Human dietary exposure to heavy metals via the consumption of greenshell mussels (Perna canaliculus Gmelin 1791) from the Bay of Islands, northern New Zealand

Cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb) and tin (Sn) concentrations were determined using ICP-MS in soft tissues (wet wt.) from whole greenshell mussels (Perna canaliculus) collected from Urapukapuka-Rawhiti Island, Opua Marina, Waitangi Bridge and Opua Wharf from the Bay of Islands, northern New Zealand (NZ). All samples had metal concentrations well below the Food Standards Australia and New Zealand (FSANZ) maximum limits and were comparable to, or less than, concentrations observed in previous NZ studies. Based on the average values detected in the current study, the concentrations of heavy metals ingested in a ‘typical diet’ containing greenshell mussels are below the provisional tolerable weekly intake (PTWI). However, Māori (indigenous people of New Zealand), Pacific Islanders and Asians consume a far greater quantity of seafood (and therefore heavy metals) than the general public of New Zealand and could potentially consume enough shellfish to exceed the PTWI for Cd (but not for Hg, As, Pb or Sn). Although our results, based on the current PTWIs, indicate no significant health risk to greenshell mussel consumers in this region, PTWIs change over time; concentrations which were thought to be safe are later found to be harmful. Additionally, differences in individual human susceptibilities to various toxins could increase the risk of harm for consumers with low tolerance to heavy metals. We suggest that a survey of the frequency, amount and species consumed by groups whose diet may be largely shellfish-based is required to enable a more comprehensive risk assessment to be made.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.     

NMR Profiling of Exhaled Breath Condensate Defines Different Metabolic Phenotypes of Non-Cystic Fibrosis Bronchiectasis

Nuclear-magnetic-resonance (NMR) profiling of exhaled breath condensate (EBC) provides insights into the pathophysiology of bronchiectasis by identifying specific biomarkers. We evaluated whether NMR-based metabolomics discriminates the EBC-derived metabolic phenotypes (“metabotypes”) of 41 patients with non-cystic fibrosis (nCF) bronchiectasis of various etiology [24 subjects with Primary Ciliary Dyskinesia (PCD); 17 patients with bronchiectasis not associated with PCD (nCF/nPCD)], who were compared to 17 healthy subjects (HS). NMR was used for EBC profiling, and Orthogonal Projections to Latent Structures with partial least-squares discriminant analysis (OPLS-DA) was used as a classifier. The results were validated by using the EBC from 17 PCD patients not included in the primary analysis. Different statistical models were built, which compared nCF/nPCD and HS, PCD and HS, all classes (nCF/nPCD-PCD-HS), and, finally, PCD and nCF/nPCD. In the PCD-nCF/nPCD model, four statistically significant metabolites were able to discriminate between the two groups, with only a minor reduction of the quality parameters. In particular, for nCF/nPCD, acetone/acetoin and methanol increased by 21% and 18%, respectively. In PCD patients, ethanol and lactate increased by 25% and 28%, respectively. They are all related to lung inflammation as methanol is found in the exhaled breath of lung cancer patients, acetone/acetoin produce toxic ROS that damage lung tissue in CF, and lactate is observed in acute inflammation. Interestingly, a high concentration of ethanol hampers cilia beating and can be associated with the genetic defect of PCD. Model validation with 17 PCD samples not included in the primary analysis correctly predicted all samples. Our results indicate that NMR of EBC discriminates nCF/nPCD and PCD bronchiectasis patients from HS, and patients with nCF/nPCD from those with PCD. The metabolites responsible for between-group separation identified specific metabotypes, which characterize bronchiectasis of a different etiology.     

Avocado (Persea americana Mill.) by-products and their impact: from bioactive compounds to biomass energy and sorbent material for removing contaminants. A review

Avocado industry produces enormous by-products and represents an important source of raw material in food and non-food applications. This review aims to focus the attention on the valorisation of avocado wastes recycling to produce different materials with important industrial and environmental impacts. In fact, peels and seeds can be reused in food and cosmetic fields due to the presence of bioactive ingredients such as polyphenols; thanks to their antioxidant and antinflammatory activities. In addition, both peels and seeds can be reused in the production of carbonaceous materials with important consequences for environmental pollution in the removal of contaminants from water. Interesting applications of avocado wastes in photocatalysis and biofuel production are also discussed. All the utilisations attest the great potential of recycling avocado by-products, a little known resource.     

Anti- and pro-oxidant activity of Cichorium genus vegetables and effect of thermal treatment in biological systems

The antiradical activity of water soluble components in six vegetables belonging to the Cichorium genus, i.e., three cultivars of red intybus species var. silvestre (Treviso, Chioggia, Verona red chicories), a white intybus species var. foliosum (Belgian chicory), and two vegetables of the endivia species var. latifolium (escarole chicory) and var. crispum (“crispa” chicory), were studied using two biological systems consisting of: (1) microsome membrane rat hepatocyties in which oxidative damage was induced by CCl₄; (2) gram-positive bacterium, Staphylococcus aureus cultures, subjected to damage with cumene hydroperoxyde. The obtained results show that in both systems the red vegetables possess the strongest antioxidant properties and contain different antioxidant compounds whether at a low or high molecular weight, but only those of high molecular-weight (MW > 3500 Da) are able to act as antioxidants in all the used systems. The lower MW fraction (MW < 3500 Da) showed itself to be pro-oxidant in the microsome system. The effects of thermal treatments such as boiling, freezing and freeze-drying were also investigated.     

Screening for adolescent problem drinking: Validation of a multidimensional instrument for case identification.

This research tested the thesis that adolescent problem drinking may be manifest in any of four independent domains (measured by the 24-item screening instrument, the Adolescent Drinking Inventory: Drinking and You): drinking-related loss of control, social indicators, psychological indicators, and physical indicators. Clinical assessments of 264 adolescents referred for screening revealed that more than half of the variation in clinical assessment of problem drinking severity was captured by these four domains and that two of the four domains (loss of control and psychological indicators) made an independent contribution to clinical assessment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling the health care costs of geriatric inpatients.

This paper extends a method for modeling the survival of patients in hospitals to allow the expected cost to be estimated for the patients' accumulated duration of time in care. An extension of Bayesian network (BN) theory has previously been developed to model patients' survival time in hospitals with respect to the graphical and probabilistic representation of the interrelationships between the patients' clinical variables. Unlike previous BN techniques, this extended model can accommodate continuous times that are skewed in nature. This paper presents the theory behind such an approach and extends it by attaching a cost variable to the survival times, enabling the costing and efficient management of groups of patients in hospitals. An application of the model is illustrated by considering a group of 4260 patients admitted into the geriatric department of a U.K. hospital between 1994-1997. Results are derived for the distribution for their length of stay in the hospital and associated costs. The model's practical use is highlighted by illustrating how hospital managers could benefit using such a method for investigating the influence of future decisions and policy changes on the hospital's expenditure.     

Dominic I: Progress toward domain independence in design by iterative redesign

This paper describes the first working version of a program called Dominic that performs design by iterative redesign in a domain-independent manner. The paper describes in detail the program's strategy, which stresses the concept of redesign dependencies to guide its redesign process. Dominic has been successfully tested in four different domains. Its performance on two of these (v-belt drive design and design of extruded heat sinks) is presented here. The redesign class of design problems on which Dominic works is that large class of problems that are intellectually manageable and solvable without subdivision into smaller parts. This includes the various subproblems ultimately created when large complex problems are decomposed for solution. Dominic is a hill-climbing algorithm, similar in this respect to standard optimization methods. However, its problem formulation or input language is more flexible for some design applications than optimization techniques. Work is continuing on a Dominic II in an effort to overcome some of the limitations of Dominic.     

Accelerating Scientific Discovery Through Computation and Visualization III. Tight-Binding Wave Functions for Quantum Dots

This is the third in a series of articles that describe, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing, visualization, and machine learning to accelerate scientific discovery. In this article we focus on the use of high performance computing and visualization for simulations of nanotechnology.