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Concurrent drinking and gambling is prevalent among young adults and may increase negative consequences associated with each behavior. The effects of alcohol, initial gambling outcomes, gambling-related cognitions, and impulsivity on gambling behavior were evaluated. Initial gambling outcomes, gambling-related cognitions, and impulsivity were also assessed as potential moderators of the relation between alcohol and gambling behavior. Participants (N = 130) were randomly assigned to receive active placebo or alcohol (0.84 g/kg and 0.76 g/kg for men and women, respectively) and were invited to wager on a simulated slot machine programmed to produce 1 of 3 initial outcomes (win, breakeven, or loss) before beginning a progressive loss schedule. Alcohol consumption was associated with larger average bets and more rapid loss of all available funds, though no evidence was found for predicted main effects and interactions for gambling persistence. The effect of impulsivity was moderated by beverage condition, such that higher levels of impulsivity were associated with larger average bets for participants in the placebo but not the alcohol group. Results have direct implications for individual-focused and public-health interventions.

AbstractDengue is a mosquito-borne viral infection that has spread throughout the tropical world over the past 60 years and now affects over half the world’s population. The geographical range of dengue is expected to further expand due to ongoing global phenomena including climate change and urbanization. We applied statistical mapping techniques to the most extensive database of case locations to date to predict global environmental suitability for the virus as of 2015. We then made use of climate, population and socioeconomic projections for the years 2020, 2050 and 2080 to project future changes in virus suitability and human population at risk. This study is the first to consider the spread of Aedes mosquito vectors to project dengue suitability. Our projections provide a key missing piece of evidence for the changing global threat of vector-borne disease and will help decision-makers worldwide to better prepare for and respond to future changes in dengue risk.

Early life stress is associated with risk for developing alcohol use disorders (AUDs) in adulthood. Though the neurobiological mechanisms underlying this vulnerability are not well understood, evidence suggests that aberrant glucocorticoid and noradrenergic system functioning play a role. The present study investigated the long-term consequences of chronic exposure to elevated glucocorticoids during adolescence on the risk of increased alcohol-motivated behavior, and on amygdalar function in adulthood. A discovery-based analysis of the amygdalar phosphoproteome using mass spectrometry was employed, to identify changes in function. Adolescent corticosterone (CORT) exposure increased alcohol, but not sucrose, self-administration, and enhanced stress-induced reinstatement with yohimbine in adulthood. Phosphoproteomic analysis indicated that the amygdala phosphoproteome was significantly altered by adolescent CORT exposure, generating a list of potential novel mechanisms involved in the risk of alcohol drinking. In particular, increased phosphorylation at serines 296–299 on the α2A adrenergic receptor (α2AAR), mediated by the G-protein coupled receptor kinase 2 (GRK2), was evident after adolescent CORT exposure. We found that intra-amygdala infusion of a peptidergic GRK2 inhibitor reduced alcohol seeking, as measured by progressive ratio and stress reinstatement tests, and induced by the α2AAR antagonist yohimbine. These results suggest that GRK2 represents a novel target for treating stress-induced motivation for alcohol which may counteract alterations in brain function induced by adolescent stress exposure.

IntroductionTo revisit the formulation of the mean chord length in microdosimetry and replace it by the particle mean free path appropriate for modelings in radiobiology.MethodsWe perform a collision‐by‐collision followed by event‐by‐event Geant4 Monte Carlo simulation and calculate double‐averaged stepping length, 〈〈l〉〉, for a range of target sizes from mm down to μm and depth in water. We consider 〈〈l〉〉 to represent the particle mean free path.ResultsWe show that 〈〈l〉〉 continuously drops as a function of depth and asymptotically saturates to a minimum value in low energies, where it exhibits a universal scaling behavior, independent of particle nominal beam energy. We correlate 〈〈l〉〉 to linear density of DNA damage, complexities of initial lethal lesions and illustrate a relative difference between predictive RBEs in model calculations using mean chord length vs the proposed mean free path. We demonstrate consistency between rapid increase in RBE within and beyond the Bragg peak and 〈〈l〉〉, a decreasing function of depth.Discussion and conclusionAn interplay between localities in imparted energy at nanometer scale and subsequent physio‐chemical processes, causalities and pathways in DNA damage requires substitution of geometrical chord length of cell nuclei by mean‐free path of proton and charged particles to account for a mean distance among sequential collisions in DNA materials. To this end, the event averaging over cell volume in the current microdosimetry formalism must be superseded by the collision averaging scored within the volume. The former, is fundamentally a global attribute of the cell nuclei surfaces and boundaries and is characterized by their membrane diameters, hence such global indices are not appropriate to quantitatively represent the radiobiological strength of the particles and their RBE variabilities that is associated with the sensitivities to local structure of the collisions and their spatio‐temporal collective patterns in DNA materials.

AbstractProgression of chronic infections to end‐stage diseases and poor treatment results are frequently associated with alcohol abuse. Alcohol metabolism suppresses innate and adaptive immunity leading to increased viral load and its spread. In case of hepatotropic infections, viruses accelerate alcohol‐induced hepatitis and liver fibrosis, thereby promoting end‐stage outcomes, including cirrhosis and hepatocellular carcinoma (HCC). In this review, we concentrate on several unexplored aspects of these phenomena, which illustrate the combined effects of viral/bacterial infections and alcohol in disease development. We review alcohol‐induced alterations implicated in immunometabolism as a central mechanism impacting metabolic homeostasis and viral pathogenesis in Simian immunodeficiency virus/human immunodeficiency virus infection. Furthermore, in hepatocytes, both HIV infection and alcohol activate oxidative stress to cause lysosomal dysfunction and leakage and apoptotic cell death, thereby increasing hepatotoxicity. In addition, we discuss the mechanisms of hepatocellular carcinoma and tumor signaling in hepatitis C virus infection. Finally, we analyze studies that review and describe the immune derangements in hepatotropic viral infections focusing on the development of novel targets and strategies to restore effective immunocompetency in alcohol‐associated liver disease. In conclusion, alcohol exacerbates the pathogenesis of viral infections, contributing to a chronic course and poor outcomes, but the mechanisms behind these events are virus specific and depend on virus–alcohol interactions, which differ among the various infections.

We wanted to determine whether transcatheter Ethiodol-based capillary embolization in combination with carboplatin could improve the efficiency of a 1:1 Ethiodol-ethanol mixture (EEM) to ablate kidneys that been inoculated with VX-2 carcinoma.The right kidney in 34 New Zealand white rabbits were inoculated with fresh VX-2 tumor fragments. One week later, the kidneys were subjected to transarterial treatment (4-5 rabbits/group): Saline infusion (Group 1); carboplatin infusion (5 or 10 mg, Groups 2A and 2B); carboplatin-Ethiodol (CE) alone (Group 3) and followed by main renal artery occlusion with ethanol (RAO) (Group 4); carboplatin-EEM (C-EEM) followed by RAO (Group 5); carboplatin infusion followed by EEM plus RAO (Group 6); and EEM followed by RAO (Group 7). The animals were followed for up to 3-weeks. The treated kidneys were evaluated angiographically and macroscopically. The kidneys that showed successful embolization macroscopically were entirely cut into serial sections, and these were examined microscopically. Histologically, the kidneys were evaluated on the basis of the residual tumor found in the serial sections.The results obtained with carboplatin infusion alone (Groups 2A and 2B) and CE without RAO (Group 3) were similar to those of the control animals (Group 1). Kidneys from Groups 4-7 demonstrated macroscopically successful embolization with histologically proven complete renal parenchyma infarction; however, some residual tumor was evident in all but one animal.None of the Ethiodol-based modalities combined with locoregional carboplatin were more efficacious for tumor ablation than EEM alone.

Areas of co-occurrence between two species (sympatry) are often thought to arise in regions where abiotic conditions are conducive to both species and are therefore intermediate between regions where either species occurs alone (allopatry). Depending on historical factors or interactions between species, however, sympatry might not differ from allopatry, or, alternatively, sympatry might actually be more extreme in abiotic conditions relative to allopatry. Here, we evaluate these three hypothesized patterns for how sympatry compares to allopatry in abiotic conditions. We use two species of congeneric spadefoot toads, Spea multiplicata and S. bombifrons, as our study system. To test these hypotheses, we created ecological niche models (specifically using Maxent) for both species to create a map of the joint probability of occurrence of both species. Using the results of these models, we identified three types of locations: two where either species was predicted to occur alone (i.e., allopatry for S. multiplicata and allopatry for S. bombifrons) and one where both species were predicted to co-occur (i.e., sympatry). We then compared the abiotic environment between these three location types and found that sympatry was significantly hotter and drier than the allopatric regions. Thus, sympatry was not intermediate between the alternative allopatric sites. Instead, sympatry occurred at one extreme of the conditions occupied by both species. We hypothesize that biotic interactions in these extreme environments facilitate co-occurrence. Specifically, hybridization between S. bombifrons females and S. multiplicata males may facilitate co-occurrence by decreasing development time of tadpoles. Additionally, the presence of alternative food resources in more extreme conditions may preclude competitive exclusion of one species by the other. This work has implications for predicting how interacting species will respond to climate change, because species interactions may facilitate survival in extreme habitats.