Copper Stimulation of Tetrahydrocannabinol and Cannabidiol Production in Hemp (Cannabis sativa L.) Is Copper-Type, Dose, and Cultivar Dependent.

Copper (Cu) is an element widely used as a pesticide for the control of plant diseases. Cu is also known to influence a range of plant secondary metabolisms. However, it is not known whether Cu influences the levels of the major metabolites in hemp (Cannabis sativa L.), tetrahydrocannabinol (THC) and cannabidiol (CBD). This study investigated the impact of Cu on the levels of these cannabinoids in two hemp cultivars, Wife and Merlot, under field conditions, as a function of harvest time (August-September), Cu type (nano, bulk, or ionic), and dose (50, 100, and 500 ppm). In Wife, Cu caused significant temporal increases in THC and CBD production during plant growth, reaching increases of 33% and 31% for THC and 51% and 16.5% for CBD by harvests 3 and 4, respectively. CuO nanoparticles at 50 and 100 ppm significantly increased THC and CBD levels, compared to the control, respectively, by 18% and 27% for THC and 19.9% and 33.6% for CBD. These nanospecific increases coincided with significantly more Cu in the inflorescences (buds) than in the control and bulk CuO treatments. Contrarily, no temporal induction of the cannabinoids by Cu was noticed in Merlot, suggesting a cultivar-specific response to Cu. However, overall, in Merlot, Cu ions, but not particulate Cu, induced THC and CBD levels by 27% and 36%, respectively, compared to the control. Collectively, our findings provide information with contrasting implications in the production of these cannabinoids, where, dependent on the cultivar, metabolite levels may rise above the 0.3% regulatory threshold for THC but to a more profitable level for CBD. Further investigations with a wider range of hemp cultivars, CuO nanoparticle (NP) doses, and harvest times would clarify the significance and broader implications of the findings.

Results from Lung Cancer Screening Outreach Utilizing a Mobile CT Scanner in an Urban Area.

INTRODUCTION: Lung cancer screening using low-dose (LD) CT reduces lung cancer-specific and all-cause mortality in high-risk individuals, although significant barriers to screening remain. We assessed the outreach of a mobile lung cancer screening program to increase screening accessibility and early detection of lung cancer. METHODS: We placed a mobile CT unit in a high-traffic area in New York City and offered free screening to all eligible patients. Characteristics of the mobile screening cohort were compared with those of our hospital-based screening cohort. RESULTS: Between December 9, 2019, and January 30, 2020, a total of 216 patients underwent mobile LDCT screening. Compared with the hospital-based screening cohort, mobile screening participants were significantly more likely to be younger, be uninsured, and have lower smoking intensity and were less likely to meet 2013 US Preventive Services Task Force guidelines (but would meet their 2021 guidelines) and self-identify as White race and Hispanic ethnicity. Asian New Yorkers were substantially underrepresented in both hospital and mobile screening cohorts, compared with their level of representation in New York City. Two patients were diagnosed with lung cancer and were treated. Potentially clinically significant non-lung cancer findings were identified in 28.2%, most commonly moderate-severe coronary artery calcification and emphysema. CONCLUSIONS: Mobile LDCT screening is useful and effective in detecting lung cancer and other significant findings and may engage a distinct high-risk patient demographic. Disproportionately low screening rates among certain high-risk populations highlight the imperative of implementing strategies aimed at understanding health behaviors and access barriers for diverse populations. Effective care-navigation services, facilitating high-quality care for all patients, are critical.

A Collaborative Emergency Medicine and Radiology Pulmonary Nodule Program: Identification of Associated Efficacy and Outcomes.

PURPOSE: Incidental radiologic findings are commonplace, but the episodic nature of emergency department (ED) care makes it challenging to ensure that patients obtain appropriate follow-up. Rates of follow-up range from 30% to 77%, with some studies demonstrating that more than 30% have no follow-up at all. The aim of this study is to describe and analyze the outcomes of a collaborative emergency medicine and radiology initiative to establish a formal workflow for the follow-up of pulmonary nodules identified during ED care. METHODS: A retrospective analysis was performed of patients referred to the pulmonary nodule program (PNP). Patients were divided into two categories: those with follow-up and those who do not have post-ED follow-up. The primary outcome was determining follow-up rates and outcomes, including patients referred for biopsy. The characteristics of patients who completed follow-up compared with those lost to follow-up were also examined. RESULTS: A total of 574 patients were referred to the PNP. Initial follow-up was established in 390 (69.1%); 30.8% were considered lost to follow-up, and more than half of these patients did not respond to initial contact. There were minimal differences in characteristics between patients in these two categories. Of the 259 patients who completed PNP follow-up, 26 were referred for biopsy (13%). CONCLUSIONS: The PNP provided effective transitions of care and potentially improved patient health care. Strategies to further enhance follow-up adherence will provide iterative improvement of the program. The PNP provides an implementation framework for post-ED pulmonary nodule follow-up in other health care systems and can be modified for use with other incidental diagnostic findings.

Influence of CuO Nanoparticle Aspect Ratio and Surface Charge on Disease Suppression in Tomato (Solanum lycopersicum).

Nanoparticles (NPs) have been shown to deliver micronutrients to plants to improve health, increase biomass, and suppress disease. Nanoscale properties such as morphology, size, composition, and surface chemistry have all been shown to impact nanomaterial interactions with plant systems. An organic-ligand-free synthesis method was used to prepare positively charged copper oxide (CuO) nanospikes, negatively charged CuO nanospikes, and negatively charged CuO nanosheets with exposed (001) crystal faces. X-ray photoelectron spectroscopy measurements show that the negative charge correlates to increased surface concentration of O on the NP surface, whereas relatively higher Cu concentrations are observed on the positively charged surfaces. The NPs were then used to treat tomato (Solanum lycopersicum) grown in soil infested with Fusarium oxysporum f. sp. lycopersici under greenhouse conditions. The negatively charged CuO significantly reduced disease progression and increased biomass, while the positively charged NPs and a CuSO4 salt control had little impact on the plants. Self-assembled monolayers were used to mimic the leaf surface to understand the intermolecular interactions between the NPs and the plant leaf; the data demonstrate that NP electrostatics and hydrogen-bonding interactions play an important role in adsorption onto leaf surfaces. These findings have important implications for the tunable design of materials as a strategy for the use of nano-enabled agriculture to increase food production.

Machine Learning-Assisted Carbon Dot Synthesis: Prediction of Emission Color and Wavelength.

Carbon dots (CDs) have attracted great attention in a range of applications due to their bright photoluminescence, high photostability, and good biocompatibility. However, it is challenging to design CDs with specific emission properties because the syntheses involve many parameters, and it is not clear how each parameter influences the CD properties. To help bridge this gap, machine learning, specifically an artificial neural network, is employed in this work to characterize the impact of synthesis parameters on and make predictions for the emission color and wavelength for CDs. The machine reveals that the choice of reaction method, purification method, and solvent relate more closely to CD emission characteristics than the reaction temperature or time, which are frequently tuned in experiments. After considering multiple models, the best performing machine learning classification model achieved an accuracy of 94% in predicting relative to actual color. In addition, hybrid (two-stage) models incorporating both color classification and an artificial neural network k-ensemble model for wavelength prediction through regression performed significantly better than either a standard artificial neural network or a single-stage artificial neural network k-ensemble regression model. The accuracy of the model predictions was evaluated against CD emission wavelengths measured from experiments, and the minimum mean average error is 25.8 nm. Overall, the models developed in this work can effectively predict the photoluminescence emission of CDs and help design CDs with targeted optical properties.

Adding value in the era of COVID-19: Increasing usage of a patient-centered radiology consultation service.

OBJECTIVE: To examine the effects of COVID-19 pandemic on our department's Radiology Consultation Service (RCS) related to breast imaging, and how utilization of the provided services may have differed as compared to prior to the pandemic. MATERIALS AND METHODS: A retrospective cohort study of patients and health care providers who consulted the RCS, as well as those patients who had a screening mammogram and/or ultrasound between January 1, 2019 and September 1, 2020. Consultations were performed by an RRA, RN and one of 17 breast imaging radiologists assigned to consults on daily. Descriptive statistics were performed to describe the study subject population. RESULTS: Between January 1, 2020 and July 31, 2020, a total of 1623 consultations were performed, in comparison to the control period from the year prior (January 1, 2019 to July 31, 2019), when a total of 1398 consultations were performed, representing a 16% increase in one year. Between March 1, 2020 and June 30, 2020, a total of 679 consultations were performed, in comparison to the control period from the year prior (March 1, 2019 to June 30, 2019), when 583 consultations were performed, representing a 16.5% increase in a four-month period. 350 out of 679 (36.8%) consultations addressed COVID concerns. CONCLUSIONS: While much of radiology experienced an unprecedented decrease in imaging studies during the initial peak of COVID-19 crisis, the RCS at our institution showed a significant increase in services provided, evolving to address pressing concerns related to COVID-19.

Investigation of the Post-Synthetic Confinement of Fluorous Liquids Inside Mesoporous Silica Nanoparticles.

Perfluorocarbon (PFC) filled nanoparticles are increasingly being investigated for various biomedical applications. Common approaches for PFC liquid entrapment involve surfactant-based emulsification and Pickering emulsions. Alternatively, PFC liquids are capable of being entrapped inside hollow nanoparticles via a postsynthetic loading method (PSLM). While the methodology for the PSLM is straightforward, the effect each loading parameter has on the PFC entrapment has yet to be investigated. Previous work revealed incomplete filling of the hollow nanoparticles. Changing the loading parameters was expected to influence the ability of the PFC to fill the core of the nanoparticles. Hence, it would be possible to model the loading mechanism and determine the influence each factor has on PFC entrapment by tracking the change in loading yield and efficiency of PFC-filled nanoparticles. Herein, neat PFC liquid was loaded into silica nanoparticles and extracted into aqueous phases while varying the sonication time, concentration of nanoparticles, volume ratio between aqueous and fluorous phases, and pH of the extraction water. Loading yields and efficiency were determined via 19F nuclear magnetic resonance and N2 physisorption isotherms. Sonication time was indicated to have the strongest correlation to loading yield and efficiency; however, method validation revealed that the current model does not fully explain the loading capabilities of the PSLM. Confounding variables and more finely controlled parameters need to be considered to better predict the behavior and loading capacity by the PSLM and warrants further study.

Influence of the Spatial Distribution of Cationic Functional Groups at Nanoparticle Surfaces on Bacterial Viability and Membrane Interactions.

While positively charged nanomaterials induce cytotoxicity in many organisms, much less is known about how the spatial distribution and presentation of molecular surface charge impact nanoparticle-biological interactions. We systematically functionalized diamond nanoparticle surfaces with five different cationic surface molecules having different molecular structures and conformations, including four small ligands and one polymer, and we then probed the molecular-level interaction between these nanoparticles and bacterial cells. Shewanella oneidensis MR-1 was used as a model bacterial cell system to investigate how the molecular length and conformation of cationic surface charges influence their interactions with the Gram-negative bacterial membranes. Nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) demonstrate the covalent modification of the nanoparticle surface with the desired cationic organic monolayers. Surprisingly, bacterial growth-based viability (GBV) and membrane damage assays both show only minimal biological impact by the NPs functionalized with short cationic ligands within the concentration range tested, yet NPs covalently linked to a cationic polymer induce strong cytotoxicity, including reduced cellular viability and significant membrane damage at the same concentration of cationic groups. Transmission electron microscopy (TEM) images of these NP-exposed bacterial cells show that NPs functionalized with cationic polymers induce significant membrane distortion and the production of outer membrane vesicle-like features, while NPs bearing short cationic ligands only exhibit weak membrane association. Our results demonstrate that the spatial distribution of molecular charge plays a key role in controlling the interaction of cationic nanoparticles with bacterial cell membranes and the subsequent biological impact. Nanoparticles functionalized with ligands having different lengths and conformations can have large differences in interactions even while having nearly identical zeta potentials. While the zeta potential is a convenient and commonly used measure of nanoparticle charge, it does not capture essential differences in molecular-level nanoparticle properties that control their biological impact.

Cobalt Release from a Nanoscale Multiphase Lithiated Cobalt Phosphate Dominates Interaction with Shewanella oneidensis MR-1 and Bacillus subtilis SB491.

Cobalt phosphate engineered nanomaterials (ENMs) are an important class of materials that are used as lithium ion battery cathodes, catalysts, and potentially as super capacitors. As production of these nanomaterials increases, so does the likelihood of their environmental release; however, to date, there are relatively few investigations of the impact of nanoscale metal phosphates on biological systems. Furthermore, nanomaterials used in commercial applications are often multiphase materials, and analysis of the toxic potential of mixtures of nanomaterials has been rare. In this work, we studied the interactions of two model environmental bacteria, Shewanella oneidensis MR-1 and Bacillus subtilis, with a multiphase lithiated cobalt phosphate (mLCP) nanomaterial. Using a growth-based viability assay, we found that mLCP was toxic to both bacteria used in this study. To understand the observed toxicity, we screened for production of reactive oxygen species (ROS) and release of Co2+ from mLCP using three abiotic fluorophores. We also used Newport Green DCF dye to show that cobalt was taken up by the bacteria after mLCP exposure. Using transmission electron microscopy, we noted that the mLCP was not associated with the bacterial cell surface. In order for us to further probe the mechanism of interaction of mLCP, the bacteria were exposed to an equivalent dose of cobalt ions that dissolved from mLCP, which recapitulated the changes in viability when the bacteria were exposed to mLCP, and it also recapitulated the observed bacterial uptake of cobalt. Taken together, this implicates the release of cobalt ions and their subsequent uptake by the bacteria as the major toxicity mechanism of mLCP. The properties of the ENM govern the release rate of cobalt, but the toxicity does not arise from nanospecific effects-and importantly, the chemical composition of the ENM may dictate the oxidation state of the metal centers and thus limit ROS production.

Chronic exposure to complex metal oxide nanoparticles elicits rapid resistance in Shewanella oneidensis MR-1.

Engineered nanoparticles are incorporated into numerous emerging technologies because of their unique physical and chemical properties. Many of these properties facilitate novel interactions, including both intentional and accidental effects on biological systems. Silver-containing particles are widely used as antimicrobial agents and recent evidence indicates that bacteria rapidly become resistant to these nanoparticles. Much less studied is the chronic exposure of bacteria to particles that were not designed to interact with microorganisms. For example, previous work has demonstrated that the lithium intercalated battery cathode nanosheet, nickel manganese cobalt oxide (NMC), is cytotoxic and causes a significant delay in growth of Shewanella oneidensis MR-1 upon acute exposure. Here, we report that S. oneidensis MR-1 rapidly adapts to chronic NMC exposure and is subsequently able to survive in much higher concentrations of these particles, providing the first evidence of permanent bacterial resistance following exposure to nanoparticles that were not intended as antibacterial agents. We also found that when NMC-adapted bacteria were subjected to only the metal ions released from this material, their specific growth rates were higher than when exposed to the nanoparticle. As such, we provide here the first demonstration of bacterial resistance to complex metal oxide nanoparticles with an adaptation mechanism that cannot be fully explained by multi-metal adaptation. Importantly, this adaptation persists even after the organism has been grown in pristine media for multiple generations, indicating that S. oneidensis MR-1 has developed permanent resistance to NMC.

Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a.

Wound healing is a physiological reparative response to injury and a well-orchestrated process that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, and wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. Herein, we investigate the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to high glucose in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~3.5-fold) four days post-wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to ~80%), increased granulation tissue thickness (by 2.5-fold) and accelerated wound closure (53% after nine days) compared to scrambled anti-miR controls in db/db mice. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene SMAD1 in ECs nine days post-wounding of diabetic mice. In addition, high glucose reduced activity of the SMAD1-3'-UTR. Diabetic dermal wounds treated with LNA-anti-miR-26a had increased expression of ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.

Mental Health Screening Outcomes in a Pediatric Specialty Care Setting.

OBJECTIVE: To evaluate whether a psychosocial screening program that included free and flexible access to mental health (MH) consultation resulted in increased rate of consultations. STUDY DESIGN: This is a post hoc review of a clinical screening program in a pediatric food allergy clinic in New York City. Screening was limited to 2 days per week, providing an opportunity to compare screened and nonscreened cohorts. Previous results from more than 1000 other families were analyzed to create the 1-page screening questionnaire. Participants were children with allergies and their parents who sought care at the clinic between March and September 2013. Parents were screened for distress and quality of life burden related to their child's allergy, and children were screened for anxiety, bullying, and quality of life. The predefined primary outcome was the percentage of families who received the free MH consultation after screening vs no-screening days in the allergy clinic. RESULTS: The 3143 encounters during the study period included 1171 on screening days and 1972 on no-screening days. Most (86%) eligible families completed the screen. Almost one-half (44%) met the initial screening thresholds. A total of 71 families (6.1% of screening days encounters) were referred to a MH consultation after a secondary review, but only 11 (1% of screening days encounters) scheduled a MH appointment. Eighteen families from the no-screening days came to a MH evaluation (1% of no-screening days encounters). CONCLUSION: Screening did not lead to enhanced MH follow-up. Resources may be better used on ensuring the availability of MH care rather than on screening in pediatric specialty clinics.

MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling.

RATIONALE: The rapid induction and orchestration of new blood vessels are critical for tissue repair in response to injury, such as myocardial infarction, and for physiological angiogenic responses, such as embryonic development and exercise. OBJECTIVE: We aimed to identify and characterize microRNAs (miR) that regulate pathological and physiological angiogenesis. METHODS AND RESULTS: We show that miR-26a regulates pathological and physiological angiogenesis by targeting endothelial cell (EC) bone morphogenic protein/SMAD1 signaling in vitro and in vivo. MiR-26a expression is increased in a model of acute myocardial infarction in mice and in human subjects with acute coronary syndromes. Ectopic expression of miR-26a markedly induced EC cycle arrest and inhibited EC migration, sprouting angiogenesis, and network tube formation in matrigel, whereas blockade of miR-26a had the opposite effects. Mechanistic studies demonstrate that miR-26a inhibits the bone morphogenic protein/SMAD1 signaling pathway in ECs by binding to the SMAD1 3'-untranslated region, an effect that decreased expression of Id1 and increased p21(WAF/CIP) and p27. In zebrafish, miR-26a overexpression inhibited formation of the caudal vein plexus, a bone morphogenic protein-responsive process, an effect rescued by ectopic SMAD1 expression. In mice, miR-26a overexpression inhibited EC SMAD1 expression and exercise-induced angiogenesis. Furthermore, systemic intravenous administration of an miR-26a inhibitor, locked nucleic acid-anti-miR-26a, increased SMAD1 expression and rapidly induced robust angiogenesis within 2 days, an effect associated with reduced myocardial infarct size and improved heart function. CONCLUSIONS: These findings establish miR-26a as a regulator of bone morphogenic protein/SMAD1-mediated EC angiogenic responses, and that manipulating miR-26a expression could provide a new target for rapid angiogenic therapy in ischemic disease states.

Effects of presentation mode and repeated familiarization on intelligibility of dysarthric speech.

Clinical measures of speech intelligibility are widely used as one means of characterizing the speech of individuals with dysarthria. Many variables associated with both the speaker and the listener contribute to what is actually measured as intelligibility. The present study explored the effects of presentation modality (audiovisual vs. audio-only information) and the effects of speaker-specific familiarization across 4 trials on the intelligibility of speakers with mild and severe dysarthria associated with cerebral palsy. Results revealed that audiovisual information did not enhance intelligibility relative to audio-only information for 4 of the 5 speakers studied. The one speaker whose intelligibility increased when audiovisual information was presented had the most severe dysarthria and concomitant motor impairments. Results for speakerspecific repeated familiarization were relatively homogeneous across speakers, demonstrating significant intelligibility score improvements across 4 trials and, in particular, a significant improvement in intelligibility between the 1st and 4th trials.