Face Off: 3D-Printed Masks as a Cost-Effective and Reusable Alternative to N95 Respirators: A Feasibility Study.

BACKGROUND: One of the best methods for protection against respiratory diseases is the use of an N95 mask. Supply shortages have demonstrated a significant need for effective alternatives to N95 masks. Benefits of 3D-printed respirators over N95s include reduced cost and ease of production, widespread availability, reusability/sterilizability, and customizability. 3D-printed mask designs have been downloaded thousands of times; however, there is little to no data on the efficacy of these potential alternatives. METHODS: Three of the most popular 3D-printed respirator designs were modified to allow for the Occupational Safety and Health Administration (OSHA) quantitative fit testing that disperses saline into the ambient air and determines concentrations within the mask during multiple trials. Five volunteers conducted standardized fit tests of these masks, as well as an N95 and a KN95, and the results were compared. RESULTS: One of the 3D-printed respirators, low poly COVID-19 face mask respirator (mask 2), achieved a fit factor greater than 100 in every trial, representing sufficient fit according to OSHA protocols. The N95 mask achieved a sufficient fit in 60% of the trials, and none of the remaining masks provided a suitable fit factor reliably according to the OSHA fit test. Further trials showed no change in fit factor when different 3D-printable plastics are used or when a widely available high efficiency particulate air (HEPA) filter was used. CONCLUSION: 3D-printed respirators provide a possible alternative to N95 masks to protect against respiratory pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fit testing results demonstrate that certain 3D-printed mask designs may exceed the fit of N95 masks.

The Anesthesiologist as Translational Scientist.

Translational science seeks to accelerate the multi-step process by which scientific discoveries are transformed into therapies that can improve the health of individuals and their communities. To facilitate crossing the traditional boundaries between basic and clinical research for instance, a systematic understanding of the scientific and operational principles that underlie each step of the translational cycle is developed to identify and address barriers to translation. Skills required by translational scientists, such as being systems thinkers and process innovators, overlap with those of anesthesiologists, and therefore, it is no surprise that anesthesiologists have contributed to this field. Indeed, the safety and efficacy of anesthesia care has greatly evolved over many decades because anesthesiologists have recognized the importance of readily incorporating physiological and pharmacological basic research findings into clinical practice. This article highlights the characteristics that make anesthesiologists well suited to be translational scientists. We also discuss one example of anesthesiology contributing to the field of translational science during the COVID-19 pandemic. We show that anesthesiologists, regardless of their specific clinical or research interests, have the skill set to become effective and critical players in the field of translational science and emphasize the importance of continued leadership in this field to academic anesthesiology.

Attenuation of pulmonary injury by an inhaled MMP inhibitor in the endotoxin lung injury model.

Acute respiratory distress syndrome (ARDS) is characterized by pulmonary edema and poor gas exchange resulting from severe inflammatory lung injury. Neutrophilic infiltration and increased pulmonary vascular permeability are hallmarks of early ARDS and precipitate a self-perpetuating cascade of inflammatory signaling. The biochemical processes initiating these events remain unclear. Typically associated with extracellular matrix degradation, recent data suggest matrix metalloproteinases (MMPs) are regulators of pulmonary inflammation. To demonstrate that inhalation of a broad MMP inhibitor attenuates LPS induced pulmonary inflammation. Nebulized CGS27023AM (CGS) was administered to LPS-injured mice. Pulmonary CGS levels were examined by mass spectroscopy. Inflammatory scoring of hematoxylin-eosin sections, examination of vascular integrity via lung wet/dry and bronchoalveolar lvage/serum FITC-albumin ratios were performed. Cleaved caspase-3 levels were also assessed. Differential cell counts and pulse-chase labeling were utilized to determine the effects of CGS on neutrophil migration. The effects of CGS on human neutrophil migration and viability were examined using Boyden chambers and MTT assays. Nebulization successfully delivered CGS to the lungs. Treatment decreased pulmonary inflammatory scores, edema, and apoptosis in LPS treated animals. Neutrophil chemotaxis was reduced by CGS treatment, with inhalation causing significant reductions in both the total number and newly produced bromodeoxyuridine-positive cells infiltrating the lung. Mechanistic studies on cells isolated from humans demonstrate that CGS-treated neutrophils exhibit decreased chemotaxis. The protective effect observed following treatment with a nonspecific MMP inhibitor indicates that one or more MMPs mediate the development of pulmonary edema and neutrophil infiltration in response to LPS injury. In accordance with this, inhaled MMP inhibitors warrant further study as a potential new therapeutic avenue for treatment of acute lung injury.

Multimodality molecular imaging of the alveolar-capillary barrier in lung disease using albumin based optical and PET tracers.

Inflammatory changes caused by viruses, bacteria, exposure to toxins, commonly used drugs and even surgical intervention have the potential of causing abnormal epithelial permeability, which is manifest as infiltrative processes on computed tomography (CT), including the widespread infiltrates seen in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS). We utilized a previously published mouse model of ARDS, intranasal delivery of LPS, to induce the alveolar-capillary barrier permeability seen in lung disease. We intravenously injected mice with Cy7 or 68-Gallium (68Ga) labeled mouse albumin and imaged using optical imaging (OI)/CT and PET. We observed significantly increased lung levels of Cy7-albumin on 3D OI/CT, which matched the abnormal appearance on microCT. This uptake correlated with fluorescence seen on sectioned lungs. To examine the translational potential of these findings, we radiolabeled albumin with 68Ga. We found that in mice with LPS-induced lung injury, 68Ga-albumin PET correlated with our optical imaging findings and demonstrated abnormal activity in the lung fields, indicative of abnormal epithelial permeability. These findings indicate 68Ga-albumin can be utilized as a sensitive translational radiotracer for quantifying the abnormal epithelial permeability that is seen in various lung pathologies, including COVID-19 induced pneumonia and ARDS. The ability to use Cy7-albumin 3D OI/CT imaging as a preclinical translational surrogate for 68Ga-albumin offers an accessible high throughput means to rapidly screen potential therapeutics against lung diseases that clinically manifest with endothelial permeability.

A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure.

Macrophage infiltration is common to both emphysema and atherosclerosis, and cigarette smoke down-regulates the macrophage cholesterol efflux transporter ATP binding cassette (ABC)A1. This decreased cholesterol efflux results in lipid-laden macrophages. We hypothesize that cigarette smoke adversely affects cholesterol transport via an ABCA1-dependent mechanism in macrophages, enhancing TLR4/myeloid differentiation primary response gene 88 (Myd88) signaling and resulting in matrix metalloproteinase (MMP) up-regulation and exacerbation of pulmonary inflammation. ABCA1 is significantly down-regulated in the lung upon smoke exposure conditions. Macrophages exposed to cigarette smoke in vivo and in vitro exhibit impaired cholesterol efflux correlating with significantly decreased ABCA1 expression, up-regulation of the TLR4/Myd88 pathway, and downstream MMP-9 and MMP-13 expression. Treatment with liver X receptor (LXR) agonist restores ABCA1 expression after short-term smoke exposure and attenuates the inflammatory response; after long-term smoke exposure, there is also attenuated physiologic and morphologic changes of emphysema. In vitro, treatment with LXR agonist decreases macrophage inflammatory activation in wild-type but not ABCA1 knockout mice, suggesting an ABCA1-dependent mechanism of action. These studies demonstrate an important association between cigarette smoke exposure and cholesterol-mediated pathways in the macrophage inflammatory response. Modulation of these pathways through manipulation of ABCA1 activity effectively blocks cigarette smoke-induced inflammation and provides a potential novel therapeutic approach for the treatment of chronic obstructive pulmonary disease.-Sonett, J., Goldklang, M., Sklepkiewicz, P., Gerber, A., Trischler, J., Zelonina, T., Westerterp, M., Lemaître, V., Okada, V., D'Armiento, J. A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure.

MyOncofertility.org: a web-based patient education resource supporting decision making under severe emotional and cognitive overload.

Kristin, a 38-year-old female with breast cancer, was scheduled to begin treatment a week after receiving her diagnosis. Although she was in a four-year-long relationship, she had never thought about having kids. Kristin was told that embryo banking (IVF) was the best option for fertility preservation, and she had to decide immediately if she wanted biological children in order to start an egg-retrieval cycle. Because no other options were provided and she was uncertain about freezing embryos with her partner, she ended up foregoing fertility preservation prior to the treatments that ultimately left her infertile. Ethan, a 19-year-old male, was in the hospital for four days awaiting surgery to remove a pelvic sarcoma. The surgery required removal of his testes rendering him infertile. During those four days, no one talked to him or his family about sperm banking, even though it could hve been accomplished in a matter of minutes.

Reduced blockade by extracellular Mg(2+) is permissive to NMDA receptor activation in cerebellar granule neurons that model a migratory phenotype.

NMDA receptors (NMDAR) contribute to neuronal development throughout the CNS. However, their mode(s) of activation preceding synaptic maturation is unclear, as they are not co-localized with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) which normally provide sufficient depolarization to relieve voltage-dependent blockade by Mg(2+). We used cerebellar granule neurons (CGNs) cultured at a near-physiological KCl concentration to examine maturation-dependent changes in NMDAR responses. In contrast, most studies use KCl-supplemented medium to promote survival. At 2-4 days in vitro CGNs: (i) express developmental markers resembling the in vivo migratory phenotype; (ii) maintain a basal amount of calcium responsive element-binding protein phosphorylation that requires NMDARs and calcium/calmodulin-dependent kinases, but not AMPARs; (iii) exhibit NMDA-mediated Ca(2+) influx not effectively blocked by ambient Mg(2+) (0.75 mM) or AMPARs; (iv) maintain a more depolarized resting membrane potential and increased resistance compared to synaptically-connected CGNs. Moreover, migrating CGNs in explant cultures demonstrate NMDA-mediated Ca(2+) influx not effectively blocked by 0.75 mM Mg(2+), and NMDAR but not AMPAR antagonists slow migration. These data suggest the biophysical properties of immature CGNs render NMDARs less sensitive to Mg(2+) blockade, enhancing the likelihood of activation in the absence of AMPAR depolarization.