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Yoann Montigaud,1 Jérémie Pourchez,1 Lara Leclerc,1 Olivier Tillement,2 Anthony Clotagatide,3,4 Clémence Bal,5 Noël Pinaud,5 Nobuyasu Ichinose,6 Bei Zhang,7 Sophie Perinel,3,4 François Lux,2,8 Yannick Crémillieux,5 Nathalie Prevot3,4 1Mines Saint-Etienne, Univ Lyon, Univ Jean Monnet, INSERM, U 1059 Sainbiose, Centre CIS, Saint-Etienne, France; 2Institut Lumière Matière, Université de Lyon, Villeurbanne, France; 3INSERM U 1059 Sainbiose, Université Jean Monnet, Saint-Etienne, France; 4CHU Saint-Etienne, Saint-Etienne, France; 5IBIO, Bordeaux, France; 6Canon Medical Systems Corporation, Otawara, Japan; 7Canon Medical Systems Europe, Zoetermeer, Netherlands; 8Institut Universitaire de France (IUF), Paris, FranceCorrespondence: Jérémie PourchezMines Saint-Etienne, 158 Cours Fauriel, CS 62362, Saint-Etienne, Cedex 2 42023, FranceTel +33 4 77 42 01 80Email pourchez@emse.frPurpose: This study aims at determining lung distribution of gadolinium-based polysiloxane nanoparticles, AGuIX® (small rigid platform – SRP), as a potential theranostic approach by the pulmonary route.Methods: First, the aerodynamic size distribution and the aerosol output rate were thoroughly characterized. Then, a multimodal approach using magnetic resonance (MR) and gamma-camera (GC) imaging allows to assess the deposition of the aerosolised nanoparticles in the respiratory tract using isolated ventilated porcine lungs.Results: The SRP has proven to be radiolabelled by radioisotope with a good yield. Crude SRP or radiolabelled ones showed the same aerodynamic size distribution and output as a conventional molecular tracer, as sodium fluoride. With MR and GC imaging approaches, the nebulised dose represented about 50% of the initial dose of nanoparticles placed in the nebuliser. Results expressed as proportions of the deposited aerosol showed approximately a regional aerosol deposition of 50% of the deposited dose in the lungs and 50% in the upper airways. Each technique assessed a homogeneous pattern of deposited nanoparticles in Lungs. MR observed a strong signal enhancement with the SRP, similar to the one obtained with a commonly used MRI contrast agent, gadoterate meglumine.Conclusion: As a known theranostic approach by intravenous administration, SRP appeared to be easily aerosolised with a conventional nebuliser. The present work proves that pulmonary administration of SRP is feasible in a human-like model and allows multimodal imaging with MR and GC imaging. This work presents the proof of concept of SRP nebulisation and aims to generate preclinical data for the potential clinical transfer of SRP for pulmonary delivery.Keywords: aerosol, pulmonary delivery, ex vivo model, MRI, SPECT/CT, theranostic

The aim of this study was to quantify the number of non-airborne bacteria that can passively penetrate the layers of four mask types (surgical mask, community face mask type 1 (CFM1), biocidal CFM1 and CFM2) and to determine the influence of wearing conditions for the surgical type. A mask wearer simulator consisting of a 3D anatomical replica of the upper airway connected to a breathing pump was used. Wearing time, filtration quality of the mask, fit (loose vs. tight) and breathing parameters (tidal volume, respiratory rate) were tested. A Staphylococcus epidermidis inoculum was applied to the inner layer. After the wearing simulation, the layers were separated and the bacteria counted. After four hours, no or only a few bacteria were present in the middle and outer layers. Most remained in the inner layer. Surgical mask and CFM1 retained more bacteria and provided a breeding ground for germs. The biocidal CFM1 rapidly reduced the number in the inner layer. The breathing parameters had no influence, in contrast to fit and wearing time. These results confirm that the standard test for bacterial filtration efficiency, which includes the active penetration of airborne bacteria into aerosol droplets, is the most objective measure of the ability of bacteria to penetrate through the mask layers, as the passive penetration ability of non-airborne bacteria is insignificant., (© 2024. The Author(s).)

Ticks are important vectors of bacterial, viral and protozoan pathogens of humans and animals worldwide. Candidatus Midichloria mitochondrii (hereafter M. mitochondrii) is a highly abundant bacterial endosymbiont found in many tick species, including two medically important ticks respectively found in Europe and Australia, Ixodes ricinus and Ixodes holocyclus. The present study aimed to determine the symbiont's biological role by identifying lateral gene transfer (LGT) events, characterising the transcriptome, and performing differential expression analyses. Metatranscriptomic data revealed that M. mitochondrii species in I. ricinus and I. holocyclus were equipped with the metabolic potential and were actively transcribing the genes for several important roles including heme, biotin and folate synthesis, oxidative stress response, osmotic regulation, and ATP production in microaerobic conditions. Differential expression analyses additionally showed an upregulation in stringent response and DNA repair genes in M. mitochondrii of I. holocyclus nymphs compared to adults. Low rates of differential expression suggest the symbiont may lack global gene regulation, as observed in other endosymbionts. Moreover, the identification of an LGT event and the proposed specialisation of the M. mitochondrii strains, mIxholo1 and mIxholo2, for different I. holocyclus life stages highlight the complex interactions between M. mitochondrii and their tick hosts., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

We newly report 25 provincial records of rove beetles (Coleoptera: Staphylinidae) from the province of Quebec from the following subfamilies: Steninae (1), Euaesthetinae (1), Omaliinae (2), Oxyporinae (1), Paederinae (1), Proteininae (1), Pselaphinae (2), Scaphidiinae (2), Scydmaeninae (2), Staphylininae (11) and Tachyporinae (1). Among these, two species are also reported for the first time from Ontario, two from Nova Scotia, and five are new Canadian records. We also report the first supporting data for Suniusmelanocephalus (Fabricius, 1792) and Scopaeusminutus Erichson, 1840 for Quebec, and of Arpediumschwarzi Fauvel, 1878, Phyllodrepapunctiventris (Fauvel, 1878), and Sepedophilusbasalis (Erichson, 1839) for Ontario. Specimen data and diagnoses are provided for each species, as well as references for identification where available., Competing Interests: The authors have declared that no competing interests exist.

Background: Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects of nicotine salts are still largely unknown, and the chemical diversity of e-liquids limits the comparison between different studies to determine the contribution of each compound to the cytotoxicity of EC aerosols. Therefore, the aim of this study was to evaluate the toxicological profile of controlled composition e-liquid aerosols to accurately determine the effects of each ingredient based on exposure at the air-liquid interface., Methods: Human lung epithelial cells (A549) were exposed to undiluted aerosols of controlled composition e-liquids containing various ratios of propylene glycol (PG)/vegetable glycerin (VG) solvents, freebase nicotine, organic acids, nicotine salts, and flavoured commercial e-liquids. Exposure of 20 puffs was performed at the air-liquid interface following a standard vaping regimen. Toxicological outcomes, including cytotoxicity, inflammation, and oxidative stress, were assessed 24 h after exposure., Results: PG/VG aerosols elicited a strong cytotoxic response characterised by a 50% decrease in cell viability and a 200% increase in lactate dehydrogenase (LDH) production, but had no effects on inflammation and oxidative stress. These effects occurred only at a ratio of 70/30 PG/VG, suggesting that PG is the major contributor to aerosol cytotoxicity. Both freebase nicotine and organic acids had no greater effect on cell viability and LDH release than at a 70/30 PG/VG ratio, but significantly increased inflammation and oxidative stress. Interestingly, the protonated form of nicotine in salt showed a stronger proinflammatory effect than the freebase nicotine form, while benzoic acid-based nicotine salts also induced significant oxidative stress. Flavoured commercial e-liquids was found to be cytotoxic at a threshold dose of ≈ 330 µg/cm²., Conclusion: Our results showed that aerosols of e-liquids consisting only of PG/VG solvents can cause severe cytotoxicity depending on the concentration of PG, while nicotine salts elicit a stronger pro-inflammatory response than freebase nicotine. Overall, aerosols from fourth-generation devices can cause different toxicological effects, the nature of which depends on the chemical composition of the e-liquid., (© 2024. The Author(s).)

During herbivory, chewing insects deposit complex oral secretions (OS) onto the plant wound. Understanding how plants respond to the different cues of herbivory remains an active area of research. In this study, we used an herbivory-mimick experiment to investigate the early transcriptional response of rice plants leaves to wounding, OS, and OS microbiota from Spodoptera frugiperda larvae. Wounding induced a massive early response associated to hormones such as jasmonates. This response switched drastically upon OS treatment indicating the activation of OS specific pathways. When comparing native and dysbiotic OS treatments, we observed few gene regulation. This suggests that in addition to wounding the early response in rice is mainly driven by the insect compounds of the OS rather than microbial. However, microbiota affected genes encoding key phytohormone synthesis enzymes, suggesting an additional modulation of plant response by OS microbiota., (© 2024. The Author(s).)

This work aims to investigate bronchodilator delivery with the use of different vaping drug delivery systems (VDDS) by determining the dose equivalence delivered in relation to different references: a clinical jet nebulizer, a pMDI (pressurized metered dose inhaler) and a DPI (dry powder inhaler). Three different bronchodilators were used (terbutaline, salbutamol hemisulfate, ipratropium bromide). The e-liquids contained the active pharmaceutical ingredient (API) in powder form. Two different VDDS were tested (JUUL and a GS AIR 2 atomizer paired with a variable lithium-ion battery (i-stick TC 40 W), 1.5 ohm resistance, and 15 W power). Samples were collected using a glass twin impinger (GTI). High-performance liquid chromatography (HPLC) was used to quantify the drugs. A next-generation impactor (NGI) was used to measure the particle size distribution. Terbutaline emerged as the optimal API for bronchodilator delivery in both VDDS devices. It achieved the delivery of a respirable dose of 20.05 ± 4.2 µg/puff for GS AIR 2 and 2.98 ± 0.52 µg/puff for JUUL. With these delivered doses, it is possible to achieve a dose equivalence similar to that of a jet nebulizer and DPI, all while maintaining a reasonable duration, particularly with the GS AIR 2. This study is the first to provide evidence that vaping bronchodilators work only with appropriate formulation, vaping technology, and specific drugs, depending on their thermal degradation properties.

To investigate potential correlations between human exposure to inhaled particles and pathological effects, the biological monitoring of nanoparticles in broncho-alveolar lavages (BAL) from patients has been proposed. To better understand the underlying mechanisms of toxicity, we propose to couple this biomonitoring of nanoparticles to their in vitro toxicity assessment. However, BAL obtained from regular clinical practice are conditioned with sodium hypochlorite solution (in a 50% v/v ratio), which is toxic to cells. The aim of this study was to develop a protocol to neutralize sodium hypochlorite, allowing to properly investigate the toxicity of the nanoparticles BAL contain. We first tried to neutralize chemically the sodium hypochlorite using H 2 O 2 , ascorbic acid or sodium ascorbate but this approach was unsuccessful. In addition, standard toxicology assays (MTT, LDH) could not be used because of interference with neutralizing solutions. We thus changed strategy and used ultracentrifugation to isolate nanoparticles from the sodium hypochlorite solution, with satisfactory extraction yields (88 to 100%). We then incubated the extracted nanoparticles with macrophages from the RAW264.7 cell line and assessed the cell viability and pro-inflammatory response. This study can be used as a proof-of-concept for further study of the biological impact of nanoparticles. This approach paves the way for studies aiming at a better understanding of the aetiology of some idiopathic diseases and underlying mechanisms., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Successful aerosol therapy in mechanically ventilated patients depends on multiple factors. Among these, position of nebulizer in ventilator circuit and humidification of inhaled gases can strongly influence the amount of drug deposited in airways. Indeed, the main objective was to preclinically evaluate impact of gas humidification and nebulizer position during invasive mechanical ventilation on whole lung and regional aerosol deposition and losses. Ex vivo porcine respiratory tracts were ventilated in controlled volumetric mode. Two conditions of relative humidity and temperature of inhaled gases were investigated. For each condition, four different positions of vibrating mesh nebulizer were studied: (i) next to the ventilator, (ii) right before humidifier, (iii) 15 cm to the Y-piece adapter and (iv) right after the Y-piece. Aerosol size distribution were calculated using cascade impactor. Nebulized dose, lung regional deposition and losses were assessed by scintigraphy using 99m technetium-labeled diethylene-triamine-penta-acetic acid. Mean nebulized dose was 95% ± 6%. For dry conditions, the mean respiratory tract deposited fractions reached 18% (± 4%) next to ventilator and 53% (± 4%) for proximal position. For humidified conditions, it reached 25% (± 3%) prior humidifier, 57% (± 8%) before Y-piece and 43% (± 11%) after this latter. Optimal nebulizer position is proximal before the Y-piece adapter showing a more than two-fold higher lung dose than positions next to the ventilator. Dry conditions are more likely to cause peripheral deposition of aerosols in the lungs. But gas humidification appears hard to interrupt efficiently and safely in clinical use. Considering the impact of optimized positioning, this study argues to maintain humidification., (© 2023. The Author(s).)

Introduction: We describe the vaping and smoking habits of French adolescents aged 15-16 years in the Loire department with a view to assess the impact of e-cigarette experimentation and use on their smoking behavior., Methods: This quantitative, cross-sectional, single-center and observational study conducted from January to July 2019 targeted 6622 students aged 15-16 years attending public high school in the Loire department, France., Results: A total of 4937 (74.6%) adolescents were included. Of these, 73.2% were non-vapers and 72.2% non-smokers; 66.0% of adolescents were non-vapers and non-smokers. Slightly less than half of adolescents had experimented with e-cigarettes (44.6%), more than half of whom (26.8%) continued to use vaping products, with 6.02% vaping daily. Likewise, a little less than half of adolescents had experimented with smoked tobacco (42.4%), more than half of whom (27.8%) continued to use smoking products, with 10.3% smoking daily. Vapers and smokers (20.6%) tended to begin with the use of smoked tobacco and to progress to the dual use of vaping and smoked tobacco products. Vaping had a positive effect, as 71.8% of vapers who smoked tobacco before initiating vaping stopped or reduced smoking following their progression to this double use. More than half of tobacco users are daily users while this daily use affects only 1/3 boys and 1/6 girls for vape. Finally, nearly 80.7% of adolescents who had never smoked before vaping did not smoke at the time of the study., Conclusions: Our data suggest that vaping has a rather marginal impact on smoking initiation among French adolescents aged 15-16 years in the Loire department. They therefore neither confirm nor completely disprove the gateway effect theory, relating to use of tobacco subsequent to vaping., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2023 Wamba A. et al.)

Background: We assessed/compared the evolution of tobacco and e-cigarette experimentation and use among French adolescents of the Loire department aged 15-16 years., Methods: A descriptive, cross-sectional/observational study conducted in 2018-2020 among 7,950 Year 11 pupils attending 27 public secondary schools of the Loire department, France., Results: From 2018 to 2020, 66.18% of adolescents were "non-vapers and non-smokers", 19.76% were "vapers and smokers", 7.90% were "non-vapers and smokers" and 6.15% were "vapers and non-smokers". E-cigarette experimentation was more prevalent than tobacco experimentation (44.92% vs 41.67%), and daily vaping was less prevalent than daily smoking (5.40% vs 10.24%). More boys than girls were daily vapers or daily smokers. A decrease was observed in tobacco experimentation (from 41.22% in 2018 to 39.73% in 2020) and e-cigarette experimentation (from 50.28% in 2018 to 41.25% in 2020). Current vaping remained stable, with an increase in daily vaping. French adolescent vapers frequently use e-liquids with little or no nicotine or with fruit or sweet flavours., Conclusions: Adolescents used e-cigarettes mainly for experimental and/or recreational purposes, with no intention of progression to daily smoking. Although the design of this study is not longitudinal and caution must be exercised, from our cross-sectional observational study data, it appears that the proportion of "non-vapers and non-smokers" tended to increase. "Smokers" tended to progress to the dual use of vaping and smoked tobacco, with the likely intention to reduce or quit smoking., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Face masks are often recommended in community settings to prevent the airborne transmission of respiratory viruses or bacteria. Our first objective was to develop an experimental bench to assess the viral filtration efficiency (VFE) of a mask with a methodology similar to the normative measurement of bacterial filtration efficiency (BFE) used to determine the filtration performance of medical masks. Then, using three categories of masks of increasing filtration quality (two types of community masks and one type of medical mask), filtration performances measured ranged from 61.4 to 98.8% of BFE and from 65.5 to 99.2% of VFE. A strong correlation (r = 0.983) between bacterial and viral filtration efficiency was observed for all types of masks and for the same droplets size in the 2-3 µm range. This result confirms the relevance of the EN14189:2019 standard using bacterial bioaerosols to evaluate mask filtration, to also extrapolate mask performances whatever their filtration quality against viral bioaerosols. Indeed, it appears that the filtration efficiency of masks (for micrometer droplet sizes and low bioaerosol exposure times) depends mainly on the size of the airborne droplet, rather than on the size of the infectious agent contained in that droplet., (© 2023. The Author(s).)

Spontaneous symmetry breaking underlies much of our classification of phases of matter and their associated transitions 1-3 . The nature of the underlying symmetry being broken determines many of the qualitative properties of the phase; this is illustrated by the case of discrete versus continuous symmetry breaking. Indeed, in contrast to the discrete case, the breaking of a continuous symmetry leads to the emergence of gapless Goldstone modes controlling, for instance, the thermodynamic stability of the ordered phase 4,5 . Here, we realize a two-dimensional dipolar XY model that shows a continuous spin-rotational symmetry using a programmable Rydberg quantum simulator. We demonstrate the adiabatic preparation of correlated low-temperature states of both the XY ferromagnet and the XY antiferromagnet. In the ferromagnetic case, we characterize the presence of a long-range XY order, a feature prohibited in the absence of long-range dipolar interaction. Our exploration of the many-body physics of XY interactions complements recent works using the Rydberg-blockade mechanism to realize Ising-type interactions showing discrete spin rotation symmetry 6-9 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This study aims to evaluate the impact of the nasal delivery technique and nebulizing technologies (using different frequencies of oscillating airflow) for acoustic aerosol targeting of maxillary sinuses. Sodium fluoride (chemical used as a marker), tobramycin (drug used as a marker) and 99m Tc-DTPA (radiolabel aerosol) were used to assess the intrasinus aerosol deposition on a nasal cast. Two commercial medical devices (PARI SINUS nebulizer and NL11SN ATOMISOR nebulizer) and various nasal delivery techniques (one or two nostrils connected to the aerosol inlet, the patient with the soft palate closed or open during the acoustic administration of the drug, the presence or not of flow resistance in the nostril opposite to the one allowing the aerosol to be administered) were evaluated. The closed soft palate condition showed a significant increase in drug deposition even though no significant difference in the rest of the nasal fossae was noticed. Our results clearly demonstrated a higher intrasinus aerosol deposition (by a factor 2-3; respectively 0.03 ± 0.007% vs. 0.003 ± 0.0002% in the right maxillary sinus and 0.027 ± 0.006% vs. 0.013 ± 0.004% in the left maxillary sinus) using the acoustic airflow generated by the PARI SINUS compared to the NL11SN ATOMISOR. The results clearly demonstrated that the optimal conditions for aerosol deposition in the maxillary sinuses were obtained with a closed soft palate. Thus, the choice of the nebulizing technology (and mainly the frequency of the pulsating aerosol generated) and also the recommendation of the best nasal delivery technique are key factors to improve intrasinus aerosol deposition.