Invasive Exploitation and the Multiplicative Hypothesis: Polyvictimization and Adolescent Depression Symptoms in Nepal.

Adverse effects of childhood maltreatment experience and adolescent depression symptoms are theorized to be more profound for adolescents who have suffered multiple maltreatments (polyvictimization). New theoretical insights into the study of polyvictimization suggest that it must be studied using a multiplicative logic, particularly when maltreatment is characterized by invasive exploitation. This study, for the first time, examined the concept of invasive exploitation in the context of polyvictimization and its association with adolescent depression symptoms. The study used a random, three stage probability proportional to size (PPS) cluster sample of 565 mother-adolescent dyads in Kathmandu, Nepal, and also examined the protective effects of maternal empathy. We hypothesized that (a) singly, the empirical categories of maltreatment (neglect, physical abuse, and child sexual abuse) would associate positively with adolescent depressive symptoms and (b) main effects held constant, the interaction effects of a child sexual abuse X neglect and a child sexual abuse X physical abuse would be positive. Regression with clustering corrections found that neglect (B = 3.17, p < .01) and sexual abuse (B = 3.48, p < .05) positively associated with adolescent depression symptoms. Results support the multiplicative invasive exploitation polyvictimization hypothesis (child sexual abuse X neglect interaction; B = 6.14, p < .05). The positive neglect X sexual abuse interaction is consistent with the theory that sexual abuse is distinct as invasive exploitation, and demonstrates that the multiplicative hypothesis can be fruitfully applied to the study of polyvictimization. Interventions targeting polyvictims with experience of invasive exploitation and studies aiming to provide deeper insights into sexual abuse as invasive exploitation are needed.

Do family order and neighbor intervention against intimate partner violence protect children from abuse? Findings from Kathmandu.

Drawing on previous research on intimate partner violence, child maltreatment, and informal social control, we hypothesized relationships between child abuse severity and (1) protective informal social control of intimate partner violence (ISC_IPV) by neighbors, (2) intimate terrorism, (3) family order, and (4) the power of mothers in intimate relationships. In what we believe may be a first study of physical child abuse by parents in Nepal, we used a three stage cluster approach to draw a random sample of 300 families in Kathmandu. Random effects regression models were used to test the study hypotheses. The analyses found support for hypotheses one and two, but with an important caveat. Although observed (actual) protective ISC_IPV had the hypothesized negative association with child abuse severity, in one of our models perceived protective ISC_IPV was positively associated with child abuse severity. The models clarify that the overall direction of protective ISC_IPV appears to be negative (protective), but the positive finding is important to consider for both research and practice. A significant relationship between family order and child abuse severity was found, but the direction was negative rather than positive as in hypothesis three. Implications for neighborhood research and typological research on IPV and child maltreatment are discussed.

Fenofibrate antagonizes Chk2 activation by inducing Wip1 expression: implications for cell proliferation and tumorigenesis.

AIMS: Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARalpha) agonist that has been widely used to treat dyslipidemia. Previous studies have suggested that fenofibrate plays a role in cell proliferation and the development of hepatocarcinoma, but the underlying mechanism has not been fully characterized. In this report, we investigated whether fenofibrate treatment affected on the machinery of cell cycle checkpoint using nocodazole-induced cell cycle arrest. MAIN METHODS: The human normal liver cell line, CCL13 cells were treated with nocodazole and fenofibrate. Flow cytometry was performed for cell cycle analysis, and checkpoint kinase 2 (Chk2) and phosphatase Wip1 were analyzed by Western blot. KEY FINDINGS: Fenofibrate treatment overrode nocodazole-induced G2/M cell cycle arrest in a PPARalpha-independent manner. Mechanistically, fenofibrate treatment inhibited phosphorylation of checkpoint kinase Chk2 induced by nocodazole, and increased the expression of Wip1, a negative regulator of Chk2, suggesting that fenofibrate suppressed the nocodazole-induced G2/M cell cycle checkpoint through Wip1-mediated inhibition of Chk2 activation. SIGNIFICANCE: These results reveal a novel role of fenofibrate in cell cycle checkpoint control and provide a possible mechanistic explanation for how fenofibrate promotes cell proliferation and carcinogenesis.

Fenofibrate Reduces Age-related Hypercholesterolemia in Normal Rats on a Standard Diet.

Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR alpha), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.

Potential role of Homer-2a on cutaneous vascular anomaly.

Homer protein was identified based on its rapid induction in rat hippocampal granule cell neurons following excitatory synaptic activity. Although the presence of the Homer gene in the peripheral tissues has been observed in previous reports, the physiological function of the Homer protein in these tissues has not been noted. In this experiment, a Homer-2a cDNA fragment was successfully amplified by RTPCR in the involuting phase of human hemangioma but not in the human vascular malformation and normal vessel. After isolation of full Homer cDNA in a mouse liver cDNA library, E1-deleted recombinant adenovirus expressing the Homer protein (Adv.CMV.mHomer-2a) was constructed to determine its physiological function in peripheral tissues. Adv.CMV.mHomer2a, but not Adv.CMV.LacZ (recombinant adenovirus expressing Beta-galactosidase), strongly inhibited the growth rate of HUVECs (human umbilical vein endothelial cells) probably via inducing apoptosis determined by acridine orange/ethidium bromide (AO/EB) staining methods. This study suggests that the Homer gene is present in human specimens in the involuting phase of hemangioma, and it might be involved in the growth control.