Bulletin of Environmental Contamination and Toxicology - Systemic pesticides, such as the neonicotinoid imidacloprid, can be introduced into aquatic ecosystems through contaminated plant material,... 相似文献
Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ‐plaques and synapse loss, with rTg21221 mice, which overexpress wild‐type human tau. When compared to the APP/PS1 mice without human tau, the cross‐sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque‐associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild‐type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque‐associated synapse loss. 相似文献
Technological progress has led to changes in the antenatal screening programmes, most significantly the introduction of non-invasive prenatal testing (NIPT). The availability of a new type of testing changes the type of information that the parent(s) require before, during and after screening to mitigate anxiety about the testing process and results.
Objectives
To identify the extent to which economic evaluations of NIPT have accounted for the need to provide information alongside testing and the associated costs and health outcomes of information provision.
Methods
A systematic review of economic evaluations of NIPTs (up to February 2018) was conducted. Medline, Embase, CINAHL and PsychINFO were searched using an electronic search strategy combining a published economic search filter (from NHS economic evaluations database) with terms related to NIPT and screening-related technologies. Data were extracted using the Consolidated Health Economic Evaluation Reporting Standards framework and the results were summarised as part of a narrative synthesis.
Results
A total of 12 economic evaluations were identified. The majority of evaluations (n = 10; 83.3%) involved cost effectiveness analysis. Only four studies (33.3%) included the cost of providing information about NIPT in their economic evaluation. Two studies considered the impact of test results on parents’ quality of life by allowing utility decrements for different outcomes. Some studies suggested that the challenges of valuing information prohibited their inclusion in an economic evaluation.
Conclusion
Economic evaluations of NIPTs need to account for the costs and outcomes associated with information provision, otherwise estimates of cost effectiveness may prove inaccurate.
There are approximately 33.4 million adults living with HIV worldwide of which an estimated 15.7 million are women. Although there has been enormous progress in the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of paramount importance, but vaccine-based and microbicidal approaches are still in their infancy. Since women acquire the virus largely through sexual intercourse, we developed liposomal systems potentially suitable for intra-vaginal use to prevent HIV-1 infection. We formulated liposomes from a range of naturally-occurring and synthetic lipids with varying physicochemical properties, and tested their ability to inhibit infection of transformed cells that express receptors specific to the virus. We identified formulations with the most favorable balance between decreasing HIV infection and causing cytotoxicity (i.e. therapeutic index). The therapeutic index improved with increasing cardiolipin content, and degree of unsaturation. Tissue reaction to these formulations was benign after intra-vaginal instillation in an in vivo female mouse model. These results support the potential use of cardiolipin-based liposomes enriched with synthetic lipids as microbicides for the prevention of HIV infection in women. 相似文献
Strategies to optimize biomaterial chemistry for applications in vascular tissue engineering attempt to promote endothelial and smooth muscle cell recruitment into porous material constructs. The primary objective is to facilitate relevant tissue formation in a wound healing versus pro-inflammatory manner. The present work investigated the interactive co-cellular response of human monocytes and human vascular smooth muscle cells (VSMCs) with a novel degradable, polar/hydrophobic/ionic (D-PHI) polyurethane and compared it to a commercially available biomaterial, poly-lactic-glycolic acid (PLGA) as well as tissue culture polystyrene (TCPS). D-PHI triggered a smaller pro-inflammatory response (acid phosphatase, esterase, tumor necrosis factor-α) at later time points (>14?d) than PLGA suggesting that monocytes may be transitioning to a more wound-healing phenotype on the D-PHI surface. When D-PHI was coated with collagen, monocyte cell attachment did not differ with the native D-PHI; however, PLGA showed significant differences between collagen coated versus uncoated surfaces. There were more VSMCs and monocytes attached in co-culture to D-PHI when compared to PLGA. Co-cultures on D-PHI released more IL-10 (anti-inflammatory) than monocytes cultured alone, while the VSMCs retained the expression of its marker protein calponin. Together the above data suggest that co-culturing monocytes with VSMCs may aid in stimulating the attachment of VSMCs to D-PHI while eliciting the desired functional phenotypes for both monocytes (i.e. low inflammation based on IL-10 values) and VSMCs (expressing calponin, a marker of contractility). Moreover, the results of this study demonstrated that D-PHI performed equally or better to PLGA in terms of the assayed biological parameters. 相似文献