Respiratory Delivery Research Articles

Technical features of vaping drug delivery system for bronchodilator delivery

PurposeSeveral technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS). MethodsTerbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (Cirrus TM 2, 2 mL of terbutaline at 2.5 mg/mL). ResultsGS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization. ConclusionWe proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design.

Clinical Outcomes of Stereotactic Body Radiation Therapy across Treatment Platforms Employing Varied Approaches to Respiratory Management at a Single Institution

<h3>Purpose/Objective(s)</h3> Stereotactic Body Radiation Therapy (SBRT) has been the standard of care for early-stage non-small cell lung cancer patients who do not undergo surgery since soon after the publication of RTOG 0236. Since then, various linear accelerator platforms have been employed with a variety of approaches to respiratory management, treatment planning and treatment delivery. Comparisons of local control and survival end points using a variety of treatment platforms in addition to respiratory management techniques have not been reported. Here, we present the results of our analysis of clinical outcomes at a single institution across multiple treatment platforms representative of the available technology since the widespread adoption of SBRT for early-stage lung cancer. <h3>Materials/Methods</h3> Consecutive patients who underwent SBRT for early-stage lung cancer between 2011 and 2018 at a single institution were retrospectively analyzed. Treatments were planned and delivered with standardized simulation, dose and fractionation per institutional guidelines. Overall Survival (OS), Local Control (LC), Distant Metastasis Free Survival (DMFS), and Progression Free Survival (PFS) were calculated for the entire cohort. Log rank comparisons of all survival endpoints were then calculated by treatment platform: stereoscopic orthogonal kV x-ray localization with conventional Linac (Linac1), volumetric cone beam CT localization with conventional Linac (Linac2), and megavoltage CT with helical tomotherapy (Linac3). Comparisons were also performed by respiratory management technique: free breath (FB), breath hold (BH) or end expiration respiratory gating (RG). <h3>Results</h3> A total of 240 patients were included in the analysis. Treatment platform utilization was well balanced in the group: 28% on Linac1, 32% on Linac2, and 40% on Linac3. The majority of patients were treated with FB, 72%. Median OS for the entire cohort was 50 months. The crude rate of local recurrence was 7%. Kaplan-Meier estimate of LC for the entire cohort was 94% at 3 years. The median time to local recurrence was not reached. LC was not impacted by treatment platform, p = 0.897, or respiratory management technique, p = 0.623. Comparisons by treatment platform and respiratory management technique revealed no significant differences in OS, DMFS, and PFS. <h3>Conclusion</h3> Irrespective of treatment platform or approach to respiratory management, SBRT remains highly effective at providing durable LC in patients with early-stage lung cancer. Differences in treatment delivery platform and respiratory management do not significantly influence other disease control and survival outcomes.

A Review of Non-Invasive Drug Delivery through Respiratory Routes.

With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinson’s disease, Alzheimer’s disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.

Deployment of Tele-ICU Respiratory Therapy and the Creation of an eRT Service Line

Summary Penn Medicine launched a 24-7 telemedicine respiratory therapist (eRT) service as part of its tele–critical care medicine (tele-CCM) service serving seven hospitals and more than 320 critical care beds. Service line interventions were focused on protocolized evidence-based practices, safety, documentation compliance, and urgent emergent ad hoc clinical needs. Concomitantly, the eRTs were available to respond to urgent and emergent interventions on the basis of the clinical bedside situation. Their activity was triggered by Penn E-lert staff (serving the tele-ICUs), bedside staff, algorithmic trigger software, or the eRT’s own review of a patient’s clinical condition. A standardized data collection was deployed to gather information about the interventions. The value of the eRT service was defined in terms of estimated lives saved by implementing the standards of care earlier than the bedside staff would or acute respiratory distress syndrome (ARDS) algorithmic trigger and by intervening during emergent and urgent clinical request, improving care delivery, and complying with best clinical practices, and by the time freed for onsite staff to perform other duties. Between May 2020 and August 2021, eRTs registered 31,609 activities; 97.8% of interventions were related to the routine established workflows, while 1.9% were urgent and 0.3% emergent. In 51.2% of all eRT accomplished activities, no communication with other staff was needed. When communication did take place, eRTs connected with the bedside respiratory therapist in 36.7% of interactions, followed by house staff (7.2%), advanced practice providers (5.2%), and registered nurses (1.6%). The eRTs communicated via phone (81.4%), asynchronous text platform (16%), or tele-CCM software (1.4%). While prompted by staffing, safety, and logistics challenges during a Covid-19 surge, the resulting eRT service line has been well received and has become a part of the standard of care. Overall efficiency of respiratory care service delivery was increased as Penn retained staff and increased the flexibility of bedside therapists. Furthermore, the eRT service detected unfavorable practice patterns in ARDS treatment and intervened before the ARDS algorithmic trigger was activated or acted upon. Some of the tasks can be accomplished by the eRT in a shorter amount of time than it would take bedside staff. In addition, the remote staffing reduced personal protective equipment utilization. All of these gains translated into postpandemic time savings. Penn’s experience shows that the eRT care model can be transformed into a system-valued proposition and retained with sustained benefit beyond the pandemic surge.

Anesthesia management in a pregnant patient with neurofibromatosis

Neurofibromatosis (NF) is a genetic and multisystemic disease with autosomal dominant transition. It can affect anesthesia applications by affecting more than one system. In the presence of neurofibromas in the airway, it can cause airway obstruction and difficulties in respiratory delivery during general anesthesia. The presence of tumors affecting the central nervous system makes spinal anesthesia risky. Anesthesiologists should act with awareness of each multisystemic complication when evaluating and managing patients. This case report aims to present our general anesthesia practice in an elective cesarean operation in a pregnant patient with neurofibromatosis type 1.

Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2

The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.

Spray freeze drying to solidify Nanosuspension of Cefixime into inhalable microparticles.

Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to obtain dried nanosuspension of cefixime with improved dissolution profile, good dispersibility, and excellent inhalation performance. Nanoprecipitation was utilized to prepare nanoparticles (NPs). Nanosuspensions of cefixime were solidified via SFD to access inhalable microparticles. The aerosolization efficiencies were evaluated through twin stage impinger (TSI). Laser light scattering and scanning electron microscopy (SEM) provided assistance to determine the particle size/size distribution and morphology, respectively. Amorphous/ crystalline states of materials were examined via differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Release profiles of candidate preparations were evaluated. The fine particle fraction (FPF) ranged from 18.96 ± 0.76 to 79.28 ± 0.45%. The highest value resulted from trehalose with NP/carrier ratio of 1:1 and leucine 20%. The particle size varied from 5.24 ± 0.97 to 10.17 ± 1.01μm. The most and the least size distribution were achieved in mannitol and trehalose containing formulations, respectively. The majority of samples demonstrated ideally spherical morphology with diverse degrees of porosity and without needle-shaped structure. Percentages of release in F7 and F8 were 89.33 ± 0.88% and 93.54 ± 1.02%, respectively, via first 10min. SFD of nanosuspensions can be established as a platform for the pulmonary delivery of poorly water-soluble molecules of cefixime. Trehalose and raffinose with a lower ratio of NP to the carrier and higher level of leucine could be introduced as favorable formulations for further respiratory delivery of cefixime.

426. COVID-19 Infection Prevention Practices That Exceed CDC Guidance: Balancing Extra Caution Against Impediments to Care

BackgroundAt the outset of the COVID-19 pandemic, healthcare workers (HCWs) raised concerns about personal risks of acquiring infection during patient care. This led to more stringent infection prevention practices than CDC guidelines during a time of uncertainty about transmission and limited U.S. testing capacity. Hospitals were challenged to protect against true COVID-19 exposure risks, while avoiding use of unproven measures that could interfere with timely, high quality care. We evaluated hospital experiences with HCW COVID-19 exposure concerns impacting clinical workflow/management. MethodsWe conducted a 32-question structured survey of hospital infection prevention leaders (one per hospital) from CDC Prevention Epicenters, University of California (CA) Health system, HCA Healthcare, and the Southern CA Metrics Committee between May–Dec, 2020. We assessed facility characteristics and COVID-19 exposure concerns causing changes in respiratory care, procedure delays/modifications, requests to change infection prevention processes, disruptions in routine medical care, and health impacts of PPE overuse. Percentages were calculated among respondents for each question.ResultsRespondents represented 53 hospitals: 22 (42%) were small (< 200 beds), 14 (26%) medium (200-400 beds), and 17 (32%) large ( >400 beds) facilities. Of these, 11 (21%) provided Level 1 trauma care, and 22 (41%) provided highly immunocompromised patient care; 75% had cared for a substantial number of COVID-19 cases before survey completion. Majority reported changes in respiratory care delivery (71%-87%), procedural delays (75%-87%), requests to change infection prevention controls/protocols (58%-96%), and occupational health impacts of PPE overuse including skin irritation (98%) and carbon dioxide narcosis symptoms (55%) (Table).ConclusionHCW concerns over work-related COVID-19 exposure contributed to practice changes, many of which are unsupported by CDC guidance and resulted in healthcare delivery delays and alterations in clinical care. Pandemic planning and response must include the ability to rapidly develop evidence to guide infection prevention practice. Disclosures Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Eunice J. Blanchard, MSN RN, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Deborah S. Yokoe, MD, MPH, Nothing to disclose Jonathan Grein, MD, Gilead (Other Financial or Material Support, Speakers fees) Stuart H. Cohen, MD, Seres (Research Grant or Support) Kimberly N. Smith, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Brandon Carver, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

Patient-Ventilator Dyssynchrony in Critically Ill Patients.

Patient–ventilator dyssynchrony is a mismatch between the patient’s respiratory efforts and mechanical ventilator delivery. Dyssynchrony can occur at any phase throughout the respiratory cycle. There are different types of dyssynchrony with different mechanisms and different potential management: trigger dyssynchrony (ineffective efforts, autotriggering, and double triggering); flow dyssynchrony, which happens during the inspiratory phase; and cycling dyssynchrony (premature cycling and delayed cycling). Dyssynchrony has been associated with patient outcomes. Thus, it is important to recognize and address these dyssynchronies at the bedside. Patient–ventilator dyssynchrony can be detected by carefully scrutinizing the airway pressure–time and flow–time waveforms displayed on the ventilator screens along with assessing the patient’s comfort. Clinicians need to know how to depict these dyssynchronies at the bedside. This review aims to define the different types of dyssynchrony and then discuss the evidence for their relationship with patient outcomes and address their potential management.

Synthesis, Physicochemical Characterization, In Vitro 2D/3D Human Cell Culture, and In Vitro Aerosol Dispersion Performance of Advanced Spray Dried and Co-Spray Dried Angiotensin (1-7) Peptide and PNA5 with Trehalose as Microparticles/Nanoparticles for Targeted Respiratory Delivery as Dry Powder Inhalers.

The peptide hormone Angiotensin (1—7), Ang (1—7) or (Asp-Arg-Val-Tyr-Ile-His-Pro), is an essential component of the renin–angiotensin system (RAS) peripherally and is an agonist of the Mas receptor centrally. Activation of this receptor in the CNS stimulates various biological activities that make the Ang (1—7)/MAS axis a novel therapeutic approach for the treatment of many diseases. The related O-linked glycopeptide, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-D-Glc)-amide (PNA5), is a biousian revision of the native peptide hormone Ang (1—7) and shows enhanced stability in vivo and greater levels of brain penetration. We have synthesized the native Ang (1—7) peptide and the glycopeptide, PNA5, and have formulated them for targeted respiratory delivery as inhalable dry powders. Solid phase peptide synthesis (SPPS) successfully produced Ang (1—7) and PNA5. Measurements of solubility and lipophilicity of raw Ang (1—7) and raw PNA5 using experimental and computational approaches confirmed that both the peptide and glycopeptide have high-water solubility and are amphipathic. Advanced organic solution spray drying was used to engineer the particles and produce spray-dried powders (SD) of both the peptide and the glycopeptide, as well as co-spray-dried powders (co-SD) with the non-reducing sugar and pharmaceutical excipient, trehalose. The native peptide, glycopeptide, SD, and co-SD powders were comprehensively characterized, and exhibited distinct glass transitions (Tg) consistent with the amorphous glassy state formation with Tgs that are compatible with use in vivo. The homogeneous particles displayed small sizes in the nanometer size range and low residual water content in the solid-state. Excellent aerosol dispersion performance with a human DPI device was demonstrated. In vitro human cell viability assays showed that Ang (1—7) and PNA5 are biocompatible and safe for different human respiratory and brain cells.

Evaluation of the stability of a spray-dried tuberculosis vaccine candidate designed for dry powder respiratory delivery

Particle engineering via spray drying was used to develop a dry powder presentation of an adjuvanted tuberculosis vaccine candidate. This presentation utilizing a trileucine-trehalose excipient system was designed to be both thermostable and suitable for respiratory delivery. The stability of the spray-dried vaccine powder was assessed over one year at various storage temperatures (-20, 5, 25, 40, 50 °C) in terms of powder stability, adjuvant stability, and antigen stability. A formulation without trileucine was included as a control. The results showed that the interior particle structure and exterior particle morphology of the powder was maintained for one year at 40 °C, while the control case exhibited a small extent of particle fusing under the same storage conditions. Moisture content was maintained, and powder solid state remained amorphous for all storage temperatures. Aerosol performance was assessed with a commercial dry powder inhaler in combination with a human mouth-throat model. The emitted dose and lung dose were maintained for all samples after one year at temperatures up to 40 °C. Nanoemulsion size and oil content of the adjuvant system were maintained after one year at temperatures up to 40 °C, and the agonist content was maintained after one year at temperatures up to 25 °C. The antigen was completely degraded in the control formulation at seven months of storage at 40 °C; by contrast, 45% of the antigen was still present in the trehalose-trileucine formulation after one year of storage at 50 °C. Comparatively, the antigen was completely degraded in a liquid sample of the vaccine candidate after only one month of storage at 37 °C. The spray-dried trehalose-trileucine vaccine powder clearly maintained its inhalable properties after one year’s storage at high temperatures and improved overall thermostability of the vaccine.

Electrospray propelled by ionic wind in a bipolar system for direct delivery of charge reduced nanoparticles

We present a conceptual design to generate and deliver nanoparticles in one unique system based on electrohydrodynamic atomisation (EHDA) without the restriction of the collector. The present EHDA bipolar configuration consists of a capillary nozzle and a pin, both act as emitters and as the reference electrodes of each other. Under an applied voltage, the capillary nozzle sprays droplets while the pin generates ion wind via corona discharge. During spraying process, droplets’ charge is significantly reduced by interacting with counter ions and propelled away from the electrodes by the momentum of ion winds accumulated from corona discharge. Thus, the present technique can yield promising applications in effective respiratory delivery of nanomedicine.

Respiratory delivery of favipiravir-tocilizumab combination through mucoadhesive protein-lipidic nanovesicles: prospective therapeutics against COVID-19.

Coronavirus disease 19 (COVID-19) is the prime global health concern of the year 2020. Infecting more than 112 million individuals so far, this pandemic has already reported more than 2.4 million deaths around the world. With such high infectivity and mortality, effective treatment intervention is the need of the hour. The integration of medical science with nanotechnology may solve the current problem by exploring collective benefits. In this manuscript, we theoretically proposed the duo-combination of an approved antiviral i.e. favipiravir along with an immunomodulator i.e. tocilizumab loaded in protein-lipid nanovesicles as an effective anti-COVID-19 therapeutic. This proposed nanomedicine delivered through the respiratory mode may enhance the effectiveness of the antiviral and help in restricting the virus and associated complications, utilizing both anti-viral activity and immunomodulation in COVID-19 patients. This proposed nanomedicine could be an effective treatment modality for the severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) infected patients.

STING activation in alveolar macrophages and group 2 innate lymphoid cells suppresses IL-33-driven type 2 immunopathology.

2′3′-cGAMP is known as a nonclassical second messenger and small immune modulator that possesses potent antitumor and antiviral activities via inducing the stimulator of IFN genes–mediated (STING-mediated) signaling pathway. However, its function in regulating type 2 immune responses remains unknown. Therefore, we sought to determine a role of STING activation by 2′3′-cGAMP in type 2 inflammatory reactions in multiple mouse models of eosinophilic asthma. We discovered that 2′3′-cGAMP administration strongly attenuated type 2 lung immunopathology and airway hyperreactivity induced by IL-33 and a fungal allergen, Aspergillus flavus. Mechanistically, upon the respiratory delivery, 2′3′-cGAMP was mainly internalized by alveolar macrophages, in which it activated the STING/IFN regulatory factor 3/type I IFN signaling axis to induce the production of inhibitory factors containing IFN-α, which blocked the IL-33–mediated activation of group 2 innate lymphoid (ILC2) cells in vivo. We further demonstrated that 2′3′-cGAMP directly suppressed the proliferation and function of both human and mouse ILC2 cells in vitro. Taken together, our findings suggest that STING activation by 2′3′-cGAMP in alveolar macrophages and ILC2 cells can negatively regulate type 2 immune responses, implying that the respiratory delivery of 2′3′-cGAMP might be further developed as an alternative strategy for treating type 2 immunopathologic diseases such as eosinophilic asthma.

Book Reviews

McGonigal K. Avery; 2021. Paperback; 272 pages.Are you one of those people who need a little extra motivation to get off the couch and move? Reading A The Joy of Movement might provide that extra motivation. We all know that exercise improves mental and physical health, but McGonigal adds 1 more important element to be aware of—there is joy to be found in moving. This joy is not only for the avid runner but for anyone who just moves. In The Joy of Movement, McGonigal describes the extraordinary physiological mechanisms that lead to improved psychological health.Some of the most important new information regarding exercise is about the endocannabinoid system. New research has shown that the “runner’s high” is not due to endorphins but to endocannabinoids. These cannabis-like molecules are produced by our bodies in response to 20 minutes of medium-intensity exercise such as fast walking, jogging, or swimming. The molecules are small enough to cross the blood-brain barrier, producing positive psychological benefits such as reduced anxiety, contentment, and feeling more connected to others.One of the most interesting tidbits of information in the book is about the correlation between the number of steps you take each day and anxiety and depression. According to McGonigal, research shows that feelings of anxiety and depression along with diminished life satisfaction are associated with an average of less than 5649 steps per day. This fact should concern all of us, because most Americans average only 4774 steps per day. If you are unable to walk as many as 10 000 steps per day, it is good to know that at least 6000 steps can help elevate your mood and thoughts.Last but not least, McGonigal explains why so many of us hate going to the gym: Our brains prefer the outdoors or “green exercise.” According to McGonigal, exercising outdoors provides the immediate benefit of allowing our brains to disengage, resulting in feelings of selflessness, a lack of self-consciousness, and a strong sense of connection to others and nature. Being active outdoors also produces a sense of refuge and a feeling of being sheltered or protected—an effect similar to that produced by meditation.The Joy of Movement is a worthwhile read, especially if you are looking for the latest on exercise neuroscience.Gordon J, West D. Wiley; 2019. Hardcover; 112 pages.Are you a carrot, an egg, or a coffee bean? According to Gordon and West, life can weaken us, harden us, or release a power in us that can help us transform our environment. The Coffee Bean is a quick and easy read, with a powerful message told through the story of Abe. Abe is a young man who brings the lesson of the coffee bean with him through school, the military, and the business world. He transforms his environment rather than letting it change him.Knapp R. LWW; 2018. Paperback; 416 pages.This updated second edition offers a plain-language guide to providing care to patients with a variety of respiratory disorders. The author uses an engaging style and humor along with her expertise to provide the essential information. The topics covered and the ease of reading make this book an ideal reference for new nurses or nurses new to the content. The topics covered include respiratory assessment, airway maintenance, oxygen delivery, ventilatory support, treating infection and inflammation, and chest drainage systems.Oluo I. Seal Press; 2019. Paperback; 255 pages.So You Want to Talk About Race is a book that can help the reader engage in conversations and actions to address racism. Through the lenses of her expertise and lived experiences, Oluo explores concepts associated with race such as racism, privilege, intersectionality, microaggressions, and the model minority myth. She provides a unique perspective that may help a person of privilege better understand how small actions can have a great impact on someone who has been affected by systemic racism. Oluo also suggests boundaries for people of color when engaging in these conversations. So You Want to Talk About Race is a quick and compelling book; it provides an overview that may highlight areas that the reader may wish to seek additional information about. A discussion guide is included, should you wish to have additional conversations with a group. Increasing your awareness can help you act intentionally to address racism.

&lt;i&gt;De novo&lt;/i&gt; Design of a Highly Specific Inhibitor of Integrin Αvβ6 for Pulmonary Fibrosis

We describe the de novo design of hyperstable inhibitory proteins that bind to human αvβ6 with sub-nanomolar affinity and with >1000x specificity over other RGD (Arg-Gly-Asp)-binding integrins. The crystal structure of the inhibitor closely matches the design model, with affinity and specificity arising not only from an RGDLXX(L/I)-containing loop but also a second loop that contacts the β6 subunit. The designed inhibitor blocks αvβ6 -mediated TGF-β signalling in vitro and specifically targets αvβ6 (+) tumors in vivo. When administered via intraperitoneal injection or as an inhaled therapeutic, the inhibitor reduces fibrotic burden in bleomycin induced lung fibrosis in mice. Taken together, these results illustrate the power of de novo protein design in creating highly specific integrin inhibitors with therapeutic potential for immuno-oncology and the treatment of pulmonary fibrosis, and highlight direct respiratory system delivery of small stable high affinity binding proteins as a new therapeutic modality.

Organic Solution Advanced Spray-Dried Microparticulate/Nanoparticulate Dry Powders of Lactomorphin for Respiratory Delivery: Physicochemical Characterization, In Vitro Aerosol Dispersion, and Cellular Studies.

The purpose of this study was to formulate Lactomorphin (MMP2200) in its pure state as spray-dried(SD) powders, and with the excipient Trehalose as co-spray-dried(co-SD) powders; for intranasal and deep lung administration with Dry Powder Inhalers (DPI). Lactomorphin is a glycopeptide which was developed for the control of moderate to severe pain. Particles were rationally designed and produced by advanced spray drying particle engineering in a closed mode from a dilute organic solution. Comprehensive physicochemical characterization using different analytical techniques was carried out to analyze the particle size, particle morphology, particle surface morphology, solid-state transitions, crystallinity/non-crystallinity, and residual water content. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR), and Confocal Raman Microscopy (CRM) confirmed the particles’ chemical homogeneity. The solubility and Partition coefficient (LogP) of Lactomorphin were determined by the analytical and computational methodology and revealed the hydrophilicity of Lactomorphin. A thermal degradation study was performed by exposing samples of solid-state Lactomorphin to a high temperature (62 °C) combined with zero relative humidity (RH) and to a high temperature (62 °C) combined with a high RH (75%) to evaluate the stability of Lactomorphin under these two different conditions. The solid-state processed particles exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device to reach lower airways. The cell viability resazurin assay showed that Lactomorphin is safe up to 1000 μg/mL on nasal epithelium cells, lung cells, endothelial, and astrocyte brain cells.

A decoy to neutralize SARS-CoV-2

Coronavirus Many efforts to develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the interaction between the spike protein, which decorates the surface of the virus, and its host receptor, human angiotensin-converting enzyme 2 (hACE2). Linsky et al. describe a de novo design strategy that allowed them to engineer decoy proteins that bind to the spike protein by replicating the hACE2 interface. The best decoy, CTC-445, bound with low nanomolar affinity, and selection of viral mutants that decrease binding is unlikely because this would also affect binding to hACE2. A bivalent version of CTC-445 bound even more tightly, neutralized SARS-CoV-2 infection of cells, and protected hamsters from a SARS-CoV-2 challenge. The stable decoy has the potential for respiratory therapeutic delivery. Science , this issue p. [1208][1] [1]: /lookup/doi/10.1126/science.abe0075

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2.

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

An evaluation of manual tidal volume and respiratory rate delivery during simulated resuscitation.

Excessive minute ventilation during cardiac arrest may cause lung injury and decrease the effectiveness of cardiopulmonary resuscitation (CPR). However, little is known about how clinicians deliver tidal volumes and respiratory rates during CPR. In this cross-sectional study, licensed practitioners attending an American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) course performed CPR and manual ventilation on a high-fidelity simulator during the megacode portion of the course. Delivered tidal volumes and respiratory rates were measured on a monitor. During the first scenario, results were not displayed to participants, but were displayed during the second scenario. Fifty-two clinicians participated in this study. Average height was 169 (157,178) cm. Pre-monitor display tidal volumes delivered were larger in male participants compared to female participants (684.6±134.4 vs 586.7±167.6ml, P=0.05). Those using medium-sized gloves delivered smaller tidal volumes than those using small or large gloves. Twenty-two (42.3%) delivered tidal volume in the range of 5-8ml/kg of predicted body weight for the simulation manikin, and 35 (67.3%) delivered tidal volumes with >20% variability among breaths. All participants met the target respiratory rate around 10 breaths/min. Tidal volume delivery varied greatly during manual ventilation and fewer than half participants delivered tidal volume at 5-8ml/kg to the manikin. Sex and glove size appeared to impact tidal volume delivery when the participants were unaware of what they were delivering. Participants were able to meet the target respiratory rate around 10 without audio or visual feedback.