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    Determination of Nicotine Protonation State in E-Liquids by Low-Resolution Benchtop NMR Spectroscopy

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    Over several years, e-liquids with "nicotine salts" have gained considerable popularity. These e-liquids have a low pH, at which nicotine occurs mostly in its monoprotonated form. Manufacturers usually accomplish this by the addition of an organic acid, such as levulinic acid, benzoic acid, or lactic acid. Nicotine in its protonated form can be more easily inhaled, enhancing the addictiveness and attractiveness of products. Several techniques have been described for measuring the protonation state of nicotine in e-liquids. However, nuclear magnetic resonance (NMR) spectroscopy is particularly suited for this purpose because it can be performed on unaltered e-liquids. In this article, we demonstrate the suitability of a benchtop NMR (60 MHz) instrument for determining the protonation state of nicotine in e-liquids. The method is subsequently applied to measure the protonation state of 33 commercially available e-liquids and to investigate whether the vaping process alters the protonation state of nicotine. For this purpose, the protonation state in the condensed aerosol obtained by automated vaping of different e-liquids was compared with that of the original e-liquids. Two distinct populations were observed in the protonation state of nicotine in commercial e-liquids: free-base (fraction of free-base nicotine αfb > 0.80) and protonated (αfb < 0.40). For 30 e-liquids out of 33, the information on the packaging regarding the presence of nicotine salt was in agreement with the observed protonation state. Three e-liquids contained nicotine salt, even though this was not stated on the packaging. Measuring the protonation state of nicotine before and after (machine) vaping revealed that the protonation state of e-liquids is not affected by vaping. In conclusion, it is possible to determine the nicotine protonation state with the described method. Two clusters can be distinguished in the protonation state of commercial e-liquids, and the protonation state of nicotine remains unchanged after vaping

    Citizen monitoring network ‘train traffic in America’ –noise pollution from train traffic mapped with citizen science

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    Met citizen science doen burgers en wetenschappers samen onderzoek. Dat is nu ook gebeurd bij een onderzoek naar geluidhinder door treinverkeer in het dorp America (Limburg). Daaruit bleek dat citizen science onderzoek een gedetailleerd lokaal beeld kan geven van geluidniveaus en acute geluidhinder. De onderzoeksaanpak hielp om vragen en zorgen van lokale inwoners over hun leefomgeving te beantwoorden. Dit gaf hen vertrouwen in het wetenschappelijke onderzoek. Citizen science kan daarmee een goede aanvulling zijn op hoe geluidniveaus nu volgens de wet worden vastgesteld. Het onderzoek bevestigde dat voorbijkomende treinen geluidpieken veroorzaken waar inwoners acute ernstige hinder van hebben. Dit gebeurt zowel overdag als ’s nachts. Over het algemeen toonde het onderzoek aan dat inwoners die volgens berekeningen meer blootstaan aan geluid van treinverkeer, inderdaad hogere geluidniveaus meten. Daarnaast ervaren zij relatief meer hinder en slaapverstoring dan mensen die aan lager geluid blootstaan. Inwoners wilden actief meedenken over het onderzoek. Een reden hiervoor was dat ze de gebruikelijke manier om geluidniveaus te berekenen, volgens landelijke regels, niet geschikt vinden voor hun situatie. Bijvoorbeeld omdat geluidpieken en het aantal treinen dat ‘s nachts rijdt, niet genoeg zijn terug te zien in de berekende geluidniveaus. Ook wilden ze meer aandacht voor de beleving van geluid in de omgeving, in plaats van alleen te kijken hoe hard het geluid is in decibellen. Bij de inwoners is frustratie en soms ook wantrouwen ontstaan door de manier waarop (overheid)instanties omgaan met geluidhinder door treinen. De inwoners van America hebben dit onderzoek samen met het RIVM uitgevoerd. Met geluidmeters hebben ze zelf gemeten hoeveel geluid de voorbijkomende goederen- en passagierstreinen maakten. Deze meetgegevens waren meteen zichtbaar op een openbare website. Via een vragenlijst en een app lieten ze weten hoe ze het treinverkeer beleefden en hoe dit hun welzijn en gezondheid beïnvloedde. Ook gaven de onderzoekers uitleg over de resultaten. Het RIVM heeft dit onderzoek met eigen geld betaald. Het wil meer ervaring opdoen met citizen science om meer kennis over een gezonde leefomgeving te ontwikkelen vanuit maatschappelijke zorgen en vragen.In citizen science, citizens and scientists work together on research. This approach was recently used for a study into noise pollution from train traffic in the village of America (Limburg). The study showed that citizen science research can provide a detailed local understanding of noise levels and acute annoyance. It helped address questions and concerns from local residents about their living environment, which increased residents' trust in the scientific research. This shows that citizen science can be a valuable addition to the current legally established methods for determining noise levels. The study confirmed that passing trains cause noise peaks that cause significant (acute) annoyance to residents, both during the day and at night. Overall, the study showed that people who live in places with a high calculated noise load from railroad traffic measure higher noise levels. They also experience more annoyance and sleep disturbance. Residents actively wanted to contribute to the study. One reason for this was because they felt that the conventional method of calculating noise levels, according to national regulations, was unsuitable for their situation. For instance, residents felt that noise peaks and the number of trains running at night were not adequately reflected in the calculated noise levels. They also expressed a wish for a greater focus on the perception of sound in their living environment, rather than solely on the intensity in decibels. Frustration and sometimes mistrust has arisen among residents due to the way government agencies handle train noise pollution. The residents of America conducted this study in cooperation with RIVM. Using noise meters, they personally measured the noise generated by passing freight and passenger trains. The measurement data were immediately accessible on a public website. In addition, the residents expressed how they perceived train traffic and how it influenced their well-being and health through a questionnaire and an app. The researchers, in turn, provided explanations for the results. RIVM funded this study out of its own resources, as it aims to gain more experience with citizen science in order to develop knowledge about a healthy living environment based on societal concerns and questions

    Calculating the impact of the National Prevention Agreement – subagreement on smoking. Will the 2040 ambitions be reached?

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    De Nederlandse overheid wil dat er minder mensen roken, overgewicht hebben of te veel alcohol drinken. Om dat te bereiken, is in 2018 het Nationaal Preventieakkoord met doelen voor 2040 afgesloten. Hiervoor heeft de overheid met meer dan zeventig partijen afspraken gemaakt. Het RIVM heeft berekend of de doelen in 2040 worden gehaald met de afspraken zoals ze nu worden uitgevoerd. Het RIVM heeft hiervoor berekend hoe de situatie in 2040 zal zijn met én zonder de afspraken. Uit de berekening blijkt dat het aantal mensen dat rookt in 2040 iets verder zal zijn gedaald met de afspraken dan zonder de afspraken. Maar de gestelde doelen worden met de afspraken niet gehaald. Extra en stevigere maatregelen zijn nodig om deze doelen te bereiken. Denk bijvoorbeeld aan extra prijsverhogingen, naast de verhogingen die al zijn afgesproken. Het doel is dat in 2040 minder dan vijf procent van de volwassenen en geen enkele jongere meer rookt. Volgens de berekeningen zal door de afspraken naar schatting ongeveer 10 procent van de volwassenen roken. Zonder afspraken zou dat 13 procent zijn. Het aantal jongeren (12 t/m 16 jaar) dat rookt, zal in 2040 door de afspraken ongeveer vier procent zijn, in plaats van vijf procent zonder de afspraken. Het duurder maken van sigaretten en shag bleek het meest effectieve middel om mensen te laten stoppen met roken of te voorkomen dat ze ermee beginnen. In dit onderzoek is niet gekeken naar het roken van elektronische sigaretten (vapen).The Dutch government wants to reduce the number of people who smoke, are overweight or consume excessive amounts of alcohol. To this end, the National Prevention Agreement was drawn up in 2018, with goals for 2040. In this context, the government made agreements with over 70 different parties. RIVM has calculated whether the agreements, as they are currently being implemented, will be enough to reach the goals for 2040. RIVM has calculated what the situation will look like in 2040 both with and without the agreements. The calculations show that the agreements will result in slightly less people smoking in 2040, compared to the situation without the agreements. However, the agreements will not result in the goals being met. More and stricter measures will be necessary to meet these goals. For example, additional price increases could be introduced, alongside the previously agreed increases. The goal for 2040 is to reduce the number of adults who smoke to less than 5 per cent and to reduce the number of young people smoking to zero. According to the calculations, the agreements will result in an estimated 10 per cent of adults smoking. Without agreements, this would be 13 per cent. The agreements will also result in around 4 per cent of young people (between 12 and 16 years old) smoking in 2040, compared to 5 per cent without the agreements. Making cigarettes and roll-your-own tobacco more expensive would be the most effective way of getting people to quit smoking or preventing them from ever beginning. Vaping was not included in this study

    Antifungal Resistance in Pulmonary Aspergillosis.

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    Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and acute invasive pulmonary aspergillosis (IPA). In addition, chronic colonization may occur in cystic fibrosis (CF). Aspergillus fumigatus represents the main pathogen, which may employ different morphotypes, for example, conidia, hyphal growth, and asexual sporulation, in the various Aspergillus diseases. These morphotypes determine the ease by which A. fumigatus can adapt to stress by antifungal drug exposure, usually resulting in one or more resistance mutations. Key factors that enable the emergence of resistance include genetic variation and selection. The ability to create genetic variation depends on the reproduction mode, including, sexual, parasexual, and asexual, and the population size. These reproduction cycles may take place in the host and/or in the environment, usually when specific conditions are present. Environmental resistance is commonly characterized by tandem repeat (TR)-mediated mutations, while in-host resistance selection results in single-resistance mutations. Reported cases from the literature indicate that environmental resistance mutations are almost exclusively present in patients with IA indicating that the risk for in-host resistance selection is very low. In aspergilloma, single-point mutations are the dominant resistance genotype, while in other chronic Aspergillus diseases, for example, ABPA, CPA, and CF, both TR-mediated and single-resistance mutations are reported. Insights into the pathogenesis of resistance selection in various Aspergillus diseases may help to improve diagnostic and therapeutic strategies

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