Concerns with 3D filament fused fabrication (FFF) printer emissions have increased due to release of nanoplastic particles, plasticizers, and volatile mixtures. At present, few data exist examining polycarbonate emissions from 3D FFF printers and potential adverse health effects on liver following inhalation exposure. This study aimed to investigate hepatic toxicity following inhalation exposure to 3D FFF polycarbonate (PC) emissions in rats. It was postulated that increasing levels of inhaled 3D printer PC emissions initiate adverse liver histopathologic alterations associated with oxidative stress, inflammation, lipid and sterol metabolism markers. Sprague-Dawley rats were whole-body exposed to 3D FFF PC emissions (2.42 mg particulate/m3) for 4 hr/day, 4 days/week for 1, 4, 8, 15, or 30 days. Liver tissue was assessed for changes in inflammation, oxidative stress, fatty acid, lipid, sterol metabolism, and adverse liver pathology. One day exposure resulted in altered inflammation, glucose, fatty acid, and sterol metabolism gene biomarkers in 3D FFF PC-exposed animals compared to HEPA filter controls. Following 8-day treatment, 3D FFF PC animals exhibited decreased glutathione S-transferase activity. After 30 days exposure, liver pathology characterized by dilated sinusoids, clear hepatocyte cytoplasm, and focal leukocyte infiltrate were detected in 3D FFF PC-exposed animals which were markedly similar to bisphenol A-induced liver alterations. Data suggest that bisphenol A levels in 3D FFF PC emissions may partially be responsible for observed adverse liver phenotype. This study informs future hazard characterization for 3D FFF PC- induced liver toxicity and implementing intervention practices for thermoplastic emissions in additive manufacturing applications.

Supplemental air filtration can reduce indoor exposure to hazardous aerosols without requiring modifications to building heating, ventilation, and air conditioning (HVAC) systems. Portable air cleaners were widely used during the COVID-19 pandemic, but they can have drawbacks including noise, space obstruction, and electrical cord safety considerations. Built-in air filtration units are an alternative to provide supplemental air filtration. We conducted a case study of a HEPA air filtration unit installed in the ceiling of a conference room using radial laminar flow or square cone ceiling air supply diffusers. A respiratory aerosol simulator exhaled aerosol particles (0.3 to 10 mu m), and the particle concentrations were measured in the personal breathing zones of three breathing simulators representing a speaker and two meeting participants. For the speaker, using one square cone supply diffuser reduced inhalation exposure by 49 % to 81 % while using two square supply diffusers reduced exposure by 68 % to 93 %. For the participants, the exposures were reduced by 23 % to 64 % with one square supply diffuser and 58 % to 86 % with two square supply diffusers. Results when using the radial supply air diffusers were more variable and more dependent on the simulator layouts. Combining the use of cloth face masks on all simulators with the ceiling unit reduced the speaker's exposure by 87 % to 99 % and the participants' exposures by 84 % to 97 %. In most cases the ceiling air filtration unit provided protection against simulated respiratory aerosol particles comparable to that seen previously with portable air cleaners.

The use of two-dimensional organomodified nanoclays (ONCs) to improve nanocomposite properties continues to grow. Recent evidence suggests that airborne nanoclays in occupational environments pose an inhalation hazard; however, health risks and the underlying mechanisms remain undefined. In vivo studies evaluating pre- and post-incinerated ONC exposures found that cytotoxicity, inflammation, and fibrotic signaling responses are coating- and incineration status-dependent. We hypothesized that physicochemical property differences associated with coating presence/absence and incineration status of nanoclays will elicit changes in key events (KE) in exposed human small airway epithelial (SAECs) and normal lung fibroblast (NHLF) cells that contribute to pulmonary lung fibrosis. Using multiplex high-throughput screening strategies, SAEC and NHLF cells were acutely exposed (0-20 μg/cm2) to pristine nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS), to evaluate how ONC characteristics influence several KE in the pulmonary fibrosis adverse outcome pathway. In vitro exposure to pre-incinerated nanoclay induced organic coating-dependent cytotoxicity in SAECs. CloisNa caused disruption of mitochondrial membrane potential, which coincided with loss in viability in both cell types. Clois30B exposure caused dose-dependent SAEC cytotoxicity, micronuclei formation, and mitochondrial hyperpolarization in SAECs and NHLFs. Incinerated nanoclays were noncytotoxic but elicited a SAEC mitochondrial radical and pro-inflammatory response. Direct in vitro exposure to NHLFs exhibited particle-dependent increased live cell count, reactive oxygen species production, and α-smooth muscle actin expression. Nanoclay-exposed NHLFs (0.6 μg/cm2) possessed elevated collagen I levels while the same mass dose in vivo (300 μg/lung) favored elevated fibronectin and collagen III deposition for CloisNa and CS. In conclusion, organic coating presence and incineration status influenced nanoclays' effects on cellular interaction, membrane integrity, inflammation, fibroblast activation, and collagen accumulation in exposed cell models. Although pre-incinerated nanoclay exposure promoted collagen accumulation in vitro, it was a poor predictor of in vivo model reticular fiber deposition.

Abstract Background Organomodified nanoclays (ONC), two-dimensional montmorillonite with organic coatings, are increasingly used to improve nanocomposite properties. However, little is known about pulmonary health risks along the nanoclay life cycle even with increased evidence of airborne particulate exposures in occupational environments. Recently, oropharyngeal aspiration exposure to pre- and post-incinerated ONC in mice caused low grade, persistent lung inflammation with a pro-fibrotic signaling response with unknown mode(s) of action. We hypothesized that the organic coating presence and incineration status of nanoclays determine the inflammatory cytokine secretary profile and cytotoxic response of macrophages. To test this hypothesis differentiated human macrophages (THP-1) were acutely exposed (0–20 µg/cm2) to pristine, uncoated nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS) followed by cytotoxicity and inflammatory endpoints. Macrophages were co-exposed to lipopolysaccharide (LPS) or LPS-free medium to assess the role of priming the NF-κB pathway in macrophage response to nanoclay treatment. Data were compared to inflammatory responses in male C57Bl/6J mice following 30 and 300 µg/mouse aspiration exposure to the same particles. Results In LPS-free media, CloisNa exposure caused mitochondrial depolarization while Clois30B exposure caused reduced macrophage viability, greater cytotoxicity, and significant damage-associated molecular patterns (IL-1α and ATP) release compared to CloisNa and unexposed controls. LPS priming with low CloisNa doses caused elevated cathepsin B/Caspage-1/IL-1β release while higher doses resulted in apoptosis. Clois30B exposure caused dose-dependent THP-1 cell pyroptosis evidenced by Cathepsin B and IL-1β release and Gasdermin D cleavage. Incineration ablated the cytotoxic and inflammatory effects of Clois30B while I-CloisNa still retained some mild inflammatory potential. Comparative analyses suggested that in vitro macrophage cell viability, inflammasome endpoints, and pro-inflammatory cytokine profiles significantly correlated to mouse bronchioalveolar lavage inflammation metrics including inflammatory cell recruitment. Conclusions Presence of organic coating and incineration status influenced inflammatory and cytotoxic responses following exposure to human macrophages. Clois30B, with a quaternary ammonium tallow coating, induced a robust cell membrane damage and pyroptosis effect which was eliminated after incineration. Conversely, incinerated nanoclay exposure primarily caused elevated inflammatory cytokine release from THP-1 cells. Collectively, pre-incinerated nanoclay displayed interaction with macrophage membrane components (molecular initiating event), increased pro-inflammatory mediators, and increased inflammatory cell recruitment (two key events) in the lung fibrosis adverse outcome pathway.

OBJECTIVES:A cure for cancer is out of reach for most patients due to chemoresistance. Cancer-associated fibroblasts (CAFs) play a vital role in cancer chemoresistance, but detailed understanding of the process particularly in chemoresistant lung cancer is lacking. In this study, we investigated programmed death-ligand 1 (PDL-1) as a potential biomarker for CAF-induced chemoresistance and evaluated its role and the underlying mechanisms of chemoresistance in non-small cell lung cancer (NSCLC).MATERIALS AND METHODS:A systemic search of gene expression profiles of multiple tissues in NSCLC was carried out to determine the expression intensities of traditional fibroblast biomarkers and CAF-secreted protumorigenic cytokines. PDL-1 expression in CAFs was analyzed by ELISA, Western blotting, and flow cytometry. Human cytokine array was used to identify specific cytokines secreted from CAFs. Role of PDL-1 in NSCLC chemoresistance was assessed using CRISPR/Cas9 knockdown and various functional assays including MTT, cell invasion, sphere formation, and cell apoptosis. In vivo experiments were conducted using a co-implantation xenograft mouse model with live cell imaging and immunohistochemistry.RESULTS:We demonstrated that chemotherapy-stimulated CAFs promoted tumorigenic and stem cell-like properties of NSCLC cells, which contribute to their chemoresistance. Subsequently, we revealed that PDL-1 expression is upregulated in chemotherapy-treated CAFs and is associated with poor prognosis. Silencing PDL-1 expression suppressed CAFs' ability to promote stem cell-like properties and invasiveness of lung cancer cells, favoring chemoresistance. Mechanistically, an upregulation of PDL-1 in chemotherapy-treated CAFs led to an increase in hepatocyte growth factor (HGF) secretion, which stimulates cancer progression, cell invasion, and stemness of lung cancer cells, while inhibiting apoptosis.CONCLUSION:Our results show that PDL-1-positive CAFs modulate stem cell-like properties of NSCLC cells by secreting elevated HGF, thereby promoting chemoresistance. Our finding supports PDL-1 in CAFs as a chemotherapy response biomarker and as a drug delivery and therapeutic target for chemoresistant NSCLC.

Tetrazolium reduction and resazurin assays are the mainstay of routine in vitro toxicity batteries. However, potentially erroneous characterization of cytotoxicity and cell proliferation can arise if verification of baseline interaction of test article with method employed is neglected. The current investigation aimed to demonstrate how interpretation of results from several standard cytotoxicity and proliferation assays vary in dependence on contributions from the pentose phosphate pathway (PPP). Non-tumorigenic Beas-2B cells were treated with graded concentrations of benzo[a]pyrene (B[a]P) for 24 and 48 h prior to cytotoxicity and proliferation assessment with commonly used MTT, MTS, WST1, and Alamar Blue assays. B[a]P caused enhanced metabolism of each dye assessed despite reductions in mitochondrial membrane potential and was reversed by 6-aminonicotinamide (6AN)—a glucose-6-phosphate dehydrogenase inhibitor. These results demonstrate differential sensitivity of standard cytotoxicity assessments on the PPP, thus (1) decoupling “mitochondrial activity” as an interpretation of cellular formazan and Alamar Blue metabolism, and (2) demonstrating the implicit requirement for investigators to sufficiently verify interaction of these methods in routine cytotoxicity and proliferation characterization. The nuances of method-specific extramitochondrial metabolism must be scrutinized to properly qualify specific endpoints employed, particularly under the circumstances of metabolic reprogramming.

Many respiratory diseases, including COVID-19, can be spread by aerosols expelled by infected people when they cough, talk, sing, or exhale. Exposure to these aerosols indoors can be reduced by portable air filtration units (air cleaners). Homemade or Do-It-Yourself (DIY) air filtration units are a popular alternative to commercially produced devices, but performance data is limited. Our study used a speaker-audience model to examine the efficacy of two popular types of DIY air filtration units, the Corsi-Rosenthal cube and a modified Ford air filtration unit, in reducing exposure to simulated respiratory aerosols within a mock classroom. Experiments were conducted using four breathing simulators at different locations in the room, one acting as the respiratory aerosol source and three as recipients. Optical particle spectrometers monitored simulated respiratory aerosol particles (0.3-3 mu m) as they dispersed throughout the room. Using two DIY cubes (in the front and back of the room) increased the air change rate as much as 12.4 over room ventilation, depending on filter thickness and fan airflow. Using multiple linear regression, each unit increase of air change reduced exposure by 10%. Increasing the number of filters, filter thickness, and fan airflow significantly enhanced the air change rate, which resulted in exposure reductions of up to 73%. Our results show DIY air filtration units can be an effective means of reducing aerosol exposure. However, they also show performance of DIY units can vary considerably depending upon their design, construction, and positioning, and users should be mindful of these limitations.

ABSTRACTTo limit community spread of SARS-CoV-2, CDC recommends universal masking indoors, maintaining 1.8 m of physical distancing, adequate ventilation, and avoiding crowded indoor spaces. Several studies have examined the independent influence of each control strategy in mitigating transmission in isolation, yet controls are often implemented concomitantly within an indoor environment. To address the influence of physical distancing, universal masking, and ventilation on very fine respiratory droplets and aerosol particle exposure, a simulator that coughed and exhaled aerosols (the source) and a second breathing simulator (the recipient) were placed in an exposure chamber. When controlling for the other two mitigation strategies, universal masking with 3-ply cotton masks reduced exposure to 0.3–3 µm coughed and exhaled aerosol particles by > 77% compared to unmasked tests, whereas physical distancing (0.9 or 1.8 m) significantly changed exposure to cough but not exhaled aerosols. The effectiveness of ventilation depended upon the respiratory activity, i.e., coughing or breathing, as well as the duration of exposure time. Our results demonstrate that a combination of administrative and engineering controls can reduce personal inhalation exposure to potentially infectious very fine respiratory droplets and aerosol particles within an indoor environment.PRACTICAL IMPLICATIONSUniversal masking provided the most effective strategy in reducing inhalational exposure to simulated aerosols.Physical distancing provided limited reductions in exposure to small aerosol particles.Ventilation promotes air mixing in addition to aerosol removal, thus altering the exposure profile to individuals.A combination of mitigation strategies can effectively reduce exposure to potentially infectious aerosols.

BACKGROUND During the COVID-19 pandemic, face masks are used as source control devices to reduce the expulsion of respiratory aerosols from infected people. Modifications such as mask braces, earloop straps, knotting and tucking, and double masking have been proposed to improve mask fit. However, the data on source control are limited. METHODS The effectiveness of mask fit modifications was determined by conducting fit tests on human subjects and simulator manikins and by performing simulated coughs and exhalations using a source control measurement system. RESULTS Medical masks without modification blocked ≥56% of cough aerosols and ≥42% of exhaled aerosols. Modifying fit by crossing the earloops or placing a bracket under the mask did not increase performance, while using earloop toggles, an earloop strap, and knotting and tucking the mask increased performance. The most effective modifications for improving source control performance were double masking and using a mask brace. Placing a cloth mask over a medical mask blocked ≥85% of cough aerosols and ≥91% of exhaled aerosols. Placing a brace over a medical mask blocked ≥95% of cough aerosols and ≥99% of exhaled aerosols. CONCLUSION Fit modifications can greatly improve the performance of face masks as source control devices for respiratory aerosols.

With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-Omptm3Mom/MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.

Engineered nanomaterials (ENMs) come in a wide array of shapes, sizes, surface coatings, and compositions, and often possess novel or enhanced properties compared to larger sized particles of the same elemental composition. To ensure the safe commercialization of products containing ENMs, it is important to thoroughly understand their potential risks. Given that ENMs can be created in an almost infinite number of variations, it is not feasible to conduct in vivo testing on each type of ENM. Instead, new approach methodologies (NAMs) such as in vitro or in chemico test methods may be needed, given their capacity for higher throughput testing, lower cost, and ability to provide information on toxicological mechanisms. However, the different behaviors of ENMs compared to dissolved chemicals may challenge safety testing of ENMs using NAMs. In this study, member agencies within the Interagency Coordinating Committee on the Validation of Alternative Methods were queried about what types of ENMs are of agency interest and whether there is agency-specific guidance for ENM toxicity testing. To support the ability of NAMs to provide robust results in ENM testing, two key issues in the usage of NAMs, namely dosimetry and interference/bias controls, are thoroughly discussed.

A study was made on the effect of vanadium, in both the tetravalent state in vanadyl sulphate and in the pentavalent state in sodium meta-vanadate, and ortho-vanadate, on the proteolysis of azocasein by two serine proteases, trypsin and subtilisin and two cysteine proteases bromelain and papain. Also the proteolysis of bovine azoalbumin by serine proteases was considered. An inhibitory effect was present in all cases, except meta-vanadate with subtilisin. The oxidation level of vanadium by itself did not determine the inhibition kinetics, which also depended on the type and composition of the vanadium containing molecule and on the enzyme assayed. The pattern of inhibition was similar for proteases belonging to the same class. The highest inhibition was obtained with meta-vanadate on papain and with vanadyl sulphate on bromelain.

There is strong evidence associating the indoor environment with transmission of SARS-CoV-2, the virus that causes COVID-19. SARS-CoV-2 can spread by exposure to droplets and very fine aerosol particles from respiratory fluids that are released by infected persons. Layered mitigation strategies, including but not limited to maintaining physical distancing, adequate ventilation, universal masking, avoiding overcrowding, and vaccination, have shown to be effective in reducing the spread of SARS-CoV-2 within the indoor environment. Here, we examine the effect of mitigation strategies on reducing the risk of exposure to simulated respiratory aerosol particles within a classroom-style meeting room. To quantify exposure of uninfected individuals (Recipients), surrogate respiratory aerosol particles were generated by a breathing simulator with a headform (Source) that mimicked breath exhalations. Recipients, represented by three breathing simulators with manikin headforms, were placed in a meeting room and affixed with optical particle counters to measure 0.3–3 µm aerosol particles. Universal masking of all breathing simulators with a 3-ply cotton mask reduced aerosol exposure by 50% or more compared to scenarios with simulators unmasked. While evaluating the effect of Source placement, Recipients had the highest exposure at 0.9 m in a face-to-face orientation. Ventilation reduced exposure by approximately 5% per unit increase in air change per hour (ACH), irrespective of whether increases in ACH were by the HVAC system or portable HEPA air cleaners. The results demonstrate that mitigation strategies, such as universal masking and increasing ventilation, reduce personal exposure to respiratory aerosols within a meeting room. While universal masking remains a key component of a layered mitigation strategy of exposure reduction, increasing ventilation via system HVAC or portable HEPA air cleaners further reduces exposure.

Universal mask wearing is recommended to help control the spread of COVID-19. Masks reduce the expulsion of aerosols of respiratory fluids into the environment (called source control) and offer some protection to the wearer. Masks are often characterized using filtration efficiency, airflow resistance, and manikin or human fit factors, which are standard metrics used for personal protective devices. However, none of these metrics are direct measurements of how effectively a mask blocks coughed and exhaled aerosols. We studied the source control performance of 15 cloth masks (face masks, neck gaiters, and bandanas), two medical masks, and two N95 filtering facepiece respirators by measuring their ability to block aerosols ≤ 7 μm expelled during simulated coughing and exhalation (called source control collection efficiency). These measurements were compared with filtration efficiencies, airflow resistances, and fit factors measured on manikin headforms and humans. Collection efficiencies for the cloth masks ranged from 17% to 71% for coughing and 35% to 66% for exhalation. Filtration efficiencies for the cloth masks ranged from 1.4% to 98%, while the fit factors were 1.3 to 7.4 on headforms and 1.0 to 4.0 on human subjects. The Spearman's rank correlation coefficients between the source control collection efficiencies and the standard metrics ranged from 0.03 to 0.68 and were significant in all but two cases. However, none of the standard metrics were strongly correlated with source control performance. A better understanding of the relationships between source control collection efficiency, filtration efficiency, airflow resistance, and fit factor is needed.

ABSTRACT Face masks reduce the spread of infectious respiratory diseases such as COVID-19 by blocking aerosols produced during coughs and exhalations (“source control”). Masks also slow and deflect cough and exhalation airflows, which changes the dispersion of aerosols. Factors such as the directions in which people are facing (orientation) and separation distance also affect aerosol dispersion. However, it is not clear how masking, orientation, and distance interact. We placed a respiratory aerosol simulator (“source”) and a breathing simulator (“recipient”) in a 3 m x 3 m chamber and measured aerosol concentrations for different combinations of masking, orientation, and separation distance. When the simulators were front-to-front during coughing, masks reduced the 15-minute mean aerosol concentration at the recipient by 92% at 0.9 and 1.8 m separation. When the simulators were side-by-side, masks reduced the concentration by 81% at 0.9 m and 78% at 1.8 m. During breathing, masks reduced the aerosol concentration by 66% when front-to-front and 76% when side-by-side at 0.9 m. Similar results were seen at 1.8 m. When the simulators were unmasked, changing the orientations from front-to-front to side-by-side reduced the cough aerosol concentration by 59% at 0.9 m and 60% at 1.8 m. When both simulators were masked, changing the orientations did not significantly change the concentration at either distance during coughing or breathing. Increasing the distance between the simulators from 0.9 m to 1.8 m during coughing reduced the aerosol concentration by 25% when no masks were worn but had little effect when both simulators were masked. During breathing, when neither simulator was masked, increasing the separation reduced the concentration by 13%, which approached significance, while the change was not significant when both source and recipient were masked. Our results show that universal masking reduces exposure to respiratory aerosol particles regardless of the orientation and separation distance between the source and recipient.

SARS-CoV-2, the virus that causes COVID-19, can be spread by exposure to droplets and aerosols of respiratory fluids that are released by infected persons when they cough, sing, talk, or exhale. To reduce indoor transmission of SARS-CoV-2 between persons, CDC recommends measures including physical distancing, universal masking (the use of face masks in public places by everyone who is not fully vaccinated), and increased room ventilation (1). Ventilation systems can be supplemented with portable high efficiency particulate air (HEPA) cleaners* to reduce the number of infectious particles in the air and provide enhanced protection from transmission between persons (2); two recent reports found that HEPA air cleaners in classrooms could reduce overall aerosol particle concentrations by ≥80% within 30 minutes (3,4). To investigate the effectiveness of portable HEPA air cleaners and universal masking at reducing exposure to exhaled aerosol particles, the investigation team used respiratory simulators to mimic a person with COVID-19 and other, uninfected persons in a conference room. The addition of two HEPA air cleaners that met the Environmental Protection Agency (EPA)-recommended clean air delivery rate (CADR) (5) reduced overall exposure to simulated exhaled aerosol particles by up to 65% without universal masking. Without the HEPA air cleaners, universal masking reduced the combined mean aerosol concentration by 72%. The combination of the two HEPA air cleaners and universal masking reduced overall exposure by up to 90%. The HEPA air cleaners were most effective when they were close to the aerosol source. These findings suggest that portable HEPA air cleaners can reduce exposure to SARS-CoV-2 aerosols in indoor environments, with greater reductions in exposure occurring when used in combination with universal masking.

A 57-year-old white man developed Hashimoto's thyroiditis, bullous pemphigoid, and autoimmune neutropenia during the last year of his life. In addition, he had alopecia universalis since the age of 21 and rheumatoid arthritis since the age of 38. This unique constellation of autoimmune diseases has not been reported previously. Its significance is discussed in relation to the polyglandular failure syndrome and thymoma-related autoimmune disease.

Universal masking is one of the prevention strategies recommended by CDC to slow the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). As of February 1, 2021, 38 states and the District of Columbia had universal masking mandates. Mask wearing has also been mandated by executive order for federal property* as well as on domestic and international transportation conveyances.† Masks substantially reduce exhaled respiratory droplets and aerosols from infected wearers and reduce exposure of uninfected wearers to these particles. Cloth masks§ and medical procedure masks fit more loosely than do respirators (e.g., N95 facepieces). The effectiveness of cloth and medical procedure masks can be improved by ensuring that they are well fitted to the contours of the face to prevent leakage of air around the masks' edges. During January 2021, CDC conducted experimental simulations using pliable elastomeric source and receiver headforms to assess the extent to which two modifications to medical procedure masks, 1) wearing a cloth mask over a medical procedure mask (double masking) and 2) knotting the ear loops of a medical procedure mask where they attach to the mask's edges and then tucking in and flattening the extra material close to the face (knotted and tucked masks), could improve the fit of these masks and reduce the receiver's exposure to an aerosol of simulated respiratory droplet particles of the size considered most important for transmitting SARS-CoV-2. The receiver's exposure was maximally reduced (>95%) when the source and receiver were fitted with modified medical procedure masks. These laboratory-based experiments highlight the importance of good fit to optimize mask performance. Until vaccine-induced population immunity is achieved, universal masking is a highly effective means to slow the spread of SARS-CoV-2** when combined with other protective measures, such as physical distancing, avoiding crowds and poorly ventilated indoor spaces, and good hand hygiene. Innovative efforts to improve the fit of cloth and medical procedure masks to enhance their performance merit attention.

Although children and young adults are reportedly at lower risk for severe disease and death from infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), than are persons in other age groups (1), younger persons can experience infection and subsequently transmit infection to those at higher risk for severe illness (2-4). Although at lower risk for severe disease, some young adults experience serious illness, and asymptomatic or mild cases can result in sequelae such as myocardial inflammation (5). In the United States, approximately 45% of persons aged 18-22 years were enrolled in colleges and universities in 2019 (6). As these institutions reopen, opportunities for infection increase; therefore, mitigation efforts and monitoring reports of COVID-19 cases among young adults are important. During August 2-September 5, weekly incidence of COVID-19 among persons aged 18-22 years rose by 55.1% nationally; across U.S. Census regions,* increases were greatest in the Northeast, where incidence increased 144.0%, and Midwest, where incidence increased 123.4%. During the same period, changes in testing volume for SARS-CoV-2 in this age group ranged from a 6.2% decline in the West to a 170.6% increase in the Northeast. In addition, the proportion of cases in this age group among non-Hispanic White (White) persons increased from 33.8% to 77.3% during May 31-September 5. Mitigation and preventive measures targeted to young adults can likely reduce SARS-CoV-2 transmission among their contacts and communities. As colleges and universities resume operations, taking steps to prevent the spread of COVID-19 among young adults is critical (7).