Advances in chemistry of chromone aminomethyl derivatives

Chromones play an important role in the design and discovery of new pharmacologically active compounds. A large volume of reports dedicated to synthesis and study of properties of nitrogen-containing chromone derivatives show important role of chromone alkaloid-like compounds. The present review covers achievements in the field of synthesis of chromone aminomethyl derivatives as one of perspective scaffolds

Synthesis and transformation of 6-aminomethyl derivatives of 7-hydroxy-2'-fluoroisoflavones

Mannich aminomethylation of 8-methyl-7-hydroxy-2'-fluoroisoflavones applying bis-(N,N-dimethylamino)methane afforded C-6 substituted N,N-dimethylaminomethyl derivatives. Subsequent acetylation of these compounds in acetic anhydride in the presence of potassium acetate provided access to the corresponding acetoxymethyl derivatives that were converted to hydroxymethyl- and alkoxymethyl-substituted 7-hydroxyisoflavonoids. Addition of 3-(N,N-dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one or 1,3-dimethyl-5-aminopyrazole with thermally generated ortho-quinone methides led to hetero-Diels–Alder or Michael adducts

Peer Rejection and Friendships in Children with Attention-Deficit/Hyperactivity Disorder: Contributions to Long-Term Outcomes

Even after evidence-based treatment, Attention- Deficit/Hyperactivity Disorder (ADHD) is associated with poor long-term outcomes. These outcomes may be partly explained by difficulties in peer functioning, which are common among children with ADHD and which do not respond optimally to standard ADHD treatments. We examined whether peer rejection and lack of dyadic friendships experienced by children with ADHD after treatment contribute to long-term emotional and behavioral problems and global impairment, and whether having a reciprocal friend buffers the negative effects of peer rejection. Children with Combined type ADHD (N0300) enrolled in the Multimodal Treatment Study of Children with ADHD (MTA) were followed for 8 years. Peer rejection and dyadic friendships were measured with sociometric assessments after the active treatment period (14 or 24 months after baseline; M ages 9.7 and 10.5 years, respectively). Outcomes included delinquency, depression, anxiety, substance use, and general impairment at 6 and 8 years after baseline (Mean ages 14.9 and 16.8 years, respectively). With inclusion of key covariates, including demographics, symptoms ofADHD, ODD, and CD, and level of the outcome variable at 24 months, peer rejection predicted cigarette smoking, delinquency, anxiety, and global impairment at 6 years and global impairment at 8 years after baseline. Having a reciprocal friend was not, however, uniquely predictive of any outcomes and did not reduce the negative effects of peer rejection. Evaluating and addressing peer rejection in treatment planning may be necessary to improve long-term outcomes in children with ADHD

Comparisons of Types of Exposure to Violence Within and Across Contexts in Predicting the Perpetration of Dating Aggression

It is widely accepted that adolescents exposed to violence are more likely to become perpetrators of dating aggression. However, it remains unclear whether the effects of exposure to violence on later perpetration of dating aggression vary based on the nature of the violence exposure (e.g., witnessing versus being a victim) and the contexts of exposure to violence. Thus, the relationships between two types of exposure to violence (witnessing and victimization) in early adolescence and perpetrating dating aggression in late adolescence were compared within and across three social contexts: the home, the community, and the school. Participants included 484 youth (51% females; 81% African–Americans, 18% European–Americans, 1% Hispanic or Other). Information on exposure to violence were collected at Waves 1 and 2 during early adolescence (Wave 1: M = 11.8 years old; Wave 2: M = 13.2 years old) and dating aggression data were collected during late adolescence (Wave 3: M = 18.0 years old). The results showed that across all contexts witnessing violence was a more consistent predictor of later dating aggression relative to victimization. Being exposed to violence in the home either via observation or victimization was a stronger predictor of physical dating aggression and threatening behaviors compared to being exposed to violence in the school. These findings provide a deeper understanding of the roles of various forms of exposure to violence during early adolescence in perpetrating dating aggression later in the life course

The relationship between pain severity and alcohol use among school-aged children and adolescents : the moderating role of drinking motives

Objective. Evidence from adult samples suggests a co-occurrence between pain and alcohol abuse. However, studies in adolescents are scarce and results are inconsistent, with some studies observing heightened and others observing reduced alcohol consumption in adolescents suffering from pain. We hypothesized that in adolescents the association between pain and alcohol use will be moderated by drinking motives. Methods. Data from a large representative sample of Flemish school children and adolescents (N = 10,650, 50.8% boys, age range = 10-21 years, M-age = 514.33 years) were collected as part of the World Health Organization collaborative Health Behaviour in School-Aged Children (HBSC) survey. Pain severity was graded based on a pediatric pain classification system that accounts for both pain intensity and disability. Alcohol consumption was operationalized using two variables: frequency of drinking and drunkenness. The Drinking Motives Questionnaire-Revised was used to capture drinking motives; it assesses four motive categories (enhancement, coping, social, and conformity). Results. Findings indicated that higher pain severity was associated with greater frequency of alcohol use and drunkenness. However, drinking motives moderated this association. The positive association between pain severity and drinking frequency was stronger in case of high conformity motives. Likewise, the association between pain severity and drunkenness frequency was stronger at high levels of conformity motives and reached significance only at high levels of coping motives. Conclusions. Our findings suggest that specific drinking motives are linked to problematic alcohol use in adolescents with pain. Future studies using a longitudinal design are needed to draw conclusions about direction of effects

Discriminating Between Children With ADHD and Classmates Using Peer Variables

Objective: Impaired peer relationships have long been recognized as one of the major functional problems of children with ADHD, but no specific guidelines on clinical levels of impairment in this domain exist. Method: This study used Receiver Operating Characteristics methodology to determine what aspects of peer functioning best discriminate between children with ADHD and their classmates. Optimal cutoffs indicative of clinical levels of impairment associated with ADHD diagnosis were determined for all variables. The participants were 165 children with AD/HD who were part of the Multimodal Treatment Study of Children With ADHD and their 1,298 classmates. Results: Variables that best discriminated between children with ADHD and their classmates included peer rejection and negative imbalance between given and received liking ratings (i.e., children with ADHD liked others more than they were liked). Conclusion: Peer rejection and negative imbalance show most promise for identifying clinically significant levels of peer relationship impairment in children with ADHD. (J. of Att. Dis. 2009; 12(4) 372-380)

Genetic and Informatic Analyses Implicate Kif12 as a Candidate Gene within the Mpkd2 Locus That Modulates Renal Cystic Disease Severity in the Cys1cpk Mouse.

We have previously mapped the interval on Chromosome 4 for a major polycystic kidney disease modifier (Mpkd) of the B6(Cg)-Cys1cpk/J mouse model of recessive polycystic kidney disease (PKD). Informatic analyses predicted that this interval contains at least three individual renal cystic disease severity-modulating loci (Mpkd1-3). In the current study, we provide further validation of these predicted effects using a congenic mouse line carrying the entire CAST/EiJ (CAST)-derived Mpkd1-3 interval on the C57BL/6J background. We have also generated a derivative congenic line with a refined CAST-derived Mpkd1-2 interval and demonstrated its dominantly-acting disease-modulating effects (e.g., 4.2-fold increase in total cyst area;

Are sexual media exposure, parental restrictions on media use and co-viewing TV and DVDs with parents and friends associated with teenagers' early sexual behaviour?

Sexual content in teenagers' media diets is known to predict early sexual behaviour. Research on sexual content has not allowed for the social context of media use, which may affect selection and processing of content. This study investigated whether sexual media content and/or contextual factors (co-viewing, parental media restrictions) were associated with early sexual behaviour using 2251 14–15 year-olds from Scotland, UK. A third (<i>n</i> = 733) reported sexual intercourse. In multivariable analysis the likelihood of intercourse was lower with parental restriction of sexual media and same-sex peer co-viewing; but higher with mixed-sex peer co-viewing. Parental co-viewing, other parental restrictions on media and sexual film content exposure were not associated with intercourse. Findings suggest the context of media use may influence early sexual behaviour. Specific parental restrictions on sexual media may offer more protection against early sex than other restrictions or parental co-viewing. Further research is required to establish causal mechanisms

Racial disparities in fifth-grade sun protection: Evidence from the Healthy Passages study

Background/Objectives: Despite rising skin cancer rates in children, multiple studies reveal inadequate youth sun-protective behavior (eg, sunscreen use). Using Healthy Passages data for fifth-graders, we set out to determine sunscreen adherence in these children and investigated factors related to sunscreen performance. Methods: Survey data were collected from 5119 fifth-graders and their primary caregivers. Logistic regression was used to assess associations between sunscreen adherence and performance of other preventive health behaviors (eg, flossing, helmet use) and examine predictors of sunscreen adherence. Analyses were repeated in non-Hispanic black, Hispanic, and non-Hispanic white subgroups. Results: Five thousand one hundred nineteen (23.4%) children almost always used sunscreen, 5.9% of non-Hispanic blacks (n = 1748), 23.7% of Hispanics (n = 1802), and 44.8% of non-Hispanic whites (n = 1249). Performing other preventive health behaviors was associated with higher odds of sunscreen adherence (all P \u3c.001), with the greatest association with flossing teeth (odds ratio = 2.41, 95% confidence interval = 1.86-3.13, P \u3c.001). Factors for lower odds of sunscreen adherence included being male and non-Hispanic black or Hispanic and having lower socioeconomic status. School-based sun-safety education and involvement in team sports were not significant factors. Conclusion: Our data confirm low use of sun protection among fifth-graders. Future research should explore how public health success in increasing prevalence of other preventive health behaviors may be applied to enhance sun protection messages. Identifying risk factors for poor adherence enables providers to target patients who need more education. Improving educational policies and content in schools may be an effective way to address sun safety

Factors to Predict Positive Results of Gonadotropin Releasing Hormone Stimulation Test in Girls with Suspected Precocious Puberty

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty