Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade.

There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation. Consistent with this, we observed significantly increased lipid droplets, with subsequent mobilization to mitochondria. These changes were abrogated in cells deficient for the essential autophagy gene ATG5 Accordingly, inhibition of PLA2 significantly decreased lipid droplets, decreased oxidative phosphorylation, and increased apoptosis. Together, these results describe how treatment-induced autophagy provides nutrients for cancer cell survival and identifies novel cotreatment strategies to override this survival advantage.

Characterization of Fusarium oxysporum f. sp. pisi Associated with Root Rot of Field Pea in North Dakota and the Effects of Temperature on Aggressiveness.

Fusarium root rot is an important disease of field pea (Pisum sativum var. sativum L.) that occurs everywhere pea is grown, causing yield loss of up to 75%. Fusarium root rot is caused by a complex of Fusarium species, most notably Fusarium solani in the Pacific Northwest of the United States and F. avenaceum in the northern Great Plains of the United States and Canada. F. oxysporum f. sp. pisi (Fop) was frequently isolated from peas exhibiting root rot symptoms in North Dakota during recent surveys. Fop causes wilt (races 1, 5, and 6) and near wilt (race 2) on pea. However, its contribution to pea root rot remains unclear. Fop race was determined for isolates from North Dakota pea root rot surveys. ND Fop isolates were evaluated for root rot pathogenicity and aggressiveness at standard and elevated temperatures. Results from greenhouse wilt assays indicated that all Fop races exist in North Dakota, with race 2 most prevalent among the 25 North Dakota isolates evaluated. Root rot evaluations conducted at 21/18°C and 25/19°C day/night temperatures demonstrated that most Fop isolates were as aggressive or more aggressive than F. solani and F. avenaceum under both temperature regimes. Aggressiveness of Fop isolates tended to increase at elevated assay temperatures. Results from these experiments indicate that Fop may be an important contributor to the root rot complex of field pea in North Dakota and should be considered in integrated pest management strategies, including pea breeding efforts to improve resistance to Fusarium root rot.[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Efficacy of dental evacuation systems for aerosol exposure mitigation in dental clinic settings.

Dental personnel are ranked among the highest risk occupations for exposure to SARS-CoV-2 due to their close proximity to the patient's mouth and many aerosol generating procedures encountered in dental practice. One method to reduce aerosols in dental settings is the use of intraoral evacuation systems. Intraoral evacuation systems are placed directly into a patient's mouth and maintain a dry field during procedures by capturing liquid and aerosols. Although multiple intraoral dental evacuation systems are commercially available, the efficacy of these systems is not well understood. The objectives of this study were to evaluate the efficacy of four dental evacuation systems at mitigating aerosol exposures during simulated ultrasonic scaling and crown preparation procedures. We conducted real-time respirable (PM4) and thoracic (PM10) aerosol sampling during ultrasonic scaling and crown preparation procedures while using four commercially available evacuation systems: a high-volume evacuator (HVE) and three alternative intraoral systems (A, B, C). Four trials were conducted for each system. Respirable and thoracic mass concentrations were measured during procedures at three locations including (1) near the breathing zone (BZ) of the dentist, (2) edge of the dental operatory room approximately 0.9 m away from the mannequin mouth, and (3) hallway supply cabinet located approximately 1.5 m away from the mannequin mouth. Respirable and thoracic mass concentrations measured during each procedure were compared with background concentrations measured in each respective location. Use of System A or HVE reduced thoracic (System A) and respirable (HVE) mass concentrations near the dentist's BZ to median background concentrations most often during the ultrasonic scaling procedure. During the crown preparation, use of System B or HVE reduced thoracic (System B) and respirable (HVE or System B) near the dentist's BZ to median background concentrations most often. Although some differences in efficacy were noted during each procedure and aerosol size fraction, the difference in median mass concentrations among evacuation systems was minimal, ranging from 0.01 to 1.48 µg/m3 across both procedures and aerosol size fractions.

Direct-reading instruments for aerosols: A review for occupational health and safety professionals part 1: Instruments and good practices.

With advances in technology, there are an increasing number of direct-reading instruments available to occupational health and safety professionals to evaluate occupational aerosol exposures. Despite the wide array of direct-reading instruments available to professionals, the adoption of direct-reading technology to monitor workplace exposures has been limited, partly due to a lack of knowledge on how the instruments operate, how to select an appropriate instrument, and challenges in data analysis techniques. This paper presents a review of direct-reading aerosol instruments available to occupational health and safety professionals, describes the principles of operation, guides instrument selection based on the workplace and exposure, and discusses data analysis techniques to overcome these barriers to adoption. This paper does not cover all direct-reading instruments for aerosols but only those that an occupational health and safety professional could use in a workplace to evaluate exposures. Therefore, this paper focuses on instruments that have the most potential for workplace use due to their robustness, past workplace use, and price with regard to return on investment. The instruments covered in this paper include those that measure aerosol number concentration, mass concentration, and aerosol size distributions.

The Specificity of the Persistent IgM Neutralizing Antibody Response in Zika Virus Infections among Individuals with Prior Dengue Virus Exposure.

Dengue viruses (DENV) and Zika virus (ZIKV) are related mosquito-borne flaviviruses with similar disease manifestations, vector ecologies, and geographic ranges. The ability to differentiate these viruses serologically is vital due to the teratogenic nature of ZIKV and the potential confounding of preexisting cross-reactive anti-DENV antibodies. Here, we illustrate the kinetics of the IgM neutralizing antibody (NAb) response using longitudinal samples ranging from acute ZIKV infection to late convalescence from individuals with evidence of prior DENV infection. By serially depleting antibody isotypes prior to the neutralization assay, we determined that IgM contributes predominantly to ZIKV neutralization and is less cross-reactive than the IgG NAb. The IgM NAb peaked around 14 days (95% confidence interval [95% CI], 13 to 15) and had a median duration of 257 days (95% CI, 133 to 427). These results demonstrate the persistence of IgM NAb after ZIKV infection and imply its potential role in diagnosis, vaccine evaluation, serosurveillance, and research on flavivirus-host interactions.

Houston hurricane Harvey health (Houston-3H) study: assessment of allergic symptoms and stress after hurricane Harvey flooding.

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall. METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 unique participants from four sites across Harris County at two times: within approximately 1-month of Harvey (T1, n = 206) and approximately 12-months after Harvey (T2, n = 266), including 125 individuals who participated at both time points. Using a self-administered questionnaire, participants reported details on demographics, flood-related exposures, and health outcomes, including allergic symptoms and stress. RESULTS: The majority of participants reported hurricane-related flooding in their homes at T1 (79.1%) and T2 (87.2%) and experienced at least one allergic symptom after the hurricane (79.4% at T1 and 68.4% at T2). In general, flood-exposed individuals were at increased risk of upper respiratory tract allergic symptoms, reported at both the T1 and T2 time points, with exposures to dirty water and mold associated with increased risk of multiple allergic symptoms. The mean stress score of study participants at T1 was 8.0 ± 2.1 and at T2, 5.1 ± 3.2, on a 0-10 scale. Participants who experienced specific flood-related exposures reported higher stress scores when compared with their counterparts, especially 1 year after Harvey. Also, a supplementary paired-samples analysis showed that reports of wheezing, shortness of breath, and skin rash did not change between T1 and T2, though other conditions were less commonly reported at T2. CONCLUSION: These initial Houston-3H findings demonstrate that flooding experiences that occurred as a consequence of Hurricane Harvey had lasting impacts on the health of Houstonians up to 1 year after the hurricane.

Development and deployment of an at-home strength and conditioning program to support a phase I trial in persons with chronic spinal cord injury.

STUDY DESIGN: Nonrandomized clinical trial (NCT02354625). OBJECTIVES: As a part of a Phase I clinical trial to assess the safety of autologous human Schwann cells (ahSC) in persons with chronic spinal cord injury (SCI), participants engaged in a multimodal conditioning program pre- and post-ahSC transplantation. The program included a home-based strength and endurance training program to prevent lack of fitness and posttransplantation detraining from confounding potential ahSC therapeutic effects. This paper describes development, deployment, outcomes, and challenges of the home-based training program. SETTING: University-based laboratory. METHODS: Development phase: two men with paraplegia completed an 8-week laboratory-based 'test' of the home-based program. Deployment phase: the first four (two males, two females) participant cohort of the ahSC trial completed the program at home for 12 weeks pre and 20 weeks post ahSC transplant. RESULTS: Development phase: both participants improved their peak aerobic capacity (VO2peak) (≥17%), peak power output (POpeak) (≥8%), and time to exhaustion (TTE) (≥7%). Deployment phase: pretransplant training minimally increased fitness in the two male participants (≥6% POpeak and ≥9% TTE). The two women had no POpeak changes and slight TTE changes (+2.6 and -1.2%, respectively.) All four participants detrained during the posttransplant recovery period. After posttransplant retraining, all four participants increased TTE (4-24%), three increased VO2peak (≥11%), and two increased POpeak (≥7%). CONCLUSIONS: Home-based strength and condition programs can be effective and successfully included in therapeutic SCI trials. However, development of these programs requires substantial content knowledge and experience.

6 feet apart but working together.

Prior to COVID-19, the field of genetic counseling was responding to a workforce shortage in patient-facing roles through efforts to increase the training capacity within existing programs, as well as development of new programs. These efforts were hindered by the number and capacity of fieldwork training sites. COVID-19 heightened this barrier with a sudden restriction on student training for an indefinite period of time. The onset of these restrictions highlighted the need to think creatively and, more importantly, collaboratively for ways to not only expand but also maintain fieldwork training capacity. Described here are two different collaborative efforts in response to pandemic-related cancellations of important curriculum components: 1) the development of clinical simulation experiences and coursework shared between two ACGC accredited training programs; and 2) the creation of a virtual laboratory curriculum between an ACGC accredited training program and a non-academic laboratory partner. This Professional Issues paper illustrates how collaboration with our academic and non-academic colleagues benefits students, training programs and non-academic partners beyond the needs of the initial crisis of a global pandemic.

Using Context as an Assist in Word Solving: The Contributions of 25 Years of Research on the Interactive Strategies Approach.

Recently, there has been growing concern about how to most effectively support the literacy development of beginning and struggling readers with regard to helping them learn to effortlessly identify the huge number of words that proficient readers ultimately learn to read with automaticity. Some, noting the critical importance of phonics instruction in learning to read in an alphabetic writing system, take the position that students should attend only to alphabetic information in word-solving attempts. However, long-standing theories of the development of word-reading skills support the value of teaching students to use both alphabetic and contextual information in word solving in interactive and confirmatory ways. The authors summarize 25 years of research in which beginning and struggling readers were taught to use both code- and meaning/context-based strategies for word solving and were provided with explicit, responsive instruction focused on the alphabetic code. The authors present brief summaries of theoretical explanations of the word-learning process. Then, the authors summarize six experimental studies that, together, included students in kindergarten through fourth grade and involved the implementation of the Interactive Strategies Approach in the primary grades and an extension of the approach with middle elementary students with reading difficulties. The studies resulted in substantially improved reading outcomes among treatment versus business-as-usual groups. The authors contend that using both phonics- and context-based information facilitates the ability to build sight vocabulary, which in turn enables readers to turn their attention to the most important goal of literacy learning: meaning construction.

A randomized controlled trial of group cognitive remediation therapy for anorexia nervosa: Effects on set-shifting tasks for inpatient adults and adolescents.

OBJECTIVE: The aim of this randomized controlled trial with a parallel design was to evaluate the effect of brief, cognitive remediation therapy (CRT) for anorexia nervosa (AN) on set-shifting. METHOD: Two hundred seventy-five inpatient adults and adolescents with AN (mean age = 23.1; SD = 12.7) were randomly assigned (using simple randomization procedures) to either a CRT or control condition. All participants received treatment as usual; however, the CRT condition completed five CRT group sessions in lieu of other group therapies provided on the unit. Set-shifting abilities were evaluated by: (a) neuropsychological measures and (b) experimental cognitive behavior therapy thought records. Blinding of group assignment occurred during baseline assessment and ended following group commencement. RESULTS: Data from 135 CRT and 140 control condition participants were analyzed. On all neuropsychological measures, results revealed no between group condition effects, but did show statistically significant time effects, with medium to large effect sizes. Thought record analysis revealed a significant condition by age interaction effect where adults in the CRT condition generated significantly more alternative thoughts and had stronger believability of alternative thoughts than children, a trend that was not found in the control condition. This yielded moderate to large effect sizes of.0.56 and 0.72, respectively. DISCUSSION: Based on traditional neuropsychological measures, these findings do not suggest a differential effect of CRT for AN in the format applied. However, results suggest that CRT may have some increased beneficial cognitive effect for adults, as compared to children, based on thought record analysis.

Gerontological social work and cardiac rehabilitation.

Cardiac rehabilitation is a setting in which integrating social work services can benefit older adults. Many cardiac rehabilitation patients endorse symptoms of stress and depression following a cardiac event, impeding their ability to participate fully in cardiac rehabilitation services or recover from a heart attack. Gerontologically trained social workers can improve the care of older adults with heart disease in a variety of ways and this paper discusses the potential roles social workers can play in enhancing care. Two examples demonstrating how community academic partnerships can lead to improved options for older adults following a heart attack are discussed. First, using a microsystems approach, social workers embedded within cardiac rehabilitation may improve patient quality of life, address social service needs, provide mental health treatment, and assist in the completion of standard cardiac rehabilitation assessments. Second, using a macrosystems approach, social workers can help communities by developing partnerships to establish infrastructure for new cardiac rehabilitation clinics that are integrated with mental health services in rural areas. Social workers can serve an important role in addressing the psychological or social service needs of cardiac rehabilitation patients while increasing access to care.

Probability Models Based on Soil Properties for Predicting Presence-Absence of Pythium in Soybean Roots.

Associations between soil properties and Pythium groups on soybean roots were investigated in 83 commercial soybean fields in North Dakota. A data set containing 2877 isolates of Pythium which included 26 known spp. and 1 unknown spp. and 13 soil properties from each field were analyzed. A Pearson correlation analysis was performed with all soil properties to observe any significant correlation between properties. Hierarchical clustering, indicator spp., and multi-response permutation procedures were used to identify groups of Pythium. Logistic regression analysis using stepwise selection was employed to calculate probability models for presence of groups based on soil properties. Three major Pythium groups were identified and three soil properties were associated with these groups. Group 1, characterized by P. ultimum, was associated with zinc levels; as zinc increased, the probability of group 1 being present increased (α = 0.05). Pythium group 2, characterized by Pythium kashmirense and an unknown Pythium sp., was associated with cation exchange capacity (CEC) (α < 0.05); as CEC increased, these spp. increased. Group 3, characterized by Pythium heterothallicum and Pythium irregulare, were associated with CEC and calcium carbonate exchange (CCE); as CCE increased and CEC decreased, these spp. increased (α = 0.05). The regression models may have value in predicting pathogenic Pythium spp. in soybean fields in North Dakota and adjacent states.

Living With Chronic Pain After Spinal Cord Injury: A Mixed-Methods Study.

OBJECTIVE: To identify the relative importance of positive (facilitators) and negative (barriers) contributors to living with chronic pain after spinal cord injury (SCI). DESIGN: Mixed-methods: (1) Qualitative (n=35): individual, semistructured, open-ended interviews identifying facilitator/barrier themes; (2) Quantitative (n=491): converting the most common themes into statements and quantifying agreement with these in an online survey to determine relative importance, underlying dimensions, and their associations with perceived difficulty in dealing with pain. SETTING: University-based research setting and general community. PARTICIPANTS: Volunteers (N=526) with SCI experiencing moderate to severe chronic pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interview guides, facilitator/barrier statements, and pain inventories. RESULTS: Exploratory factor analyses reduced agreement ratings into 4 facilitators (information regarding pain and treatments, resilience, coping, medication use) and 5 barriers (poor health care communication, pain impact and limitations, poor communication about pain, difficult nature of pain, treatment concerns). Greater "pain impact and limitations," "difficult nature of pain," "poor communication from provider," lower "resilience," greater "medication use," and younger age predicted greater difficulty in dealing with pain (r=.75; F=69.02; P<.001). CONCLUSIONS: This study revealed multiple facilitators and barriers to living with chronic pain after SCI. The principal barrier, "poor health care communication," indicated that consumers do not receive adequate information from their health care providers regarding pain. "Information regarding pain and treatments" had greater agreement scores and factor loadings than all other facilitators, indicating that most participants view provider-patient communication and educational efforts regarding pain and pain management as priorities and critical needs. Further initiatives in these areas are important for improving pain management post-SCI.

A Simple and Disposable Sampler for Inhalable Aerosol.

The state-of-the-art for personal sampling for inhalable aerosol hazards is constrained by issues of sampler cost and complexity; these issues have limited the adoption and use of some samplers by practicing hygienists. Thus, despite the known health effects of inhalable aerosol hazards, personal exposures are routinely assessed for only a small fraction of the at-risk workforce. To address the limitations of current technologies for inhalable aerosol sampling, a disposable inhalable aerosol sampler was developed and evaluated in the laboratory. The new sampler is designed to be less expensive and simpler to use than existing technologies. The sampler incorporates a lightweight internal capsule fused to the sampling filter. This capsule-filter assembly allows for the inclusion of particles deposited on the internal walls and inlet, thus minimizing the need to wash or wipe the interior sampling cassette when conducting gravimetric analyses. Sampling efficiency and wall losses were tested in a low-velocity wind tunnel with particles ranging from 9.5 to 89.5 µm. The results were compared to the proposed low-velocity inhalability criterion as well as published data on the IOM sampler. Filter weight stability and time-to-equilibrium were evaluated as these factors affect the practicality of a design. Preliminary testing of the new sampler showed good agreement with both the IOM and the proposed low-velocity inhalability curve. The capsule and filter assemblies reached equilibrium within 25h of manufacturing when conditioned at elevated temperatures. After reaching equilibrium, the capsule-filter assemblies were stable within 0.01mg.

The effects of synthesis method on the physical and chemical properties of dextran coated iron oxide nanoparticles.

Iron oxide nanoparticles coated with dextran were synthesized via four variations on the co-precipitation method. The methods ranged from in situ formation of the nanoparticles within the dextran solution to the adsorption of dextran to the nanoparticle surface following nucleation and extensive washing. The timing of the addition of dextran into the reaction mixture was found to greatly influence the physical and chemical properties of the magnetic nanoparticles. Batches of dextran coated iron oxide nanoparticles were synthesized by each method in triplicate, and the nanoparticles were further crosslinked with epichlorohydrin. The properties of the nanoparticles such as size, percentage of dextran coating, stability in solution, crystallinity, and magnetic properties were evaluated. The simultaneous semi-two-step method injected the reducing agent and the dextran solution into the reaction vessel at the same time. This method resulted in the greatest batch-to-batch reproducibility of nanoparticle properties and the least variation in nanoparticles synthesized in the same batch. The two-step method resulted in the greatest variation of the characteristics examined between batches. The one-step method was synthesized with both five grams and one gram of dextran to investigate the effects of solution viscosity on the resulting nanoparticle characteristics. The one-step method with five grams of dextran resulted in nanoparticles with significantly smaller crystal sizes (5.4 ± 1.9 nm) and lower specific adsorption rate (SAR) values (138.4 ± 13.6 W/g) in an alternating magnetic field (58 kA/m, 292 kHz). However, this method resulted in nanoparticles that were very stable in PBS over 12 hours, which is most likely due to the greater dextran coating (60.0 ± 2.7 weight percent). For comparison, the simultaneous semi-two-step method generated nanoparticles 179.2 ± 18.3 nm in diameter (crystal size 12.1 ± 0.2 nm) containing 18.3 ± 1.2 weight percent dextran with a SAR value of 321.1 ± 137.3 W/g.

Identification and Pathogenicity of Pythium on Soybean in North Dakota.

The oomycete Pythium comprises one of the most important groups of seedling pathogens affecting soybean. There has been limited research on Pythium spp. pathogenic on soybean in the northern Great Plains. The objectives of this research were to isolate and identify Pythium spp. infecting soybean in North Dakota and to test their pathogenicity. Identification of Pythium spp. was achieved using molecular techniques and morphological features. A total of 26 known Pythium spp. and three unknown species were recovered from soybean seedling roots collected from 125 fields between 2011 and 2012. In 2011, the three most abundant species isolated were P. ultimum, Pythium sp. (unknown; GenBank HQ643777.1), and P. heterothallicum, representing 21, 16, and 12% of 2,675 isolates, respectively. More species and isolates were obtained in 2011, a wet and cool year, compared with 2012, which was dry and warm. The majority of Pythium spp. caused pre-emergence damping-off on soybean with less than 50% emergence in a 2-week test using infested soil at 23°C. In contrast, in the presence of P. orthogonon, P. nunn, or P. rostratifingens there was approximately 80% or greater emergence and most plants survived for several weeks, although lesions were observed on roots. Mortierella spp., a zygomycete, was commonly isolated along with Pythium spp. in 2012, but not in 2011. This is the first report of P. kashmirense, P. minus, P. periilum, P. rostratifingens, P. terrestris, P. viniferum, and P. violae as pathogens of soybean seedlings. In addition, this is the first report of P. kashmirense, P. viniferum, and P. terrestris in the United States.

An empirical model of human aspiration in low-velocity air using CFD investigations.

Computational fluid dynamics (CFD) modeling was performed to investigate the aspiration efficiency of the human head in low velocities to examine whether the current inhaled particulate mass (IPM) sampling criterion matches the aspiration efficiency of an inhaling human in airflows common to worker exposures. Data from both mouth and nose inhalation, averaged to assess omnidirectional aspiration efficiencies, were compiled and used to generate a unifying model to relate particle size to aspiration efficiency of the human head. Multiple linear regression was used to generate an empirical model to estimate human aspiration efficiency and included particle size as well as breathing and freestream velocities as dependent variables. A new set of simulated mouth and nose breathing aspiration efficiencies was generated and used to test the fit of empirical models. Further, empirical relationships between test conditions and CFD estimates of aspiration were compared to experimental data from mannequin studies, including both calm-air and ultra-low velocity experiments. While a linear relationship between particle size and aspiration is reported in calm air studies, the CFD simulations identified a more reasonable fit using the square of particle aerodynamic diameter, which better addressed the shape of the efficiency curve's decline toward zero for large particles. The ultimate goal of this work was to develop an empirical model that incorporates real-world variations in critical factors associated with particle aspiration to inform low-velocity modifications to the inhalable particle sampling criterion.

Computational fluid dynamics investigation of human aspiration in low velocity air: orientation effects on nose-breathing simulations.

An understanding of how particles are inhaled into the human nose is important for developing samplers that measure biologically relevant estimates of exposure in the workplace. While previous computational mouth-breathing investigations of particle aspiration have been conducted in slow moving air, nose breathing still required exploration. Computational fluid dynamics was used to estimate nasal aspiration efficiency for an inhaling humanoid form in low velocity wind speeds (0.1-0.4 m s(-1)). Breathing was simplified as continuous inhalation through the nose. Fluid flow and particle trajectories were simulated over seven discrete orientations relative to the oncoming wind (0, 15, 30, 60, 90, 135, 180°). Sensitivities of the model simplification and methods were assessed, particularly the placement of the recessed nostril surface and the size of the nose. Simulations identified higher aspiration (13% on average) when compared to published experimental wind tunnel data. Significant differences in aspiration were identified between nose geometry, with the smaller nose aspirating an average of 8.6% more than the larger nose. Differences in fluid flow solution methods accounted for 2% average differences, on the order of methodological uncertainty. Similar trends to mouth-breathing simulations were observed including increasing aspiration efficiency with decreasing freestream velocity and decreasing aspiration with increasing rotation away from the oncoming wind. These models indicate nasal aspiration in slow moving air occurs only for particles <100 µm.

High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies.

Inhalable lung surfactant-based carriers composed of synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG), along with paclitaxel (PTX), were designed and optimized as respirable dry powders using organic solution co-spray-drying particle engineering design. These materials can be used to deliver and treat a wide variety of pulmonary diseases with this current work focusing on lung cancer. In particular, this is the first time dry powder lung surfactant-based particles have been developed and characterized for this purpose. Comprehensive physicochemical characterization was carried out to analyze the particle morphology, surface structure, solid-state transitions, amorphous character, residual water content, and phospholipid bilayer structure. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy. PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX release was measured over weeks. In vitro cellular characterization on lung cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of paclitaxel from co-spray-dried DPPC/DPPG (co-SD DPPC/DPPG) lung surfactant-based carrier particles and the cytotoxicity of the particles via pulmonary cell viability analysis, fluorescent microscopy imaging, and transepithelial electrical resistance (TEER) testing at air-interface conditions. In vitro aerosol performance using a Next Generation Impactor™ (NGI™) showed measurable powder deposition on all stages of the NGI and was relatively high on the lower stages (nanometer aerodynamic size). Aerosol dispersion analysis of these high-performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3 µm with excellent aerosol dispersion performance as exemplified by high values of emitted dose, fine particle fractions, and respirable fractions.

Uncertainty in aspiration efficiency estimates from torso simplifications in computational fluid dynamics simulations.

Computational fluid dynamics (CFD) has been used to report particle inhalability in low velocity freestreams, where realistic faces but simplified, truncated, and cylindrical human torsos were used. When compared to wind tunnel velocity studies, the truncated models were found to underestimate the air's upward velocity near the humans, raising questions about aspiration estimation. This work compares aspiration efficiencies for particles ranging from 7 to 116 µm using three torso geometries: (i) a simplified truncated cylinder, (ii) a non-truncated cylinder, and (iii) an anthropometrically realistic humanoid body. The primary aim of this work is to (i) quantify the errors introduced by using a simplified geometry and (ii) determine the required level of detail to adequately represent a human form in CFD studies of aspiration efficiency. Fluid simulations used the standard k-epsilon turbulence models, with freestream velocities at 0.1, 0.2, and 0.4 m s(-1) and breathing velocities at 1.81 and 12.11 m s(-1) to represent at-rest and heavy breathing rates, respectively. Laminar particle trajectory simulations were used to determine the upstream area, also known as the critical area, where particles would be inhaled. These areas were used to compute aspiration efficiencies for facing the wind. Significant differences were found in both vertical velocity estimates and the location of the critical area between the three models. However, differences in aspiration efficiencies between the three forms were <8.8% over all particle sizes, indicating that there is little difference in aspiration efficiency between torso models.