Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype

INTRODUCTION: Esmirtazapine is evaluated as a novel drug for treatment of insomnia. PURPOSE: The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control. METHODS: Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine. RESULTS: Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected. CONCLUSION: It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving

Microbiological contamination of cubicle curtains in an out-patient podiatry clinic

<p>Abstract</p> <p>Background</p> <p>Exposure to potential pathogens on contaminated healthcare garments and curtains can occur through direct or indirect contact. This study aimed to identify the microorganisms present on podiatry clinic curtains and measure the contamination pre and post a standard hospital laundry process.</p> <p>Method</p> <p>Baseline swabs were taken to determine colony counts present on cubical curtains before laundering. Curtains were swabbed again immediately after, one and three weeks post laundering. Total colony counts were calculated and compared to baseline, with identification of micro-organisms.</p> <p>Results</p> <p>Total colony counts increased very slightly by 3% immediately after laundry, which was not statistically significant, and declined significantly (p = 0.0002) by 56% one-week post laundry. Three weeks post laundry colony counts had increased by 16%; although clinically relevant, this was not statistically significant. The two most frequent microorganisms present throughout were <it>Coagulase Negative Staphylococcus </it>and <it>Micrococcus </it>species. Laundering was not completely effective, as both species demonstrated no significant change following laundry.</p> <p>Conclusion</p> <p>This work suggests current laundry procedures may not be 100% effective in killing all microorganisms found on curtains, although a delayed decrease in total colony counts was evident. Cubicle curtains may act as a reservoir for microorganisms creating potential for cross contamination. This highlights the need for additional cleaning methods to decrease the risk of cross infection and the importance of maintaining good hand hygiene.</p

Plexiform neurofibroma of the submandibular gland in patient with von Recklinghausen's disease

Plexiform neurofibroma of the submandibular gland is an extremely rare tumor. Herein, we report a case of plexiform neurofibroma in a patient with a von Recklinghausen's disease (NF-1) who presented with a submandibular mass mimicking a submandibular gland tumor. Complete surgical excision provides the best treatment and final diagnosis. A neurofibroma should be considered in the differential diagnosis for submandibular mass

Empowerment and Parent Gain as Mediators and Moderators of Distress in Mothers of Children with Autism Spectrum Disorders

Mothers of children with Autism Spectrum Disorders (ASD) experience considerable amounts of distress and experiences of crisis. The Family Adjustment and Adaptation Response model provides a theory for understanding the experience of distress and family crisis in families, and the purpose of the present study was to examine experiences of distress in mothers of individuals with ASD using this framework. We specifically investigated how parent empowerment and positive gain are related to their experiences of distress, whether as mediators or as moderators of child aggression. Participants included 156 mothers of children with ASD ranging in age from 4 – 21 years. Mothers completed an online survey of demographics, problem behaviors, family empowerment, positive gain, and distress. We conducted path analyses of multiple mediation and moderation. Results indicated that greater child problem behavior was related to less parent empowerment, which was related to greater maternal distress, supporting empowerment as a partial mediator. At the same time, greater child aggression was not related to maternal distress in mothers who report high rates of positive gain, suggesting that parent gain functions as a moderator. The implications for how and when clinicians intervene with families of children with ASD are discussed

The UNC-45 Chaperone Is Critical for Establishing Myosin-Based Myofibrillar Organization and Cardiac Contractility in the Drosophila Heart Model

UNC-45 is a UCS (UNC-45/CRO1/She4P) class chaperone necessary for myosin folding and/or accumulation, but its requirement for maintaining cardiac contractility has not been explored. Given the prevalence of myosin mutations in eliciting cardiomyopathy, chaperones like UNC-45 are likely to be equally critical in provoking or modulating myosin-associated cardiomyopathy. Here, we used the Drosophila heart model to examine its role in cardiac physiology, in conjunction with RNAi-mediated gene silencing specifically in the heart in vivo. Analysis of cardiac physiology was carried out using high-speed video recording in conjunction with movement analysis algorithms. unc-45 knockdown resulted in severely compromised cardiac function in adults as evidenced by prolonged diastolic and systolic intervals, and increased incidence of arrhythmias and extreme dilation; the latter was accompanied by a significant reduction in muscle contractility. Structural analysis showed reduced myofibrils, myofibrillar disarray, and greatly decreased cardiac myosin accumulation. Cardiac unc-45 silencing also dramatically reduced life-span. In contrast, third instar larval and young pupal hearts showed mild cardiac abnormalities, as severe cardiac defects only developed during metamorphosis. Furthermore, cardiac unc-45 silencing in the adult heart (after metamorphosis) led to less severe phenotypes. This suggests that UNC-45 is mostly required for myosin accumulation/folding during remodeling of the forming adult heart. The cardiac defects, myosin deficit and decreased life-span in flies upon heart-specific unc-45 knockdown were significantly rescued by UNC-45 over-expression. Our results are the first to demonstrate a cardiac-specific requirement of a chaperone in Drosophila, suggestive of a critical role of UNC-45 in cardiomyopathies, including those associated with unfolded proteins in the failing human heart. The dilated cardiomyopathy phenotype associated with UNC-45 deficiency is mimicked by myosin knockdown suggesting that UNC-45 plays a crucial role in stabilizing myosin and possibly preventing human cardiomyopathies associated with functional deficiencies of myosin

Age, period, and cohort analysis of regular dental care behavior and edentulism: A marginal approach

<p>Abstract</p> <p>Background</p> <p>To analyze the regular dental care behavior and prevalence of edentulism in adult Danes, reported in sequential cross-sectional oral health surveys by the application of a marginal approach to consider the possible clustering effect of birth cohorts.</p> <p>Methods</p> <p>Data from four sequential cross-sectional surveys of non-institutionalized Danes conducted from 1975-2005 comprising 4330 respondents aged 15+ years in 9 birth cohorts were analyzed. The key study variables were seeking dental care on an annual basis (ADC) and edentulism. For the analysis of ADC, survey year, age, gender, socio-economic status (SES) group, denture-wearing, and school dental care (SDC) during childhood were considered. For the analysis of edentulism, only respondents aged 35+ years were included. Survey year, age, gender, SES group, ADC, and SDC during childhood were considered as the independent factors. To take into account the clustering effect of birth cohorts, marginal logistic regressions with an independent correlation structure in generalized estimating equations (GEE) were carried out, with PROC GENMOD in SAS software.</p> <p>Results</p> <p>The overall proportion of people seeking ADC increased from 58.8% in 1975 to 86.7% in 2005, while for respondents aged 35 years or older, the overall prevalence of edentulism (35+ years) decreased from 36.4% in 1975 to 5.0% in 2005. Females, respondents in the higher SES group, in more recent survey years, with no denture, and receiving SDC in all grades during childhood were associated with higher probability of seeking ADC regularly (<it>P </it>< 0.05). The interaction of SDC and age (<it>P </it>< 0.0001) was significant. The probabilities of seeking ADC were even higher among subjects with SDC in all grades and aged 45 years or older. Females, older age group, respondents in earlier survey years, not seeking ADC, lower SES group, and not receiving SDC in all grades were associated with higher probability of being edentulous (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>With the use of GEE, the potential clustering effect of birth cohorts in sequential cross-sectional oral health survey data could be appropriately considered. The success of Danish dental health policy was demonstrated by a continued increase of regular dental visiting habits and tooth retention in adults because school dental care was provided to Danes in their childhood.</p