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Background Methods Results Conclusions In clinical routine, health care professionals with various levels of experience assess left ventricular ejection fraction (LVEF) by echocardiography. The aim was to investigate to what extent visual and Simpson's biplane assessment of LVEF, using two‐dimensional (2D) transthoracic echocardiography (TTE), is affected by the evaluator's experience.Ultrasound images of 140 patients were assessed, visually and with Simpson's biplane method, by six evaluators divided into three groups based on echocardiographic experience level (beginner, intermediate and expert). The evaluators were blinded to each other's LVEF assessments. Bland‐Altman analyses (bias±SD) were performed to assess agreement. P‐values < 0.05 with the performed paired t‐test were considered statistically significant.Level of agreement in LVEF was good between evaluators within the expert group: visual = LVEFexpert 1 vs LVEFexpert 2: −0.4 ± 6.4 (p = 0.46); Simpson's biplane = LVEFexpert 1 vs LVEFexpert 2: 0.96 ± 7.0 (p = 0.11), somewhat lower within the intermediate group: visual = LVEFintermediate 1 vs LVEFintermediate 2: −1.2 ± 4.4 (p = 0.004); Simpson's biplane = LVEFintermediate 1 vs LVEF intermediate 2: −3.3 ± 5.0 (p < 0.001) and lowest for beginners: visual = LVEFbeginner 1 vs LVEFbeginner 2: 2.3 ± 9.8 (p = 0.007), Simpson's biplane = LVEFbeginner 1 vs LVEF beginner 2: −1.8 ± 8.7 (p = 0.02). The agreement between LVEFexpert and LVEFs by the two other groups was: visual = LVEFexpert vs LVEFbeginner: 1.5 ± 6.0 (p = 0.005); LVEFintermediate: −3.0 ± 4.4 (p < 0.001) and Simpson's biplane = LVEFexpert vs LVEFbeginner: 3.2 ± 6.3 (p < 0.001); LVEFintermediate: −2.2 ± 4.7 (p < 0.001).The evaluator's level of experience affects visual and Simpson's biplane assessment of LVEF by 2D‐TTE, with highest variability being among beginners. Furthermore, a second opinion is recommended when assessing reduced LVEF even for evaluators with intermediate and expert experience. [ABSTRACT FROM AUTHOR]

As a result of the European Single Use Plastic Directive and as part of the transition to a circular economy, plastic food contact materials (FCMs) are being replaced, often by renewable plant-based materials. This research aimed to identify which chemical substances are present in plant-based materials. In 2022 a total of 28 samples of the latter materials from the Dutch market were analysed for 313 active substances from plant protection products, 47 per- and polyfluoralkyl substances (PFASs) and 27 heavy metals and other elements. Ten samples contained plant protection products that are not authorised in the EU. Most materials contained PFASs at trace or even high levels. Three out of four investigated sugar cane materials contained 6:2 fluorotelomer alcohol at levels up to 1.7 mg/kg. High contents of aluminium, manganese, iron, zinc, and barium were found. Other heavy metals, such as arsenic, lead and mercury were found in relatively low contents. A broad GC-MS screening was performed, which revealed the presence of plant extractable, plasticisers, antioxidants and hydrocarbons, which were not all authorised for FCMs, but may be present as non-intentionally added substances.

The lack of extreme water level fluctuations in managed, non-peat forming wetland ecosystems can result in decreased productivity through the loss of heterogeneity of these ecosystems. Stochastic disruption, such as a water level drawdown, can effectively reverse this effect and return the wetland to a more productive state, associated with higher biodiversity through new vegetation development. Yet, aside from the effect on vegetation dynamics, little is known about longer-term effects (30 years) of a water level drawdown, hereafter referred to as legacy effects, and how this may impact future water level drawdowns. Here, we aim to unravel the legacy effects of a water level drawdown, stand alone and along a water level gradient, on seed bank properties and nutrient availability in a eutrophic clay wetland. To identify these, we studied the hydrologically managed nature reserve Oostvaardersplassen in the Netherlands. Here, one section was subjected to a multi-year water level drawdown and another section was kept inundated. We determined seed bank properties in both areas, spatially and along a soil elevation gradient (20 cm). Nutrient availability was measured by taking sediment samples along the water level gradient and through experimental manipulation of the water level in an indoor mesocosm experiment. Germination was higher in locations with a water level drawdown history, especially at relatively high elevations. Additionally, the proportion of pioneer species in the seed bank was higher in the water level drawdown area. Overall, nutrient concentrations were higher compared to other aquatic systems. Nutrient availability was higher in the inundated area and did not respond to the water level gradient. We conclude that 30 years after an induced water level drawdown there is no depletion of nutrients, while we still observe a legacy effect in the number of viable seeds in the seed bank., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kerstin Bouma reports financial support was provided by Vereniging van Bos- en Natuurterreineigenaren. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Tay-Sachs and Sandhoff diseases are genetic disorders resulting from mutations in HEXA or HEXB , which code for the α- and β-subunits of the heterodimer β-hexosaminidase A (HexA), respectively. Loss of HexA activity results in the accumulation of GM2 ganglioside (GM2) in neuronal lysosomes, culminating in neurodegeneration and death, often by age 4. Previously, we combined critical features of the α- and β-subunits of HexA into a single subunit to create a homodimeric enzyme known as HexM. HexM is twice as active as HexA and degrades GM2 in vivo , making it a candidate for enzyme replacement therapy (ERT). Here we show HexM production is scalable to meet ERT requirements and we describe an approach that enhances its cellular uptake via co-expression with an engineered GlcNAc-1-phosphotransferase that highly phosphorylates lysosomal proteins. Further, we developed a HexA overexpression system and functionally compared the recombinant enzyme to HexM, revealing the kinetic differences between the enzymes. This study further advances HexM as an ERT candidate and provides a convenient system to produce HexA for comparative studies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stuart Kornfeld reports a relationship with M6P Therapeutics that includes: equity or stocks. Cuong Do reports a relationship with M6P Therapeutics that includes: equity or stocks. Brian Mark and Don Mahuran has patent #US 10400227 B2 issued to M6P Therapeutics (non-exclusive) and New Hope Research Foundation (non-exclusive). Stuart A. Kornfeld, Balraj Doray, Wang Lee, Lin Liu has patent #US10907139B2 pending to M6P Therapeutics., (©2021TheAuthors.PublishedbyElsevierB.V.)

Consumers using air fresheners are exposed to the emitted ingredients, including fragrances, via the respiratory tract. Several fragrances are known skin sensitizers, but it is unknown whether inhalation exposure to these chemicals can induce respiratory sensitization. Effects on the immune system were assessed by testing a selection of five fragrance allergens in the respiratory local lymph node assay (LLNA). The probability and extent of exposure were assessed by measuring concentrations of the 24 known fragrance allergens in 109 air fresheners. It was shown that the most frequently used fragrances in air fresheners were D-limonene and linalool. In the respiratory LLNA, these fragrances were negative. Of the other tested chemicals, only isoeugenol induced a statistically significant increase in cell proliferation. Consumer exposure was assessed in more detail for D-limonene, linalool, and isoeugenol by using exposure modeling tools. It was shown that the most frequently used fragrances in air fresheners, D-limonene, and linalool gave rise to a higher consumer exposure compared with isoeugenol. To evaluate whether the consumer exposure to these fragrances is low or high, these levels were compared with measured air concentrations of diisocyanates, known human respiratory sensitizers. This comparison showed that consumer exposure from air fresheners to D-limonene, linalool, and isoeugenol is considerably lower than occupational exposure to diisocyanates. By combing this knowledge on sensitizing potency with the much lower exposure compared to diisocyanates it seems highly unlikely that isoeugenol can induce respiratory sensitization in consumers using air fresheners.