Self-report methodology for quantifying standardized cannabis consumption in milligrams delta-9-tetrahydrocannabinol.

Background: There is currently no format-independent method to determine delta-9-tetrahydrocannabinol (THC) in milligrams for self-report studies.Objectives: Validate self-report method for quantifying mg THC from commercially available cannabis products using product labeling, which includes both net weight and product potency.Methods: 53 adult cannabis users (24 M, 29F), 21-39 years of age (M = 28.38, SD = 4.15), were instructed to report daily use via a weekly survey for two consecutive weeks, provide product label photographs, abstain from use for 24 h, submit a urine sample and complete the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) and the Marijuana Craving Questionnaire - Short Form (MCQ-SF). Milligrams of THC were determined by multiplying quantity of product used by its THC concentration. Urine was analyzed for the urine metabolite 11-nor-carboxy-THC (THC-COOH) via liquid chromatography mass spectroscopy. THC and THC-COOH values were log10 transformed prior to correlational analyses.Results: Median daily THC consumption was 102.53 mg (M = 203.68, SD = 268.13). Thirty-three (62%) of the 53 participants reported using two or more formats over the 2-week period. There was a significant positive correlation between log10 THC-COOH and log10 THC mg (r(41) = .59, p < .001), log10 THC mg and MCQ-SF score (r(41) = .59, p < .001), and log10 THC mg dose and CUDIT-R score, (r(41) = .39, p = .010).Conclusion: Our label-based methodology provides consumption information across all modalities of cannabis use in standard units that can be combined across products for calculation of dose. It is a viable and valid method for quantifying mg of THC consumed and can be utilized in any region where cannabis is legal, and labeling is regulated.

'Personality and bipolar disorder: personality profiles of patients with remitted bipolar disorder and matched controls in a Danish sample'.

BACKGROUND: The aim of the study was to investigate whether patients with bipolar disorder (BD) in remission differ in personality traits compared with a healthy control group. METHODS: A sample of patients with BD (n = 44) was compared with an individually matched control group (n = 44) using the Danish version of the Revised NEO Personality Inventory (NEO PI-R). Paired t-tests were used to analyze differences between the two groups and multiple regression models to evaluate predictors of NEO scores in the patient group. RESULTS: Patients with BD reported significantly higher scores on both Neuroticism and Openness to Experience and lower scores on Conscientiousness. No differences were found on Extraversion and Agreeableness. The effect size for Neuroticism and its facets had a range from 0.77 to 1.45 SD.Statistically significant group differences were seen on 15 of 30 lower-level traits within all five high-order dimensions. There were large effect sizes for Trust (0.77) and Self-discipline (0.85), while the other statistically significant group differences were smaller with effect sizes in the range from 0.43 to 0.74 SD.However, patients with BD showed a profile with high-order dimensions and lower-level traits within one standard deviation from the mean score except for the lower-level trait Depression. CONCLUSIONS: Our findings suggest that patients with BD differ from healthy control persons with respect to higher levels of Neuroticism, Openness to Experience and lower scores on Agreeableness and on Conscientiousness, but prospective studies are needed to evaluate the implications of this finding.

Natural product derivative Gossypolone inhibits Musashi family of RNA-binding proteins.

BACKGROUND: The Musashi (MSI) family of RNA-binding proteins is best known for the role in post-transcriptional regulation of target mRNAs. Elevated MSI1 levels in a variety of human cancer are associated with up-regulation of Notch/Wnt signaling. MSI1 binds to and negatively regulates translation of Numb and APC (adenomatous polyposis coli), negative regulators of Notch and Wnt signaling respectively. METHODS: Previously, we have shown that the natural product (-)-gossypol as the first known small molecule inhibitor of MSI1 that down-regulates Notch/Wnt signaling and inhibits tumor xenograft growth in vivo. Using a fluorescence polarization (FP) competition assay, we identified gossypolone (Gn) with a > 20-fold increase in Ki value compared to (-)-gossypol. We validated Gn binding to MSI1 using surface plasmon resonance, nuclear magnetic resonance, and cellular thermal shift assay, and tested the effects of Gn on colon cancer cells and colon cancer DLD-1 xenografts in nude mice. RESULTS: In colon cancer cells, Gn reduced Notch/Wnt signaling and induced apoptosis. Compared to (-)-gossypol, the same concentration of Gn is less active in all the cell assays tested. To increase Gn bioavailability, we used PEGylated liposomes in our in vivo studies. Gn-lip via tail vein injection inhibited the growth of human colon cancer DLD-1 xenografts in nude mice, as compared to the untreated control (P < 0.01, n = 10). CONCLUSION: Our data suggest that PEGylation improved the bioavailability of Gn as well as achieved tumor-targeted delivery and controlled release of Gn, which enhanced its overall biocompatibility and drug efficacy in vivo. This provides proof of concept for the development of Gn-lip as a molecular therapy for colon cancer with MSI1/MSI2 overexpression.

Surface Adsorption of Suwannee River Humic Acid on TiO2 Nanoparticles: A Study of pH and Particle Size.

TiO2 nanoparticles are some of the most widely used metal oxide nanomaterials mainly because of their diverse industrial applications. Increasing usage of these nanoparticles raises concerns about the potential adverse effects on the environment. Humic acid is a ubiquitous component of the natural organic matter in the environment that is known to get adsorbed onto nanoparticle surfaces. In this study, adsorption of humic acid on TiO2 nanoparticles of two different sizes (5 and 22 nm) is studied at different environmentally relevant pH values using attenuated total reflectance Fourier transformation infrared spectroscopy. These vibrational spectra provide insights into the nature of the adsorption process (extent of adsorption and reversibility) as a function of pH as well as information about the bonding to the surface. Additionally, the impact of humic acid adsorption on surface charge and agglomeration has been investigated. Interestingly, the results show that the humic acid adsorption is strongly pH-dependent and that adsorption of humic acid on TiO2 nanoparticles alters the extent of agglomeration and modifies the zeta potential and surface charges depending on the pH, thus potentially increasing the bioavailability of TiO2 nanoparticles in the environment.

Sequestration of U(VI) from Acidic, Alkaline, and High Ionic-Strength Aqueous Media by Functionalized Magnetic Mesoporous Silica Nanoparticles: Capacity and Binding Mechanisms.

Uranium(VI) exhibits little adsorption onto sediment minerals in acidic, alkaline or high ionic-strength aqueous media that often occur in U mining or contaminated sites, which makes U(VI) very mobile and difficult to sequester. In this work, magnetic mesoporous silica nanoparticles (MMSNs) were functionalized with several organic ligands. The functionalized MMSNs were highly effective and had large binding capacity for U sequestration from high salt water (HSW) simulant (54 mg U/g sorbent). The functionalized MMSNs, after U exposure in HSW simulant, pH 3.5 and 9.6 artificial groundwater (AGW), were characterized by a host of spectroscopic methods. Among the key novel findings in this work was that in the HSW simulant or high pH AGW, the dominant U species bound to the functionalized MMSNs were uranyl or uranyl hydroxide, rather than uranyl carbonates as expected. The surface functional groups appear to be out-competing the carbonate ligands associated with the aqueous U species. The uranyl-like species were bound with N ligand as η2 bound motifs or phosphonate ligand as a monodentate, as well as on tetrahedral Si sites as an edge-sharing bidentate. The N and phosphonate ligand-functionalized MMSNs hold promise as effective sorbents for sequestering U from acidic, alkaline or high ionic-strength contaminated aqueous media.

Nano-Bio Interactions of Porous and Nonporous Silica Nanoparticles of Varied Surface Chemistry: A Structural, Kinetic, and Thermodynamic Study of Protein Adsorption from RPMI Culture Medium.

Understanding complex chemical changes that take place at nano-bio interfaces is of great concern for being able to sustainably implement nanomaterials in key applications such as drug delivery, imaging, and environmental remediation. Typical in vitro assays use cell viability as a proxy to understanding nanotoxicity but often neglect how the nanomaterial surface can be altered by adsorption of solution-phase components in the medium. Protein coronas form on the nanomaterial surface when incubated in proteinaceous solutions. Herein, we apply a broad array of techniques to characterize and quantify protein corona formation on silica nanoparticle surfaces. The porosity and surface chemistry of the silica nanoparticles have been systematically varied. Using spectroscopic tools such as FTIR and circular dichroism, structural changes and kinetic processes involved in protein adsorption were evaluated. Additionally, by implementing thermogravimetric analysis, quantitative protein adsorption measurements allowed for the direct comparison between samples. Taken together, these measurements enabled the extraction of useful chemical information on protein binding onto nanoparticles in solution. Overall, we demonstrate that small alkylamines can increase protein adsorption and that even large polymeric molecules such as poly(ethylene glycol) (PEG) cannot prevent protein adsorption in these systems. The implications of these results as they relate to further understanding nano-bio interactions are discussed.

Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer.

BACKGROUND: Resistance to antiestrogen therapy is a major clinical challenge in the treatment of estrogen receptor α (ER)-positive breast cancer. The aim of the study was to explore the growth promoting pathways of antiestrogen resistant breast cancer cells to identify biomarkers and novel treatment targets. METHODS: Antiestrogen sensitive and resistant T47D breast cancer cell lines were used as model systems. Parental and fulvestrant resistant cell lines were subjected to a kinase inhibitor library. Kinase inhibitors preferentially targeting growth of fulvestrant resistant cells were identified and the growth inhibitory effect verified by dose-response cell growth experiments. Protein expression and phosphorylation were investigated by western blot analysis. Cell cycle phase distribution and cell death were analyzed by flow cytometry. To evaluate Aurora kinase B as a biomarker for endocrine resistance, immunohistochemistry was performed on archival primary tumor tissue from breast cancer patients who have received adjuvant endocrine treatment with tamoxifen. RESULTS: The selective Aurora kinase B inhibitor barasertib was identified to preferentially inhibit growth of fulvestrant resistant T47D breast cancer cell lines. Compared with parental cells, phosphorylation of Aurora kinase B was higher in the fulvestrant resistant T47D cells. Barasertib induced degradation of Aurora kinase B, caused mitotic errors, and induced apoptotic cell death as measured by accumulation of SubG1 cells and PARP cleavage in the fulvestrant resistant cells. Barasertib also exerted preferential growth inhibition of tamoxifen resistant T47D cell lines. Finally, high percentage of Aurora kinase B positive tumor cells was significantly associated with reduced disease-free and overall survival in 261 ER-positive breast cancer patients, who have received tamoxifen as first-line adjuvant endocrine treatment. CONCLUSIONS: Our results indicate that Aurora kinase B is a driving factor for growth of antiestrogen resistant T47D breast cancer cell lines, and a biomarker for reduced benefit of tamoxifen treatment. Thus, inhibition of Aurora kinase B, e.g. with the highly selective kinase inhibitor barasertib, could be a candidate new treatment for breast cancer patients with acquired resistance to antiestrogens.

Chemical Insight into the Adsorption of Chromium(III) on Iron Oxide/Mesoporous Silica Nanocomposites.

Magnetic iron oxide/mesoporous silica nanocomposites consisting of iron oxide nanoparticles embedded within mesoporous silica (MCM-41) and modified with aminopropyl functional groups were prepared for application to Cr(III) adsorption followed by magnetic recovery of the nanocomposite materials from aqueous solution. The composite materials were extensively characterized using physicochemical techniques, such as powder X-ray diffraction, thermogravimetric and elemental analysis, nitrogen adsorption, and zeta potential measurements. For aqueous Cr(III) at pH 5.4, the iron oxide/mesoporous silica nanocomposite exhibited a superior equilibrium adsorption capacity of 0.71 mmol/g, relative to 0.17 mmol/g for unmodified mesoporous silica. The aminopropyl-functionalized iron oxide/mesoporous silica nanocomposites displayed an equilibrium adsorption capacity of 2.08 mmol/g, the highest adsorption capacity for Cr(III) of all the materials evaluated in this study. Energy-dispersive spectroscopy (EDS) with transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) experiments provided insight into the chemical nature of the adsorbed chromium species.

Perceived Factors That Facilitate or Prevent the Use of Speech-Generating Devices in Bilingual Individuals With Aphasia.

PURPOSE: The aim of this study was to explore practicing speech-language pathologists' (SLPs') perceptions of factors that could facilitate or prevent the use of speech-generating devices (SGDs) in bilingual individuals with aphasia. Specifically, this exploratory study sought to identify the facilitators and barriers to SGD use in individuals with culturally and linguistically diverse backgrounds. METHOD: An online survey was distributed to SLPs through an e-mail listserv and social media of an augmentative and alternative communication company. This article focused on the results of the survey items related to (a) the presence of bilingual individuals with aphasia on an SLP's caseload, (b) training related to SGD or bilingual aphasia, and (c) barriers and facilitators to SGD use. A thematic analysis was conducted to analyze the barriers and facilitators to SGD use reported by the respondents. RESULTS: A total of 274 SLPs who met the inclusion criteria had experience in implementing SGD for people with aphasia. Regarding relevant training, our results indicated that very few SLPs received bilingual aphasia intervention training (17.22%) or bilingual SGD training (0.56%) in graduate school. The results from our thematic analysis revealed four major themes of barriers and facilitators to SGD use, including (a) hardware and software, (b) cultural and language content, (c) SLP's cultural and linguistic competency, and (d) resources. CONCLUSIONS: Practicing SLPs reported several barriers to SGD use in bilinguals with aphasia. Most notably, language barriers for monolingual SLPs were seen as the greatest barrier to language recovery in individuals with aphasia whose primary language is not English. Several other barriers were consistent with previous research, such as financial factors and insurance disparities. The top three most important factors that facilitate SGD use in bilinguals with aphasia, as identified by the respondents, include user-friendly symbol organization, personalized words, and ease of programming.

Preparation of a versatile bifunctional zeolite for targeted imaging applications.

Bifunctional zeolite Y was prepared for use in targeted in vivo molecular imaging applications. The strategy involved functionalization of the external surface of zeolite Y with chloropropyltriethoxysilane followed by reaction with sodium azide to form azide-functionalized NaY, which is amenable to copper(1)-catalyzed click chemistry. In this study, a model alkyne (4-pentyn-1-ol) was attached to the azide-terminated surface via click chemistry to demonstrate feasibility for attachment of molecular targeting vectors (e.g., peptides, aptamers) to the zeolite surface. The modified particle efficiently incorporates the imaging radioisotope gallium-68 ((68)Ga) into the pores of the azide-functionalized NaY zeolite to form a stable bifunctional molecular targeting vector. The result is a versatile "clickable" zeolite platform that can be tailored for future in vivo molecular targeting and imaging modalities.

Framework stability of nanocrystalline NaY in aqueous solution at varying pH.

Nanocrystalline zeolites are emerging as important materials for a variety of potential applications in industry and medicine. Reducing the particle size to less than 100 nm results in advantages for nanocrystalline zeolites relative to micrometer-sized zeolite crystals, such as very large total and external specific surface areas and reduced diffusion path lengths. Understanding the physical and chemical properties of zeolite nanocrystals is imperative for further development and application of nanocrystalline zeolites. In this study, the framework stability of nanocrystalline NaY zeolite with a crystal size of 66 nm and Si/Al = 1.74 was investigated at pH 7.4, 4, 2, and 1. The solids and solutions were analyzed using several different analytical techniques. The relative crystallinity and crystal size and morphology of the solids were examined by powder X-ray diffraction (XRD) and transmission electron microscopy (TEM), respectively. The aluminum content, Si/Al, and coordination were monitored by inductively coupled plasma/optical emission spectroscopy (ICP/OES), X-ray photoelectron spectroscopy (XPS), and aluminum-27 solid-state magic-angle spinning NMR. As the acidity of the medium increased, the framework stability of nanocrystalline NaY decreased. Treatment of the zeolite samples at pH 1 resulted in complete degradation of the zeolite framework after 1 h. An increase in Si/Al was also observed, suggesting the selective removal of aluminum at low pH.

DFT calculations of EPR parameters for copper(II)-exchanged zeolites using cluster models.

The coordination environment of Cu(II) in hydrated copper-exchanged zeolites was explored through the use of density functional theory (DFT) calculations of EPR parameters. Extensive experimental EPR data are available in the literature for hydrated copper-exchanged zeolites. The copper complex in hydrated copper-exchanged zeolites was previously proposed to be [Cu(H(2)O)(5)OH](+) based on empirical trends in tetragonal model complex EPR data. In this study, calculated EPR parameters for the previously proposed copper complex, [Cu(H(2)O)(5)OH](+), were compared to model complexes in which Cu(II) was coordinated to small silicate or aluminosilicate clusters as a first approximation of the impact of the zeolitic environment on the copper complex. Interpretation of the results suggests that Cu(II) is coordinated or closely associated with framework oxygen atoms within the zeolite structure. Additionally, it is proposed that the EPR parameters are dependent on the Si/Al ratio of the parent zeolite.

Cold-induced hyperphagia requires AgRP neuron activation in mice.

To maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake but has no effect on energy expenditure. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure.

Insight into the copper coordination environment in the prion protein through density functional theory calculations of EPR parameters.

Density functional theory (DFT) calculations of Cu(II) electron paramagnetic resonance (EPR) parameters for the octarepeat unit of the prion protein were conducted. Model complexes were constructed and optimized using the crystal structure of the octarepeat unit of the prion protein. Copper g and A tensors and nitrogen hyperfine and quadrupole coupling constants were calculated using DFT. Solvent effects were incorporated using the conductor-like screening model as well as through the inclusion of explicit water molecules. Calculations using the model with an additional axial water molecule added to the coordination sphere of the Cu(II) metal center give the best qualitative agreement for the copper g and A tensors. The S-band experimental EPR spectra were interpreted in light of the DFT calculations of the directly coordinated nitrogen hyperfine coupling constants which indicate that the three directly coordinated nitrogen atoms in the octarepeat unit are not equivalent. These results demonstrate that DFT calculations of EPR parameters can provide important insight with respect to the structural interpretation of experimental EPR data.

Effect of crystal size and surface functionalization on the cytotoxicity of silicalite-1 nanoparticles.

In this report, we describe the synthesis and characterization of nanocrystalline silicalite (the purely siliceous form of the zeolite, ZSM-5) of defined crystal size and surface functionalization and determine the effect on the type and degree of cytotoxicity induced in two distinct model cell lines. The silicalite materials were characterized by powder X-ray diffraction, dynamic light scattering and zeta potential, solid state NMR, thermal gravimetric analysis, and nitrogen adsorption using the BET method to determine specific surface area. The silicalite samples were functionalized with amino, thiol, and carboxy groups and had crystal sizes of approximately 30, 150, and 500 nm. The cytotoxicities of the silicalite samples with different crystal sizes and different surface functional groups were investigated using human embryonic kidney 293 (HEK-293) cells and RAW264.7 macrophage cell lines. We used the lactic dehydrogenase release assay to measure damage to the cell membrane, the caspase 3/7 activity assay to measure key molecules involved in apoptosis, and the Annexin V-propidium iodide staining method to provide visual confirmation of the types of cell death induced. We have shown that the impact of size and surface functionalization of silicalite nanoparticles on cell toxicity and mechanism of cell death is cell type-dependent. Thirty nanometer silicalite nanoparticles were nontoxic in RAW264.7 cells relative to untreated controls but caused necrosis in HEK293 cells. Carboxy-functionalized 500 nm silicalite nanoparticles resulted in apoptosis and necrosis in RAW264.7 cells and predominantly activated apoptosis in HEK293 cells.

Density functional theory investigation of EPR parameters for tetragonal Cu(II) model complexes with oxygen ligands.

Density functional theory (DFT) calculations of the electron paramagnetic resonance (EPR) parameters for a series of tetragonal Cu(II) model complexes were conducted. Model complexes containing four oxygen atoms directly coordinated to a Cu(II) metal center were chosen because of their importance in the Peisach-Blumberg truth tables and their frequent use in the interpretation of EPR spectra of Cu(II) proteins and copper-containing catalysts. Molecular g- and copper A-tensors were calculated using the BP86 and B3LYP density functionals. The DFT calculations reproduce the experimentally observed trends in the parallel components of the A- and g-tensors. Important insight into the structural basis for the empirical trends in g( parallel) and A( parallel) was obtained from the DFT calculations. Notably, g( parallel) systematically increases and A( parallel) systematically decreases with increasing Cu-O equatorial bond length. These results have been used to provide structural insight into copper EPR data for copper-exchanged zeolites.

Mechanochemically-assisted solvent-free and template-free synthesis of zeolites ZSM-5 and mordenite.

Aluminosilicate-based zeolite materials, such as ZSM-5 and mordenite, are well-studied as catalysts. Typical approaches to synthesize these zeolites require either templates or seeds to direct ordered crystal growth and both of these are expensive and add to the complexity of zeolite synthesis. In this paper, we describe a solvent-free and template-free method to synthesize crystalline ZSM-5 and mordenite zeolites without any added seed crystals. Key to the success of this approach is a mechanochemical precursor pre-reaction step. High-energy ball-milling is used to initiate a solid-state metathesis (exchange) reaction between Na2SiO3 and Al2(SO4)3 reagents, forming crystalline Na2SO4 and well-mixed aluminosilicate precursor. The solid precursor mixture is thermally converted to crystalline ZSM-5 or mordenite at moderate 180 °C temperatures without solvents or an organic amine structure directing template. Variations in Si/Al ratios in the precursor mixture and additions of solid NaOH to the mechanochemical reaction were found to influence the subsequent growth of either crystalline ZSM-5 or mordenite zeolites. The crystalline zeolites from this solvent-free and template free method have high ∼300 m2 g-1 surface areas directly from the synthesis without requiring high-temperature calcination. These materials are also comparably active to their commercial counterparts in cellulose and glucose biomass catalytic conversion to hydroxymethylfurfural.

Quantification of gabapentin polymorphs in gabapentin/excipient mixtures using solid state 13C NMR spectroscopy and X-ray powder diffraction.

Gabapentin was used as a model pharmaceutical compound with susceptibility to polymorphic transformation as a function of environmental and mechanical stress. The utility of 13C CP/MAS NMR and XRPD as stability-indicating methods to quantify polymorphic transformation kinetics was investigated. Polymorphic Form II and III were distinguishable based on their chemical shift and distinct diffraction peak differences. Reproducible and accurate quantification of polymorphic composition in the presence of selected excipients was demonstrated using both signals from 13C CP/MAS NMR spectra and XRPD patterns. The effect of excipients on polymorphic transformations (Form II→III) was determined by measuring the transformation after co-milling. Both 13C CP/MAS NMR and XRPD were capable of measuring polymorphic composition in co-milled excipient mixtures without excipient peak interference. The amounts of Form III present in co-milled mixtures containing colloidal silicon dioxide, starch, hydroxy propyl cellulose and dibasic calcium phosphate were 8.7, 21, 33, and 39mol%, respectively. A quenching procedure for obtaining 13C CP/MAS NMR spectra and environmentally-controlled XRPD were devised to determine polymorphic transformation kinetics of co-milled excipient mixtures during storage.