Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.

Control of Drug-Excipient Particle Attributes with Droplet Microfluidic-based Extractive Solidification Enables Improved Powder Rheology.

PURPOSE: Industrial implementation of continuous oral solid dosage form manufacturing has been impeded by the poor powder flow properties of many active pharmaceutical ingredients (APIs). Microfluidic droplet-based particle synthesis is an emerging particle engineering technique that enables the production of neat or composite microparticles with precise control over key attributes that affect powder flowability, such as particle size distribution, particle morphology, composition, and the API's polymorphic form. However, the powder properties of these microparticles have not been well-studied due to the limited mass throughputs of available platforms. In this work, we produce spherical API and API-composite microparticles at high mass throughputs, enabling characterization and comparison of the bulk powder flow properties of these materials and greater understanding of how particle-scale attributes correlate with powder rheology. METHODS: A multi-channel emulsification device and an extractive droplet-based method are harnessed to synthesize spherical API and API-excipient particles of artemether. As-received API and API crystallized in the absence of droplet confinement are used as control cases. Particle attributes are characterized for each material and correlated with a comprehensive series of powder rheology tests. RESULTS: The droplet-based processed artemether particles are observed to be more flowable, less cohesive, and less compressible than conventionally synthesized artemether powder. Co-processing the API with polycaprolactone to produce composite microparticles reduces the friction of the powder on stainless steel, a common equipment material. CONCLUSIONS: Droplet-based extractive solidification is an attractive particle engineering technique for improving powder processing and may aid in the implementation of continuous solid dosage form manufacturing.

Humanitarian and primary healthcare needs of refugee women and children in Afghanistan.

This Commentary describes the situation and healthcare needs of Afghans returning to their country of origin. With more than 600,000 Afghans returned from Pakistan and approximately 450,000 Afghans returned from Iran in 2016, the movement of people, which has been continuing in 2017, presents additional burden on the weak health system and confounds new health vulnerabilities especially for women and children. Stewardship and response is required at all levels: the central Ministry of Public Health, Provincial Health Departments and community leaders all have important roles, while continued support from development partners and technical experts is needed to assist the health sector to address the emergency and primary healthcare needs of returnee and internally displaced women, children and families.

A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis.

The histone methyltransferase EZH2 is frequently mutated in germinal center-derived diffuse large B-cell lymphoma and follicular lymphoma. To further characterize these EZH2 mutations in lymphomagenesis, we generated a mouse line where EZH2(Y641F) is expressed from a lymphocyte-specific promoter. Spleen cells isolated from the transgenic mice displayed a global increase in trimethylated H3K27, but the mice did not show an increased tendency to develop lymphoma. As EZH2 mutations often coincide with other mutations in lymphoma, we combined the expression of EZH2(Y641F) by crossing these transgenic mice with Eµ-Myc transgenic mice. We observed a dramatic acceleration of lymphoma development in this combination model of Myc and EZH2(Y641F). The lymphomas show histologic features of high-grade disease with a shift toward a more mature B-cell phenotype, increased cycling and gene expression, and epigenetic changes involving important pathways in B-cell regulation and function. Furthermore, they initiate disease in secondary recipients. In summary, EZH2(Y641F) can collaborate with Myc to accelerate lymphomagenesis demonstrating a cooperative role of EZH2 mutations in oncogenesis. This murine lymphoma model provides a new tool to study global changes in the epigenome caused by this frequent mutation and a promising model system for testing novel treatments.

Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons.

Modern society enables a shortening of sleep times, yet long-term consequences of extended wakefulness on the brain are largely unknown. Essential for optimal alertness, locus ceruleus neurons (LCns) are metabolically active neurons that fire at increased rates across sustained wakefulness. We hypothesized that wakefulness is a metabolic stressor to LCns and that, with extended wakefulness, adaptive mitochondrial metabolic responses fail and injury ensues. The nicotinamide adenine dinucleotide-dependent deacetylase sirtuin type 3 (SirT3) coordinates mitochondrial energy production and redox homeostasis. We find that brief wakefulness upregulates SirT3 and antioxidants in LCns, protecting metabolic homeostasis. Strikingly, mice lacking SirT3 lose the adaptive antioxidant response and incur oxidative injury in LCns across brief wakefulness. When wakefulness is extended for longer durations in wild-type mice, SirT3 protein declines in LCns, while oxidative stress and acetylation of mitochondrial proteins, including electron transport chain complex I proteins, increase. In parallel with metabolic dyshomeostasis, apoptosis is activated and LCns are lost. This work identifies mitochondrial stress in LCns upon wakefulness, highlights an essential role for SirT3 activation in maintaining metabolic homeostasis in LCns across wakefulness, and demonstrates that extended wakefulness results in reduced SirT3 activity and, ultimately, degeneration of LCns.

Label-free direct visual analysis of hydrolytic enzyme activity using aqueous two-phase system droplet phase transitions.

Dextran hydrolysis-mediated conversion of polyethylene glycol (PEG)-dextran (DEX) aqueous two-phase system droplets to a single phase was used to directly visualize Dextranase activity. DEX droplets were formed either by manual micropipetting or within a continuous PEG phase by computer controlled actuation of an orifice connecting rounded channels formed by backside diffused light lithography. The time required for the two-phase to one-phase transition was dependent on the Dextranase concentration, pH of the medium, and temperature. The apparent Michaelis constants for Dextranase were estimated based on previously reported catalytic constants, the binodal polymer concentration curves for PEG-DEX phase transition for each temperature, and pH condition. The combination of a microfluidic droplet system and phase transition observation provides a new method for label-free direct measurement of enzyme activity.

The evaluation of a palliative care programme for people suffering from life-limiting diseases.

AIMS AND OBJECTIVES: To report on the effectiveness of an eight-week palliative care programme in Hong Kong. BACKGROUND: A recent survey reported that the quality of palliative care services in Hong Kong ranked the 20th among 40 countries and it is far behind other Asian countries. There are disagreement and inadequate communication in clinical decision-making among patients, families and healthcare professionals, and that the nurses lack sufficient knowledge and skills in providing palliative care and advance care planning. DESIGN: A pretest post-test design and semi-structured interviews were adopted. METHODS: A total of 108 home care patients with life-limiting disease and their family caregivers in Hong Kong were recruited to complete a set of questionnaire including The McGill Quality of Life Questionnaire for Hong Kong Chinese and the Family Satisfaction Scale before and after they attended an eight-week programme. The programme comprised the elements of symptom management, intensive communication on advance care planning and psychosocial intervention. RESULTS: Pearson's chi-square tests and Wilcoxon matched paired tests show a general trend that the patients' quality of life was improved after the programme. Their understanding and active participation in advance care planning was also improved. The hospital readmission rate and the days of hospital stays were significantly reduced. In qualitative interview, four major themes were identified that are as follows: improvement in the communication of treatment plans and after-death arrangements, symptom management, emotional support and suggested areas of improvement. CONCLUSION: The study supports the benefit of implementing a palliative care programme to patients with life-limiting disease. Patients demonstrated improved understanding and changed behaviour as regards the preparation for death and dying after the eight-week programme. RELEVANCE TO CLINICAL PRACTICE: The programme could be replicated in other hospitals and infirmaries that offer home care services.

A Rare Case of Small Bowel Obstruction in a 15-Year-Old Girl: Internal Hernia Associated with Meckel's Diverticulum.

BACKGROUND Meckel's diverticulum is a congenital remnant of the omphalomesenteric duct and is the most common congenital gastrointestinal malformation. Most patients are asymptomatic, but a rare presentation is with subacute small bowel obstruction (SBO) due to herniation of bowel loops through an internal hernia formed by the Meckel's diverticulum and adjacent mesentery that forms an internal hernia. This report is of a 15-year-old girl presenting as an emergency with vomiting and small bowel obstruction due to an internal hernia associated with Meckel's diverticulum. CASE REPORT We present a case of a 15-year-old girl who presented to the Children's Emergency (CE) department with persistent vomiting and abdominal distension and tenderness. X-rays demonstrated dilated small bowel loops, prompting admission under Pediatric Surgery (PAS). A subsequent computed tomography (CT) scan was performed, which demonstrated multiple dilated small bowel loops, confirming SBO, and a blind-ending "C-shaped" bowel loop at the region of the terminal ileum. A diagnostic laparotomy was performed, which confirmed the presence of a Meckel's diverticulum. The tip of the Meckel's diverticulum was adherent to part of the small bowel mesentery, forming an internal hernia defect through which a loop of proximal ileum had herniated, resulting in SBO. She then underwent a laparoscopy-assisted transumbilical Meckel's diverticulectomy (LATUM). The patient recovered uneventfully and was discharged on the 4th postoperative day. CONCLUSIONS In children presenting with SBO, the possibility of Meckel's diverticulum as an etiology should be considered as a differential diagnosis. Early diagnosis and prompt intervention will improve clinical outcomes and avoid complications.

Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells.

Processing of pre-miRNA through Dicer1 generates an miRNA duplex that consists of an miRNA and miRNA* strand. Despite the general view that miRNA*s have no functional role, we further investigated miRNA* species in 10 deep-sequencing libraries from mouse and human tissue. Comparisons of miRNA/miRNA* ratios across the miRNA sequence libraries revealed that 50% of the investigated miRNA duplexes exhibited a highly dominant strand. Conversely, 10% of miRNA duplexes showed a comparable expression of both strands, whereas the remaining 40% exhibited variable ratios across the examined libraries, as exemplified by miR-223/miR-223* in murine and human cell lines. Functional analyses revealed a regulatory role for miR-223* in myeloid progenitor cells, which implies an active role for both arms of the miR-223 duplex. This was further underscored by the demonstration that miR-223 and miR-223* targeted the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase axis and that high miR-223* levels were associated with increased overall survival in patients with acute myeloid leukemia. Thus, we found a supporting role for miR-223* in differentiating myeloid cells in normal and leukemic cell states. The fact that the miR-223 duplex acts through both arms extends the complexity of miRNA-directed gene regulation of this myeloid key miRNA.

Competitive repair by naturally dispersed repetitive DNA during non-allelic homologous recombination.

Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and Saccharomyces cerevisiae/Saccharomyces bayanus hybrid diploids. We find that DNA double-strand breaks (DSBs) induce NAHR-dependent rearrangements using Ty elements located 12 to 48 kilobases distal to the break site. This break-distal recombination (BDR) occurs frequently, even when allelic recombination can repair the break using the homolog. Robust BDR-dependent NAHR demonstrates that sequences very distal to DSBs can effectively compete with proximal sequences for repair of the break. In addition, our analysis of NAHR partner choice between Ty repeats shows that intrachromosomal Ty partners are preferred despite the abundance of potential interchromosomal Ty partners that share higher sequence identity. This competitive advantage of intrachromosomal Tys results from the relative efficiencies of different NAHR repair pathways. Finally, NAHR generates deleterious rearrangements more frequently when DSBs occur outside rather than within a Ty repeat. These findings yield insights into mechanisms of repeat-mediated genome rearrangements associated with evolution and cancer.

Microfluidic automation using elastomeric valves and droplets: reducing reliance on external controllers.

This paper gives an overview of elastomeric valve- and droplet-based microfluidic systems designed to minimize the need of external pressure to control fluid flow. This Concept article introduces the working principle of representative components in these devices along with relevant biochemical applications. This is followed by providing a perspective on the roles of different microfluidic valves and systems through comparison of their similarities and differences with transistors (valves) and systems in microelectronics. Despite some physical limitation of drawing analogies from electronic circuits, automated microfluidic circuit design can gain insights from electronic circuits to minimize external control units, while implementing high-complexity and high-throughput analysis.

Precisely targeted delivery of cells and biomolecules within microchannels using aqueous two-phase systems.

Laminar and pulsatile flow of aqueous solutions in microfluidic channels can be useful for controlled delivery of cells and molecules. Dispersion effects resulting from diffusion and convective disturbances, however, result in reagent delivery profiles becoming blurred over the length of the channels. This issue is addressed partially by using oil-in-water phase systems. However, there are limitations in terms of the biocompatibility of these systems for adherent cell culture. Here we present a fully biocompatible aqueous two-phase flow system that can be used to pattern cells within simple microfluidic channel designs, as well as to deliver biochemical treatments to cells according to discrete boundaries. We demonstrate that aqueous two-phase systems are capable of precisely delivering cells as laminar patterns, or as islands by way of forced droplet formation. We also demonstrate that these systems can be used to precisely control chemical delivery to preformed monolayers of cells growing within channels. Treatments containing trypsin were localized more reliably using aqueous two-phase delivery than using conventional delivery in aqueous medium.

Determinants of evolution and progression of acute ovine ischemic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: The optimal treatment of moderate ischemic mitral regurgitation (IMR) remains contested. Thus, radiopaque markers were implanted on valvular structures to investigate the geometric and hemodynamic variables associated with the evolution and progression of acute ovine IMR. METHODS: Eight adult sheep underwent implantation of five radiopaque markers on the edge of the posterior mitral leaflet (PML), and five on the edge of the anterior mitral leaflet (AML). Eight additional markers were sewn around the mitral annulus (MA). The animals were studied immediately after surgery, using biplane videofluoroscopy and transesophageal echocardiography. Data were acquired at Baseline and at two time points (IMR1 and IMR2) during acute snare occlusion of the proximal left circumflex coronary artery and progressive IMR. The orthogonal distance of each leaflet edge marker to the least-squares annular plane, mitral annular area (MAA), and septal-lateral diameter (SL) were calculated at end-systole. The leaflet tenting area (TA) was calculated at valve center (CENT) and near the anterior (ACOM) and posterior (PCOM) commissures. RESULTS: The degree of MR was 0.6 +/- 0.4, 1.8 +/- 0.7, and 2.8 +/- 0.7 for Baseline, IMR1, and IMR2, respectively (p < 0.005). IMR1 was associated with annular dilatation and leaflet restriction near the valve center, and prolapse near the PCOM versus Baseline. Although both left ventricular pressure (LVP) and left ventricular dP/dt decreased significantly from IMR1 to IMR 2, there were no differences in leaflet or annular geometry. CONCLUSION: The initiation of moderate IMR was associated with significant alterations in annular and leaflet geometry, but only a small decrease in LV systolic function, was needed for IMR progression. These data suggest that the surgical repair and optimization of LV function may be important in combination to treat moderate IMR, as only small hemodynamic deterioration and perturbations in valvular geometry are necessary for significant IMR progression.

Drug Development in Soft Tissue Sarcomas: Novel Targets and Recent Early Phase Trial Results.

Soft tissue sarcomas are a heterogeneous group of rare malignancies with few effective standard therapies. Our understanding of the underlying biology driving tumorigenesis in these mesenchymal tumors have led to a growth in drug development for soft tissue sarcomas. This review focuses on novel targets in soft tissue sarcomas, describes early clinical trial results of drugs directed at these targets, and discusses the data surrounding the use of these compounds in clinical practice and rationale for possible future US Food and Drug Administration approvals.

Regional mitral leaflet opening during acute ischemic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: Diastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics were quantified along the entire valvular coaptation line in an ovine model of acute IMR. METHODS: Ten radiopaque markers were sutured in pairs on the anterior (A1-E1) and corresponding posterior (A2-E2) leaflet edges from the anterior (A1/A2) to the posterior (E1/E2) commissure in 11 adult sheep. Immediately after surgery, 4-D marker coordinates were obtained before and during occlusion of the proximal left circumflex coronary artery. Distances between marker pairs were calculated throughout the cardiac cycle every 16.7 ms. Leaflet opening was defined as the time after end-systole (ES) when the first derivative of the distance between marker pairs was greater than a threshold value of 3 cm/s. Valve opening velocity was defined as the maximum slope of marker pair tracings. RESULTS: Hemodynamics were consistent with acute ischemia, as reflected by increased MR grade (0.5 +/- 0.3 versus 2.3 +/- 0.7, p < 0.05), decreased contractility (dP/dt(max): 1,948 +/- 598 versus 1,119 +/- 293 mmHg/s, p < 0.05), and slower left ventricular relaxation rate (dP/dt(min): -1,079 +/- 188 versus -538 +/- 147 mmHg/s, p < 0.05). During ischemia, valve opening occurred earlier (A1/A2: 112 +/- 28 versus 83 +/- 43 ms, B1/B2: 105 +/- 32 versus 68 +/- 35 ms, C1/C2: 126 +/- 25 versus 74 +/- 37 ms, D1/D2: 114 +/- 28 versus 71 +/- 34 ms, E1/E2: 125 +/- 29 versus 105 +/- 33 ms; all p < 0.05) and was slower (A1/A2: 16.8 +/- 9.6 versus 14.2 +/- 9.4 cm/s, B1/B2: 40.4 +/- 9.9 versus 32.2 +/- 10.0 cm/s, C1/C2: 59.0 +/- 14.9 versus 50.4 +/- 18.1 cm/s, D1/D2: 34.4 +/- 10.4 versus 25.5 +/- 10.9 cm/s; all p < 0.05), except at the posterior edge (E1/E2: 13.3 +/- 8.7 versus 10.6 +/- 7.2 cm/s). The sequence of regional mitral leaflet separation along the line of coaptation did not change with ischemia. CONCLUSION: Acute posterolateral left ventricular ischemia causes earlier leaflet opening, probably due to a MR-related elevation in left-atrial pressure; reduces leaflet opening velocity, potentially reflecting an impaired left ventricular relaxation rate; and does not perturb the homogeneous temporal pattern of regional valve opening along the line of coaptation. Future studies will confirm whether these findings are apparent in patients with chronic IMR, and may help to refine the current strategies used to treat IMR.

Ionic Liquid Aqueous Two-Phase Systems From a Pharmaceutical Perspective.

Aqueous Two-Phase Systems (ATPSs) have been extensively studied for their ability to simultaneously separate and purify active pharmaceutical ingredients (APIs) and key intermediates with high yields and high purity. Depending on the ATPS composition, it can be adapted for the separation and purification of cells, nucleic acids, proteins, antibodies, and small molecules. This method has been shown to be scalable, allowing it to be used in the milliliter scale for early drug development to thousands of liters in manufacture for commercial supply. The benefits of ATPS in pharmaceutical separations is increasingly being recognized and investigated by larger pharmaceutical companies. ATPSs use identical instrumentation and similar methodology, therefore a change from traditional methods has a theoretical low barrier of adoption. The cost of typical components used to form an ATPS at large scale, particularly that of polymer-polymer systems, is the primary challenge to widespread use across industry. However, there are a few polymer-salt examples where the increase in yield at commercial scale justifies the cost of using ATPSs for macromolecule purification. More recently, Ionic Liquids (ILs) have been used for ATPS separations that is more sustainable as a solvent, and more economical than polymers often used in ATPSs for small molecule applications. Such IL-ATPSs still retain much of the attractive characteristics such as customizable chemical and physical properties, stability, safety, and most importantly, can provide higher yield separations of organic compounds, and efficient solvent recycling to lower financial and environmental costs of large scale manufacturing.

Microfluidic droplet liquid reactors for active pharmaceutical ingredient crystallization by diffusion controlled solvent extraction.

A novel method for crystallization utilizing solvent/antisolvent extraction in microfluidic droplet liquid reactors has been developed for rapid and low-cost screening of crystal polymorphism (i.e. molecular crystallographic arrangement or internal structure) and habit (i.e. crystallographic shape or external structure). The method involves a ternary solvent system consisting of a dispersed phase of two miscible fluids, one in which the active pharmaceutical ingredient (API) is soluble (solvent) and one in which the API is insoluble (antisolvent). The solvent/antisolvent dispersed phase is immiscible with a third continuous phase. Crystallization of an API, GSK1, was controlled within droplets by altering the rate of solvent extraction from droplets into the continuous phase, thereby decreasing API solubility. Crystal size, habit, and population per droplet were directly impacted by the solvent's rate of extraction. Single crystals were grown in individual droplets by slow extraction of solvent into the surrounding continuous phase, which occurs when crystal growth gradually reduces API concentration such that it is maintained within the metastable zone throughout extraction. Rapid extraction of solvent from droplets results in API concentration significantly exceeding its metastable limit, producing a greater number of crystal nuclei compared to slow extraction conditions. When holding constant solubilized API mass per droplet, crystal sizes were larger for slow extraction rates (l = 96.3, w = 16.6 µm) compared to fast extraction rates (l = 48.8, w = 9.5 µm) as a result of crystal growth occurring on fewer crystal nuclei per droplet. Crystal habit can be controlled by adjusting the solvent extraction rate and consequently the saturation, where minimal saturation resulted in a rhombohedral habit and comparatively higher saturation resulted in an acicular habit with a higher aspect ratio. Antisolvents were tested using two hydrophobic APIs demonstrating the method's capability for rapidly identifying favorable crystal morphologies for downstream manufacturability using miniscule amounts of API.

Effect of chronotropy and inotropy on stitch tension in the edge-to-edge mitral repair.

BACKGROUND: Our prior studies suggest that mitral annular septal-lateral (SL) diameter is the chief determinant of "Alfieri stitch" tension, but hemodynamic parameters may also play a role. We approximated the central edge of the mitral leaflets with a miniature force transducer to measure tension (T) at the leaflet approximation point during inotropic and chronotropic stimulation. METHODS AND RESULTS: Eight sheep were studied under open-chest conditions immediately after surgical placement of a miniature force transducer to approximate the leaflets and implantation of radiopaque markers on the LV and mitral annulus (MA). Chronotropic stimulation was induced with atrial pacing at 130 minutes(-1) (n=5) whereas inotropic state was increased with i.v. CaCl2 bolus (n=8). Hemodynamic data, stitch tension, and 3-D marker coordinates were obtained throughout the cardiac cycle before and during each intervention. Peak stitch tension (T(MAX)) under all conditions was observed in diastole and temporally correlated with peak annular SL (SL(MAX)) size. Atrial pacing did not change peak transducer tension or annular size. Calcium infusion also did not alter peak transducer tension (0.29+/-0.11 versus 0.32+/-0.10 N; P=NS) and only slightly reduced SL dimension (29.9+/-3.3 versus 29.3+/-3.5 mm; P<0.05). CONCLUSION: Isolated increase in heart rate or inotropic state did not alter peak stitch tension whereas enhanced contractile state decreased SL diameter minimally. These data, combined with those from our previous study, suggest that geometric (SL diameter) rather than hemodynamic parameters are the main determinants of "Alfieri stitch" tension. This implies that any interventional or surgical edge-to-edge repair performed without concomitant annular reduction to limit the SL dimension could expose the leaflet junction to forces which could limit repair durability.

Potential interactions of drug-natural health products and natural health products-natural health products among children.

OBJECTIVE: To determine the frequency of concurrent use of conventional medications and natural health products (NHP) and their potential interactions in children arriving at an emergency department. STUDY DESIGN: A survey of parents and patients 0 to 18 years at a large pediatric ED in Toronto, Ontario, Canada. RESULTS: A total of 1804 families were interviewed in this study. Concurrent drug-NHP use was documented in 355 (20%) of patients and 269 (15%) of NHP users were receiving more than one NHP simultaneously. Theoretically possible NHP-drug or NHP-NHP interactions in the preceding 3 months were identified in 285 (16%) children. There were 35 different NHP-medication interaction pairs and 41 NHP-NHP interaction pairs. NHP-medication interactions were predominantly pharmacokinetic (modified absorption, 35%); potential NHP-NHP interactions were mostly pharmacodynamic (increased risk of bleeding, 47%). CONCLUSIONS: Medications are used concurrently with NHP in every fifth pediatric patient in the emergency department and many NHP users are receiving more than 1 NHP simultaneously. One quarter of all paired medication-NHP or NHP-NHP could potentially cause interactions. Although we can not confirm that these were true interactions resulting in clinical symptoms, parents and health care providers need to balance the potential benefit of concurrent NHP-medication use with its potential harms.