School-based drug prevention programs: a review of what works

This article examines the effectiveness of school-based drug prevention programs in preventing illicit drug use. Our article reports the results of a systematic review of the evaluation literature to answer three fundamental questions: (1) do school-based drug prevention programs reduce rates of illicit drug use? (2) what features are characteristic of effective programs? and (3) do these effective program characteristics differ from those identified as effective in reviews of school-based drug prevention of licit substance use (such as alcohol and tobacco)? Using systematic review and meta-analytic techniques, we identify the characteristics of schoolbased drug prevention programs that have a significant and beneficial impact on ameliorating illicit substance use (i.e., narcotics) among young people. Successful intervention programs typically involve high levels of interactivity, time-intensity, and universal approaches that are delivered in the middle school years. These program characteristics aligned with many of the effective program elements found in previous reviews exploring the impact of school-based drug prevention on licit drug use. Contrary to these past reviews, however, our analysis suggests that the inclusion of booster sessions and multifaceted drug prevention programs have little impact on preventing illicit drug use among school-aged children. Limitations of the current review and policy implications are discussed.

Anion induced displacement studies in naphthalene diimide containing interpenetrated and interlocked structures

This article describes investigations into the development of supramolecular systems capable of sensing anions through either displacement type assays or molecular motion. An electron deficient naphthalene diimide thread and electron rich isophthalamide naphthohydroquinone macrocycle was shown to form a coloured pseudorotaxane assembly. Investigations into the ability of such interpenetrated systems to sense anions colorimetrically were undertaken. Anion complexation to the isophthalamide group of the macrocycle causes displacement of the naphthodiimide thread resulting in the loss of colour. The enhanced mechanically bonded binding strength between the naphthodiimide axle and the naphthohydroquinone groups of the macrocycle wheel in the corresponding rotaxane structure however, was found to negate the anion induced displacement process.

Association between infant feeding patterns and diarrhoeal and respiratory illness: a cohort study in Chittagong, Bangladesh

Background In developing countries, infectious diseases such as diarrhoea and acute respiratory infections are the main cause of mortality and morbidity in infants aged less than one year. The importance of exclusive breastfeeding in the prevention of infectious diseases during infancy is well known. Although breastfeeding is almost universal in Bangladesh, the rates of exclusive breastfeeding remain low. This cohort study was designed to compare the prevalence of diarrhoea and acute respiratory infection (ARI) in infants according to their breastfeeding status in a prospective cohort of infants from birth to six months of age. Methods A total of 351 pregnant women were recruited in the Anowara subdistrict of Chittagong. Breastfeeding practices and the 7-day prevalence of diarrhoea and ARI were recorded at monthly home visits. Prevalences were compared using chi-squared tests and logistic regression. Results A total of 272 mother-infant pairs completed the study to six months. Infants who were exclusively breastfed for six months had a significantly lower 7-day prevalence of diarrhoea [AOR for lack of EBF = 2.50 (95%CI 1.10, 5.69), p = 0.03] and a significantly lower 7-day prevalence of ARI [AOR for lack of EBF = 2.31 (95%CI 1.33, 4.00), p < 0.01] than infants who were not exclusively breastfed. However, when the association between patterns of infant feeding (exclusive, predominant and partial breastfeeding) and illness was investigated in more detail, there was no significant difference in the prevalence of diarrhoea between exclusively [6.6% (95% CI 2.8, 10.4)] and predominantly breastfed infants [3.7% (95% CI 0.09, 18.3), (p = 0.56)]. Partially breastfed infants had a higher prevalence of diarrhoea than the others [19.2% (95% CI 10.4, 27.9), (p = 0.01)]. Similarly, although there was a large difference in prevalence in acute respiratory illness between exclusively [54.2% (95%CI 46.6, 61.8)] and predominantly breastfed infants [70.4% (95%CI 53.2, 87.6)] there was no significant difference in the prevalence (p = 0.17). Conclusion The findings suggest that exclusive or predominant breastfeeding can reduce rates of morbidity significantly in this region of rural Bangladesh.

Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence

Abstract Opioid drugs, such as morphine, are among the most effective analgesics available. However, their utility for the treatment of chronic pain is limited by side effects including tolerance and dependence. Morphine acts primarily through the mu-opioid receptor (MOP-R) , which is also a target of endogenous opioids. However, unlike endogenous ligands, morphine fails to promote substantial receptor endocytosis both in vitro, and in vivo. Receptor endocytosis serves at least two important functions in signal transduction. First, desensitization and endocytosis act as an "off" switch by uncoupling receptors from G protein. Second, endocytosis functions as an "on" switch, resensitizing receptors by recycling them to the plasma membrane. Thus, both the off and on function of the MOP-R are altered in response to morphine compared to endogenous ligands. To examine whether the low degree of endocytosis induced by morphine contributes to tolerance and dependence, we generated a knockin mouse that expresses a mutant MOP-R that undergoes morphine-induced endocytosis. Morphine remains an excellent antinociceptive agent in these mice. Importantly, these mice display substantially reduced antinociceptive tolerance and physical dependence. These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence