Humidity during high‐frequency oscillatory ventilation compared to intermittent positive pressure ventilation in extremely preterm neonates: An in vitro and in vivo observational study

International audienceBackground: Inappropriate humidification of inspired gas during mechanical ventilation can impair lung development in extremely low birthweight (ELBW) infants. Humidification depends on multiple factors, such as the heater-humidifier device used, type of ventilation, and environmental factors. Few studies have examined inspired gas humidification in these infants, especially during high-frequency oscillatory ventilation (HFOV). Our objective was to compare humidity during HFOV and intermittent positive pressure ventilation (IPPV), in vitro and in vivo.Methods: In vitro and in vivo studies used the same ventilator during both HFOV and IPPV. The bench study used a neonatal test lung and two heater-humidifiers with their specific circuits; the in vivo study prospectively included preterm infants born before 28 weeks of gestation.Results: On bench testing, mean absolute (AH) and relative (RH) humidity values were significantly lower during HFOV than IPPV (RH = 79.4 ± 8.1% vs. 89.0 ± 6.2%, p < 0.001). Regardless of the ventilatory mode, mean RH significantly differed between the two heater-humidifiers (89.6 ± 6.7% vs 78.7 ± 6.8%, p = 0.003). The in vivo study included 10 neonates (mean ± SD gestational age: 25.7 ± 0.9 weeks and birthweight: 624.4 ± 96.1 g). Mean RH during HFOV was significantly lower than during IPPV (74.6 ± 5.7% vs. 83.0 ± 6.7%, p = 0.004).Conclusion: RH was significantly lower during HFOV than IPPV, both in vitro and in vivo. The type of heater-humidifier also influenced humidification. More systematic measurements of humidity of inspired gas, especially during HFOV, should be considered to optimize humidification and consequently lung protection in ELBW infants

Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

International audienceNanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adults due in the vast majority to the EWS-FLI1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-FLI1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA

Patient-Ventilator Synchrony in Extremely Premature Neonates during Non-Invasive Neurally Adjusted Ventilatory Assist or Synchronized Intermittent Positive Airway Pressure: A Randomized Crossover Pilot Trial

International audienceIntroduction: Synchronization of non-invasive ventilation is challenging in extremely premature infants. We compared patient-ventilator synchrony between non-invasive neurally adjusted ventilatory assist (NIV-NAVA) using transdiaphragmatic (Edi) catheter and synchronized intermittent positive airway pressure (SiPAP) using an abdominal trigger. Methods: This study was a monocentric, randomized, crossover trial in premature infants born before 28 weeks of gestation, aged 3 days or more, and below 32 weeks postmenstrual age. NIV-NAVA and SiPAP were applied in a random order for 2 h with analysis of data from the second hour. The primary outcome was the asynchrony index. Results: Fourteen patients were included (median [IQR] gestational age at birth 25.6 (25.3–26.4) weeks, median [IQR] birth weight 755 [680–824] g, median [IQR] postnatal age 26.5 [19.8–33.8] days). The median (IQR) asynchrony index was significantly lower in NIV-NAVA versus SiPAP (49.9% [44.1–52.6] vs. 85.8% [74.2–90.9], p &#x3c; 0.001). Ineffective efforts and auto-triggering were significantly less frequent in NIV-NAVA versus SiPAP (3.0% vs. 32.0% p &#x3c; 0.001 and 10.0% vs. 26.6%, p = 0.004, respectively). Double triggering was significantly less frequent in SiPAP versus NIV-NAVA (0.0% vs. 9.0%, p &#x3c; 0.001). No significant difference was observed for premature cycling and late cycling. Peak Edi and swing Edi were significantly lower in NIV-NAVA as compared to SiPAP (7.7 [6.1–9.9] vs. 11.0 [6.7–14.5] μV, p = 0.006; 5.4 [4.2–7.6] vs. 7.6 [4.3–10.8] μV, p = 0.007, respectively). No significant difference was observed between NIV-NAVA and SiPAP for heart rate, respiratory rate, COMFORTneo scores, apnoea, desaturations, or bradycardias. Discussion/Conclusion: NIV-NAVA markedly improves patient-ventilator synchrony as compared to SiPAP in extremely premature infants

Plasma hydrogenated cationic detonation nanodiamonds efficiently deliver to human cells in culture functional siRNA targeting the Ewing sarcoma junction oncogene

International audienceThe expression of a defective gene can lead to major cell dysfunctions among which cell proliferation and tumor formation. One promising therapeutic strategy consists in silencing the defective gene using small interfering RNA (siRNA). In previous publications we showed that diamond nanocrystals (ND) of primary size 35 nm, rendered cationic by polyethyleneimine-coating, can efficiently deliver siRNA into cell, which further block the expression of EWS/FLI-1 oncogene in a Ewing sarcoma disease model. However, a therapeutic application of such nanodiamonds requires their elimination by the organism, particularly in urine, which is impossible for 35 nm particles. Here, we report that hydrogenated cationic nanodiamonds of primary size 7 nm (ND-H) have also a high affinity for siRNA and are capable of delivering them in cells. With siRNA/ND-H complexes, we measured a high inhibition efficacy of EWS/FLI-1 gene expression in Ewing sarcoma cell line. Electron microscopy investigations showed ND-H in endocytosis compartments, and especially in macropinosomes from which they can escape before siRNA degradation occurred. In addition, the association of EWS/FLI-1 silencing by the siRNA/ND-H complex with a vincristine treatment yielded a potentiation of the toxic effect of this chemotherapeutic drug. Therefore ND-H appears as a promising delivery agent in anti-tumoral gene therapy

Rare-earth doped nanoferroelectric as an all-optical electric field sensor

International audienceUp/down-conversion photoluminescence from the rare-earth-doped nanocrystals have attracted a lot of interest because of their unique optical properties useful in various fields, including biophotonics and nanomedicine research [1-3]. Here, we use ferroelectric materials whose intrinsic polarization and crystal structure are responsive to external stimuli, e.g. electric field, mechanical stress, or temperature, as the matrix for welcoming the optically sensitive rare-earth elements [4-5]. As an illustration, we show here how we design a rare-earth-based ferroelectric sensor to detect the real-time local electric potential that, e.g. exists in biological neuronal networks for better understanding neuronal circuits functions in normal and pathological conditions. We prepare Yb3+/Er3+ co-doped BaTiO3 (BTO) nanocrystals via the hydrothermal method using a complex of BaCO3, CH3COOH, Yb(NO3)3, Er(CH3COO)3 and Ti(C3H7O)4 as precursors. The obtained Yb3+/Er3+ -doped BTO nanocrystals have a cubic shape with edge sizes of 150 nm and show up and down-conversion signals when optically excited with 980 nm and 488 nm laser wavelength, respectively. Under a bias voltage, an enhancement of 14 % in up-conversion emission intensity is observed at ~550nm line emission, which indicates that the single Yb3+/Er3+ -doped BTO nanocrystal has a good electric-field response and might be taken into consideration for the aforementioned biological applications.[1] J. Loo et al., Coordination Chemistry Reviews 400, 213042 (2019)[2] G. Chen et al., Chemical Reviews 114, 5161 (2014)[3] K. Shahzad et al., Materials Science and Engineering: C 119, 111444 (2021)[4] J. Hao et al., Angewandte Chemie International Edition 50, 6876 (2011)[5] C. Paillard et al., Advanced Materials 28, 5153 (2016

Ferroelectric texture of individual barium titanate nanocrystals

Ferroelectric materials display exotic polarization textures at the nanoscale that could be used to improve the energetic efficiency of electronic components. The vast majority of studies were conducted in two dimensions on thin films, that can be further nanostructured, but very few studies address the situation of individual isolated nanocrystals synthesized in solution, while such structures could open other field of applications. In this work, we experimentally and theoretically studied the polarization texture of ferroelectric barium titanate (BaTiO3 , BTO) nanocrystals (NC) attached to a conductive substrate and surrounded by air. We synthesized NC of well defined 1 quasi-cubic shape and 160 nm average size, that conserve the tetragonal structure of BTO at room temperature. We then investigated the inverse piezoelectric properties of such pristine individual NC by vector piezoresponse force microscopy (PFM), taking particular care of suppressing electrostatic artifacts. In all the NC studied, we could not detect any vertical PFM signal, and the maps of the lateral response all displayed larger displacement amplitude on the edges with deformations converging toward the center. Using fieldphase simulations dedicated to ferroelectric nanostructures, we were able to predict the equilibrium polarization texture. These simulations revealed that the NC core is composed of 180° up and down domains defining the polar axis, that rotate by 90° in the two facets orthogonal to this axis, eventually lying within these planes forming a layer of about 10 nm thickness mainly composed of 180° domains along an edge. From this polarization distribution we predicted the lateral PFM response, that revealed to be in very good qualitative agreement with the experimental observations. This work positions PFM as a relevant tool to evaluate the potential of complex ferroelectric nanostructures to be used as sensors