)
-
Cinacalcet use and the risk of cardiovascular events, fractures and mortality in chronic kidney disease patients with secondary hyperparathyroidism
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 2103-
-
Tidskriftsartikel (refereegranskat)abstract
- With the aim to expand the randomized controlled trial evidence of cinacalcet treatment to the unselected, general chronic kidney disease (CKD) population we analysed a large inception cohort of CKD patients in the region of Stockholm, Sweden 2006–2012 (both non-dialysis, dialysis and transplanted) with evidence of secondary hyperparathyroidism (SHPT). We used marginal structural models to account for both confounding by indication and time-dependent confounding. Over 37 months, 435/3,526 (12%) initiated cinacalcet de novo. Before cinacalcet initiation, parathyroid hormone (PTH) had increased progressively to a median of 636ng/L. After cinacalcet initiation, PTH declined, as did serum calcium and phosphate. In total, 42% of patients experienced a fatal/non-fatal cardiovascular event, 32% died and 9% had a new fracture. The unadjusted cardiovascular odds ratio (OR) associated with cinacalcet treatment was 1.01 (95% confidence interval: 0.83, 1.22). In the fully weighted model, the cardiovascular odds was lower in cinacalcet treated patients (OR 0.67: 0.48, 0.93). The adjusted ORs for all-cause mortality and for fractures were 0.79 (0.56, 1.11) and 1.08 (0.59, 1.98) respectively. Our study suggests cinacalcet treatment improves biochemical abnormalities in the wider CKD population, and adds real-world support that treating SHPT with cinacalcet may have beneficial effects on cardiovascular outcomes.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Lennox, Robert J., et al.
(författare)
-
Electronic tagging and tracking aquatic animals to understand a world increasingly shaped by a changing climate and extreme weather events
- 2024
-
Ingår i: Canadian Journal of Fisheries and Aquatic Sciences. - 0706-652X .- 1205-7533. ; 81:3, s. 326-339
-
Tidskriftsartikel (refereegranskat)abstract
- Despite great promise for understanding the impacts and extent of climate change and extreme weather events on aquatic animals, their species, and ecological communities, it is surprising that electronic tagging and tracking tools, like biotelemetry and biologging, have not been extensively used to understand climate change or develop and evaluate potential interventions that may help adapt to its impacts. In this review, we provide an overview of methodologies and study designs that leverage available electronic tracking tools to investigate aspects of climate change and extreme weather events in aquatic ecosystems. Key interventions to protect aquatic life from the impacts of climate change, including habitat restoration, protected areas, conservation translocations, mitigations against interactive effects of climate change, and simulation of future scenarios, can all be greatly facilitated by using electronic tagging and tracking. We anticipate that adopting animal tracking to identify phenotypes, species, or ecosystems that are vulnerable or resilient to climate change will help in applying management interventions such as fisheries management, habitat restoration, invasive species control, or enhancement measures that prevent extinction and strengthen the resilience of communities against the most damaging effects of climate change. Given the scalability and increasing accessibility of animal tracking tools for researchers, tracking individual organisms will hopefully also facilitate research into effective solutions and interventions against the most extreme and acute impacts on species, populations, and ecosystems.
|
|
