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[This corrects the article DOI 10.1371/journal.pone.0261397.].Sulfoxaflor is a new insecticide which acts on the nicotinic acetylcholine receptor (nAChRs) in a similar way to neonicotinoids. However, sufloxaflor (SFX) is thought to act in a different manner and is thus proposed as an alternative in crop protection. The goal of this study is to evaluate the toxicity of SFX and its sublethal effect on the honeybee Apis mellifera after acute exposure. In toxicological assay studies, the LD50 value and sublethal dose (corresponding to the NOEL no observed effect level) were 96 and 15 ng/bee, respectively. Using the proboscis extension response paradigm, we found that an SFX dose of 15 ng/bee significantly impairs learning and memory retrieval when applied 12 h before conditioning or 24 h after olfactory conditioning. SFX had no effect on honeybee olfactory performance when exposure happened after the conditioning. Relative quantitative PCR experiments performed on the six nicotinic acetylcholine receptor subunits demonstrated that they are differently expressed in the honeybee brain after SFX exposure, whether before or after conditioning. We found that intoxicated bees with learning defects showed a strong expression of the Amelβ1 subunit. They displayed overexpression of Amelα9 and Amelβ2, and down-regulation of Amelα1, Amelα3 and Amelα7 subunits. These results demonstrated for the first time that a sublethal dose of SFX could affect honeybee learning and memory performance and modulate the expression of specific nAChR subunits in the brain.Clinical studies in healthy volunteers challenged with lipopolysaccharide (LPS), a constituent of the cell wall of Gram-negative bacteria, represent a key model to characterize the Toll-like receptor 4 (TLR4)-mediated inflammatory response. Here, we developed a mathematical modelling framework to quantitatively characterize the dynamics and inter-individual variability of multiple inflammatory biomarkers in healthy volunteer LPS challenge studies. Data from previously reported LPS challenge studies were used, which included individual-level time-course data for tumour necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP). A one-compartment model with first-order elimination was used to capture the LPS kinetics. The relationships between LPS and inflammatory markers was characterized using indirect response (IDR) models. Delay differential equations were applied to quantify the delays in biomarker response profiles. For LPS kinetics, our estimates of clearance and volume of distribution were 35.7 L h-1 and 6.35 L, respectively. CDK2-IN-73 purchase Our model adequately captured the dynamics of multiple inflammatory biomarkers. The time delay for the secretion of TNF-α, IL-6 and IL-8 were estimated to be 0.924, 1.46 and 1.48 h, respectively. A second IDR model was used to describe the induced changes of CRP in relation to IL-6, with a delayed time of 4.2 h. The quantitative models developed in this study can be used to inform design of clinical LPS challenge studies and may help to translate preclinical LPS challenge studies to humans.
Sustained elevated concentration of GHGs is predicted to increase global mortality. With the Australian health sector responsible for 7% of the nation's GHG emissions, the benefits and costs of various decarbonisation trajectories are currently being investigated. To assist with this effort, we model the impact earlier decarbonisation has on temperature-related mortality.
We used DICE-EMR, an Integrated Assessment Model with an endogenous mortality response, to simulate Australian GHG trajectories and estimate the temperature-related mortality impact of early decarbonisation. We modelled a linear decline of the Australian health sector's and economy's GHG annual emissions to net-zero targets of 2040 and 2050.
Deaths averted and monetary-equivalent welfare gain.
Decarbonisation of the Australian health sector by 2050 and 2040 is projected to avert an estimated 69,000 and 77,000 global temperature-related deaths respectively in a Baseline global emissions scenario. Australian economy decarbonisation by 2050 and 2040 is projected to avert an estimated 988,000 and 1,101,000 global deaths respectively. Assuming a low discount rate and high global emissions trajectory, we estimate a monetary equivalent welfare gain of $151 billion if the Australian health sector decarbonises by 2040, only accounting for the benefits in reducing temperature-related mortality.
Earlier decarbonisation has a significant impact on temperature-related mortality. Many uncertainties exist and health impacts other than temperature-related mortality are not captured by this analysis. Nevertheless, such models can help communicate the health risk of climate change and improve climate policy decision making.
Earlier decarbonisation has a significant impact on temperature-related mortality. Many uncertainties exist and health impacts other than temperature-related mortality are not captured by this analysis. Nevertheless, such models can help communicate the health risk of climate change and improve climate policy decision making.[This corrects the article DOI 10.1371/journal.pone.0240153.].Implicit math = male stereotypes have been found in early childhood and are linked to girls' disproportionate disengagement from math-related activities and later careers. Yet, little is known about how malleable children's automatic stereotypes are, especially in response to brief interventions. In a sample of 336 six- to eleven-year-olds, we experimentally tested whether exposure to a brief story vignette intervention with either stereotypical, neutral, or counter-stereotypical content (three conditions math = boy vs. neutral vs. math = girl) could change implicit math-gender stereotypes. Results suggested that children's implicit math = male stereotypes were indeed responsive to brief stories that either reinforced or countered the widespread math = male stereotype. Children exposed to the counter-stereotypical stories showed significantly lower (and non-significant) stereotypes compared to children exposed to the stereotypical stories. Critically, exposure to stories that perpetuated math = male stereotypes significantly increased math-gender stereotypes over and above baseline, underscoring that implicit gender biases that are readily formed during this period in childhood and even brief exposure to stereotypical content can strengthen them. As a secondary question, we also examined whether changes in stereotypes might also lead to changes in implicit math self-concept. Evidence for effects on implicit self-concept were not statistically significant.Exosome DNA (exoDNA) can be used for liquid biopsy. This study was the first to use droplet digital PCR (ddPCR) to detect tumor-specific mutations in exoDNA and to evaluate the prognosis of hepatocellular carcinoma (HCC) patients. 60 HCC patients were enrolled in the study. We used ddPCR to detect c.747 G > T mutation in TP53 gene. We analyzed the correlation between detectable mutation in exoDNA and clinicopathologic characteristics using Multivariate logistics regression analysis. We performed Cox regression to assess the correlation between mutation frequency (mutant droplets/total droplets, MD/TD) and prognostic. We found that 48 of 60 patients had c.747 G > T mutation in TP53 gene in exoDNA (80.0%). We found that detectable mutation in exoDNA and age were associated with microvascular invasion (MVI) (P 67%) had shorted median recurrence-free survival (RFS) with 63 days (range, 53-202 days), compared with 368 days (range, 51-576 days) for patients with low-frequency mutation ( less then 67%) (HR4.61; 95% CI, 1.70-12.48; P = 0 .003). We also found that high-frequency mutation was associated with poor prognosis though patients had better pathological characteristics, such as AFP ( less then 400 ng/mL), Liver cirrhosis (Negative), Tumor thrombus (Negative), Tumor numbers (Single) and Post-operation TACE (Executed). We provided evidence that the mutations in exoDNA might be used to predict patients with poor RFS.Abbreviations TP53 Tumor protein p53; ExoDNA Exosomal DNA; HCC Hepatocellular carcinoma; ddPCR Droplet digital Polymerase Chain Reaction (PCR); MD/TD The ratio of mutant droplets/total droplets; AFP Alpha-fetoprotein; MVI Microvascular invasion; RFS Recurrence-free survival.
Patient satisfaction is a subjective attitudinal response of a client to a health institution's services and a pillar of quality assurance. Patients who are happy with their treatment are much more likely to stick with it, improve quickly, and function normally. Satisfied patients are more compliant, improve faster, and are more functional. However, there haven't been enough studies conducted across the country, and none have been conducted in this study area. As a result, the purpose of the study was to estimate the size of patient satisfaction and associated determinants at Dilla University Referral Hospital's psychiatry unit in Dilla, 2020.
This was a hospital-based cross-sectional study design utilized using a simple random sampling technique. To assess patient satisfaction, we used the 24-item Mental Health Service Satisfaction Scale which was a validated tool in Ethiopia. The link between the outcome and the independent variable was determined using linear regression analysis (P< 0.05).
This sto the hospital were identified as variables that could be improved by working with different stakeholders.We investigated trophic dynamics of Hg in the polluted Baltic Archipelago Sea using established trophic magnification (TMFs) and biomagnification factors (BMFs) on a comprehensive set of bird, fish, and invertebrate species. As different ecological and ecophysiological species traits may affect trophic dynamics, we explored the effect of food chain (benthic, pelagic, benthopelagic) and thermoregulatory strategy on trophic total Hg (THg) dynamics, using different approaches to accommodate benthopelagic species and normalize for trophic position (TP). We observed TMFs and most BMFs greater than 1, indicating overall THg biomagnification. We found significantly higher pelagic TMFs (3.58-4.02) compared to benthic ones (2.11-2.34) when the homeotherm bird species were excluded from models, but not when included. This difference between the benthic and pelagic TMFs remained regardless of how the TP of benthopelagic species was modeled, or whether TMFs were normalized for TP or not. TP-corrected BMFs showed a larger range (0.44-508) compared to BMFs representing predator-prey concentration ratios (0.05-82.2). Overall, the present study shows the importance of including and evaluating the effect of ecological and ecophysiological traits when investigating trophic contaminant dynamics.Globoid cell leukodystrophy (Krabbe disease) is a fatal neurodegenerative, demyelinating disease caused by dysfunctional activity of galactosylceramidase (GALC), leading to the accumulation of glycosphingolipids including psychosine. While oligodendrocytes have been extensively studied due to their high levels of GALC, the contribution of astrocytes to disease pathogenesis remains to be fully elucidated. In the current study, we generated induced pluripotent stem cells (iPSCs) from two donors with infantile onset Krabbe disease and differentiated them into cultures of astrocytes. Krabbe astrocytes recapitulated many key findings observed in humans and rodent models of the disease, including the accumulation of psychosine and elevated expression of the pro-inflammatory cytokine IL-6. Unexpectedly, Krabbe astrocytes had higher levels of glucosylceramide and ceramide, and displayed compensatory changes in genes encoding glycosphingolipid biosynthetic enzymes, suggesting a shunting away from the galactosylceramide and psychosine pathway.
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