Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS).

BACKGROUND: Pharmacogenomics describes the link between gene variations (polymorphisms) and drug responses. In view of the implementation of precision medicine in personalized healthcare, pharmacogenetic tests have recently been introduced in the clinical practice. However, the translational aspects of such tests have been limited due to the lack of robust population-based evidence. MATERIALS: In this paper we present a novel pharmacogenetic panel (iDNA Genomics-PGx-CNS or PGx-CNS), consisting of 24 single nucleotide polymorphisms (SNPs) on 13 genes involved in the signaling or/and the metabolism of 28 approved drugs currently administered to treat diseases of the Central Nervous System (CNS). We have tested the PGx-CNS panel on 501 patient-derived DNA samples from a southeastern European population and applied biostatistical analyses on the pharmacogenetic associations involving drug selection, dosing and the risk of adverse drug events (ADEs). RESULTS: Results reveal the occurrences of each SNP in the sample and a strong correlation with the European population. Nonlinear principal component analysis strongly indicates co-occurrences of certain variants. The metabolization efficiency (poor, intermediate, extensive, ultra-rapid) and the frequency of clinical useful pharmacogenetic, associations in the population (drug relevance), are also described, along with four exemplar clinical cases illustrating the strong potential of the PGx-CNS panel, as a companion diagnostic assay. It is noted that pharmacogenetic associations involving copy number variations (CNVs) or the HLA gene were not included in this analysis. CONCLUSIONS: Overall, results illustrate that the PGx-CNS panel is a valuable tool supporting therapeutic medical decisions, urging its broad clinical implementation.

Assessing the effect of manual physical activity on proximal hand phalanges using Hellenistic and modern skeletal samples from Greece.

In humans, physical activity is an important regulator of bone size. Furthermore, hand bones have been proposed as a potential avenue for assessing patterns of manual activity. However, there are very few studies presenting a metric comparison of proximal hand phalanges among different populations. Moreover, an osteoarchaeological approach to the manual activities performed by an ancient population is yet to be made. In this framework, this study aims at assessing and interpreting the metric variation in these bones between a documented modern Greek sample (20th century) and a Hellenistic sample from Demetrias (3rd-1st century BCE), in terms of size and sexual dimorphism. Ancient males were significantly larger than females for ten phalangeal measurements out of 35. Even though the degree of sexual dimorphism was lower in the Hellenistic material (the maximum sexual dimorphism observed - 12.46%) than in modern sample (the maximum observed - 21.19%), the ranking of rays and bone parts by sexual dimorphism was similar in both populations. No metric difference was observed between modern and ancient males, whereas ancient females were larger than modern females in seven dimensions (the maximum variation observed was 11.58%), which involved the bases and midshafts of phalanges. Given that these dimensions are affected by the degree of muscular recruitment for the formation of various hand grips, it is suggested that ancient females were involved in manual activities of greater grasping variance than modern females. Indeed, the historical and archaeological sources suggest that sexual distribution of labour in the Hellenistic society seems to explain the differences estimated between the sexes and the two populations under study.

Osteometric sex determination using proximal foot phalanges from a documented human skeletal collection.

Diagnosing sex is vital for developing biological profiles from human skeletal remains. For that purpose, osteometric evaluation of bone size has proven to be usually effective. The present study investigates the degree of sexual dimorphism in proximal foot phalanges from a documented human skeletal collection, known as the Athens collection. Furthermore, it utilizes the data for the development of sex-discriminant formulas in Greek population. The material used consists of 749 proximal foot phalanges (left and right), which belong to 174 adult individuals (91 males and 83 females) that lived during the 20(th) century. The degree of sexual dimorphism reached as high as 16.76 %, with the left side demonstrating higher sexual dimorphism. The 1(st) proximal foot phalanges are proven to be the most sexually dimorphic among the bones of the sample. The minimum sexual dimorphism observed was in the maximum lengths of phalanges, whereas the most sexually dimorphic measurement was the medio-lateral width at midshaft. The discriminant functions developed provide classification accuracies that ranged between 77.1 % and 90.9 % for left and between 72.2 % and 86.6 % for right proximal foot phalanges. The results of this study suggest that proximal foot phalanges are useful for sex determination in Greek population.