The Epigenetic Controller Lysine-Specific Demethylase 1 (LSD1) Regulates the Outcome of Hepatitis C Viral Infection.

Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. The host epigenetic changes induced by HCV lead to metabolic dysfunction and malignant transformation. Lysine-specific demethylase 1 (LSD1) is an epigenetic controller of critical cellular functions that are essential for HCV propagation. We investigated the putative role of LSD1 in the establishment of HCV infection using genetic engineering and pharmacological inhibition to alter endogenous LSD1 levels. We demonstrated for the first time that HCV replication was inhibited in LSD1-overexpressing cells, while specific HCV proteins differentially fine-tuned endogenous LSD1 expression levels. Electroporation of the full-length HCV genome and subgenomic replicons in LSD1 overexpression enhanced translation and partially restored HCV replication, suggesting that HCV might be inhibited by LSD1 during the early steps of infection. Conversely, the inhibition of LSD1, followed by HCV infection in vitro, increased viral replication. LSD1 was shown to participate in an intriguing antiviral mechanism, where it activates endolysosomal interferon-induced transmembrane protein 3 (IFITM3) via demethylation, leading endocytosed HCV virions to degradation. Our study proposes that HCV-mediated LSD1 oscillations over countless viral life cycles throughout chronic HCV infection may promote epigenetic changes related to HCV-induced hepatocarcinogenesis.

Trends in referral patterns to presurgical evaluation at a European reference center.

PURPOSE: To determine if growing evidence for epilepsy surgery as an early treatment option is reflected in the decrease of latencies between epilepsy onset and referral for presurgical evaluation METHODS: Retrospective analysis of latencies in 1646 patients (children and adults) from the time of epilepsy diagnosis to first presurgical workup in the period from 1999 to 2019 based on electronic patient charts at a tertiary epilepsy center. Time spans 1999-2009 and 2010-2019, prior to and following the ILAE definition of pharmacoresistance, and the role of etiological factors were assessed. RESULTS: Over the whole period, the mean latency between diagnosis and a presurgical workup was 15.3 y. There was a significant reduction in the latencies between the periods 1999-2009 (16.9 y) and 2010-2019 (13.4 y), (p < 0.0001). In a linear regression analysis, the latency decreased by 2.6 months/year from 17.4 in 1999 to 13.1 y in 2019 (p < 0.001). Subgroup analyses showed significant decreases in latency to presurgical evaluation in patients with hippocampal sclerosis from 24.4 to 19.5 y, in malformations of cortical development from 16.4 to 13.2 y, and in nonlesional patients from 18.1 to 12.8 y, in contrast to patients with MR evidence for brain tumors with similar latencies across time (10.5 vs. 9.5 y, n.s.). CONCLUSION: The reduction of the time span to a first presurgical evaluation was highly significant over time, yet moderate in its degree. Overall, the aim of early diagnostic evaluation for epilepsy surgery options after established pharmacoresistance was only achieved for a minority of patients.

Overview of Mpox Outbreak in Greece in 2022-2023: Is It Over?

In May 2022, for the first time, multiple cases of mpox were reported in several non-endemic countries. The first ever case of the disease in Greece was confirmed on 8 June 2022, and a total of 88 cases were reported in the country until the end of April 2023. A multidisciplinary response team was established by the Greek National Public Health Organization (EODY) to monitor and manage the situation. EODY's emergency response focused on enhanced surveillance, laboratory testing, contact tracing, medical countermeasures, and the education of health care providers and the public. Even though management of cases was considered successful and the risk from the disease was downgraded, sporadic cases continue to occur. Here, we provide epidemiological and laboratory features of the reported cases to depict the course of the disease notification rate. Our results suggest that measures for raising awareness as well as vaccination of high-risk groups of the population should be continued.

Effects of cenobamate on cognitive performance of epilepsy patients.

PURPOSE: Cenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance. METHOD: Efficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions. RESULTS: The median CNB dose at T1 was 125 mg/day (range: 50 - 250 mg/day). Most patients received 2-3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p < .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency. CONCLUSION: Most of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

Hepatitis Viruses Control Host Immune Responses by Modifying the Exosomal Biogenesis Pathway and Cargo.

The development of smart immune evasion mechanisms is crucial for the establishment of acute and chronic viral hepatitis. Hepatitis is a major health problem worldwide arising from different causes, such as pathogens, metabolic disorders, and xenotoxins, with the five hepatitis viruses A, B, C, D, and E (HAV, HBV, HCV, HDV, and HEV) representing the majority of the cases. Most of the hepatitis viruses are considered enveloped. Recently, it was reported that the non-enveloped HAV and HEV are, in reality, quasi-enveloped viruses exploiting exosomal-like biogenesis mechanisms for budding. Regardless, all hepatitis viruses use exosomes to egress, regulate, and eventually escape from the host immune system, revealing another key function of exosomes apart from their recognised role in intercellular communication. This review will discuss how the hepatitis viruses exploit exosome biogenesis and transport capacity to establish successful infection and spread. Then, we will outline the contribution of exosomes in viral persistence and liver disease progression.

Attitudes and Awareness Toward Pharmacogenomics and Personalized Medicine Adoption Among Health Sciences Trainees: Experience from Greece and Lessons for Europe.

The increasing incorporation of genomics in clinical practice underscores the need to improve genomics knowledge and familiarity among future health care providers. To this end, it is important to consider both the "push" and the "pull" factors that shape or determine the transition of new personalized medicine (PM) discoveries to clinical practice. One of the pull factors involves the attitudes, values, and education of the user communities such as patients, physicians, and scientists who are poised to use the PM diagnostics. Among the push factors are often health scientists who contribute to PM science and development efforts. Seen in this light, health sciences trainees represent both the push and pull factors, not to mention the next generation of stakeholders and innovation actors who will make PM a reality in mainstream medical practice in the future. Τhis study aimed at investigating and comparing awareness and attitudes (ethical and other) on pharmacogenomics (PGx) and PM adoption among undergraduate students from the school of health sciences and other students. A convenience sample was used in this survey in two groups of students: 205 students from the School of Health Sciences and 141 students from other schools (e.g., biology, computer engineering, and business administration) of the University of Patras, Greece, and mostly at undergraduate education level. We observed that despite the relatively low level of awareness about genetics, PGx, and relevant notions, both groups of students were very optimistic about the genetic testing usefulness and professed their positive anticipations about PGx on disease management. Thus, health sciences students and those in other faculties appeared to be avid proponents of genetics testing and in favor of public endorsement of the concepts of individually tailored medicine. This case study in Greece is one of the first studies on perceptions and attitudes toward PGx testing and PM in Southern Europe. Of importance, the study informs the prospects and challenges on the push and pull factors of PM innovation while offering potential lessons for future PM curriculum needs in health sciences in other countries in Europe.

The origins of entasis: illusion, aesthetics or engineering?

A typical characteristic of columns in Doric temples is entasis; a slight convexity in the body of a column. Often, and particularly in guide-books, it is suggested that entasis is intended to compensate for an illusion of concavity in columns with truly straight sides. We have investigated whether any such visual illusion exists, both in parallel sided and in tapering columns in a series of experiments, finding little evidence to support any illusion-compensation theory. Further, we explored the possibility that entasis was employed for purely aesthetic reasons, but the results do not support this conclusion. Finally, evidence supporting an engineering role for entasis is presented.