Optimising pacemaker therapy and medical therapy in pacemaker patients for heart failure: protocol for the OPT-PACE randomised controlled trial

Introduction: Permanent artificial pacemaker implantation is a safe and effective treatment for bradycardia and is associated with extended longevity and improved quality of life. However, the most common long-term complication of standard pacemaker therapy is pacemaker-associated heart failure. Pacemaker follow-up is potentially an opportunity to screen for heart failure to assess and optimise patient devices and medical therapy. Methods and analysis: The study is a multicentre, phase-3 randomised trial. The 1200 participants will be people who have a permanent pacemaker for bradycardia for at least 12 months, randomly assigned to undergo a transthoracic echocardiogram with their pacemaker check, thereby tailoring their management directed by left ventricular function or the pacemaker check alone, continuing with routine follow-up. The primary outcome measure is time to all-cause mortality or heart failure hospitalisation. Secondary outcomes include external validation of our risk stratification model to predict onset of heart failure and quality of life assessment. Ethics and Dissemination: The trial design and protocol have received national ethical approval (12/YH/0487). The results of this randomised trial will be published in international peer-reviewed journals, communicated to healthcare professionals and patient involvement groups and highlighted using social media campaigns. Trial registration number: NCT01819662

Circadian Consequence of Socio-Sexual Interactions in Fruit Flies Drosophila melanogaster

In fruit flies Drosophila melanogaster, courtship is an elaborate ritual comprising chasing, dancing and singing by males to lure females for mating. Courtship interactions peak in the night and heterosexual couples display enhanced nighttime activity. What we do not know is if such socio-sexual interactions (SSI) leave long-lasting after-effects on circadian clock(s). Here we report the results of our study aimed at examining the after-effects of SSI (as a result of co-habitation of males and females in groups) between males and females on their circadian locomotor activity rhythm. Males undergo reduction in the evening activity peak and lengthening of circadian period, while females show a decrease in overall activity. Such after-effects, at least in males, require functional circadian clocks during SSI as loss-of-function clock mutants and wild type flies interacting under continuous light (LL), do not display them. Interestingly, males with electrically silenced Pigment Dispersing Factor (PDF)-positive ventral lateral (LNv) clock neurons continue to show SSI mediated reduction in evening activity peak, suggesting that the LNv clock neurons are dispensable for SSI mediated after-effects on locomotor activity rhythm. Such after-effects in females may not be clock-dependent because clock manipulated females with prior exposure to males show decrease in overall activity, more or less similar to rhythmic wild type females. The expression of SSI mediated after-effects requires a functional olfactory system in males because males with compromised olfactory ability do not display them. These results suggest that SSI causes male-specific, long-lasting changes in the circadian clocks of Drosophila, which requires the presence of functional clocks and intact olfactory ability in males

Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: prevalence and characterization

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID). Anxiety and social withdrawal are considered core features of the FXS phenotype, yet there is limited diagnostic evidence of the prevalence of formal anxiety disorders in FXS. This study assessed the prevalence of anxiety disorders in a sample of 58 males and 39 females with FXS (ages 5.0–33.3 years). Participants’ parents completed the Anxiety Disorders Interview Schedule (ADIS-IV), a clinical interview based on DSM-IV criteria, and the Anxiety Depression and Mood Scale (ADAMS), a psychiatric disorders screening instrument normed in ID. We conducted cognitive (IQ) and autism (AUT) assessments and surveyed medication use. Despite a high rate of psychopharmacological treatment, 86.2% of males and 76.9% of females met criteria for an anxiety disorder, with social phobia and specific phobia the most commonly diagnosed. Proband status, gender, and IQ were not significantly related to any anxiety disorders, however significantly higher rates of a few anxiety disorders were found in older age and AUT groups. Significant correlations between ADIS diagnoses and ADAMS scores provided cross-validation of instruments, indicating that the ADIS is suitable for use in FXS. A greater percentage of our sample met criteria for most anxiety disorders than has been reported in other ID groups or the general population. The rate of anxiety compared to general ID suggests that the FMR1 full mutation confers an especially high risk for these disorders, regardless of factors commonly associated with FXS clinical involvement. A thorough clinical assessment and treatment of anxiety should be included in the FXS standard of care

Accessory gland as a site for prothoracicotropic hormone controlled ecdysone synthesis in adult male insects

Insect steroid hormones (ecdysteroids) are important for female reproduction in many insect species and are required for the initiation and coordination of vital developmental processes. Ecdysteroids are also important for adult male physiology and behavior, but their exact function and site of synthesis remains unclear, although previous studies suggest that the reproductive system may be their source. We have examined expression profiles of the ecdysteroidogenic Halloween genes, during development and in adults of the flour beetle Tribolium castaneum. Genes required for the biosynthesis of ecdysone (E), the precursor of the molting hormone 20-hydroxyecdysone (20E), are expressed in the tubular accessory glands (TAGs) of adult males. In contrast, expression of the gene encoding the enzyme mediating 20E synthesis was detected in the ovaries of females. Further, Spookiest (Spot), an enzyme presumably required for endowing tissues with competence to produce ecdysteroids, is male specific and predominantly expressed in the TAGs. We also show that prothoracicotropic hormone (PTTH), a regulator of E synthesis during larval development, regulates ecdysteroid levels in the adult stage in Drosophila melanogaster and the gene for its receptor Torso seems to be expressed specifically in the accessory glands of males. The composite results suggest strongly that the accessory glands of adult male insects are the main source of E, but not 20E. The finding of a possible male-specific source of E raises the possibility that E and 20E have sex-specific roles analogous to the vertebrate sex steroids, where males produce primarily testosterone, the precursor of estradiol. Furthermore this study provides the first evidence that PTTH regulates ecdysteroid synthesis in the adult stage and could explain the original finding that some adult insects are a rich source of PTTH

Bioaccumulation and Toxicity of Organic Chemicals in Terrestrial Invertebrates

Terrestrial invertebrates are key components in ecosystems, with crucial roles in soil structure, functioning, and ecosystem services. The present chapter covers how terrestrial invertebrates are impacted by organic chemicals, focusing on up-to-date information regarding bioavailability, exposure routes and general concepts on bioaccumulation, toxicity, and existing models. Terrestrial invertebrates are exposed to organic chemicals through different routes, which are dependent on both the organismal traits and nature of exposure, including chemical properties and media characteristics. Bioaccumulation and toxicity data for several groups of organic chemicals are presented and discussed, attempting to cover plant protection products (herbicides, insecticides, fungicides, and molluscicides), veterinary and human pharmaceuticals, polycyclic aromatic compounds, polychlorinated biphenyls, flame retardants, and personal care products. Chemical mixtures are also discussed bearing in mind that chemicals appear simultaneously in the environment. The biomagnification of organic chemicals is considered in light of the consumption of terrestrial invertebrates as novel feed and food sources. This chapter highlights how science has contributed with data from the last 5 years, providing evidence on bioavailability, bioaccumulation, and toxicity derived from exposure to organic chemicals, including insights into the main challenges and shortcomings to extrapolate results to real exposure scenarios

The effects of colemanite and ulexite additives on the geotechnical index properties of bentonite and sand-bentonite mixtures

© 2018, Springer Nature Switzerland AG.Bentonite-sand mixtures are generally used in landfill liners. The properties of bentonite-sand mixtures should not change by time. For that reason, it is necessary to improve the properties of bentonites and bentonite-sand mixtures. In this study, the boron minerals namely colemanite and ulexite were added to the bentonite and bentonite-sand mixtures in order to improve their consistency limits and compaction characteristics. The boron additives were added 5, 10, 15, 20% to the bentonite and the liquid limits and plastic limits were determined. The boron additives were added to the 10% bentonite + 90% sand and 20% bentonite + 80% sand mixtures and compaction characteristics were determined in the presence of colemanite and ulexite. As the ulexite ratio increased, the liquid limit value decreased, but as the colemanite ratio increased, the liquid limit value increased. The 20% ulexite and colemanite addition, decreased the liquid limit values of bentonite 8.4% and 13.8%, respectively. As the concentration of boron additives increase, the optimum water content of the mixtures increases. This effect is more significant at 10% bentonite + 90% sand. As ulexite and colemanite content increases the maximum dry unit weight of the bentonite-sand mixtures increase. The effect is more significant at the colemanite additive and at 10% bentonite + 90% sand mixture