Lead (Pb) is one of the most toxic and persistent elements and may adversely affect both humans and wildlife. Given the risks posed to humans, lead is listed among priority substances of public health importance worldwide. In fish, available studies deal with high doses, and the potential hazard of Pb at low concentrations is largely unknown. Given its well-demonstrated translational value for human toxicity research, we used zebrafish as a model species. Embryos were exposed to two environmentally relevant concentrations of lead (2.5 and 5 µg/L) from 6 h post-fertilization and analyzed after 48, 96, and 144 h. The morphological abnormality arose after 48 h, and the incidence and intensity were dose and time dependent. Spinal and tail deformities were the most frequently detected alterations. Pb also modulated the expression of genes involved in the toxicological responses (sod and mt), thus demonstrating that zebrafish’s early stages are able to mount an adaptive response. Moreover, ldh and β-catenin were significantly upregulated in all groups, whereas wnt3 expression was increased in the high concentration group. Our results confirm that zebrafish embryos and larvae are valuable early warning indicators of pollution and may play a major role in ecosystems and human health monitoring.
ObjectiveWe aimed at identifying baseline predictive factors for emergency department (ED) readmission, with hospitalisation/death, in patients with COVID-19 previously discharged from the ED. We also developed a disease progression velocity index.Design and settingRetrospective cohort study of prospectively collected data. The charts of consecutive patients with COVID-19 discharged from the Reggio Emilia (Italy) ED (2 March 2 to 31 March 2020) were retrospectively examined. Clinical, laboratory and CT findings at first ED admission were tested as predictive factors using multivariable logistic models. We divided CT extension by days from symptom onset to build a synthetic velocity index.Participants450 patients discharged from the ED with diagnosis of COVID-19.Main outcome measureED readmission within 14 days, followed by hospitalisation/death.ResultsOf the discharged patients, 84 (18.7%) were readmitted to the ED, 61 (13.6%) were hospitalised and 10 (2.2%) died. Age (OR=1.05; 95% CI 1.03 to 1.08), Charlson Comorbidity Index 3 versus 0 (OR=11.61; 95% CI 1.76 to 76.58), days from symptom onset (OR for 1-day increase=0.81; 95% CI 0.73 to 0.90) and CT extension (OR for 1% increase=1.03; 95% CI 1.01 to 1.06) were associated in a multivariable model for readmission with hospitalisation/death. A 2-day lag velocity index was a strong predictor (OR for unit increase=1.21, 95% CI 1.08 to 1.36); the model including this index resulted in less information loss.ConclusionsA velocity index combining CT extension and days from symptom onset predicts disease progression in patients with COVID-19. For example, a 20% CT extension 3 days after symptom onset has the same risk as does 50% after 10 days.
Lead (Pb), due to its high toxicity and bioaccumulation tendency, is one of the top three pollutants of concern for both humans and wildlife and occupies second place in the Priority List of Hazardous Substances. In freshwater fish, Pb is mainly absorbed through the gills, where the greatest accumulation occurs. Despite the crucial role of gills in several physiological functions such as gas exchange, water balance, and osmoregulation, no studies evaluated the effects of environmentally relevant concentrations of Pb on this organ, and existing literature only refers to high levels of exposure. Herein we investigated for the first time the molecular and morphological effects induced by two low and environmentally relevant concentrations of Pb (2.5 and 5 μg/L) on the gills of Danio rerio, a model species with a high translational value for human toxicity. It was demonstrated that Pb administration at even low doses induces osmoregulatory dysfunctions by affecting Na+/K+-ATPase and AQP3 expression. It was also shown that Pb upregulates MTs as a protective response to prevent cell damage. Modulation of SOD confirms that the production of reactive oxygen species is an important toxicity mechanism of Pb. Histological and morphometric analysis revealed conspicuous pathological changes, both dose- and time-dependent.
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