Emmanouil Magiorkinis

The global spread of hepatitis C virus 1a and 1b: a phylodynamic and phylogeographic analysis.

Using phylodynamic and phylogeographic methods, Angelos Hatzakis and colleagues find that the global spread of Hepatitis C virus coincided with widespread use of transfused blood and with the expansion of intravenous drug use.

Dating the origin and dispersal of hepatitis B virus infection in humans and primates.

The origin of hepatitis B virus (HBV) infection in humans and other primates remains largely unresolved. Understanding the origin of HBV is crucial because it provides a framework for studying the burden, and subsequently the evolution, of HBV pathogenicity with respect to changes in human population size and life expectancy. To investigate this controversy we examined the relationship between HBV phylogeny and genetic diversity of modern humans, investigated the timescale of global HBV dispersal, and tested the hypothesis of HBV‐human co‐divergence. We find that the global distribution of HBV genotypes and subgenotypes are consistent with the major prehistoric modern human migrations. We calibrate the HBV molecular clock using the divergence times of different indigenous human populations based on archaeological and genetic evidence and show that HBV jumped into humans around 33,600 years ago; 95% higher posterior density (HPD): 22,000‐47,100 years ago (estimated substitution rate: 2.2 × 10−6; 95% HPD: 1.5‐3.0 × 10−6 substitutions/site/year). This coincides with the origin of modern non‐African humans. Crucially, the most pronounced increase in the HBV pandemic correlates with the global population increase over the last 5,000 years. We also show that the non‐human HBV clades in orangutans and gibbons resulted from cross‐species transmission events from humans that occurred no earlier than 6,100 years ago. Conclusion: Our study provides, for the first time, an estimated timescale for the HBV epidemic that closely coincides with dates of human dispersals, supporting the hypothesis that HBV has been co‐expanding and co‐migrating with human populations for the last 40,000 years. (HEPATOLOGY 2013)

Increasing Prevalence of HIV-1 Subtype A in Greece: Estimating Epidemic History and Origin

BACKGROUND In North America and Europe, human immunodeficiency virus (HIV)-1 infection has typically been dominated by subtype B transmission. More recently, however, non-B subtypes have been increasingly reported in Europe. METHODS We analyzed 1158 HIV-1-infected individuals in Greece by DNA sequencing and phylogenetic analyses of protease and partial reverse-transcriptase regions. RESULTS We found that the prevalence of non-B subtypes has increased over time and that this significant trend can be mainly attributed to subtype A, which eventually surpassed subtype B in prevalence in 2004 (42% and 33%, respectively). Multivariate analysis revealed that the year of HIV diagnosis was independently associated with subtype A infection (odds ratio for being infected with subtype A for a 10-year increase in the time period of diagnosis, 2.09 [95% confidence interval, 1.36-3.24]; P<.001). Phylogenetic analysis revealed that the subtype A epidemic in Greece is the result of a single founder event. The date of the most recent common ancestor of the subtype A in Greece was estimated to be 1977.9 (95% highest posterior density interval, 1973.7-1981.9). CONCLUSIONS Subtype A circulates among the long-term residents of Greece. This is in contrast to the situation in most European countries, in which infection with non-B genetic forms is associated either with being an immigrant or heterosexual or with intravenous drug use.

Hallmarks in the history of epilepsy: Epilepsy in antiquity

The purpose of this article is to highlight the hallmarks of epilepsy as a disease and symptom during antiquity and especially during Ancient Greece and Rome. A thorough study of texts, medical books, and reports along with a review of the available literature in PubMed was undertaken. Observations on epilepsy date back to the medical texts of the Assyrians and Babylonians, almost 2000 years B.C. Considered initially as a divine malady or demonic possession, epilepsy was demythologized by the Father of Medicine, Hippocrates, who was the first to set in dispute its divine origin. Physicians in the early post-Hippocratic era did not make any important contribution regarding the mechanisms of epileptic convulsions, but contributed mainly in the field of nosology and systemization of symptoms.

Molecular characterization of occult hepatitis B cases in Greek blood donors

The use of sensitive nucleic acid testing for hepatitis B virus in blood donors revealed a number of HBV DNA(+) cases among HBsAg(−) donors, a status known as occult HBV infection. The purpose of this study was the serological and molecular characterization of occult HBV infection in Greek blood donors. A prospective study was undertaken in order to identify occult HBV infection cases in blood donors. As part of the routine screening of blood donations in Greece, blood units were screened individually by a multiplex HIV‐1/HCV/HBV nucleic acid assay. Initially reactive samples were retested with discriminatory assays. HBV DNA(+)/HBsAg(−) samples were tested further for HBV serological markers and HBV DNA was quantified by real‐time PCR. Molecular characterization was performed by sequencing the envelope and polymerase genes of HBV. Preliminary screening revealed 21 occult cases with the following patterns: anti‐HBc only: 7 donors, anti‐HBc/anti‐HBs: 7 donors, anti‐HBc/anti‐HBe: 5 donors, anti‐HBc/anti‐HBs/anti‐HBe: 2 donors. In all cases, the HBV DNA load was <351 IU/ml. Sequencing was successful in 10 donors (classified within genotype D) revealing several amino acid substitutions related to diagnostic escape and antiviral resistance. HBsAg diagnostic failure and low viral replication in occult HBV infection carriers could possibly be attributed to multiple changes in envelope and polymerase regions, respectively. J. Med. Virol. 81:815–825, 2009.

Integrating Phylodynamics and Epidemiology to Estimate Transmission Diversity in Viral Epidemics

The epidemiology of chronic viral infections, such as those caused by Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV), is affected by the risk group structure of the infected population. Risk groups are defined by each of their members having acquired infection through a specific behavior. However, risk group definitions say little about the transmission potential of each infected individual. Variation in the number of secondary infections is extremely difficult to estimate for HCV and HIV but crucial in the design of efficient control interventions. Here we describe a novel method that combines epidemiological and population genetic approaches to estimate the variation in transmissibility of rapidly-evolving viral epidemics. We evaluate this method using a nationwide HCV epidemic and for the first time co-estimate viral generation times and superspreading events from a combination of molecular and epidemiological data. We anticipate that this integrated approach will form the basis of powerful tools for describing the transmission dynamics of chronic viral diseases, and for evaluating control strategies directed against them.

Fine-needle aspiration (FNA) biopsy: historical aspects.

This study aims to present the origins and the historical evolution of fine-needle aspiration biopsy and to also underline its importance in the history of modern cytology. The article focuses on the advances made in the 20th century that have led to the modern techniques associated with the procedure. The authors conducted a thorough review of early reports on needle biopsy, particularly those published during 19th and 20th century, examining in brief also the origins of the needle biopsy. The first report on the use of needle puncture is referred in early writings of Arab medicine. In the early 20th century, Martin and Ellis are considered to be the founders of modern needle aspiration techniques. The German doctor Mannheim was the first to publish reports suggesting the use of fine needles with a small gauge. The establishment and world-wide expansion of FNA should be attributed to the representatives of the Swedish School of Cytopathology. The school embraced FNA in the second half of the 20th century while serving as a training ground for doctors around the world. The history of needle biopsy spans ten centuries. However, the development and establishment of the technique in its modern form took place primarily during the twentieth century. Today, FNA is considered an important cytologic technique with sufficient diagnostic accuracy, especially when applied in cases of lung and prostate cancer.

Phylogenetic Reconstruction of a Known HIV-1 CRF04_cpx Transmission Network Using Maximum Likelihood and Bayesian Methods

The CRF04_cpx strains of HIV-1 accounts for approximately 2–10% of the infected population in Greece, across different transmission risk groups. CRF04_cpx was the lineage documented in an HIV-1 transmission network in Thessalonica, northern Greece. Most of the transmissions occurred through unprotected heterosexual contacts between 1989 and 1993. Blood samples were available for six patients, obtained 6–10 years later, except for one patient sampled in 1991. Our objective was to examine whether the transmission history is compatible with the evolutionary tree of the virus, in partial gag, partial env, and partial gag+env. The inferred phylogenetic tree obtained using maximum likelihood and Bayesian methods in partial gag+env was much closer to the transmission tree than that using either env or gag separately. Our findings suggest that the epidemiological relationships among patients who have been infected by a common source correspond almost exactly to the evolutionary trees of the virus, given that enough phylogenetic signal is present in the alignment. Moreover, we found evidence that recombination is not the most parsimonious explanation for the phylogenetic incongruence between gag and env. For patients with known infection dates, the estimated dates of the coalescent events obtained using molecular clock calculations based on a newly developed Bayesian method in gag + env were in agreement with the actual infection dates.

Mutations associated with genotypic resistance to antiretroviral therapy in treatment naïve HIV-1 infected patients in Greece.

The widespread use of antiviral drugs against HIV has increased the prevalence of HIV-1 resistant strains among naïve individuals due to transmission of resistant strains. The purpose of this study was to investigate the presence of HIV-1 strains harboring resistance mutations in naïve patients in Greece. Blood samples were collected from 25 individuals. The DNA sequence of protease and partial reverse transcriptase regions (codons 41-223) were obtained by direct sequencing. Our results showed the absence of any primary resistance mutations in the study population. However, we were able to identify high prevalence of sequence polymorphisms at positions in reverse transcriptase region associated mainly with resistance to NNRTIs. Moreover, in protease region several secondary mutations were detected, suggesting the higher genetic variability of this region. The clinical significance of the polymorphisms associated with reduced susceptibility to NNRTIs remains to be clarified.

A brief history of apoptosis: from ancient to modern times.

The purpose of this article is to sketch the evolution of research on cell death and apoptosis from ancient to modern times. Early use of the term can be found in the texts of Hippocrates, whereas the first description of apoptotic cell death should be attributed to Rudolf Virchow. Glucksman, in 1951, rediscovered and reviewed cell death during embryonic development. Milestone discoveries in biology in the 20th century led biologists to the discovery of apoptotic mechanisms, soon after the definition of apoptosis by Kerr in 1972. The involvement of programmed cell death in the pathogenesis of various diseases and abnormalities gave a huge boost in the research of apoptosis. Nowadays, research is focused on the elucidation of apoptotic mechanisms, since the possibility of modulating cell death by targeting specific factors involved in the whole process could be the key for cure of diseases such as cancer, Alzheimer’s disease, and AIDS.