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Purpose To estimate the association between Attention-Deficit/Hyperactivity Disorder (ADHD) in children in preschool and primary school, and prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) by timing and duration. Methods This study was based on the Norwegian Mother, Father and Child Cohort Study linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR) and the Norwegian Prescription Database (NorPD). NSAID exposure was identified by maternal self-report in pregnancy. Child diagnosis of ADHD was obtained from NPR and NorPD. Symptoms of ADHD at age 5 years were measured using Conners' Parent Rating Scale-Revised, where higher scores correspond to more symptoms. To account for time-varying exposure and confounders, marginal structural models were fitted to estimate hazard ratios and mean difference in z-scores. Results The analyses on ADHD diagnosis and ADHD symptoms included 56 340 and 34 961 children respectively. Children exposed to NSAIDs prenatally had no increased risk of ADHD diagnosis (first trimester: HR 1.12, 95% CI 0.86;1.45, second trimester: HR 0.98, 95% CI 0.69;1.38, third trimester: HR 0.68, 95% CI 0.31; 1.46) or ADHD symptoms (first trimester: standardized mean difference 0.03, 95% CI -0.03;0.09, second trimester: standardized mean difference 0.03, 95% CI -0.04;0.11, third trimester: standardized mean difference 0.11, 95% CI -0.03; 0.25). There was no duration-response relationship for either outcome. Conclusion Though non-differential misclassification of the exposure may have attenuated results, these findings are reassuring and suggest no substantially increased risk of ADHD diagnosis or symptoms in children prenatally exposed to NSAIDs, regardless of timing or duration.

PURPOSE An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age. METHODS The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17-18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales. RESULTS A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89-1.22) and OR = 1.10 (95%CI: 0.95-1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence. CONCLUSION The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John Wiley & Sons, Ltd.

Benzodiazepine-like drugs (z-hypnotics) are the most commonly used drugs for treatment of insomnia in Norway. Z-hypnotics are recommended for short-term treatment not exceeding 4 weeks. We aimed to study the use of z-hypnotics in the adult population in Norway with focus on recurrent use in new users, treatment intensity and co-medication with benzodiazepines and opioids in long-term users. Data were obtained from the Norwegian Prescription Database. New users in 2009 were followed through 2013. Recurrent z-hypnotic use was defined as new fillings at least once in each of the four 365-day follow-up periods. Age groups of 18-39, 40-64 and 65+ years were analysed separately for men and women. In 2013, 354,571 (8.9%) of the population filled at least one prescription of z-hypnotics and the prevalence was relatively stable over time. Among the 92,911 new users of z-hypnotics in 2009, 13,996 (16.8%) received z-hypnotics all four 365-day periods of follow-up. In these long-term recurrent users, the treatment intensity was high already the second year, with mean annual amounts of 199 and 169 DDDs per patient in men and women, respectively. The interquartile differences were greatest in the youngest age group. 27.9% of the long-term recurrent users of z-hypnotics used benzodiazepines the fourth year and 33.9% used opioids. The proportions with co-medication increased with level of z-hypnotic treatment intensity. Overall, many z-hypnotic users had medicines dispensed for longer periods than recommended, and co-medications with drugs that may reinforce the central depressing and intoxicating effects were common.

Objectives To estimate the association between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and motor development in children considering the effect of maternal symptoms of anxiety and depression before, during and after pregnancy. Design Population-based prospective pregnancy cohort study. Setting The Norwegian Mother and Child Cohort study (MoBa) (1999–2008). Population A total of 51 404 singleton pregnancies. Methods Self-reported use of SSRIs was collected for the 6 months before pregnancy and prospectively during pregnancy. We used ordinal logistic regression as the statistical analysis. Main outcome measures Motor development was assessed by maternal reports of fine and gross motor development at child age 3 years by items from the Ages and Stages Questionnaire (ASQ). The maternal ASQ scores were compared with data from a MoBa sub-study where clinicians assessed motor development with the Gross and Fine Motor Mullen scales of early learning. Results In all 381 women (0.7%) reported use of SSRIs during pregnancy, of these 159 reported on at least two questionnaires (prolonged use). Prolonged SSRI exposure was associated with a delay in fine motor development, odds ratio 1.42 (95% CI 1.07–1.87) compared with no SSRI exposure, after adjusting for symptoms of anxiety and depression before and during pregnancy. Severity of maternal depression seemed to explain the association only partially. Stratifying on depression after pregnancy had no impact on the estimated effect of SSRIs. Conclusions Prolonged prenatal exposure to SSRIs was weakly associated with a delayed motor development at age 3 years, but not to the extent that the delay was of clinical importance. Tweetable abstract Long-term prenatal SSRI exposure is weakly associated with delayed motor development independent of depression.

We investigated 197 anaerobic isolates recovered from blood cultures in the period 2009-2013. The isolates included were Bacteroides spp., Clostridium spp., Prevotella spp., Fusobacterium spp. and Gram-positive anaerobic cocci (GPAC). Identification results by MALDI-TOF MS were compared to those obtained by 16S rRNA sequencing, and the MICs of benzylpenicillin, clindamycin, piperacillin-tazobactam, meropenem and metronidazole were determined by Etests. The MALDI-TOF MS correctly identified 94.9% of the anaerobes to the genus level, and 86.8% to the species level, with errors mainly among the non-fragilis Bacteroides spp. and GPAC. About 73.3% of the isolates were non-susceptible to penicillin, mainly due to high resistance rates in the Bacteroides spp. (99.2%) and Prevotella spp. (69.2%). About 18.5% of the isolates were clindamycin resistant. Piperacillin-tazobactam had an excellent activity against all anaerobes except the non-fragilis Bacteroides spp., of which 43.8% were non-susceptible. The clinical significance of such a high resistance rate is unclear. Meropenem and metronidazole were the most active antibiotics, with 96.9% and 97.9% of the isolates being susceptible.

Objective To examine the association between maternal use of selective serotonin reuptake inhibitors (SSRI) in pregnancy and language competence in their children at age three taking into account maternal symptoms of anxiety and depression. Design Population-based prospective pregnancy cohort study. Setting The Norwegian Mother and Child Cohort Study; recruited pregnant women from 1999 through 2008. Population 45 266 women with 51 748 singleton pregnancies. Methods The association between short- or long-term use of SSRI during pregnancy and language competence in the child was investigated using multinomial logistic regression with three outcome categories: long, complicated sentences, fairly complete sentences and language delay. Main outcome measures Children's language competence at age three measured by maternal report on a validated language grammar scale. Results Women reported use of SSRI in 386 (0.7%) pregnancies. Of these, 161 (42%) reported long-term use. Compared with children whose mothers took no SSRI, using the best language category as the reference, adjusted relative risk ratios (RRR) of having fairly complete sentences were 1.21 (95% CI 0.85–1.72) and 2.28 (1.54–3.38) for short- and long-term SSRI use, respectively. The adjusted RRRs of language delay were 0.86 (0.42–1.76) and 2.30 (1.21–4.37). Symptoms of anxiety and depression in pregnancy were independently related to language delay, adjusted RRR 1.25 (1.03–1.50) and 1.83 (1.40–2.40) for short- and long-term symptoms, respectively. Conclusions Prolonged use of SSRI during pregnancy was associated with lower language competence in children by age three independently of depression. Having symptoms of depression throughout pregnancy had an independent effect.

Purpose An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age. Methods The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17–18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales. Results A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89–1.22) and OR = 1.10 (95%CI: 0.95–1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence. Conclusion The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John Wiley & Sons, Ltd. This is the peer reviewed version of the following article: Skovlund, E., Handal, M., Selmer, R., Brandlistuen, R. E., and Skurtveit, S. (2017) Language competence and communication skills in 3-year-old children after prenatal exposure to analgesic opioids. Pharmacoepidemiol Drug Saf, 26: 625–634., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/pds.4170/abstract . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Locked until 07 february 2018 due to copyright restrictions

Aims This study describes the use of prescribed drugs among women in opioid maintenance treatment (OMT) prior to, and during, pregnancy. Design This cohort study was based on data from two nationwide databases: the Medical Birth Registry of Norway and the Norwegian Prescription Database. Setting Norway, 2004–2010. Participants OMT drugs were dispensed to 138 women with 159 pregnancies. Measurements All prescription drugs dispensed to women in OMT three months prior to, and during, pregnancy were studied. Amounts of benzodiazepines, z-hypnotics and opioid analgesics dispensed during pregnancy were studied and bivariate analysis was used to study neonatal outcomes of OMT pregnancies with and without such co-medication. Findings The prevalence of prescription drug use by pregnant OMT women was high both during the three-month period prior to (69%), and during (81%), pregnancy. The proportion of pregnant women that was dispensed anti-infectives (48%) and/or drugs acting on the nervous system (45%) during any time in pregnancy was especially high. In 21%, 15% and 13% of the pregnancies the women were dispensed benzodiazepine anxiolytics, opioid analgesics or benzodiazepine hypnotics respectively. Only 5% of the OMT women were dispensed antidepressants. Malformations were significantly more common among children born to mothers in OMT that received co-medication with opioids, benzodiazepines or z-hypnotics. Conclusions A higher proportion of women in opioid maintenance treatment in Norway use prescription drugs prior to, and during, pregnancy than pregnant women in the general population. Co-medication with drugs with abuse potential may increase the risk of adverse pregnancy outcomes and this need to be further addressed.

Statins are known to inhibit growth of a number of cancer cells, but their mechanism of action is not well established. In this study, human prostate adenocarcinoma PC-3 and breast adenocarcinoma MCF-7 cell lines were used as models to investigate the mechanism of action of atorvastatin, one of the statins. Atorvastatin was found to induce apoptosis in PC-3 cells at a concentration of 1 μM, and in MCF-7 cells at 50 μM. Initial survey of possible pathway using various pathway-specific luciferase reporter assays showed that atorvastatin-activated antioxidant response element (ARE), suggesting oxidative stress pathway may play a role in atorvastatin-induced apoptosis in both cell lines. Among the antioxidant response genes, heme oxygenase-1 (HO-1) was significantly up-regulated by atorvastatin. Pre-incubation of the cells with geranylgeranyl pyrophosphate blocked atorvastatin-induced apoptosis, but not up-regulation of HO-1, suggesting that atorvastatin-induced apoptosis is dependent on GTPase activity and up-regulation of HO-1 gene is not. Six ARE-like elements (designated StRE1 [stress response element] through StRE6) are present in the HO-1 promoter. Atorvastatin was able to activate all of the elements. Because these StRE sites are present in clusters in HO-1 promoter, up-regulation of HO-1 by atorvastatin may involve multiple StRE sites. The role of HO-1 in atorvastatin-induced apoptosis in PC-3 and MCF-7 remains to be studied.

Osteoporosis ("secondary" osteoporosis) and avascular necrosis (AVN) of the femoral head are well-known adverse effects of corticosteroid therapy. Statins have been reputed to increase bone strength and bone density. In this study, we evaluated the effect of atorvastatin calcium on the flexural properties (3-point bending strength and modulus) of corticosteroid (methylprednisolone acetate) treated rabbit femurs and tibias. Our study hypothesis was that the use of statins would counteract the loss of bone strength caused by corticosteroid treatment. The 40 rabbits were divided into 5 groups: control, corticosteroid alone and corticosteroid combined with oral doses of atorvastatin calcium (2, 10, or 20 mg/day). A daily oral dose of atorvastatin calcium treatment for 70 days weakened the long bones of methylprednisolone acetate treated rabbits irrespective of the dosage (2, 10, or 20 mg). Cortical bone strength was assessed using the 3-point bending test at the end of the study period. A daily oral dose of atorvastatin calcium did not attenuate the loss of cortical bone strength caused by corticosteroid treatment in rabbits. It appeared to decrease that bone strength. If these results hold true in humans, they would have wide applicability given the frequent combined use of corticosteroids and statins in many patients.

Background The use of prescribed opioids for chronic non-cancer pain is increasing in many countries. It is, therefore, important to investigate predictors for repeated use of opioids in young non-cancer patients. Objective The aim of this study was to prospectively evaluate adolescent smoking and its association with repeated use of prescription opioids in adolescents/young adults without cancer. Methods The study population consisted of 11,809 15–16 year old participants (86% participation rate) in the Norwegian Youth Health Surveys carried out in 2000–2003. The exposure variable, self reported smoking status, was registered in the youth surveys along with potential confounders. Repeated use of opioids, defined as 4+ prescriptions recorded in the nationwide Norwegian Prescription Database during 2004–2008, was used as outcome measure. Results Among the participants included in our study, 161 had redeemed 4+ prescriptions for opioids. Daily adolescent smoking was associated with repeated use of opioids with an adjusted OR of 2.2 (95% CI 1.3–3.5). Conclusions Daily smoking at 15–16 years of age was associated with increased risk of incident repeated use of prescribed opioids later in life. Our study suggests that smoking dependence in adolescents may predict longer lasting and/or higher levels of opioid use. Copyright © 2010 John Wiley & Sons, Ltd.

Entamoeba histolytica is known for its extraordinary capacity to destroy human tissues, leading to invasive diseases such as ulcerative colitis or extra-intestinal abscesses. In order to identify the virulence factors of this parasite phenotypes and proteomes of two recently identified genetically related cell lines (A and B), derived from the laboratory E. histolytica isolate HM-1:IMSS, were compared. Both cell lines are indistinguishable on the basis of highly polymorphic tandem repeat DNA sequences. However, cell line A is incapable to induce liver abscesses in experimentally infected rodents, whereas cell line B provokes considerable abscesses. Phenotypic analyses revealed increased hemolytic activity, lower growth rate, smaller cell size, reduced cysteine peptidase activity and lower resistance to nitric oxide stress for cell line A. In contrast, no differences between the two cell lines were found for cytopathic activity, erythrophagocytosis, digestion of erythrocytes or resistance to complement, hydrogen peroxide and superoxide radical anions. Proteomic comparison by 2-D DIGE followed by MS, identified a total of 21 proteins with higher abundance in cell line A and ten proteins with higher abundance in cell line B. Remarkably, three differentially up-regulated antioxidants were exclusively found in the pathogenic cell line B. Notably, only for two differentially regulated proteins, namely a Fe-hydrogenase and a C2 domain protein, a similar type was found at the level of transcription. Summarized, a defined set of different proteins could be identified between cell lines A and B. These molecules may have an important role in amoeba pathogenicity.

Over the last 10-15 yr antibiotic resistance has increased in the oral microflora. The beta-lactam antibiotics, i.e., penicillins and cephalosporins, are the most frequently used antimicrobial agents. Unfortunately, the efficiency of these drugs is increasingly being challenged by the emergence of resistant bacteria, which is mainly due to their production of beta-lactamases. In this paper, mechanisms of antibiotic resistance are reviewed, with emphasis on beta-lactamases. This review also discusses how the presence of beta-lactamases in oral microorganisms may affect the treatment of oral diseases. Dentists can influence the emerging global crisis of antibiotic resistance by carefully evaluating the indications for antibiotic treatment. General guidelines for when and how to use antibiotics in dentistry are reviewed.

Faculty should learn to use constructive criticism to improve teaching, as we do in the case of research.

Morphine-6beta-glucuronide is a major metabolite of morphine with potent analgesic actions. To explore the importance of this opiate when administered as a drug by its own or in morphine action, we studied the locomotor activity response to morphine and morphine-6-glucuronide in drug-naive C57 BL/6JBom mice. The effects of administration of the two opiates on a battery of 7 different locomotor activities were studied and compared to saline controls. A dose of 20 micromol/kg morphine-6-glucuronide resulted in more locomotion than the same dose of morphine, while at higher doses (up to 120 micromol/kg), similar increases for most locomotor behaviours were recorded for both drugs. Pretreatment with naltrindole indicated that the delta-receptors play an equivalent but minor role in mediating both morphine-6-glucuronide and morphine hyperlocomotion. Administration of high naltrexone doses (10 mg/kg) completely abolished the locomotor stimulation induced by both opiates. However, at intermediate naltrexone doses of 0.25 and 0.5 mg/kg, morphine-induced behaviours was completely inhibited while morphine-6-glucuronide induced behaviours demonstrated partial resistance to naltrexone inhibition. The mu1-specific receptor antagonist naloxonazine caused 75% reduction of morphine induced behaviours and only 50% inhibition of morphine-6-glucuronide induced behaviors. Taken together our observations indicated general similarity but also marked differences between morphine and morphine-6-glucuronide with respect to opiate receptors mediating the locomotor stimulatory effect.

79 taxa of desmids belongig to 17 genera were observed in 17 samples collected from several parts in Basrah district, South Iraq. 3 genera viz. Actinotaenium, Docidium and Spondylosum, and 41 taxa are new records for Iraqi waters. Distribution of taxa in the area studied as well as in the whole country (when available) are given. Some slight morphological variations in desmids were observed due to the alkaline nature of water.