The Construction and Psychometric Properties of the Questionnaire for Online Sexual Solicitation and Interaction of Minors With Adults.

The objective of this study was to develop a questionnaire to assess the online sexual solicitation and interactions of minors with adults in order to document the extent of this problem. The questionnaire was constructed in four phases: (a) a review of the previous literature; (b) interviews with convicted online child-sex offenders; (c) a review of the questionnaire items by experts; and (d) a pilot study of the questionnaire administered to adolescents. The validation sample consisted of 2,731 minors (12-15 years old, 50.6% girls). Exploratory factor analysis revealed a two-factor structure. The first factor, called "sexual solicitation," included items referring to sexual requests from an adult to a minor. The second factor, termed "sexualized interactions," included items indicating an adult groomed a minor with the purpose of committing a sexual offense. Of participants, 12.6% reported sexual solicitations, and 7.9% reported sexualized interactions. These findings open possible directions for research on the characteristics and consequences of online sexual solicitation and abusive interactions.

Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice.

Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1ß, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3ß-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma.

Running Exercise in Obese Pregnancies Prevents IL-6 Trans-signaling in Male Offspring.

PURPOSE: Maternal obesity is known to predispose the offspring to impaired glucose metabolism and obesity associated with low-grade inflammation and hypothalamic dysfunction. Because preventive approaches in this context are missing to date, we aimed to identify molecular mechanisms in the offspring that are affected by maternal exercise during pregnancy. METHODS: Diet-induced obese mouse dams were divided into a sedentary obese (high-fat diet [HFD]) group and an obese intervention (HFD-running intervention [RUN]) group, which performed voluntary wheel running throughout gestation. Male offspring were compared with the offspring of a sedentary lean control group at postnatal day 21. RESULTS: HFD and HFD-RUN offspring showed increased body weight and white adipose tissue mass. Glucose tolerance testing showed mild impairment only in HFD offspring. Serum interleukin-6 (IL-6) levels, hypothalamic and white adipose tissue IL-6 gene expressions, and phosphorylation of signal transducer and activator of transcription 3 in HFD offspring were significantly increased, whereas HFD-RUN was protected against these changes. The altered hypothalamic global gene expression in HFD offspring showed partial normalization in HFD-RUN offspring, especially with respect to IL-6 action. CONCLUSION: Maternal exercise in obese pregnancies effectively reduces IL-6 trans-signaling and might be the underlying mechanism for the amelioration of glucose metabolism at postnatal day 21 independent of body composition.

Prevention of early postnatal hyperalimentation protects against activation of transforming growth factor-ß/bone morphogenetic protein and interleukin-6 signaling in rat lungs after intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) is intimately linked with postnatal catch-up growth, leading to impaired lung structure and function. However, the impact of catch-up growth induced by early postnatal hyperalimentation (HA) on the lung has not been addressed to date. OBJECTIVE: The aim of this study was to investigate whether prevention of HA subsequent to IUGR protects the lung from 1) deregulation of the transforming growth factor-ß(TGF-ß)/bone morphogenetic protein (BMP) pathway, 2) activation of interleukin (IL)-6 signaling, and 3) profibrotic processes. METHODS: IUGR was induced in Wistar rats by isocaloric protein restriction during gestation by feeding a control (Co) or a low-protein diet with 17% or 8% casein, respectively. On postnatal day 1 (P1), litters from both groups were randomly reduced to 6 pups per dam to induce HA or adjusted to 10 pups and fed with standard diet: Co, Co with HA (Co-HA), IUGR, and IUGR with HA (IUGR-HA). RESULTS: Birth weights in rats after IUGR were lower than in Co rats (P < 0.05). HA during lactation led to accelerated body weight gain from P1 to P23 (Co vs. Co-HA, IUGR vs. IUGR-HA; P < 0.05). At P70, prevention of HA after IUGR protected against the following: 1) activation of both TGF-ß [phosphorylated SMAD (pSMAD) 2; plasminogen activator inhibitor 1 (Pai1)] and BMP signaling [pSMAD1; inhibitor of differentiation (Id1)] compared with Co (P < 0.05) and Co or IUGR (P < 0.05) rats, respectively; 2) greater mRNA expression of interleukin (Il) 6 and Il13 (P < 0.05) as well as activation of signal transducer and activator of transcription 3 (STAT3) signaling (P < 0.05) after IUGR-HA; and 3) greater gene expression of collagen Iα1 and osteopontin (P < 0.05) and increased deposition of bronchial subepithelial connective tissue in IUGR-HA compared with Co and IUGR rats. Moreover, HA had a significant additive effect (P < 0.05) on the increased enhanced pause (indicator of airway resistance) in the IUGR group (P < 0.05) at P70. CONCLUSIONS: This study demonstrates a dual mechanism in IUGR-associated lung disease that is 1) IUGR-dependent and 2) HA-mediated and thereby offers new avenues to develop innovative preventive strategies for perinatal programming of adult lung diseases.

Early postnatal hyperalimentation impairs renal function via SOCS-3 mediated renal postreceptor leptin resistance.

Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism.

Developmental regulation of inflammatory cytokine-mediated Stat3 signaling: the missing link between intrauterine growth restriction and pulmonary dysfunction?

Intrauterine growth restriction (IUGR) is a risk factor for impairment of lung function in adolescence and adulthood. Inflammatory and proliferative processes linking IUGR and perturbed extracellular matrix (ECM) as an underlying mechanism have not been addressed so far. Therefore, in this study, we aimed to investigate the developmental regulation of inflammatory and profibrotic processes in the lung subsequent to IUGR. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 28 and P70. Lungs were obtained at P1, P42, and P70 for assessment of mRNA, protein expression, immunohistochemistry, and gelatinolytic activity. Both respiratory system resistance and compliance were impaired subsequent to IUGR at P28 and this impairment was even more pronounced at P70. In line with these results, the expression of ECM components and metabolizing enzymes was deregulated. The deposition of collagen was increased at P70. In addition, the expression of inflammatory cytokines and both the activity and the expression of target genes of Stat3 signaling were dynamically regulated, with unaltered or decreased expression at P1 and significantly increased expression art P70. Taken together, these data give evidence for an age-dependent impairment of lung function as a result of a developmentally regulated increase in inflammatory and profibrotic processes subsequent to IUGR.

Hypothalamic JNK1 and IKKß activation and impaired early postnatal glucose metabolism after maternal perinatal high-fat feeding.

Hypothalamic inflammation has been demonstrated to be an important mechanism in the pathogenesis of obesity-induced type 2 diabetes mellitus. Feeding pregnant and lactating rodents a diet rich in saturated fatty acids has consistently been shown to predispose the offspring for the development of obesity and impaired glucose metabolism. However, hypothalamic inflammation in the offspring has not been addressed as a potential underlying mechanism. In this study, virgin female C57BL/6 mice received high-fat feeding starting at conception until weaning of the offspring at postnatal d 21. The offspring developed increased body weight, body fat content, and serum leptin concentrations during the nursing period. Analysis of hypothalamic tissue of the offspring at postnatal d 21 showed up-regulation of several members of the toll-like receptor 4 signaling cascade and subsequent activation of c-Jun N-terminal kinase 1 and IκB kinase-ß inflammatory pathways. Interestingly, glucose tolerance testing in the offspring revealed signs of impaired glucose tolerance along with increased hepatic expression of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. In addition, significantly increased hepatic and pancreatic PGC1α expression suggests a role for sympathetic innervation in mediating the effects of hypothalamic inflammation to the periphery. Taken together, our data indicate an important role for hypothalamic inflammation in the early pathogenesis of glucose intolerance after maternal perinatal high-fat feeding.

Inhibition of TGF-ß signaling and decreased apoptosis in IUGR-associated lung disease in rats.

Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-ß system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-ß signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-ß system was determined at P1 and P70. TGF-ß signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-ß1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-ß signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-ß-regulated ECM components (e.g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-ß signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-ß signaling may contribute to the pathological processes of IUGR-associated lung disease.

Persistent changes within the intrinsic kidney-associated NPY system and tubular function by litter size reduction.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with an increased risk of renal diseases in adulthood. However, while low-birth-weight-infants often undergo accelerated postnatal growth, the impact of postnatal environmental factors such as nutrition and early postnatal stressors on renal development and function remains unclear. In this context, Neuropeptide Y (NPY) may act as a critical factor. NPY is a sympathetic coneurotransmitter involved in blood pressure regulation and tubular function. Yet, little is known about the expression and function of endogenous NPY in the kidney and the functional relevance for the transmission of persistent postnatal-induced effects. METHODS: (1) IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. (2) Litter size was reduced to 6 (LSR6) or 10 (LSR10) male neonates. To differentiate the effect of postnatal nutrition and stressors, we additionally included home-cage-control animals without any postnatal manipulation. Animals were sacrificed at Day 70. RESULTS: Litter size reduction (LSR) to 6 but not IUGR increased messenger RNA expression of endogenous NPY and down-regulated the NPY-receptors Y1 and Y2. Furthermore, dipeptidylpeptidase IV (DPPIV)--an enzyme that cleaves NPY--was decreased after LSR. Expression and the phosphorylation of mitogen-activated protein kinase 42/44 (intracellular signalling pathway of the receptor Y1) were altered. An impaired renal function with pronounced kaliuresis and natriuresis was observed at Day 70 after LSR. CONCLUSIONS: Postnatal nutrition and stressors such as LSR lead to dysregulated signalling of NPY. These data demonstrate that factors in the early postnatal environment exert important changes in the tubular function, which may predispose to corresponding pathology.

Psychometric properties of a Spanish version of the UPPS-P impulsive behavior scale: reliability, validity and association with trait and cognitive impulsivity.

Impulsivity is a multifaceted construct central to several forms of psychopathology. Recently, Lynam, Smith, Whiteside, and Cyders (2006) developed the UPPS-P scale, a multidimensional inventory that assesses 5 personality pathways contributing to impulsive behavior: negative urgency, lack of perseverance, lack of premeditation, sensation seeking, and positive urgency. In this study, we aimed (a) to analyze the psychometric properties of a Spanish version of the UPPS-P scale and (b) to explore the relationship between the different dimensions of the UPPS-P scale and conceptually related constructs including trait measures derived from different models of impulsive personality (the Gray's [1987] and Plutchik's [1984] models) and a state measure of cognitive impulsivity, the Delay-Discounting Test (Kirby, Petry, & Bickel, 1999). We administered the UPPS-P scale along with the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (Torrubia, Avila, Molto, & Caseras, 2001), the Plutchik Impulsivity Scale (Plutchik & Van Praag, 1989), and the Delay-Discounting Test to a sample of 150 undergraduate students. Results showed that the Spanish adaptation of the UPPS-P scale have appropriate psychometric properties. Different dimensions of the UPPS-P were differentially associated with predicted conceptually related constructs. We conclude that the Spanish adaptation of the UPPS-P scale is a useful instrument for fine-grained assessment of impulsivity in Spanish-speaking adult population.

MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder.

The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, and also to obtain preliminary data regarding efficacy. Although this study was originally planned to include 29 subjects, political pressures led to the closing of the study before it could be finished, at which time only six subjects had been treated. Preliminary results from those six subjects are presented here. We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.