The Biological and Clinical Role of the Telomerase Reverse Transcriptase Gene in Glioblastoma: A Potential Therapeutic Target?

Glioblastoma IDH-wildtype represents the most lethal and frequent primary tumor of the central nervous system. Thanks to important scientific efforts, we can now investigate its deep genomic assessment, elucidating mutated genes and altered biological mechanisms in addition to its clinical aggressiveness. The telomerase reverse transcriptase gene (TERT) is the most frequently altered gene in solid tumors, including brain tumors and GBM IDH-wildtype. In particular, it can be observed in approximately 80–90% of GBM IDH-wildtype cases. Its clonal distribution on almost all cancer cells makes this gene an optimal target. However, the research of effective TERT inhibitors is complicated by several biological and clinical obstacles which can be only partially surmounted. Very recently, novel immunological approaches leading to TERT inhibition have been investigated, offering the potential to develop an effective target for this altered protein. Here, we perform a narrative review investigating the biological role of TERT alterations on glioblastoma and the principal obstacles associated with TERT inhibitions in this population. Moreover, we discuss possible combination treatment strategies to overcome these limitations

The Environmental Cleanliness and Clutter Scale (ECCS) in the management of sanitary risks in dwellings of hoarders in North Italy

Abstract: The aims of this work were to apply the Environmental Cleanliness and Clutter Scale (ECCS) in order to assess domestic squalor in dwellings of hoarders, prevent sanitary risks, and intervene in solving the problem. Methods: The ECCS is a domestic squalor scale, developed as a quantitative descriptive tool, based on ten items and a four-point scale. ECCS was applied in addition to the usual procedure during 40 site inspections in Milan, in two different surveys of dwellings of hoarders (2016 and 2019). A correction only for companion animal hoarders was introduced. Results: In the first investigation, which included animal accumulation, our 20 raters reported six cases of mild squalor and six and eight respectively of moderate and severe squalor. After our correction for animal hoarders’ dwellings, we identified six cases of mild, four of moderate, and ten of severe squalor. In the second part of our assessment involving another 20 home visits, object hoarding only was assessed in order to evaluate the reliability of the ECCS method. We found varying total scores between the operators with different experience on this issue, but the same evaluation of the severity of the squalor in 14/15 (93%) cases therefore resulted in the same type of intervention. Conclusion: The ECCS score made an evaluation of the severity of hoarding/squalor, and supported the Local Health Protection Agency personnel in making decisions about timing and type of intervention

Do we really need hazard prevention at the expense of safeguarding death dignity in covid-19?

To date, little is known regarding the transmission risks of SARS-CoV-2 infection for subjects involved in handling, transporting, and examining deceased persons with known or suspected COVID-19 positivity at the time of death. This experimental study aims to define if and/or how long SARS-CoV-2 persists with replication capacity in the tissues of individuals who died with/from COVID-19, thereby generating infectious hazards. Sixteen patients who died with/from COVID-19 who underwent autopsy between April 2020 and April 2021 were included in this study. Based on PMI, all samples were subdivided into two groups: ‘short PMI’ group (eight subjects who were autopsied between 12 to 72 h after death); ‘long PMI’ (eight subjects who were autopsied between 24 to 78 days after death). All patients tested positive for RT-PCR at nasopharyngeal swab both before death and on samples collected during post-mortem investigation. Moreover, a lung specimen was collected and frozen at −80◦ C in order to perform viral culture. The result was defined based on the cytopathic effect (subjective reading) combined with the positivity of the RT-PCR test (objective reading) in the supernatant. Only in one sample (PMI 12 h), virus vitality was demonstrated. This study, supported by a literature review, suggests that the risk of cadaveric infection in cases of a person who died from/with COVID-19 is extremely low in the first hours after death, becoming null after 12 h after death, confirming the World Health Organization (WHO) assumed in March 2020 and suggesting that the corpse of a subject who died from/with COVID-19 should be generally considered not infectious

Molecular mechanisms related to hormone inhibition resistance in prostate cancer

Management of metastatic or advanced prostate cancer has acquired several therapeutic approaches that have drastically changed the course of the disease. In particular due to the high sensitivity of prostate cancer cells to hormone depletion, several agents able to inhibit hormone production or binding to nuclear receptor have been evaluated and adopted in clinical practice. However, despite several hormonal treatments being available nowadays for the management of advanced or metastatic prostate cancer, the natural history of the disease leads inexorably to the development of resistance to hormone inhibition. Findings regarding the mechanisms that drive this process are of particular and increasing interest as these are potentially related to the identification of new targetable pathways and to the development of new drugs able to improve our patients’ clinical outcomes

Beyond Imaging and Genetic Signature in Glioblastoma: Radiogenomic Holistic Approach in Neuro-Oncology

Glioblastoma (GBM) is a malignant brain tumor exhibiting rapid and infiltrative growth, with less than 10% of patients surviving over 5 years, despite aggressive and multimodal treatments. The poor prognosis and the lack of effective pharmacological treatments are imputable to a remarkable histological and molecular heterogeneity of GBM, which has led, to date, to the failure of precision oncology and targeted therapies. Identification of molecular biomarkers is a paradigm for comprehensive and tailored treatments; nevertheless, biopsy sampling has proved to be invasive and limited. Radiogenomics is an emerging translational field of research aiming to study the correlation between radiographic signature and underlying gene expression. Although a research field still under development, not yet incorporated into routine clinical practice, it promises to be a useful non-invasive tool for future personalized/adaptive neuro-oncology. This review provides an up-to-date summary of the recent advancements in the use of magnetic resonance imaging (MRI) radiogenomics for the assessment of molecular markers of interest in GBM regarding prognosis and response to treatments, for monitoring recurrence, also providing insights into the potential efficacy of such an approach for survival prognostication. Despite a high sensitivity and specificity in almost all studies, accuracy, reproducibility and clinical value of radiomic features are the Achilles heel of this newborn tool. Looking into the future, investigators’ efforts should be directed towards standardization and a disciplined approach to data collection, algorithms, and statistical analysis

The human microbiota and prostate cancer: Friend or foe?

The human microbiome is gaining increasing attention in the medical community, as knowledge on its role not only in health but also in disease development and response to therapies is expanding. Furthermore, the connection between the microbiota and cancer, especially the link between the gut microbiota and gastrointestinal tumors, is becoming clearer. The interaction between the microbiota and the response to chemotherapies and, more recently, to immunotherapy has been widely studied, and a connection between a peculiar type of microbiota and a better response to these therapies and a different incidence in toxicities has been hypothesized. As knowledge on the gut microbiota increases, interest in the residing microbial population in other systems of our body is also increasing. Consequently, the urinary microbiota is under evaluation for its possible implications in genitourinary diseases, including cancer. Prostate cancer is the most common cancer in the male population; thus, research regarding its etiology and possible factors correlated to disease progression or the response to specific therapies is thriving. This review has the purpose to recollect the current knowledge on the relationship between the human microbiota and prostate cancer

Review adverse effects of anabolic-androgenic steroids: A literature review

Anabolic-androgenic steroids (AASs) are a large group of molecules including endoge-nously produced androgens, such as testosterone, as well as synthetically manufactured derivatives. AAS use is widespread due to their ability to improve muscle growth for aesthetic purposes and athletes’ performance, minimizing androgenic effects. AAS use is very popular and 1–3% of US inhabitants have been estimated to be AAS users. However, AASs have side effects, involving all organs, tissues and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, thereby, their abuse is considered a public health issue. The aim of the proposed review is to highlight the most recent evidence regarding the mechanisms of action of AASs and their unwanted effects on organs and lifestyle, as well as suggesting that AAS misuse and abuse lead to adverse effects in all body tissues and organs. Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related damage in the whole body. The cardiovascular system and the reproductive system are the most frequently involved apparatuses. Epidemiology as well as the molecular and pathological mechanisms involved in the neuropsychiatric side-effects of AAS abuse are still unclear, further research is needed in this field. In addition, diagnostically reliable tests for AAS abuse should be standardized. In this regard, to prevent the use of AASs, public health measures in all settings are crucial. These measures consist of improved knowledge among healthcare workers, proper doping screening tests, educational interventions, and updated legislation

Sudden cardiac death in anabolic-androgenic steroid users: A literature review

Background and objectives: Anabolic-androgenic steroids (AASs) are a group of synthetic molecules derived from testosterone and its related precursors. AASs are widely used illicitly by adolescents and athletes, especially by bodybuilders, both for aesthetic uses and as performance enhancers to increase muscle growth and lean body mass. When used illicitly they can damage health and cause disorders affecting several functions. Sudden cardiac death (SCD) is the most common medical cause of death in athletes. SCD in athletes has also been associated with the use of performance-enhancing drugs. This review aimed to focus on deaths related to AAS abuse to investigate the cardiac pathophysiological mechanism that underlies this type of death, which still needs to be fully investigated. Materials and Methods: This review was conducted using PubMed Central and Google Scholar databases, until 21 July 2020, using the following key terms: “((Sudden cardiac death) OR (Sudden death)) AND ((androgenic anabolic steroid) OR (androgenic anabolic steroids) OR (anabolic-androgenic steroids) OR (anabolic-androgenic steroid))”. Thirteen articles met the inclusion and exclusion criteria, for a total of 33 reported cases. Results: Of the 33 cases, 31 (93.9%) were males while only 2 (61%) were females. Mean age was 29.79 and, among sportsmen, the most represented sports activity was bodybuilding. In all cases there was a history of AAS abuse or a physical phenotype suggesting AAS use; the total usage period was unspecified in most cases. In 24 cases the results of the toxicological analysis were reported. The most detected AASs were nandrolone, testosterone, and stanozolol. The most frequently reported macroscopic alterations were cardiomegaly and left ventricular hypertrophy, while the histological alterations were foci of fibrosis and necrosis of the myocardial tissue. Conclusions: Four principal mechanisms responsible for SCD have been proposed in AAS abusers: the atherogenic model, the thrombosis model, the model of vasospasm induced by the release of nitric oxide, and the direct myocardial injury model. Hypertrophy, fibrosis, and necrosis represent a substrate for arrhythmias, especially when combined with exercise. Indeed, AAS use has been shown to change physiological cardiac remodeling of athletes to pathophysiological cardiac hypertrophy with an increased risk of life-threatening arrhythmias