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Introduction: Communicating the risks associated with nicotine and tobacco use to adolescents can be challenging, especially with the current tobacco market's attempt to capture the attention of youths. Text message interventions have emerged to address the need to improve tobacco risk communication. This article informs the design of a message library for tobacco risk communication that is based on the transtheoretical model and addresses the risk of multiple tobacco products. Methods: We draw findings from this study from two phases. Phase 1 involved six remote focus group discussions (n = 25) and an in-depth interview, and Phase 2 involved online ideation sessions (n = 11) that led to the current version of the messages. We conducted the study within a larger project for the design and testing of a tobacco prevention program. With thematic analysis and the affinity mapping technique, two research team members identified repeated topics and relevant quotes to organize them into themes and subthemes. Results: In Phase 1, thematic analysis revealed four major themes: 1) Adolescents' gap in tobacco knowledge, 2) Social influence and popularity, 3) Attitude toward marketing, and 4) Text message framing preferences. During Phase 2, participants generated 1-to-7 iterations of the original messages. Votings and discussions resulted in a library of 306 messages under 7 sections, categorized based on the processes of change from the transtheoretical model. Conclusion: The current study presents key insights crucial for developing and evaluating a library of tobacco prevention text messages that is scientifically valid and successfully resonates with today's adolescents. Our future plan is to go beyond this initial message development and vet the message library by adolescents and expert reviewers in tobacco risk communication. Future research may consider developing messages that are tailored based on gender, ethnicity, and other factors that are predictive of tobacco use. [ABSTRACT FROM AUTHOR]

Introduction: Considering the dangers of adolescent tobacco use, the successful design of behavioral programs is crucial for tobacco prevention. According to preliminary research, social game interventions can improve adolescent tobacco outcomes. The current qualitative study aims to (1) uncover the gaming elements that adolescents deem important for a positive learning experience, and (2) confirm these gaming elements with adolescents who are presented with a tobacco prevention game concept that applies these elements. Methods: Findings from this study are drawn from two phases. Phase 1 involved in-person focus group discussions (n = 15) and Phase 2 included three online focus groups and a paired interview with another set of adolescents (n = 15). The study was conducted under a project that aimed to design and test a social game-based tobacco prevention program for adolescents (Storm-Heroes). With open coding and thematic analysis, two research team members identified repeated topics and relevant quotes to organize them into themes. The themes evolved as new content was identified during the process. This process was repeated until thematic saturation was reached. Results: Thematic analysis across Phase 1 and Phase 2 revealed four major themes: 1) Balance during gaming challenges, 2) Healthy social interaction, 3) Performance and creative freedom, and 4) Fictional world and game mechanics for tobacco prevention. Conclusion: This study identified specific intervention features that best fit the needs of adolescents in the context of a social game for tobacco prevention. For future research, we will use a participatory approach to allow adolescents to take part in the design process, improve Storm-Heroes, and develop health promotional messages that can be incorporated into the program. Ultimately, a board game for tobacco prevention is expected to bring adolescents together to create lasting memories that nudge them away from tobacco use and the harm it can cause. [ABSTRACT FROM AUTHOR]

Background: P-glycoprotein (P-gp), a member of the ATP Binding Cassette B1 subfamily (ABCB1), confers resistance to clinically relevant anticancer drugs and targeted chemotherapeutics. However, paradoxically P-glycoprotein overexpressing drug resistant cells are "collaterally sensitive" to non-toxic drugs that stimulate its ATPase activity. Methods: Cell viability assays were used to determine the effect of low concentrations of tamoxifen on the proliferation of multidrug resistant cells (CHORC5 and MDA-Doxo400), expressing P-gp, their parental cell lines (AuxB1 and MDA-MB-231) or P-gp-CRISPR knockout clones of AuxB1 and CHORC5 cells. Western blot analysis was used to estimate P-gp expression in different cell lines. Apoptosis of tamoxifen-induced cell death was estimated by flow cytometry using Annexin-V-FITC stained cells. Oxidative stress of tamoxifen treated cells was determined by measuring levels of reactive oxygen species and reduced thiols using cell-permeant 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) and 5,5-dithio-bis-(2-nitrobenzoic acid) DTNB, respectively. Results: In this report, we show that P-gp-expressing drug resistant cells (CHORC5 and MDA-Doxo400) are collaterally sensitive to the anti-estrogen tamoxifen or its metabolite (4-hydroxy-tamoxifen). Moreover, P-gp-knockout clones of CHORC5 cells display complete reversal of collateral sensitivity to tamoxifen. Drug resistant cells exposed to low concentrations of tamoxifen show significant rise in reactive oxygen species, drop of reduced cellular thiols and increased apoptosis. Consistent with the latter, CHORC5 cells expressing high levels of human Bcl-2 (CHORC5-Bcl-2) show significant resistance to tamoxifen. In addition, the presence of the antioxidant N-acetylcysteine or P-gp ATPase inhibitor, PSC-833, reverse the collateral sensitivity of resistant cells to tamoxifen. By contrast, the presence of rotenone (specific inhibitor of mitochondria complex I) synergizes with tamoxifen. Conclusion: This study demonstrates the use of tamoxifen as collateral sensitivity drug that can preferentially target multidrug resistant cells expressing P-gp at clinically achievable concentrations. Given the widespread use of tamoxifen in the treatment of estrogen receptor-positive breast cancers, this property of tamoxifen may have clinical applications in treatment of P-gp-positive drug resistant breast tumors. [ABSTRACT FROM AUTHOR]

The emergence of drug resistance remains an obstacle in the clinical treatment of cancer. Recent developments in the studies of drug resistance have identified compounds such as verapamil and tamoxifen that specifically target ABCB1-expressing multidrug-resistant (MDR) cells, through an ATP-dependent ROS-generating mechanism. In this report, we demonstrate that treatment of ABCB1-expressing MDR cells (CHORC5 or MDA-Doxo400) or individual clones of the latter with sub-lethal concentrations of tamoxifen or verapamil down-regulates ABCB1 protein and mRNA expression in surviving clones. Consequently, tamoxifen- and verapamil-treated cells show increased sensitivity to chemotherapeutic drugs (e.g. colchicine and doxorubicin) and decreased sensitivity to collateral sensitivity drugs (e.g. verapamil and tamoxifen). Importantly, we show for the first time that down-regulation of ABCB1 expression resulting from tamoxifen treatment and CRISPR-knockout of ABCB1 expression up-regulate α-enolase (enolase I) protein levels and activity. These findings demonstrate a possible effect of ABCB1 expression on the metabolic homeostasis of MDR cells. Moreover, given the use of tamoxifen to prevent the recurrence of oestrogen receptor-positive breast cancer, the findings of this study may be clinically important in modulating activity of other drugs. [ABSTRACT FROM AUTHOR]

The translocator protein (TSPO) is a five-helix transmembrane protein localized to the outer mitochondria membrane. Radioligand binding assays and chemical crosslinking showed TSPO to be a high affinity cholesterol-binding protein. In this report, we show that TSPO in mitochondrial fractions from MA-10 mouse tumour Leydig cells can interact directly and competitively with the clickable photoreactive cholesterol analogue. PhotoClick cholesterol showed saturable photoaffinity labelling of TSPO that could be specifically immunoprecipitated with anti-TSPO antibody, following the click reaction with the fluorescent-azide probe, tetramethylrhodamine (TAMRA)-azide. Moreover, excess cholesterol reduced the photolabelling of both total mitochondrial proteins and TSPO. Together, the results of this study demonstrated direct binding of PhotoClick cholesterol to TSPO and that this interaction occurs at physiologically relevant site(s). [ABSTRACT FROM AUTHOR]

Tobacco smoking remains a public health problem among adolescents in the United States. While Web-based interventions for smoking prevention have been successful at the individual level, there is still an urgent need to understand their engagement capabilities and their effects at the social level. In the current study, we aimed to (1) learn about adolescents' subjective experience with a Web-based program called a smoking prevention interactive experience (ASPIRE), (2) obtain suggestions for improvement in ASPIRE content, (3) identify psychological outcomes of ASPIRE, and (4) explore outcomes of social interaction. After a randomized controlled trial with 110 adolescents, 20 adolescent users of ASPIRE, aged 11–18, were randomly selected to participate in one-on-one interviews at four after-school programs in Houston, Texas. Interviews involved questions concerning adolescents' experience with the intervention. Qualitative data were coded and analyzed using a constant comparison approach for the generation of themes. Describing their experience with ASPIRE, participants expressed comfort in material that is tailored to their demographic and preferred interactive activities over entertaining videos. Presenting suggestions for improvement, participants mainly reported the need to include gaming features into ASPIRE. Presenting psychological outcomes, they expressed emotional engagement in the program, shifts in attitudes and beliefs, and unwillingness to smoke. Finally, as outcomes of social interaction, participants reported engagement with others in discussions about tobacco and their need to hold smokers accountable for their actions. Adolescents' reports moved from their individual experience with ASPIRE to their active interactions with family members and friends and their attempt to persuade others to quit smoking. Future Web-based programs for adolescents may be designed with tailoring and game play in mind, in order to provide mobilization skills and foster social interactions against smoking. [ABSTRACT FROM AUTHOR]

The pigment hemozoin is a natural by-product of the metabolism of hemoglobin by the parasites which cause malaria. Previously, hemozoin was demonstrated to have a very high nonlinear optical response enabling third harmonic generation (THG) imaging. In this study, we present a complete characterization of the nonlinear THG response of natural hemozoin in malaria-infected red blood cells, as well as in pure isostructural synthesized hematin anhydride, in order to determine optimal imaging parameters for detection. Our study demonstrates the wavelength range for optimal pulsed femtosecond laser excitation of THG from hemozoin crystals. In addition, we show the hemozoin crystal detection as a function of crystal size, incident laser power, and the emission response of the hemozoin crystals to different incident laser polarization states. Our systematic measurements of the nonlinear optical response from hemozoin establish detection limits, which are essential for the optimal design of malaria detection technologies that exploit the THG response of hemozoin. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The increase in the mobilities of neurofilament subunits on SDS-PAGE after dephosphorylation was reversed upon boiling in urea or trifluoroacetylation of lysine ε-amino groups. Trifluoroacetylation of native and dephosphorylated neurofilaments also resulted in an overall increase in the phosphorylation of the three subunits by the catalytic subunit of cyclic-AMP-dependent protein kinase. The gel-etectrophoretic mobility of neurofilament subunits was also shown to be influenced by carboxylic amino acid residues, as neutralization of these moieties by glycinamidation increased the mobilities of all three subunits on SDS-PAGE. Neurofilament subunits that were both glycinamidated and dephosphorylated had apparent molecular masses of approximately 60 kDa, 112 kDa and 138 kDa. The major sites of these changes in the two largest subunits were shown to be the carboxyterminal tail domains, which are known to contain high percentages of glutamate. Since interspecies differences in the apparent molecular masses of neurofilament subunits were shown to persist after glycinamidation and dephosphorylation, they appear to be due to differences in polypeptide chain length, rather than glutamate content. [ABSTRACT FROM AUTHOR]

P-glycoprotein (P-gp) plays a fundamental role in multidrug resistance. The quantity of P-gp relates to the degree of drug resistance. A comparison was made between P-gps in mouse and hamster cell lines in both Laemmli and modified Fairbanks gel systems. Both proteins are derived from precursors of similar size that undergo differential N-linked glycosylation. The electrophoretic mobility and the amount of P-gp are remarkably dependent on the conditions of analysis. Notably, boiling P-gp before Laemmli gel elec-trophoresis decreases its mobility by an amount that is equivalent to ≈15 kDa and results in an apparent diminution in the amount of protein. The latter effect can give a false impression concerning the quantity of P-gp in cells. [ABSTRACT FROM PUBLISHER]