Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients.

BACKGROUND: Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes. METHODS: The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients. RESULTS: Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p = 0.013) and use of other antipsychotics (p = 0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p = 0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p = 0.029). CONCLUSION: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.

Tendons and ligaments of the Rangifer tarandus metapodial and hoof.

Rangifer tarandus, the northern species including both reindeer and caribou, is a pillar of northern ecosystems and the lives of northern peoples. As the only domestic cervid, reindeer are important not only to the herders and hunters who presently interact with them, but also to zooarchaeologists and palaeontologists tracing their histories. Unfortunately, limited anatomical information on Rangifer tarandus muscles is available beyond descriptions of the large muscle groups. The lower limb and hoof in particular is poorly documented. This is problematic, as this important body part has the potential to be informative in zooarchaeological analyses of habitual activity, especially in regards to historical animal health, movement, and habitual activity. Better understanding of the hoof can additionally be useful to herders and veterinarians seeking to provide veterinary care for living animals. This study has used dissections and comparisons of the reindeer hoof with other domestic ungulates to document both the common and unique structures in Rangifer tarandus hooves, including the presence and attachment points of these structures. As these structures have proved unique, especially in regards to the dewclaw, it is important that other ungulates not be used exclusively in the analysis of Rangifer tarandus remains.