Exploring Factors Influencing Changes in Incidence and Severity of Multisystem Inflammatory Syndrome in Children

Multisystem inflammatory syndrome (MIS-C) is a rare condition associated with COVID-19 affecting children, characterized by severe and aberrant systemic inflammation leading to nonspecific symptoms, such as gastrointestinal, cardiac, respiratory, hematological, and neurological disorders. In the last year, we have experienced a progressive reduction in the incidence and severity of MIS-C, reflecting the worldwide trend. Thus, starting from the overall trend in the disease in different continents, we reviewed the literature, hypothesizing the potential influencing factors contributing to the reduction in cases and the severity of MIS-C, particularly the vaccination campaign, the spread of different SARS-CoV-2 variants (VOCs), and the changes in human immunological response. The decrease in the severity of MIS-C and its incidence seem to be related to a combination of different factors rather than a single cause. Maturation of an immunological memory to SARS-CoV-2 over time, the implication of mutations of key amino acids of S protein in VOCs, and the overall immune response elicited by vaccination over the loss of neutralization of vaccines to VOCs seem to play an important role in this change

Feasibility and effectiveness assessment of sars-cov-2 antigenic tests in mass screening of a pediatric population and correlation with the kinetics of viral loads

The gold standard for diagnosis of SARS-CoV-2 infection has been nucleic acid amplification tests (NAAT). However, rapid antigen detection kits (Ag-RDTs), may offer advantages over NAAT in mass screening, generating results in minutes, both as laboratory-based test or point-of-care (POC) use for clinicians, at a lower cost. We assessed two different POC Ag-RDTs in mass screening versus NAAT for SARS-CoV-2 in a cohort of pediatric patients admitted to the Pediatric Emergency Unit of IRCCS—Polyclinic of Sant’Orsola, Bologna (from November 2020 to April 2021). All patients were screened with nasopharyngeal swabs for the detection of SARS-CoV-2-RNA and for antigen tests. Results were obtained from 1146 patients. The COVID-19 Ag FIA kit showed a baseline sensitivity of 53.8% (CI 35.4–71.4%), baseline specificity 99.7% (CI 98.4–100%) and overall accuracy of 80% (95% CI 0.68–0.91); the AFIAS COVID-19 Ag kit, baseline sensitivity of 86.4% (CI 75.0–93.9%), baseline specificity 98.3% (CI 97.1–99.1%) and overall accuracy of 95.3% (95% CI 0.92– 0.99). In both tests, some samples showed very low viral load and negative Ag-RDT. This disagreement may reflect the positive inability of Ag-RDTs of detecting antigen in late phase of infection. Among all cases with positive molecular test and negative antigen test, none showed viral loads > 106 copies/mL. Finally, we found one false Ag-RDTs negative result (low cycle thresholds; 9 × 105 copies/mL). Our results suggest that both Ag-RDTs showed good performances in detection of high viral load samples, making it a feasible and effective tool for mass screening in actively infected children

Post-Traumatic Headache in Children after Minor Head Trauma: Incidence, Phenotypes, and Risk Factors

Minor head trauma (MHT) is very frequent in children and post-traumatic headache (PTH) is one of its most common complications; however, its management is still a challenge. We aimed to assess the incidence and clinical characteristics of, and risk factors for, PTH among children referred to our pediatric emergency department (PED) for MHT. A total of 193 patients aged 3–14 years evaluated for MTH were enrolled and followed up for 6 months through phone calls and/or visits. PTH occurred in 25/193 patients (13%). PTH prevalence was significantly higher in school-aged (≥6 years) than in pre-school-aged children (21.6% vs. 4.9%, respectively, p < 0.009). Females were found to be more affected. The median time of onset was 4.6 days after MHT; resolution occurred in a median of 7 weeks. In 83.3% of patients, PTH subsided in <3 months, while in 16.7% it persisted longer. A total of 25% of children exhibited the migraine and 75% the tension-type variant. Our analysis indicates the presence of headache upon arrival in PED, isolated or associated with nausea and dizziness, as a factor predisposing the patient to the development of PTH. Our findings could be useful to identify children at risk for PTH for specific follow-up, family counseling, and treatment

Immune response against adenovirus in acute upper respiratory tract infections in immunocompetent children

During acute upper respiratory tract infections (AURTIs) caused by Adenoviruses, the mix of severe clinical presentation, together with elevation of white blood cells (WBCs) and C-reactive protein (CRP), often mimicking bacterial infection, leads to an inappropriate use of antibiotics. We studied 23 immunocompetent children admitted to our Pediatric Emergency Unit with signs of acute Adenoviral AURTIs, aiming at better clarifying the biological background sustaining this clinical presentation. Infection etiology was tested with nasopharyngeal swabs, serology, and DNA-PCR. During fever peaks and subsequent recovery, we assessed WBC count with differential, CRP, procalcitonin, serum concentration of six inflammatory cytokines, and lymphocyte subset populations. Results: IL-6 and IL-8 were found elevated in the acute phase, whereas a significant decrease during recovery was found for IL-6 and IL-10. We highlighted an increase of B lymphocytes in the acute phase; conversely, during recovery, an increase in T regulatory cells was noted. Monocytes and leukocytes were found markedly elevated during fever peaks compared to convalescence. All patients recovered uneventfully. The composition of lymphocyte population subsets and serum alterations are the main drivers of an overprescribed antibiotic. Examination of hospital admissions and performance is needed in further investigations to rule out bacterial infections or inflammatory syndromes

Investigation on the Association of Differential Evolution and Constructal Design for Geometric Optimization of Double Y-Shaped Cooling Cavities Inserted into Walls with Heat Generation

In the constructal design method, the comprehension of the effect of design on the system performance is crucial to understanding the contributions of the degrees of freedom or constraints in the system evolution in direction of optimal configurations. However, problems with many degrees of freedom are prohibitive of optimization with exhaustive search, requiring meta-heuristic strategies. Therefore, the investigation of the optimization algorithms is essential. This work investigates the canonical differential evolution algorithm associated with the constructal design for the geometric optimization of an isothermal double Y-shaped cooling cavity inserted into a wall with internal heat generation. The effect of four degrees of freedom over the thermal performance of the system is investigated using sixteen different combinations of differential evolution algorithms: four variations of mutation parameter, two values of amplification factor (F) and two values of crossover rate (CR). The non-parametric statistical methods of Kruskal–Wallis and Dunn test were used to identify the parameters that improve the meta-heuristic efficiency. Results indicated that the proposed methodology selected the proper combination of DE algorithm parameters (CR, F, and mutation) that led to the best effect of degrees of freedom over the thermal performance in all optimization levels investigated

Constructal Design of Convective Y-Shaped Cavities by Means of Genetic Algorithm

In the present work constructal design is employed to optimize the geometry of a convective, Y-shaped cavity that intrudes into a solid conducting wall. The main purpose is to investigate the influence of the dimensionless heat transfer parameter a over the optimal geometries of the cavity, i.e., the ones that minimize the maximum excess of temperature (or reduce the thermal resistance of the solid domain). The search for the best geometry has been performed with the help of a genetic algorithm (GA). For square solids (H/L ¼ 1.0) the results obtained with an exhaustive search (which is based on solution of all possible geometries) were adopted to validate the GA method, while for H/L 6 ¼ 1.0 GA is used to find the best geometry for all degrees of freedom investigated here: H/L, t 1 /t 0 , L 1 /L 0 , and a (four times optimized). The results demonstrate that there is no universal optimal shape that minimizes the thermal field for all values of a investigated. Moreover, the temperature distribution along the solid domain becomes more homogeneous with an increase of a, until a limit where the configuration of "optimal distribution of imperfections" is achieved and the shape tends to remain fixed. Finally, it has been highlighted that the GA method proved to be very effective in the search for the best shapes with the number of required simulations much lower (8 times for the most difficult situation) than that necessary for exhaustive search

Predicting capsule fill weight from in-situ powder density measurements using terahertz reflection technology

The manufacturing of the majority of solid oral dosage forms is based on the densification of powder. A good understanding of the powder behavior is therefore essential to assure high quality drug products. This is particularly relevant for the capsule filling process, where the powder bulk density plays an important role in controlling the fill weight and weight variability of the final product. In this study we present a novel approach to quantitatively measure bulk density variations in a rotating container by means of terahertz reflection technology. The terahertz reflection probe was used to measure the powder density using an experimental setup that mimics a lab-scale capsule filling machine including a static sampling tool. Three different grades of α-lactose monohydrate excipients specially designed for inhalation application were systematically investigated at five compression stages. Relative densities predicted from terahertz reflection measurements were correlated to off-line weight measurements of the collected filled capsules. The predictions and the measured weights of the powder in the capsules were in excellent agreement, where the relative density measurements of Lactohale 200 showed the strongest correlation with the respective fill weight (R 2 =0.995). We also studied how the density uniformity of the powder bed was impacted by the dosing process and the subsequent filling of the holes (with excipient powder), which were introduced in the powder bed after the dosing step. Even though the holes seemed to be filled with new powder (by visual inspection), the relative density in these specific segments were found to clearly differ from the undisturbed powder bed state prior to dosing. The results demonstrate that it is feasible to analyze powder density variations in a rotating container by means of terahertz reflection measurements and to predict the fill weight of collected capsules

Demonstrator of Time Services based on European GNSS signals: the H2020 DEMETRA Project

During 2015-2016, a European Consortium of 15 partners from 8 different countries, developed the DEMETRA (DEMonstrator of EGNSS services based on Time Reference Architecture), a project funded by the European Union in the frame of the Horizon 2020 program. This project aims at developing and experimenting time dissemination services dedicated to specific users like traffic control, energy distribution, finance, telecommunication, and scientific institutions. Nine services have been developed. These services provide time dissemination with accuracy levels from millisecond to the sub-ns, and also additional services like certification, calibration, or integrity. Five of these services are based on the European GNSS. After a development phase (see PTTI 2016 presentation) the full DEMETRA system has been working during six months for demonstration. The paper will report about the experimentation results, showing performances and limits of the proposed time dissemination services, aiming to foster the exploitation of the European GNSS for timing applications