Emotional distress may increase risk for self-medication and lower risk for mood-related drinking consequences in adolescents

The current study examines indicators of emotional distress and coping that may define sub-populations of adolescents at risk for two potential affect-related mechanisms underlying substance misuse: self-medication and mood-related drinking consequences. Although theory and empirical evidence point to the salience of affect-related drinking to current and future psychopathology, we have little knowledge of whether or for whom such mood-related processes exist in adolescents because few studies have used methods that optimally match the phenomenon to the level of analysis. Consequently, the current study uses multi-level modeling in which daily reports of negative mood and alcohol use are nested within individuals to examine whether adolescents with more emotional distress and poorer coping skills are more likely to evidence self-medication and moodrelated drinking consequences. Seventy-five adolescents participated in a multi-method, multi-reporter study in which they completed a 21-day experience sampling protocol assessing thrice daily measures of mood and daily measures of alcohol use. Results indicate that adolescents reporting greater anger are more likely to evidence self-medication. Conversely, adolescents displaying lower emotional distress and more active coping are more likely to evidence mood-related drinking consequences. Implications for identifying vulnerable sub-populations of adolescents at risk for these mechanisms of problematic alcohol use are discussed.peer-reviewe

The impact of observed parental emotion socialization on adolescent self-medication

The purpose of this study was to examine the relationship between observed parental emotion socialization (PES) and negative affect-motivated substance use among adolescents (i.e., self-medication). Although research consistently shows that parenting relates to adolescent negative affect and substance use respectively, the current study specifically addressed the under-researched area of parents’ impact on self-medication using a new observational measure of PES and experience sampling methodology to assess self-medication as a daily process. Thus, this study had two main aims. The first was to examine the structure and function of the new observational PES measure. The second was to test substantive questions regarding the impact of PES on adolescent self-medication using both a unidimensional and typological approach to PES. Further, adolescent gender differences in the relation between PES and self-medication were examined. Sixty-five 14-year-old adolescents (and parents) who were predominantly female (52% and 94% for adolescents and parents, respectively) and Caucasian (58%) were recruited from a larger school-based survey for substance use risk. Dyads participated in intensive home-based interviews to assess adolescent self-medication through a three-week experience sampling procedure and PES through an observation-based adolescent stress disclosure task. Demographics and other parenting measures were completed by adolescents and parents separately. Reliability and validity analyses were conducted for the measure of observed PES and revealed good inter-rater reliability, promising validity, and a structure generally consistent with the existing PES literature. Multi-level modeling analyses testing the substantive hypotheses revealed limited support for the role of adolescent gender or a unidimensional approach to PES in self-medication. However, interactions between emotion-coaching and emotion-dismissing PES resulted in two different PES styles (i.e., disengaged and over-involved) that best predicted self-medication. Results are discussed with consideration of the importance of PES styles and their effects on self-medication through compromised emotion regulation and interpersonal processes. Implications for future research and intervention are also discussed

Development and application of an antibiotic spectrum index for benchmarking antibiotic selection patterns across hospitals

Standard metrics for antimicrobial use consider volume but not spectrum of antimicrobial prescribing. We developed an antibiotic spectrum index (ASI) to classify commonly used antibiotics based on activity against important pathogens. The application of this index to hospital antibiotic use reveals how this tool enhances current antimicrobial stewardship metrics.Infect Control Hosp Epidemiol 2017;38:993–997</jats:p

The Association Between Observed Parental Emotion Socialization and Adolescent Self-Medication

The current study examined the moderating influence of observed parental emotion socialization (PES) on self-medication in adolescents. Strengths of the study include the use of a newly developed observational coding system further extending the study of PES to adolescence, the use of an experience sampling method to assess the daily covariation between negative affect and substance use, and a focus on PES styles defined by the interaction of emotion-dismissing and emotion–coaching behaviors. Using multi-leveling modeling, we tested PES as a moderator of daily negative mood-substance use relation in a sample of 65 elevated-risk adolescents (48% male, 58% Caucasian, with a median age of 14). Results showed a three-way interaction between emotion-coaching PES, emotion-dismissing PES and daily negative mood in predicting daily substance use. Results are discussed in terms of the importance of PES styles and their effects on self-medication through compromised emotion regulation and interpersonal processes

Conduct Problems Moderate Self-Medication and Mood-Related Drinking Consequences in Adolescents

We tested whether conduct problems moderate the relation between negative mood and drinking in adolescents as consistent with either a self-medication or a drinking consequences model

Enhanced Disease Susceptibility 1 and Salicylic Acid Act Redundantly to Regulate Resistance Gene-Mediated Signaling

Resistance (R) protein–associated pathways are well known to participate in defense against a variety of microbial pathogens. Salicylic acid (SA) and its associated proteinaceous signaling components, including enhanced disease susceptibility 1 (EDS1), non–race-specific disease resistance 1 (NDR1), phytoalexin deficient 4 (PAD4), senescence associated gene 101 (SAG101), and EDS5, have been identified as components of resistance derived from many R proteins. Here, we show that EDS1 and SA fulfill redundant functions in defense signaling mediated by R proteins, which were thought to function independent of EDS1 and/or SA. Simultaneous mutations in EDS1 and the SA–synthesizing enzyme SID2 compromised hypersensitive response and/or resistance mediated by R proteins that contain coiled coil domains at their N-terminal ends. Furthermore, the expression of R genes and the associated defense signaling induced in response to a reduction in the level of oleic acid were also suppressed by compromising SA biosynthesis in the eds1 mutant background. The functional redundancy with SA was specific to EDS1. Results presented here redefine our understanding of the roles of EDS1 and SA in plant defense

Biodistribution and in Vivo Activities of Tumor-Associated Macrophage-Targeting Nanoparticles Incorporated with Doxorubicin

Tumor-associated macrophages (TAMs) are increasingly considered a viable target for tumor imaging and therapy. Previously, we reported that innovative surface-functionalization of nanoparticles may help target them to TAMs. In this report, using poly(lactic-co-glycolic) acid (PLGA) nanoparticles incorporated with doxorubicin (DOX) (DOX-NPs), we studied the effect of surface-modification of the nanoparticles with mannose and/or acid-sensitive sheddable polyethylene glycol (PEG) on the biodistribution of DOX and the uptake of DOX by TAMs in tumor-bearing mice. We demonstrated that surface-modification of the DOX-NPs with both mannose and acid-sensitive sheddable PEG significantly increased the accumulation of DOX in tumors, enhanced the uptake of the DOX by TAMs, but decreased the distribution of DOX in mononuclear phagocyte system (MPS), such as liver. We also confirmed that the acid-sensitive sheddable PEGylated, mannose-modified DOX-nanoparticles (DOX-AS-M-NPs) targeted TAMs because depletion of TAMs in tumor-bearing mice significantly decreased the accumulation of DOX in tumor tissues. Furthermore, in a B16-F10 tumor-bearing mouse model, we showed that the DOX-AS-M-NPs were significantly more effective than free DOX in controlling tumor growth but had only minimum effect on the macrophage population in mouse liver and spleen. The AS-M-NPs are promising in targeting cytotoxic or macrophage-modulating agents into tumors to improve tumor therapy

Pathway analysis of genome-wide data improves warfarin dose prediction

Background: Many genome-wide association studies focus on associating single loci with target phenotypes. However, in the setting of rare variation, accumulating sufficient samples to assess these associations can be difficult. Moreover, multiple variations in a gene or a set of genes within a pathway may all contribute to the phenotype, suggesting that the aggregation of variations found over the gene or pathway may be useful for improving the power to detect associations. Results: Here, we present a method for aggregating single nucleotide polymorphisms (SNPs) along biologically relevant pathways in order to seek genetic associations with phenotypes. Our method uses all available genetic variants and does not remove those in linkage disequilibrium (LD). Instead, it uses a novel SNP weighting scheme to down-weight the contributions of correlated SNPs. We apply our method to three cohorts of patients taking warfarin: two European descent cohorts and an African American cohort. Although the clinical covariates and key pharmacogenetic loci for warfarin have been characterized, our association metric identifies a significant association with mutations distributed throughout the pathway of warfarin metabolism. We improve dose prediction after using all known clinical covariates and pharmacogenetic variants in VKORC1 and CYP2C9. In particular, we find that at least 1% of the missing heritability in warfarin dose may be due to the aggregated effects of variations in the warfarin metabolic pathway, even though the SNPs do not individually show a significant association. Conclusions: Our method allows researchers to study aggregative SNP effects in an unbiased manner by not preselecting SNPs. It retains all the available information by accounting for LD-structure through weighting, which eliminates the need for LD pruning

Genome-Wide Tissue-Specific Occupancy of the Hox Protein Ultrabithorax and Hox Cofactor Homothorax in Drosophila

The Hox genes are responsible for generating morphological diversity along the anterior-posterior axis during animal development. The Drosophila Hox gene Ultrabithorax (Ubx), for example, is required for specifying the identity of the third thoracic (T3) segment of the adult, which includes the dorsal haltere, an appendage required for flight, and the ventral T3 leg. Ubx mutants show homeotic transformations of the T3 leg towards the identity of the T2 leg and the haltere towards the wing. All Hox genes, including Ubx, encode homeodomain containing transcription factors, raising the question of what target genes Ubx regulates to generate these adult structures. To address this question, we carried out whole genome ChIP-chip studies to identify all of the Ubx bound regions in the haltere and T3 leg imaginal discs, which are the precursors to these adult structures. In addition, we used ChIP-chip to identify the sites bound by the Hox cofactor, Homothorax (Hth). In contrast to previous ChIP-chip studies carried out in Drosophila embryos, these binding studies reveal that there is a remarkable amount of tissue- and transcription factor-specific binding. Analyses of the putative target genes bound and regulated by these factors suggest that Ubx regulates many downstream transcription factors and developmental pathways in the haltere and T3 leg. Finally, we discovered additional DNA sequence motifs that in some cases are specific for individual data sets, arguing that Ubx and/or Hth work together with many regionally expressed transcription factors to execute their functions. Together, these data provide the first whole-genome analysis of the binding sites and target genes regulated by Ubx to specify the morphologies of the adult T3 segment of the fly

Argo data 1999-2019: two million temperature-salinity profiles and subsurface velocity observations from a global array of profiling floats.

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Wong, A. P. S., Wijffels, S. E., Riser, S. C., Pouliquen, S., Hosoda, S., Roemmich, D., Gilson, J., Johnson, G. C., Martini, K., Murphy, D. J., Scanderbeg, M., Bhaskar, T. V. S. U., Buck, J. J. H., Merceur, F., Carval, T., Maze, G., Cabanes, C., Andre, X., Poffa, N., Yashayaev, I., Barker, P. M., Guinehut, S., Belbeoch, M., Ignaszewski, M., Baringer, M. O., Schmid, C., Lyman, J. M., McTaggart, K. E., Purkey, S. G., Zilberman, N., Alkire, M. B., Swift, D., Owens, W. B., Jayne, S. R., Hersh, C., Robbins, P., West-Mack, D., Bahr, F., Yoshida, S., Sutton, P. J. H., Cancouet, R., Coatanoan, C., Dobbler, D., Juan, A. G., Gourrion, J., Kolodziejczyk, N., Bernard, V., Bourles, B., Claustre, H., D'Ortenzio, F., Le Reste, S., Le Traon, P., Rannou, J., Saout-Grit, C., Speich, S., Thierry, V., Verbrugge, N., Angel-Benavides, I. M., Klein, B., Notarstefano, G., Poulain, P., Velez-Belchi, P., Suga, T., Ando, K., Iwasaska, N., Kobayashi, T., Masuda, S., Oka, E., Sato, K., Nakamura, T., Sato, K., Takatsuki, Y., Yoshida, T., Cowley, R., Lovell, J. L., Oke, P. R., van Wijk, E. M., Carse, F., Donnelly, M., Gould, W. J., Gowers, K., King, B. A., Loch, S. G., Mowat, M., Turton, J., Rama Rao, E. P., Ravichandran, M., Freeland, H. J., Gaboury, I., Gilbert, D., Greenan, B. J. W., Ouellet, M., Ross, T., Tran, A., Dong, M., Liu, Z., Xu, J., Kang, K., Jo, H., Kim, S., & Park, H. Argo data 1999-2019: two million temperature-salinity profiles and subsurface velocity observations from a global array of profiling floats. Frontiers in Marine Science, 7, (2020): 700, doi:10.3389/fmars.2020.00700.In the past two decades, the Argo Program has collected, processed, and distributed over two million vertical profiles of temperature and salinity from the upper two kilometers of the global ocean. A similar number of subsurface velocity observations near 1,000 dbar have also been collected. This paper recounts the history of the global Argo Program, from its aspiration arising out of the World Ocean Circulation Experiment, to the development and implementation of its instrumentation and telecommunication systems, and the various technical problems encountered. We describe the Argo data system and its quality control procedures, and the gradual changes in the vertical resolution and spatial coverage of Argo data from 1999 to 2019. The accuracies of the float data have been assessed by comparison with high-quality shipboard measurements, and are concluded to be 0.002°C for temperature, 2.4 dbar for pressure, and 0.01 PSS-78 for salinity, after delayed-mode adjustments. Finally, the challenges faced by the vision of an expanding Argo Program beyond 2020 are discussed.AW, SR, and other scientists at the University of Washington (UW) were supported by the US Argo Program through the NOAA Grant NA15OAR4320063 to the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) at the UW. SW and other scientists at the Woods Hole Oceanographic Institution (WHOI) were supported by the US Argo Program through the NOAA Grant NA19OAR4320074 (CINAR/WHOI Argo). The Scripps Institution of Oceanography's role in Argo was supported by the US Argo Program through the NOAA Grant NA15OAR4320071 (CIMEC). Euro-Argo scientists were supported by the Monitoring the Oceans and Climate Change with Argo (MOCCA) project, under the Grant Agreement EASME/EMFF/2015/1.2.1.1/SI2.709624 for the European Commission