The quest for an effective and safe personalized cell therapy using epigenetic tools

In the presence of different environmental cues that are able to trigger specific responses, a given genotype has the ability to originate a variety of different phenotypes. This property is defined as plasticity and allows cell fate definition and tissue specialization. Fundamental epigenetic mechanisms drive these modifications in gene expression and include DNA methylation, histone modifications, chromatin remodeling, and microRNAs. Understanding these mechanisms can provide powerful tools to switch cell phenotype and implement cell therapy. Environmentally influenced epigenetic changes have also been associated to many diseases such as cancer and neurodegenerative disorders, with patients that do not respond, or only poorly respond, to conventional therapy. It is clear that disorders based on an individual\u2019s personal genomic/epigenomic profile can rarely be successfully treated with standard therapies due to genetic heterogeneity and epigenetic alterations and a personalized medicine approach is far more appropriate to manage these patients. We here discuss the recent advances in small molecule approaches for personalized medicine, drug targeting, and generation of new cells for medical application. We also provide prospective views of the possibility to directly convert one cell type into another, in a safe and robust way, for cell-based clinical trials and regenerative medicine

Hepatitis a epidemic in men who have sex with men (MSM) in milan, Italy

Background and aim of the work: Hepatitis A is an infectious disease characterized by fecal-oral transmission; however, a rise in sexually-transmitted cases has been observed, particularly among \u201cmen who have sex with men\u201d. In Europe, a Hepatitis A epidemic occurred among men who have sex with men between 2016 and 2018. The aim of this study is to describe this Hepatitis A epidemic in the city of Milan and to analyze the incidence of Sexually Transmitted Diseases co-infection among Hepatitis A cases. Methods: Hepatitis A cases were traced and identified. Epidemiological data were collected and Hepatitis A vaccination was investigated. Cases were georeferenced, calculating incidence rates for each Milan Municipality. Viral genotypic analysis was carried out. Results: 353 cases were reported in Milan. Incidence rates resulted significantly higher in males (RR 18.1 CI9 5% 11.5 - 28.4). 70 cases reported foreign travel. 172 cases reported \u201cMen who have Sex with Men\u201d behaviour. Genotypic analysis revealed correlation with strains of the European \u201cMen who have Sex with Men\u201d epidemic. Georeferencing showed asymmetric case distribution. Only 12 cases reported Hepatitis A vaccination. The Relative Risk for syphilis infection among Hepatitis A cases was 133.9 (95% CI 81.7 - 219.7) and 29.7 (95%CI 9.5 - 92.7) for gonorrhea. Conclusions: Most genotyped cases (93.7%) correlated to the European Hepatitis A epidemic among Men who have Sex with Men. Georeferencing showed a greater incidence of Hepatitis A cases in areas characterized by the homosexual community. The higher incidence of Sexually Transmitted Diseases co-infection in Hepatitis A cases correlated to clusters responsible for the European Hepatitis A epidemic, suggests increased sexual promiscuity among Men who have Sex with Men. These data support the need for Hepatitis A vaccination programs and sensitization of Men who have Sex with Men to the adoption of safe sexual practices

Hot planets around cool stars - two short-period mini-Neptunes transiting the late K-dwarf TOI-1260

Stars and planetary system

Mass determinations of the three mini-Neptunes transiting TOI-125

Stars and planetary system

Erase and Rewind : Epigenetic Conversion of Cell Fate

The potential of cell therapy in regenerative medicine has greatly expanded thanks to the availability of sources of pluripotent cells. In particular, induced pluripotent stem cells (iPS) have dominated the scenario in the last years for their ability to proliferate and differentiate into specific cell types. Nevertheless, the concerns inherent to the cell reprogramming process, limit iPS use in therapy and pose questions on the long-term behavior of these cells. In particular, despite the development of virus-free methods for their obtainment, a major and persisting drawback, is related to the acquisition of a stable pluripotent state, that is un-physiological and may lead to cell instability. The increased understanding of epigenetic mechanisms has paved the way to the use of \u201csmall molecules\u201d and \u201cepigenetic modifiers\u201d that allow the fine tuning of cell genotype and phenotype. In particular, it was demonstrated that an adult mature cell could be directly converted into a different cell type with the use of these chemicals, obtaining a new patient-specific cell, suitable for cell therapy. This approach is simple and direct and may represent a very promising tool for the regenerative medicine of several and diverse degenerative diseases

The online sexual offender: what we know to date

Introduction: Online grooming is an active communicative entrapment network involving a wide range of techniques. The interactions that groomers have with minors online are complex. The purpose of the present literature review is to contribute to the existing knowledge base regarding online sex offender typologies, predatory tactics and techniques. Evidence acquisition: We conducted a review of the current literature by an initial database research of papers published since 1990. Three independent reviewers selected relevant articles, initially based on title and abstract analysis, then by full text in order to make a final determination. After the final selection, a total of 21 articles were reviewed. Evidence synthesis: Overall, abundant data describing both groomer characteristics and grooming strategies are available in the literature, with authors attempting to analyze and adapt these to ever-complex models. However, the various models often feel redundant, determining a certain difficulty in understanding which would be the most suitable model to apply, making comparing data from different studies oftentimes troublesome. Conclusions: In our opinion, it would be desirable to reach a consensus on fewer univocally- interpretable models that would be easier to adopt as preventive tools against online grooming, in combination with other strategies. The present study may provide parents and guardians with information useful for keeping their youth safer while online, as well as data that may assist in the development of policy recommendations and prevention strategies, overall aiming to reduce the phenomenon of online grooming

Self-sampling versus physician-sampling of oropharyngeal swabs for molecular detection of respiratory viruses: a pilot study

Aim: This pilot study evaluated the adequacy of self-collected oropharyngeal swabs compared to those collected by trained physicians for molecular detection of respiratory viruses. Method: Oropharyngeal swabs1 were collected from influenza like-illness cases in Lombardy during the 2018/2019 season. Two groups of samples were considered: group 1) 131 swabs collected by general practitioners operating within the Italian Influenza Surveillance Network; group 2) 131 swabs self-collected by hospital healthcare workers (doctors, nurses, technicians, in-training students) after being trained on the sampling procedure by both an explanatory brochure describing the steps of swab collection, point-by-point, and a telephone call to a study staff member who guided sample collection. RNA was extracted from each swab and tested for the detection of the human ribonuclease P gene (RNP) by real-time RT-PCR. Samples with a cycle threshold (Ct)<35 were considered adequate for further virological analysis. Respiratory syncytial virus (RSV) was detected by real-time RT-PCR. Results: All samples were positive to RNP detection with Ct<35. The mean Ct value was 25.46 (SD: \ub12.40; range: 18.65-30.10) for swabs collected by physicians and 25.93 (SD: \ub12.22; range: 19.48-33.13) for self-collected swabs, with no statistically significant difference (p=0.10). RSV-positivity rates were similar among both groups (10.9% vs 7.3%; p=0.39). Conclusions: Self-collected oropharyngeal swabs resulted adequate and comparable to those collected by trained physicians for molecular detection of respiratory viruses. Self-sampling can be a worthwhile strategy of sample collection to implement molecular surveillance of respiratory viruses or to evaluate vaccine effectiveness involving population at lower costs