Mitral Annular Elasticity Determines Severity of Regurgitation in Barlow's Mitral Valve Disease.

OBJECTIVES: Barlow's mitral valve disease with late systolic mitral regurgitation provides diagnostic and therapeutic challenges. The mechanisms of the regurgitation are still unclear. We hypothesized that the onset and the severity of late systolic regurgitation are determined by annulus dynamics and the mechanical stresses imposed by the left ventricle. METHODS: Ten patients with Barlow's mitral valve disease and mitral annulus disjunction (MAD) were compared with 10 healthy controls. Resting blood pressure was measured, and transthoracic three-dimensional echocardiography was analyzed using a holographic display that allows tracking and measurements of mitral annulus surface area (ASA) throughout the cardiac cycle. A novel annulus elastance index (dASA/dP) was calculated between aortic valve opening and onset of mitral regurgitation. Severity of MAD was quantified as the disjunction index (mm × degree). Leaflet coaptation area was calculated using a finite element model. RESULTS: Peak systolic ASAs in controls and patients were 9.3 ± 0.6 and 21.1 ± 3.1 cm2, respectively (P < .001). In patients, the ASA increased rapidly during left ventricular ejection, and onset of mitral regurgitation coincided closely with peak upslope of annulus area change (dASA/dt). The finite element model showed a close association between rapid annulus displacement and coaptation area deficit in Barlow's mitral valve disease. Systolic annulus elastance index (0.058 ± 0.036 cm2/mm Hg) correlated strongly with disjunction index (r = 0.91, P < .0001). Moreover, regurgitation volume showed a positive correlation with systolic blood pressure (r = 0.80, P < .01). CONCLUSION: The present pilot study supports the hypothesis that annulus dilatation may accentuate mitral valve regurgitation in patients with Barlow's mitral valve disease. A novel annulus elastance index may predict the severity of mitral valve regurgitation in selected patients.

Application of Decomposition Analysis of Spatial Accessibility (DASA) in Health Services Research.

Withdrawal mapping is effective in showing the educational impact of residency programs and medical schools. It is often used for advocacy and education purposes, but it lacks grounding in the theoretical foundation of spatial accessibility research. This study proposes an improved technique called Decomposition Analysis of Spatial Accessibility, or DASA, to decompose spatial accessibility by applying the withdrawal mapping concept to the classical 2SFCA application. This study applies the DASA technique to three case studies with policy implications. The first case study details the contribution of Black surgeons to public access to the surgical workforce. The second case study details the contribution of international medical graduates from the original seven travel-ban countries. The third case study demonstrates the market competition between family physicians and general pediatricians. The study showcases the usefulness (particularly for workforce-planning for underserved populations) of the DASA technique in understanding subgroup contributions in spatial accessibility analyses.

A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2-Induced Glycolytic Reprogramming in Glioblastoma.

PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM. EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/µmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma. RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation. CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

Degradation of the residual textile mixture cetyltrimethylammonium bromide/remazol yellow gold RNL-150%/reactive blue BF-5G: evaluation photo-peroxidation and photo-Fenton processes in LED and UV-C photoreactors.

This article presents a study on the degradation of a residual textile mixture composed of cationic surfactant cetyltrimethylammonium bromide (CTAB) and the remazol yellow gold RNL-150% and reactive blue BF-5G textile dyes. This was carried out by employing the photo-peroxidation and photo-Fenton processes in LED and UV-C photoreactors. The photo-Fenton process was the most efficient as regards the degradation of the CTAB and dye mixture, for both types of radiation. In the kinetic study, degradations of 99% were obtained in 180 min for the chromophore groups using both types of radiation. The degradation of the CTAB and aromatic groups was, meanwhile, an average of 25% when employing LED radiation. The behavior of the degradation reaction was pseudo-first-order. Toxicity tests indicated that the solutions were better able to grow seeds and bacteria after treatment with the photo-Fenton process, using both types of radiation. The photo-Fenton processes carried out by employing LED and UV-C photoreactors were able to degrade the CTAB and dye mixture, thus highlighting the efficiency of LED radiation when its power (three times smaller) is compared to that of UV-C radiation. This process, therefore, represents an alternative for use in textile wastewater treatment systems.

Tumor treating fields (TTFields) impairs aberrant glycolysis in glioblastoma as evaluated by [18F]DASA-23, a non-invasive probe of pyruvate kinase M2 (PKM2) expression.

Despite the anti-proliferative and survival benefits from tumor treating fields (TTFields) in human glioblastoma (hGBM), little is known about the effects of this form of alternating electric fields therapy on the aberrant glycolysis of hGBM. [18F]FDG is the most common radiotracer in cancer metabolic imaging, but its utility in hGBM is impaired due to high glucose uptake in normal brain tissue. With TTFields, radiochemistry, Western blot, and immunofluorescence microscopy, we identified pyruvate kinase M2 (PKM2) as a biomarker of hGBM response to therapeutic TTFields. We used [18F]DASA-23, a novel radiotracer that measures PKM2 expression and which has been shown to be safe in humans, to detect a shift away from hGBM aberrant glycolysis in response to TTFields. Compared to unexposed hGBM, [18F]DASA-23 uptake was reduced in hGBM exposed to TTFields (53%, P< 0.05) or temozolomide chemotherapy (33%, P > 0.05) for 3 d. A 6-d TTFields exposure resulted in a 31% reduction (P = 0.043) in 60-min uptake of [18F]DASA-23. [18F]DASA-23 was retained after a 10 but not 30-min wash-out period. Compared to [18F]FDG, [18F]DASA-23 demonstrated a 4- to 9-fold greater uptake, implying an improved tumor-to-background ratio. Furthermore, compared to no-TTFields exposure, a 6-d TTFields exposure caused a 35% reduction in [18F]DASA-23 30-min uptake compared to only an 8% reduction in [18F]FDG 30-min uptake. Quantitative Western blot analysis and qualitative immunofluorescence for PKM2 confirmed the TTFields-induced reduction in PKM2 expression. This is the first study to demonstrate that TTFields impairs hGBM aberrant glycolytic metabolism through reduced PKM2 expression, which can be non-invasively detected by the [18F]DASA-23 radiotracer.

Specific Non-Reducing Ends in Heparins from Different Animal Origins: Building Blocks Analysis Using Reductive Amination Tagging by Sulfanilic Acid.

Heparins are linear sulfated polysaccharides widely used as anticoagulant drugs. Their nonreducing-end (NRE) has been little investigated due to challenges in their characterization, but is known to be partly generated by enzymatic cleavage with heparanases, resulting in N-sulfated glucosamines at the NRE. Uronic NRE (specifically glucuronic acids) have been isolated from porcine heparin, with GlcA-GlcNS,3S,6S identified as a porcine-specific NRE marker. To further characterize NRE in heparinoids, a building block analysis involving exhaustive heparinase digestion and subsequent reductive amination with sulfanilic acid was performed. This study describes a new method for identifying heparin classical building blocks and novel NRE building blocks using strong anion exchange chromatography on AS11 columns for the assay, and ion-pair liquid chromatography-mass spectrometry for building block identification. Porcine, ovine, and bovine intestine heparins were analyzed. Generally, NRE on these three heparins are highly sulfated moieties, particularly with 3-O sulfates, and the observed composition of the NRE is highly dependent on heparin origin. At the highest level of specificity, the isolated marker was only detected in porcine heparin. However, the proportion of glucosamines in the NRE and the proportion of glucuronic/iduronic configurations in the NRE uronic moieties greatly varied between heparin types.

Sulfonated glycosaminoglycan bioinspired carbon dots for effective cellular labelling and promotion of the differentiation of mesenchymal stem cells.

Although carbon dots (CDs) have been synthesized and applied in a variety of biological fields, such as disease diagnosis and gene/drug delivery, the exploration of facile bioinspired synthesis and applications of CDs is still of great significance. Particularly, recent increasing research has clearly confirmed that nanomaterials can affect a series of physiological behaviors and functions of mesenchymal stem cells (MSCs) (e.g., differentiation and pluripotency). Therefore, it is very important to develop multifunctional nanomaterials to simultaneously realize the cellular labelling and regulation of MSC behaviors in practical applications. Herein, sulfonated glycosaminoglycan-bioinspired CDs as bi-functional nanomaterials were ingeniously designed for cellular imaging and promoting the differentiation of rat bone MSCs (rBMSCs) in different culture media, which simultaneously met the two fundamental requirements in the field of MSC-based treatments (e.g., precisely directing the differentiation of MSCs and effective cellular labeling). These bifunctional CDs were successfully prepared via one-pot hydrothermal synthesis by using d-glucosamine hydrochloride (GA·HCl) and sodium p-styrenesulfonate (NaSS) as the reactants. The synthesized CDs with a uniform particle size (around 4 nm) dispersed well in aqueous solutions and exhibited remarkable fluorescence stability under different conditions. Additionally, cell viability and proliferation results demonstrated that the CDs possessed good biocompatibility, having negligible effects on the self-renewal potential of rBMSCs. The as-prepared CDs presented a cytoplasmatic distribution after being ingested by rBMSCs; thus, they are particularly suitable for cellular imaging. More importantly, the addition of CDs to osteogenic and chondrogenic induction media (OIM and CIM), respectively, was capable of effectively promoting the osteogenic and chondrogenic differentiation of rBMSCs due to the generation of reactive oxygen species (ROS) while having no influence on their pluripotency. In brief, this study not only implements a cellular labeling method based on CDs that were synthesized by a biomimicking strategy, but also paves a new way to regulate the differentiation of MSCs by designing multifunctional nanomaterials; this will enable the extensive development of facile synthesis methods and new applications of CDs and will also provide some research foundations for MSC-based fields.

Application of novel bacterial consortium for biodegradation of aromatic amine 2-ABS using response surface methodology.

There is a strong need to develop purification methods for textile industrial wastewater containing toxic azo dyes. The reductive cleavage of azo dyes can be made by anaerobic bacteria, but the products of aromatic amines require an aerobic process. In this study a novel bacterial dye degrading consortium (DDC) of five isolated strains identified with 16S rRNA sequence: Proteus mirabilis (KR732288), Bacillus anthracis (KR732289), Enterobacter hormaechei (KR732290), Pseudomonas aeruginosa (KR732293) and Serratia rubidaea (KR732296) were used to aerobically decompose metabolite 2-aminobenxenesulfonic acid (2-ABS), as a model compound. The effect of three variables: temperature (28-42 °C), pH (5.0-8.0) and initial concentration of 2-ABS (5-40 ppm) was investigated in terms of degradation and chemical oxygen demand (COD) removal. Central composite design matrixand response surface methodology (RSM) were used for experimental design to evaluate theinteraction of the three process variables. The results show that up to 95% degradation and COD 90% removal are possible at optimal values of 32.4 ppm 2-ABS, pH 6.6 and a temperature of 35.7 °C. The theoretical response variables predicted by the developed RSM model was supported the experimental results. The optimized degradation of 2-ABS and COD removal were further confirmed by UV-HPLC analysis.

Synthesis of sulfonated chitosan-derived carbon-based catalysts and their applications in the production of 5-hydroxymethylfurfural.

A novel sulfonated chitosan-derived carbon-based catalyst was successfully prepared via isoamyl nitrite-assisted sulfanilic acid sulfonation, and its catalytic activity was examined using dehydration of fructose. The structural and chemical properties of sulfonated chitosan-derived carbon were characterized by SEM, FTIR, XRD, XPS, element analysis, N2 adsorption-desorption experiment, and acid-base titration experiment. KOH was used as activating agent in the synthesizing of carbon supports, and it was found that properly increasing the dose of KOH during activation stage had a positive effect on the subsequent sulfonation of prepared activated carbon. 4KSCC, with the highest sulfonation degree (2.04 mmol/g), exhibited high performance for the conversion of fructose to HMF in various solvent, and an optimal HMF yield of 80.9% was obtained at 140 °C in 40 min. In addition, the reusability of 4KSCC for fructose dehydration was fairly good.

Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2.

PURPOSE: To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers. METHODS: We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software. RESULTS: All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 µSv/MBq. CONCLUSION: We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03539731 (registered 28 May 2018).

Sulfonated graphene oxide and titanium dioxide coated with nanostructured polyaniline nanocomposites as an efficient cathode catalyst in microbial fuel cells.

In this study, sulfonated graphene oxide (SGO) was synthesized as potential conducting matrix to improve the properties of catalyst for single chamber microbial fuel cells (SC-MFCs). Here, TiO2 and Polyaniline (PAni) nanoparticles were anchored over SGO and the resulting SGO-TiO2-PAni nanocomposites were used as a potential cathode catalyst in MFCs. We have also examined the performance of SGO-TiO2-PAni compared to GO-TiO2-PAni and TiO2-PAni catalyst. The structural and morphological analyses were examined using a variety of characterization techniques. TiO2 nanoparticles bridged PAni and SGO through hydrogen bonding/electrostatic interaction and improved the thermal stability of SGO-TiO2-PAni catalyst. The electrochemical characterizations of these nanocatalysts suggest that the SGO-TiO2-PAni showed higher reduction current value (-0.46 mA), enhanced stability, and lower internal resistance (46.2 Ω) in comparison to GO-TiO2-PAni and TiO2-PAni towards oxygen reduction reactions (ORR). Consequently, MFC using SGO-TiO2-PAni demonstrated a maximum power density of 904.18 mWm-2 than that of GO-TiO2-PAni (734.12 mWm-2), TiO2-PAni (561.5 mWm-2) and Pt/C (483.5 mWm-2). The enhanced catalytic activity of SGO-TiO2-PAni catalyst was ascribed to the high electronic conductivity and long-term permanence of the nanocomposite. These superior electrochemical results suggested that the SGO-TiO2-PAni catalyst could be applied as a potential alternative to the commercial Pt/C cathode catalyst for the application of MFCs.

A streamlined workflow for twoplexing of N-linked glycan analysis using light (12C6) and heavy (13C6) isotopologues of 3-aminobenzenesulfonic acid.

Comparative glycosylation analysis of biopharmaceuticals requires the development of methods that deliver the necessary throughput, support structural elucidation and relative quantitation of glycans released from therapeutics. The current study presents the development and applicability assessment of a twoplex approach using light and heavy isotopolouges of 3-aminobenzenesulfonic acid (3-ASA) under wet labeling conditions followed by UHPLC-MS analysis in data dependent acquisition mode. Excellent labelling efficiency, >90%, was achieved for both the light and heavy variants of the reagent. Glycan distributions of two human IgG lots labeled by light and heavy isotopolouges were identical, demonstrating no labeling bias introduced by either of the isotopologues. Peak area distributions of glycan profiles of two human IgG lots were compared to 2-aminobenzamide (2-AB) and RapiFluor-MS protocols. The comparison led to identical results in peak area distribution across the three dyes, but differences in chromatographic selectivity attributed to the different tags. MS1 based relative quantitation was further validated by releasing glycans from the same lot of human IgG, with glycan pools obtained labeled with light and heavy isotopologues separately, followed by mixing and clean-up of the same amount of light and heavy labeled glycan pools. MS analyses of each glycan resulted in a ratio of light and heavy XIC in the range of 0.97 ≤ x ≤ 1.05, demonstrating the method is amenable for the relative quantitation of glycans. Excellent correlation between the relative quantitation data of N-glycans from two human IgG N-glycan pools using the twoplex approach and ratios from peak area distribution calculated from the fluorescent chromatogram was observed (r = 0.986), further corroborating the reliability of the method and its potential applicability in the biopharmaceutical industry. Highly informative HCD-MS2 spectra dominated mostly by Y- and Z-type single and double glycosidic fragment ions facilitate structural interpretation of the oligosaccharides.

A multichannel system integrating molecularly imprinted conductive polymers for ultrasensitive voltammetric determination of four steroid hormones in urine.

This work reports on a modularized electrochemical method for the determination of the hormones cortisol, progesterone, testosterone and 17ß-estradiol in urine. These hormones were employed as templates when generating molecular imprints from aniline and metanilic acid by electropolymerization on the surface of screen-printed electrodes. The electrically conductive imprint was characterized by SEM, AFM and cyclic voltammetry. A four-channel system was then established to enable simultaneous determination of the hormones by cyclic voltammetry. The detection limits for cortisol, progesterone, testosterone and 17ß-estradiol are as low as 2, 2.5, 10 and 9 ag·mL-1 (for S/N = 3). Graphical abstract A four-channel system was established to enable simultaneous determination of 4 steroid hormones by cyclic voltammetry and by using moleculalry imprinted polymers.

DABs are inorganic carbon pumps found throughout prokaryotic phyla.

Bacterial autotrophs often rely on CO2 concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the components of CCMs is lacking. Here, we performed a genome-wide barcoded transposon screen to identify essential and CCM-related genes in the γ-proteobacterium Halothiobacillus neapolitanus. Screening revealed that the CCM comprises at least 17 and probably no more than 25 genes, most of which are encoded in 3 operons. Two of these operons (DAB1 and DAB2) contain a two-gene locus that encodes a domain of unknown function (Pfam: PF10070) and a putative cation transporter (Pfam: PF00361). Physiological and biochemical assays demonstrated that these proteins-which we name DabA and DabB, for DABs accumulate bicarbonate-assemble into a heterodimeric complex, which contains a putative ß-carbonic anhydrase-like active site and functions as an energy-coupled inorganic carbon (Ci) pump. Interestingly, DAB operons are found in a diverse range of bacteria and archaea. We demonstrate that functional DABs are present in the human pathogens Bacillus anthracis and Vibrio cholerae. On the basis of these results, we propose that DABs constitute a class of energized Ci pumps and play a critical role in the metabolism of Ci throughout prokaryotic phyla.

Colorimetric detection of the ß-agonist ractopamine in animal feed, tissue and urine samples using gold-silver alloy nanoparticles modified with sulfanilic acid.

A highly sensitive, selective and simple method was proposed for colorimetric detection of ractopamine on the basis of the interaction between ractopamine and sulfanilic acid-modified gold-silver alloy nanoparticles (AuAgNPs). The AuAgNPs were prepared by the reduction of HAuCl4 and AgNO3 with sodium citrate in aqueous medium and further modified by sulfanilic acid. The interaction of ractopamine with sulfanilic acid induced rapid aggregation of sulfanilic acid-modified AuAgNPs along with an optical colour change, leading to precise quantification which could be detected by absorptiometry. Under the optimum conditions, the absorbance ratio (A600/A435) of sulfanilic acid-modified AuAgNPs exhibited a linear relationship with the concentration of ractopamine in the range of 4.5-31.6 ng/mL. The detection limit of ractopamine was 1.5 ng/mL. The established novel colorimetric detection method showed high selectivity towards ractopamine. The method was successfully applied to detect ractopamine in spiked pork, swine feed and swine urine samples with excellent recoveries from 94.4% to 112.5%. These results demonstrated that the proposed new method has a good potential for practical applications.

Benzenesulfonamides act as open-channel blockers on KV3.1 potassium channel.

KV3.1 blockers can serve as modulators of the rate of action potential firing in neurons with high rates of firing such as those of the auditory system. We studied the effects of several bioisosteres of N-alkylbenzenesulfonamides, and molecules derived from sulfanilic acid on KV3.1 channels, heterologously expressed in L-929 cells, using the whole-cell patch-clamp technique. Only the N-alkyl-benzenesulfonamides acted as open-channel blockers on KV3.1, while molecules analogous to PABA (p-aminobenzoic acid) and derived from sulfanilic acids did not block the channel. The IC50 of six N-alkyl-benzenesulfonamides ranged from 9 to 55 µM; and the Hill coefficient suggests the binding of two molecules to block KV3.1. Also, the effects of all molecules on KV3.1 were fully reversible. We look for similar features amongst the molecules that effectively blocked the channel and used them to model a blocker prototype. We found that bulkier groups and amino-lactams decreased the effectiveness of the blockage, while the presence of NO2 increased the effectiveness of the blockage. Thus, we propose N-alkylbenzenesulfonamides as a new class of KV3.1 channel blockers.

Sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic AR42J cells.

We studied the effects of the tartrazine-metabolite sulfanilic acid on the physiology of pancreatic AR42J cells. Sulfanilic acid (1 µM-1 mM) induced a slow and progressive increase in intracellular free-calcium concentration that reached a plateau. The effect of sulfanilic acid was not concentration-dependent. Stimulation of cells with thapsigargin (1 µM) after treatment with sulfanilic acid (1 mM) induced a smaller Ca2+ response compared with that obtained with thapsigargin alone. Sulfanilic acid induced a concentration-dependent production of reactive oxygen species; however, this effect was not Ca2+-dependent. Depolarization of mitochondrial membrane potential was observed at the concentration of 1 mM sulfanilic acid. In the presence of the compound a decrease in the GSH/GSSG ratio was observed. A decrease in the expression of superoxide dismutase 2 was noted. Finally, stimulation of cells with CCK-8 led to a concentration-dependent increase of trypsin secretion that was impaired by pretreatment of cells with sulfanilic acid. Preincubation of cells with the antioxidant melatonin (100 µM) reduced the effect of sulfanilic acid on trypsin secretion. We conclude that sulfanilic acid might induce oxidative stress, which could alter Ca2+ signaling and enzyme secretion in pancreatic AR42J cells. This creates a situation potentially leading to damage of the exocrine pancreas.

Degradation of textile dyes Remazol Yellow Gold and reactive Turquoise: optimization, toxicity and modeling by artificial neural networks.

In this work, the degradation of Remazol Yellow Gold RNL-150% and Reactive Turquoise Q-G125 were investigated using AOP: photolysis, UV/H2O2, Fenton and photo-Fenton. It was found that the photo-Fenton process employing sunlight radiation was the most efficient, obtaining percentages of degradation above 87%. The ideal conditions for the degradation of the dyes were determined from a factorial design 23 and study of the [H2O2] ([H2O2] equal to 100 mg·L-1); [Fe] equal to 1 mg·L-1 and pH between 3 and 4. In the kinetic study, a degradation of more than 97% was obtained after 150 min for the chromophoric groups and 91% for the aromatic compounds. The experimental data obtained presented a good fit to the nonlinear kinetic model. The model of artificial neural networks multilayer perceptron (MLP) (4-11-5) using the software Statistica 8.0 enabled the modeling of the degradation process and showed a better prediction of the data. The toxicity to the seeds of Lactuca sativa and the bacteria Escherichia coli and Salmonella enteritidis allowed to evaluate the effectiveness of the process. The results of this study suggest that the use of photo-Fenton process with sunlight radiation is an effective way to degrade the dyes under study.

Made from concentrate? A national web survey assessing dab use in the United States.

BACKGROUND: Cannabis concentrates, including dabs, contain extremely high levels of Δ9-tetrahydrocannabinol (THC). Although these products appear to be gaining popularity among recreational cannabis consumers, little data exists regarding concentrate use in the US. We conducted a national web-based survey to examine patterns of concentrate use, specifically dabbing. METHODS: 4077 respondents completed a survey designed to assess the use of conventional flower cannabis relative to dabs. Individuals provided information about frequency and magnitude of use, and also completed the Marijuana Motives Measure and Severity of Dependence Scale to examine whether dab users have different motives for use and/or demonstrate more severe consequences of use compared to those who only use conventional flower products. RESULTS: 58% of respondents reported they had tried dabs at least once and 36.5% endorsed regular use (once a month or more). Those who use regularly use dabs were significantly more likely to report using for experimentation (feeling "curious") relative to reasons for using conventional flower products. Interestingly, motives reflecting positive effects (i.e., coping, sleep problems, relieving social anxiety) were endorsed more highly for flower use. In addition, regular dab users reported being more worried about their use of cannabis products relative to those who had tried dabs but did not use regularly. CONCLUSIONS: Results indicate that cannabis consumers do not necessarily choose dabs over flower products for positive effects, but rather appear to choose these highly potent products for experimentation. As concentrate use may lead to increased cannabis-related problems, studies directly assessing concentrate users are needed.

Structural basis of malodour precursor transport in the human axilla.

Mammals produce volatile odours that convey different types of societal information. In Homo sapiens, this is now recognised as body odour, a key chemical component of which is the sulphurous thioalcohol, 3-methyl-3-sulfanylhexan-1-ol (3M3SH). Volatile 3M3SH is produced in the underarm as a result of specific microbial activity, which act on the odourless dipeptide-containing malodour precursor molecule, S-Cys-Gly-3M3SH, secreted in the axilla (underarm) during colonisation. The mechanism by which these bacteria recognise S-Cys-Gly-3M3SH and produce body odour is still poorly understood. Here we report the structural and biochemical basis of bacterial transport of S-Cys-Gly-3M3SH by Staphylococcus hominis, which is converted to the sulphurous thioalcohol component 3M3SH in the bacterial cytoplasm, before being released into the environment. Knowledge of the molecular basis of precursor transport, essential for body odour formation, provides a novel opportunity to design specific inhibitors of malodour production in humans.