148 results on '"Brewster ME"'
Search Results
2. Iatrogenic Pancreatic Cyst Perforation Successfully Managed by a Minimally Invasive Combined Endoscopic;Laparoscopic Approach.
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Elmunzer BJ, Boetticher NC, Mobley CM, Brewster ME, and Sonnenday CJ
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- 2010
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3. Appearance of Aminorex as a Designer Analog of Methylaminorex
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Brewster, ME and Davis, FT
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A case in which aminorex (cis± 4,5-dihydro-5-phenyl-2-oxazolamine) was prepared as a “designer” analog of a controlled substance, methylaminorex (cis± 4,5-dihydro-4-methyl-5-phenyl-2-oxazolamine) is described. The confiscated drug sample was analyzed by high-field (300-mHz) proton nuclear magnetic resonance (NMR) and carbon-13 NMR spectroscopy, as well as electron impact mass spectrometry (70 eV). These examinations proved conclusively that the material in question was aminorex.
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- 1991
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4. A Fatality Involving U4Euh, A Cyclic Derivative of Phenylpropanolamine
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Davis, FT and Brewster, ME
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A fatality following ingestion of diazepam and 4,5-dihydro-4-methyl-5-phenyl-2-oxazolamine, a cyclic derivative of phenylpropanolamine known as U4EuH or 4-methyl aminorex, is described. Solid dosage samples of U4EuH were analyzed using gas chromatography, ultraviolet and infrared spectroscopy, nuclear magnetic resonance, and mass spectrometry. Physiological fluids were analyzed quantitatively by gas chromatography and qualitatively by gas chromatography-mass spectrometry. Concentrations of 4,5-dihydro-4-methyl-5-phenyl-2-oxazolamine were: in blood 21.3 mg/L; in urine 12.3 mg/L. Diazepam concentration in blood was 0.8 mg/L.
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- 1988
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5. Traumatic life events, everyday discrimination, and posttraumatic symptoms among sexual minority men.
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Parent MC, Arriaga AS, Yang J, and Brewster ME
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Objective: Experiences of everyday discrimination are linked with mental health issues for sexual minority individuals, including posttraumatic symptoms (PTS), yet it is unclear whether experiences of discrimination are linked with PTS after accounting for the influence of traumatic life events. This study sought to increase understanding of the link between everyday discrimination and PTS, among sexual minority men., Method: A sample of 290 gay men living in the United States completed an online survey including measures of traumatic life events, everyday discrimination, and PTS., Results: Logistic regressions supported a link between everyday discrimination and meeting the cutoff for PTS, after accounting for traumatic life events. Furthermore, everyday discrimination was linked with higher scores on all symptom clusters of PTS., Conclusions: Study results provide support for a link between everyday discrimination and PTS at levels exceeding clinical cutoffs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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- 2024
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6. Privilege and distress intolerance at the margins: Exploring the role of critical consciousness and entitlement.
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Brewster ME, Velez BL, Motulsky W, Snow OR, Glaeser E, Goates JD, Roberts N, Orlandoni T, and López Molina D
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With a U.S.-based sample of 219 people of color with diverse sexual orientations, the present study aimed to reveal how perceived privilege may be associated with distress intolerance, and the mediating roles of critical consciousness and entitlement. Data were also used to explore the interaction of sexual orientation status (heterosexual or sexual minority) with these paths. Via path analysis, we found that privilege was unrelated to critical consciousness, yielded a positive direct link to entitlement, and had a negative direct link to distress intolerance. Tests of indirect relations showed that privilege had a significant indirect relation to distress intolerance via entitlement but not critical consciousness. Regarding moderation analyses, the Privilege × Sexual Minority Status interaction predicting entitlement, privilege was significantly positively associated with entitlement among both heterosexual and sexual minority participants, but the association was significantly stronger for heterosexual participants. For the Critical Consciousness × Sexual Minority Status interaction predicting distress intolerance, the association of critical consciousness with distress intolerance was nonsignificant for both heterosexual and sexual minority participants, but the association changed direction and was significantly stronger for sexual minority participants. Indirect relations did not differ for sexual minority or heterosexual participants. Implications for future research and intervention are addressed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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- 2024
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7. Minority stress, repetitive negative thinking, and internalizing symptoms in sexual minorites: Does cognitive content matter?
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Pellicane MJ, Brewster ME, and Ciesla JA
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- Adult, Humans, Cognition, Mental Health, Sexual Behavior, Anxiety psychology, Pessimism psychology, Sexual and Gender Minorities
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Background: The Psychological Mediation Framework theorizes that repetitive negative thinking (RNT) mediates the relationship between minority stress and mental health, and this theory has been consistently supported by previous research. Yet, it is unclear whether the process or content of RNT is more important in the development of internalizing symptoms in sexual minorities. Consequently, the goal of the current study was to use structural equation modeling to determine whether there are significant indirect effects of repetitive negative thought content in the relationship between minority stress and internalizing psychopathology., Methods: Measures of RNT, internalizing symptoms, and proximal minority stress were completed online by 205 cisgender sexual minority adults. Structural equation modeling was used to examine indirect effects of proximal stress on internalizing symptoms through content-independent RNT, depressive rumination, and sexual orientation-related rumination., Results: Significant direct effects of proximal minority stress on internalizing symptoms were observed. Indirect effects of proximal stress on internalizing symptoms were observed for content-independent RNT and depressive rumination, but not sexual orientation-related rumination., Conclusions: The current study provides evidence that the process and affective valence of RNT contributes more to internalizing symptoms in sexual minorities when compared with sexual orientation-related content. Theoretical and clinical implications are discussed., (© 2023 The Authors. Journal of Clinical Psychology published by Wiley Periodicals LLC.)
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- 2023
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8. The hidden curriculum of academic writing: Toward demystifying manuscript preparation in counseling psychology.
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Moradi B, Brewster ME, Grzanka PR, and Miller MJ
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- Humans, Counseling, Curriculum, Databases, Factual, Publishing, Writing
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In this article, we aim to unpack some of the hidden curriculum in publishing successfully in the Journal of Counseling Psychology (JCP) and other academic outlets. The many unspoken and implicit considerations behind writing a successful academic article can reinforce epistemic exclusions around class, gender, race, sexuality, and other axes of power that ultimately limit who gets to publish in academic journals and about what. Thus, we work to articulate the processes behind writing an academic article. Specifically, we offer suggestions for (a) writing compelling, precise, and parsimonious introductions, (b) clearly addressing the goals of the study via an accurate and detailed description of the method, (c) aligning analytic decisions with the research questions or hypotheses and the data parameters at hand, and (d) discussing the story of data in the context of prior scholarship, study limitations, and real-world implications. Where applicable, we provide concrete examples of published studies to "unhide" writing processes and to illustrate the invisible narratives and intentions behind key writing practices. We also present a checklist as an easy-to-reference companion to this article to help demystify the writing process. This article aligns with the commitment of JCP's editorial leadership to play an active role in opening up the scholarly publication process so that the pipeline of manuscripts submitted to and accepted by JCP shapes a more inclusive future for the field. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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- 2023
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9. Toward Nonbinary Nuance in Research and Care: Mapping Differences in Gender Affirmation and Transgender Congruence in an Online National U.S. Survey.
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Breslow AS, Wojcik H, Cox R Jr, Tran NM, and Brewster ME
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Purpose: To close gaps in transgender health research, we mapped trends in gender affirmation processes (i.e., social, legal, and psychological transitions) that are unique among nonbinary (NB) transgender adults when compared with transgender women (TW) and transgender men (TM). Methods: Data were drawn from the Columbia Trans Empowerment Survey ( N =707), an online national study conducted between 2014 and 2015 in the United States. We used one-way analysis of variance tests, chi-square tests, Kruskal-Wallis tests, and post hoc analyses to estimate differences in gender affirmation processes and transgender congruence between: (1) NB adults, n =271, 38%; (2) TW, n =291, 41%; and (3) TM, n =145, 21%. We then identified bivariate correlations between variables of interest. Results: In the full sample ( n =707), we found significant positive bivariate correlations between pursuing gender affirmation and transgender congruence. In terms of demographics, NB participants were significantly more likely to be queer (42.1%), polyamorous (25.5%), unemployed (44.8%), and younger (median=22) than TW and TM. They also reported taking significantly fewer gender affirmation processes, with significant differences between the three groups in terms of particular experiences. The NB participants also reported significantly lower rates of transgender congruence, specifically lower appearance congruence though similar gender identity acceptance. Conclusion: The NB transgender adults in this sample report unique identity-related characteristics, including significantly lower rates of medical/social transition as well as decreased transgender congruence. These data are among the first to describe unique pathways by which NB adults, TW, and TM may pursue gender affirmation and interact with providers as they navigate congruence, transition, and well-being., Competing Interests: No competing financial interests exist., (© Aaron S. Breslow et al. 2021; Published by Mary Ann Liebert, Inc.)
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- 2021
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10. Death anxiety and death acceptance in atheists and other nonbelievers.
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Sawyer JS, Brewster ME, and Ertl MM
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- Female, Humans, Male, United States, Anxiety, Religion and Psychology
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This study explores how age, certainty of belief, belief in science and gender is related to death anxiety and death acceptance. Results from a sample of atheists and other nonbelievers ( N = 270) in the United States suggested that age and certainty of belief were significantly related to death anxiety and death acceptance, while belief in science was not a significant predictor. In addition, women reported higher levels of death anxiety compared to men. Implications and directions for future research in death perspectives for atheists and other nonbelievers are discussed.
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- 2021
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11. Adonis on the Apps: Online Objectification, Self-Esteem, and Sexual Minority Men.
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Breslow AS, Sandil R, Brewster ME, Parent MC, Chan A, Yucel A, Bensmiller N, and Glaeser E
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The recent proliferation of mobile dating applications ("apps") has led to profound shifts in the ways sexual minority men (SMM) connect with others and themselves (Anderson, Holland, Koc, & Haslam, 2018). These apps, which often categorize users by factors such as body build, may promote sexual harassment and objectification (Griffiths, Murray, Krug, & McLean, 2018), potentially compounding already disproportionate body image concerns among this population (Daniel & Bridges, 2010). To test relations of app use and online objectification, we examined a path model testing tenets of objectification theory (Fredrickson & Roberts, 1997) among a national sample of 230 SMM. We measured direct and indirect relations between patterns of app use (i.e., number of apps used, app use frequency), online objectification, internalization of sociocultural standards of attractiveness, two psychological reactions (i.e., body surveillance, body satisfaction), and self-esteem, a mental health risk particularly salient among SMM. The present study demonstrated support for expansions of objectification theory both online and among SMM. Regarding direct relations, number of apps used (though not app use frequency) was positively related with objectification, internalization, and body surveillance, and negatively related with body satisfaction and self-esteem. Variables yielded indirect relations via internalization, body surveillance, and body satisfaction. Implications of our findings, as well as limitations and implications for future research and practice, are discussed.
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- 2020
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12. It's like herding cats: Atheist minority stress, group involvement, and psychological outcomes.
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Brewster ME, Velez BL, Geiger EF, and Sawyer JS
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- Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Stress, Psychological diagnosis, United States epidemiology, Young Adult, Minority Groups psychology, Secularism, Self Concept, Social Stigma, Stress, Psychological psychology
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Using minority stress theory with a sample of 522 atheist people from the United States, the present study examined the associations of discrimination, proximal minority stressors (stigma consciousness, internalized antiatheism, outness as atheist), and atheist group involvement with psychological distress and self-esteem. Atheist group involvement was associated positively with outness and self-esteem, and negatively with discrimination. Structural equation modeling indicated that discrimination and stigma consciousness yielded significant positive direct relations with distress, whereas outness yielded a significant negative direct relation with distress. Relatedly, discrimination yielded a significant negative direct relation with self-esteem and outness yielded a significant positive direct relation with self-esteem. There was a significant positive unique indirect relation of antiatheist discrimination with distress via the mediating role of stigma consciousness, but no other proximal variables. Multigroup invariance testing of this model did not yield evidence that the pattern of relations of the minority stressors with mental health outcomes differed significantly between participants who were and who were not involved in an atheist group. Implications of these findings for research, practice, and advocacy are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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- 2020
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13. Working with gender-expansive clients in psychotherapy.
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Brewster ME, Motulsky W, and Glaeser E
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- Adult, Female, Humans, Male, Psychotherapy, Sexual and Gender Minorities
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Gender expansive individuals of all ages are at an elevated risk for mental and physical health problems compared not only to the general population, but also to lesbian, gay, and bisexual individuals. Yet mental healthcare providers tend to be underprepared to provide services to this population, which is due in part to the dearth of scholarship on how to provide competent care to gender-expansive people. The present article introduces themes and terminology crucial to working with this population, as well as three case studies-two individuals and one family-highlighting the nuances inherent in workng with gender expansive clients. We conclude by offering ways to conceptualize each case, and by highlighting certain areas that we believe deserve specific considerations from care providers., (© 2019 Wiley Periodicals, Inc.)
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- 2019
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14. Unpacking body image concerns and disordered eating for transgender women: The roles of sexual objectification and minority stress.
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Brewster ME, Velez BL, Breslow AS, and Geiger EF
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- Adolescent, Adult, Aged, Cross-Sectional Studies, Defense Mechanisms, Dehumanization, Feeding and Eating Disorders epidemiology, Female, Gender Identity, Humans, Middle Aged, Self Concept, Sexual Behavior psychology, Sexual and Gender Minorities psychology, Stress, Psychological epidemiology, Young Adult, Body Image psychology, Feeding and Eating Disorders psychology, Stress, Psychological psychology, Transgender Persons psychology
- Abstract
Synthesizing both objectification theory (Fredrickson & Roberts, 1997) and minority stress theory (Meyer, 2003), the present study used a pantheoretical model of dehumanization (Moradi, 2013) to examine body image concerns and disordered eating symptomatology with 205 transgender women from the United States. Objectification theory constructs (i.e., sexual objectification, internalization of sociocultural standards of attractiveness, body surveillance, body dissatisfaction) and minority stress-related variables (i.e., antitransgender discrimination) were examined as direct and indirect predictors of disordered eating. Results of a latent variable SEM (with a higher-order dehumanization factor comprised of sexual objectification and discrimination) generally provided support for our hypothesized direct and indirect relations. As expected, dehumanization was related directly to internalization and disordered eating and had significant indirect links to body surveillance, body dissatisfaction, and disordered eating via internalization. Potential implications of a pantheoretical model for future research with transgender women are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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- 2019
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15. Assessing posttraumatic growth, complicated grief, and psychological distress in bereaved atheists and believers.
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Sawyer JS and Brewster ME
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- Adult, Female, Humans, Male, Middle Aged, United States, Grief, Posttraumatic Growth, Psychological, Psychological Distress, Religion and Psychology
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The present study examines how meaning and belief in God or god(s) is related to bereavement outcomes. Data from 299 participants residing in the United States indicated that the variables of search for meaning, presence of meaning, and belief in God or god(s) were significantly related to posttraumatic growth, complicated grief, and psychological distress. Results from this study can be used to identify appropriate clinical strategies for mental health practitioners working with bereaved clients and will expand the breadth of literature on bereavement with atheist populations in the United States.
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- 2019
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16. Is Minority Stress in the Eye of the Beholder? A Test of Minority Stress Theory with Christians.
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Parent MC, Brewster ME, Cook SW, and Harmon KA
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- Female, Humans, Male, Prejudice psychology, Christianity, Discrimination, Psychological, Minority Groups psychology, Stress, Psychological psychology
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Studies using minority stress theory have focused on the experiences of numerical and social power minorities, though majority individuals may also perceive themselves to be minorities. We explored minority stress theory among a sample of members of a numerically and socially dominant group: Christians in the USA. Perceiving oneself to be a member of a minority as a Christian was associated with stress indirectly via perceived experiences of faith-based discrimination (i.e., harassment due to being Christian). Being more open about one's religion moderated the relationship between experiences of faith-based discrimination and stress, such that those who were open about their faith reported a stronger relationship between experiences of faith-based discrimination and stress. These findings indicate that perceptions of minority status are important to understanding stress and have implications for minority/majority dialogues.
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- 2018
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17. Improving the Field of LGBTQ Psychology: Strategies for Amplifying Bisexuality Research.
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Pollitt AM, Brimhall AL, Brewster ME, and Ross LE
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Bisexuality has been critically understudied despite decades of research demonstrating pronounced disparities among bisexual populations. To better understand the state of bisexual research in the field of LGBTQ psychology, we conducted a content analysis of abstracts published in the Psychology of Sexual Orientation and Gender Diversity ( PSOGD ). Of 223 articles published in PSOGD , less than 1% were focused on bisexual populations. Many studies used "bisexuality" in their titles or as a keyword even when they contained little to no focus on bisexuality. Results from the content analysis are consistent with content analyses on medical and sexualities literatures. We highlight important strategies for improving the quantity and quality of bisexual research in LGBTQ psychology, including but limited to careful attention to bisexuality from study development to dissemination.
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- 2018
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18. Lesbian women and household labor division: A systematic review of scholarly research from 2000 to 2015.
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Brewster ME
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- Female, Humans, Interpersonal Relations, Role, Sexual and Gender Minorities, Activities of Daily Living, Family Characteristics, Homosexuality, Female
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Recent studies have begun to attend to distribution of household labor within same-gender couples compared to heterosexual couples, yet much of the available research with lesbian couples has attempted to superimpose division of household labor frameworks developed with heterosexual couples (e.g., gender role socialization, exchange bargaining theories) to fit the experiences of same-gender couples. Using two academic search databases, the present article provides a systematic review of the available 28 peer-reviewed articles published from 2000-2015 about lesbian partnerships and household labor divisions. Results indicate that lesbian couples engage in a more equal distribution of household labor than heterosexual couples, and that lesbian women often opt to eschew traditional gendered divisions of chores in favor of other factors such as quality of task or ability. The systematic review uncovered notable constraints in the demography of participants (e.g., race, socioeconomic status, geographic location) across studies. Strategies for deepening the depth and breadth of this line of work for future researchers, and implications for relationship satisfaction are also discussed.
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- 2017
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19. From awareness to action: Examining predictors of lesbian, gay, bisexual, and transgender (LGBT) activism for heterosexual people.
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Jones KN and Brewster ME
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- Female, Humans, Male, Social Justice, Social Theory, Surveys and Questionnaires, United States, Awareness, Heterosexuality psychology, Sexual and Gender Minorities psychology, Social Support
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In recent history, heterosexual allies have played an integral role in promoting change for lesbian, gay, bisexual, and transgender (LGBT) populations in the United States; however, questions have been raised as to what drives heterosexual allies to promote change via activism. To delineate factors important in engagement in activism, 207 self-identified heterosexual allies completed an online survey measuring components associated with LGBT activism using Bandura's (1986) model of triadic reciprocal determinism: personal factors (ally identity, social justice self-efficacy and outcome expectations, empathetic perspective taking, and gender) and environmental factors (social justice related supports and barriers, positive marginality, and education level) to predict behaviors (LGBT activism). A hierarchical multiple regression analysis revealed a model accounting for 62% of the variance in LGBT activism, with dimensions of ally identification, social justice self-efficacy, outcome expectations, and education level emerging as significant predictors of engagement in activism behaviors. Empathetic perspective taking and social justice related barriers predicted lack of engagement in LGBT activism, however. Supporting the notion that personal and environmental factors simultaneously impact engagement in LGBT activism. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)
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- 2017
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20. Footprints in the Sand: Personal, Psychological, and Relational Profiles of Religious, Spiritual, and Atheist LGB Individuals.
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Foster AB, Brewster ME, Velez BL, Eklund A, and Keum BT
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- Adolescent, Adult, Female, Humans, Male, Mental Health, Middle Aged, Self Concept, Homosexuality psychology, Religion, Sexual and Gender Minorities psychology, Spiritualism
- Abstract
The present study offers a comparison of the demographic features and lived experiences of lesbian, gay, and bisexual (LGB) individuals with religious, spiritual, or atheist (R/S/A) belief systems. In this sample of 212 participants, the relationship of participants' R/S/A beliefs to personal variables (e.g., age, gender, race), mental health variables (e.g., life satisfaction, psychological distress, internalized heterosexism, self-esteem), and relational variables (e.g., outness, connection to LGBTQ communities) were assessed. Correlational analyses indicated that level of R/S/A belief was unrelated to self-esteem, life satisfaction, or psychological distress; however, greater religious belief was correlated positively and significantly with internalized heterosexism and outness as LGB. To test the interactions of R/S/A beliefs and categorical variables of interest (e.g., race), log-linear analyses with follow-up chi-square tests were conducted. Findings suggested more similarities than differences for LGB people across R/S/A systems of belief. Limitations and implications for future research are discussed.
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- 2017
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21. Building a pantheoretical model of dehumanization with transgender men: Integrating objectification and minority stress theories.
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Velez BL, Breslow AS, Brewster ME, Cox R, and Foster AB
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- Adolescent, Adult, Body Image, Compulsive Behavior psychology, Exercise psychology, Female, Gender Identity, Humans, Male, Personal Satisfaction, Prejudice psychology, Young Adult, Dehumanization, Minority Groups psychology, Models, Psychological, Psychological Theory, Stress, Psychological complications, Stress, Psychological psychology, Transgender Persons psychology
- Abstract
With a national sample of 304 transgender men, the present study tested a pantheoretical model of dehumanization (Moradi, 2013) with hypotheses derived from objectification theory (Fredrickson & Roberts, 1997), minority stress theory (Meyer, 2003), and prior research regarding men's body image concerns. Specifically, we tested common objectification theory constructs (internalization of sociocultural standards of attractiveness [SSA], body surveillance, body satisfaction) as direct and indirect predictors of compulsive exercise. We also examined the roles of transgender-specific minority stress variables-antitransgender discrimination and transgender identity congruence-in the model. Results of a latent variable structural equation model yielded mixed support for the posited relations. The direct and indirect interrelations of internalization of SSA, body surveillance, and body satisfaction were consistent with prior objectification theory research, but only internalization of SSA yielded a significant direct relation with compulsive exercise. In addition, neither internalization of SSA nor body surveillance yielded significant indirect relations with compulsive exercise. However, antitransgender discrimination yielded predicted indirect relations with body surveillance, body satisfaction, and compulsive exercise, with transgender congruence playing a key mediating role in most of these relations. The implications of this pantheoretical model for research and practice with transgender men are discussed. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)
- Published
- 2016
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22. Perceived experiences of atheist discrimination: Instrument development and evaluation.
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Brewster ME, Hammer J, Sawyer JS, Eklund A, and Palamar J
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- Adolescent, Adult, Aged, Aged, 80 and over, Factor Analysis, Statistical, Female, Humans, Loneliness, Male, Middle Aged, Perception, Reproducibility of Results, Social Stigma, Stress, Psychological complications, Stress, Psychological psychology, Young Adult, Prejudice psychology, Psychometrics methods, Religion, Religion and Psychology, Secularism, Surveys and Questionnaires
- Abstract
The present 2 studies describe the development and initial psychometric evaluation of a new instrument, the Measure of Atheist Discrimination Experiences (MADE), which may be used to examine the minority stress experiences of atheist people. Items were created from prior literature, revised by a panel of expert researchers, and assessed psychometrically. In Study 1 (N = 1,341 atheist-identified people), an exploratory factor analysis with 665 participants suggested the presence of 5 related dimensions of perceived discrimination. However, bifactor modeling via confirmatory factor analysis and model-based reliability estimates with data from the remaining 676 participants affirmed the presence of a strong "general" factor of discrimination and mixed to poor support for substantive subdimensions. In Study 2 (N = 1,057 atheist-identified people), another confirmatory factor analysis and model-based reliability estimates strongly supported the bifactor model from Study 1 (i.e., 1 strong "general" discrimination factor) and poor support for subdimensions. Across both studies, the MADE general factor score demonstrated evidence of good reliability (i.e., Cronbach's alphas of .94 and .95; omega hierarchical coefficients of .90 and .92), convergent validity (i.e., with stigma consciousness, β = .56; with awareness of public devaluation, β = .37), and preliminary evidence for concurrent validity (i.e., with loneliness β = .18; with psychological distress β = .27). Reliability and validity evidence for the MADE subscale scores was not sufficient to warrant future use of the subscales. Limitations and implications for future research and clinical work with atheist individuals are discussed. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)
- Published
- 2016
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23. Evaluation of Three Amorphous Drug Delivery Technologies to Improve the Oral Absorption of Flubendazole.
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Vialpando M, Smulders S, Bone S, Jager C, Vodak D, Van Speybroeck M, Verheyen L, Backx K, Boeykens P, Brewster ME, Ceulemans J, Novoa de Armas H, Van Geel K, Kesselaers E, Hillewaert V, Lachau-Durand S, Meurs G, Psathas P, Van Hove B, Verreck G, Voets M, Weuts I, and Mackie C
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- Animals, Desiccation, Drug Compounding, Drug Delivery Systems, Humidity, Male, Mebendazole administration & dosage, Mebendazole pharmacokinetics, Methylcellulose analogs & derivatives, Mouth Mucosa metabolism, Povidone, Rats, Rats, Sprague-Dawley, Suspensions, Vitamin E chemistry, Antinematodal Agents administration & dosage, Antinematodal Agents pharmacokinetics, Mebendazole analogs & derivatives
- Abstract
This study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH. All formulations remained amorphous at 25°C/60% RH. Only the MPSDD formulation containing HPMCAS-M and 3/7 (wt./wt.) FLU/OMS did not crystallize following 40°C/75% RH exposure. The OMS and MPSDD formulations contained the lowest and highest amount of hydrolyzed degradant, respectively. All formulations were dosed to rats at 20 mg/kg in suspension. One FLU/OMS formulation was also dosed as a capsule blend. Plasma concentration profiles were determined following a single dose. In vivo findings show that the OMS capsule and suspension resulted in the overall highest area under the curve and Cmax values, respectively. These results cross-evaluate various amorphous formulations and provide a link to enhanced biopharmaceutical performance., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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24. Understanding affiliate stigma faced by heterosexual family and friends of LGB people: A measurement development study.
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Robinson MA and Brewster ME
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- Adult, Aged, Aged, 80 and over, Bisexuality statistics & numerical data, Factor Analysis, Statistical, Female, Heterosexuality statistics & numerical data, Homosexuality, Female statistics & numerical data, Homosexuality, Male statistics & numerical data, Humans, Male, Middle Aged, Psychometrics, Qualitative Research, Reproducibility of Results, Shame, Bisexuality psychology, Family psychology, Friends psychology, Homosexuality, Female psychology, Homosexuality, Male psychology, Interpersonal Relations, Social Stigma
- Abstract
The present study describes the development and psychometric evaluation of the Lesbian, Gay, Bisexual Affiliate Stigma Measure (LGB-ASM). Existing qualitative research and feedback from experts in stigma research contributed to the development of 48 items that were subjected to psychometric evaluation resulting in the final 17-item measure. Exploratory factor analysis of data from 471 LGB affiliates (family members and close friends of LGB individuals) resulted in 3 factors reflecting experiences of LGB affiliate stigma including (a) public discrimination/rejection affiliate stigma, (b) vicarious affiliate stigma, and (c) public shame affiliate stigma. Confirmatory factor analysis of data from a separate 101 participants supported the stability of the 3-factor model. Further psychometric evaluation of the measure resulted in evidence supporting the reliability (i.e., Cronbach's alphas of .71 to .93), convergent validity (i.e., with stigma consciousness, r = .17 to .45; with awareness of public devaluation, r = .18 to .28), and discriminant validity (i.e., with socially desirable responding, r = -.16 to .05). The final 17-item LGB-ASM yielded 2-to 3-week test-retest reliability coefficients of .74 to .76 with a sample of 61 participants. Exploratory links between the LGB-ASM and psychological distress (using the Hopkins Symptom Checklist-21) were evaluated., ((c) 2016 APA, all rights reserved).)
- Published
- 2016
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25. Minority stress and the moderating role of religious coping among religious and spiritual sexual minority individuals.
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Brewster ME, Velez BL, Foster A, Esposito J, and Robinson MA
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- Adolescent, Adult, Aged, Defense Mechanisms, Female, Humans, Male, Middle Aged, Stress, Psychological prevention & control, Young Adult, Adaptation, Psychological, Minority Groups psychology, Religion and Psychology, Sexual Behavior psychology, Stress, Psychological psychology
- Abstract
In prior research with primarily heterosexual religious and spiritual individuals, positive and negative forms of religious coping have been posited to moderate the links between minority stressors and psychological outcomes (Kim, Kendall, & Webb, 2015; Szymanski & Obiri, 2011). With a sample of 143 sexual minority people, the present study extended these hypotheses by examining the moderating roles of positive and negative religious coping in the link of 2 sexual minority-specific minority stress variables (heterosexist discrimination, internalized heterosexism) with psychological distress and well-being. In partial support of our hypotheses, we found that positive religious coping moderated the relation of internalized heterosexism and psychological well-being such that greater positive religious coping weakened the deleterious impact of internalized heterosexism on psychological well-being. Negative religious coping did not moderate any links. As the first test of the moderating roles of religious coping styles in the sexual minority stress-psychological distress link, the present study yields important findings for research and practice with religious and spiritual sexual minority individuals. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)
- Published
- 2016
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26. Coping Styles and Suicide in Racially and Ethnically Diverse Lesbian, Bisexual, and Queer Women.
- Author
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Rabinovitch AE, Perrin PB, Tabaac AR, and Brewster ME
- Abstract
The purpose of the current study was to examine whether coping strategies are associated with past suicidal ideation and history of suicide attempts among sexual minority women (SMW). Participants were 150 racially and ethnically diverse lesbian, bisexual, queer, or "other" nonheterosexual-identified cisgender women who were recruited as part of a national online survey on the experiences of SMW. Simultaneous multiple regressions suggested that coping styles significantly explained 20.3% of the variance in past suicidal ideation and 30.4% of the variance in lifetime history of suicide attempts. Within these regressions, self-blame coping positively predicted past suicidal ideation, and religious coping and venting coping were associated with a higher lifetime history of suicide attempts. Based on these findings, directions for future research and interventions to reduce suicide risk among SMW are discussed.
- Published
- 2015
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27. High speed electrospinning for scaled-up production of amorphous solid dispersion of itraconazole.
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Nagy ZK, Balogh A, Démuth B, Pataki H, Vigh T, Szabó B, Molnár K, Schmidt BT, Horák P, Marosi G, Verreck G, Van Assche I, and Brewster ME
- Subjects
- Antifungal Agents administration & dosage, Antifungal Agents chemistry, Calorimetry, Differential Scanning, Chemistry, Pharmaceutical methods, Crystallization, Drug Industry methods, Itraconazole chemistry, Microspheres, Solubility, Solvents chemistry, X-Ray Diffraction, Itraconazole administration & dosage, Nanofibers, Polymers chemistry, Technology, Pharmaceutical methods
- Abstract
High speed electrospinning (HSES), compatible with pharmaceutical industry, was used to demonstrate the viability of the preparation of drug-loaded polymer nanofibers with radically higher productivity than the known single-needle electrospinning (SNES) setup. Poorly water-soluble itraconazole (ITRA) was formulated with PVPVA64 matrix polymer using four different solvent-based methods such as HSES, SNES, spray drying (SD) and film casting (FC). The formulations were assessed in terms of improvement in the dissolution rate of ITRA (using a "tapped basket" dissolution configuration) and analysed by SEM, DSC and XRPD. Despite the significantly increased productivity of HSES, the obtained morphology was very similar to the SNES nanofibrous material. ITRA transformed into an amorphous form, according to the DSC and XRPD results, in most cases except the FC samples. The limited dissolution of crystalline ITRA could be highly improved: fast dissolution occurred (>90% within 10min) in the cases of both (the scaled-up and the single-needle) types of electrospun fibers, while the improvement in the dissolution rate of the spray-dried microspheres was significantly lower. Production of amorphous solid dispersions (ASDs) with the HSES system proved to be flexibly scalable and easy to integrate into a continuous pharmaceutical manufacturing line, which opens new routes for the development of industrially relevant nanopharmaceuticals., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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28. Downstream processing of polymer-based amorphous solid dispersions to generate tablet formulations.
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Démuth B, Nagy ZK, Balogh A, Vigh T, Marosi G, Verreck G, Van Assche I, and Brewster ME
- Subjects
- Chemistry, Pharmaceutical, Rheology, Drug Compounding methods, Polymers chemistry, Tablets chemistry
- Abstract
Application of amorphous solid dispersions (ASDs) is considered one of the most promising approaches to increase the dissolution rate and extent of bioavailability of poorly water soluble drugs. Such intervention is often required for new drug candidates in that enablement, bioavailability is not sufficient to generate a useful product. Importantly, tableting of ASDs is often complicated by a number of pharmaceutical and technological challenges including poor flowability and compressibility of the powders, compression-induced phase changes or phase separation and slow disintegration due to the formation of a gelling polymer network (GPN). The design principles of an ASD-based system include its ability to generate supersaturated systems of the drug of interest during dissolution. These metastable solutions can be prone to precipitation and crystallization reducing the biopharmaceutical performance of the dosage form. The main aim of the research in this area is to maintain the supersaturated state and optimally enhance bioavailability, meaning that crystallization should be delayed or inhibited during dissolution, as well as in solid phase (e.g., during manufacturing and storage). Based on the expanding use of ASD technology as well as their downstream processing, there is an acute need to summarize the results achieved to this point to better understand progress and future risks. The aim of this review is to focus on the conversion of ASDs into tablets highlighting results from various viewpoints., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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29. Negotiating multiple marginalizations: experiences of South Asian LGBQ individuals.
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Sandil R, Robinson M, Brewster ME, Wong S, and Geiger E
- Subjects
- Acculturation, Adult, Asia, Southeastern ethnology, Female, Homosexuality, Female psychology, Homosexuality, Male psychology, Humans, Male, Middle Aged, Stress, Psychological psychology, United States, Homosexuality psychology, Sexual and Gender Minorities psychology, Social Marginalization psychology
- Abstract
Drawing from minority stress (Meyer, 2003) and feminist multicultural (Brown, 1994) theories, the present study investigated the additive and interactive relations between 2 types of external minority stress (heterosexist discrimination and racist events) and 4 internal stress processes related to identifying as a South Asian American lesbian, gay, bisexual, and queer (LGBQ) person (internalized heterosexism, acculturation, enculturation, and outness as LGBQ) with psychological distress. With 142 participants, Pearson's correlations, multiple regression, and simultaneous multiple moderation analyses were conducted. Experiences of heterosexist discrimination, racist events, and internalized heterosexism were correlated positively with psychological distress and enculturation was correlated negatively. In a test of the additive model, heterosexist discrimination, racist events, and internalized heterosexism accounted for significant and unique variance in psychological distress, but outness, acculturation, and enculturation did not. To test the interactive model, the simultaneous moderating roles of the internal stress processes were examined in the links between the external minority stressors to psychological distress. Only outness as LGBQ emerged as a moderator. The link between racist events and psychological distress was exacerbated in instances of higher outness, such that respondents with high racist events and high outness reported the highest levels of psychological distress. Clinical implications of these findings are discussed and future research directions focused on the needs of South Asian American LGBQ people are suggested., ((PsycINFO Database Record (c) 2015 APA, all rights reserved).)
- Published
- 2015
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30. Nanosuspension for the delivery of a poorly soluble anti-cancer kinase inhibitor.
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Danhier F, Ucakar B, Vanderhaegen ML, Brewster ME, Arien T, and Préat V
- Subjects
- Administration, Oral, Animals, Antineoplastic Agents chemistry, Area Under Curve, Drug Screening Assays, Antitumor, Humans, Hydrogen-Ion Concentration, Maximum Tolerated Dose, Mice, Mice, Nude, Micelles, Nanoparticles chemistry, Neoplasm Transplantation, Neoplasms drug therapy, Polymers chemistry, Solubility, Suspensions, Antineoplastic Agents administration & dosage, Drug Delivery Systems, Macrocyclic Compounds administration & dosage, Protein Kinase Inhibitors administration & dosage, beta-Cyclodextrins chemistry
- Abstract
We hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG₇₅₀-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the nano-formulations presented a size below 200 nm. Injections of the highest possible dose of the three nano-formulations did not induce any side effects in mice. In contrast, the maximum tolerated dose of the control Captisol solution was 20-fold lower than its highest possible dose. The highest regrowth delay of A-431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension, administered intravenously, at a dose of 650 mg/kg. After intravenous and oral administration, the AUC₀₋∞ of MTKi-327 nanosuspension was 2.4-fold greater than that of the Captisol solution. Nanosuspension may be considered as an effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327 maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327, (iii) its ability to enhance the administered dose and (iv) its higher efficacy., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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31. Moving beyond the binary with disordered eating research: a test and extension of objectification theory with bisexual women.
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Brewster ME, Velez BL, Esposito J, Wong S, Geiger E, and Keum BT
- Subjects
- Adolescent, Adult, Aged, Body Dysmorphic Disorders diagnosis, Body Dysmorphic Disorders psychology, Feeding and Eating Disorders psychology, Female, Humans, Internal-External Control, Middle Aged, Prejudice psychology, Psychometrics, Shame, Social Values, Surveys and Questionnaires, Young Adult, Biomedical Research statistics & numerical data, Bisexuality psychology, Feeding and Eating Disorders diagnosis, Feeding and Eating Disorders therapy, Gender Identity, Psychological Theory
- Abstract
In predicting disordered eating, the core model of objectification theory (Fredrickson & Roberts, 1997) has been replicated and extended in research across most sexual minority groups (e.g., Haines et al., 2008; Wiseman & Moradi, 2010), but not bisexual women. The present study tested the tenets of objectification theory with a sample of 316 bisexual women and further extended this theory by examining the roles of 2 minority stressors-antibisexual discrimination and internalized biphobia-that are contextually salient for bisexual women. A latent variable structural equation model was conducted, and the model yielded a good fit to the data. Antibisexual discrimination and internalized biphobia (but not sexual objectification experiences) yielded significant unique links with internalization of sociocultural standards of attractiveness (internalization of CSA). Next, internalization of CSA yielded a significant unique link with body surveillance. In addition, antibisexual discrimination, internalization of CSA, and body surveillance yielded significant unique links with body shame. Finally, sexual objectification experiences, internalization of CSA, and body shame yielded significant unique links with eating disorder symptomatology. Beyond the direct relations, antibisexual discrimination yielded significant positive indirect links with body surveillance, body shame, and eating disorder symptoms. Internalization of CSA yielded significant positive indirect links with body shame and eating disorder symptoms. Lastly, body surveillance yielded a significant positive indirect link with eating disorder symptoms. Implications for research and practice with bisexual women are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
- Published
- 2014
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32. Navigating the borderlands: the roles of minority stressors, bicultural self-efficacy, and cognitive flexibility in the mental health of bisexual individuals.
- Author
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Brewster ME, Moradi B, DeBlaere C, and Velez BL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bisexuality statistics & numerical data, Female, Humans, Male, Mental Disorders, Middle Aged, Minority Groups psychology, Minority Groups statistics & numerical data, Prejudice psychology, Prejudice statistics & numerical data, Surveys and Questionnaires, Young Adult, Adaptation, Psychological physiology, Bisexuality psychology, Cognition physiology, Mental Health statistics & numerical data, Self Efficacy, Stress, Psychological psychology
- Abstract
The present study examined the relations of minority stressors (i.e., experiences of prejudice, expectations of stigma, internalized biphobia, outness/concealment of bisexuality) as well as posited mental health promoters (i.e., bicultural self-efficacy, cognitive flexibility) with psychological distress and well-being in a sample of 411 bisexual people. Most of the minority stress variables were related positively with psychological distress and negatively with well-being, whereas the mental health-promoting variables were related negatively with psychological distress and positively with well-being. Results also indicated that expectations of stigma mediated the associations of antibisexual prejudice with greater distress and lower well-being, internalized biphobia was related directly with greater distress and lower well-being, and outness was linked with some costs and benefits. Moderated mediation analyses offered some evidence consistent with cognitive flexibility (but not bicultural self-efficacy) as a moderator. Specifically, within the mediation models, cognitive flexibility moderated the unique direct relation of antibisexual prejudice with psychological well-being, the relation of antibisexual prejudice with expectations of stigma, and the indirect relations of antibisexual prejudice with distress and well-being through the mediating role of expectations of stigma. These moderations were consistent with the expected buffering role of cognitive flexibility, but they also revealed that some of this buffering effect is exhausted in the context of high prejudice. Limitations of the study as well as implications for future research and practice with bisexual populations are discussed.
- Published
- 2013
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33. Testing the tenets of minority stress theory in workplace contexts.
- Author
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Velez BL, Moradi B, and Brewster ME
- Subjects
- Adult, Bisexuality psychology, Bisexuality statistics & numerical data, Female, Homosexuality psychology, Homosexuality statistics & numerical data, Humans, Male, Minority Groups statistics & numerical data, Prejudice psychology, Sex Distribution, Sexuality statistics & numerical data, Social Support, Workplace statistics & numerical data, Job Satisfaction, Minority Groups psychology, Sexuality psychology, Social Stigma, Stress, Psychological psychology, Workplace psychology
- Abstract
The links of minority stressors (workplace discrimination, expectations of stigma, internalized heterosexism, and identity management strategies) with psychological distress and job satisfaction were examined in a sample of 326 sexual minority employees. Drawing from minority stress theory and the literature on the vocational experiences of sexual minority people, patterns of mediation and moderation were tested. Minority stressors were associated with greater distress and lower job satisfaction. A mediation model was supported in which the links of discrimination and internalized heterosexism with psychological distress were mediated by a concealment-focused identity management strategy (i.e., avoiding), and the links of discrimination, expectations of stigma, and internalized heterosexism with job satisfaction were mediated by a disclosure-focused identity management strategy (i.e., integrating). Tests of moderation indicated that for sexual minority women (but not men), the positive association of discrimination with distress was stronger at higher levels of internalized heterosexism than at lower levels. In addition, lower levels of internalized heterosexism and concealment strategies (i.e., counterfeiting and avoiding) and higher levels of a disclosure strategy (i.e., integrating) were associated with higher job satisfaction in the context of low discrimination, but this buffering effect disappeared as level of discrimination increased. The implications of these findings for minority stress research are discussed, and clinical recommendations are made.
- Published
- 2013
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- View/download PDF
34. Evaluation of gastrointestinal drug supersaturation and precipitation: strategies and issues.
- Author
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Bevernage J, Brouwers J, Brewster ME, and Augustijns P
- Subjects
- Animals, Chemical Precipitation, Chemistry, Pharmaceutical, Drug Delivery Systems, Gastrointestinal Tract metabolism, Humans, Intestinal Absorption, Solubility, Pharmaceutical Preparations chemistry
- Abstract
Supersaturating drug delivery systems (SDDS) hold the promise of enabling intestinal absorption for difficult-to-formulate, poorly soluble drug candidates based on a design approach that includes (1) converting the drug into a high energy or rapidly dissolving system which presents a supersaturated solution to the gastrointestinal environment and (2) dosage form components that act to stabilize the formed metastable drug solution through nucleation and/or crystal growth inhibition. The appropriate development and study of SDDS require that useful and biorelevant supersaturation and precipitation assays are available. This review summarizes different methodological aspects of currently available in vitro assays, including the generation of supersaturation (solvent shift, pH shift or formulation-induced), the quantification of supersaturation and the detection of precipitation. Also down-scaled approaches, including 96-well plate setups, are described and situated in the pharmaceutical development cycle based on their consumption of API as well as time requirements. Subsequently, the ability to extrapolate in vitro supersaturation assessment to the in vivo situation is discussed as are direct and indirect clinical tools that can shed light on SDDS. By emphasizing multiple variables that affect the predictive power of in vitro assays (e.g. the nature of the test media, hydrodynamics, temperature and sink versus non-sink conditions), this review finally highlights the need for further harmonization and biorelevance improvement of currently available in vitro procedures for supersaturation and precipitation evaluation., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
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35. Professor Valentino J. Stella: scientist, mentor, entrepreneur, family man, and giant in pharmaceutical chemistry.
- Author
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Oliyai R, Brewster ME, Ozeki T, Rajewski RA, and Charman W
- Subjects
- Drug Carriers history, History, 20th Century, History, 21st Century, Humans, Pharmacokinetics, Prodrugs history, Teaching history, United States, Biomedical Research history, Chemistry, Pharmaceutical history, Entrepreneurship history, Family Relations, Mentors history, Technology, Pharmaceutical history
- Published
- 2012
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36. Cyclodextrins as functional excipients: methods to enhance complexation efficiency.
- Author
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Loftsson T and Brewster ME
- Subjects
- Chemistry, Pharmaceutical, Models, Chemical, Solubility, Technology, Pharmaceutical methods, Cyclodextrins chemistry, Drug Carriers, Excipients chemistry, Pharmaceutical Preparations chemistry
- Abstract
Cyclodextrins have gained currency as useful solubilizing excipients with an ever increasing list of beneficial properties and functionalities. Although their use in liquid dosage forms including oral and parenteral solutions is straightforward, their application to solids can be confounded by the added bulk that is contributed to the formulation. This factor has limited the use of cyclodextrin in tablets and relates systems mainly to potent drug substances. Increasing the ability of cyclodextrins to complex with drug through a manipulation of their complexation efficiency (CE) may expand the use of these materials to the increasing list of drug candidates and marketed drugs who may benefit from this technology. This brief review assesses tools and materials that have been suggested for increasing the CE for pharmaceutically useful cyclodextrins and drugs. The relative importance of impacting the drug solubility (S(0) ) and phase-solubility isotherm slope is discussed in the context of drug ionization and salt use; the impact of polymers, charge interactions, and charge shielding; and the coincidental formation of other complex types in the media. The influence of drug form as well as supersaturation is also discussed in the context of the responsible mechanisms along with aggregation, inclusion, and noninclusion complex formation., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
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37. Transgender individuals' workplace experiences: the applicability of sexual minority measures and models.
- Author
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Brewster ME, Velez B, DeBlaere C, and Moradi B
- Subjects
- Adolescent, Adult, Aged, Bisexuality psychology, Career Choice, Gender Identity, Homosexuality psychology, Humans, Middle Aged, Psychometrics statistics & numerical data, Reproducibility of Results, Social Identification, Young Adult, Job Satisfaction, Minority Groups psychology, Models, Psychological, Personality Inventory statistics & numerical data, Prejudice, Social Environment, Social Perception, Transsexualism psychology
- Abstract
The present study explored whether 3 existing measures of workplace constructs germane to the experiences of sexual minority people could be modified to improve their applicability with transgender individuals. To this end, the Workplace Heterosexist Experiences Questionnaire (WHEQ; C. R. Waldo, 1999); the Lesbian, Gay, Bisexual, and Transgendered Climate Inventory (LGBTCI; B. J. Liddle, D. A. Luzzo, A. L. Hauenstein, & K. Schuck, 2004); and the Workplace Sexual Identity Management Measure (WSIMM; M. Z. Anderson, J. M. Croteau, Y. B. Chung, & T. M. DiStefano, 2001) were modified to explicitly address the experiences of transgender individuals. Data from a sample of 263 transgender individuals were used to evaluate the psychometric properties of the modified measures. Analyses of the structures of the modified measures (Transgender Forms [TF]) suggested an alternative 2-factor structure for the WHEQ-TF, but provided support for the previously observed unidimensional structure for the LGBTCI-TF, and a slightly modified 3-factor structure for the WSIMM-TF. Cronbach's alpha reliability coefficients for scale or subscale items across the 3 measures were acceptable. Criterion-related validity was evident in theoretically consistent patterns of correlations between scores on the 3 modified measures and scores on indicators of job satisfaction and outness. These data provide preliminary support for transgender-specific versions of measures of 3 key constructs in the sexual minority vocational behavior research., ((c) 2012 APA, all rights reserved.)
- Published
- 2012
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38. Supersaturating drug delivery systems: fast is not necessarily good enough.
- Author
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Augustijns P and Brewster ME
- Subjects
- Biological Availability, Chemical Precipitation, Delayed-Action Preparations chemistry, Drug Stability, Solubility, Solutions chemistry, Chemistry, Pharmaceutical, Drug Delivery Systems
- Abstract
An emerging technology subtype that has been adopted by formulators to address low-solubility issues is the supersaturating drug delivery system; this system is based on the "spring" and "parachute" design elements, which have been applied to lipid-based formulations, S(M)EDDS, solid dispersions, nano-based systems, and many others. This broad formulation approach attempts to delicately balance the need of creating intraluminal drug concentrations in excess of its thermodynamic solubility while at the same time providing for sufficient solution stability to allow for useful drug absorption. The conundrum created is that the higher the extent of supersaturation, the lower the physical stability of the metastable solution based on an increased tendency for a solubilized drug to precipitate. Traditional dissolution testing is a touchstone of formulation development based on the need for useful dissolution rates and drug availability. Dissolution testing is likewise important in the development and characterization of enabling and supersaturating drug delivery systems; however, their execution and interpretation are distinct from that associated with conventional dosage forms. The nature of the dissolution assay (sink versus nonsink, apparatus type, and rate and extent of supersaturation) can impact the ability to efficiently use the dissolution data in the configuration of these enabling formulations., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2012
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39. Self-assembly of cyclodextrin complexes: effect of temperature, agitation and media composition on aggregation.
- Author
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Messner M, Kurkov SV, Maraver Palazón M, Álvarez Fernández B, Brewster ME, and Loftsson T
- Subjects
- 2-Hydroxypropyl-beta-cyclodextrin, Hexadimethrine Bromide chemistry, Hydrocortisone chemistry, Molecular Weight, Nanoparticles, Particle Size, Permeability, Solubility, Temperature, Water chemistry, Ethanol chemistry, Hydrocortisone administration & dosage, Polymers chemistry, beta-Cyclodextrins chemistry
- Abstract
Recently it has been shown that aggregation of drug/cyclodextrin inclusion complexes is strongly influenced by the drug molecule in addition to self-assembling tendencies of the cyclodextrin itself in aqueous media. Whereas the mechanistic basis of cyclodextrin self-assembly is known, the driving forces for complex aggregation are still unknown. In the present study, the influence of temperature on hydrocortisone/2-hydroxypropyl-β-cyclodextrin complex aggregation is investigated as are influences associated with the addition of ethanol or water soluble polymers to the aqueous systems. Furthermore the effect of stirring on the aggregation is assessed. Size exclusion permeability studies were conducted to estimate complex aggregation tendencies. The results indicate that self-assembled complex aggregates are metastable and notably become smaller with increasing temperature and the addition of ethanol. Water soluble polymers also reduce the size of the complex aggregates. Specifically, hexadimethrine bromide had the greatest impact, since addition of this compound eliminated aggregates from the systems or reduced their size below the molecular weight cut-off of the sizing membrane (8 kDa). Similar observations are made when aqueous solutions of hydrocortisone and 2-hydroxypropyl-β-cyclodextrin are equilibrated by stirred., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
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40. Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes.
- Author
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Loftsson T and Brewster ME
- Subjects
- Absorption drug effects, Animals, Biological Availability, Cell Membrane chemistry, Cyclodextrins administration & dosage, Cyclodextrins chemistry, Drug Compounding, Excipients administration & dosage, Excipients chemistry, Humans, Hydrophobic and Hydrophilic Interactions, Permeability drug effects, Water, Cell Membrane drug effects, Cyclodextrins pharmacology, Excipients pharmacology, Pharmacokinetics
- Abstract
Objectives: Cyclodextrins are useful solubilizing excipients that have gained currency in the formulator's armamentarium based on their ability to temporarily camouflage undesirable physicochemical properties. In this context cyclodextrins can increase oral bioavailability, stabilize compounds to chemical and enzymatic degradation and can affect permeability through biological membranes under certain circumstances. This latter property is examined herein as a function of the published literature as well as work completed in our laboratories., Key Findings: Cyclodextrins can increase the uptake of drugs through biological barriers if the limiting barrier component is the unstirred water layer (UWL) that exists between the membrane and bulk water. This means that cyclodextrins are most useful when they interact with lipophiles in systems where such an UWL is present and contributes significantly to the barrier properties of the membrane. Furthermore, these principles are used to direct the optimal formulation of drugs in cyclodextrins. A second related critical success factor in the formulation of cyclodextrin-based drug product is an understanding of the kinetics and thermodynamics of complexation and the need to optimize the cyclodextrin amount and drug-to-cyclodextrin ratios. Drug formulations, especially those targeting compartments associated with limited dissolution (i.e. the eye, subcutaneous space, etc.), should be carefully designed such that the thermodynamic activity of the drug in the formulation is optimal meaning that there is sufficient cyclodextrin to solubilize the drug but not more than that. Increasing the cyclodextrin concentration decreases the formulation 'push' and may reduce the bioavailability of the system., Conclusions: A mechanism-based understanding of cyclodextrin complexation is essential for the appropriate formulation of contemporary drug candidates., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)
- Published
- 2011
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41. Self-assembly of cyclodextrins: the effect of the guest molecule.
- Author
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Messner M, Kurkov SV, Flavià-Piera R, Brewster ME, and Loftsson T
- Subjects
- 2-Hydroxypropyl-beta-cyclodextrin, Chromatography, High Pressure Liquid, Diffusion Chambers, Culture, Drug Stability, Membranes, Artificial, Permeability, Phase Transition, Solubility, Drug Carriers chemistry, Pharmaceutical Preparations administration & dosage, Pharmaceutical Preparations chemistry, beta-Cyclodextrins chemistry
- Abstract
The principle action by which cyclodextrins solubilize compounds is via inclusion complex formation. However, data suggest that cyclodextrins and their complexes also aggregate in solution and this aggregation contributes to their ability to solubilize poorly water-soluble materials. The current effort aims at better understanding the role of guest molecule nature (i.e. its structural and functional peculiarities) in cyclodextrin complex aggregation as well as in the aggregate stability assessed using a cellophane membrane permeability assay. A test set of 11 acidic, basic and neutral drugs and antibacterial agents (i.e. guests) were examined with regard to their interaction with hydroxypropyl-β-cyclodextrin (HPβCD) and the resulting ability of the formed aggregates to move through a semi-permeable membrane of various molecular weight cut-off values. The data suggested that the interaction of HPβCD with certain guests resulted in the formation of structure large enough to poorly penetrate semi-permeable membrane. The aggregates appeared to be highly dynamic in that there were no qualitative differences between systems that were diluted immediately prior to permeation experiments and those allowed to equilibrate. Pharmaceutical polymers which have been shown to enhance solubilizing efficiency of cyclodextrins had little or no effect on the stability of the aggregates using the permeability paradigm as an endpoint with the exception of carboxymethylcellulose., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
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42. Self-assembly of cyclodextrin complexes: aggregation of hydrocortisone/cyclodextrin complexes.
- Author
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Messner M, Kurkov SV, Brewster ME, Jansook P, and Loftsson T
- Subjects
- Particle Size, Permeability, Solubility, Cyclodextrins chemistry, Excipients chemistry, Hydrocortisone chemistry, Nanoparticles
- Abstract
Cyclodextrins (CDs) are well known functional excipients for solubilization and stabilization of drugs in aqueous formulations as well as enabling adjuncts for increasing the oral bioavailability of solid dosage forms. More recently a number of the valuable properties of these CDs have been ascribed to nanoparticulate aggregation in addition to its ability to form molecular inclusion complexes. The purpose of this study is to identify and characterize the aggregation of CD inclusion complexes with a model drug, hydrocortisone, in saturated solutions which are more relevant to drug formulation than highly dilute systems. Penetration studies of complexes through membranes and phase solubility relationships were assessed for saturated hydrocortisone solutions with the parent CDs, namely αCD, βCD, γCD or with various water-soluble derivatives, i.e., 2-hydroxypropyl-βCD (HPβCD), 2-hydroxypropyl-γCD (HPγCD) or sulfobutyl ether-β-CD (SBEβCD). The data indicate that βCD and γCD form micro-aggregates with hydrocortisone resulting in non-linear phase-solubility relationships. By contract, the other studies of CDs or CD derivatives were found to form nanoaggregates with hydrocortisone resulting in linear solubilization relationships. Permeability profiles were evaluated for the systems formed and are described in three sections specifically a section (section I) where flux is linear (Fickian) as a function of CD concentration, a section (section II) where flux deviates in a negative fashion from linearity but still increases as the CD concentration increases and a section (section III) where flux is independent of the cyclodextrin concentration. Diminished values of flux can be interpreted based on the formation of nanoaggregates of hydrocortisone/CD complexes. Extrapolation of section I data made it possible to obtain theoretical flux values which could be used to estimate the fraction of complexes and drug which participate in aggregation. The CDs which appeared to demonstrate the lowest tendency to form complex aggregates were αCD and SBEβCD, due to their low complexation efficacy and repulsive forces, respectively. Complex aggregates with these CDs are also smaller with maximum size between 50 and 100 kDa. HPβCD and HPγCD complex aggregates manifested a maximum size above 100 kDa and the fraction of drug which participates in complex aggregation with these species is higher than for the other materials assessed. In the case of 90 mM HPγCD solution, data suggest that 87% of all hydrocortisone is tied up in the form of aggregates. These high concentrations were confirmed by TEM which found most particles in the 3-5 nm range but rarely particles as large as 10 and 20 nm. Speculation on the mechanism of the aggregation processes and equilibrium constants are provided but these tend to punctuate our limited understanding of these potentially important processes., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
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43. Physicochemical properties of the amorphous drug, cast films, and spray dried powders to predict formulation probability of success for solid dispersions: etravirine.
- Author
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Weuts I, Van Dycke F, Voorspoels J, De Cort S, Stokbroekx S, Leemans R, Brewster ME, Xu D, Segmuller B, Turner YT, Roberts CJ, Davies MC, Qi S, Craig DQ, and Reading M
- Subjects
- Chemical Phenomena, Chemistry, Pharmaceutical, Drug Carriers administration & dosage, Drug Carriers chemistry, Drug Stability, Microchemistry methods, Nanospheres chemistry, Nanospheres ultrastructure, Nitriles, Polymers chemistry, Powders, Pyridazines administration & dosage, Pyrimidines, Reverse Transcriptase Inhibitors administration & dosage, Solubility, Suspensions, Pyridazines chemistry, Reverse Transcriptase Inhibitors chemistry, Technology, Pharmaceutical
- Abstract
Solid dispersion technology represents an enabling approach to formulate poorly water-soluble drugs. While providing for a potentially increased oral bioavailability secondary to an increased drug dissolution rate, amorphous dispersions can be limited by their physical stability. The ability to assess formulation risk in this regard early in development programs can not only help in guiding development strategies but can also point to critical design elements in the configuration of the dosage form. Based on experience with a recently approved solid dispersion-based product, Intelence® (etravirine), a three part strategy is suggested to predict early formulate-ability of these systems. The components include an assessment of the amorphous form, a study of binary drug/carrier cast films and the evaluation of a powder of the drug and polymer processed in a manner relevant to the intended final dosage form. A variety of thermoanalytical, spectroscopic, and spectrophotometric approaches were applied to study the prepared materials. The data suggest a correlation between the glass forming ability and stability of the amorphous drug and the nature of the final formulation. Cast films can provide early information on miscibility and stabilization and assessment of processed powders can help define requirements and identify issues with potential final formulations., (Copyright © 2010 Wiley-Liss, Inc. and the American Pharmacists Association)
- Published
- 2011
- Full Text
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44. Pharmaceutical applications of cyclodextrins: basic science and product development.
- Author
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Loftsson T and Brewster ME
- Subjects
- Biological Availability, Chemistry, Pharmaceutical, Cyclodextrins pharmacokinetics, Excipients pharmacokinetics, Solubility, Technology, Pharmaceutical, Cyclodextrins chemistry, Drug Delivery Systems, Excipients chemistry, Pharmaceutical Preparations administration & dosage
- Abstract
Objectives: Drug pipelines are becoming increasingly difficult to formulate. This is punctuated by both retrospective and prospective analyses that show that while 40% of currently marketed drugs are poorly soluble based on the definition of the biopharmaceutical classification system (BCS), about 90% of drugs in development can be characterized as poorly soluble. Although a number of techniques have been suggested for increasing oral bioavailability and for enabling parenteral formulations, cyclodextrins have emerged as a productive approach. This short review is intended to provide both some basic science information as well as data on the ability to develop drugs in cyclodextrin-containing formulations., Key Findings: There are currently a number of marketed products that make use of these functional solubilizing excipients and new product introduction continues to demonstrate their high added value. The ability to predict whether cyclodextrins will be of benefit in creating a dosage form for a particular drug candidate requires a good working knowledge of the properties of cyclodextrins, their mechanism of solubilization and factors that contribute to, or detract from, the biopharmaceutical characteristics of the formed complexes., Summary: We provide basic science information as well as data on the development of drugs in cyclodextrin-containing formulations. Cyclodextrins have emerged as an important tool in the formulator's armamentarium to improve apparent solubility and dissolution rate for poorly water-soluble drug candidates. The continued interest and productivity of these materials bode well for future application and their currency as excipients in research, development and drug product marketing., (© 2010 The Authors. Journal compilation © 2010 Royal Pharmaceutical Society of Great Britain.)
- Published
- 2010
- Full Text
- View/download PDF
45. Iatrogenic pancreatic cyst perforation successfully managed by a minimally invasive combined endoscopic–laparoscopic approach.
- Author
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Elmunzer BJ, Boetticher NC, Mobley CM, Brewster ME, and Sonnenday CJ
- Subjects
- Abdominal Pain etiology, Adult, Digestive System Surgical Procedures adverse effects, Endoscopy adverse effects, Female, Gallstones complications, Gallstones surgery, Hernia, Abdominal etiology, Hernia, Abdominal surgery, Humans, Laparoscopy adverse effects, Necrosis surgery, Pancreas pathology, Pancreatic Cyst etiology, Pancreatitis complications, Pancreatitis surgery, Pneumoperitoneum etiology, Endoscopy methods, Iatrogenic Disease, Laparoscopy methods, Pancreatic Cyst surgery
- Abstract
Endoscopic treatment of walled-off pancreatic necrosis is becoming more prevalent in clinical practice, although perforation may complicate 5% of cases, and efficient management of this complication is imperative. In this report, we present a case of necrosis cavity perforation successfully managed by a combined laparoscopic–endoscopic approach, with a novel method of luminal defect closure.
- Published
- 2010
- Full Text
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46. Application of PAMPA-models to predict BBB permeability including efflux ratio, plasma protein binding and physicochemical parameters.
- Author
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Mensch J, Jaroskova L, Sanderson W, Melis A, Mackie C, Verreck G, Brewster ME, and Augustijns P
- Subjects
- Algorithms, Caco-2 Cells, Chemistry, Pharmaceutical, Drug Compounding, Humans, Least-Squares Analysis, Linear Models, Molecular Structure, Pharmaceutical Preparations chemistry, Pharmaceutical Preparations classification, Protein Binding, Solubility, Structure-Activity Relationship, Blood-Brain Barrier metabolism, Capillary Permeability, Models, Biological, Pharmaceutical Preparations metabolism
- Abstract
This study examines whether algorithms to predict brain penetration of 88 drug candidates could benefit from inclusion of PAMPA data such as Peff, flux and membrane retention. Specifically the ability to fit experimentally derived LogBB data with PAMPA information and compound related physicochemical and structural parameters was assessed. Collected data were analyzed by partial least square analysis and various regression models for LogBB. Four PAMPA methodologies were evaluated in this study including: (1) a PAMPA-BLM (black lipid membrane) model, (2) a PAMPA-DS (double sink) model, (3) a PAMPA-BBB (blood-brain barrier) model and (4) a PAMPA-BBB-UWL (unstirred water layer). Additionally, plasma protein binding (PPB) experiments and a Caco-2 assay were performed to determine the unbound fraction in plasma and the efflux ratio, respectively, for subsets of the selected compounds. This information was combined with the obtained PAMPA data in an effort to improve the predictions of LogBB. Taken in aggregate, the results presented, suggest that the PAMPA-BLM parameters are the most important contributors to predict the LogBB. The optimized multiple linear regression (MLR) relationship including the PAMPA-BLM properties demonstrated a slightly improved prediction compared to the model without the PAMPA-BLM parameters. Including the plasma protein binding of 15 compounds resulted in a significantly improved PAMPA-BLM prediction of LogBB, while integrating the efflux ratio with PAMPA-BLM or PAMPA-BBB Peff values, resulted in improved classification of brain permeable [BBB + (LogBB >or= 0)] and impermeable [BBB--(LogBB < 0)] compounds.
- Published
- 2010
47. Active and passive tumor targeting of a novel poorly soluble cyclin dependent kinase inhibitor, JNJ-7706621.
- Author
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Danhier F, Ucakar B, Magotteaux N, Brewster ME, and Préat V
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Apoptosis drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Drug Compounding, Drug Synergism, HeLa Cells, Humans, Lactones chemistry, Liver Neoplasms, Experimental drug therapy, Mice, Mice, Inbred Strains, Micelles, Nanoparticles, Paclitaxel chemistry, Paclitaxel pharmacokinetics, Paclitaxel therapeutic use, Particle Size, Polyesters chemistry, Polyglactin 910 chemistry, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors therapeutic use, Solubility, Surface Properties, Triazoles chemistry, Triazoles pharmacokinetics, Triazoles therapeutic use, Xenograft Model Antitumor Assays, Antineoplastic Agents administration & dosage, Cyclin-Dependent Kinases antagonists & inhibitors, Drug Carriers chemistry, Paclitaxel administration & dosage, Protein Kinase Inhibitors administration & dosage, Triazoles administration & dosage
- Abstract
The anti-cancer cyclin dependent kinase (CDK) inhibitors are poorly soluble drugs. The aims of this work were (i) to formulate a novel CDK inhibitor, JNJ-7706621, in polymeric micelles and nanoparticles, (ii) to compare passive and active targeting on tumor growth and (iii) to evaluate the potential synergy of JNJ-7706621 with Paclitaxel. Therefore, JNJ-7706621 was encapsulated in self-assembling diblock copolymers made up of epsilon-caprolactone (CL) and trimethylene carbonate (TMC) (PEG-p-(CL-co-TMC)) polymeric micelles and in (poly(lactide-co-glycolide)) (PLGA)-based PEGylated nanoparticles (passive targeting) as well as in RGD-grafted nanoparticles (active targeting). In vivo, the transplantable liver tumor growth was more decreased by active targeting with RGD-grafted nanoparticles than by passive targeting with micelles or ungrafted nanoparticles. Moreover, a synergy between JNJ-7706621 and Paclitaxel was demonstrated. Therefore, active targeting of JNJ-7706621-loaded nanocarriers may be considered as an effective anti-cancer drug delivery system for cancer chemotherapy, particularly in combination with Paclitaxel., (Copyright 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
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48. Evaluation of various PAMPA models to identify the most discriminating method for the prediction of BBB permeability.
- Author
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Mensch J, Melis A, Mackie C, Verreck G, Brewster ME, and Augustijns P
- Subjects
- Animals, Caco-2 Cells, Humans, Lipids chemistry, Male, Pharmaceutical Preparations administration & dosage, Pharmaceutical Preparations chemistry, Predictive Value of Tests, Rats, Solubility, Structure-Activity Relationship, Swine, Thermodynamics, Blood-Brain Barrier metabolism, Cell Membrane Permeability, Membranes, Artificial, Models, Biological, Pharmaceutical Preparations metabolism
- Abstract
The Parallel Artificial Membrane Permeability Assay (PAMPA) has been successfully introduced into the pharmaceutical industry to allow useful predictions of passive oral absorption. Over the last 5 years, researchers have modified the PAMPA such that it can also evaluate passive blood-brain barrier (BBB) permeability. This paper compares the permeability of 19 structurally diverse, commercially available drugs assessed in four different PAMPA models: (1) a PAMPA-BLM (black lipid membrane) model, (2) a PAMPA-DS (Double Sink) model, (3) a PAMPA-BBB model and (4) a PAMPA-BBB-UWL (unstirred water layer) model in order to find the most discriminating method for the prediction of BBB permeability. Both the PAMPA-BBB model and the PAMPA-BLM model accurately identified compounds which pass the BBB (BBB+) and those which poorly penetrate the BBB (BBB-). For these models, BBB+ and BBB- classification ranges, in terms of permeability values, could be defined, offering the opportunity to validate the paradigm with in vivo data. The PAMPA models were subsequently applied to a set of 14 structurally diverse internal J&J candidates with known log (brain/blood concentration) (LogBB) values. Based on these LogBB values, BBB classifications were established (BBB+: LogBB0 >or=; BBB-: LogBB<0). PAMPA-BLM resulted in three false positive identifications, while PAMPA-BBB misclassified only one compound. Additionally, a Caco-2 assay was performed to determine the efflux ratio of all compounds in the test set. The false positive that occurred in both models was shown to be related to an increased efflux ratio. Both the PAMPA-BLM and the PAMPA-BBB models can be used to predict BBB permeability of compounds in combination with an assay that provides p-gp efflux data, such as the Caco-2 assay., ((c) 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
49. Monoglyceride-based self-assembling copolymers as carriers for poorly water-soluble drugs.
- Author
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Rouxhet L, Dinguizli M, Latere Dwan'isa JP, Ould-Ouali L, Twaddle P, Nathan A, Brewster ME, Rosenblatt J, Ariën A, and Préat V
- Subjects
- Caco-2 Cells, Capsules, Cell Survival drug effects, Chemistry, Pharmaceutical, Drug Compounding, Flocculation, Humans, Hypromellose Derivatives, Inhibitory Concentration 50, Kinetics, Methylcellulose analogs & derivatives, Methylcellulose chemistry, Micelles, Molecular Weight, Monoglycerides toxicity, Particle Size, Polyethylene Glycols toxicity, Solubility, Succinic Anhydrides toxicity, Surface Properties, Technology, Pharmaceutical methods, Drug Carriers, Monoglycerides chemical synthesis, Pharmaceutical Preparations chemistry, Polyethylene Glycols chemical synthesis, Solvents chemistry, Succinic Anhydrides chemical synthesis, Water chemistry
- Abstract
To develop self-assembling polymers forming polymeric micelles and increasing the solubility of poorly soluble drugs, amphiphilic polymers containing a hydrophilic PEG moiety and a hydrophobic moiety derived from monoglycerides and polyethers were designed. The biodegradable copolymers were obtained via a polycondensation reaction of polyethylene glycol (PEG), monooleylglyceride (MOG) and succinic anhydride (SA). Polymers with molecular weight below 10,000 g/mol containing a minimum of 40 mol% PEG and a maximum of 10 mol% MOG self-assembled spontaneously in aqueous media upon gentle mixing. They formed particles with a diameter of 10 nm although some aggregation was evident. The critical micellar concentration varied between 3x10(-4) and 4x10(-3) g/ml, depending on the polymer. The cloud point (> or = 66 degrees C) and flocculation point (> or = 0.89 M) increased with the PEG chain length. At a 1% concentration, the polymers increased the solubility of poorly water-soluble drug candidates up to 500-fold. Drug solubility increased as a function of the polymer concentration. HPMC capsules filled with these polymers disintegrated and released model drugs rapidly. Polymer with long PEG chains had a lower cytotoxicity (MTT test) on Caco-2 cells. All of these data suggest that the object polymers, in particular PEG1000/MOG/SA (45/5/50) might be potential candidates for improving the oral biopharmaceutical performance of poorly soluble drugs.
- Published
- 2009
- Full Text
- View/download PDF
50. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability?
- Author
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Brouwers J, Brewster ME, and Augustijns P
- Subjects
- Administration, Oral, Animals, Biological Availability, Drug Delivery Systems trends, Humans, Pharmaceutical Preparations administration & dosage, Pharmaceutical Preparations chemistry, Pharmaceutical Preparations metabolism, Solubility drug effects, Time Factors, Drug Delivery Systems methods
- Abstract
Contemporary pharmaceutical pipelines are often highly populated with poorly water-soluble drug candidates necessitating novel formulation technologies to provide dosage forms with appropriate biopharmaceutical properties. The configuration of supersaturating drug delivery systems (SDDS) is a promising concept to obtain adequate oral bioavailability. SDDS contain the drug in a high energy or otherwise rapidly dissolving form such that intraluminal concentrations above the saturation solubility of the drug are generated. For the strategy to be useful, the formed supersaturated solution must then be stabilized to allow for significant absorption and eventually sufficient bioavailability. The stabilization of a supersaturated solution can be accomplished by adding precipitation inhibitors which may act through a variety of mechanisms. The goal of this review is to assess methods and excipients associated with the development of SDDS and provide some context for their use. In addition, the future directions and factors likely to contribute to or detract from optimal dosage form selection are assessed. This includes a discussion on the potential effect of the gastrointestinal physiology on the ability to attain and maintain supersaturation as this information is essential in designing useful formulations based on the supersaturating concept., (Copyright 2009 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
- View/download PDF
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