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Sleep is a fundamental biological necessity, the lack of which has severe repercussions on the mental and physical well-being in individuals of all ages. The phrase "sleep-disordered breathing (SDB)" indicates a wide array of conditions characterized by snoring and/or respiratory distress due to increased upper airway resistance and pharyngeal collapsibility; these range from primary snoring to obstructive sleep apnea (OSA) and occur in all age groups. In the general pediatric population, the prevalence of OSA varies between 2% and 5%, but in some particular clinical conditions, it can be much higher. While adenotonsillar hypertrophy ("classic phenotype") is the main cause of OSA in preschool age (3-5 years), obesity ("adult phenotype") is the most common cause in adolescence. There is also a "congenital-structural" phenotype that is characterized by a high prevalence of OSA, appearing from the earliest ages of life, supported by morpho-structural abnormalities or craniofacial changes and associated with genetic syndromes such as Pierre Robin syndrome, Prader-Willi, achondroplasia, and Down syndrome. Neuromuscular disorders and lysosomal storage disorders are also frequently accompanied by a high prevalence of OSA in all life ages. Early recognition and proper treatment are crucial to avoid major neuro-cognitive, cardiovascular, and metabolic morbidities.

Background: In children with primary ciliary dyskinesia (PCD), measures more sensitive than spirometry are needed to characterize underlying pulmonary impairment. Electrical impedance tomography (EIT) is a promising noninvasive method for monitoring the distribution of lung ventilation, and it does not require patient collaboration. We aimed to provide an assessment of the feasibility and clinical usefulness of EIT in characterizing lung impairment in children with PCD, compared to spirometry and multiple breath nitrogen washout (MBWN 2 ) test., Methods: Children and adolescents with PCD underwent MBWN 2 test as first respiratory assessment, followed by EIT monitoring and spirometry during outpatient follow-up., Results: We included 12 out of 16 individuals regularly followed at our clinic. A total of 41.7% (5/12) showed abnormal forced expiratory volume in 1 s (FEV 1 ), whereas 11/12 (91.7%) had abnormal ventilation inhomogeneity measured with MBWN 2 test. Using EIT, the global inhomogeneity (GI TOT ) index showed moderate to strong correlation with FEV 1 (ρ = -0.55, 95% confidence interval [CI]: -0.87 to 0.02) and ranged from 37 to 44, with the highest inhomogeneity detected in the dorsal right quadrant. GI TOT was moderately correlated with RV/TLC %predicted (ρ = 0.38, 95% CI: -0.17 to 0.74), while we detected a weak correlation between GI TOT and lung clearance index (ρ = 0.29, 95% CI: -0.45 to 0.82)., Conclusion: EIT appears promising as a noninvasive technique to characterize ventilation distribution in children with PCD, thus providing a complementary assessment to static and dynamic lung function measures of PCD disease., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

The use of 13 C-labeled molecular probes is essential to explore altered metabolic pathways in human pathologies. The analysis of the different 13 C isotopologues resulting from these changes in metabolic pathways is essential to understand the different biological processes involved. We propose an NMR methodology consisting of eight different NMR experiments performed under HRMAS conditions to explore metabolic pathways in unprocessed pathological cells and tissues. This methodology has the potential to study human pathologies in the medical field and to enable the analysis of the mode of action of therapeutic treatments.

Motivation: Identification and removal of micro-scale residual tumor tissue during brain tumor surgery are key for survival in glioma patients. For this goal, High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) spectroscopy-based assessment of tumor margins during surgery has been an effective method. However, the time required for metabolite quantification and the need for human experts such as a pathologist to be present during surgery are major bottlenecks of this technique. While machine learning techniques that analyze the NMR spectrum in an untargeted manner (i.e. using the full raw signal) have been shown to effectively automate this feedback mechanism, high dimensional and noisy structure of the NMR signal limits the attained performance., Results: In this study, we show that identifying informative regions in the HRMAS NMR spectrum and using them for tumor margin assessment improves the prediction power. We use the spectra normalized with the ERETIC (electronic reference to access in vivo concentrations) method which uses an external reference signal to calibrate the HRMAS NMR spectrum. We train models to predict quantities of metabolites from annotated regions of this spectrum. Using these predictions for tumor margin assessment provides performance improvements up to 4.6% the Area Under the ROC Curve (AUC-ROC) and 2.8% the Area Under the Precision-Recall Curve (AUC-PR). We validate the importance of various tumor biomarkers and identify a novel region between 7.97 ppm and 8.09 ppm as a new candidate for a glioma biomarker., Availability and Implementation: The code is released at https://github.com/ciceklab/targeted_brain_tumor_margin_assessment. The data underlying this article are available in Zenodo, at https://doi.org/10.5281/zenodo.5781769., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pompe disease (PD) is a disorder of glycogen metabolism conditioning a progressive and life conditioning myopathy. Enzyme replacement therapy (ERT) is currently the best treatment option for PD, but is not resolutive. While other potential therapeutic approaches have been reported before, these have never been tried as co- treatments. L-alanine oral supplementation (LAOS) has been proven to reduce muscle breakdown: we hereby report the first case of supplementation on a PD patient on ERT., Case Presentation: F. is a 9 y.o. infantile onset Pompe Disease (IOPD) girl ERT-treated since age 1 developing a progressive myopathy. We started her on LAOS and performed assessments at baseline, 6 and 9 months. At baseline, F.'s weight, height and BMI were within normal ranges, while body composition showed low fat mass -FM and high resting energy expenditure-REE levels. After LAOS, a progressive FM increase and REE reduction could be observed both at 6 and 9 months., Conclusions: ERT is not curative for PD patients thus additional treatments could be considered to improve outcomes. Our patient showed physical signs of inability to accumulate energy when exclusively on ERT, while FM increase and REE reduction occurred when supplemented with LAOS, likely reflecting anabolic pathways' implementation. This is the first case reporting potential LAOS benefits in PD-on ERT patients. Longitudinal case control studies are yet needed to evaluate possible efficacy of combined LAOS And ERT treatment in PD patients., (© 2022. The Author(s).)

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has milder presentation in children than in adults, mostly requiring only supportive therapy. The immunopathogenic course of COVID-19 can be divided in two distinct but overlapping phases: the first triggered by the virus itself and the second one by the host immune response (cytokine storm). Respiratory failure or systemic involvement as Multisystem Inflammatory Syndrome in Children (MIS-C) requiring intensive care are described only in a small portion of infected children. Less severe lung injury in children could be explained by qualitative and quantitative differences in age-related immune response. Evidence on the best therapeutic approach for COVID-19 lung disease in children is lacking. Currently, the approach is mainly conservative and based on supportive therapy. However, in hospitalized children with critical illness and worsening lung function, antiviral therapy with remdesivir and immunomodulant treatment could be considered the "therapeutic pillars.", Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gatti, Piotto, Lelii, Pensabene, Madini, Cerrato, Hassan, Aliberti, Bosis, Marchisio and Patria.)

The design of advanced miniaturized ultra-low power interfaces for sensors is extremely important for energy-constrained monitoring applications, such as wearable, ingestible and implantable devices used in the health and medical field. Capacitive sensors, together with their correspondent digital-output readout interfaces, make no exception. Here, we analyse and design a capacitance-to-digital converter, based on the recently introduced iterative delay-chain discharge architecture, showing the circuit inner operating principles and the correspondent design trade-offs. A complete design case, implemented in a commercial 180 nm CMOS process, operating at 0.9 V supply for a 0-250 pF input capacitance range, is presented. The circuit, tested by means of detailed electrical simulations, shows ultra-low energy consumption (≤1.884 nJ/conversion), excellent linearity (linearity error 15.26 ppm), good robustness against process and temperature corners (conversion gain sensitivity to process corners variation of 114.0 ppm and maximum temperature sensitivity of 81.9 ppm/°C in the -40 °C, +125 °C interval) and medium-low resolution of 10.3 effective number of bits, while using only 0.0192 mm2 of silicon area and employing 2.93 ms for a single conversion.