Safety of the use of face masks in pediatric age

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Gating Properties of <i>SCN5A</i> Mutations and the Response to Mexiletine in Long-QT Syndrome Type 3 Patients

Background— Mexiletine (Mex) has been proposed as a gene-specific therapy for patients with long-QT syndrome type 3 (LQT3) caused by mutations in the cardiac sodium channel gene ( SCN5A ). The degree of QT shortening and the protection from arrhythmias vary among patients harboring different mutations. We tested whether the clinical response to Mex in LQT3 could be predicted by the biophysical properties of the different mutations. Methods and Results— We identified 4 SCN5A mutations in 5 symptomatic LQT3 patients with different responses to Mex (6 to 8 mg · kg −1 · d −1 ). We classified the mutations as sensitive to Mex (P1332L, R1626P; ≥10% of QTc shortening and QTc <500 ms or no arrhythmias) or insensitive to Mex (S941N, M1652R; negligible or no QTc shortening and sudden death). We measured Na + current from HEK 293 cells transfected with wild-type (WT) or mutant Nav1.5. All mutations showed impaired inactivation of Na + current, but the mutations identified in patient responders to Mex (P1332L, R1626P) showed a hyperpolarizing shift of V 1/2 of steady-state inactivation. Furthermore, Mex produced use-dependent block with the order R1626P=P1332L>S941N=WT>M1652R, suggesting that Mex-sensitive mutants present prolonged recovery from Mex block. Conclusions— We propose that voltage dependence of channel availability and shifts of V 1/2 of steady-state inactivation correlate with the clinical response observed in LQT3 patients. This supports the view that the response to Mex is mutation specific and that in vitro testing may help to predict the response to therapy in LQT3

Comment on Jaworska, J. et al. Consensus on the application of lung ultrasound in pneumonia and bronchiolitis in children

To the editor: [...

Mutations in the Cardiac Ryanodine Receptor Gene (hRyR2) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is a genetic arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. The electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with calcium overload and the delayed afterdepolarizations observed during digitalis toxicity. We speculated that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease; therefore, we considered the human cardiac ryanodine receptor gene (hRyR2) a likely candidate for this genetically transmitted arrhythmic disorder. METHODS AND RESULTS: Twelve patients presenting with typical catecholaminergic polymorphic ventricular tachycardia in the absence of structural heart abnormalities were identified. DNA was extracted from peripheral blood lymphocytes, and single-strand conformation polymorphism analysis was performed on polymerase chain reaction-amplified exons of the hRyR2 gene. Four single nucleotide substitutions leading to missense mutations were identified in 4 probands affected by the disease. Genetic analysis of the asymptomatic parents revealed that 3 probands carried de novo mutations. In 1 case, the identical twin of the proband died suddenly after having suffered syncopal episodes. The fourth mutation was identified in the proband, in 4 clinically affected family members, and in none of 3 nonaffected family members in a kindred with 2 sudden deaths that occurred at 16 and 14 years, respectively, in the sisters of the proband. CONCLUSIONS: We demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia

A new calculation of atmospheric neutrino flux: the FLUKA approach.

Abstract Preliminary results from a full 3-D calculation of atmospheric neutrino fluxes using the FLUKA interaction model are presented and compared to previous existing calculations. This effort is motivated mainly by the 3-D capability and the satisfactory degree of accuracy of the hadron-nucleus models embedded in the FLUKA code. Here we show examples of benchmarking tests of the model with cosmic ray experiment results. A comparison of our calculation of the atmospheric neutrino flux with that of the Bartol group, for E ν > 1 GeV, is presented

Growing Role of 3D In Vitro Cell Cultures in the Study of Cellular and Molecular Mechanisms: Short Focus on Breast Cancer, Endometriosis, Liver and Infectious Diseases

Over the past decade, the development of three-dimensional (3D) models has increased exponentially, facilitating the unravelling of fundamental and essential cellular mechanisms by which cells communicate with each other, assemble into tissues and organs and respond to biochemical and biophysical stimuli under both physiological and pathological conditions. This section presents a concise overview of the most recent updates on the significant contribution of different types of 3D cell cultures including spheroids, organoids and organ-on-chip and bio-printed tissues in advancing our understanding of cellular and molecular mechanisms. The case studies presented include the 3D cultures of breast cancer (BC), endometriosis, the liver microenvironment and infections. In BC, the establishment of 3D culture models has permitted the visualization of the role of cancer-associated fibroblasts in the delivery of exosomes, as well as the significance of the physical properties of the extracellular matrix in promoting cell proliferation and invasion. This approach has also become a valuable tool in gaining insight into general and specific mechanisms of drug resistance. Given the considerable heterogeneity of endometriosis, 3D models offer a more accurate representation of the in vivo microenvironment, thereby facilitating the identification and translation of novel targeted therapeutic strategies. The advantages provided by 3D models of the hepatic environment, in conjunction with the high throughput characterizing various platforms, have enabled the elucidation of complex molecular mechanisms underlying various threatening hepatic diseases. A limited number of 3D models for gut and skin infections have been developed. However, a more profound comprehension of the spatial and temporal interactions between microbes, the host and their environment may facilitate the advancement of in vitro, ex vivo and in vivo disease models. Additionally, it may pave the way for the development of novel therapeutic approaches in diverse research fields. The interested reader will also find concluding remarks on the challenges and prospects of using 3D cell cultures for discovering cellular and molecular mechanisms in the research areas covered in this review

Nano-biocomposite films with modified cellulose nanocrystals and synthesized silver nanoparticles

Ternary nano-biocomposite films based on poly(lactic acid) (PLA) with modified cellulose nanocrystals (s-CNC) and synthesized silver nanoparticles (Ag) have been prepared and characterized. The functionalization of the CNC surface with an acid phosphate ester of ethoxylated nonylphenol favoured its dispersion in the PLA matrix. The positive effects of the addition of cellulose and silver on the PLA barrier properties were confirmed by reductions in the water permeability (WVP) and oxygen transmission rate (OTR) of the films tested. The migration level of all nano-biocomposites in contact with food simulants were below the permitted limits in both non-polar and polar simulants. PLA nano-biocomposites showed a significant antibacterial activity influenced by the Ag content, while composting tests showed that the materials were visibly disintegrated after 15 days with the ternary systems showing the highest rate of disintegration under composting conditions.L.V. would like to acknowledge the financial support from MIUR, PRIN 2010–11 project entitled “Nanomed” (prot.2010FPTBSH 009). M.P. and A.J. acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness (MAT2011-28648-C02-1)

Hep3Gel: A Shape-Shifting Extracellular Matrix-Based, Three-Dimensional Liver Model Adaptable to Different Culture Systems

Drug-induced hepatotoxicity is a leading cause of clinical trial withdrawal. Therefore, in vitro modeling the hepatic behavior and functionalities is not only crucial to better understand physiological and pathological processes but also to support drug development with reliable high-throughput platforms. Different physiological and pathological models are currently under development and are commonly implemented both within platforms for standard 2D cultures and within tailor-made chambers. This paper introduces Hep3Gel: a hybrid alginate-extracellular matrix (ECM) hydrogel to produce 3D in vitro models of the liver, aiming to reproduce the hepatic chemomechanical niche, with the possibility of adapting its shape to different manufacturing techniques. The ECM, extracted and powdered from porcine livers by a specifically set-up procedure, preserved its crucial biological macromolecules and was embedded within alginate hydrogels prior to crosslinking. The viscoelastic behavior of Hep3Gel was tuned, reproducing the properties of a physiological organ, according to the available knowledge about hepatic biomechanics. By finely tuning the crosslinking kinetics of Hep3Gel, its dualistic nature can be exploited either by self-spreading or adapting its shape to different culture supports or retaining the imposed fiber shape during an extrusion-based 3D-bioprinting process, thus being a shape-shifter hydrogel. The self-spreading ability of Hep3Gel was characterized by combining empirical and numerical procedures, while its use as a bioink was experimentally characterized through rheological a priori printability evaluations and 3D printing tests. The effect of the addition of the ECM was evident after 4 days, doubling the survival rate of cells embedded within control hydrogels. This study represents a proof of concept of the applicability of Hep3Gel as a tool to develop 3D in vitro models of the liver

Assessment of respiratory function in infants and young children wearing face masks during the COVID-19 pandemic

Importance: Face masks have been associated with effective prevention of diffusion of viruses via droplets. However, the use of face masks among children, especially those aged younger than 3 years, is debated, and the US Centers for Disease Control and American Academy of Physicians recommend the use of face mask only among individuals aged 3 years or older.Objective: To examine whether the use of surgical facial masks among children is associated with episodes of oxygen desaturation or respiratory distress.Design, Setting, and Participants: This cohort study was conducted from May through June 2020 in a secondary-level hospital pediatric unit in Italy. Included participants were 47 healthy children divided by age (ie, group A, aged ≤24 months, and group B, aged &gt;24 months to ≤144 months). Data were analyzed from May through June 2020.Interventions: All participants were monitored every 15 minutes for changes in respiratory parameters for the first 30 minutes while not wearing a surgical face mask and for the next 30 minutes while wearing a face mask. Children aged 24 months and older then participated in a walking test for 12 minutes.Main Outcomes and Measures: Changes in respiratory parameters during the use of surgical masks were evaluated.Results: Among 47 children, 22 children (46.8%) were aged 24 months or younger (ie, group A), with 11 boys (50.0%) and median (interquartile range [IQR]) age 12.5 (10.0-17.5) months, and 25 children (53.2%) were aged older than 24 months to 144 months or younger, with 13 boys (52.0%) and median (IQR) age 100.0 (72.0-120.0) months. During the first 60 minutes of evaluation in the 2 groups, there was no significant change in group A in median (IQR) partial pressure of end-tidal carbon dioxide (Petco2; 33.0 [32.0-34.0] mm Hg; P for Kruskal Wallis =.59), oxygen saturation (Sao2; 98.0% [97.0%-99.0%]; P for Kruskal Wallis =.61), pulse rate (PR; 130.0 [115.0-140.0] pulsations/min; P for Kruskal Wallis =.99), or respiratory rate (RR; 30.0 [28.0-33.0] breaths/min; P for Kruskal Wallis =.69) or for group B in median (IQR) Petco2 (36.0 [34.0-38.0] mm Hg; P for Kruskal Wallis =.97), Sao2 (98.0% [97.0%-98.0%]; P for Kruskal Wallis =.52), PR (96.0 [84.0-104.5] pulsations/min; P for Kruskal Wallis test=.48), or RR (22.0 [20.0-25.0] breaths/min; P for Kruskal Wallis =.55). After the group B walking test, compared with before the walking test, there was a significant increase in median (IQR) PR (96.0 [84.0-104.5] pulsations/min vs 105.0 [100.0-115.0] pulsations/min; P&lt;.02) and RR (22.0 [20.0-25.0] breaths/min vs 26.0 [24.0-29.0] breaths/min; P&lt;.05).Conclusions and Relevance: This cohort study among infants and young children in Italy found that the use of facial masks was not associated with significant changes in Sao2 or Petco2, including among children aged 24 months and younger