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Is there a "missing device" for respiratory personal protection? Does it exist an easy-to-use device, allowing extensive use in everyday settings by the population, maximizing tolerability and low visual and physical invasiveness protecting from a wide range of threats including airborne pathogens, hence including the particle range of fine and ultrafine particles? Looking at the recent past, in the urgency of finding ready-to-use solutions for the respiratory protection of the population during the outbreak of the SARS-CoV-2 pandemic, devices for occupational safety have been used, such as filtering face masks. These are devices intended for workers operating during work shifts in environments characterized by potential high risk, known a priori, often directly sensible; this makes wearers motivated to tolerate discomfort for a given period to face a localized risk, and safety managers determined to supervise compliance with usage specifications. Their use by general population has implied known shortcomings, such as weak compatibility with relational work and activities, low tolerability during prolonged use, low compliance with the proper use of the device, all of this lessening actual protection. The need for a new perspective has emerged, targeting effectiveness in whole daily life, rather than punctual efficacy. Nasal filters are promising candidates to protect individuals throughout the day during the most varied activities, but they lack a systematic definition as a device and as a product; it follows that the high complexity needed to reach an effective performance envelop is generally underestimated. By reviewing available literature, the present paper draws on the experience from the pandemic and infers systematic product specifications and characterization methods for a new, effective personal respiratory protection device; these specifications are compared with the stringent constraints associated with the endonasal applications and, based on air filtration state of the art, quantifies the need for technology disruption and outlining possible new development paths., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In recent years, Electrospinning (ES) has been revealed to be a straightforward and innovative approach to manufacture functionalized nanofiber-based membranes with high filtering performance against fine Particulate Matter (PM) and proper bioactive properties. These qualities are useful for tackling current issues from bacterial contamination on Personal Protective Equipment (PPE) surfaces to the reusability of both disposable single-use face masks and respirator filters. Despite the fact that the conventional ES process can be upscaled to promote a high-rate nanofiber production, the number of research works on the design of hybrid materials embedded in electrospun membranes for face mask application is still low and has mainly been carried out at the laboratory scale. In this work, a multi-needle ES was employed in a continuous processing for the manufacturing of both pristine Poly (Vinylidene Fluoride- co -Hexafluoropropylene) (PVDF-HFP) nanofibers and functionalized membrane ones embedded with TiO 2 Nanoparticles (NPs) (PVDF-HFP@TiO 2 ). The nanofibers were collected on Polyethylene Terephthalate (PET) nonwoven spunbond fabric and characterized by using Scanning Electron Microscopy and Energy Dispersive X-ray (SEM-EDX), Raman spectroscopy, and Atomic Force Microscopy (AFM) analysis. The photocatalytic study performed on the electrospun membranes proved that the PVDF-HFP@TiO 2 nanofibers provide a significant antibacterial activity for both Staphylococcus aureus (~94%) and Pseudomonas aeruginosa (~85%), after only 5 min of exposure to a UV-A light source. In addition, the PVDF-HFP@TiO 2 nanofibers exhibit high filtration efficiency against submicron particles (~99%) and a low pressure drop (~3 mbar), in accordance with the standard required for Filtering Face Piece masks (FFPs). Therefore, these results aim to provide a real perspective on producing electrospun polymer-based nanotextiles with self-sterilizing properties for the implementation of advanced face masks on a large scale.

An innovative nasal filter was tested, based on aerodynamic air filtration and not on conventional air filtration by means of mesh filters. A custom testing system was designed and three sizes of the filter have been tested vs. monodispersed SiO 2 particles sized 5 μm, 1 μm, and 0.5 μm under cycling flow of 6 liters per minute, provided by an artificial lung breather simulating spontaneous breathing. Accelerated testing was implemented, challenging filters with a maximum load of 200 mg per cubic meter. All three filters' sizes showed initial filtration efficiencies above 90% vs. all particles' sizes, decreased to not less than 80% after 30 min of accelerated testing, corresponding to 4.5 days of continuous use at 2 mg challenge, this value being associated with hazardous air conditions in the PSI scale. Results in this study indicate that nasal filters based on aerodynamic air filtration can provide fine and ultrafine filtration, offering protection in day-to-day life from risks associated with pollens, mites, PM, pollutants, and respiratory infectious agents, introducing acceptable respiratory resistance., Competing Interests: EI and AP are employed by Labor, Rome, Italy. This research was funded by HSD s.r.l. (Italy), the owner of the device under test. HSD s.r.l. had the following involvement with the study: decision to submit it for publication., (© 2023 Saravanan, Broccolo, Ali, Toh, Mulyana, Beng, Imperi and Picano.)

Hairy cell leukemia (HCL) shows unique clinicopathological and biological features. HCL responds well to purine analogs but relapses are frequent and novel therapies are required. BRAF-V600E is the key driver mutation in HCL and distinguishes it from other B-cell lymphomas, including HCL-like leukemias/lymphomas (HCL-variant and splenic marginal zone lymphoma). The kinase-activating BRAF-V600E mutation also represents an ideal therapeutic target in HCL. Here, we investigated the biological and therapeutic importance of the activated BRAF-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway in HCL by exposing in vitro primary leukemic cells purified from 26 patients to clinically available BRAF (vemurafenib; dabrafenib) or MEK (trametinib) inhibitors. Results were validated in vivo in samples from vemurafenib-treated HCL patients within a phase 2 clinical trial. BRAF and MEK inhibitors caused, specifically in HCL (but not HCL-like) cells, marked MEK/ERK dephosphorylation, silencing of the BRAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression signature, downregulation of the HCL markers CD25, tartrate-resistant acid phosphatase, and cyclin D1, smoothening of leukemic cells' hairy surface, and, eventually, apoptosis. Apoptosis was partially blunted by coculture with bone marrow stromal cells antagonizing MEK-ERK dephosphorylation. This protective effect could be counteracted by combined BRAF and MEK inhibition. Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL., (© 2015 by The American Society of Hematology.)