Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803 in vitro and in vivo in NB xenografts.

The prognosis for children with recurrent and/or refractory neuroblastoma (NB) is dismal. The receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is highly expressed on the surface of NB cells, provides a potential target for novel immunotherapeutics. Anti-ROR1 chimeric antigen receptor engineered ex vivo expanded peripheral blood natural killer (anti-ROR1 CAR exPBNK) cells represent this approach. N-803 is an IL-15 superagonist with enhanced biological activity. In this study, we investigated the in vitro and in vivo anti-tumor effects of anti-ROR1 CAR exPBNK cells with or without N-803 against ROR1+ NB models. Compared to mock exPBNK cells, anti-ROR1 CAR exPBNK cells had significantly enhanced cytotoxicity against ROR1+ NB cells, and N-803 further increased cytotoxicity. High-dimensional analysis revealed that N-803 enhanced Stat5 phosphorylation and Ki67 levels in both exPBNK and anti-ROR1 CAR exPBNK cells with or without NB cells. In vivo, anti-ROR1 CAR exPBNK plus N-803 significantly (p < 0.05) enhanced survival in human ROR1+ NB xenografted NSG mice compared to anti-ROR1 CAR exPBNK alone. Our results provide the rationale for further development of anti-ROR1 CAR exPBNK cells plus N-803 as a novel combination immunotherapeutic for patients with recurrent and/or refractory ROR1+ NB.

The surge in heart rate and blood pressure at respiratory event termination is dampened in children with down syndrome.

BACKGROUND: Children with Down syndrome (DS) have a high prevalence of sleep disordered breathing (SDB) and altered cardiovascular autonomic control. We aimed to analyze the effect of DS on the surge in heart rate (HR) and pulse transit time (PTT, an inverse surrogate measure of blood pressure change) at respiratory event termination. METHODS: 44 children (3-19 y) with DS and 44 typically developing (TD) children matched for SDB severity, age and sex underwent overnight polysomnography. Multilevel modelling determined the effect of DS on HR and PTT changes between a 10s pre-event to the latter half of each respiratory event (late-event) and 15s post-event during NREM and REM, accounting for SDB severity and event length. RESULTS: The children with DS had a significantly smaller % change in HR late-event to post-event (NREM: DS 26.4 % ± 17.5 % (mean ± SD), TD 30.7 % ± 21.0 %; REM DS 16.9 % ± 15.3 %, TD 21.0 % ± 14.0 %; p < 0.05 for both) compared with TD children for obstructive events, and central events (13.2 % ± 17.0 %, TD 18.8 % ± 17.0 %; p < 0.01) during REM. %change in PTT was significantly smaller in the DS group during NREM and REM from pre-event and late-event to post-event compared with TD children for obstructive and central events. CONCLUSION: These results suggest children with DS have dampened HR and BP responses to respiratory events compared with TD children. Whether this is symptomatic of autonomic dysfunction or a protective factor for the cardiovascular system in children with DS remains to be elucidated.

Effects of saline submersion at body temperature on airway supportive devices including a novel nasopharyngeal device produced using 3D-printing.

PURPOSE: This study investigated dimension changes of various nasopharyngeal airways, including a novel self-supporting device, after saline submersion at body temperature to simulate in-vivo use. Dimension changes over time may reduce efficacy during long-term use and require sizing adjustments or limits on duration of use. MATERIALS AND METHODS: Cuffless Covidien endotracheal tubes, pediatric Rusch fixed flange polyvinyl chloride nasal airway tubes, pediatric Rusch Robertazzi style Mediprene nasal airway tubes, and novel silicone elastomer self-supporting nasopharyngeal airways were fully submerged in 0.9 % normal saline solution incubated at 37 degrees Celsius for 15 days. All devices had tube length and wall thickness measured after 0, 1, 2, 3, 4, 5, 10, and 15 days. The 95 % confidence intervals of tube dimensions at each date were compared with the 95 % confidence intervals at day 0. RESULTS: The Covidien ET tube, Rusch PVC NPA, and ssNPA tube lengths and wall thicknesses did not change significantly over 15 days. The Rusch Mediprene NPAs had a statistically significant increase in length starting at day 1 and wall thickness at day 2. CONCLUSIONS: The novel ssNPA did not expand in the in-vitro environment, supporting its safety for extended use. The PVC NPA and ET tube dimensions also remained stable. However, the Rusch Mediprene NPAs had significant length expansion after 1 day of submersion, indicating a considerable risk of expansion during extended use with potential implications for patient care. Silicone and PVC NPA dimensions remained stable when saturated, indicating these materials may be more appropriate for extended use.

A Diels-Alder probe for discovery of natural products containing furan moieties.

Natural products (NPs) are fantastic sources of inspiration for novel pharmaceuticals, oftentimes showing unique bioactivity against interesting targets. Specifically, NPs containing furan moieties show activity against a variety of diseases including fungal infections, and cancers. However, it is challenging to discover and isolate these small molecules from cell supernatant. The work described herein showcases the development of a molecular probe that can covalently modify furan moieties via a [4 + 2] Diels-Alder cycloaddition, making them easily identifiable on liquid chromatography-mass spectrometry (LC-MS). The molecular probe, which undergoes this reaction with a variety of furans, was designed with both a UV-tag and a mass tag to enable easy identification. The probe has been tested with a variety of purified furans, including natural products, methylenomycin furan (MMF) hormones, and MMF derivatives. Moreover, the molecular probe has been tested in crude supernatants of various Streptomyces strains and enables identification of MMFs.

The changing landscape of electrical stimulation language mapping with subdural electrodes and stereoelectroencephalography for pediatric epilepsy: A literature review and commentary.

Electrical stimulation mapping (ESM) is used to locate the brain areas supporting language directly within the human cortex to minimize the risk of functional decline following epilepsy surgery. ESM is completed by utilizing subdural grid or depth electrodes (stereo-electroencephalography [sEEG]) in combination with behavioral evaluation of language. Despite technological advances, there is no standardized method of assessing language during pediatric ESM. To identify current clinical practices for pediatric ESM of language, we surveyed neuropsychologists in the Pediatric Epilepsy Research Consortium. Results indicated that sEEG is used for functional mapping at >80% of participating epilepsy surgery centers (n = 13/16) in the United States. However, >65% of sites did not report a standardized protocol to map language. Survey results indicated a clear need for practice recommendations regarding ESM of language. We then utilized PubMed/Medline and PsychInfo to identify 42 articles that reported on ESM of language, of which 18 met inclusion criteria, which included use of ESM/signal recording to localize language regions in children (<21 years) and a detailed account of the procedure and language measures used, and region-specific language localization outcomes. Articles were grouped based on the language domain assessed, language measures used, and the brain regions involved. Our review revealed the need for evidence-based clinical guidelines for pediatric language paradigms during ESM and a standardized language mapping protocol as well as standardized reporting of brain regions in research. Relevant limitations and future directions are discussed with a focus on considerations for pediatric language mapping.

Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A.

Antifibrinolytic drugs are used extensively for on-demand treatment of severe acute bleeding. Controlling fibrinolysis may also be an effective strategy to prevent or lessen chronic recurring bleeding in bleeding disorders such as hemophilia A (HA), but current antifibrinolytics have unfavorable pharmacokinetic profiles. Here, we developed a long-lasting antifibrinolytic using small interfering RNA (siRNA) targeting plasminogen packaged in clinically used lipid nanoparticles (LNPs) and tested it to determine whether reducing plasmin activity in animal models of HA could decrease bleeding frequency and severity. Treatment with the siRNA-carrying LNPs reduced circulating plasminogen and suppressed fibrinolysis in wild-type and HA mice and dogs. In HA mice, hemostatic efficacy depended on the injury model; plasminogen knockdown improved hemostasis after a saphenous vein injury but not tail vein transection injury, suggesting that saphenous vein injury is a murine bleeding model sensitive to the contribution of fibrinolysis. In dogs with HA, LNPs carrying siRNA targeting plasminogen were as effective at stabilizing clots as tranexamic acid, a clinical antifibrinolytic, and in a pilot study of two dogs with HA, the incidence of spontaneous or excess bleeding was reduced during 4 months of prolonged knockdown. Collectively, these data demonstrate that long-acting antifibrinolytic therapy can be achieved and that it provides hemostatic benefit in animal models of HA.

Impact Deceleration Differences on Natural Grass Versus Synthetic Turf High School Football Fields.

American football has the highest rate of concussions in United States high school sports. Within American football, impact against the playing surface is the second-most common mechanism of injury. The objective of this study was to determine if there is a difference in impact deceleration between natural grass and synthetic turf high school football fields. A Century Body Opponent Bag (BOB) manikin was equipped with a Riddell football helmet and 3 accelerometers were placed on the forehead, apex of the head, and right ear. The manikin was dropped from a stationary position onto its front, back, and left side onto natural grass (n = 10) and synthetic turf (n = 9) outdoor football fields owned and maintained by public and private institutions on O'ahu, Hawai'i. Data was collected on 1,710 total drops. All accelerometers in forward and backward falls, and 1 accelerometer in side falls showed significantly greater impact deceleration on synthetic turf compared to the natural grass surfaces (P < .05). The results of this study provide evidence-based rationale to inform youth sports policies, particularly those aimed at injury prevention through safer playing environments and equipment.

Association of Fentanyl Test Strip Use, Perceived Overdose Risk, and Naloxone Possession among People Who Use Drugs.

Background: As opioid overdoses continue rising, interventions are needed to expand naloxone carriage, an opioid overdose reversal agent. Use of fentanyl test strips (FTS) might promote naloxone carriage. This study examines the relationship between FTS use, perceived overdose risk, and naloxone carriage in Wisconsin, United States. Methods: In a survey of people who use drugs (n = 341) in southern Wisconsin, respondents were asked about FTS use, perceived overdose risk, and how often they (1) have naloxone, (2) have more than one dose of naloxone, and (3) the number of naloxone doses possessed currently. Likert responses were mapped to an integer scale. Ordinal and linear multivariable regression examined the relationship between FTS use and study outcomes while adjusting for respondent characteristics. Results: Most respondents were male (59.6%), identified heroin as their drug of choice (70.7%) and reported intravenous use (87.9%). In unadjusted models, FTS use was associated with more often having naloxone (OR: 2.10; p = 0.005), more often having multiple naloxone doses (OR: 2.98; p < 0.001), and possessing a greater number of naloxone doses (dose count difference: 2.85; p = 0.001). In adjusted models, FTS use was associated with more often having multiple naloxone doses (OR: 2.29; p = 0.005) and possessing a greater number of naloxone doses (dose count difference: 2.25, p = 0.020). Conclusions: Individuals who use FTS more often carry multiple doses relative to individuals who do not use FTS. Given that naloxone carriage is critical for reducing opioid overdose risk, expanding FTS use may offer a strategy to reduce opioid overdose rates via improved naloxone carriage.

Anticipation or avoidance: internal medicine resident experiences performing invasive bedside procedures.

Background: Internal Medicine (IM) residents are required to perform bedside procedures for diagnostic and therapeutic purposes. Residents' experiences with procedures vary widely, for unclear reasons. Objective: To explore IM residents' experiences with performing bedside procedures and to identify barriers and facilitators to obtaining sufficient experience. Methods: Using an inductive, thematic approach, we conducted five individual semi-structured interviews and one focus group with seven IM residents (12 residents in total) during the 2017-2018 academic year at a Canadian tertiary care centre. We used iterative, open-ended questions to elicit residents' experiences, and barriers and facilitators, to performing bedside procedures. Transcripts were analyzed for themes using Braun and Clarke's method. Results: We identified four themes 1) Patient-specific factors such as body habitus and procedure urgency; 2) Systems factors such as time constraints and accessibility of materials; 3) Faculty factors including availability to supervise, comfort level, and referral preferences, and 4) Resident-specific factors including preparation, prior experiences, and confidence. Some residents expressed procedure-related anxiety and avoidance. Conclusion: Educational interventions aimed to improve procedural efficiency and ensure availability of supervisors may help facilitate residents to perform procedures, yet may not address procedure-related anxiety. Further study is required to understand better how procedure-averse residents can gain confidence to seek out procedures.

Contexte: Les résidents en médecine interne (MI) sont amenés à effectuer des procédures au chevet du patient à des fins diagnostiques et thérapeutiques. Les expériences des résidents en lien avec ces procédures varient considérablement, et ce sans raison évidente. Objectif: Explorer les expériences des résidents en MI lors des procédures effectuées au chevet du patient et identifier les facteurs qui entravent ou, au contraire, facilitent l'acquisition d'une expérience suffisante. Méthodes: En utilisant une approche inductive et thématique, nous avons mené cinq entrevues individuelles semi-structurées et un groupe de discussion avec sept résidents de MI (12 résidents au total) dans un centre de soins tertiaires canadien au cours de l'année universitaire 2017-2018. Nous avons utilisé des questions ouvertes itératives pour recueillir les expériences des résidents lors des procédures faites au chevet du patient, ainsi qu'identifier les obstacles et les facilitateurs de ces interventions. Les transcriptions d'entrevues ont été analysées pour identifier les thèmes émergents selon la méthode de Braun et Clarke. Résultats: Nous avons relevé quatre thèmes : 1) les facteurs spécifiques aux patients comme la morphologie du patient et l'urgence de la procédure; 2) les facteurs systémiques comme les contraintes de temps et l'accessibilité du matériel; 3) les facteurs liés corps professoral, notamment leur disponibilité pour superviser, leur niveau de confort et leur propension à orienter certaines procédures vers d'autres collègues; et 4) les facteurs spécifiques aux résidents, à savoir la préparation, les expériences antérieures et la confiance. Certains résidents ont exprimé vivre de l'anxiété face aux procédures et de l'évitement. Conclusion: Les initiatives éducatives visant à améliorer l'efficacité des procédures et à assurer la disponibilité de superviseurs peuvent faciliter leur réalisation par les résidents, mais elles peuvent ne pas atténuer l'anxiété reliée aux procédures. Des études supplémentaires sont nécessaires pour mieux comprendre comment accroître la confiance des résidents qui sont réticents face aux procédures au chevet du patient.

Chelation-Based Route to Aluminum-Free Layered Transition Metal Carbides (MXenes).

MXenes are of much interest because of their electrochemical, electronic, and surface chemical properties that arise from their structure and stoichiometry. The integrity and the nature of the terminal groups on the basal planes of MXene sheets depend strongly on the method used to etch the parent MAX (M = transition metal, A = Al, X = C, N, B) compound. Aluminum removal typically involves a high concentration of aqueous HF, HCl/LiF mixtures, or fluoride solutions of strong acids. HF etching is problematic because it leaves insoluble AlF3 in the product, degrades the crystallinity of the nanosheets, and results in the termination of the basal planes with F, O, or OH groups. Here, we demonstrate the use of HF at a low concentration in tandem with a chelating agent, N,N'-dihydroxyoctanediamide (suberohydroxamic acid), to selectively etch the archetypical MAX compound Ti3AlC2 at room temperature. X-ray absorption spectroscopy (XAS) of the etched materials shows that the carbide nature of bonding in the parent MAX structure is retained in the MXene layers. The stability of the MXene in aqueous suspensions is also significantly improved relative to MXene products made by etching in concentrated HF solutions.

Assessing 'readiness' by tracking fluctuations in daily sleep duration and their effects on daily mood, motivation, and sleepiness.

STUDY OBJECTIVES: Consumer sleep trackers issue daily guidance on 'readiness' without clear empirical basis. We investigated how self-rated mood, motivation, and sleepiness (MMS) levels are affected by daily fluctuations in sleep duration, timing, and efficiency and overall sleep regularity. We also determined how temporally specific these associations are. METHODS: 119 healthy university students (64 female, mean age = 22.54 ± 1.74 years) wore a wearable sleep tracker and undertook twice-daily smartphone-delivered ecological momentary assessment of mood, motivation, and sleepiness at post-wake and pre-bedtime timings for 2-6 weeks. Naps and their duration were reported daily. Nocturnal sleep on 2471 nights were examined using multilevel models to uncover within-subject and between-subject associations between sleep duration, timing, efficiency, and nap duration on following day MMS ratings. Time-lagged analyses examined the temporal specificity of these associations. Linear regression models investigated associations between MMS ratings and sleep variability, controlling for sleep duration. RESULTS: Nocturnal sleep durations were short (6.03 ± 0.71 h), and bedtimes were late (1:42AM ± 1:05). Within-subjects, nocturnal sleep longer than a person's average was associated with better mood, higher motivation, and lower sleepiness after waking. Effects of such longer sleep duration lingered for mood and sleepiness till the pre-bedtime window (all Ps < .005) but did not extend to the next day. Between-subjects, higher intraindividual sleep variability, but not sleep duration, was associated with poorer mood and lower motivation after waking. Longer average sleep duration was associated with less sleepiness after waking and lower motivation pre-bedtime (all Ps < .05). Longer naps reduced post-nap sleepiness and improved mood. Controlling for nocturnal sleep duration, longer naps also associated with lower post-waking sleepiness on the following day. CONCLUSIONS: Positive connections between nocturnal sleep and nap duration with MMS are temporally circumscribed, lending credence to the construction of sleep-based, daily 'readiness' scores. Higher sleep duration variability lowers an individual's post waking mood and motivation. CLINICAL TRIAL ID: ClinicalTrials.gov NCT04880629.

Clinical Importance of Differentiating Epstein-Barr Virus (EBV)-Positive Plasmacytoma From Plasmablastic Lymphoma: Another Unique Case of EBV-Positive Plasmacytoma in an Immunocompetent Patient.

Epstein-Barr virus (EBV)-positive plasmacytoma is a rare and unique plasma cell neoplasm that could arise in immunocompetent individuals. Given the molecular and immunohistochemical similarity of EBV-positive plasmacytomas to their significantly more aggressive counterpart, plasmablastic lymphoma (PBL), providers must distinguish between the two neoplasms. This case elucidates a presentation of EBV-positive plasmacytomas in a healthy, immunocompetent individual originating in the C4/C5 cervical neck region. The patient's clinical presentation, in combination with the surgical pathology from the mass biopsy, pointed toward EBV-positive plasmacytoma. Factors such as cellular proliferation rate, cellular atypia, and immunohistochemical staining help differentiate the two diseases. This case will further help providers in the oncologic world to identify these masses.

Synthesis of Gamma-Butyrolactone Hormones Enables Understanding of Natural Product Induction.

Bacteria produce natural products (NPs) via biosynthetic gene clusters. Unfortunately, many biosynthetic gene clusters are silent under traditional laboratory conditions. To access novel NPs, a better understanding of their regulation is needed. γ-Butyrolactones, including the A-factor and Streptomyces coelicolor butanolides, SCBs, are a major class of Streptomyces' hormones. Study of these hormones has been limited due to challenges in accessing them in stereochemically pure forms. Herein, we describe an efficient route to (R)-paraconyl alcohol, a key intermediate for these molecules, as well as a biocatalytic method to access the exocyclic hydroxyl group that differentiates A-factor-type from SCB-type hormones. Utilizing these methods, a library of hormones have been synthesized and tested in a green fluorescent protein reporter assay for their ability to relieve repression by the repressor ScbR. This allowed the most quantitative structure-activity relationship of γ-butyrolactones and a cognate repressor to date. Bioinformatics analysis strongly suggests that many other repressors of NP biosynthesis likely bind similar molecules. This efficient, diversifiable synthesis will enable further investigation of the regulation of NP biosynthesis.

Comparison of fMRI language laterality with and without sedation in pediatric epilepsy.

Functional MRI is an essential component of presurgical language mapping. In clinical settings, young children may be sedated for the MRI with the functional stimuli presented passively. Research has found that sedation changes language activation in healthy adults and children. However, there is limited research comparing sedated and unsedated functional MRI in pediatric epilepsy patients. We compared language activation patterns in children with epilepsy who received sedation for functional MRI to the ones who did not. We retrospectively identified the patients with focal epilepsy who underwent presurgical functional MRI including Auditory Descriptive Decision Task at Boston Children's Hospital from 2014 to 2022. Patients were divided into sedated and awake groups, based on their sedation status during functional MRI. Auditory Descriptive Decision Task stimuli were presented passively to the sedated group per clinical protocol. We extracted language activation maps contrasted against a control task (reverse speech) in the Frontal and Temporal language regions and calculated separate language laterality indexes for each region. We considered positive laterality indexes as left dominant, negative laterality indexes as right dominant, and absolute laterality indexes <0.2 as bilateral. We defined 2 language patterns: typical (i.e., primarily left-sided) and atypical. Typical pattern required at least one left dominant region (either frontal or temporal) and no right dominant region. We then compared the language patterns between the sedated and awake groups. Seventy patients met the inclusion criteria, 25 sedated, and 45 awake. Using the Auditory Descriptive Decision Task paradigm, when adjusted for age, handedness, gender, and laterality of lesion in a weighted logistic regression model, the odds of the atypical pattern were 13.2 times higher in the sedated group compared to the awake group (Confidence Interval: 2.55-68.41, p-value < 0.01). Sedation may alter language activation patterns in pediatric epilepsy patients. Language patterns on sedated functional MRI with passive tasks may not represent language networks during wakefulness, sedation may differentially suppress some networks, or require a different task or method of analysis to capture the awake language network. Given the critical surgical implication of these findings, additional studies are needed to better understand how sedation impacts the functional MRI blood oxygenation level-dependent signal. Consistent with current practice, sedated functional MRI should be interpreted with greater caution and requires additional validation as well as research on post-surgical language outcomes.

Mindfulness-based therapy for smoking cessation and mental health: a randomised controlled trial.

INTRODUCTION: Effective smoking cessation programmes are essential for assisting smokers in quitting, indirectly lowering mortality and morbidity associated with smoking. Numerous studies have indicated positive outcomes when using mindfulness treatment (MT) to treat psychological or behavioural health issues. Although to date, no study has looked at the effectiveness of online MT for quitting smoking while addressing mental health, particularly among the Asian population. Therefore, this study compares the efficiency of online MT to traditional counselling therapy (CT) in aiding smoking cessation programmes while also addressing mental health. MATERIALS AND METHODS: A randomised control study with a two-group, single-blind design and baseline evaluation was selected. Social media sites were used to advertise for participants, who were then admitted after meeting the requirements. Participants who met the eligibility requirements were randomly split into two groups. Each group received a total of three sessions of online therapy (MT or CT), once every two weeks, as well as one phone call per week as reinforcement. At the beginning and end of the intervention, participants completed questionnaires (1st week and 5th week). Generalized Estimating Equation (GEE) statistical analysis was used to analyse all the variables. RESULTS: The MT group experienced a statistically significant decrease in cigarette consumption (ß: -3.50, 95% Wald CI: - 4.62, -2.39) compared to the CT group over time. Furthermore, the MT group demonstrated significant improvements in their scores for the AAQ-2, anxiety, stress, depression and mindfulness compared to the CT group. CONCLUSION: Online MT is more successful at assisting smokers in lowering their daily cigarette intake and supporting their mental health during the smoking cessation process. Further longitudinal comparisons of the effectiveness of online MT should be undertaken using online platforms in future studies.

Association Between Cycle Threshold Value and Vaccination Status Among Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Cases in Ontario, Canada, in December 2021.

Background: Increased immune evasion by emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and occurrence of breakthrough infections raise questions about whether coronavirus disease 2019 vaccination status affects SARS-CoV-2 viral load among those infected. This study examined the relationship between cycle threshold (Ct) value, which is inversely associated with viral load, and vaccination status at the onset of the Omicron wave onset in Ontario, Canada. Methods: Using linked provincial databases, we compared median Ct values across vaccination status among polymerase chain reaction-confirmed Omicron variant SARS-CoV-2 cases (sublineages B.1.1.529, BA.1, and BA.1.1) between 6 and 30 December 2021. Cases were presumed to be Omicron based on S-gene target failure. We estimated the relationship between vaccination status and Ct values using multiple linear regression, adjusting for age group, sex, and symptom status. Results: Of the 27 029 presumed Omicron cases in Ontario, the majority were in individuals who had received a complete vaccine series (87.7%), followed by unvaccinated individuals (8.1%), and those who had received a booster dose (4.2%). The median Ct value for post-booster dose individuals (18.3 [interquartile range, 15.4-22.3]) was significantly higher than that for unvaccinated (17.9 [15.2-21.6]; P = .02) and post-vaccine series individuals (17.8 [15.3-21.5]; P = .005). Post-booster dose cases remained associated with a significantly higher median Ct value than cases in unvaccinated individuals (P ≤ .001), after adjustment for covariates. Compared with values in persons aged 18-29 years, Ct values were significantly lower among most age groups >50 years. Conclusions: While slightly lower Ct values were observed among unvaccinated individuals infected with Omicron compared with post-booster dose cases, further research is required to determine whether a significant difference in secondary transmission exists between these groups.

Expanding current definitions of environmental stewardship through organizational mission statement analysis.

In recent years, environmental stewardship has been emphasized as one solution to social-ecological sustainability concerns, especially at the local scale. The Stewardship Mapping and Assessment Project (STEW-MAP) is a national research program developed by the USDA Forest Service that has been implemented at numerous locations in the United States and internationally. This study compared the mission statements of environmental stewardship groups in the Los Angeles River Watershed to previously proposed definitions and frameworks of organizational environmental stewardship to see how well they were reflected. A thematic analysis of the mission statements was also carried out to identify locally important themes and priorities. Results show that, although often consistent, the mission statements do not always reflect existing concepts around environmental stewardship. Additionally, environmental stewardship is not always explicit in the mission statements of organizations that are known to conduct these activities. We suggest that non-traditional groups that engage in stewardship work (i.e., research institutions) as well as groups focused on social issues are overlooked actors in sustainable city goals. A more comprehensive definition of environmental stewardship may be needed to bridge the gap between research and practice.

LC-MS/MS quantitation of non-psychotropic cannabinoid cannabidiol in aqueous humor.

Cannabidiol (CBD) is the most abundant non-psychotropic phytocannabinoid isolated from Cannabis sativa. To support preclinical studies of ocular pharmacology of CBD, a bioanalytical method was developed and validated for quantification of CBD in aqueous humor using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Aqueous humor samples were subjected to protein precipitation by acetonitrile, followed by chromatographic separation using reversed phase LC on a Raptor ARC-18 column with mobile phase A: 0.1 % (v/v) formic acid in water (B) 0.1 % formic acid in acetonitrile (B) as eluents. Detection was carried out with a triple quadrupole mass spectrometer with electrospray ionization operated in positive ion mode. Stable-isotope labeled CBD (CBD-d3) was used as internal standard. The total run time was 8 min. Quantification was accomplished within the validated concentration range of 0.5-500 ng/mL for CBD using a 5 µL sample. The lower limit of quantitation was 0.5 ng/mL. Inter- and intra-day precision is 4.737-7.620 % and 3.426-5.830 %, respectively. Inter- and intra-day accuracy ranged between 99.01 % and 100.2 % and 99.85-101.4 % respectively. The extraction recoveries were found to be 66.06 ± 5.146 %. The established method was successfully applied to investigate ocular pharmacokinetics of CBD in mice. Following intraperitoneal (i.p.) administration of 50 mg/kg CBD, its concentration reaches a Cmax of 71.55 ± 36.64 ng/mL in aqueous humor, with a Tmax of 2 h and a half-life of 1.046 h. The AUC was 183.4 ± 49.17 ng * h/mL. The development and validation of this LC-MS/MS method is an important step toward the goal of assessing the aqueous humor concentrations of CBD and correlating the concentrations of this phytocannabinoid with its ocular pharmacologic effects.

Ibuprofen dosing measurement accuracy using infants' versus children's ibuprofen: a randomized crossover comparison.

BACKGROUND: Ibuprofen liquid comes in two pediatric concentrations: 200 mg/5 mL for infants and 100 mg/5 mL for children. This study aimed to investigate the misdosing of ibuprofen liquid products by comparing administration accuracy with differing pediatric concentrations and dosages. METHODS: Subject selection included 116 volunteers. Participants were provided with the children's ibuprofen package including the dosing cup, the infants' ibuprofen package including the infant dosing dropper, and a 5 mL syringe. Each subject drew up a specified dose of infants' ibuprofen and children's ibuprofen and deposited each sample into a graduated cylinder. The dose (70 or 100 mg) and order of concentration usage (infants' first or children's first) were randomized. RESULTS: A total of 116 subjects, with a mean age of 32 ± 14 years, participated in the study. Mean absolute dosing errors for all trials, including those who made no errors, were significantly higher for infants' ibuprofen compared to children's ibuprofen: 39 vs. 27 mg (p = 0.036). A total of 31% of all ibuprofen dosage experiments (71 of 232 trials) had greater than 50% error of the assigned dose. CONCLUSION: Dosage errors using infants' ibuprofen were significantly higher than the children's ibuprofen. This suggests that removing the infant form from consumer availability may help reduce dosing errors when administering ibuprofen to pediatric patients. IMPACT: Pediatric misdosing is a significant problem with over-the-counter medications, such as ibuprofen. A previous study found that 51% of patients under the age of 10 were inaccurately dosed with antipyretic medication, including ibuprofen, with an increased incidence in infants. We found significantly more dosing errors with the infant concentration (200 mg/5 mL) as opposed to the children's concentration (100 mg/5 mL), 39 vs. 27 mg, respectively (p = 0.036). We believe that this research is beneficial to pediatric patient caregivers, clinicians, and policymakers to identify the problem of inaccurate ibuprofen dosing and to propose a way to mitigate this by having one concentration easily accessible.