Fearlessness as an Underlying Mechanism Leading to Conduct Problems: Testing the INTERFEAR Model in a Community Sample in Spain.

Conduct problems (CP) in childhood and adolescence have a significant impact on the individual, family, and community. To improve treatment for CP, there is a need to improve the understanding of the developmental pathways leading to CP in boys and girls. Prior research has linked the child's fearlessness and callous-unemotional (CU) traits, as well as experiences of parental warmth and punitive parenting, to CP. However, few studies have tested the interplay of these factors in contributing to future CP development. The present study aimed to test the InterFear model, which suggests that fearlessness in early childhood leads to CP through an indirect pathway involving low positive parenting, high negative/punitive parenting, and callous-unemotional (CU) traits. The sample included 2467 Spanish children (48.1% girls; Mage = 4.25; SD = 0.91), followed up across a five-year period. Besides a direct association between fearlessness in early childhood and future CP, the results found an indirect pathway whereby fearlessness reduces positive parenting and increases punitive parenting, which contributes to the development of CU traits and sets the stage for CP in later childhood. The specific indirect effect from fearlessness to CP via CU traits accounted for most of the variance, suggesting the existence of a temperamental pathway independent of parental variables. Further, two additional indirect pathways, exclusive of fearlessness, were identified, which started with low parental warmth and positive parenting, leading to CP via CU traits. These findings support the InterFear model, demonstrating multiple pathways to CP with the involvement of fearlessness, parenting practices, and CU traits. This model might play a pivotal role in the development of targeted prevention and intervention strategies for CP.

Fearlessness as an Underlying Mechanism Leading to Conduct Problems: Testing the Intermediate Effects of Parenting, Anxiety, and callous-unemotional Traits.

This study investigates whether the longitudinal association between fearlessness and conduct problems (CP) is mediated by warm and harsh parenting, parent-child conflict, anxiety, and callous-unemotional (CU) traits. The constructs under investigation were assessed at five different time points, spanning a period of eight years. A multi-informant approach was followed, collecting data from parents and teachers (N = 2,121; 47% girls). The structural equation model pointed to both direct and indirect pathways between fearlessness and CP. Specifically, findings suggested that Time 1 fearlessness (age 3-5 years) increased the likelihood of Time 2 (age 4-6 years) harsh parenting and Time 3 (age 5-7 years) parent-child conflict. Further, fearlessness was positively associated with Time 4 (age 8-10) callous-unemotional traits and Time 5 (age 11-13) CP. The total indirect effect from fearlessness to CP through these variables was significant, although the specific indirect effect from fearlessness to CU traits to CP accounted for most of the variance. Warm parenting and anxiety did not mediate the association between fearlessness and CP. In addition to the identified pathways connecting fearlessness to CP, findings pointed to the existence of multiple developmental pathways to future CP, as well as gender differences in longitudinal associations.

Tissue inhibitor of metalloproteinase-2 as a multifunctional molecule of which the expression is associated with adverse prognosis of patients with urothelial bladder carcinomas.

PURPOSE: Tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinase (MMP) activity controlling the breakdown of extracellular matrix components and, thus, play an important role in the process of invasion and metastasis. Moreover, there are several new functions, growth control, apoptosis, and angiogenesis-, in which TIMPs seem to be involved. The aim of this study was to elucidate the role of TIMP-2 in human urothelial cancer assessing TIMP-2 protein expression in 106 urothelial bladder carcinomas and evaluating its importance relative to clinicopathologic parameters (age, gender, histological grade, and stage) and patient survival, as well as to markers associated with cell growth and apoptosis (Ki-67, p53, and bcl-2). EXPERIMENTAL DESIGN: Immunohistochemistry (avidin-biotin complex method-horseradish peroxidase) was performed to detect TIMP-2, Ki-67, p53, and bcl-2 proteins using monoclonal and polyclonal antibodies. Statistical analysis was univariate and multivariate. RESULTS: TIMP-2 immunohistochemical expression was observed in stromal fibroblasts and in cancerous cells in 26.4% and 69.8% of cases, respectively. TIMP-2 stromal but not cancerous cell expression associated significantly with the high histological grade of carcinomas (P < 0.0001) and the advanced stage of the disease (P = 0.001). TIMP-2 either stromal or cancerous cell expression correlated significantly with the expression of Ki-67 proliferation indice (P = 0.02 and P = 0.044, respectively) and the mutant p53 protein (P = 0.043 and P = 0.045, respectively). In univariate survival analysis patients with positive TIMP-2 stromal cell immunohistochemical expression had a significantly worse overall survival in comparison with TIMP-2 stromal cell-negative patients (log rank test: P = 0.0002). However, in multivariate survival analysis the only independent survival factors were the stage of the disease and patient age. CONCLUSIONS: TIMP-2 protein expression in either the stromal or cancerous cells is associated with the proliferation index Ki-67 and the apoptosis-related protein p53. These findings are in keeping with in vitro studies reporting a growth-promoting ability of TIMP-2 and its involvement in apoptosis regulation. On the other hand, TIMP-2 stromal cell expression only was associated with adverse prognosis of urothelial bladder cancer patients.