Synthetic Cannabinoid Identification in Cases Associated with Blue Lotus and Valerian Root.

Synthetic cannabinoids emerged in the early 21st century and have continued to evolve and flourish to present day. Like other novel psychoactive substances (NPS), synthetic cannabinoids have been sold under the guise of legitimate products. Some examples include "potpourri," "incense," and herbal material. Between May 2020 and December 2023, Drug Chemistry Lab (Chem Lab) received 29 seized drug cases mentioning "blue lotus" or "valerian root." In 90% of these cases, at least one exhibit contained one or more synthetic cannabinoids. During the same timeframe, Toxicology Lab (Tox Lab) received 65 toxicology cases that contained synthetic cannabinoids and/or their corresponding hydrolyzed metabolites where case history mentioned "blue lotus." The most frequently observed compounds between laboratories were 5F-MDMB-PICA, ADB-BUTINACA, and MDMB-4en-PINACA. Innocuous branding and marketing may deceive law enforcement, investigators, and healthcare providers into believing that the adverse effects of erratic behavior, sedation, slurred speech, and hallucinations are a result of toxicity from botanical extracts (e.g., apomorphine and nuciferine in blue lotus). Due to the dangerous nature of these NPS, it is recommended that synthetic cannabinoid screening is performed on all cases where there is suspected use of vaping products suggested to contain "blue lotus" or "valerian root" as drug vendors continue to conceal the presence of these compounds.

Pulmonary embolism from right ventricular myxoma in a child with undiagnosed Carney complex.

Pediatric pulmonary embolism occurs in 8.6-57 per 100,000 hospitalised children. We report a novel case of bilateral pulmonary emboli in a child presenting with dyspnoea who was found to have large right ventricular myxoma and subsequent diagnosis of Carney complex. After resection of the right ventricular myxoma and bilateral pulmonary embolectomy, she had a full recovery and an excellent outcome.

Development and Temporal Validation of a Machine Learning Model to Predict Clinical Deterioration.

OBJECTIVES: Early warning scores detecting clinical deterioration in pediatric inpatients have wide-ranging performance and use a limited number of clinical features. This study developed a machine learning model leveraging multiple static and dynamic clinical features from the electronic health record to predict the composite outcome of unplanned transfer to the ICU within 24 hours and inpatient mortality within 48 hours in hospitalized children. METHODS: Using a retrospective development cohort of 17 630 encounters across 10 388 patients, 2 machine learning models (light gradient boosting machine [LGBM] and random forest) were trained on 542 features and compared with our institutional Pediatric Early Warning Score (I-PEWS). RESULTS: The LGBM model significantly outperformed I-PEWS based on receiver operating characteristic curve (AUROC) for the composite outcome of ICU transfer or mortality for both internal validation and temporal validation cohorts (AUROC 0.785 95% confidence interval [0.780-0.791] vs 0.708 [0.701-0.715] for temporal validation) as well as lead-time before deterioration events (median 11 hours vs 3 hours; P = .004). However, LGBM performance as evaluated by precision recall curve was lesser in the temporal validation cohort with associated decreased positive predictive value (6% vs 29%) and increased number needed to evaluate (17 vs 3) compared with I-PEWS. CONCLUSIONS: Our electronic health record based machine learning model demonstrated improved AUROC and lead-time in predicting clinical deterioration in pediatric inpatients 24 to 48 hours in advance compared with I-PEWS. Further work is needed to optimize model positive predictive value to allow for integration into clinical practice.

Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats.

Air pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of the target tissue and systemic effects are poorly understood. A prototypic inducer of stress, ozone causes respiratory and systemic multiorgan effects through activation of a neuroendocrine stress response. The goal of this study was to assess transcriptomic signatures of multiple tissues and serum metabolomics to understand how neuroendocrine and adrenal-derived stress hormones contribute to multiorgan health outcomes. Male Wistar Kyoto rats (12-13 weeks old) were exposed to filtered air or 0.8 ppm ozone for 4-hours, and blood/tissues were collected immediately post-exposure. Each tissue had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 in hypothalamus, 2,516 in adrenals, 1,333 in liver, 1,242 in adipose, and 5,102 in muscle (adjusted p-value < 0.1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, of which 447 were significantly altered in ozone-exposed rats (adjusted p-value < 0.1, absolute fold change > 20%). A total of 6 genes were differentially expressed in all 6 tissues. Glucocorticoid signaling, hypoxia, and GPCR signaling were commonly changed, but ozone induced tissue-specific changes in oxidative stress, immune processes, and metabolic pathways. Genes upregulated by TNF-mediated NFkB signaling were differentially expressed in all ozone-exposed tissues, but those defining inflammatory response were tissue-specific. Upstream predictor analysis identified common mediators of effects including glucocorticoids, although the specific genes responsible for these predictors varied by tissue. Metabolomic analysis showed major changes in lipids, amino acids, and metabolites linked to the gut microbiome, concordant with transcriptional changes identified through pathway analysis within liver, muscle, and adipose tissues. The distribution of receptors and transcriptional mechanisms underlying the ozone-induced stress response are tissue-specific and involve induction of unique gene networks and metabolic phenotypes, but the shared initiating triggers converge into shared pathway-level responses. This multi-tissue transcriptomic analysis, combined with circulating metabolomic assessment, allows characterization of the systemic inhaled pollutant-induced stress response.

Alternative Approaches for Expanding the Air Force's Task Force True North Program.

The Air Force seeks to maximize airman fitness and minimize threats to individual and unit readiness, such as domestic and sexual violence and suicide. The purpose of the Air Force's Task Force True North (TFTN) is to provide effective prevention and treatment programs to airmen in need by embedding health care providers directly into units. In this study, the authors identify potential courses of action (COAs) for expanding the TFTN program, including estimating each approach's associated manpower requirements, recruiting requirements, total costs, and implementation timelines. In developing these COAs, the authors analyzed embedded behavioral and physical health programs in the Army, Navy, Marine Corps, and U.S. Special Operations Command; developed a framework for analyzing mental, physical, and social squadron risk levels; developed personnel packages for low-, medium-, and high-risk squadrons; and estimated the costs of implementing these personnel packages under different timelines. In addition to detailing these COAs, the authors provide recommendations on best practices for the Air Force to follow as it expands the TFTN program.

Untargeted Metabolomic Analysis of Sjögren-Larsson Syndrome Reveals a Distinctive Pattern of Multiple Disrupted Biochemical Pathways.

Sjögren-Larsson syndrome (SLS) is a rare inherited neurocutaneous disease characterized by ichthyosis, spastic diplegia or tetraplegia, intellectual disability and a distinctive retinopathy. SLS is caused by bi-allelic mutations in ALDH3A2, which codes for fatty aldehyde dehydrogenase (FALDH) and results in abnormal lipid metabolism. The biochemical abnormalities in SLS are not completely known, and the pathogenic mechanisms leading to symptoms are still unclear. To search for pathways that are perturbed in SLS, we performed untargeted metabolomic screening in 20 SLS subjects along with age- and sex-matched controls. Of 823 identified metabolites in plasma, 121 (14.7%) quantitatively differed in the overall SLS cohort from controls; 77 metabolites were decreased and 44 increased. Pathway analysis pointed to disrupted metabolism of sphingolipids, sterols, bile acids, glycogen, purines and certain amino acids such as tryptophan, aspartate and phenylalanine. Random forest analysis identified a unique metabolomic profile that had a predictive accuracy of 100% for discriminating SLS from controls. These results provide new insight into the abnormal biochemical pathways that likely contribute to disease in SLS and may constitute a biomarker panel for diagnosis and future therapeutic studies.

Risk of in-hospital Deterioration for Children with Single Ventricle Physiology.

Children with single ventricle physiology (SV) are at high risk of in-hospital morbidity and mortality. Identifying children at risk for deterioration may allow for earlier escalation of care and subsequently decreased mortality.We conducted a retrospective chart review of all admissions to the pediatric cardiology non-ICU service from 2014 to 2018 for children < 18 years old. We defined clinical deterioration as unplanned transfer to the ICU or inpatient mortality. We selected children with SV by diagnosis codes and defined infants as children < 1 year old. We compared demographic, vital sign, and lab values between infants with and without a deterioration event. We evaluated vital sign and medical therapy changes before deterioration events.Among infants with SV (129 deterioration events over 225 admissions, overall 25% with hypoplastic left heart syndrome), those who deteriorated were younger (p = 0.001), had lower baseline oxygen saturation (p = 0.022), and higher baseline respiratory rate (p = 0.022), heart rate (p = 0.023), and hematocrit (p = 0.008). Median Duke Pediatric Early Warning Score increased prior to deterioration (p < 0.001). Deterioration was associated with administration of additional oxygen support (p = 0.012), a fluid bolus (p < 0.001), antibiotics (p < 0.001), vasopressor support (p = 0.009), and red blood cell transfusion (p < 0.001).Infants with SV are at high risk for deterioration. Integrating baseline and dynamic patient data from the electronic health record to identify the highest risk patients may allow for earlier detection and intervention to prevent clinical deterioration.

Patient-Reported Outcomes Correlate With Microbial Community Composition Independent of Mucosal Inflammation in Pediatric Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel diseases (IBDs) involve an aberrant host response to intestinal microbiota causing mucosal inflammation and gastrointestinal symptoms. Patient-reported outcomes (PROs) are increasingly important in clinical care and research. Our aim was to examine associations between PROs and fecal microbiota in patients 0 to 22 years of age with IBD. METHODS: A longitudinal, prospective, single-center study tested for associations between microbial community composition via shotgun metagenomics and PROs including stool frequency and rectal bleeding in ulcerative colitis (UC) and abdominal pain and stool frequency in Crohn's disease (CD). Mucosal inflammation was assessed with fecal calprotectin. A negative binomial mixed-effects model including clinical characteristics and fecal calprotectin tested for differentially abundant species and metabolic pathways by PROs. RESULTS: In 70 CD patients with 244 stool samples, abdominal pain correlated with increased relative abundance of Haemophilus and reduced Clostridium spp. There were no differences relative to calprotectin level. In 23 UC patients with 76 samples, both rectal bleeding and increased stool frequency correlated with increased Klebsiella and reduced Bacteroides spp. Conversely, UC patients with lower calprotectin had reduced Klebsiella. Both UC and CD patients with active symptoms exhibited less longitudinal microbial community stability. No differences in metabolic pathways were observed in CD. Increased sulfoglycolysis and ornithine biosynthesis correlated with symptomatic UC. CONCLUSIONS: Microbial community composition correlated with PROs in both CD and UC. Metabolic pathways differed relative to PROs in UC, but not CD. Data suggest that microbiota may contribute to patient symptoms in IBD, in addition to effects of mucosal inflammation.

Optimization of novel loop-mediated isothermal amplification with colorimetric image analysis for forensic body fluid identification.

Accurate presumptive and confirmatory test use for forensic body fluid identification is essential for gaining contextual information for crime scene investigators. Loop-mediated isothermal amplification (LAMP) is an ideal method for forensic body fluid identification because it is highly specific and generates multi-sized amplicon DNA, and successful amplification results can be read out colorimetrically. Here, we show preliminary data on a LAMP method that rapidly identifies body fluids including venous blood, semen, and saliva, based on colorimetric response and image analysis. The method is designed for easy implementation into forensic casework protocols with minimal disruption to DNA analysis. LAMP naturally increases target specificity due to the use of multiple primers for one target and mRNA targets were used for tissue and human specificity. With colorimetric detection as an inherent part of LAMP, samples that are positive or negative for any of the body fluids are readily identified by image capture and analysis, thus eliminating subjectivity. Results show by using the 3D-printed imaging system specific color ranges can be set for easy determination of body fluids. The resulting color change can be seen in <30 min using a universal temperature and primer concentration for all body fluids. This simple method and imaging system allow for minimal hands-on time with objective image analysis and presents a pathway for creating a new potential method for forensic body fluid identification.

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn's Disease.

BACKGROUND: The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations. METHODS: We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn's disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP <250 µg/g, with clinical response defined as a weighted Pediatric Crohn's Disease Activity Index <12.5 or Δ>17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs). RESULTS: Among 56 CD patients, ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934, P < 0.001) and nCD64 <6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of >9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP <250 and FCP <100, respectively. We found patients achieving end of induction trough >5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels <5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031). CONCLUSIONS: This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

Real-World Infliximab Pharmacokinetic Study Informs an Electronic Health Record-Embedded Dashboard to Guide Precision Dosing in Children with Crohn's Disease.

Standard-of-care infliximab dosing regimens were developed prior to the routine use of therapeutic drug monitoring and identification of target concentrations. Not surprisingly, subtherapeutic infliximab concentrations in pediatric Crohn's disease (CD) are common. The primary aim was to conduct a real-world pharmacokinetic (PK) evaluation to discover blood biomarkers of rapid clearance, identify exposure targets, and a secondary aim to translate PK modeling to the clinic. In a multicenter observational study, 671 peak and trough infliximab concentrations from 78 patients with CD were analyzed with a drug-tolerant assay (Esoterix; LabCorp, Calabasas, CA). Individual area under the curve (AUC) estimates were generated as a measure of drug exposure over time. Population PK modeling (nonlinear mixed-effect modeling) identified serum albumin, antibody to infliximab, erythrocyte sedimentation rate (ESR), and neutrophil CD64 as biomarkers for drug clearance. Week 14 and week 52 biochemical remitters (fecal calprotectin < 250 µg/g) had higher infliximab exposure (AUC) throughout induction. The optimal infliximab AUC target during induction for week 14 biochemical remission was 79,348 µg*h/mL (area under the receiver operating characteristic curve (AUROC) 0.77, [0.63-0.90], 85.7% sensitive, and 64.3% specific) with those exceeding the AUC target more likely to achieve a surgery-free week 52 biochemical remission (OR 4.3, [1.2-14.6]). Pretreatment predictors for subtherapeutic week 14 AUC included neutrophil CD64 > 6 (OR 4.5, [1.4-17.8]), ESR > 30 mm/h (OR 3.8, [1.4-11]), age < 10 years old (OR 4.2, [1.2-20]), and weight < 30 kg (OR 6.6, [2.1-25]). We created a decision-support PK dashboard with an iterative process and embedded the modeling program within the electronic health record. Model-informed precision dosing guided by real-world PKs is now available at the bedside in real-time.

Cardiac arrest in the paediatric intensive care unit: defining the problem and developing solutions.

Thousands of children experience a cardiac arrest event in the hospital each year, with more than half of these patients not surviving to hospital discharge. Cardiopulmonary resuscitation (CPR) depth, rate, velocity and percentage of high-quality chest compressions are modifiable factors associated with improved survival. Therefore, we created a novel and standardised process to track and analyse cardiac arrests in the Duke paediatric intensive care unit (PICU). Our aim was to identify areas for improved American Heart Association (AHA) compliance and implement education and communication-based initiatives to enhance early recognition of at-risk patients leading to improved outcomes. From January 2017 to December 2018, all cardiac arrests in our PICU were tracked, reviewed and presented at monthly morbidity and mortality conference. We used the data to track compliance with AHA guidelines and identify opportunities for improvement. Through these efforts, we established a multidisciplinary cardiac arrest education and review programme. Over the 2-year period, we tracked 45 cardiac arrests, which comprised 2% of all PICU admissions. In 2017, during the first year of development, 16 of 22 arrests (73%) were not reported to code committee members in time for complete review. Of the six cardiac arrests with complete reviews, only 17% followed AHA guidelines. In 2018, all 23 arrest events were communicated and 76% of resuscitations were found to be compliant with AHA guidelines. Survival of patients to discharge was 47% in 2017 and increased to 63% in 2018 with similar percentage of PICU admissions having a cardiac arrest between the 2 years. The primary aim of this project was to establish a multidisciplinary comprehensive cardiac arrest review process. This programme allowed for comprehensive analysis of individual events, promoted quality improvement initiatives and improved consistent delivery of high-quality CPR.

Extracorporeal Membrane Oxygenation for Hemodynamic Support.

Extracorporeal membrane oxygenation was first successfully achieved in 1975 in a neonate with meconium aspiration. Neonatal extracorporeal membrane oxygenation has expanded to include hemodynamic support in cardiovascular collapse before and after cardiac surgery, medical heart disease, and rescue therapy for cardiac arrest. Advances in pump technology, circuit biocompatibility, and oxygenators efficiency have allowed extracorporeal membrane oxygenation to support neonates with increasingly complex pathophysiology. Contraindications include extreme prematurity, extremely low birth weight, lethal chromosomal abnormalities, uncontrollable hemorrhage, uncontrollable disseminated intravascular coagulopathy, and severe irreversible brain injury. The future will involve collaboration to guide and evolve evidence-based practices for this life-sustaining therapy.

Insights from the Inclusive Environments and Metrics in Biology Education and Research Network: Our Experience Organizing Inclusive Biology Education Research Events.

In contrast to efforts focusing on improving inclusion in STEM classrooms from kindergarten through undergraduate (K-16), efforts to improve inclusion in scientific meetings and conferences, important hubs of STEM culture, are more recent. Markers of inclusion that are sometimes overlooked at these events can include the composition of panels, how workshops are run, the affordability of conferences, and various other mechanisms that maintain pre-existing hierarchies and norms that limit the participation of early-career researchers and individuals of minoritized cultural, linguistic, and economic backgrounds. The Inclusive Environments and Metrics in Biology Education and Research (iEMBER) network coordinates efforts of researchers from many fields interested in diversity and inclusion in biology education. Given the concerns regarding inclusion at professional meetings, iEMBER has developed and implemented several practices in planning and executing our meetings to make them more inclusive. In this report, we share our experiences developing inclusive meetings on biology education research and discuss the outcomes of such efforts. Specifically, we present our approach to planning and executing the iEMBER 2019 conference and the National Association of Biology Teachers iEMBER 2019 workshop. This report adds to the growing body of resources on inclusive meetings, provides readers with an account of how such an attempt at implementation might unfold, and complements existing theories and work relating to the importance and functioning of such meetings in terms of representation in STEM.

Microbial Shifts and Shorter Time to Bowel Resection Surgery Associated with C. difficile in Pediatric Crohn's Disease.

BACKGROUND: Clostridioides difficile infection and colonization are common in pediatric Crohn's disease (CD). Our aims were to test the relationship between C. difficile positivity and bowel resection surgery and to characterize microbial shifts associated with C. difficile carriage and surgery. METHODS: A retrospective single-center study of 75 pediatric CD patients tested for association between C. difficile carriage and bowel resection surgery. A prospective single-center study of 70 CD patients utilized C. difficile testing and shotgun metagenomic sequencing of fecal samples to define microbiota variation stratified by C. difficile carriage or history of surgery. RESULTS: The rate of bowel resection surgery increased from 21% in those without C. difficile to 67% in those with (P = 0.003). From a Kaplan-Meier survival model, the hazard ratio for time to first surgery was 4.4 (95% CI, 1.2-16.2; P = 0.00) in patients with positive C. difficile testing in the first year after diagnosis. Multivariable logistic regression analysis confirmed this association (odds ratio 16.2; 95% CI, 2.2-120; P = 0.006). Larger differences in microbial abundance and metabolic pathways were observed in patients with prior surgery than in those with C. difficile carriage. Depletion of Alistipes and Ruminococcus species and reduction in methionine biosynthesis were noted in patients with both C. difficile carriage and past surgery. CONCLUSIONS: A positive C. difficile test during the first year after diagnosis is associated with decreased time to first bowel resection surgery in pediatric Crohn's disease. Depletion of beneficial commensals and methionine biosynthesis in patients with C. difficile carriage may contribute to increased risk for surgery.

A novel loop-mediated isothermal amplification method for identification of four body fluids with smartphone detection.

Messenger RNA profiling for body fluid identification (bfID) is a useful approach to collect contextual information associated with a crime. Current methods require costly fluorescent probes, lengthy amplification protocols and/or time-consuming sample preparation. To simplify this process, we developed a bfID method that has the potential to be rapid in analysis time, inexpensive and fluorescence-free, combining a universal operating procedure with a high-throughout (microwell plate) platform for simultaneous detection of mRNA markers from whole blood, semen, saliva, and vaginal fluid. Full bfID sample preparation and analysis of 23 samples was completed in under 3 h using smart phone optical detection and analysis and show efficacy of the method in a validated blind study. The results provide an efficient, sensitive and specific approach to supplement the current biochemical tests in a forensic laboratory.

A CURE Biochemistry Laboratory Module to Study Protein-Protein Interactions by NMR Spectroscopy.

Design of undergraduate laboratory courses that provide meaningful research-based experiences enhance undergraduate curricula and prepare future graduate students for research careers. In this article, a Course-based Undergraduate Research Experience (CURE) laboratory module was designed for upper-division undergraduate biochemistry and chemistry students. The laboratory module enabled students to build upon recently published data in the literature to decipher atomistic insight for an essential protein-protein interaction in human biology through the use of biomolecular NMR spectroscopy. Students compared their results with published data with the goal of identifying specific regions of the protein-protein interaction responsible for triggering an allosteric conformational change. The laboratory module introduced students to basic and advance laboratory techniques, including protein purification, NMR spectroscopy, and analysis of protein structure using molecular visualization software.

Elevated Pretreatment Plasma Oncostatin M Is Associated With Poor Biochemical Response to Infliximab.

BACKGROUND: We hypothesized that elevations of plasma Oncostatin M (OSM) would be associated with infliximab nonresponse. METHODS: Plasma OSM was measured in Crohn disease patients pre-infliximab with biochemical response (>50% reduction in fecal calprotectin) as the primary outcome. RESULTS: The median OSM in biochemical responders was 86 (69-148) pg/mL compared with 166 (74-1766) pg/mL in nonresponders (P = 0.03). Plasma OSM > 143.5 pg/mL was 71% sensitive and 78% specific for biochemical nonresponse (area under the curve 0.71). Early biochemical nonremission was also associated with an elevated neutrophil CD64 expression (odds ratio 8.9, P = 0.011). CONCLUSIONS: Elevated preinfliximab plasma OSM and nCD64 surface expression were both associated with poor biochemical outcomes.