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  1. Article: Exposure to Adverse Life Events among Children Transitioning into Adolescence: Intersections of Socioeconomic Position and Race.

    Assari, Shervin / Najand, Babak / Donovan, Alexandra

    Journal of mental health & clinical psychology

    2024  Volume 8, Issue 1, Page(s) 5–15

    Abstract: Background: Racism is shown to diminish the protective effects of family socioeconomic position (SEP) resources for racial minorities compared to the majority groups, a pattern called minorities' diminished returns. Our existing knowledge is minimal ... ...

    Abstract Background: Racism is shown to diminish the protective effects of family socioeconomic position (SEP) resources for racial minorities compared to the majority groups, a pattern called minorities' diminished returns. Our existing knowledge is minimal about diminished returns of family SEP indicators on reducing exposure to adverse life events among children transitioning into adolescence.
    Aim: To compare diverse racial groups for the effects of family income and family structure on exposure to adverse life events of pre-adolescents transitioning to adolescence.
    Methods: In this longitudinal study, we analyzed data from 22,538 observations belonging to racially diverse groups of American 9-10-year-old children (n = 11,878) who were followed while transitioning to adolescence. The independent variables were family income and family structure. The primary outcome was the number of stressful life events with impact on adolescents, measured by the Life History semi-structured interview. Mixed-effects regression models were used for data analysis to adjust for data nested to individuals, families, and centers.
    Results: Family income and married family structure had an overall inverse association with children's exposure to adverse life events during transition to adolescence. However, race showed significant interactions with family income and family structure on exposure to adverse life events. The protective effects of family income and married family structure were weaker for African American than White adolescents. The protective effect of family income was also weaker for mixed/other race than White adolescents.
    Conclusion: While family SEP is protective against children's exposure to adverse life events, this effect is weaker for African American and mixed/other race compared to White youth.
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    DOI 10.29245/2578-2959/2024/1.1293
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effort-based decision making in response to high-dose androgens: role of dopamine receptors.

    Donovan, Alexandra / Wood, Ruth I

    Behavioural pharmacology

    2022  Volume 33, Issue 7, Page(s) 435–441

    Abstract: Introduction: Anabolic-androgenic steroids (AAS) are performance-enhancing drugs used by both world-class and rank-and-file athletes. AAS abuse has been linked with risky decision-making, ranging from drunk driving to abusing multiple drugs. Our lab ... ...

    Abstract Introduction: Anabolic-androgenic steroids (AAS) are performance-enhancing drugs used by both world-class and rank-and-file athletes. AAS abuse has been linked with risky decision-making, ranging from drunk driving to abusing multiple drugs. Our lab uses operant behavior in rats to test the effects of AAS (testosterone) on decision making. In our previous study, testosterone caused rats to work harder for food reward during an effort discounting (ED) task. ED is sensitive to dopamine in the nucleus accumbens, and AAS alter accumbens dopamine receptor expression. Accordingly, we determined if testosterone increases response to dopamine receptor antagonists during ED.
    Methods: Rats were treated chronically with high-dose testosterone (7.5 mg/kg; n = 9) or vehicle (n = 9). We measured baseline preference for the large reward in an ED task, where rats choose between a small easy reward (one lever press for one sugar pellet) and a large difficult reward (2, 5, 10, or 15 presses for three pellets). Preference for the large reward was measured after administration of D1-like (SCH23390, 0.01 mg/kg) or D2-like (eticlopride, 0.06 mg/kg) receptor antagonists.
    Results: At baseline, testosterone- and vehicle-treated rats showed similar preference for the large reward lever (FR5, testosterone: 68.6 ± 9.7% and vehicle: 85.7 ± 2.5%). SCH23390 reduced large reward preference significantly in both groups (FR5, testosterone: 41.3 ± 9.2%; vehicle: 49.1 ± 8.2%; F(1,16) = 17.7; P < 0.05). Eticlopride decreased large reward preference in both groups, but more strongly in testosterone-treated rats (FR5: testosterone: 37.0 ± 9.7%; vehicle: 56.3 ± 7.8%; F(1,16) = 35.3; P < 0.05).
    Conclusion: Testosterone increases response to dopamine D2-like receptor blockade, and this contributes to previously observed changes in decision-making behaviors.
    MeSH term(s) Androgens/metabolism ; Androgens/pharmacology ; Animals ; Conditioning, Operant ; Decision Making ; Dopamine/metabolism ; Dopamine Antagonists/metabolism ; Dopamine Antagonists/pharmacology ; Humans ; Nucleus Accumbens/metabolism ; Performance-Enhancing Substances/metabolism ; Performance-Enhancing Substances/pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Dopamine D1/metabolism ; Reward ; Salicylamides ; Sugars/metabolism ; Sugars/pharmacology ; Testosterone/pharmacology
    Chemical Substances Androgens ; Dopamine Antagonists ; Performance-Enhancing Substances ; Receptors, Dopamine D1 ; Salicylamides ; Sugars ; Testosterone (3XMK78S47O) ; eticlopride (J8M468HBH4) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2022-09-14
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1027374-8
    ISSN 1473-5849 ; 0955-8810
    ISSN (online) 1473-5849
    ISSN 0955-8810
    DOI 10.1097/FBP.0000000000000687
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  3. Article ; Online: Neuroendocrine mechanisms in the links between early life stress, affect, and youth substance use: A conceptual model for the study of sex and gender differences.

    Donovan, Alexandra / Assari, Shervin / Grella, Christine / Shaheen, Magda / Richter, Linda / Friedman, Theodore C

    Frontiers in neuroendocrinology

    2024  Volume 73, Page(s) 101121

    Abstract: Early life stress (ELS) is defined as an acute or chronic stressor that negatively impacts a child's development. ELS is associated with substance use and mental health problems. This narrative literature review focuses on sex and gender differences in ... ...

    Abstract Early life stress (ELS) is defined as an acute or chronic stressor that negatively impacts a child's development. ELS is associated with substance use and mental health problems. This narrative literature review focuses on sex and gender differences in the effects of ELS on 1) adolescent neuroendocrine development; 2) pubertal brain maturation; and 3) development of internalizing symptoms and subsequent substance use. We posit that ELS may generate larger hormonal dysregulation in females than males during puberty, increasing internalizing symptoms and substance use. Future research should consider sex and gender differences in neuroendocrine developmental processes when studying the link between ELS and negative health outcomes.
    MeSH term(s) Humans ; Substance-Related Disorders/physiopathology ; Adolescent ; Sex Characteristics ; Neurosecretory Systems/metabolism ; Male ; Female ; Stress, Psychological/metabolism ; Stress, Psychological/physiopathology ; Adverse Childhood Experiences ; Adolescent Development/physiology
    Language English
    Publishing date 2024-01-20
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 390985-2
    ISSN 1095-6808 ; 0532-7466 ; 0091-3022
    ISSN (online) 1095-6808
    ISSN 0532-7466 ; 0091-3022
    DOI 10.1016/j.yfrne.2024.101121
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  4. Thesis ; Online: Comparative Biophysical Analysis of APOE3 and APOE4

    Donovan, Alexandra

    A Mechanistic Investigation

    2017  

    Abstract: Apolipoprotein E is an exchangeable apolipoprotein whose isoforms are associated with various disease risk profiles. Individuals bearing the APOE ϵ4 allele are at increased risk for developing Alzheimer’s disease compared to those bearing the APOE ϵ3 ... ...

    Abstract Apolipoprotein E is an exchangeable apolipoprotein whose isoforms are associated with various disease risk profiles. Individuals bearing the APOE ϵ4 allele are at increased risk for developing Alzheimer’s disease compared to those bearing the APOE ϵ3 allele. The two isoforms differ in amino acid at position 112: apoE3 bears a Cys while apoE4 bears an Arg. It is hypothesized that the Cys to Arg substitution in apoE4 causes a decrease in stability in comparison to apoE3, which is exaggerated at endosomal pH <6.0. In our study, changes in secondary structure were monitored using circular dichroism at pH 7.4 and pH 3.5. Chemical denaturation indicated that both apoE3 and apoE4 retained their helical secondary structure at the lower pH, with a biphasic and monophasic guanidine HCl denaturation profile, respectively. Tertiary structure was monitored at both pH’s through fluorescence spectral characteristics and mobility of a fluorescent probe attached to each of the 7 major amphipathic α-helices of apoE3 and apoE4. The data showed decreases in fluorescence emission (FE), changes in fluorescence polarization (FP), and fluctuations in probe mobility, which were interpreted as likely formation of a molten globule. Formation of a molten globule appeared to occur during denaturation primarily for apoE4, and thermodynamic parameters of apoE4 showed a lower stability than apoE3, with a larger effect of pH. Taken together, our results suggest that the acidic pH in the endosomal compartments could interact with the native structure of apoE4 to generate a molten globule state that is able to bind endosomal membranes, other proteins, or itself. This study offers mechanistic insight into the impact of the single residue difference between apoE3 and apoE4 with regard to folding/unfolding behavior, and with regard to its physiological and pathological implications.
    Keywords Biochemistry|Biophysics
    Subject code 612
    Language ENG
    Publishing date 2017-01-01 00:00:01.0
    Publisher California State University, Long Beach
    Publishing country us
    Document type Thesis ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Cooperative responses in rats playing a 2 × 2 game: Effects of opponent strategy, payoff, and oxytocin.

    Donovan, Alexandra / Ryan, Erin / Wood, Ruth I

    Psychoneuroendocrinology

    2020  Volume 121, Page(s) 104803

    Abstract: The present study tested cooperation in rats playing a 2 × 2 game (2 players, 2 responses) in an operant chamber, where players choose to cooperate or defect without knowledge of their partner's choice. We evaluated cooperative responses in rats ( ... ...

    Abstract The present study tested cooperation in rats playing a 2 × 2 game (2 players, 2 responses) in an operant chamber, where players choose to cooperate or defect without knowledge of their partner's choice. We evaluated cooperative responses in rats (Subjects) playing different games [iterated Prisoner's Dilemma (IPD), Stag Hunt] with a Stooge partner utilizing different response strategies [Tit-for-tat (TFT), Win-stay, Lose-shift (WSLS), Random], and we determined the effects of oxytocin (OT). IPD trial outcomes and payoffs included mutual cooperation (reward, R, 3 sugar pellets each), mutual defection (punishment, P, 1 pellet each), or unilateral defection (temptation, T, 5 pellets) and cooperation (sucker, S, 0 pellets). Stag Hunt was similar, except that T = 2 pellets. We hypothesized that Subjects would make more cooperative responses when playing Stag Hunt vs IPD, when playing IPD with a Stooge using TFT vs WSLS or Random, and when treated with OT. At baseline, Subjects' overall likelihood of cooperation was unaffected by the game (IPD vs SH) or by the Stooges' response strategy (TFT, WSLS, Random). Cooperative responses earned Subjects more pellets, except when playing with a Stooge using a random strategy. Trial outcomes (R, T, S or P) also varied by game and strategy, although the mutual defection (P) was the most common. Systemic pretreatment with OT increased Subjects' cooperative responses, resulting in fewer P and more R outcomes. In particular, IPD-Random Subjects were more cooperative, even at the expense of earning fewer pellets. These results demonstrate that OT increases cooperative behavior in rats playing 2 × 2 games.
    MeSH term(s) Animals ; Behavior, Animal/drug effects ; Behavior, Animal/physiology ; Cooperative Behavior ; Game Theory ; Male ; Motivation ; Oxytocin/pharmacology ; Prisoner Dilemma ; Punishment ; Rats ; Rats, Long-Evans ; Reward
    Chemical Substances Oxytocin (50-56-6)
    Language English
    Publishing date 2020-08-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 197636-9
    ISSN 1873-3360 ; 0306-4530
    ISSN (online) 1873-3360
    ISSN 0306-4530
    DOI 10.1016/j.psyneuen.2020.104803
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  6. Article ; Online: Outcomes of patients with blastoid and pleomorphic variant mantle cell lymphoma.

    Gerson, James N / Handorf, Elizabeth / Villa, Diego / Gerrie, Alina S / Chapani, Parv / Li, Shaoying / Medeiros, L Jeffrey / Wang, Michael / Cohen, Jonathon B / Churnetski, Michael / Hill, Brian T / Sawalha, Yazeed / Hernandez-Ilizaliturri, Francisco J / Kothari, Shalin / Vose, Julie M / Bast, Martin / Fenske, Timothy / Rao Gari, Swapna Narayana / Maddocks, Kami J /
    Bond, David / Bachanova, Veronika / Kolla, Bhaskar / Chavez, Julio / Shah, Bijal / Lansigan, Frederick / Burns, Timothy / Donovan, Alexandra M / Wagner-Johnston, Nina / Messmer, Marcus / Mehta, Amitkumar / Anderson, Jennifer K / Reddy, Nishitha / Kovach, Alexandra E / Landsburg, Daniel J / Glenn, Martha / Inwards, David J / Ristow, Kay / Karmali, Reem / Kaplan, Jason B / Caimi, Paolo F / Rajguru, Saurabh / Evens, Andrew / Klein, Andreas / Umyarova, Elvira / Pulluri, Bhargavi / Amengual, Jennifer E / Lue, Jennifer K / Diefenbach, Catherine / Fisher, Richard I / Barta, Stefan K

    Blood advances

    2023  Volume 7, Issue 24, Page(s) 7393–7401

    Abstract: Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively ... ...

    Abstract Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P < .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P < .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P < .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P < .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P < .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival.
    MeSH term(s) Adult ; Humans ; Lymphoma, Mantle-Cell/therapy ; Lymphoma, Mantle-Cell/drug therapy ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Risk Assessment ; Progression-Free Survival
    Language English
    Publishing date 2023-10-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023010757
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    Zs.A 7153: Show issues Location:
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  7. Article ; Online: Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era.

    Gerson, James N / Handorf, Elizabeth / Villa, Diego / Gerrie, Alina S / Chapani, Parv / Li, Shaoying / Medeiros, L Jeffrey / Wang, Michael I / Cohen, Jonathon B / Calzada, Oscar / Churnetski, Michael C / Hill, Brian T / Sawalha, Yazeed / Hernandez-Ilizaliturri, Francisco J / Kothari, Shalin / Vose, Julie M / Bast, Martin A / Fenske, Timothy S / Narayana Rao Gari, Swapna /
    Maddocks, Kami J / Bond, David / Bachanova, Veronika / Kolla, Bhaskar / Chavez, Julio / Shah, Bijal / Lansigan, Frederick / Burns, Timothy F / Donovan, Alexandra M / Wagner-Johnston, Nina / Messmer, Marcus / Mehta, Amitkumar / Anderson, Jennifer K / Reddy, Nishitha / Kovach, Alexandra E / Landsburg, Daniel J / Glenn, Martha / Inwards, David J / Karmali, Reem / Kaplan, Jason B / Caimi, Paolo F / Rajguru, Saurabh / Evens, Andrew / Klein, Andreas / Umyarova, Elvira / Pulluri, Bhargavi / Amengual, Jennifer E / Lue, Jennifer K / Diefenbach, Catherine / Fisher, Richard I / Barta, Stefan K

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2019  Volume 37, Issue 6, Page(s) 471–480

    Abstract: Purpose: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit ... ...

    Abstract Purpose: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger.
    Patients and methods: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed.
    Results: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2).
    Conclusion: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.
    MeSH term(s) Adult ; Age Factors ; Aged ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/mortality ; Humans ; Lymphoma, Mantle-Cell/mortality ; Lymphoma, Mantle-Cell/pathology ; Lymphoma, Mantle-Cell/therapy ; Male ; Middle Aged ; North America ; Progression-Free Survival ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Rituximab/adverse effects ; Rituximab/therapeutic use ; Time Factors ; Transplantation, Autologous ; Young Adult
    Chemical Substances Antineoplastic Agents, Immunological ; Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2019-01-07
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.18.00690
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