Supporting open access to clinical trial data for researchers: The Duke Clinical Research Institute-Bristol-Myers Squibb Supporting Open Access to Researchers Initiative.

There are growing calls for sponsors to increase transparency by providing access to clinical trial data. In response, Bristol-Myers Squibb and the Duke Clinical Research Institute have collaborated on a new initiative, Supporting Open Access to Researchers. The aim is to facilitate open sharing of Bristol-Myers Squibb trial data with interested researchers. Key features of the Supporting Open Access to Researchers data sharing model include an independent review committee that ensures expert consideration of each proposal, stringent data deidentification/anonymization and protection of patient privacy, requirement of prespecified statistical analysis plans, and independent review of manuscripts before submission for publication. We believe that these approaches will promote open science by allowing investigators to verify trial results as well as to pursue interesting secondary uses of trial data without compromising scientific integrity.

Critical tissue residue approach linking accumulated metals in aquatic insects to population and community-level effects.

Whole body Zn concentrations in individuals (n = 825) from three aquatic insect taxa (mayflies Rhithrogena spp. and Drunella spp. and the caddisfly Arctopsyche grandis) were used to predict effects on populations and communities (n = 149 samples). Both mayflies accumulated significantly more Zn than the caddisfly. The presence/absence of Drunella spp. most reliably distinguished sites with low and high Zn concentrations; however, population densities of mayflies were more sensitive to increases in accumulated Zn. Critical tissue residues (634 µg/g Zn for Drunella spp. and 267 µg/g Zn for Rhithrogena spp.) caused a 20% reduction in maximum (90th quantile) mayfly densities. These critical tissue residues were associated with exposure to 7.0 and 3.9 µg/L dissolved Zn for Drunella spp. and Rhithrogena spp., respectively. A threshold in a measure of taxonomic completeness (observed/expected) was observed at 5.4 µg/L dissolved Zn. Dissolved Zn concentrations associated with critical tissue residues in mayflies were also associated with adverse effects in the aquatic community as a whole. These effects on populations and communities occurred at Zn concentrations below the U.S. EPA hardness-adjusted continuous chronic criterion.

Hibiscus Tea and its Therapeutic Potential in Weight Reduction: Integrative Review / Chá de Hibiscus e seu Potencial Terapêutico na Redução de Peso: Revisão Integrativa

The calyx of the Hibiscus plant are used in the form of an infusion in popular medicine with the purpose of contributing to the weight loss of its users. Therefore, the objective of this work was to verify in the literature the therapeutic potential of Hibiscus sabdariffa tea for weight loss. This is an integrative review done in the following databases: Scopus, PubMed, Science Direct, Web of Science. The final sample consisted of 6 articles. Half of the selected articles had the clear objective of evaluating weight loss, the others evaluated anti-metabolic and anti-stress properties, obesity-related adipogenesis and control of lipid indicators. In the selected studies, the most used part of the plant was the calyx, being fresh and dry. Factors such as the concentration and form of supply of the Hibiscus sabdariffa extract seem to be points to be taken into account in experiments that have food intake as an influence on the other variables. The studies brought evidence that Hibiscus sabdariffa extracts contribute to weight loss and to the suppression of weight gain in human and animal groups with metabolic disorders, without change for the healthy human/animal group. However, studies on the long-term maintenance of weight loss, once achieved, the efficacy and safety of its use, are still insufficient according to the collected evidence.(AU)

Os cálices da planta Hibiscus são utilizados na forma de infusão na medicina popular com o propósito de contribuir na perda ponderal de seus usuários. Diante disto, o trabalho teve como objetivo verificar na literatura o potencial terapêutico do chá de Hibiscus sabdariffa para a perda ponderal. Trata-se de uma revisão integrativa realizada nas bases: Scopus, PubMed, Science Direct, Web of Science. A amostra final foi formada por 6 artigos. Metade dos artigos selecionados tinham como objetivo claro avaliar a perda de peso, os demais avaliavam as propriedades antimetabólicas e antiestresse, adipogênese relacionada à obesidade e controle dos indicadores lipídicos. Nos estudos selecionados, a parte da planta mais utilizada foi o cálice, sendo eles frescos e secos. Fatores como a concentração e a forma de fornecimento do extrato do Hibiscus sabdariffa parecem ser pontos a serem levados em consideração em experimentos que tenham a ingestão alimentar como influência sobre as demais variáveis. Os estudos trouxeram evidencias de que os extratos de Hibiscus sabdariffa contribuem para a perda de peso e para a supressão do ganho de peso em grupos humanos e animais com disfunções metabólicas, sem alteração para o grupo de humanos/animais saudáveis. No entanto, estudos sobre a manutenção a longo prazo da perda de peso, uma vez alcançada, a eficácia e segurança de seu uso, ainda são insuficientes de acordo com as evidências coletadas.(AU)

Environmental implications of the use of sulfidic back-bay sediments for dune reconstruction - Lessons learned post Hurricane Sandy.

Some barrier-island dunes damaged or destroyed by Hurricane Sandy's storm surges in October 2012 have been reconstructed using sediments dredged from back bays. These sand-, clay-, and iron sulfide-rich sediments were used to make berm-like cores for the reconstructed dunes, which were then covered by beach sand. In November 2013, we sampled and analyzed partially weathered materials collected from the cores of reconstructed dunes. There are generally low levels of metal toxicants in the reconstructed dune materials. However oxidation of reactive iron sulfides by percolating rainwater produces acid-sulfate pore waters, which evaporate during dry periods to produce efflorescent gypsum and sodium jarosite salts. The results suggest use of sulfidic sediments in dune reconstruction has both drawbacks (e.g., potential to generate acid runoff from dune cores following rainfall, enhanced corrosion of steel bulwarks) and possible benefits (e.g., efflorescent salts may enhance structural integrity).

In vitro and in vivo effects of an alpha3 neuronal nicotinic acetylcholine receptor antisense oligonucleotide.

In the mammalian central nervous system (CNS), a family of alpha and beta subunits (alpha2-7, beta2-4) assemble to form both hetero- and homopentameric neuronal nicotinic acetylcholine receptors (nAChRs). In contrast to alpha4beta2 and alpha7, the predominant brain subtypes, far less is known regarding the functional expression and significance of alpha3-containing nAChRs in the CNS. In trying to better understand the role alpha3 in the CNS, an antisense knockdown strategy was utilized in the present studies. Specifically, Isis 106567 was identified out of 80 antisense oligonucleotides (aONs) designed and screened for their ability to reduce alpha3 mRNA expression in PC-12 cells. In addition to reducing alpha3 mRNA by greater than 75%, Isis 106567 attenuated nicotine-induced calcium influx in alpha3-expressing F11 cells. In vivo studies revealed significant reduction of alpha3 mRNA levels in both thalamus and medial habenula, regions known to express alpha3, following continuous (7 days) intracerebroventricular (i.c.v.) infusion of Isis 106567 in rats. Consistent with functional alpha3 knockdown, epibatidine-induced c-Fos expression in the medial habenula was attenuated in aON-treated rats. Known physiological responses elicited by epibatidine, such as hypothermia and micturition, were not affected by alpha3 aON treatment. However, the incidence of epibatidine-induced seizures was reduced in alpha3-antisense aON-treated rats, suggesting that alpha3 may be involved in mediating seizures produced by the nAChR agonist. Results of our studies suggest that Isis 106567 may be a useful in vivo tool for characterizing the functional significance of alpha3 expression in the CNS.

Species comparison and pharmacological characterization of rat and human CB2 cannabinoid receptors.

Pharmacological effects of cannabinoid ligands are thought to be mediated through cannabinoid CB1 and CB2 receptor subtypes. Sequence analysis revealed that rat and human cannabinoid CB2 receptors are divergent and share 81% amino acid homology. Pharmacological analysis of the possible species differences between rat and human cannabinoid CB2 receptors was performed using radioligand binding and functional assays. Pronounced species selectivity at the rat cannabinoid CB2 receptor (50- to 140-fold) was observed with AM-1710 (3-(1,1-Dimethyl-heptyl)-1-hydroxy-9-methoxy-benzo[c]chromen-6-one) and AM-1714 (3-(1,1-Dimethyl-heptyl)-1-9-dihydroxy-benzo[c]chromen-6-one). In contrast, JWH-015 ((2-Methyl-1-propyl-1H-indol-3-yl)-napthalen-1-yl-methanone) was 3- to 10-fold selective at the human cannabinoid CB2 receptor. Endocannabinoid ligands were more human receptor selective. Cannabinoid CB2 receptor antagonist, AM-630 ((6-Iodo-2-methyl-1-(2-morpholin-4-yl-ethyl)-1H-indol-3-yl)-(4-methoxy-phenyl)-methanone) was more potent at the rat receptor in radioligand binding and functional assays than that of the human receptor. The findings of the pharmacological differences between the human and rat cannabinoid CB2 receptors in this study provide critical information for characterizing cannabinoid ligands in in vivo rodent models for drug discovery purpose.

Linking geological and health sciences to assess childhood lead poisoning from artisanal gold mining in Nigeria.

BACKGROUND: In 2010, Médecins Sans Frontières discovered a lead poisoning outbreak linked to artisanal gold processing in northwestern Nigeria. The outbreak has killed approximately 400 young children and affected thousands more. OBJECTIVES: Our aim was to undertake an interdisciplinary geological- and health-science assessment to clarify lead sources and exposure pathways, identify additional toxicants of concern and populations at risk, and examine potential for similar lead poisoning globally. METHODS: We applied diverse analytical methods to ore samples, soil and sweep samples from villages and family compounds, and plant foodstuff samples. RESULTS: Natural weathering of lead-rich gold ores before mining formed abundant, highly gastric-bioaccessible lead carbonates. The same fingerprint of lead minerals found in all sample types confirms that ore processing caused extreme contamination, with up to 185,000 ppm lead in soils/sweep samples and up to 145 ppm lead in plant foodstuffs. Incidental ingestion of soils via hand-to-mouth transmission and of dusts cleared from the respiratory tract is the dominant exposure pathway. Consumption of water and foodstuffs contaminated by the processing is likely lesser, but these are still significant exposure pathways. Although young children suffered the most immediate and severe consequences, results indicate that older children, adult workers, pregnant women, and breastfed infants are also at risk for lead poisoning. Mercury, arsenic, manganese, antimony, and crystalline silica exposures pose additional health threats. CONCLUSIONS: Results inform ongoing efforts in Nigeria to assess lead contamination and poisoning, treat victims, mitigate exposures, and remediate contamination. Ore deposit geology, pre-mining weathering, and burgeoning artisanal mining may combine to cause similar lead poisoning disasters elsewhere globally.