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1.
Child Dev ; 95(1): 177-190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37593928

RESUMO

Three preregistered experiments, conducted in 2021, investigated whether English-speaking American preschoolers (N = 120; 4-6 years; 54 females, predominantly White) and adults (N = 80; 18-52 years; 59 females, predominantly Asian) metonymically extend owners' names to owned objects-an extension not typically found in English. In Experiment 1, 5- and 6-year-olds and adults extended names to owned objects over duplicates (d = 0.34 in children; d = 1.13 in adults). In Experiment 2, 5- and 6-year-olds and adults extended names to owned over borrowed objects (d = 1.37 in children; d = 4.34 in adults). Experiment 3 replicated this finding with 4-year-olds (d = 0.43). Thus, English-speaking preschoolers can acquire semantic generalizations, even those not present in their language.


Assuntos
Desenvolvimento da Linguagem , Idioma , Adulto , Criança , Pré-Escolar , Feminino , Humanos , População Branca , Povo Asiático
2.
Psychol Sci ; 34(6): 696-704, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37068125

RESUMO

Although adults use metaphors to guide their thinking and reasoning, less is known about whether metaphors might facilitate cognition earlier in development. Previous research shows that preschoolers understand metaphors, but less is known about whether preschoolers can learn from metaphors. The current preregistered experiment investigated whether adults (n = 64) and 3- and 4-year-olds (n = 128) can use metaphors to make new inferences. In a between-subjects design, participants heard information about novel artifacts, conveyed through either only positive metaphors (e.g., "Daxes are suns") or positive and negative metaphors (e.g., "Daxes are suns. Daxes are not clouds."). In both conditions, participants of all ages successfully formed metaphor-consistent inferences about abstract, functional features of the artifacts (e.g., that daxes light up rather than let out water). Moreover, participants frequently provided explanations appealing to the metaphors when justifying their responses. Consequently, metaphors may be a powerful learning mechanism from early childhood onward.


Assuntos
Cognição , Metáfora , Humanos , Adulto , Pré-Escolar , Cognição/fisiologia , Resolução de Problemas , Audição
3.
Front Public Health ; 9: 653106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026713

RESUMO

Early childhood development (ECD) parenting interventions can improve child developmental outcomes in low-resource settings, but information about their implementation lags far behind evidence of their effectiveness, hindering their generalizability. This study presents results from an implementation evaluation of Msingi Bora ("Good Foundation" in Swahili), a group-based responsive stimulation and nutrition education intervention recently tested in a cluster randomized controlled trial across 60 villages in rural western Kenya. Msingi Bora successfully improved child cognitive, receptive language, and socioemotional outcomes, as well as parenting practices. We conducted a mixed methods implementation evaluation of the Msingi Bora trial between April 2018 and November 2019 following the Consolidated Advice for Reporting ECD implementation research (CARE) guidelines. We collected qualitative and quantitative data on program inputs, outputs, and outcomes, with a view to examining how aspects of the program's implementation, such as program acceptance and delivery fidelity, related to observed program impacts on parents and children. We found that study areas had initially very low levels of familiarity or knowledge of ECD among parents, community delivery agents, and even supervisory staff from our partner non-governmental organization (NGO). We increased training and supervision in response, and provided a structured manual to enable local delivery agents to successfully lead the sessions. There was a high level of parental compliance, with median attendance of 13 out of 16 fortnightly sessions over 8 months. For delivery agents, all measures of delivery performance and fidelity increased with program experience. Older, more knowledable delivery agents were associated with larger impacts on parental stimulation and child outcomes, and delivery agents with higher fidelity scores were also related to improved parenting practices. We conclude that a group-based parenting intervention delivered by local delivery agents can improve multiple child and parent outcomes. An upfront investment in training local trainers and delivery agents, and regular supervision of delivery of a manualized program, appear key to our documented success. Our results represent a promising avenue for scaling similar interventions in low-resource rural settings to serve families in need of ECD programming. This trial is registered at ClinicalTrials.gov, NCT03548558, June 7, 2018. https://clinicaltrials.gov/ct2/show/NCT03548558.


Assuntos
Desenvolvimento Infantil , Poder Familiar , Criança , Pré-Escolar , Humanos , Quênia , Pais , População Rural
4.
Front Oncol ; 8: 504, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30460196

RESUMO

Background: Colorectal cancer (CRC) incidence is rising in the young, yet the age of those affected is not clearly defined. In this study, we identify such cohorts and define clinicopathological features of early-onset colon and rectal cancers. Methods: The Surveillance, Epidemiology and End Results Program (SEER) database was queried to compare clinicopathological characteristics of colon and rectal cancers diagnosed during 1973-1995 with those diagnosed during 1995-2014. Results: We identified 430,886 patients with colon and rectal cancers. From 1973-1995 to 1995-2014, colon cancer incidence increased in patients aged 20-44 years, while rectal cancer incidence increased in patients aged ≤54 years. The percent change of cancer incidence was greatest for rectal cancer with a 41.5% (95% confidence interval (CI): 37.4-45.8%) increase compared to a 9.8% (CI: 6.2-13.6%) increase in colon cancer. Colon cancer has increased in tumors located in ascending, sigmoid, and rectosigmoid locations. Adenocarcinoma histology has increased in both colon and rectal cancers (P < 0.01), but mucinous and signet ring cell subtypes have not increased (P = 0.13 and 0.08, respectively). Incidence increases were race-specific, with rectal cancer seeing similar rises in white (38.4%, CI: 33.8-43.1%) and black populations (38.0%, CI: 26.2-51.2%), while colon cancer as a whole saw a rise in white (11.5%, CI: 7.2-15.9%) but not black populations (-6.8%, CI: -14.6-1.9%). Conclusions: Our study underscores the existence of key differences between early-onset colon (20-44 years) and rectal cancers (≤54 years) and provides evidence-based inclusion criteria for future investigations. We recommend that future research of CRC in the young should avoid investigating these cases as a single entity.

5.
J Gastrointest Oncol ; 9(3): 517-526, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29998017

RESUMO

BACKGROUND: Adjuvant therapy for gastric adenocarcinoma has shown a survival advantage, though it may be underutilized. The purpose of this study is to examine how infrequently adjuvant therapy is administered with curative intent gastrectomy for node positive gastric cancer and the long-term effects to patients. METHODS: The National Cancer Database was queried from 2006-2013 for patients with node positive gastric adenocarcinoma undergoing a potentially curative gastrectomy. Overall survival was compared between patients who received adjuvant chemotherapy or chemoradiation and those who did not. RESULTS: Of 2,565 patients, 793 (30.9%) patients did not receive any adjuvant chemotherapy or radiation therapy, while 147 (5.7%) received peri-operative chemotherapy and 723 (28.2%) received post-operative chemoradiation. From 2006-2013, the percentage of patients receiving peri-operative chemotherapy rose from 1.1% to 9.9%, while those receiving post-operative chemoradiation decreased from 39.7% to 21.6%. The adjusted restricted mean survival time over 5 years for no adjuvant therapy was 27.7 months, peri-operative chemotherapy was 39.6 months, and post-operative chemoradiation was 37.7 months (P<0.0001). CONCLUSIONS: Approximately one third of patients treated for node positive gastric cancer undergo surgical resection without adjuvant therapy. This is associated with poorer survival, highlighting the need for improvement in multimodality care and cancer outcomes.

6.
J Gastrointest Oncol ; 9(2): 231-240, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29755761

RESUMO

BACKGROUND: Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care. METHODS: The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared. RESULTS: A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% vs. 8.4%, P<0.0001). Colon and gastric GISTs were less likely to receive systemic therapy compared to rectal GISTs (34.2% vs. 34.0% vs. 55.2%, P<0.0001). Adjuvant systemic therapy conveyed a survival advantage to rectal GISTs (HR =0.47, P=0.042) but not colon GISTs. There was a negative impact of adjuvant therapy on survival for colon GISTs <5 cm (HR =3.41, P=0.032). CONCLUSIONS: Patients with rectal GISTs live longer than those with colon and gastric GISTs, and adjuvant therapy prolongs their survival. Many patients with colon GISTs are treated with adjuvant therapy despite a detrimental effect on survival. Tumor biology of colon and rectal GISTs needs to be better studied to tailor treatment.

7.
J Pers Soc Psychol ; 114(1): 131-152, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28737418

RESUMO

Although both scholars and lay people are fascinated with charismatic individuals, relatively few theorists have attempted to define charisma. Much of the empirical research examining charisma has focused on leadership. Even within that literature, however, theorists have focused on charisma's outcomes, leaving unarticulated what charisma actually is. Here, we tested an operational conceptualization of charisma in the context of everyday life. Specifically, we proposed that charisma is composed of the interpersonally focused dimensions of influence (the ability to guide others) and affability (the ability to make other people feel comfortable and at ease). We validated this conceptualization in a series of studies. In Studies 1-3, we used exploratory and confirmatory factor analyses to construct a short 6-item measure of charisma, the General Charisma Inventory. Next, in Study 4, we used round-robin evaluations and informant reports to establish the interpersonal nature of charisma. Finally, we examined the incremental validity of the scale in the context of dyadic interactions and tested the impact of charisma on perceptions of persuasiveness from voices. We found that (a) lay people possess a consensual conception of charisma; (b) charisma consists of a composition of quantifiable dimensions; (c) charisma is distinct from other constructs of interest to psychologists and leadership theorists; (d) charisma is observable; and (e) assessments of charisma predict real world outcomes. Thus, the current work not only comprehensively conceptualizes and measures charisma as an empirical construct, but also demonstrates its potential importance for the routine interactions that people experience every day. (PsycINFO Database Record


Assuntos
Liderança , Personalidade , Psicometria/normas , Comportamento Social , Percepção Social , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/instrumentação , Psicometria/métodos , Reprodutibilidade dos Testes , Adulto Jovem
8.
Cogn Psychol ; 99: 17-43, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29132016

RESUMO

Five experiments compared preschool children's performance to that of adults and of non-human animals on match to sample tasks involving 2-item or 16-item arrays that varied according to their composition of same or different items (Array Match-to-Sample, AMTS). They establish that, like non-human animals in most studies, 3- and 4-year-olds fail 2-item AMTS (the classic relational match to sample task introduced into the literature by Premack, 1983), and that robust success is not observed until age 6. They also establish that 3-year-olds, like non-human animal species, succeed only when they are able to encode stimuli in terms of entropy, a property of an array (namely its internal variability), rather than relations among the individuals in the array (same vs. different), whereas adults solve both 2-item and 16-item AMTS on the basis of the relations same and different. As in the case of non-human animals, the acuity of 3- and 4-year-olds' representation of entropy is insufficient to solve the 2-item same-different AMTS task. At age 4, behavior begins to contrast with that of non-human species. On 16-item AMTS, a subgroup of 4-year-olds induce a categorical rule matching all-same arrays to all-same arrays, while matching other arrays (mixed arrays of same and different items) to all-different arrays. These children tend to justify their choices using the words "same" and "different." By age 4 a number of our participants succeed at 2-item AMTS, also justifying their choices by explicit verbal appeals using words for same and different. Taken together these results suggest that the recruitment of the relational representations corresponding to the meaning of these words contributes to the better performance over the preschool years at solving array match-to-sample tasks.


Assuntos
Comportamento Animal/fisiologia , Desenvolvimento Infantil/fisiologia , Formação de Conceito/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adulto , Animais , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
World J Surg Oncol ; 14(1): 12, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26769110

RESUMO

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, accounts for 3% of newly diagnosed cases of colorectal cancer. While a partial or subtotal colectomy is indicated for early stage disease, there is a paucity of data addressing locally advanced disease involving the foregut. CASE PRESENTATION: We report two patients with hereditary nonpolyposis colorectal cancer presenting with locally advanced colon cancer surgically managed by pancreaticoduodenectomy with en bloc partial colectomy and a review of the literature. CONCLUSIONS: Locally advanced colorectal cancer in HNPCC is a rare clinical entity that requires special surgical consideration. Multidisciplinary treatment, including multi-visceral resection, offers the best long-term outcome.


Assuntos
Adenocarcinoma/cirurgia , Colectomia , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Pancreaticoduodenectomia , Adenocarcinoma/patologia , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
10.
Arthritis Rheumatol ; 68(2): 410-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26360522

RESUMO

OBJECTIVE: Outcomes of total hip arthroplasty (THA) in patients with psoriasis have been poorly studied. This study was undertaken to assess whether patients with psoriatic arthritis (PsA) or those with cutaneous psoriasis (PsC) without evidence of inflammatory joint disease are at an increased risk for worse outcomes after THA as compared to patients with osteoarthritis (OA). METHODS: Among subjects in a prospective THA registry, PsA and PsC cases were identified by International Classification of Diseases, Ninth Revision codes, and all cases were matched with patients with OA as controls. Analyses were performed to identify predictors of poor postoperative pain or function. RESULTS: Of the 289 potential cases of PsA or PsC, 63 with PsA and 153 with PsC were validated. Self-report data were available postoperatively from 75% of PsA patients, 69% of PsC patients, and 94% of OA controls. In total, 51% of PsA patients and 56% of PsC patients were male, compared to 45% of OA controls (P = 0.04). Body mass index was higher in those with PsA or PsC (P = 0.002 versus controls). There were no differences in race or education between the 3 groups. PsA patients and PsC patients had more comorbidities than OA controls. PsA patients were more likely than PsC patients and OA controls to be current or previous smokers. Moreover, 54% of PsA patients were being treated with biologics or nonbiologic disease-modifying antirheumatic drugs, compared to 8% of PsC patients. There were no significant differences in pre- or postoperative Western Ontario and McMaster Universities OA Index scores for pain or function between the 3 groups. Short-Form 36 mental component summary scores were significantly better in the OA controls, both pre- and postoperatively (P = 0.006 and P < 0.001, respectively, versus PsA or PsC). EuroQol 5-domain health-related quality of life scores were significantly worse postoperatively for those with PsA or PsC (P < 0.0001 versus OA controls). In regression analyses, neither PsA nor PsC were risk factors for worse THA outcomes. Satisfaction with the outcomes of THA was similarly high among all 3 groups (P = 0.54). CONCLUSION: Neither PsA nor PsC are risk factors for poor outcomes after THA. This is important information to convey to patients with either PsA or PsC who are contemplating surgical intervention with THA.


Assuntos
Artrite Psoriásica/cirurgia , Osteoartrite do Quadril/cirurgia , Sistema de Registros , Idoso , Artrite Psoriásica/complicações , Artroplastia de Quadril , Estudos de Casos e Controles , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoartrite do Quadril/complicações , Estudos Prospectivos , Psoríase/complicações , Resultado do Tratamento
11.
J Rheumatol ; 43(1): 46-53, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26628605

RESUMO

OBJECTIVE: Although new treatments for rheumatoid arthritis (RA) are extremely effective in preventing disease progression, rates of total knee replacement (TKR) continue to rise. The ongoing need for TKR is problematic, especially as functional outcomes in patients with RA have been reported to be worse than in patients with osteoarthritis (OA). The purpose of this study is to assess pain, function, and quality of life 2 years after TKR in contemporary patients with RA compared with patients with OA. METHODS: Primary TKR cases enrolled between May 1, 2007 and July 1, 2010 in a single institution TKR registry were eligible for this study. Validated RA cases were compared with OA at baseline and at 2 years. RESULTS: We identified 4456 eligible TKR, including 136 RA. Compared with OA, RA TKR had significantly worse preoperative Western Ontario and McMaster Universities Osteoarthritis Index pain (55.9 vs 46.6, p < 0.0001) and function (58.7 vs 47.3, p < 0.0001); however, there were no differences at 2 years. Within RA, there was no difference for patients who were treated with biologic disease-modifying antirheumatic drugs versus those who did not in pain (p = 0.41) or function (p = 0.39) at 2 years. In a multivariate regression, controlling for multiple potential confounders, there was no independent association of RA with 2-year pain (p = 0.18) or function (p = 0.71). Satisfaction was high for both RA and OA. CONCLUSION: Patients with RA undergoing primary TKR have excellent 2-year outcomes, comparable with OA, in spite of worse preoperative pain and function. In this contemporary cohort, RA is not an independent risk factor for poor outcomes.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Qualidade de Vida , Idoso , Análise de Variância , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/reabilitação , Artroplastia do Joelho/reabilitação , Estudos de Coortes , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/reabilitação , Medição da Dor , Dor Pós-Operatória/fisiopatologia , Dor Pós-Operatória/reabilitação , Cuidados Pós-Operatórios , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do Tratamento
12.
J Clin Rheumatol ; 20(7): 363-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25275762

RESUMO

BACKGROUND: While rates of total hip replacement (THR) in spondyloarthritis are increasing, contemporary outcomes are not well described. OBJECTIVES: This study analyzes 2-year outcomes in a contemporary cohort of ankylosing spondylitis (AS) patients undergoing THR. METHODS: A case-control study was performed using data from an institutional arthroplasty registry. Validated AS cases were matched 4:1 by age and procedure to patients with osteoarthritis (OA). Data were obtained prior to surgery and at 2 years. Multiple imputation techniques were performed to avoid systematic bias due to missing data. RESULTS: Thirty eligible AS cases were identified between May 2007 and February 2010. Ankylosing spondylitis cases had worse American Society of Anesthesia class (P < 0.001) and more comorbidities (P = 0.02) compared with OA. Ankylosing spondylitis had worse preoperative lower-extremity Western Ontario and McMaster Universities Arthritis Index pain (46.8 vs 55.4; P = 0.03), function (43.0 vs 55.1; P = 0.04), and general health status measured as SF-12 (Short-Form Health Survey) physical component scale (PCS) score (29.6 vs 36.0; P < 0.001), however, there was no difference at two years in pain (89.4 vs 92.5; P = 0.23) or function (83.9 vs 90.1; P = 0.04). Physical component scale score remained significantly worse (41.2 vs 50.1; P < 0.001). Better preoperative SF-12 PCS score significantly decreased the risk of a poor pain outcome (odds ratio, 0.06; 95% confidence interval, 0.01-0.40). Overall satisfaction was high. CONCLUSIONS: Although patients with AS in a contemporary cohort have more comorbidities and worse physical function prior to THR, they achieve similar gains as OA. In a multivariate regression controlling for multiple potential confounders including back pain, only preoperative health status measured as SF-12 PCS score was a significant risk factor for a poor 2-year pain. Among contemporary patients, AS is not an independent risk factor for poor THR outcomes.Take-Home Message Patients with AS have significant improvement in pain and function after THR.Poor preoperative function and low-back pain are not risk factors for poor THR outcomes for patients with AS.Despite improvements, low SF-12 PCS scores indicate persistent limitations due to health.


Assuntos
Artroplastia de Quadril , Espondilite Anquilosante/cirurgia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Dor Lombar/etiologia , Dor Lombar/fisiopatologia , Dor Lombar/prevenção & controle , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/complicações , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Quadril/cirurgia , Satisfação do Paciente , Recuperação de Função Fisiológica , Espondilite Anquilosante/complicações , Espondilite Anquilosante/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
13.
J Rheumatol ; 41(9): 1774-80, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25086070

RESUMO

OBJECTIVE: Total hip replacement (THR) outcomes have been worse for patients with rheumatoid arthritis (RA) compared with those who have osteoarthritis (OA). Whether this remains true in contemporary patients with RA with a high use of disease-modifying and biologic therapy is unknown. The purpose of our study is to assess pain, function, and quality of life 2 years after primary THR, comparing patients with RA and patients with OA. METHODS: Baseline and 2-year data were compared between validated patients with RA and patients with OA who were enrolled in a single-center THR registry between May 1, 2007, and February 25, 2011. RESULTS: There were 5666 eligible primary THR identified, of which 193 were for RA. RA THR had worse baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (44.8 vs 53.2, p < 0.001) and function (38.7 vs 49.9, p < 0.001) compared with OA. These differences remained after surgery: pain (88.4 vs 94.0, p < 0.001) and function (82.9 vs 91.8, p < 0.001). Patients with RA were as likely to have a significant improvement as patients with OA (Δ WOMAC > 10) in pain (94% vs 96%, p = 0.35) and function (95% vs 94%, p = 0.69), but were 4 times as likely to have worse function (WOMAC ≤ 60; 19% vs 4%, p < 0.001) and pain (12% vs 3%, p < 0.001). In multivariate logistic regression controlling for multiple potential confounders, RA increased the odds of poor postoperative function (OR 4.32, 95% CI 1.57-11.9), and in patients without a previous primary THR, worse postoperative pain (OR 3.17, 95% CI 1.06-9.53). CONCLUSION: Contemporary patients with RA have significant improvements in pain and function after THR, but higher proportions have worse 2-year pain and function. In addition, RA is an independent predictor of 2-year pain and poor function after THR, despite high use of disease-modifying therapy.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia de Quadril/efeitos adversos , Osteoartrite do Quadril/cirurgia , Dor Pós-Operatória/etiologia , Recuperação de Função Fisiológica/fisiologia , Idoso , Artrite Reumatoide/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/fisiopatologia , Qualidade de Vida , Sistema de Registros , Resultado do Tratamento
14.
Exp Cell Res ; 315(20): 3574-86, 2009 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-19619531

RESUMO

Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, alpha smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.


Assuntos
Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/farmacologia , Proliferação de Células/efeitos dos fármacos , Células do Tecido Conjuntivo/patologia , Contratura de Dupuytren/patologia , Fáscia/patologia , Metacarpo/patologia , Actinas/metabolismo , Fenômenos Biomecânicos/efeitos dos fármacos , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Células do Tecido Conjuntivo/efeitos dos fármacos , Células do Tecido Conjuntivo/metabolismo , Contratura de Dupuytren/metabolismo , Fáscia/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Expressão Gênica/genética , Humanos , Hibridização In Situ , Metacarpo/metabolismo , Estresse Mecânico
16.
J Negat Results Biomed ; 5: 13, 2006 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-16942611

RESUMO

BACKGROUND: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures. Increased cellular beta-catenin levels have been identified as characteristic of this disease. As Wnts are the most widely recognized upstream regulators of cellular beta-catenin accumulation, we have examined Wnt gene expression in surgical specimens and in DD-derived primary cell cultures grown in two-dimensional monolayer culture or in three-dimensional FPCL collagen lattice cultures. RESULTS: The Wnt expression profile of patient-matched DD and unaffected control palmar fascia tissue was determined by a variety of complimentary methods; Affymetrix Microarray analysis, specific Wnt and degenerative primer-based Reverse Transcriptase (RT)-PCR, and Real Time PCR. Microarray analysis identified 13 Wnts associated with DD and control tissues. Degenerate Wnt RT-PCR analysis identified Wnts 10b and 11, and to a lesser extent 5a and 9a, as the major Wnt family members expressed in our patient samples. Competitive RT-PCR analysis identified significant differences between the levels of expression of Wnts 9a, 10b and 11 in tissue samples and in primary cell cultures grown as monolayer or in FPCL, where the mRNA levels in tissue > FPCL cultures > monolayer cultures. Real Time PCR data confirmed the down-regulation of Wnt 11 mRNA in DD while Wnt 10b, the most frequently isolated Wnt in DD and control palmar fascia, displayed widely variable expression between the methods of analysis. CONCLUSION: These data indicate that changes in Wnt expression per se are unlikely to be the cause of the observed dysregulation of beta-catenin expression in DD.


Assuntos
Contratura de Dupuytren/metabolismo , Regulação da Expressão Gênica , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Células Cultivadas , Contratura de Dupuytren/genética , Contratura de Dupuytren/patologia , Fáscia/metabolismo , Fáscia/patologia , Humanos , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Wnt/genética , beta Catenina/genética
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