Michalodimitrakis E

Multiple Advantageous Amino Acid Variants in the NAT2 Gene in Human Populations

Background Genetic variation at NAT2 has been long recognized as the cause of differential ability to metabolize a wide variety of drugs of therapeutic use. Here, we explore the pattern of genetic variation in 12 human populations that significantly extend the geographic range and resolution of previous surveys, to test the hypothesis that different dietary regimens and lifestyles may explain inter-population differences in NAT2 variation. Methodology/Principal Findings The entire coding region was resequenced in 98 subjects and six polymorphic positions were genotyped in 150 additional subjects. A single previously undescribed variant was found (34T>C; 12Y>H). Several aspects of the data do not fit the expectations of a neutral model, as assessed by coalescent simulations. Tajimas D is positive in all populations, indicating an excess of intermediate alleles. The level of between-population differentiation is low, and is mainly accounted for by the proportion of fast vs. slow acetylators. However, haplotype frequencies significantly differ across groups of populations with different subsistence. Conclusions/Significance Data on the structure of haplotypes and their frequencies are compatible with a model in which slow-causing variants were present in widely dispersed populations before major shifts to pastoralism and/or agriculture. In this model, slow-causing mutations gained a selective advantage in populations shifting from hunting-gathering to pastoralism/agriculture. We suggest the diminished dietary availability of folates resulting from the nutritional shift, as the possible cause of the fitness increase associated to haplotypes carrying mutations that reduce enzymatic activity.

Patterns of male‐specific inter‐population divergence in Europe, West Asia and North Africa

We typed 1801 males from 55 locations for the Y‐specific binary markers YAP, DYZ3, SRY10831 and the (CA)n microsatellites YCAII and DYS413. Phylogenetic relationships of chromosomes with the same binary haplotype were condensed in seven large one‐step networks, which accounted for 95% of all chromosomes. Their coalescence ages were estimated based on microsatellite diversity. The three largest and oldest networks undergo sharp frequency changes in three areas. The more recent network 3.1A clearly discriminates between Western and Eastern European populations. Pairwise Fst showed an overall increment with increasing geographic distance but with a slope greatly reduced when compared to previous reports. By sectioning the entire data set according to geographic and linguistic criteria, we found higher Fst‐on‐distance slopes within Europe than in West Asia or across the two continents.

Physicians’ liability in interventional radiology and endovascular therapy

INTRODUCTION/OBJECTIVE Modern practice in Radiology has rapidly changed over the last decades incorporating invasive techniques. Additionally, litigation in medical practice has arisen as an important issue. This article aims to highlight issues related to malpractice in interventional radiology and endovascular therapy in order to point out the importance of the written informed consent. METHODS AND MATERIAL Search of relevant literature from the Pubmed. RESULTS The role of radiologist has been greatly transformed over the last decades. He is not only entitled to participate in the diagnosis but also he undertakes therapeutic procedures, either alone or as a member of a team. Thus the radiologist is now more exposed to actions that maximize litigation risk. Adequate communication and a written consent form seem to be mandatory before any invasive radiological procedure. Patient should know in detail the benefits and the risks of the scheduled procedure and whether the proposed therapy is a new form of treatment or part of a randomized trial. DISCUSSIONS AND CONCLUSION Interventional radiologist or physician is exposed to high litigation risk. This certainly requires an urgent adaptation of his practice and attitude to the new reality. Written patients informed consent remains an integral part of the communication between physicians and patients, and importantly is offering professional protection along these lines.

Spatially Explicit Models to Investigate Geographic Patterns in the Distribution of Forensic STRs: Application to the North-Eastern Mediterranean

Human forensic STRs used for individual identification have been reported to have little power for inter-population analyses. Several methods have been developed which incorporate information on the spatial distribution of individuals to arrive at a description of the arrangement of diversity. We genotyped at 16 forensic STRs a large population sample obtained from many locations in Italy, Greece and Turkey, i.e. three countries crucial to the understanding of discontinuities at the European/Asian junction and the genetic legacy of ancient migrations, but seldom represented together in previous studies. Using spatial PCA on the full dataset, we detected patterns of population affinities in the area. Additionally, we devised objective criteria to reduce the overall complexity into reduced datasets. Independent spatially explicit methods applied to these latter datasets converged in showing that the extraction of information on long- to medium-range geographical trends and structuring from the overall diversity is possible. All analyses returned the picture of a background clinal variation, with regional discontinuities captured by each of the reduced datasets. Several aspects of our results are confirmed on external STR datasets and replicate those of genome-wide SNP typings. High levels of gene flow were inferred within the main continental areas by coalescent simulations. These results are promising from a microevolutionary perspective, in view of the fast pace at which forensic data are being accumulated for many locales. It is foreseeable that this will allow the exploitation of an invaluable genotypic resource, assembled for other (forensic) purposes, to clarify important aspects in the formation of local gene pools.

Liability in prenatal ultrasound screening

Over the last two decades there has been a serious increase in claims for medical negligence. It has been estimated that the rate of new claims against hospital doctors in the UK is as high as 10.5%1. Additionally, claims in obstetrics particularly have accounted for 30% of the total negligence claims against health authority physicians during the 1980s. In a district of the UK in which 2500 women were giving birth annually, almost 50% of the total budget of a health care authority had to be spent on legal awards and expenses2,3. Reference should be made to the fact that the average retirement age for obstetricians is 59 as opposed to the usual retirement age of 65 for other medical professionals4. The threat of malpractice lawsuits changes the practice style of many physicians leading to defensive medicine, and the rising tide of medical negligence actions is destroying good patient–doctor relationships and driving promising junior doctors away from specialties which have become high-risk for negligence claims5. There is no doubt that there is increasing consumer awareness of the possibility of bringing a legal action, following media coverage of cases involving consumer rights and improved consumer education. Patients now expect diagnostic tests and screening to be carried out, while many tests, which are now available, were not even possible 20 years ago. To avoid litigation and complaints, it is essential that the nature of the available treatments and the risks and benefits involved be explained to patients. The incorporation of ultrasonography in the prenatal diagnostic process and the involvement of obstetricians in the performance of this test in daily practice has resulted in obstetricians being exposed to a higher litigation risk. Missing a fetal anomaly on ultrasonic investigation is the most common type of litigation involving ultrasound. Other causes include the failure to communicate the results of ultrasonic investigation in a timely fashion, and failure to perform the ultrasonic study for anomalies especially when there is clinical indication to do so6. The aim of this Editorial is to highlight important legal issues related to prenatal diagnosis using ultrasonography, which the practising obstetrician should bear in mind. Additionally, the importance of clear communication between physicians and patients and the value of informed consent is emphasized.

Forensic pathology on the threshold of the 21st century and the need for harmonization of current practice and training: the Greek concept.

Our era is characterized by the globalization of crime. This poses to all democratic countries the urgent need to reform their systems to fight crime more effectively. Forensic sciences remain an integral part of the system against crime. This scientific field can also offer valuable knowledge regarding the causes of death. From an epidemiologic point of view, this can result in better organization of prevention measures for the best interests of the community. Harmonization and collaboration in the operation of the various forensic systems that presently exist around the world is of paramount importance if effective prevention of crime and other causes of death in contemporary reality is to be achieved. In addition, revision of training in forensic pathology and forensic sciences is essential if harmonizing the forensic systems is to succeed. This report provides an overview of the wide variation in the operation of forensic systems and training. Emphasis is given to the importance of their harmonization, and an attempt is made to explore principles that may contribute along these lines. Finally, the authors provide proposals for revision of the training system in forensic pathology in Greece.

Euthanasia in Greece, Hippocrates' birthplace

Euthanasia is a controversial issue that has attracted heated debate over the last two decades. Cultural, traditional and religious considerations contribute in the forming of individual and social attitudes. Active, voluntary euthanasia is not legally accepted except in Netherlands and Australia. However even in these countries several ethical and legal issues have emerged from the application of euthanasia. In fact medical physicians stand in the frontline of the debate as they are those who should decide to act or not to act when euthanasia is requested by a patient. In Greece the vast majority of people are against euthanasia as a result of tradition and religion The influence of the Hippocratic philosophy and the humanistic teaching of the Christian Orthodox Church have made that doctors and people look at the issue of euthanasia with aversion. In addition, the law considers any such action as homicide and therefore as punishable. However, in Greece as in any democratic country, individual variations exist and the issue attracts increasing debate. This article aims to discuss the legal ramifications of euthanasia within the context of the Greek legal order and to present the religious and ethical considerations that influence the social attitude concerning to euthanasia in Greece.

Enlarging the gene-geography of Europe and the Mediterranean area to STR loci of common forensic use: longitudinal and latitudinal frequency gradients

Abstract Background: Tetranucleotide Short Tandem Repeats (STRs) for human identification and common use in forensic cases have recently been used to address the population genetics of the North-Eastern Mediterranean area. However, to gain confidence in the inferences made using STRs, this kind of analysis should be challenged with changes in three main aspects of the data, i.e. the sizes of the samples, their distance across space and the genetic background from which they are drawn. Aim: To test the resilience of the gradients previously detected in the North-Eastern Mediterranean to the enlargement of the surveyed area and population set, using revised data. Subjects and methods: STR genotype profiles were obtained from a publicly available database (PopAffilietor databank) and a dataset was assembled including >7000 subjects from the Arabian Peninsula to Scandinavia, genotyped at eight loci. Spatial principal component analysis (sPCA) was applied and the frequency maps of the nine alleles which contributed most strongly to sPC1 were examined in detail. Results: By far the greatest part of diversity was summarised by a single spatial principal component (sPC1), oriented along a SouthEast-to-NorthWest axis. The alleles with the top 5% squared loadings were TH01(9.3), D19S433(14), TH01(6), D19S433(15.2), FGA(20), FGA(24), D3S1358(14), FGA(21) and D2S1338(19). These results confirm a clinal pattern over the whole range for at least four loci (TH01, D19S433, FGA, D3S1358). Conclusions: Four of the eight STR loci (or even alleles) considered here can reproducibly capture continental arrangements of diversity. This would, in principle, allow for the exploitation of forensic data to clarify important aspects in the formation of local gene pools.

Bioethics and the Determination of Personhood

Abstract In todays technological world, humanity continuously surpasses the limits set by previous achievements. Although evidence of such progress exists in several fields of study, one clearly sees this in the medical and biotechnological fields. Despite the countless opportunities for longer, more productive lives, medicine and science have regressed in their conception of the human person. In an effort to overcome any moral and legal ramifications that research and medical practices may entail, physicians and researchers have come to reduce personhood to only a matter of biological qualities and functioning. This essay attempts to show, first of all, the classical Christian understanding of the person, currently held by the Orthodox Church. It then looks at three fields of bioethical discussion; namely, abortion, brain death, and human embryonic cloning, and shows how each issue reduces the human person to his or her biological components. The essay concludes by suggesting a return to an understanding of personhood based on personal and communal levels of relationships.

Confidentiality Governing Surgical Research Practice

Healthy subjects or patients volunteering to participate in trials expect that their privacy and autonomy will be protected. The aim of this article is to highlight issues related to confidentiality governing surgical research practice. A search of the current relevant literature was undertaken. Consent to the disclosure of any information should be sought wherever practicable, but disclosures should be kept to the minimum necessary. The data should be made anonymous where unidentifiable data serve the purpose. Where the previously described actions are not practicable for various reasons, data may be disclosed for research, provided participants have been given information about access to their records and about their right to object. Personal information may only be disclosed without individual’s consent when it is for the protection of the public interest, but this has proved too ambiguous a rubric to be useful without proper clarification. Hampering of noncommercial medical research should also be avoided, as it may cause serious damage to public health. Confidentiality in research is an important issue in the protection of the participants’ rights to privacy and autonomy, and it should be considered in the design of each study. Breach of confidentiality is legally justifiable for the sake of the public interest, but proper clarification of the law is required in order to avoid hampering noncommercial medical research that is vital for the public health.