Protocol to engineer nanofilms embedded lipid nanoparticles for controlled and targeted drug delivery (NECTAR).

We present a protocol to engineer a substrate-mediated delivery platform comprising hyaluronic acid-coated lipid nanoparticles (HALNPs) embedded into polyelectrolyte multilayer (PEM) films. This platform allows controlled spatiotemporal release of lipid nanoparticles (LNP) by embedding them within the polyelectrolyte multilayer films matrix. HALNP conjugate with antibodies also adds the ability for targeted delivery.

Independent Blinded Validation of a Tissue Systems Pathology Test to Predict Progression in Patients With Barrett's Esophagus.

Introduction: A risk prediction test was previously validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). The aim of our study was to independently validate this test to predict the risk of progression to HGD/EAC in BE patients with nondysplastic (ND), indefinite for dysplasia and low-grade dysplasia (LGD).

Methods: A single-blinded, case-control study was conducted to stratify patients with BE as low, intermediate, or high risk for progression to HGD/EAC within 5 years using a previously described risk prediction test.

Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells.

Metastatic competence of cancer cells is influenced by many factors including metabolic alterations and changes in mitochondrial biogenesis and protein homeostasis. While it is generally accepted that mitochondria play important roles in tumorigenesis, the respective molecular events that regulate aberrant cancer cell proliferation remain to be clarified. Therefore, understanding the mechanisms underlying the role of mitochondria in cancer progression has potential implications in the development of new therapeutic strategies.

Ultraspecific and Amplification-Free Quantification of Mutant DNA by Single-Molecule Kinetic Fingerprinting.

Conventional techniques for detecting rare DNA sequences require many cycles of PCR amplification for high sensitivity and specificity, potentially introducing significant biases and errors. While amplification-free methods exist, they rarely achieve the ability to detect single molecules, and their ability to discriminate between single-nucleotide variants is often dictated by the specificity limits of hybridization thermodynamics. Here we show that a direct detection approach using single-molecule kinetic fingerprinting can surpass the thermodynamic discrimination limit by 3 orders of magnitude, with a dynamic range of up to 5 orders of magnitude with optional super-resolution analysis.

CD44 Targeted Lipid Nanoparticles for MicroRNA Therapy.

MicroRNAs are small noncoding RNAs that function as powerful endogenous regulators of gene expression. Dysregulation of MicroRNA biogenesis has been correlated with the onset and progression of many human diseases. MicroRNA therapy involves the re-equilibration of aberrant intracellular MicroRNA expression profiles for long-term disease management.

A reproductive and developmental screening study of the fungal toxin ochratoxin A in Fischer rats.

The presence of the mycotoxin ochratoxin A (OTA) in cereal grains is due to the growth of toxigenic Penicillium mold on stored crops. Human exposure to OTA is higher in infants, toddlers, and children than in adolescents and adults, based on exposure assessments of ng OTA consumed/kg body weight/day. Ochratoxin A is nephrotoxic and teratogenic in animals, but its effects on juveniles exposed during the reproduction and development period have not been studied.

Serum Magnesium Concentrations in the Canadian Population and Associations with Diabetes, Glycemic Regulation, and Insulin Resistance.

Total serum magnesium (Mg) concentration (SMC) is commonly used to assess Mg status. This study reports current SMCs of Canadians and their associations with demographic factors, diabetes, and measures of glycemic control and insulin resistance using results from the Canadian Health Measures Survey cycle 3 (2012-2013). Associations were examined in adults aged 20-79 years using linear mixed models.

Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer.

MicroRNAs (miRNAs) are endogenous regulators of gene expression that play a pivotal role in biological processes spanning from global homeostasis to disease onset and progression. The ability to manipulate and induce cellular reequilibrium of deregulated miRNA expression profiles by inhibition of oncogenic miRNA or overexpression of tumor suppressor miRNA is a promising cancer strategy, but is currently hindered in application by the lack of nonviral delivery systems. Here we present a lipid nanoparticle (LNP) platform surface coated with Hyaluronic Acid (HA) for the delivery of mature tumor suppressor MicroRNA125a-5p to treat HER2 positive metastatic breast cancer.

Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells.

Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment.

Astrogliosis in a dish: substrate stiffness induces astrogliosis in primary rat astrocytes.

Astrogliosis due to brain injury or disease can lead to varying molecular and morphological changes in astrocytes. Magnetic resonance elastography and ultrasound have demonstrated that brain stiffness varies with age and disease state. However, there is a lack in understanding the role of varied stiffness on the progression of astrogliosis highlighting a critical need to engineer models that mimic disease stages.

Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery.

The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) "(PLL/SPS)4.

Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles.

Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated.

Titanium Dioxide Nanoparticles Trigger Loss of Function and Perturbation of Mitochondrial Dynamics in Primary Hepatocytes.

Titanium dioxide (TiO2) nanoparticles are one of the most highly manufactured and employed nanomaterials in the world with applications in copious industrial and consumer products. The liver is a major accumulation site for many nanoparticles, including TiO2, directly through intentional exposure or indirectly through unintentional ingestion via water, food or animals and increased environmental contamination. Growing concerns over the current usage of TiO2 coupled with the lack of mechanistic understanding of its potential health risk is the motivation for this study.

Evaluating the PAS-SIM model using a passive air sampler calibration study for pesticides.

The main objective of this study was to evaluate the performance of a model for simulating the uptake of various pesticides on passive air samplers (PAS). From 2006-2007 a series of PAS using XAD-resin were deployed at Egbert, a rural agricultural site in southern Ontario, Canada, to measure the uptake of pesticides for time periods ranging from two months to one year. A continuous increase in sequestered amounts was observed for most pesticides, except for trifluralin and pendimethalin, which could conceivably be subject to substantial degradation inside the sampler.

Estimated levels of gluten incidentally present in a Canadian gluten-free diet.

Avoiding exposure to gluten is currently the only effective treatment for celiac disease. However, the evidence suggests that for most affected individuals, exposure to less than 10 mg/day is unlikely to cause histological changes to the intestinal mucosa. The daily diet of people with celiac disease does not rely solely on gluten-free pre-packaged foods, but also on naturally gluten-free grains (e.

Modeling the uptake of neutral organic chemicals on XAD passive air samplers under variable temperatures, external wind speeds and ambient air concentrations (PAS-SIM).

The main objective of this study was to evaluate the performance and demonstrate the utility of a fugacity-based model of XAD passive air samplers (XAD-PAS) designed to simulate the uptake of neutral organic chemicals under variable temperatures, external wind speeds and ambient air concentrations. The model (PAS-SIM) simulates the transport of the chemical across the air-side boundary layer and within the sampler medium, which is segmented into a user-defined number of thin layers. Model performance was evaluated using data for polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) from a field calibration study (i.

Gluten contamination of naturally gluten-free flours and starches used by Canadians with celiac disease.

A large national investigation into the extent of gluten cross-contamination of naturally gluten-free ingredients (flours and starches) sold in Canada was performed. Samples (n = 640) were purchased from eight Canadian cities and via the internet during the period 2010-2012 and analysed for gluten contamination. The results showed that 61 of the 640 (9.

Zinc supplementation does not alter sensitive biomarkers of copper status in healthy boys.

The tolerable upper intake levels (UL) for zinc for children were based on limited data and there is concern that the UL may be set too low. The first effect of excessive zinc intake is a reduction in copper status. The primary objective of this study was to examine the effect of zinc supplementation on copper status in children.

The impact of production type and region on polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) concentrations in Canadian chicken egg yolks.

Chicken eggs from five different production types (conventional, omega-3 enriched, free range, organic and free run) were collected, when available, from three regions (west, central and east) of Canada to determine persistent organic pollutant (POP) concentrations. Total polychlorinated biphenyl (PCB) concentrations (∑37 congeners) in yolks from the eggs ranged from 0.162 ng g(-1) lipid to 24.

Bisphenol A in human placental and fetal liver tissues collected from Greater Montreal area (Quebec) during 1998-2008.

In this study, the presence of bisphenol A (BPA) in human placental and fetal liver samples collected from 1998 to 2008 was investigated to provide a more detailed analysis of the transfer of BPA across the placenta and fetal exposure to BPA. The average concentrations in placental samples were 12.6 ng g(-1) for free BPA, 17.

Internal herniation through the foramen of Winslow during pregnancy: MR findings [corrected].

We present a unique case of jaundice in pregnancy, secondary to common bile duct obstruction by an unusual internal colonic hernia. We also illustrate the benefits of using non-ionizing imaging modalities in the diagnosis and pre-operative planning of this rare condition.

Validation procedures for quantitative food allergen ELISA methods: community guidance and best practices.

This document provides supplemental guidance on specifications for the development and implementation of studies to validate the performance characteristics of quantitative ELISA methods for the determination of food allergens. It is intended as a companion document to other existing publications on method validation. The guidance is divided into two sections: information to be provided by the method developer on various characteristics of the method, and implementation of a multilaboratory validation study.

Comparison of four active and passive sampling techniques for pesticides in air.

Four sampling systems were evaluated for their ability to determine the concentrations of pesticides in the atmosphere of rural southern Ontario. Two active air samplers (AAS, high-volume and low-volume pumps) and two passive air samplers (PAS, polyurethane foam disks and XAD-resin) were deployed between March 2006 and September 2007 using different sampling frequencies (biweekly to annually) and durations (24 h to 1 yr). Concentrations of nine pesticides in air determined by the different systems were compared at time scales of two weeks, two months, and one year.

Levels and seasonal variability of pesticides in the rural atmosphere of Southern Ontario.

Air samples were collected continuously in Egbert, Ontario, which is in a rural agricultural area north of Toronto, between March 2006 and September 2007 and analyzed for pesticides of both current and historic use. The fungicide chlorothalonil was present in highest abundance with levels exceeding 2000 pg x m(-3) in the summer. Almost as abundant, with summer time concentrations around 400 to 600 pg x m(-3), were the herbicides atrazine, alachlor, and metolachlor.

Multicenter comparison of two norovirus ORF2-based genotyping protocols.

Point source norovirus outbreaks can be difficult to track due to high background levels of the virus in the environment and the limited strain variation in some genotyping regions. However, rapid and accurate source identification can limit the spread of a foodborne outbreak and reduce the number of cases. Harmonization of genotyping assays is critical for enabling the rapid exchange of sequence data nationally and internationally.