Examining the role of menthol cigarettes in progression to established T smoking among youth

Background: Menthol, a flavoring compound added to cigarettes, makes cigarettes more appealing to youth and inexperienced smokers and increases cigarettes\u27 abuse liability. However, limited studies are available on menthol\u27s role in smoking progression. Methods: To assess the association between menthol in cigarettes and progression to established smoking, we used five waves of data from the Evaluation of Public Education Campaign on Teen Tobacco Cohort Study, a nationally representative longitudinal survey of U.S. youth conducted as part of “The Real Cost” evaluation. We used discrete time survival analysis to model the occurrence of two event outcomes—progression to established, current smoking and progression to established, frequent smoking—using a logit model with a menthol use indicator as the key explanatory variable. Based on this framework, we estimated the effect of prior menthol use on the odds of smoking progression. Results: In the progression to established, current smoking model, prior menthol use was significantly associated with progression [adjusted odds ratio (aOR) = 1.80, p \u3c .05, confidence interval (CI) = (1.03–3.16)]. While results were in a similar direction for the model of progression to established, frequent smoking, the association between prior menthol use and this progression model did not reach significance [aOR=1.56, CI = (0.80–3.03)]. Conclusion: The results suggest a relationship between using menthol cigarettes and progression from experi- mental to established, current smoking among youth. This study adds to a growing literature base that supports that menthol cigarettes, compared to nonmenthol cigarettes, put youth at increased risk for regular cigarette use

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

Centimeter to decimeter hollow concretions and voids in Gale Crater sediments, Mars

Voids and hollow spheroids between ∼1 and 23 cm in diameter occur at several locations along the traverse of the Curiosity rover in Gale crater, Mars. These hollow spherical features are significantly different from anything observed in previous landed missions. The voids appear in dark-toned, rough-textured outcrops, most notably at Point Lake (sols 302-305) and Twin Cairns Island (sol 343). Point Lake displays both voids and cemented spheroids in close proximity; other locations show one or the other form. The spheroids have 1-4 mm thick walls and appear relatively dark-toned in all cases, some with a reddish hue. Only one hollow spheroid (Winnipesaukee, sol 653) was analyzed for composition, appearing mafic (Fe-rich), in contrast to the relatively felsic host rock. The interior surface of the spheroid appears to have a similar composition to the exterior with the possible exceptions of being more hydrated and slightly depleted in Fe and K. Origins of the spheroids as Martian tektites or volcanic bombs appear unlikely due to their hollow and relatively fragile nature and the absence of in-place clearly igneous rocks. A more likely explanation to both the voids and the hollow spheroids is reaction of reduced iron with oxidizing groundwater followed by some re-precipitation as cemented rind concretions at a chemical reaction front. Although some terrestrial concretion analogs are produced from a precursor siderite or pyrite, diagenetic minerals could also be direct precipitates for other terrestrial concretions. The Gale sediments differ from terrestrial sandstones in their high initial iron content, perhaps facilitating a higher occurrence of such diagenetic reactions

Interrogating a Hexokinase-Selected Small-Molecule Library for Inhibitors of Plasmodium falciparum Hexokinase

This is the published version.Parasites in the genus Plasmodium cause disease throughout the tropic and subtropical regions of the world. P. falciparum, one of the deadliest species of the parasite, relies on glycolysis for the generation of ATP while it inhabits the mammalian red blood cell. The first step in glycolysis is catalyzed by hexokinase (HK). While the 55.3-kDa P. falciparum HK (PfHK) shares several biochemical characteristics with mammalian HKs, including being inhibited by its products, it has limited amino acid identity (∼26%) to the human HKs, suggesting that enzyme-specific therapeutics could be generated. To that end, interrogation of a selected small-molecule library of HK inhibitors has identified a class of PfHK inhibitors, isobenzothiazolinones, some of which have 50% inhibitory concentrations (IC50s) of <1 μM. Inhibition was reversible by dilution but not by treatment with a reducing agent, suggesting that the basis for enzyme inactivation was not covalent association with the inhibitor. Lastly, six of these compounds and the related molecule ebselen inhibited P. falciparum growth in vitro (50% effective concentration [EC50] of ≥0.6 and <6.8 μM). These findings suggest that the chemotypes identified here could represent leads for future development of therapeutics against P. falciparum

Preliminary acoustic and oceanographic observations from the ASIAEX 2001 South China Sea Experiment

The Asian Seas International Experiment (ASIAEX) was a very successful scientific collaboration between the United States of America (USA), the People’s Republic of China (PRC), Taiwan (ROC), the Republic of Korea (ROK), Japan, Russia, and Singapore. Preliminary field experiments associated with ASIAEX began in spring of 2000. The main experiments were performed in April-August, 2001. The scientific plan called for two major acoustics experiments, the first a bottom interaction experiment in the East China Sea (ECS) and the second a volume interaction experiment in the South China Sea (SCS). In addition to the acoustics efforts, there were also extremely strong physical oceanography and geology and geophysics components to the experiments. This report will concentrate on describing the moored component of the South China Sea portion of ASIAEX 2001 performed from the Taiwan Fisheries research vessel FR1 (Fisheries Researcher 1). Information on the environmental moorings deployed from the Taiwanese oceanographic research vessel OR1 (Oceanographic Researcher 1) will also be listed here for completeness, so that the reader can pursue later analyses of the data. This report does not pursue any data analyses per se.Funding was provided by the Office of Naval Research under Grant Numbers N00014-01-1-0772, N00014-98-1-0413 and N00014-00-1-0206

Unraveling the sequence of serpentinization reactions : petrography, mineral chemistry, and petrophysics of serpentinites from MAR 15°N (ODP Leg 209, Site 1274)

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 33 (2006): L13306, doi:10.1029/2006GL025681.The results of detailed textural, mineral chemical, and petrophysical studies shed new light on the poorly constrained fluid-rock reaction pathways during retrograde serpentinization at mid-ocean ridges. Uniformly depleted harzburgites and dunites from the Mid-Atlantic Ridge at 15°N show variable extents of static serpentinization. They reveal a simple sequence of reactions: serpentinization of olivine and development of a typical mesh texture with serpentine-brucite mesh rims, followed by replacement of olivine mesh centers by serpentine and brucite. The serpentine mesh rims on relic olivine are devoid of magnetite. Conversely, domains in the rock that are completely serpentinized show abundant magnetite. We propose that low-fluid-flux serpentinization of olivine to serpentine and ferroan brucite is followed by later stages of serpentinization under more open-system conditions and formation of magnetite by the breakdown of ferroan brucite. Modeling of this sequence of reactions can account for covariations in magnetic susceptibility and grain density of the rocks.Funding for this research was provided by USSSP and NSF-OCE grant 9986135. WB acknowledges support through a fellowship by the Deep Ocean Exploration Institute