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Background: The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the BMPR2 gene. The incomplete penetrance of BMPR2 mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers pulmonary hypertension (PH) in rats with Bmpr2 mutations., Methods and Results: Male and female rats with a 71 bp monoallelic deletion in exon 1 of Bmpr2 and their wild-type siblings underwent acute and chronic RPAO. They were subjected to full high-fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced precapillary PH in male and female rats, both acutely and chronically. Bmpr2 mutant and male rats manifested more severe PH compared with their counterparts. Although wild-type rats adapted to RPAO, Bmpr2 mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male Bmpr2 rats. Chronic RPAO resulted in elevated pulmonary IL-6 (interleukin-6) expression and decreased Gdf2 expression (corrected P value<0.05 and log2 fold change>1). In this context, male rats expressed higher pulmonary levels of endothelin-1 and IL-6 than females., Conclusions: Our novel 2-hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex- and gene-related effects.

Background: The MELODY system allows for performing ultrasonography on a patient remotely and has been proposed to assess disease characteristics in the context of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this interventional crossover study was to address the feasibility of the system in children aged 1 to 10 years old., Methods: Children underwent ultrasonography with a telerobotic ultrasound system followed by a second conventional examination by a different sonographer., Results: In total, 38 children were enrolled, and 76 examinations were performed, with 76 scans analyzed. The mean [standard deviation (SD)] age of participants was 5.7 (2.7) years (range, 1-10 years). We found substantial agreement between telerobotic and conventional ultrasonography [κ=0.74 (95% CI: 0.53-0.94), P<0.005]. The mean (SD) duration was longer for telerobotic than conventional examinations [26.0 (2.5) vs. 13.9 (11.2) min, P<0.0001]. Abdominal organs and abnormalities were similarly visualized on telerobotic and conventional ultrasonography. Cardiac echocardiography provided reliable diagnoses, with non-significantly different measurements with both techniques, although the visualization score was significantly higher with conventional than telerobotic ultrasonography (P<0.05). On lung analysis, both examinations identified consolidations and pleural effusion, whereas visualization and total lung score were similar with the 2 techniques. Overall, 45% of parents reported that their children felt less pressure with the telerobotic system., Conclusions: Telerobotic ultrasonography may be effective, feasible, and well-tolerated in children., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-569/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present., Background: The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy., Methods: The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018–2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed., Conclusions: The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Context: In bright photodissociation regions (PDRs) associated to massive star formation, the presence of dense "clumps" that are immersed in a less dense interclump medium is often proposed to explain the difficulty of models to account for the observed gas emission in high-excitation lines., Aims: We aim at presenting a comprehensive view of the modeling of the CO rotational ladder in PDRs, including the high-J lines that trace warm molecular gas at PDR interfaces., Methods: We observed the 12 CO and 13 CO ladders in two prototypical PDRs, the Orion Bar and NGC 7023 NW using the instruments onboard Herschel . We also considered line emission from key species in the gas cooling of PDRs (C + , O, H 2 ) and other tracers of PDR edges such as OH and CH + . All the intensities are collected from Herschel observations, the literature and the Spitzer archive and are analyzed using the Meudon PDR code., Results: A grid of models was run to explore the parameter space of only two parameters: thermal gas pressure and a global scaling factor that corrects for approximations in the assumed geometry. We conclude that the emission in the high-J CO lines, which were observed up to J up =23 in the Orion Bar (J up =19 in NGC 7023), can only originate from small structures of typical thickness of a few 10 -3 pc and at high thermal pressures ( P th ~ 10 8 K cm -3 )., Conclusions: Compiling data from the literature, we found that the gas thermal pressure increases with the intensity of the UV radiation field given by G 0 , following a trend in line with recent simulations of the photoevaporation of illuminated edges of molecular clouds. This relation can help rationalising the analysis of high-J CO emission in massive star formation and provides an observational constraint for models that study stellar feedback on molecular clouds.

Evidence is mounting that the small bodies of our Solar System, such as comets and asteroids, have at least partially inherited their chemical composition from the first phases of the Solar System formation. It then appears that the molecular complexity of these small bodies is most likely related to the earliest stages of star formation. It is therefore important to characterize and to understand how the chemical evolution changes with solar-type protostellar evolution. We present here the Large Program "Astrochemical Surveys At IRAM" (ASAI). Its goal is to carry out unbiased millimeter line surveys between 80 and 272 GHz of a sample of ten template sources, which fully cover the first stages of the formation process of solar-type stars, from prestellar cores to the late protostellar phase. In this article, we present an overview of the surveys and results obtained from the analysis of the 3 mm band observations. The number of detected main isotopic species barely varies with the evolutionary stage and is found to be very similar to that of massive star-forming regions. The molecular content in O- and C- bearing species allows us to define two chemical classes of envelopes, whose composition is dominated by either a) a rich content in O-rich complex organic molecules, associated with hot corino sources, or b) a rich content in hydrocarbons, typical of Warm Carbon Chain Chemistry sources. Overall, a high chemical richness is found to be present already in the initial phases of solar-type star formation.

We report the detection in space of a new molecular species which has been characterized spectroscopically and fully identified from astrophysical data. The observations were carried out with the 30m IRAM telescopea. The molecule is ubiquitous as its J =2→1 transition has been found in cold molecular clouds, prestellar cores, and shocks. However, it is not found in the hot cores of Orion-KL and in the carbon-rich evolved star IRC+10216. Three rotational transitions in perfect harmonic relation J ' = 2/3/5 have been identified in the prestellar core B1b. The molecule has a 1 Σ electronic ground state and its J =2→1 transition presents the hyperfine structure characteristic of a molecule containing a nucleus with spin 1. A careful analysis of possible carriers shows that the best candidate is NS + . The derived rotational constant agrees within 0.3-0.7% with ab initio calculations. NS + was also produced in the laboratory to unambiguously validate the astrophysical assignment. The observed rotational frequencies and determined molecular constants confirm the discovery of the nitrogen sulfide cation in space. The chemistry of NS + and related nitrogen-bearing species has been analyzed by means of a time-dependent gas phase model. The model reproduces well the observed NS/NS + abundance ratio, in the range 30-50, and indicates that NS + is formed by reactions of the neutral atoms N and S with the cations SH + and NH + , respectively.

The detection of complex organic molecules (COMs) toward cold sources such as pre-stellar cores (with T<10 K), has challenged our understanding of the formation processes of COMs in the interstellar medium. Recent modelling on COM chemistry at low temperatures has provided new insight into these processes predicting that COM formation depends strongly on parameters such as visual extinction and the level of CO freeze out. We report deep observations of COMs toward two positions in the L1544 pre-stellar core: the dense, highly-extinguished continuum peak with A V ≥30 mag within the inner 2700 au; and a low-density shell with average A V ~7.5-8 mag located at 4000 au from the core's center and bright in CH 3 OH. Our observations show that CH 3 O, CH 3 OCH 3 and CH 3 CHO are more abundant (by factors ~2-10) toward the low-density shell than toward the continuum peak. Other COMs such as CH 3 OCHO, c-C 3 H 2 O, HCCCHO, CH 2 CHCN and HCCNC show slight enhancements (by factors ≤3) but the associated uncertainties are large. This suggests that COMs are actively formed and already present in the low-density shells of pre-stellar cores. The modelling of the chemistry of O-bearing COMs in L1544 indicates that these species are enhanced in this shell because i) CO starts freezing out onto dust grains driving an active surface chemistry; ii) the visual extinction is sufficiently high to prevent the UV photo-dissociation of COMs by the external interstellar radiation field; and iii) the density is still moderate to prevent severe depletion of COMs onto grains.

IRAS 04368+2557 is a solar-type (low-mass) protostar embedded in a protostellar core (L1527) in the Taurus molecular cloud, which is only 140 parsecs away from Earth, making it the closest large star-forming region. The protostellar envelope has a flattened shape with a diameter of a thousand astronomical units (1 AU is the distance from Earth to the Sun), and is infalling and rotating. It also has a protostellar disk with a radius of 90 AU (ref. 6), from which a planetary system is expected to form. The interstellar gas, mainly consisting of hydrogen molecules, undergoes a change in density of about three orders of magnitude as it collapses from the envelope into the disk, while being heated from 10 kelvin to over 100 kelvin in the mid-plane, but it has hitherto not been possible to explore changes in chemical composition associated with this collapse. Here we report that the unsaturated hydrocarbon molecule cyclic-C3H2 resides in the infalling rotating envelope, whereas sulphur monoxide (SO) is enhanced in the transition zone at the radius of the centrifugal barrier (100 ± 20 AU), which is the radius at which the kinetic energy of the infalling gas is converted to rotational energy. Such a drastic change in chemistry at the centrifugal barrier was not anticipated, but is probably caused by the discontinuous infalling motion at the centrifugal barrier and local heating processes there.

In 2006, the French Food Safety Agency (AFSSA) conducted the Second French Total Diet Study (TDS) to estimate dietary exposures to the main minerals and trace elements from 1319 samples of foods typically consumed by the French population. The foodstuffs were analysed by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave-assisted digestion. Occurrence data for lithium, chromium, manganese, cobalt, nickel, copper, zinc, selenium and molybdenum were reported and compared with results from the previous French TDS. The results indicate that the food groups presenting the highest levels of these essential trace elements were "tofu" (for Li, Mn, Ni, Cu, Zn and Mo),"fish and fish products" particularly "shellfish" (for Li, Co, Cu, Zn, Se and Mo), "sweeteners, honey and confectionery" particularly dark chocolate (for Cr, Mn, Co, Ni and Cu), "cereals and cereal products" (for Mn, Ni and Mo) and "ice cream" (for Cr, Co and Ni)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A strategy for the accurate determination in foodstuffs of seven elements liable to be interfered with (V, Cr, Fe, Co, Ni, As and Se), was successfully applied. Firstly, to reduce spectroscopic interferences, four influential factors (hexapole and quadrupole bias, helium and hydrogen flows) of the collision/reaction cell device were optimised through the experimental design methodology. Secondly, non-spectroscopic interferences, which may severely disturb the analysis of matrices containing large amounts of non-target elements, were significantly reduced by a limited decrease in the flow rate of the optimum initial nebuliser rather than with a specific time-consuming dilution. Finally, the optimised multi-element method was subjected to a full validation that demonstrated its acceptable analytical performance., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The levels of 20 essential or toxic trace elements in 159 fish, other seafood and seafood products on the French coastal market collected between January and April 2005 were measured by ICP-MS. The concentration ranges (mg/kg of fresh mass) for the elements determined were compared with previous studies. The contents of Co, Cu, Fe, Li, Mn, Se, Zn and Pb found in fish are close to or often lower than previous studies. For other seafood, comparison is difficult due to the lack of data on a more global scale. However, it should be noted that the contents of Ag were found considerably higher in this study., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: A detailed preoperative evaluation of coronary anatomy is mandatory before surgical intervention for tetralogy of Fallot. In pediatric patients, the preoperative evaluation of coronary anatomy has relied classically on conventional angiographic analysis and, more recently, on echocardiographic analysis, which have well-known limitations and complications. Recent technological improvements allow the use of multislice computed tomographic analysis to evaluate coronary artery anatomy in very young children, even those with high heart rates. The purpose of this prospective study was to assess the accuracy of preoperative dual-source computed tomographic analysis in detecting coronary artery abnormalities by using surgical findings as the reference standard., Methods: We prospectively evaluated 100 patients with tetralogy of Fallot before surgical intervention between November 2006 and September 2009 by using dual-source computed tomographic analysis with either retrospective, electrocardiographically gated, helical computed tomographic analysis or prospective, electrocardiographically triggered, sequential computed tomographic acquisition. The patients had a median age of 6.8 months (range, 1.2 months-6.8 years) and a median weight of 7.9 kg (range, 3-30 kg)., Results: Compared with surgical findings, dual-source computed tomographic analysis had 100% sensitivity and 100% specificity for detecting coronary artery abnormalities. Major coronary artery abnormalities were found in 7 (7%) patients. The radiation dose was low., Conclusions: Dual-source computed tomographic analysis is an accurate and noninvasive tool for delineating coronary artery anatomy before surgical intervention in children with tetralogy of Fallot. Dual-source computed tomographic analysis might deserve to be used routinely instead of angiographic analysis and in combination with echocardiographic analysis for the preoperative assessment of patients with tetralogy of Fallot., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

In 2006, the French Food Safety Agency (AFSSA) conducted the second French total diet study (TDS) to estimate dietary exposures of main minerals and trace elements from 1319 samples of foods habitually consumed by the French population. The foodstuffs were analysed by ICP-MS after microwave-assisted digestion. Contamination data for lead, mercury, cadmium, arsenic, antimony and aluminium were reported and compared with results from the previous French total diet study. The results are comparable with those from the rest of Europe. "Fish and fish products" and "sweeteners, honey and confectionery" were the food groups showing the highest cumulated contents in Pb, Hg, Cd, As, Al and Sb. However, observed levels remained low and were generally well below the maximum levels set by the current European regulation for lead, cadmium and mercury., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

This paper describes a validation process in compliance with the NFIEN ISO/IEC 17025 standard for the determination of the macrominerals calcium, magnesium, sodium, and potassium in foodstuffs by microsampling with flame atomic absorption spectrometry after closed-vessel microwave digestion. The French Standards Commission (Agence Francaise de Normalisation) standards NF V03-110, NF EN V03-115, and XP T-90-210 were used to evaluate this method. The method was validated in the context of an analysis of the 1322 food samples of the second French Total Diet Study (TDS). Several performance criteria (linearity, LOQ, specificity, trueness, precision under repeatability conditions, and intermediate precision reproducibility) were evaluated. Furthermore, the method was monitored by several internal quality controls. The LOQ values obtained (25, 5, 8.3, and 8.3 mg/kg for Ca, Mg, Na, and K, respectively) were in compliance with the needs of the TDS. The method provided accurate results as demonstrated by a repeatability CV (CVr) of < 7% and a reproducibility CV (CVR) of < 12% for all the elements. Therefore, the results indicated that this method could be used in the laboratory for the routine determination of these four elements in foodstuffs with acceptable analytical performance.

Deuterium enhancement of monodeuterated species has been recognized for more than 30 years as a result of chemical fractionation that results from the difference in zero-point energies of deuterated and hydrogenated molecules. The key reaction is the deuteron exchange in the reaction between HD, the reservoir of deuterium in dark interstellar clouds, and the H3+ molecular ion, leading to the production of H2D+ molecule, and the low temperature in dark interstellar clouds favours this production. Furthermore, the presence of multiply deuterated species have incited our group to proceed further and consider the subsequent reaction of H2D+ with HD, leading to D2H+, which can further react with HD to produce D3+. In pre-stellar cores, where CO was found to be depleted, this production should be increased as CO would normally destroy H3+. The first model including D2H+ and D3+ predicted that these molecules should be as abundant as H2D+. The first detection of the D2H+ was made possible by the recent laboratory measurement for the frequency of the fundamental line of para-D2H+. Here, we present observations of H2D+ and D2H+ towards a sample of dark clouds and pre-stellar cores and show how the distribution of ortho-H2D+ (1(1,0)-1(1,1)) can trace the deuterium factory in pre-stellar cores. We also present how future instrumentation will improve our knowledge concerning the deuterium enhancement of H3+.

A method validation of the total analysis of cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) in foodstuffs by inductively coupled plasma/mass spectrometry (ICP/MS) after closed vessel microwave digestion is presented. Due to the lack of reference method for ICP/MS techniques in food and, based on the project of the European Committee of Normalization (CEN/TC 275/WG 10), the Agence Française de Normalisation (AFNOR) guidelines NF V03-110 were used for the evaluation of this method based on 2 steps, sample preparation and multielement detection. Several criteria considered as compulsory (linearity, specificity, precision under repeatability conditions, and trueness) have been estimated and discussed, in addition to intermediate precision reproducibility, the limit of detection, and the limit of quantification. Furthermore, a comparison with in-house methods using electrothermal atomic absorption was performed using an external proficiency testing scheme and food samples. The results indicated that this method could be used in the laboratory for the routine determination of these 4 cumulative toxic metals in foodstuffs with acceptable analytical performance.

Study Objectives: Nasal prongs (NPs), when used to assess nasal flow, can result in dramatic increases in nasal airflow resistance (NR). The aim of this study was to investigate whether the NP-induced increases in NR could be corrected by the simultaneous use of an internal nasal dilator (ND)., Design: NR was estimated by posterior rhinomanometry, in the basal state (NRb), and while breathing with NP (NRp), with ND (NRd), and with both ND and NP (NRd + p)., Participants: The study was performed in 15 healthy subjects., Measurements and Results: NR (mean NRb [+/- SEM], 2.5 +/- 0.4 cm H(2)O/L/s) significantly decreased with ND (NRd = 1.4 +/- 0.2 cm H(2)O/L/s; p < 0.001) and significantly increased with NP (NRp = 3.8 +/- 0.8 cm H(2)O/L/s; p < 0.001). A significant logarithmic relationship was found between NRd and NRb (r(2) = 0.95; p < 0.0001), and a significant exponential relationship was found between NRp and NRb (r(2) = 0.99; p < 0.0001). While breathing with both ND and NP, NRd + p was significantly lower than NRb (1.9 +/- 1.4 cm H(2)O/L/s; p < 0.02)., Conclusions: Our results demonstrate that the ND tends to slightly overcorrect the NP-induced increase in NR and suggest that, in view of the possible effects of NPs on upper airway resistance, the combination of both devices might be used for nasal airflow monitoring during nocturnal polysomnography in patients presenting with highly resistive nares.