Air change rates and infection risk in school environments: Monitoring naturally ventilated classrooms in a northern Italian urban context.

The importance of building ventilation in avoiding long-distance airborne transmission has been highlighted with the advent of the COVID-19 pandemics. Among others, school environments, in particular classrooms, present criticalities in the implementation of ventilation strategies and their impact on indoor air quality and risk of contagion. In this work, three naturally ventilated school buildings located in northern Italy have undergone monitoring at the end of the heating season. Environmental parameters, such as CO2 concentration and indoor/outdoor air temperature, have been recorded together with the window opening configurations to develop a two-fold analysis: i) the estimation of real air change rates through the transient mass balance equation method, and ii) the individual infection risk via the Wells-Riley equation. A strong statistical correlation has been found between the air change rates and the windows opening configuration by means of a window-to-volume ratio between the total opening area and the volume of the classroom, which has been used to estimate the individual infection risk. Results show that the European Standard recommendation for air renewal could be achieved by a window opening area of at least 1.5 m2, in the most prevailing Italian classrooms. Furthermore, scenarios in which the infector agent is a teacher show higher individual infection risk than those in which the infector is a student. In addition, the outcomes serve school staff as a reference to ensure adequate ventilation in classrooms and keep the risk of infection under control based on the number of the students and the volume of the classroom.

Ventilation strategies to reduce airborne transmission of viruses in classrooms: A systematic review of scientific literature.

The recent pandemic due to SARS-CoV-2 has brought to light the need for strategies to mitigate contagion between human beings. Apart from hygiene measures and social distancing, air ventilation highly prevents airborne transmission within enclosed spaces. Among others, educational environments become critical in strategic planning to control the spread of pathogens and viruses amongst the population, mainly in cold conditions. In the event of a virus outbreak - such as COVID or influenza - many school classrooms still lack the means to guarantee secure and healthy environments. The present review examines school contexts that implement air ventilation strategies to reduce the risk of contagion between students. The analysed articles present past experiences that use either natural or mechanical systems assessed through mathematical models, numerical models, or full-scale experiments. For naturally ventilated classrooms, the studies highlight the importance of the architectural design of educational spaces and propose strategies for aeration control such as CO2-based control and risk-infection control. When it comes to implementing mechanical ventilation in classrooms, different systems with different airflow patterns are assessed based on their ability to remove airborne pathogens considering parameters like the age of air and the generation of airflow streamlines. Moreover, studies report that programmed mechanical ventilation systems can reduce risk-infection during pandemic events. In addition to providing a systematic picture of scientific studies in the field, the findings of this review can be a valuable reference for school administrators and policymakers to implement the best strategies in their classroom settings towards reducing infection risks.

TAAC - TMS Adaptable Auditory Control: A universal tool to mask TMS clicks.

BACKGROUND: Coupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (AEPs) associated to the TMS discharge noise (TMS click). This contaminating factor can be in principle prevented by playing a masking noise through earphones. NEW METHOD: Here we release TMS Adaptable Auditory Control (TAAC), a highly flexible, open-source, Matlab®-based interface that generates in real-time customized masking noises. TAAC creates noises starting from the stimulator-specific TMS click and tailors them to fit the individual, subject-specific click perception by mixing and manipulating the standard noises in both time and frequency domains. RESULTS: We showed that TAAC allows us to provide standard as well as customized noises able to effectively and safely mask the TMS click. COMPARISON WITH EXISTING METHODS: Here, we showcased two customized noises by comparing them to two standard noises previously used in the TMS literature (i.e., a white noise and a noise generated from the stimulator-specific TMS click only). For each, we quantified the Sound Pressure Level (SPL; measured by a Head and Torso Simulator - HATS) required to mask the TMS click in a population of 20 healthy subjects. Both customized noises were effective at safe (according to OSHA and NIOSH safety guidelines) and lower SPLs with respect to standard noises. CONCLUSIONS: At odds with previous methods, TAAC allows creating effective and safe masking noises specifically tailored on each TMS device and subject. The combination of TAAC with tools for the real-time visualization of TEPs can help control the influence of auditory confounds also in non-compliant patients. Finally, TAAC is a highly flexible and open-source tool, so it can be further extended to meet different experimental requirements.

A predictive micromechanically-based model for damage and permanent deformations in copolymer sutures.

An effective description of the mechanical behavior of biodegradable copolymers suture threads requires the analysis of their response under cyclic loading and the prediction of the fundamental damage and residual stretches effects. In this paper we propose a micromechanically-based model adopting a new form of Worm Like Chain free energy for the copolymer chains, which takes care of the insurgence of residual stretches on the basis of a rigorous statistical mechanics result. Under the affinity hypothesis we subsequently derive the macroscopic response of the material. The obtained model has a clear physical interpretation and depends on a small number of parameters, which can be fitted by a simple uniaxial test. The effectiveness of the theoretical results has then been verified by performing cyclic tests on Monocryl® monofilament sutures and showing the ability of the model in predicting with high accuracy the history dependence, the damage and permanent deformations in the obtained response.

Internal Delensing of Cosmic Microwave Background Polarization B-Modes with the POLARBEAR Experiment.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

A physico-chemical study on amphiphilic cyclodextrin/liposomes nanoassemblies with drug carrier potential.

In this paper, two medusa-like ACyDs, modified at the primary rim bearing four (ACyD4) and eight carbons (ACyD8) acyl chain length, and one bouquet-like CyD, modified at primary side with thiohexyl and at secondary one with oligoethylene moiety (SC6OH), were investigated for their ability to assemble in nanostructures or to form hybrid dipalmitoylphosphatidylcholine (DPPC)/ACyDs systems. The lipophilicity of these molecules and the different preparation methods used in this study (thin layer evaporation and nanoprecipitation method) significantly affect the aggregation behaviour in aqueous medium. Except for the shortest medusa-like ACyD4, the other ACyDs formed stable nanoaggregates for at least 45 days. The effect of ACyDs on the thermotropic behaviour of DPPC liposomes was also studied by differential scanning calorimetry analysis, thus elucidating their interaction with liposomes to afford hybrid liposome/ACyDs systems. The medusa-like ACyD4 cannot be used to realize nanosystems because it quickly aggregates or it induces a complete destabilization of the liposomes. At the highest concentration investigated (0.01 molar fraction), both ACyD8 and SC6OH interacted with DPPC liposomes, forming ACyD/DPPC or SC6OH/DPPC hybrid vesicular carriers.

The POLARBEAR Fourier transform spectrometer calibrator and spectroscopic characterization of the POLARBEAR instrument.

We describe the Fourier Transform Spectrometer (FTS) used for in-field testing of the POLARBEAR receiver, an experiment located in the Atacama Desert of Chile which measures the cosmic microwave background (CMB) polarization. The POLARBEAR-FTS (PB-FTS) is a Martin-Puplett interferometer designed to couple to the Huan Tran Telescope (HTT) on which the POLARBEAR receiver is installed. The PB-FTS measured the spectral response of the POLARBEAR receiver with signal-to-noise ratio >20 for ∼69% of the focal plane detectors due to three features: a high throughput of 15.1 sr cm2, optimized optical coupling to the POLARBEAR optics using a custom designed output parabolic mirror, and a continuously modulated output polarizer. The PB-FTS parabolic mirror is designed to mimic the shape of the 2.5 m-diameter HTT primary reflector, which allows for optimum optical coupling to the POLARBEAR receiver, reducing aberrations and systematics. One polarizing grid is placed at the output of the PB-FTS and modulated via continuous rotation. This modulation allows for decomposition of the signal into different harmonics that can be used to probe potentially pernicious sources of systematic error in a polarization-sensitive instrument. The high throughput and continuous output polarizer modulation features are unique compared to other FTS calibrators used in the CMB field. In-field characterization of the POLARBEAR receiver was accomplished using the PB-FTS in April 2014. We discuss the design, construction, and operation of the PB-FTS and present the spectral characterization of the POLARBEAR receiver. We introduce future applications for the PB-FTS in the next-generation CMB experiment, the Simons Array.

A prospective study of the effects of carbocysteine lysine salt on frequency of exacerbations in COPD patients treated with or without inhaled steroids.

OBJECTIVE: COPD is one of the major causes of morbidity and mortality worldwide and represents one of the most important issues for public health. Frequent exacerbations induce a faster decline in lung function and poorer quality of life, increase mortality, and have a socio-economic impact with a high burden in terms of resources and healthcare costs. The clinical trials evaluated the effect of mucolytics in COPD and showed that the long-term carbocysteine, associated with bronchodilators, anticholinergics, and steroids, reduces the frequency of exacerbations and improves the quality of life. PATIENTS AND METHODS: The aim of this prospective real-life study was to evaluate the long-term impact on exacerbations (at 1 year) in COPD patients treated with carbocysteine lysine salt (single dose of 2.7 g once a day) in addition to background therapy with or without inhaled steroids. RESULTS: In a total of 155 evaluable patients, our study showed that the addition of a single dose of carbocysteine lysine salt to background therapy determines a statistically significant reduction of the average number of exacerbations vs. the number observed in the previous year (from 1.97±0.10 to 1.03±0.11; p<0.01), irrespective of treatment with or without inhaled steroids. In particular, in patients with ≥2 exacerbations in the previous year, the addition of carbocysteine lysine salt resulted in a statistically significant reduction in the exacerbations rate from 69% to 33% and from 58% to 25%, respectively (p<0.01) in patients with or without inhaled steroids. CONCLUSIONS: In summary, our data highlighted the efficacy of long-term administration of a single daily dose of carbocysteine lysine salt (2.7 g/day) in reducing the number and rate of exacerbations in COPD patients, independently from the use of inhaled steroids.

Unveiling the influence of device stiffness in single macromolecule unfolding.

Single-molecule stretching experiments on DNA, RNA, and other biological macromolecules opened up the possibility of an impressive progress in many fields of life and medical sciences. The reliability of such experiments may be crucially limited by the possibility of determining the influence of the apparatus on the experimental outputs. Here we deduce a model that let us analytically evaluate such influence, fundamental for the interpretation of Single Molecule Force Spectroscopy experiments and intermolecular interactions phenomena. As we show, our model is coherent with previous numerical results and quantitively reproduce AFM experimental tests on titin macromolecules and P-selectin with variable probe stiffnesses.

Mediterranean essential oils as precious matrix components and active ingredients of lipid nanoparticles.

Essential oils are recognized as valuable active pharmaceutical ingredients attributed to a set of biological properties, which include antibacterial, antifungal, antiviral, antioxidant, anticancer, immune-modulatory, analgesic and anti-inflammatory activities. Their use in pharmaceutics is however compromised by their limited water solubility and low physicochemical stability (i.e. volatility, oxidation). In order to overcome these limitations, we aimed to develop nanostructured lipid carriers (NLC) as delivery systems for Mediterranean essential oils, in particular Rosmarinus officinalis L., Lavandula x intermedia "Sumian", Origanum vulgare subsp. hirtum and Thymus capitatus essential oils, selected on the basis of their antioxidant and anti-inflammatory activities. NLC composed of Softisan (as solid lipid) have been produced by phase inversion temperature (PIT) and high-pressure homogenization (HPH), using two different emulsifiers systems. Particles have been further characterized for their mean particle size, polydispersity, zeta potential, morphology and chemical interactions. Best NLC formulations were obtained with Kolliphor/Labrafil as surfactants, and using Rosmarinus, Lavandula and Origanum as essential oils (PDI between 0.126 and 0.141, Zave < 200 nm). Accelerated stability studies have also been carried out to estimate the effect of the production method and surfactant composition on the long-term stability of EOs-loaded NLC. In vitro biological cell viability and anti-inflammatory activities were evaluated in Raw 264.7 cells (macrophage cell line), while in vitro antioxidant activity was checked by DPPH assay. Lavandula and Rosmarinus NLC were shown to be the most biocompatible formulations up to a concentration of 0.1% (v/v), whereas they were able to induce a dose-dependent anti-inflammatory activity in the order Lavandula > Rosmarinus ≥ Origanum.

Measles outbreak from February to August 2017 in Messina, Italy.

INTRODUCTION: Measles continues to be a major public health issue worldwide, with high morbidity and mortality rates. The disease remains endemic in 14 European countries, including Italy where, from 2013 to 2016, over 5,000 cases have been reported. In 2017, many Italian regions, including Sicily, have reported many cases of measles. In this study, we described the latest measles outbreak in the city of Messina, from 1st February to 31st August 2017. METHODS: We considered all reported measles cases that came to the "Public Health, Epidemiology and Preventive Medicine" Operative Unit of the Messina Provincial Health Agency Prevention Department, which receives all reported cases of measles in the Messina province. RESULTS: From 1st February to 31st August 2017, a total of 59 measles cases were reported, of which 44 were confirmed, nine were classified as possible, four were probable and two cases were discarded. Of the 57 possible, probable and confirmed cases, 31 (54%) were males and 26 (46%) were females. Moreover, 54 (95%) had not been previously vaccinated while the remaining cases had documented evidence of one (two cases) or two doses (one case). Genotype B3 was identified in 39/44 cases (88,6%) by the regional reference laboratory in Palermo. CONCLUSIONS: Despite the development of an effective vaccination, unfortunately measles continues to threaten the lives of millions of children worldwide each year. The suboptimal immunization level in Italy has led to an increase in the transmission of measles with detrimental effects on both public health and ongoing measles elimination efforts.

Repurposing itraconazole to the benefit of skin cancer treatment: A combined azole-DDAB nanoencapsulation strategy.

In this work, we aimed at developing an improved topical SLN formulation combining itraconazole delivery with a coating layer of didodecyldimethylammonium bromide, thus repurposing the drug effectiveness by synergistic skin anticancer effectiveness. In order to obtain a stable SLN formulation with small homogeneously dispersed particles, a deep formulative study was developed screening three different solid lipids (Suppocire NB, Cetyl Palmitate and Dynasan 114) for the SLN preparation by the phase inversion temperature. A bluishcolored shade formulation, with homogeneous small particles size (<50 nm) was obtained only using Suppocire NB. The cytotoxicity of all SLN was tested after 24 h exposure against three adherent skin cell lines (A431, HaCaT and SK-MEL-5). Results demonstrate that both unloaded and drugloaded SLN did not significantly affect the cell viability of the non-tumoral HaCaT cell line, thus confirming the safe potential topical application of these formulations. A dose-dependent decrease in cell viability was observed for the tumoral cell lines, A431 and SK-MEL-5, with a significant reduction of the A431 cancer cell line viability. The drug molecule addition to the uncoated nanoparticles was able to increase of almost 20% the reduction of the viability of the cancer cells treated. Ours results demonstrate the potentiality of repurposing itraconazole activity by using the combined nanoencapsulation strategy with the positively charged coating layer on SLN, which can be further investigated as a promising stable and safe approach to significantly reduce the viability of skin cancer cells.

Revisiting the role of sucrose in PLGA-PEG nanocarrier for potential intranasal delivery.

The efficient design of nanocarriers is a major challenge and must be correlated with the route of administration. Intranasal route is studied for local, systemic or cerebral treatments. In order to develop nanocarriers with suitable properties for intranasal delivery, to achieve brain and to market the product, it is extremely important the simplification of the formulation in terms of raw materials. Surfactants and cryoprotectants are often added to improve structuration and/or storage of polymeric nanoparticles. PLGA-PEG nanocarriers were prepared by nanoprecipitation method evaluating the critical role of sucrose as surfactant-like and cryoprotectant, with the aim to obtain a simpler formulation compared to those proposed in other papers. Photon correlation spectroscopy and Turbiscan analysis show that sucrose is a useful excipient during the preparation process and it effectively cryoprotects nanoparticles. Among the investigated nanocarriers with different degree of PEG, PEGylated PLGA (5%) confers weak interaction between nanoparticles and mucin as demonstrated by thermal analysis and mucin particle method. Furthermore, in vitro biological studies on HT29, as epithelium cell line, does not show cytotoxicity effect for this nanocarrier at all texted concentrations. The selected nanosystem was also studied to load docetaxel, as model drug, and characterized by a technological point of view.

Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization.

Nose to brain delivery and nanotechnology are the combination of innovative strategies for molecules to reach the brain and to bypass blood brain barriers. In this work we investigated the fate of two rhodamine B labeled polymeric nanoparticles (Z-ave <250nm) of opposite surface charge in different areas of the brain after intranasal administration in rats. A preliminary screening was carried out to select the suitable positive (chitosan/poly-l-lactide-co-glycolide) nanocarrier through photon correlation spectroscopy and turbiscan. Physico-chemical and technological characterizations of poly-l-lactide-co-glycolide (negative) and chitosan/poly-l-lactide-co-glycolide (positive) fluorescent labeled nanoparticles were performed. The animals were allocated to three groups receiving negative and positive polymeric nanoparticles via single intranasal administration or no treatment. The localization of both nanocarriers in different brain areas was detected using fluorescent microscopy. Our data revealed that both nanocarriers reach the brain and are able to persist in the brain up to 48h after intranasal administration. Surface charge influenced the involved pathways in their translocation from the nasal cavity to the central nervous system. The positive charge of nanoparticles slows down brain reaching and the trigeminal pathway is involved, while the olfactory pathway may be responsible for the transport of negatively charged nanoparticles, and systemic pathways are not excluded.

Catastrophic Thinning of Dielectric Elastomers.

We provide an energetic insight into the catastrophic nature of thinning instability in soft electroactive elastomers. This phenomenon is a major obstacle to the development of giant actuators, yet it is neither completely understood nor modeled accurately. In excellent agreement with experiments, we give a simple formula to predict the critical voltages for instability patterns; we model their shape and show that reversible (elastic) equilibrium is impossible beyond their onset. Our derivation is fully analytical, does not require finite element simulations, and can be extended to include prestretch and various material models.

Micromechanical model for protein materials: From macromolecules to macroscopic fibers.

We propose a model for the mechanical behavior of protein materials. Based on a limited number of experimental macromolecular parameters (persistence and contour length) we obtain the macroscopic behavior of keratin fibers (human, cow, and rabbit hair), taking into account the damage and residual stretches effects that are fundamental in many functions of life. We also show the capability of our approach to describe the main dissipation and permanent strain effects observed in the more complex spider silk fibers. The comparison between our results and the data obtained experimentally from cyclic tests demonstrates that our model is robust and is able to reproduce with a remarkable accuracy the experimental behavior of all protein materials we tested.

Paritaprevir/ritonavir/ombitasvir+dasabuvir plus ribavirin therapy and inhibition of the anticoagulant effect of warfarin: a case report.

WHAT IS KNOWN AND OBJECTIVE: Paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD) is a direct-acting antiviral (DAA) approved for the treatment of chronic hepatitis C virus. We report on a probable interaction between PrOD with ribavirin and warfarin. CASE DESCRIPTION: Two weeks after the start of PrOD with ribavirin, the patient's international normalized ratio (INR) became subtherapeutic. Eleven weeks into therapy and following a 125% total increase in the weekly warfarin dose, therapeutic INR was achieved. Thirteen days after DAA therapy was completed and discontinued, the patient's INR became critically supratherapeutic. WHAT IS NEW AND CONCLUSION: Patients on PrOD plus ribavirin with warfarin should have INR followed closely upon initiation and discontinuation of therapy due to a probable drug interaction.

Multi-scale modelling of rubber-like materials and soft tissues: an appraisal.

We survey, in a partial way, multi-scale approaches for the modelling of rubber-like and soft tissues and compare them with classical macroscopic phenomenological models. Our aim is to show how it is possible to obtain practical mathematical models for the mechanical behaviour of these materials incorporating mesoscopic (network scale) information. Multi-scale approaches are crucial for the theoretical comprehension and prediction of the complex mechanical response of these materials. Moreover, such models are fundamental in the perspective of the design, through manipulation at the micro- and nano-scales, of new polymeric and bioinspired materials with exceptional macroscopic properties.

Innovative hybrid vs polymeric nanocapsules: The influence of the cationic lipid coating on the "4S".

Polymeric and hybrid aqueous-core nanocapsules were prepared using a low energy organic-solvent free procedure as innovative nanodevices for the ophthalmic delivery of melatonin. In order to evaluate how different cationic lipids could affect the main properties of the nanodevices, we focused our attention on mean particles size, surface charge, shape and stability (the "4S"). The results of our study confirmed the hypothesis that the coating material differently affects the overall nanoparticles properties, above all in terms of morphology: in particular, the cationic lipid dimethyldioctadecylammonium bromide allows the formation of very stable well-defined nanocapsules with non-spherical shape with sustained and prolonged drug release, thus representing a great advantage in ophthalmic application.

Innovative oral spray-dried Idebenone systems to improve patient compliance.

Idebenone is a high permeable drug with very slight water solubility that affects the dissolution rate in the biological fluids, causing an irregular and limited in vivo absorption after oral administration. Moreover, it is marketed in Europe as tablets equivalent to 150 mg, with the consequent administration of multiple dose of solid unit to obtain the correct dose, a deterrent for the patients' compliance. According to these considerations, our goal was to develop spray-dried microparticles using a soluble ß-cyclodextrin (CD) polymer and an enhancer of dissolution rate, such as carboxymethyl cellulose, to obtain a formulation easily dosable and soluble in water. The complex in solution was evaluated by phase solubility studies and the Idebenone/CD molar ratio selected was 1:1. According to Higuchi and Connors, adding carboxymethyl cellulose, a Bs-type profile was obtained. This result was due to the presence of carboxymethyl cellulose that competes with the CD in forming Idebenone microsystems, reducing of 10-fold the formulation bulk. UV-Vis absorption, (1)H nuclear magnetic resonance and circular dichroism showed the formation of the CD/Idebenone inclusion complex confirmed also by differential scanning calorimetry, Fourier transform infrared spectroscopy and fluorescence microscope (FM). The water solubility data and the in vitro dissolution tests performed in simulated gastric fluid, showed an increase of the drug water interaction due to the presence of the CD and carboxymethyl cellulose, both able to improve drug wettability, water solubility and dissolution rate. This approach seems to be suitable to produce microsystems which are able to enhance the in vivo absorption of Idebenone after oral administration and to increase the patient compliance.