Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10−14) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.

Objective: The present study aims to investigate the influence of presence and shape of cervical lesions on biomechanical behavior of mandibular first premolar, subjected to two types of occlusal loading using three-dimensional (3D) finite element method (FEM). Materials and Methods: 3D models of the mandibular premolar are created from a micro computed tomography X-ray image: model of sound mandibular premolar, model with the wedge-shaped cervical lesion (V lesion), and model with saucer-shaped cervical lesion (U lesion). By FEM, straining of the tooth tissues under functional and nonfunctional occlusal loading of 200 (N) is analyzed. For the analysis, the following software was used: CTAn program 1.10 and ANSYS Workbench (version 14.0). The results are presented in von Mises stress. Results: Values of calculated stress in all tooth structures are higher under nonfunctional occlusal loading, while the functional loading is resulted in homogeneous stress distribution. Nonfunctional load in the cervical area of sound tooth model as well as in the sub-superficial layer of the enamel resulted with a significant stress (over 50 [MPa]). The highest stress concentration on models with lesions is noticed on the apex of the V-shaped lesion, while stress in saucer U lesion is significantly lower and distributed over wider area. Conclusion: The type of the occlusal teeth loading has the biggest influence on cervical stress intensity. Geometric shape of the existing lesion is very important in the distribution of internal stress. Compared to the U-shaped lesions, V-shaped lesions show significantly higher stress concentrations under load. Exposure to stress would lead to its progression.

In this paper the age structure and the ageing population process in Bosnia and Herzegovina in the second half of the 20th century and the beginning of the 21st century is analyzed. The main reasons that caused changes in the age composition of the population and the population ageing in Bosnia and Herzegovina have been researched. The main causes of the population ageing in Bosnia and Herzegovina in the second half of the 20th century were primarily trends in fertility rates and secondarily trends in mortality rates. The economic growth of Bosnia and Herzegovina after World War II conditioned changes in the economic and educational structure of the population and with that the changes in the natural increase rates and migration balance. The war was the main cause of negative demographic changes in Bosnia and Herzegovina in the period from 1992 to 1995, and the post-war adverse socioeconomic, political and other circumstances have been the cause of negative demographic trends after 1995. The aim of this paper is to determine the level of population ageing in Bosnia and Herzegovina and the consequences this process could have on the demographic future of this country.

Mensur Vrcić , Ratko Pavlović , Sid Solaković, Erol Kovačević 1 and Ensar Abazović Faculty of Sports and Physical Education, University of Sarajevo, Bosnia and Herzegovina Faculty of Physical Education and Sports, University of East Sarajevo, Bosnia and Herzegovina 3 Clinic for Vascular Surgery, Clinical Center in Sarajevo, Bosnia and Herzegovina 4 Faculty of Kinesiology, University of Split, Croatia