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1.
Psychol Women Q ; 47(2): 213-230, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37168387

RESUMEN

Two studies (n = 1,522) examined the impact of role models in sport and science, technology, engineering, and mathematics (STEM) domains where gender discrimination has resulted in a lack of high-profile women. We examined the role of gender matching of personally known and famous exemplars on women's and men's motivation. Participants nominated a woman or man in sport (Study 1) or STEM (Study 2) who was either famous or known to them personally; they then indicated the extent to which they perceived this individual to be a motivating role model. Women and men were more motivated by personally known (vs. famous) role models. For famous exemplars, both women and men were most motivated by same-gender models (Studies 1 and 2). For personally known exemplars, men were similarly motivated by same- and other-gender models (Studies 1 and 2), but women were more motivated by same-gender models in sport (Study 1). Mediation analyses indicated that personally known (vs. famous) exemplars and, for women, same- (vs. other-) gender exemplars, were perceived as more attainable future selves and consequently were more motivating (Study 2). Given that there are fewer famous women in domains dominated by men, it is important to know if women can be inspired by personally known rather than famous individuals. These studies provide insight into the kinds of exemplars that are most motivating for women and may serve as a guide for educators and other practitioners seeking to provide the best role models for girls and women in domains dominated by men. Additional online materials for this article are available on PWQ's website athttp://journals.sagepub.com/doi/suppl/10.1177/03616843231156165.

2.
J Proteome Res ; 22(3): 942-950, 2023 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-36626706

RESUMEN

Prostate cancer (PCa) is the second leading cause of male cancer-related deaths in the United States. The pre-mature forms of prostate-specific antigen (PSA), proPSA, were shown to be associated with PCa. However, there is a technical challenge in the development of antibody-based immunoassays for specific recognition of each individual proPSA isoform. Herein, we report the development of highly specific, antibody-free, targeted mass spectrometry assays for simultaneous quantification of [-2], [-4], [-5], and [-7] proPSA isoforms in voided urine. The newly developed proPSA assays capitalize on Lys-C digestion to generate surrogate peptides with appropriate length (9-16 amino acids) along with long-gradient liquid chromatography separation. The assay utility of these isoform markers was evaluated in a cohort of 30 well-established clinical urine samples for distinguishing PCa patients from healthy controls. Under the 95% confidence interval, the combination of [-2] and [-4] proPSA isoforms yields the area under curve (AUC) of 0.86, and the AUC value for the combined all four isoforms was calculated to be 0.85. We have further verified [-2]proPSA, the dominant isoform, in an independent cohort of 34 clinical urine samples. Validation of proPSA isoforms in large-scale cohorts is needed to demonstrate their potential clinical utility.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Inmunoensayo , Isoformas de Proteínas , Espectrometría de Masas
3.
Environ Int ; 158: 106986, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34991248

RESUMEN

BACKGROUND/AIMS: Early life exposures to marine contaminants can adversely impact child health but modes of action are unclear. Human milk contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs), and may partly mediate the effects of pollutants on child health. However, the role of marine pollutants on miRNA expression in milk EVs is unexplored. METHODS: We isolated EV RNA from 333 milk samples collected between 2 and 74 days postpartum from a Faroese birth cohort born 1997-2000 and sequenced 2083 miRNAs using a targeted library preparation method. We quantified five perfluoroalkyl substances (PFAS), pesticide metabolite p,p'-dichlorodiphenyldichloroethylene (DDE), and the sum of three major polychlorinated biphenyls (ΣPCBs) in maternal serum at 34 weeks of gestation and maternal hair total mercury (Hg) at birth. We used negative binomial regressions to estimate associations between individual pollutants and 418 reliably expressed EV-miRNAs adjusted for potential confounders. We performed sparse principal components (PCs) analysis to derive the first four components of the EV-miRNA data and examined associations between pollutants and PCs using Bayesian kernel machine regression (BKMR). RESULTS: We observed no associations between pollutants and individual EV-miRNA expression after controlling the false discovery rate at 0.1. However, BKMR suggested that Hg was positively associated with PC1 and negatively associated with PC3, while ΣPCBs was negatively associated with PC3, and two PFAS were associated with PC4. Exploration of PC loadings followed by pathway analyses suggested that miRNAs in PC1 (miR-200b-3p, miR-664a-3p, miR-6738-5p, miR-429, miR-1236-5p, miR-4464, and miR-30b-5p) may be related to Hg neurotoxicity, while remaining PCs require further research. CONCLUSIONS: Our findings suggest that groups of milk EV-miRNAs may better serve as environmental biomarkers than individual miRNAs. Future studies are needed to elucidate the role of milk EV-miRNAs in child health following prenatal exposures.


Asunto(s)
Contaminantes Ambientales , Vesículas Extracelulares , MicroARNs , Teorema de Bayes , Cohorte de Nacimiento , Niño , Contaminantes Ambientales/toxicidad , Femenino , Humanos , Recién Nacido , MicroARNs/genética , Leche Humana , Madres , Embarazo
4.
Sci Rep ; 11(1): 5840, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712635

RESUMEN

Human milk plays a critical role in infant development and health, particularly in cognitive, immune, and cardiometabolic functions. Milk contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs). We aimed to characterize milk EV-miRNA profiles in a human population cohort, assess potential pathways and ontology, and investigate associations with maternal characteristics. We conducted the first study to describe the EV miRNA profile of human milk in 364 mothers from a population-based mother-infant cohort in the Faroe Islands using small RNA sequencing. We detected 1523 miRNAs with ≥ one read in 70% of samples. Using hierarchical clustering, we determined five EV-miRNA clusters, the top three consisting of 15, 27 and 67 miRNAs. Correlation coefficients indicated that the expression of many miRNAs within the top three clusters was highly correlated. Top-cluster human milk EV-miRNAs were involved in pathways enriched for the endocrine system, cellular community, neurodevelopment, and cancers. miRNA expression was associated with time to milk collection post-delivery, maternal body mass index, and maternal smoking, but not maternal parity. Future studies investigating determinants of human EV-miRNAs and associated health outcomes are needed to elucidate the role of human milk EV-miRNAs in health and disease.


Asunto(s)
Vesículas Extracelulares/genética , Regulación de la Expresión Génica , MicroARNs/genética , Leche Humana/metabolismo , Adulto , Análisis por Conglomerados , Estudios de Cohortes , Dinamarca , Femenino , Ontología de Genes , Humanos , MicroARNs/metabolismo , Embarazo , Transducción de Señal/genética , Estadística como Asunto
5.
Epigenet Insights ; 13: 2516865720904057, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32128507

RESUMEN

Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (ß = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (ß = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (qinteraction < 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids.

6.
J Stud Alcohol Drugs ; 80(1): 96-101, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30807280

RESUMEN

OBJECTIVE: Training in an inhibitory control task has produced reductions in alcohol use among heavy drinkers. However, the longevity of effects remains unknown, and much research has used suboptimal control conditions. Here, we assess the effectiveness of "Beer-NoGo" inhibitory training to reduce consumption up to 4 weeks after training compared with a "Beer-Go" control task, an online version of the Brief Alcohol Intervention (BAI), and an Oddball control condition. METHOD: Eighty-one regular drinkers were randomized into one of four training conditions. In the Beer-NoGo condition, participants responded to a letter superimposed on water-related images and refrained from responding to another letter superimposed on beer-related images. The mapping was reversed for the Beer-Go condition, whereas the Oddball control condition was presented with letters only and inhibition was not required. The last condition was an online BAI. Alcohol use was assessed using a bogus taste test and weekly alcohol consumption. RESULTS: Taste-test consumption was greater in the Beer-Go condition than in the Beer-NoGo, which did not differ from the Oddball and BAI conditions. All groups reduced alcohol intake during the study; however, in the first week the Beer-Go group reduced their drinking while the Beer-NoGo group increased. No group differences were apparent at the fourth week. CONCLUSIONS: The Beer-NoGo task did not produce effects beyond simple assessment on reducing alcohol use among regular drinkers. Previously reported training effects may be artifacts of the Beer-Go task as a suboptimal control. More robust forms of inhibitory training are necessary if a useful clinical adjunct for managing alcohol abuse is to be developed.


Asunto(s)
Consumo de Bebidas Alcohólicas/prevención & control , Intoxicación Alcohólica/prevención & control , Alcoholismo/prevención & control , Inhibición Psicológica , Adulto , Cerveza , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
7.
Artículo en Inglés | MEDLINE | ID: mdl-30583542

RESUMEN

BACKGROUND: Associations between prenatal household air pollution (HAP) exposure or cookstove intervention to reduce HAP and cord blood mononuclear cell (CBMC) mitochondrial deoxyribonucleic acid copy number (mtDNAcn), an oxidative stress biomarker, are unknown. MATERIALS AND METHODS: Pregnant women were recruited and randomized to one of two cookstove interventions, including a clean-burning liquefied petroleum gas (LPG) stove, or control. Prenatal HAP exposure was determined by serial, personal carbon monoxide (CO) measurements. CBMC mtDNAcn was measured by quantitative polymerase chain reaction. Multivariable linear regression determined associations between prenatal CO and cookstove arm on mtDNAcn. Associations between mtDNAcn and birth outcomes and effect modification by infant sex were explored. RESULTS: LPG users had the lowest CO exposures (p = 0.02 by ANOVA). In boys only, average prenatal CO was inversely associated with mtDNAcn (ß = -14.84, SE = 6.41, p = 0.03, per 1ppm increase in CO). When examined by study arm, LPG cookstove had the opposite effect in all children (LPG ß = 19.34, SE = 9.72, p = 0.049), but especially boys (ß = 30.65, SE = 14.46, p = 0.04), as compared to Control. Increased mtDNAcn was associated with improved birth outcomes. CONCLUSIONS: Increased prenatal HAP exposure reduces CBMC mtDNAcn, suggesting cumulative prenatal oxidative stress injury. An LPG stove intervention may reverse this effect. Boys appear most susceptible.


Asunto(s)
Contaminación del Aire Interior/efectos adversos , Monóxido de Carbono/efectos adversos , Culinaria/métodos , ADN Mitocondrial/efectos de los fármacos , Sangre Fetal/efectos de los fármacos , Adulto , Biomarcadores , Femenino , Ghana , Humanos , Recién Nacido , Masculino , Estrés Oxidativo , Embarazo , Resultado del Embarazo/epidemiología , Factores Sexuales , Factores Socioeconómicos , Adulto Joven
8.
Am J Psychiatry ; 172(10): 1014-21, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25998279

RESUMEN

OBJECTIVE: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use. METHOD: A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale. RESULTS: In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed. CONCLUSIONS: Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit.


Asunto(s)
Trastorno Bipolar/complicaciones , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Citidina Difosfato Colina/uso terapéutico , Nootrópicos/uso terapéutico , Adulto , Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Trastornos Relacionados con Cocaína/complicaciones , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
9.
Neuropsychopharmacology ; 37(11): 2347-54, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22669171

RESUMEN

Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1-10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.


Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Triazinas/uso terapéutico , Adolescente , Adulto , Anciano , Trastorno Bipolar/complicaciones , Trastornos Relacionados con Cocaína/complicaciones , Depresión/complicaciones , Método Doble Ciego , Femenino , Humanos , Estimación de Kaplan-Meier , Lamotrigina , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Adulto Joven
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