Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Male body size and breeding tubercles are both linked to intra-sexual dominance and reproductive success in the minnow

Male dominance hierarchies are usually linked to relative body size and to weapon size, that is, to determinants of fighting ability. Secondary sexual characters that are not directly used as weapons could still be linked to dominance if they reveal determination or overall health and vigour and hence, indirectly, fighting ability. We studied the mating behaviour of the minnow, Phoxinus phoxinus, a cyprinid fish in which males develop breeding tubercles during the spawning season. The function of these breeding tubercles is still not clear. Using microsatellite markers, we determined male reproductive success under controlled conditions. The minnows were territorial and quickly established a dominance hierarchy at the beginning of the spawning season. Dominance was strongly and positively linked to fertilization success. Although body size and number of breeding tubercles were not significantly correlated in our sample, both large males and males with many breeding tubercles were more dominant and achieved higher fertilization success than small males or males with few tubercles. We found multimale fertilization in most clutches, suggesting that sperm competition is important in this species. Females showed behaviour that may be linked to spawning decision, that is, male dominance might not be the only determinant of male reproductive success in minnows

Toxoplasmosis during pregnancy and infancy. A new approach for Switzerland.

In recent years it has become evident that screening for and treatment of acute toxoplasmosis during pregnancy may have no measurable impact on vertical transmission and neonatal morbidity and mortality. A broad lack of evidence with regard to many aspects of congenital toxoplasmosis has been recognised in a common European initiative (EUROTOXO) which reviewed several thousand published papers on the subject of toxoplasmosis during pregnancy and childhood. It was therefore clear that the strategies currently implemented in our country would, on closer inspection, no longer withstand the claim for evidence-based procedures. The arguments and call for a change of paradigm in Switzerland which follow here are the result of a national consensus-finding process involving experts from various specialities, including gynaecology/obstetrics, paediatrics/neonatology, infectiology, ophthalmology and laboratory medicine, together with representatives of the public health authorities.