Association between parental visitation and depressive symptoms among institutionalized children in Japan: a cross-sectional study.

BACKGROUND: Mental health problems are an important issue among institutionalized children. Although positive communication with parents is essential for children's well-being, it has not been sufficiently verified how interactions with parents affect mental health among institutionalized children, who have experienced childhood adversity and likely lack secure attachment formation with their parents. The objectives of this study were to investigate the association between parental visitation and depressive symptoms among institutionalized children in Japan, and to explore whether the established security of attachment interacts with that association. METHODS: A cross-sectional data from 399 institutionalized children aged 9 to 18 in Japan was used for the analysis. A mixed effects regression analysis was conducted to investigate the associations. RESULTS: Institutionalized children who had parental visitation showed higher depressive symptoms than those who did not. In particular, father's visitations were significantly associated with higher depressive symptoms. There was a significant interaction with score of secure attachment; children with low scores on secure attachment showed higher levels of depression with their father's visitation, whereas children with high scores on secure attachment did not. CONCLUSIONS: Findings suggested that parental visitation and the frequency of visitation were not actually associated with better psychological status, but that instead, father's visitations were associated with higher depressive symptoms among institutionalized children. It should be noted that our cross-sectional results cannot infer any causal relationship and do not emphasize that parental visitation should be avoided. However, it may be important to conduct careful assessment before starting parental visitation, especially when children seem to have problems with attachment formation.

Roles of attachment and self-esteem: impact of early life stress on depressive symptoms among Japanese institutionalized children.

BACKGROUND: Although exposure to early life stress is known to affect mental health, the underlying mechanisms of its impacts on depressive symptoms among institutionalized children and adolescents have been little studied. METHODS: To investigate the role of attachment and self-esteem in association with adverse childhood experiences (ACEs) and depressive symptoms, 342 children (149 boys, 193 girls; age range 9-18 years old, mean age = 13.5 ± 2.4) living in residential foster care facilities in Japan completed questionnaires related to internal working models, self-esteem, and depressive symptoms. Their care workers completed questionnaires on ACEs. RESULTS: Structural equation modeling (SEM) was created and the goodness of fit was examined (CMIN = 129.223, df = 1.360, GFI = .959, AGFI = .936, CFI = .939, RMSEA = .033). Maltreatment negatively predicted scores on secure attachment, but positively predicted scores on avoidant and ambivalent attachment. The secure attachment score negatively predicted depressive symptoms. The ambivalent attachment score positively predicted depressive symptoms both directly and through self-esteem, whereas the avoidant attachment score positively predicted depressive symptoms only directly. Maltreatment neither directly predicts self-esteem nor depressive symptoms, and parental illness/death and parental sociopathic behaviors did not predict any variables. CONCLUSIONS: Results show that the adversity of child maltreatment affects depression through attachment styles and low self-esteem among institutionalized children. Implications of child maltreatment and recommendations for child welfare services and clinical interventions for institutionalized children are discussed.

Exposure to parental verbal abuse is associated with increased gray matter volume in superior temporal gyrus.

OBJECTIVE: Exposure to parental verbal aggression (PVA) during childhood increases risk for the development of psychopathology, particularly mood and anxiety disorders. Other forms of childhood abuse have been found to be associated with alterations in brain structure. The aim of this study was to ascertain whether exposure to PVA was associated with discernible effects on brain morphology. METHODS: Optimized voxel-based morphometry was performed on 21 unmedicated, right-handed subjects (18-25 years) with histories of PVA and 19 psychiatrically healthy controls of comparable age and gender. Group differences in gray matter volume (GMV)--covaried by age, gender, parental education, financial stress, and total GMV--were assessed using high-resolution, T1-weighted, volumetric MRI data sets (Siemens 3T trio scanner). RESULTS: GMV was increased by 14.1% in the left superior temporal gyrus (STG, BA 22) (P=0.004, corrected cluster level). GMV in this cluster was associated most strongly with levels of maternal (ß=0.544, P<0.0001) and paternal (ß=0.300, P<0.02) verbal aggression and inversely associated with parental education (ß=-0.577, P<0.0001). CONCLUSION: Previous studies have demonstrated an increase in STG GMV in children with abuse histories, and found a reduction in fractional anisotropy in the arcuate fasciculus connecting Wernicke's and frontal areas in young adults exposed to PVA. These findings and the present results suggest that the development of auditory association cortex involved in language processing may be affected by exposure to early stress and/or emotionally abusive language.

An autocrine linkage between matrix metalloproteinase-14 and Tie-2 via ectodomain shedding modulates angiopoietin-1-dependent function in endothelial cells.

OBJECTIVE: The angiopoietin (Ang)-Tie-2 system plays a critical role during fetal and adult angiogenesis. Herein, we explored the Tie-2 shedding-related molecular mechanisms and the pathophysiological significance. METHODS AND RESULTS: By using a mouse hindlimb ischemia model, we observed dissociated expression between the full-length Tie-2 (fTie-2) protein and Tie-2 mRNA in thigh muscles 1 day after an ischemic operation, suggesting that fTie-2 expression was modified through the posttranscriptional regulation in vivo. A soluble form of Tie-2 produced in human umbilical vein endothelial cells was dramatically suppressed by treatment with siRNA-matrix metalloproteinase (MMP) 14 or tissue inhibitor of metalloproteinase 3, resulting in an increase in cellular fTie-2 and thereby enhancing Ang-1-dependent Akt phosphorylation and Akt-dependent endothelial functions, such as Ang-2 downregulation or an increase of endothelial viability. Phorbol-12-myristate-13 acetate (PMA) upregulates MMP-14 mRNA via protein kinase C-extracellular signal-regulated kinase pathways, and enhanced soluble Tie-2 production in an MMP-14-dependent manner, resulting in a reduction of cellular fTie-2. In addition, the PMA-induced soluble Tie-2 was mediated by the protein kinase C-extracellular signal-regulated kinase signaling pathways. Finally, downregulation of tissue inhibitor of metalloproteinase 3 and upregulation of MMP-14 mRNA were confirmed in ischemic thigh muscles 1 day after the operation. CONCLUSIONS: An autocrine linkage between the endothelial protein kinase C-MMP-14 axis and Tie-2 shedding was shown to be a novel regulatory mechanism for the Ang-Tie-2 system and may play a role in modulating endothelial function during angiogenesis.

Podoplanin in cancer cells is experimentally able to attenuate prolymphangiogenic and lymphogenous metastatic potentials of lung squamoid cancer cells.

BACKGROUND: Podoplanin, a mucin-like transmembrane glycoprotein, is reportedly expressed in a variety of malignant cells and is generally regarded as a factor for promoting tumor progression in conventional studies. By contrast, a clinicopathologically conflicting role for podoplanin, namely as a favorable prognostic factor for patients with lung/cervical squamous cell carcinoma (SCC), has recently been reported. Here, we investigated the role of podoplanin expressed in lung squamoid cancer cells (LSCCs) in experimental tumor progression. RESULTS: Using EBC-1 cells, a lung SCC cell line without podoplanin expression and with lymphogenous metastatic potential, stable transformants with or without an exogenous human podoplanin gene were established and applied to a mouse tumor implantation model. In vivo examinations revealed that exogenous podoplanin had no influence on tumor growth, whereas it significantly restrained axillary lymph node metastasis associated with the suppression of lymphangiogenesis but not angiogenesis and with the downregulation of EBC-1-derived VEGF-C but not other lymphangiogenesis-related factor mRNAs in implanted tumor tissue. In vitro examinations to clarify the mechanisms underlying the in vivo phenomena revealed that exogenous podoplanin significantly suppressed the expression of VEGF-C mRNA and of the protein, and also increased the level of phosphorylated c-jun N terminal kinase (JNK) in EBC-1 cells. The former effect of exogenous podoplanin was impaired by treatment with either JNK inhibitor sp600125 or podoplanin-siRNA, and the latter effect was impaired by treatment with podoplanin-siRNA, suggesting that podoplanin was able to activate JNK, thereby downregulating VEGF-C gene expression in LSCCs (podoplanin-JNK-VEGF-C axis). Furthermore, supporting evidence in regard to the axis present in LSCCs was obtained from similar experiments using H157 cells, another lung SCC cell line expressing endogenous podoplanin. CONCLUSIONS: Our findings suggested that LSCC-associated podoplanin was functional and could attenuate the potential for lymph node metastasis, possibly based on the suppression of tumor lymphangiogenesis; thus, podoplanin in cancer cells may become a useful biomarker to measure the malignancy of lung SCC.

Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells.

Numerous past studies have suggested a critical role of the paracrine effect between tumor vascular endothelial growth factor (VEGF)-C and lymphatic FLT-4 in solid tumor-associated lymphangiogenesis. In contrast, the pathophysiological role of tumor cell-associated FLT-4 in tumor progression remains to be elucidated. Here, we investigated this role using a tumor implantation model. SAS cells, an oral squamous carcinoma cell line expressing both VEGF-C and FLT-4 but neither FLK-1/KDR nor VEGF-D were adopted for experiments. Stable transformants of dominant-negative (dn) SAS cells were established in which the cytoplasmic domain-deleted FLT-4 was exogenously overexpressed, which can lead to inactivation of endogenous FLT-4 through competitive antagonism and is associated with down-activation of endogenous FLT-4-related intracellular signals. In vitro and in vivo proliferation assays showed lower proliferative activity of dn-SAS cells. An immunohistochemical study revealed that the tumor lymphangiogenesis was significantly suppressed, and the level of human VEGF-C mRNA was significantly lower in dn-SAS cell-derived tumor tissues. Moreover, in vitro studies demonstrated that the significant suppression of VEGF-C and VEGF-A expression was evident in dn-SAS cells or wild-type SAS cells treated with either the FLT-4 kinase inhibitor MAZ51 or the inhibitor of FLT-4-related signals. These findings together suggested that the VEGF-C/FLT-4 autocrine loop in tumor cells was a potential enhancer system to promote cancer progression, and FLT-4 in tumor tissue might become an effective target for cancer therapy.

Reduced prefrontal cortical gray matter volume in young adults exposed to harsh corporal punishment.

OBJECTIVE: Harsh corporal punishment (HCP) during childhood is a chronic, developmental stressor associated with depression, aggression and addictive behaviors. Exposure to traumatic stressors, such as sexual abuse, is associated with alteration in brain structure, but nothing is known about the potential neurobiological consequences of HCP. The aim of this study was to investigate whether HCP was associated with discernible alterations in gray matter volume (GMV) using voxel-based morphometry (VBM). METHODS: 1455 young adults (18-25 years) were screened to identify 23 with exposure to HCP (minimum 3 years duration, 12 episodes per year, frequently involving objects) and 22 healthy controls. High-resolution T1-weighted MRI datasets were obtained using Siemens 3 T trio scanner. RESULTS: GMV was reduced by 19.1% in the right medial frontal gyrus (medial prefrontal cortex; MPFC, BA10) (P=0.037, corrected cluster level), by 14.5% in the left medial frontal gyrus (dorsolateral prefrontal cortex; DLPFC, BA9) (P=0.015, uncorrected cluster level) and by 16.9% in the right anterior cingulate gyrus (BA24) (P<0.001, uncorrected cluster level) of HCP subjects. There were significant correlations between GMV in these identified regions and performance IQ on the WAIS-III. CONCLUSIONS: Exposing children to harsh HCP may have detrimental effects on trajectories of brain development. However, it is also conceivable that differences in prefrontal cortical development may increase risk of exposure to HCP.

High podoplanin expression in cancer cells predicts lower incidence of nodal metastasis in patients with lung squamous cell carcinoma.

Podoplanin is expressed in a variety of malignant cells, and is generally regarded as a factor promoting tumor progression in conventional studies. Conversely, a recent clinicopathological study has revealed that low podoplanin in cancer cells was correlated with poor prognosis of patients with stage IB lung squamous cell carcinoma (LSCC). We here evaluated the clinicopathological relationship between cancer-cell podoplanin expression and clinicopathological parameters in 40 cases of LSCC (stage I-III). Immunohistochemical podoplanin expression significantly correlated with N classification and pathological stage, but not with other clinicopathological parameters. Notably, all 16 cases with high podoplanin expression unexceptionally exhibited pathological N0 status. Cases without nodal metastasis showed a significantly higher podoplanin-positive score. Furthermore, patients with high podoplanin expression exhibited a significantly longer survival time and disease-free time. These findings suggest that immunohistochemical analysis for podoplanin may serve as a marker of risk of nodal metastasis and prognosis in patients with LSCC.

Description of environmental determinants of quality of life in children with intellectual disability in Japan using the Delphi technique.

OBJECTIVES: The present study aimed to define the framework of an environment conducive to the well-being of children with intellectually disability (CID). METHODS: A questionnaire composed of 31 items was developed through literature review. Then a 2-round Delphi survey was conducted with 3 different panels: health professionals (HPs), parents of CID, and teachers. The participants were asked to rate each item, select and rank the 10 most important items, and suggest additional ones. RESULTS: A total of 71 participants responded to the first round: 24 HPs, 22 parents, and 25 teachers. In the second round the overall response rate was 83%. At the end of the exercise, 12 items reached global consensus, i.e., in all groups. Only 5 items were ranked as most important by all groups: attitudes of family members at home; attitudes of HPs and teachers; support from family members at home; support at school (classmates and teachers); and government policies. Nevertheless, the panelists' views diverged on the remaining items. Several additional elements were suggested. CONCLUSIONS: The views of HPs, teachers, and parents are complementary for the improvement of quality of life (QOL) of CID. The present findings will be used as a basis for the development of an instrument to assess the living environment of CID.

English perceptions of elder abuse.

The purpose of this exploratory study was to investigate an English sample's perceptions on elder abuse, inflicted by adult children against their aging parents. Fifty participants (14 males, 46 females) provided examples of extreme, moderate, and mild elder abuse. As examples of extreme abuse, most participants mentioned neglect and physical aggression. Various forms of neglect and psychological abuse were their most common examples of moderate and mild abuse. References to physical aggression appeared most often as examples of extreme abuse rather than of moderate or mild abuse. Within these main categories, the specific subtypes most frequently mentioned by the sample included physical neglect, psychological neglect, verbal abuse, and deprivation. More females than males provided examples of financial abuse and physical neglect. Females were also more likely than males to list psychological neglect as an extreme form of abuse and disrespect as a form of mild abuse. At the moderate level, males referred to abuse relating to power more often than females. A positive relationship was found between age and the number of examples of physical neglect given at the moderate level and the number of examples of emotional abuse given at the mild level.