Bulimic symptoms in a sample of college women: disentangling the roles of body size, body shame and negative urgency.

Purpose This study set out to disentangle the roles of body size, body shame and negative urgency on bulimic symptomatology in a sample of college women. We predicted that body shame would mediate the relationship between body size and bulimic symptomatology: with increasing body size, the greater would be the experience of body shame and, in turn, the greater the bulimic symptomatology. We also predicted that negative urgency would exacerbate this mediation pathway, and that the moderated mediation model would occur over and above current levels of depression. METHOD: A convenience sample of 237 college women indicated their age, height and weight and then completed measures of body shame, negative urgency, depression and bulimic symptomatology. Bootstrap analysis was used to test the predicted moderation mediation model. RESULTS: The bootstrap analysis supported all predictions. Thus, with greater the increase in body size, the greater was the body shame and the more frequent bulimic symptomatology. Furthermore, negative urgency moderated the relationship between body shame and bulimic symptomatology, such that those with both higher negative urgency and body shame had more frequent bulimic symptomatology. CONCLUSIONS: Results suggest that those college women higher in both BMI and negative urgency are likely to experience higher levels of bulimic symptoms. These women may benefit from emotion regulation interventions targeted at preventing, as well as coping effectively with, the experience of body shame. LEVEL OF EVIDENCE: V: cross-sectional descriptive study.

Administration of anticonvulsive rescue medication in children-discrepancies between parents' self-reports and limited practical performance.

UNLABELLED: Quality of parents' performance in administering anticonvulsive rescue medication to their children suffering from seizures is unknown. After obtaining ethical approval, we used a questionnaire to ask parents of children with seizures, who had been prescribed rescue medications, about their experience in administering those. To assess the frequency of actually committed drug-handling errors, we let them administer rescue medications to dummy dolls. An expert panel rated the clinical risk of handling errors from "1" (lowest) to "6" (highest). Eighty-one parents completed the study. In the questionnaire, 85 % (100 %) of parents that already conducted rectal (buccal) administration reported that they had never experienced problems. The number of rectal administrations with at least one handling error (97 %, 58/60) was higher than in buccal administration (58 %; 14/24; p < 0.001). According to logistic regressions, previous use of rescue medication was not a predictor of the number of committed errors per process (n. s.). All errors were rated with a high clinical risk (class 4-6). CONCLUSION: By observing parents' administration of rescue medication to dummy dolls, we found a high frequency of clinically relevant drug-handling errors. Most parents, however, self-reported to have never experienced problems while administering rescue medications to their children. WHAT IS KNOWN: • For seizures with duration of more than 5 min, the administration of anticonvulsive rescue medication is recommended. • Outside the hospital, the administration of rescue medication to children is performed most frequently by their parents. What is New: • Most of the parents reported that they had never experienced problems in handling anticonvulsive rescue medication. • But in the observed drug-handling performances, identified errors committed by parents were alarmingly frequent and pose a high clinical risk according to an expert panel.

Divergent mechanisms underlie Smad4-mediated positive regulation of the three genes encoding the basement membrane component laminin-332 (laminin-5).

BACKGROUND: Functional inactivation of the tumor suppressor Smad4 in colorectal and pancreatic carcinogenesis occurs coincident with the transition to invasive growth. Breaking the basement membrane (BM) barrier, a prerequisite for invasive growth, can be due to tumor induced proteolytic tissue remodeling or to reduced synthesis of BM molecules by incipient tumor cells. Laminin-332 (laminin-5), a heterotrimeric BM component composed of alpha 3-, beta 3- and gamma 2-chains, has recently been identified as a target structure of Smad4 and represents the first example for expression control of an essential BM component by a tumor and invasion suppressor. Biochemically Smad4 is a transmitter of signals of the TGFbeta superfamily of cytokines. We have reported previously, that Smad4 functions as a positive transcriptional regulator of constitutive and of TGFbeta-induced transcription of all three genes encoding Laminin-332, LAMA3, LAMB3 and LAMC2. METHODS: Promoter-reporter constructs harboring 4 kb upstream regions, each of the three genes encoding Laminin-322 as well as deletion and mutations constructs were established. Promoter activities and TGFbeta induction were assayed through transient transfections in Smad4-negative human cancer cells and their stable Smad4-positive derivatives. Functionally relevant binding sites were subsequently confirmed through chromatin immunoprecipitation. RESULTS: Herein, we report that Smad4 mediates transcriptional regulation through three different mechanisms, namely through Smad4 binding to a functional SBE site exclusively in the LAMA3 promoter, Smad4 binding to AP1 (and Sp1) sites presumably via interaction with AP1 family components and lastly a Smad4 impact on transcription of AP1 factors. Whereas Smad4 is essential for positive regulation of all three genes, the molecular mechanisms are significantly divergent between the LAMA3 promoter as compared to the LAMB3 and LAMC2 promoters. CONCLUSION: We hypothesize that this divergence in modular regulation of the three promoters may lay the ground for uncoupled regulation of Laminin-332 in Smad4-deficient tumor cells in response to stromally expressed cytokines acting on budding tumor cells.

High-level inducible Smad4-reexpression in the cervical cancer cell line C4-II is associated with a gene expression profile that predicts a preferential role of Smad4 in extracellular matrix composition.

BACKGROUND: Smad4 is a tumour suppressor frequently inactivated in pancreatic and colorectal cancers. We have recently reported loss of Smad4 in every fourth carcinoma of the uterine cervix. Smad4 transmits signals from the TGF-beta superfamily of cytokines and functions as a versatile transcriptional co-modulator. The prevailing view suggests that the tumour suppressor function of Smad4 primarily resides in its capability to mediate TGF-beta growth inhibitory responses. However, accumulating evidence indicates, that the acquisition of TGF-beta resistance and loss of Smad4 may be independent events in the carcinogenic process. Through inducible reexpression of Smad4 in cervical cancer cells we wished to shed more light on this issue and to identify target genes implicated in Smad4 dependent tumor suppression. METHODS: Smad4-deficient human C4-II cervical carcinoma cells were used to establish inducible Smad4 reexpression using the commercial Tet-ontrade mark system (Clontech). The impact of Smad4 reexpression on cell growth was analysed in vitro and in vivo. Transcriptional responses were assessed through profiling on cDNA macroarrays (Clontech) and validated through Northern blotting. RESULTS: Clones were obtained that express Smad4 at widely varying levels from approximately physiological to 50-fold overexpression. Smad4-mediated tumour suppression in vivo was apparent at physiological expression levels as well as in Smad4 overexpressing clones. Smad4 reexpression in a dose-dependent manner was associated with transcriptional induction of the extracellular matrix-associated genes, BigH3, fibronectin and PAI-1, in response to TGF-beta. Smad4-dependent regulation of these secreted Smad4 targets is not restricted to cervical carcinoma cells and was confirmed in pancreatic carcinoma cells reexpressing Smad4 after retroviral transduction and in a stable Smad4 knockdown model. On the other hand, the classical cell cycle-associated TGF-beta target genes, c-myc, p21 and p15, remained unaltered. CONCLUSION: Our results show that Smad4-mediated tumour suppression in cervical cancer cells is not due to restoration of TGF-beta growth inhibitory responses. Rather, tumour cell-ECM interactions may be more relevant for Smad4-mediated tumour suppression. C4-II cells with a high level inducible Smad4 expression may serve as a model to indicate further Smad4 targets responsive to diverse environmental stimuli operative in vivo.