Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia

INTRODUCTION: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. AIMS: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. METHODS: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. RESULTS: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. CONCLUSION: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia

Ultra low background Micromegas detectors for BabyIAXO solar axion search

The International AXion Observatory (IAXO) is a large scale axion helioscope that will look for axions and axion-like particles produced in the Sun with unprecedented sensitivity. BabyIAXO is an intermediate experimental stage that will be hosted at DESY (Germany) and that will test all IAXO subsystems serving as a prototype for IAXO but at the same time as a fully-fledged helioscope with potential for discovery. One of the crucial components of the project is the ultra-low background X-ray detectors that will image the X-ray photons produced by axion conversion in the experiment. The baseline detection technology for this purpose are Micromegas (Microbulk) detectors. We will show the quest and the strategy to attain the very challenging levels of background targeted for BabyIAXO that need a multi-approach strategy coming from ground measurements, screening campaigns of components of the detector, underground measurements, background models, in-situ background measurements as well as powerful rejection algorithms. First results from the commissioning of the BabyIAXO prototype will be shown.Comment: 4 pages, 2 figures, submitted for the proceedings of the International Conference on Micro Pattern Gaseous Detectors, December 2022, Israe

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.

Fine-Scale Mapping of Natural Variation in Fly Fecundity Identifies Neuronal Domain of Expression and Function of an Aquaporin

To gain insight into the molecular genetic basis of standing variation in fitness related traits, we identify a novel factor that regulates the molecular and physiological basis of natural variation in female Drosophila melanogaster fecundity. Genetic variation in female fecundity in flies derived from a wild orchard population is heritable and largely independent of other measured life history traits. We map a portion of this variation to a single QTL and then use deficiency mapping to further refine this QTL to 5 candidate genes. Ubiquitous expression of RNAi against only one of these genes, an aquaporin encoded by Drip, reduces fecundity. Within our mapping population Drip mRNA level in the head, but not other tissues, is positively correlated with fecundity. We localize Drip expression to a small population of corazonin producing neurons located in the dorsolateral posterior compartments of the protocerebrum. Expression of Drip–RNAi using both the pan-neuronal ELAV-Gal4 and the Crz-Gal4 drivers reduces fecundity. Low-fecundity RILs have decreased Crz expression and increased expression of pale, the enzyme encoding the rate-limiting step in the production of dopamine, a modulator of insect life histories. Taken together these data suggest that natural variation in Drip expression in the corazonin producing neurons contributes to standing variation in fitness by altering the concentration of two neurohormones

Shedding Light on the Galaxy Luminosity Function

From as early as the 1930s, astronomers have tried to quantify the statistical nature of the evolution and large-scale structure of galaxies by studying their luminosity distribution as a function of redshift - known as the galaxy luminosity function (LF). Accurately constructing the LF remains a popular and yet tricky pursuit in modern observational cosmology where the presence of observational selection effects due to e.g. detection thresholds in apparent magnitude, colour, surface brightness or some combination thereof can render any given galaxy survey incomplete and thus introduce bias into the LF. Over the last seventy years there have been numerous sophisticated statistical approaches devised to tackle these issues; all have advantages -- but not one is perfect. This review takes a broad historical look at the key statistical tools that have been developed over this period, discussing their relative merits and highlighting any significant extensions and modifications. In addition, the more generalised methods that have emerged within the last few years are examined. These methods propose a more rigorous statistical framework within which to determine the LF compared to some of the more traditional methods. I also look at how photometric redshift estimations are being incorporated into the LF methodology as well as considering the construction of bivariate LFs. Finally, I review the ongoing development of completeness estimators which test some of the fundamental assumptions going into LF estimators and can be powerful probes of any residual systematic effects inherent magnitude-redshift data.Comment: 95 pages, 23 figures, 3 tables. Now published in The Astronomy & Astrophysics Review. This version: bring in line with A&AR format requirements, also minor typo corrections made, additional citations and higher rez images adde

Incidence and mortality of ischemic stroke subtypes in Joinville, Brazil: a population-based study

Aims To measure the incidence and mortality rates of ischemic stroke (IS) subtypes in Joinville, Brazil. Methods All first-ever IS patients that occurred in Joinville from January 2005 to December 2006 were identified. The IS subtypes were classified by the TOAST criteria, and the patients were followed-up for one year after IS onset. Results The age-adjusted incidence per 100,000 inhabitants was 26 (17-39) for large-artery atherosclerosis (LAA), 17 (11-27) for cardioembolic (CE), 29 (20-41) for small vessel occlusion (SVO), 2 (0.6-7) for stroke of other determined etiology (OTH) and 30 (20-43) for stroke of undetermined etiology (UND). The 1-year mortality rate per 100,000 inhabitants was 5 (2-11) for LAA, 6 (3-13) for CE, 1 (0.1-6) for SVO, 0.2 (0-0.9) for OTH and 9 (4-17) for UND. Conclusion In the population of Joinville, the incidences of IS subtypes were similar to those found in other populations. These findings highlight the importance of better detection and control of atherosclerotic risk factors

ICAR: endoscopic skull‐base surgery

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