Factors associated with commencing smoking in 12-year-old students in Catalonia (Spain): a cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>Over the last decade notable progress has been made in developed countries on monitoring smoking although experimenting with cigarettes and smoking in young people remains a serious public health problem. This paper reports a cross-sectional study at the beginning of the 3-year follow-up community study TA_BES. The aim was to study the prevalence of smoking in addition to determining predictive factors for when smoking commences in a representative population of 12-year-old first year compulsory secondary education students.</p> <p>Methods</p> <p>Twenty-nine secondary schools (N = 29) from an area of Catalonia participated in the study. In these schools 2245 students answered a questionnaire to study the attitudes, behaviors, and tobacco consumption in the subject's surrounding circle and family in relation to smoking; carbon monoxide measurements were taken by means of co-oximetry on 2 different occasions. A smoker was defined as a student who had smoked daily or occasionally in the last 30 days. For non-smokers the criteria of not considering was set up for those who answered that in the future they would not be smokers and considering those who answered that they did not rule out becoming a smoker in the future.</p> <p>Results</p> <p>Among the total 2245 students included in the analysis 157(7%) were classified as smokers. Among non-smokers we differentiated between those not considering smoking 1757 (78.3%) and those considering smoking 288 (12.8%).</p> <p>Age is among the factors related to commencing smoking. The risk of becoming a smoker increases 2.27 times/year. The influence of the group of friends with a very high risk for boys OR 149.5 and lower, albeit high, in girls OR 38.1. Tobacco consumption of parents produces different effects in young people. A smoking father does not produce alterations in the smoking behavior of young people. However having a smoking mother or former smoking is a risk factor for boys and a protective factor for girls.</p> <p>We detected a gradual risk of becoming a smoker by means of the co-oximetry test. A boy/girl with a test between 6 p.p.m and 10 p.p.m increased the probability of smoking by 2.29 and co-oximetry values > 10 p.p.m multiplied the risk 4 times over.</p> <p>Conclusions</p> <p>Results indicate that the age of commencing smoking is maintained in spite of prevalence having decreased in the last few years. The risk factors identified should be used to involve families and the educational community by offering them tobacco weaning programmes.</p

Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL™ 4.0 Generic Core Scales

<p>Abstract</p> <p>Background</p> <p>Advances in biomedical science and technology have resulted in dramatic improvements in the healthcare of pediatric chronic conditions. With enhanced survival, health-related quality of life (HRQOL) issues have become more salient. The objectives of this study were to compare generic HRQOL across ten chronic disease clusters and 33 disease categories/severities from the perspectives of patients and parents. Comparisons were also benchmarked with healthy children data.</p> <p>Methods</p> <p>The analyses were based on over 2,500 pediatric patients from 10 physician-diagnosed disease clusters and 33 disease categories/severities and over 9,500 healthy children utilizing the PedsQL™ 4.0 Generic Core Scales. Patients were recruited from general pediatric clinics, subspecialty clinics, and hospitals.</p> <p>Results</p> <p>Pediatric patients with diabetes, gastrointestinal conditions, cardiac conditions, asthma, obesity, end stage renal disease, psychiatric disorders, cancer, rheumatologic conditions, and cerebral palsy self-reported progressively more impaired overall HRQOL than healthy children, respectively, with medium to large effect sizes. Patients with cerebral palsy self-reported the most impaired HRQOL, while patients with diabetes self-reported the best HRQOL. Parent proxy-reports generally paralleled patient self-report, with several notable differences.</p> <p>Conclusion</p> <p>The results demonstrate differential effects of pediatric chronic conditions on patient HRQOL across diseases clusters, categories, and severities utilizing the PedsQL™ 4.0 Generic Core Scales from the perspectives of pediatric patients and parents. The data contained within this study represents a larger and more diverse population of pediatric patients with chronic conditions than previously reported in the extant literature. The findings contribute important information on the differential effects of pediatric chronic conditions on generic HRQOL from the perspectives of children and parents utilizing the PedsQL™ 4.0 Generic Core Scales. These findings with the PedsQL™ have clinical implications for the healthcare services provided for children with chronic health conditions. Given the degree of reported impairment based on PedsQL™ scores across different pediatric chronic conditions, the need for more efficacious targeted treatments for those pediatric patients with more severely impaired HRQOL is clearly and urgently indicated.</p

Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTXePC) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3Luc) were injected i.p. into SCID mice. Tumour growth was evaluated during sustained or intermittent courses of i.p. treatment with paclitaxel (PTX). In vitro bioluminescence strongly correlated with cell survival and cytotoxicity. Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival. As compared with intermittent therapy with Taxol®, sustained PTXePC therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times. Our results demonstrate that BLI is a useful tool in the pre-clinical evaluation of therapeutic interventions for ovarian cancer. Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTXePC implant system, which could potentially translate into successful clinical outcomes

Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in key disease regions, such as the pontine and dentate nuclei. Hsp90 inhibition has shown promising outcomes in some neurodegenerative diseases, but nothing is known about its effects in MJD. Chronic treatment of CMVMJD mice with Hsp90 inhibitor 17-DMAG resulted in a delay in the progression of their motor coordination deficits and, at 22 and 24 weeks of age, was able to rescue the uncoordination phenotype to wild-type levels; in parallel, a reduction in neuropathology was observed in treated animals. We observed limited induction of heat-shock proteins with treatment, but found evidence that 17-DMAG may be acting through autophagy, as LC3-II (both at mRNA and protein levels) and beclin-1 were induced in the brain of treated animals. This resulted in decreased levels of the mutant ataxin-3 and reduced intranuclear aggregation of this protein. Our data validate this novel mouse model as a relevant tool for the study of MJD pathogenesis and for pre-clinical studies, and show that Hsp90 inhibition is a promising therapeutic strategy for MJD.We would like to thank to Dr. Henry Paulson for providing the anti-ataxin-3 serum, Dr. Monica Sousa for the pCMV vector and to Eng. Lucilia Goreti Pinto, Lu s Martins, Miguel Carneiro and Celina Barros for technical assistance. This work was supported by Fundacao para a Ciencia e Tecnologia through the projects FEDER/FCT, POCI/SAU-MMO/60412/2004 and PTDC/SAU-GMG/64076/2006. This work was supported by Fundacao para a Ciencia e Tecnologia through fellowships SFRH/BPD/91562/2012 to A.S-F., SFRH/BD/78388/2011 to S. D-S., SFRH/BD/51059/2010 to A.N-C., and SFRH/BPD/79469/2011 to A.T-C.

Conduct disorder in girls: neighborhoods, family characteristics, and parenting behaviors

<p>Abstract</p> <p>Background</p> <p>Little is known about the social context of girls with conduct disorder (CD), a question of increasing importance to clinicians and researchers. The purpose of this study was to examine the associations between three social context domains (neighborhood, family characteristics, and parenting behaviors) and CD in adolescent girls, additionally testing for race moderation effects. We predicted that disadvantaged neighborhoods, family characteristics such as parental marital status, and parenting behaviors such as negative discipline would characterize girls with CD. We also hypothesized that parenting behaviors would mediate the associations between neighborhood and family characteristics and CD.</p> <p>Methods</p> <p>We recruited 93 15–17 year-old girls from the community and used a structured psychiatric interview to assign participants to a CD group (n = 52) or a demographically matched group with no psychiatric disorder (n = 41). Each girl and parent also filled out questionnaires about neighborhood, family characteristics, and parenting behaviors.</p> <p>Results</p> <p>Neighborhood quality was not associated with CD in girls. Some family characteristics (parental antisociality) and parenting behaviors (levels of family activities and negative discipline) were characteristic of girls with CD, but notll. There was no moderation by race. Our hypothesis that the association between family characteristics and CD would be mediated by parenting behaviors was not supported.</p> <p>Conclusion</p> <p>This study expanded upon previous research by investigating multiple social context domains in girls with CD and by selecting a comparison group who were not different in age, social class, or race. When these factors are thus controlled, CD in adolescent girls is not significantly associated with neighborhood, but is associated with some family characteristics and some types of parental behaviors. However, the mechanisms underlying these relationships need to be further investigated. We discuss possible explanations for our findings and suggest directions for future research.</p

Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

<p>Abstract</p> <p>Background</p> <p>Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC.</p> <p>Methods</p> <p>Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589.</p> <p>Results</p> <p>The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays.</p> <p>Conclusions</p> <p>We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.</p

What Do We Know About Neuropsychological Aspects Of Schizophrenia?

Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems

Trichotillomania and related disorders in children and adolescents

Eleven chronic hair pullers, 11 subjects with obsessive-compulsive disorder (OCD), and 11 subjects with a non-OCD anxiety disorder were assessed with structured interviews and the Child Behavior Checklist (CBCL). Only 4 hair pullers (36%) reported both rising tension and relief with hair pulling. Each group had significantly more internalizing than externalizing symptoms on the CBCL. Seven hair pullers (64%) had a lifetime history of at least one other axis I diagnosis. The results provide further evidence that trichotillomania in referred children and adolescents is usually a chronic disorder often associated with internalizing symptoms and psychiatric comorbidity. Rising tension followed by relief with hair pulling may be an unnecessary restriction in the diagnosis of childhood trichotillomania.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43954/1/10578_2006_Article_BF02353354.pd

No interaction between serotonin transporter gene (5-HTTLPR) polymorphism and adversity on depression among Japanese children and adolescents

Background: Identification of gene × environment interactions (G × E) for depression is a crucial step in ascertaining the mechanisms underpinning the disorder. Earlier studies have indicated strong genetic influences and numerous environmental risk factors. In relation to childhood and adolescent depression, evidence is accumulating that the quality of the parental environment is associated with serotonin biology in children. We hypothesized that maternal depression is a crucial environmental risk factor associated with serotonin-regulating genes.Methods: This study was designed to ascertain the G × E interaction for diagnosis of depression in a Japanese pediatric sample. DNA samples from 55 pediatric patients with depression and 58 healthy schoolchildren were genotyped for the 5-HTT (2 short (S) alleles at the 5-HTT locus) promoter serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphism. We examined whether an adverse parental environment, operationalized as the mother\u27s history of recurrent major depressive disorder, interacts with 5-HTTLPR polymorphism to predict patients\u27 depression symptoms.Results: Binary logistic regression analyses revealed that maternal depression (adversity), gender, and FSIQ significantly affect the diagnosis of depression among children and adolescents. However, no main effect was found for adversity or genotype. Results of multivariable logistic regression analyses using stepwise procedure have elicited some models with a good fit index, which also suggests no interaction between 5-HTTLPR and adversity on depression.Conclusions: To assess G × E interaction, data obtained from children and adolescents who had been carefully diagnosed categorically and data from age-matched controls were analyzed using logistic regression. Despite an equivocal interaction effect, adversity and gender showed significant main effects