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1.
Children (Basel) ; 10(6)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37371275

RESUMO

While the body of literature on COVID-19's impacts on family life is rapidly expanding, most studies are based entirely on self-report data, leaving a critical gap in observational studies of parent-child interactions. The goal of this study was to evaluate parent-child relationships during the COVID-19 pandemic using the observational emotional availability (EA) construct. Parents (n = 43) were assessed using the Epidemic-Pandemic Impacts Inventory (EPII), the Flourishing Scale (FLS), and the adverse childhood experiences (ACEs) questionnaires. The subcategories of the EPII were used to develop an EPII negative and an EPII positive for each parent. EA (sensitivity, structuring, nonhostility, nonintrusiveness, child responsiveness, and child involvement) was coded from filmed parent-child interactions. Separate hierarchical multiple regressions (HMRs) were run to evaluate each of the variables of interest (EPII and FLS) as predictive of EA. Child age (M = 6, SD = 4.68) and ACEs were added in subsequent steps for EPII negative and positive if the initial step was significant. For mothers (n = 25), results demonstrated EPII negative as a significant predictor of EA with child age and ACEs adding only small amount of variance to the prediction. The same HMR process was repeated for flourishing, with the covariate child age alone. For fathers (n = 18), flourishing was a significant predictor of EA and child age added only a small amount of variance to the prediction. Results indicate that experiencing high COVID-19-related stressors is associated with lower EA for mothers, but not fathers. Having high levels of flourishing during the pandemic was predictive of higher EA for fathers, but not mothers.

2.
Contemp Clin Trials ; 128: 107150, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36918091

RESUMO

BACKGROUND: Adolescent-onset type 2 diabetes (T2D) is a major public health concern of growing proportions. Prevention, therefore, is critical. Unfortunately, standard-of-care treatment for T2D prevention (e.g., exercise training) show insufficient effectiveness and do not address key modifiable barriers (e.g., depression symptoms) to exercise engagement. Depression symptoms are associated with both poorer physical fitness and greater insulin resistance, the key risk factor in adolescent-onset T2D. Thus, a targeted prevention approach that addresses depression symptoms in combination with exercise training may offer a novel approach to mitigating T2D risk. METHODS: This manuscript describes the design and study protocol for a multi-site, four-arm randomized controlled trial comparing the efficacy of group cognitive-behavioral therapy, group exercise training, and their combinations for the targeted prevention of worsening insulin resistance in N = 300 adolescent females at-risk for T2D with BMI ≥85th percentile and elevated depression symptoms. All four intervention arms will run in parallel and meet weekly for 1 h per week for 6-week to 6-week segments (12 weeks total). Outcomes are assessed at baseline, 6-week mid-treatment, 12-week follow-up, and 1-year follow-up. RESULTS: The primary outcome is insulin resistance. Key secondary outcomes include insulin sensitivity, cardiorespiratory fitness, physical activity, depression symptoms, and body measurements. CONCLUSION: Study findings will guide the ideal sequencing of two brief T2D prevention interventions for ameliorating the course of insulin resistance and lessening T2D risk in vulnerable adolescents. These interventions will likely be cost-effective and scalable for dissemination, having the potential for significant public health impact on communities at risk for T2D.


Assuntos
Terapia Cognitivo-Comportamental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Adolescente , Feminino , Diabetes Mellitus Tipo 2/prevenção & controle , Depressão/prevenção & controle , Terapia Cognitivo-Comportamental/métodos , Exercício Físico , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Fam Process ; 62(4): 1687-1708, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36347267

RESUMO

Adolescent disordered eating and obesity are interrelated and adversely relate to mental and metabolic health. Parental feeding practices have been associated with adolescent disordered eating and obesity. Yet, observable interactions related to food parenting have not been well characterized. To address this gap, N = 30 adolescents (M ± SD 14 ± 2 year) at risk for adult obesity due to above-average body mass index (BMI ≥70th percentile) or parental obesity (BMI ≥30 kg/m2 ) participated in a video-recorded parent-adolescent task to discuss a food/eating-related disagreement. Interactions were coded for individual/dyadic affect/content using the Interactional Dimensions Coding System. We examined associations of interaction qualities with parent-reported food practices, adolescent disordered eating behaviors/attitudes, and insulin resistance. Reported parenting practices were correlated with multiple interaction qualities (p-values <0.05), with the most consistent correspondence between parent-reported pressure to eat (e.g., pressure to eat more healthy foods) and negative aspects of parent-adolescent interactions. Also, after accounting for adolescent age, sex, and BMI-standard score, parent-adolescent interaction qualities were associated with adolescents' disordered eating and insulin resistance. Specifically, greater adolescent problem-solving related to less adolescent global disordered eating, shape, and weight concern (p-values <0.05); adolescent autonomy related to less weight concern (p = 0.03). Better parent communication skills were associated with less adolescent eating concern (p = 0.04), and observed dyadic mutuality related to adolescents' lower insulin resistance (p = 0.03). Parent-adolescent interaction qualities during food/eating-related disagreements show associations with parent-reported food practices and adolescent disordered eating. This method may offer a tool for measuring the qualities of parent-adolescent food/eating-related interactions. A nuanced understanding of conversations about food/eating may inform family-based intervention in youth at-risk for adult obesity.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Resistência à Insulina , Adulto , Humanos , Adolescente , Poder Familiar , Pais , Obesidade , Relações Pais-Filho , Inquéritos e Questionários
4.
J Lat Psychol ; 10(3): 225-240, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36211633

RESUMO

Youth-onset type 2 diabetes (T2D) is on the rise and may be associated with more adverse health outcomes than adult onset. Latinx adolescents are disproportionately at risk for T2D yet are underrepresented in prevention efforts. Extant interventions to prevent T2D in Latinx adolescents show limited effectiveness. Comprehensive understanding of Latinx adolescent/family needs is lacking, but necessary for cultural tailoring of T2D prevention. Researchers conducted focus groups with 32 Latinx adolescents (age 10-18 years) from Northern Colorado and 31 Spanish-speaking parents/caregivers, with 2.5-hr semistructured youth-specific and parent-specific discussions, respectively. No participants included in this study had T2D. Qualitative data were analyzed for emergent themes about barriers/facilitators of healthy living and T2D prevention preferences. Thematic content analysis yielded eight themes within three categories: barriers to healthy living, facilitators of healthy living, and program preferences. Barriers to healthy living included individual motivational factors/food preferences; financial cost and time demands of healthy eating/exercise; negative emotions; and external/relational factors such as parent feeding pressure and peer pressure/bullying. Facilitators of healthy living included individual motivational factors/enjoyment of healthy living and supportive family structure. Program preferences were for family-based programming with adolescent breakout sessions and for facilitation by culturally competent facilitators. T2D is recognized as a serious health concern among Latinx families. There is a need for culturally tailored prevention programming that, in order to be acceptable, should address cultural and socioeconomic considerations, provide coping skills for adolescent-specific psychosocial stressors, and utilize a family-based programming framework with adolescent breakout sessions and culturally competent facilitators.


La diabetes tipo 2 (DT2) que comienza en la juventud está en aumento y esta asociada con peores resultados en comparación con los de la edad adulta. Los adolescentes Latinx tienen un riesgo desproporcionado de DT2 sin embargo, no están representados en los esfuerzos de prevención. Las intervenciones existentes muestran una eficacia limitada. La comprensión sobre las necesidades de los adolescentes y las familias Latinx son escasas, pero son necesarias para prevenir DT2. Se realizaron grupos de enfoque con 32 adolescentes Latinx (de 10 a 18 añ3os) del Norte de Colorado y 31 padres de habla hispana, con sesiones de 2.5 horas para jóvenes y para padres. Ningún participante en este estudio tenía DT2. Se analizaron datos cualitativos que identificaron barreras/facilitadores para una vida sana y preferencias de programas para prevenir DT2. Las barreras incluyeron factores individuales; el costo y el tiempo para tener alimentación/ejercicio sano; emociones negativas; y factores externos como la presión de los padres/compañeros. Los facilitadores incluyeron factores individuales/disfrute de la salud y el apoyo familiar. Las preferencias fueron basada en la familia, con grupos de adolescentes y con facilitadores culturalmente competentes. La DT2 es un grave problema entre las familias Latinx. Se necesitan programas de prevención que consideren la cultura y factores socioeconómicos. También se deben proporcionar habilidades de afrontamiento de los estresores psicosociales para adolescentes, a través de facilitadores culturalmente competentes y utilizar programación basada en la familia, con actividades culturales para adolescentes.

5.
Eat Behav ; 43: 101580, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34775283

RESUMO

BACKGROUND: Mindfulness-based intervention (MBI) may offer a novel means of preventing excess weight gain in adolescents, theoretically by decreasing stress-eating through altering executive functioning (EF) and food-reward sensitivity. METHODS: N = 54 12-17y girls and boys at-risk for excess weight gain (i.e., BMI ≥70th percentile or two biological parents with reported obesity [BMI ≥30 kg/m2]) participated in a 1.5-year follow-up of a pilot randomized controlled trial comparing 6-week/6-session MBI (n = 29) and a health education (HE) control (n = 25). Laboratory stress-eating, food-reward sensitivity, EF, perceived stress, and BMI/adiposity were re-assessed at 1.5-years with validated measures. Changes from baseline to 1.5-year follow-up were explored with ANCOVA, accounting for the respective baseline outcome, age, and sex. RESULTS: Compared to MBI (M = -21, SE = 59), HE had greater increases in stress-eating from baseline to 1.5-years (M = 194, SE = 63, Cohen's d = 0.59, p = .01). There were no other between-condition differences. DISCUSSION: MBI may prevent worsening stress-eating for adolescents at-risk for excess weight gain. The potential for MBI as an intervention for stress-eating and ultimately, weight stabilization warrants testing in an adequately-powered trial.


Assuntos
Atenção Plena , Adolescente , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Masculino , Projetos Piloto , Aumento de Peso
6.
Brain Sci ; 11(8)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34439635

RESUMO

Parental influences are important for a child's behavior, overall adjustment, as well as cognitive/language development. New research is exploring how relationships with parents can influence a child's neurobiological functioning and development. In this systematic review, our first aim is to describe how the caregiving environment influences these aspects of child development. The second and main aim is to review and recommend that the concept (and measurement) of "emotional availability" may provide a new window in this continued exploration. Emotional availability (EA) refers to the capacity of a dyad to share an emotionally healthy relationship. The EA Scales assess this construct using a multi-dimensional framework, with a method to measure the affect and behavior of both the child and adult partner (caregiver). In this review, we first provide an overview of child development research, with regards to stress physiology, neuroendocrine system, genetics and epigenetics, and brain mechanisms. We then summarize the results of specific EA research in these areas, and propose a theoretical model integrating these constructs. Finally, we offer areas for future research in this area.

7.
Dev Psychobiol ; 63(6): e22127, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33991342

RESUMO

Adverse childhood experiences (ACEs) heighten the risk for adult obesity and cardiometabolic disease, but physiological factors underlying this connection are not well understood. We determined if ACEs were associated with physiological stress response and insulin resistance in adolescents at risk for adult obesity. Participants were 90 adolescents 12.0-17.5 years (50% female, 30% Hispanic/Latinx), at risk for adult obesity by virtue of above-average body mass index (BMI; kg/m2 ≥ 70th percentile) or parental obesity (BMI ≥ 30 kg/m2 ). ACEs were determined as presence (vs. absence) based upon the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Physiological stress response was measured as heart rate/blood pressure response to the Trier Social Stress Test. Homeostatic model assessment of insulin resistance was determined from fasting glucose/insulin. Sixty-one percent of adolescents reported positive ACE history. The presence of ACEs predicted greater heart rate (p < .001) and diastolic blood pressure (p = .02) response to stress, controlling for age, sex, race/ethnicity, puberty, and BMI standard score. Systolic blood pressure and insulin resistance did not differ by ACE history (p-values > .08). Findings suggest heightened sympathetic stress response in adolescence could be explanatory in how ACEs increase the risk for later cardiometabolic disease. Future studies should characterize ACEs in relationship to day-to-day variations in adolescents' stress physiology and glucose homeostasis.


Assuntos
Experiências Adversas da Infância , Resistência à Insulina , Adolescente , Adulto , Índice de Massa Corporal , Criança , Feminino , Hispânico ou Latino , Humanos , Masculino , Obesidade
8.
J Behav Med ; 44(5): 694-703, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33884531

RESUMO

Sleep difficulties may be one explanatory factor in the association between depression and insulin resistance; yet, explicit tests of this hypothesis are lacking. We determined if there was an indirect effect of depression symptoms on insulin resistance through sleep duration in adolescents at risk for excess weight gain. We also investigated whether dispositional mindfulness moderated the interconnections among depression, sleep, and insulin resistance. Ninety adolescents (14.2 ± 1.6y; 50% female) at risk for excess weight gain (body mass index [BMI, kg/m2] z score 1.6 ± 0.6) participated in the cross-sectional, baseline phase of a health behaviors study. Depression was assessed with the Center for Epidemiologic Studies-Depression Scale, sleep duration with the Sleep Habits Survey, and mindfulness with the Mindful Attention and Awareness Scale. Homeostatic model assessment of insulin resistance was determined from fasting insulin and glucose. The product-of-coefficients method was used to test the indirect effect of depression on insulin resistance through sleep duration, accounting for age, sex, BMIz, puberty, and socioeconomic status (SES). Dispositional mindfulness was tested as a moderator of the associations among depression, sleep, and insulin resistance. There was a significant indirect effect of depression on insulin resistance through sleep duration, controlling for age, sex, BMIz, puberty, and SES, 95%CI [0.001, 0.05]. Dispositional mindfulness moderated the association between sleep duration and insulin resistance, such that lower sleep duration related to greater insulin resistance only among adolescents with lower mindfulness (p < .001). Short sleep may be one explanatory factor in the depression-insulin resistance connection in adolescents at risk for excess weight gain. Adolescents with poorer mindfulness and short sleep are at highest risk for insulin resistance, whereas higher mindfulness may be protective.


Assuntos
Resistência à Insulina , Atenção Plena , Adolescente , Estudos Transversais , Depressão , Feminino , Humanos , Masculino , Sono
9.
Artigo em Inglês | MEDLINE | ID: mdl-33668149

RESUMO

During pregnancy, physical activity relates to better maternal and child mental and physical health. Accelerometry is thought to be effective for assessing free-living physical activity, but the feasibility/acceptability of accelerometer use in pregnant adolescents has not been reported. In this short communication, we conducted secondary analysis of a small pilot study to describe the feasibility/acceptability of accelerometry in pregnant adolescents and the preliminary results of physical activity characteristics. Participants were recruited from a multidisciplinary adolescent perinatal clinic. Physical activity was assessed with wrist-worn accelerometers. Feasibility was described as median days of valid wear (≥10 h of wear/day) for the total sample and the number/percentage of participants with ≥4 days of valid wear. Sensitivity analyses of wear time were performed. Acceptability ratings were collected by structured interview. Thirty-six pregnant (14.6 ± 2.1 gestational weeks) adolescents (17.9 ± 1.0 years) participated. Median days of valid wear were 4 days. Seventeen participants (51.5%) had ≥4 days of valid wear. There were no differences in characteristics of adolescents with vs. without ≥4 days of valid wear. Twenty participants (60.6%) had ≥3 days of valid wear, 24 (72.7%) ≥2 valid days, and 27 (81.8%) ≥1 valid wear day. Acceptability ratings were neutral. Assessing physical activity with accelerometry in pregnant adolescents was neither feasible nor acceptable with the current conditions. Future research should investigate additional incentives and the potential utility of a lower wear-time criterion in pregnant adolescents.


Assuntos
Acelerometria , Exercício Físico , Adolescente , Criança , Estudos de Viabilidade , Feminino , Humanos , Projetos Piloto , Gravidez , Punho
10.
Artigo em Inglês | MEDLINE | ID: mdl-32206334

RESUMO

BACKGROUND: Excess gestational weight gain (GWG) in pregnant adolescents is a major public health concern. Excess GWG increases risk of pregnancy complications as well as postpartum and offspring obesity and cardiometabolic disease. Prevention interventions for pregnant adults that target lifestyle modification (i.e., healthy eating/physical activity) show insufficient effectiveness. Pregnant adolescents have distinct social-emotional needs, which may contribute to excess GWG. From an interpersonal theoretical framework, conflict and low social support increase negative emotions, which in turn promote excess GWG through mechanisms such as overeating and physical inactivity. METHODS: The current manuscript describes the design of a pilot randomized controlled feasibility trial of adolescent interpersonal psychotherapy (IPT) to address social-emotional needs and prevent excess GWG. Up to 50 pregnant, healthy adolescents 13-19y, 12-18 weeks gestation are recruited from an interdisciplinary adolescent maternity hospital clinic and randomized to IPT + usual care or usual care alone. IPT involves 6 individual 60-minute sessions delivered by a trained behavioral health clinician during 12-30 weeks gestation. Sessions include relationship psychoeducation, emotion identification and expression, and teaching/role-playing communication skills. Between sessions, adolescents are instructed to complete a daily journal and to have conversations to work on relationship goals. Outcomes are assessed at baseline, mid-program, post-program, and 3-months postpartum. Primary outcomes are feasibility and acceptability based upon rate of recruitment, session attendance, program acceptability ratings, and follow-up retention. Secondary outcomes are perinatal social functioning, stress, depression, and eating behaviors assessed with validated surveys and interviews; perinatal physical activity and sleep measured via accelerometer; GWG from measured weights; and at 3-months postpartum only, maternal adiposity by dual energy x-ray absorptiometry, maternal insulin sensitivity derived from 2-hour oral glucose tolerance testing, and infant adiposity by air displacement plethysmography. DISCUSSION: This pilot trial will address a key gap in extant understanding of excess GWG prevention for a high-risk population of adolescents. If feasible and acceptable, brief psychotherapy to address social-emotional needs should be tested for its effectiveness to address excess GWG and postpartum maternal/infant health. If effective, such an approach has potential to interrupt an adverse, intergenerational cycle of social-emotional distress, obesity, and cardiometabolic disease among young mothers and their offspring. TRIAL REGISTRATION: ClinicalTrials.gov NCT03086161, retrospectively registered.

11.
PLoS One ; 8(1): e54150, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23349811

RESUMO

The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. ß-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and similar to p68, interacts with the AR to co-activate expression of AR target genes. Importantly, p68 forms complexes with nuclear ß-Catenin and promotes gene transcription in colon cancer indicating a functional interplay between these two proteins in cancer progression. In this study, we explore the relationship of p68 and ß-Catenin in PCa to assess their potential co-operation in AR-dependent gene expression, which may be of importance in the development of castrate resistant prostate cancer (CRPCa). We use immunoprecipitation to demonstrate a novel interaction between p68 and ß-Catenin in the nucleus of PCa cells, which is androgen dependent in LNCaP cells but androgen independent in a hormone refractory derivative of the same cell line (representative of the CRPCa disease type). Enhanced AR activity is seen in androgen-dependent luciferase reporter assays upon transient co-transfection of p68 and ß-Catenin as an additive effect, and p68-depleted Chromatin-Immunoprecipitation (ChIP) showed a decrease in the recruitment of the AR and ß-Catenin to androgen responsive promoter regions. In addition, we found p68 immunoprecipitated with the processive and non-processive form of RNA polymerase II (RNAP II) and show p68 recruited to elongating regions of the AR mediated PSA gene, suggesting a role for p68 in facilitating RNAP II transcription of AR mediated genes. These results suggest p68 is important in facilitating ß-Catenin and AR transcriptional activity in PCa cells.


Assuntos
RNA Helicases DEAD-box/metabolismo , RNA Polimerase II/metabolismo , Receptores Androgênicos/metabolismo , Transcrição Gênica , beta Catenina/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , RNA Helicases DEAD-box/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Immunoblotting , Imunoprecipitação , Masculino , Antígeno Prostático Específico/genética , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ligação Proteica , Interferência de RNA , Receptores Androgênicos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta Catenina/genética
12.
BMC Cell Biol ; 10: 82, 2009 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-19912651

RESUMO

BACKGROUND: Active pre-mRNA splicing occurs co-transcriptionally, and takes place throughout the nucleoplasm of eukaryotic cells. Splicing decisions are controlled by networks of nuclear RNA-binding proteins and their target sequences, sometimes in response to signalling pathways. Sam68 (Src-associated in mitosis 68 kDa) is the prototypic member of the STAR (Signal Transduction and Activation of RNA) family of RNA-binding proteins, which regulate splicing in response to signalling cascades. Nuclear Sam68 protein is concentrated within subnuclear organelles called SLM/Sam68 Nuclear Bodies (SNBs), which also contain some other splicing regulators, signalling components and nucleic acids. RESULTS: We used proteomics to search for the major interacting protein partners of nuclear Sam68. In addition to Sam68 itself and known Sam68-associated proteins (heterogeneous nuclear ribonucleoproteins hnRNP A1, A2/B1 and G), we identified hnRNP L as a novel Sam68-interacting protein partner. hnRNP L protein was predominantly present within small nuclear protein complexes approximating to the expected size of monomers and dimers, and was quantitatively associated with nucleic acids. hnRNP L spatially co-localised with Sam68 as a novel component of SNBs and was also observed within the general nucleoplasm. Localisation within SNBs was highly specific to hnRNP L and was not shared by the closely-related hnRNP LL protein, nor any of the other Sam68-interacting proteins we identified by proteomics. The interaction between Sam68 and hnRNP L proteins was observed in a cell line which exhibits low frequency of SNBs suggesting that this association also takes place outside SNBs. Although ectopic expression of hnRNP L and Sam68 proteins independently affected splicing of CD44 variable exon v5 and TJP1 exon 20 minigenes, these proteins did not, however, co-operate with each other in splicing regulation of these target exons. CONCLUSION: Here we identify hnRNP L as a novel SNB component. We show that, compared with other identified Sam68-associated hnRNP proteins and hnRNP LL, this co-localisation within SNBs is specific to hnRNP L. Our data suggest that the novel Sam68-hnRNP L protein interaction may have a distinct role within SNBs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo L/análise , Ribonucleoproteínas Nucleares Heterogêneas Grupo L/metabolismo , Splicing de RNA , Proteínas de Ligação a RNA/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Ribonucleoproteínas Nucleares Heterogêneas Grupo L/química , Humanos , Camundongos , Dados de Sequência Molecular , Ácidos Nucleicos/metabolismo , Proteômica
13.
Cancer Res ; 68(19): 7938-46, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18829551

RESUMO

The androgen receptor (AR) is a member of the nuclear steroid hormone receptor family and is thought to play an important role in the development of both androgen-dependent and androgen-independent prostatic malignancy. Elucidating roles by which cofactors regulate AR transcriptional activity may provide therapeutic advancement for prostate cancer (PCa). The DEAD box RNA helicase p68 (Ddx5) was identified as a novel AR-interacting protein by yeast two-hybrid screening, and we sought to examine the involvement of p68 in AR signaling and PCa. The p68-AR interaction was verified by colocalization of overexpressed protein by immunofluorescence and confirmed in vivo by coimmunoprecipitation in the PCa LNCaP cell line. Chromatin immunoprecipitation in the same cell line showed AR and p68 recruitment to the promoter region of the androgen-responsive prostate-specific antigen (PSA) gene. Luciferase reporter, minigene splicing assays, and RNA interference (RNAi) were used to examine a functional role of p68 in AR-regulated gene expression, whereby p68 targeted RNAi reduced AR-regulated PSA expression, and p68 enhanced AR-regulated repression of CD44 splicing (P = 0.008). Tyrosine phosphorylation of p68 was found to enhance coactivation of ligand-dependent transcription of AR-regulated luciferase reporters independent of ATP-binding. Finally, we observe increased frequency and expression of p68 in PCa compared with benign tissue using a comprehensive prostate tissue microarray (P = 0.003; P = 0.008). These findings implicate p68 as a novel AR transcriptional coactivator that is significantly overexpressed in PCa with a possible role in progression to hormone-refractory disease.


Assuntos
Processamento Alternativo/genética , RNA Helicases DEAD-box/fisiologia , Neoplasias da Próstata/genética , Receptores Androgênicos/metabolismo , Animais , Células COS , Células Cultivadas , Chlorocebus aethiops , RNA Helicases DEAD-box/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Antígeno Prostático Específico/genética , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , RNA Interferente Pequeno/farmacologia , Transativadores/metabolismo , Transativadores/fisiologia , Regulação para Cima
14.
Biochem Soc Trans ; 36(Pt 3): 546-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18482004

RESUMO

The mechanisms involved in the transition from androgen-dependent to androgen-independent PCa (prostate cancer) remain largely undefined. The AR (androgen receptor) is an androgen-dependent transcription factor and is thought to play an important role in the development of both androgen-dependent and -independent prostatic malignancy. AR-mediated transcription is regulated by the binding of various cofactor proteins to the AR that facilitate transcriptional initiation and elongation. Elucidating the mechanisms by which cofactors regulate AR transcriptional activity may reveal the therapeutic potential of cofactors in PCa. Current models of gene expression indicate that transcription and RNA processing are tightly coupled. In this review, we discuss how the ATP-dependent DEAD box RNA helicase p68, which has established roles in transcription and RNA processing, may function as an 'adaptor' or coupling protein to facilitate cross-talk between transcription and RNA processing in AR-regulated genes by controlling the rate of transcriptional initiation/elongation.


Assuntos
RNA Helicases DEAD-box/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , Processamento Pós-Transcricional do RNA , Receptores Androgênicos/metabolismo , Transcrição Gênica , Animais , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino
15.
Cleft Palate Craniofac J ; 44(1): 92-4, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17214535

RESUMO

OBJECTIVE: To determine the frequency of missed dental appointments among children with a cleft lip and/or palate (CL/P). DESIGN: A prospective study of failed appointments over a 12-month period. SETTING: Three different CL/P clinics within a British dental hospital. PATIENTS: Forty-five CL/P children (mean age of 8.8 years) and 45 age-matched, gender-matched, and postal code-matched noncleft patients. MAIN OUTCOME MEASURES: The overall percentage of missed appointments at three different clinics by CL/P patients and the difference in attendance rates at the pediatric dentistry clinic between CL/P and non-CL/P children. RESULTS: Pediatric dentistry had the highest rate of missed appointments (22.4%), followed by the multidisciplinary cleft clinic (9.2%) and the orthodontic clinic (8.8%). CL/P patients missed a significantly greater proportion of their pediatric dentistry appointments than noncleft children (22.4% versus 11.9%). Patients with a bilateral CL/P were significantly more likely to miss an appointment than patients with a unilateral CL/P. Age, gender, medical history, and distance traveled had no significant effect on attendance rates. CONCLUSIONS: Further work is needed to identify risk factors for poor attendance and to develop strategies to reduce the frequency of missed appointments in this vulnerable group.


Assuntos
Fenda Labial , Fissura Palatina , Unidade Hospitalar de Odontologia/estatística & dados numéricos , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adolescente , Agendamento de Consultas , Estudos de Casos e Controles , Criança , Pré-Escolar , Fenda Labial/terapia , Fissura Palatina/terapia , Assistência Odontológica para Crianças/estatística & dados numéricos , Inglaterra , Feminino , Humanos , Masculino , Ortodontia Corretiva/estatística & dados numéricos , Estudos Prospectivos , Classe Social
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