Browsing by Author "Williams, David R."
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Item 6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding(Elsevier, 2020-01-17) Powell, Katherine M.; Brown, Alexa P.; Skaggs, Cayla G.; Pulliam, Alexis N.; Berman, Alycia G.; Deosthale, Padmini; Plotkin, Lilian I.; Allen, Matthew R.; Williams, David R.; Wallace, Joseph M.; Biomedical Engineering, School of Engineering and TechnologyRaloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance.Item Coping With Racism: Moderators of the Discrimination-Adjustment Link Among Mexican-Origin Adolescents(Wiley, 2018-05) Park, Irene J.K.; Wang, Lijuan; Williams, David R.; Alegria, Margarita; IU School of MedicineWhat strategies help ethnic minority adolescents to cope with racism? The present study addressed this question by testing the role of ethnic identity, social support, and anger expression and suppression as moderators of the discrimination-adjustment link among 269 Mexican-origin adolescents (Mage = 14.1 years), 12-17 years old from the Midwestern U.S. Results from multilevel moderation analyses indicated that ethnic identity, social support, and anger suppression, respectively, significantly attenuated the relations between discrimination and adjustment problems, whereas outward anger expression exacerbated these relations. Moderation effects differed according to the level of analysis. By identifying effective coping strategies in the discrimination-adjustment link at specific levels of analysis, the present findings can guide future intervention efforts for Latino youth.Item Does anger regulation mediate the discrimination-mental health link among Mexican-origin adolescents? A longitudinal mediation analysis using multilevel modeling(American Psychological Association, 2017-02) Park, Irene J. K.; Wang, Lijuan; Williams, David R.; Alegría, Margarita; Psychiatry, School of MedicineAlthough prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present three-wave longitudinal study tested the mediating role of anger regulation in the discrimination—mental health link among 269 Mexican-origin adolescents (Mage = 14.1 years, SD = 1.6; 57% girls), 12 – 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn, more frequent outward anger expression was associated with higher levels of anxiety and depression at a given time point. Gender, age, and nativity status were not significant moderators of the hypothesized mediation models. By identifying outward anger expression as an explanatory mechanism in the discrimination-distress link among Latino youths, this study points to a malleable target for prevention and intervention efforts aimed at mitigating the detrimental impact of racism on Latino youths’ mental health during the developmentally critical period of adolescence.Item Erratum Re: “Coping With Racism: Moderators of the Discrimination—Distress Link Among Mexican-Origin Adolescents”(Wiley, 2019-01) Park, Irene J. K.; Wang, Lijuan; Williams, David R.; Alegría, Margarita; Psychiatry, School of MedicineThe publisher's final edited version of this article is available at Child Dev This corrects the article "Coping With Racism: Moderators of the Discrimination—Adjustment Link Among Mexican-Origin Adolescents" in Child Dev, volume 89 on page e293.Item Racial/Ethnic Discrimination and Mental Health in Mexican-Origin Youths and Their Parents: Testing the "Linked Lives" Hypothesis(Elsevier, 2018-04) Park, Irene J. K.; Du, Han; Wang, Lijuan; Williams, David R.; Alegría, Margarita; Psychiatry, School of MedicinePURPOSE: Using a life course perspective, the present study tested the concept of "linked lives" applied to the problem of not only how racial/ethnic discrimination may be associated with poor mental health for the target of discrimination but also how discrimination may exacerbate the discrimination-distress link for others in the target's social network-in this case, the family. METHODS: The discrimination-distress link was investigated among 269 Mexican-origin adolescents and their parents both cross-sectionally and longitudinally. It was hypothesized that parents' discrimination experiences would adversely affect their adolescent children's mental health via a moderating effect on the target adolescent discrimination-distress link. The converse was also hypothesized for the target parents. Multilevel moderation analyses were conducted to test the moderating effect of parents' discrimination experiences on the youth discrimination-distress link. We also tested the moderating effect of youths' discrimination experiences on the parent discrimination-distress link. RESULTS: Parents' discrimination experiences significantly moderated the longitudinal association between youths' discrimination stress appraisals and mental health, such that the father's discrimination experiences exacerbated the youth discrimination-depression link. Youths' discrimination stress appraisals were not a significant moderator of the cross-sectional parent discrimination-mental health association. CONCLUSIONS: Implications of these findings are discussed from a linked lives perspective, highlighting how fathers' discrimination experiences can adversely affect youths who are coping with discrimination, in terms of their mental health.Item The Role of Parents’ Ethnic-Racial Socialization Practices in the Discrimination—Depression Link among Mexican-Origin Adolescents(Taylor & Francis, 2020-05) Park, Irene J.K.; Du, Han; Wang, Lijuan; Williams, David R.; Alegría, Margarita; Psychiatry, School of MedicineThe present study investigated the moderating role of parents' ethnic-racial socialization practices (T1) in the link between adolescents' discrimination experiences (T1-T3) and adolescent anxiety and depression, respectively (T1-T3). Using a 3-wave longitudinal design with multiple informants (adolescent, mother, father) reporting on parents' ethnic-racial socialization practices, the data analytic sample comprised a total of 251 (T1) Mexican-origin families from the midwestern United States. Mother and father reports of their own ethnic-racial socialization practices (i.e., cultural socialization, preparation for bias, promotion of mistrust) were entered simultaneously into multilevel moderation models. Results from these multilevel moderation analyses indicated that fathers' promotion of mistrust was a significant moderator in the adolescent discrimination-depression link over time. Specifically, fathers' promotion of mistrust exacerbated the youth discrimination-depression association. Moreover, the difference between the moderating effects of fathers' versus mothers' promotion of mistrust on the youth discrimination-depression association was significant. Cultural socialization and preparation for bias did not significantly moderate the adolescent association between discrimination and mental health, regardless of parent gender (fathers or mothers) or mental health outcome (anxiety or depression). The results are discussed in light of a socioecological framework, with special emphasis on the importance of including (and differentiating between) both fathers and mothers in the investigation of ethnic-racial socialization and implications for future theory building, research, and clinical practice.