New Perspectives in Third Molar Auto-Transplantation: Literature Review and a Case Report of Clinical, Financial and Forensic Implications.

Third molar extraction is the most common procedure in oral and maxillofacial surgery. Third molars are considered less functional than other teeth and are often extracted. Sometimes, they are also used for auto-transplantation for the benefit of oral rehabilitation. Since many biological factors are involved in this surgical approach, herein, we outline a review of the biological characteristics of medico-legal/forensic interest, in addition to presenting a successful clinical case. A scoping review of currently available research data (following the principles of PRISMA-ScR or the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) on third molar auto-transplantation was conducted by drawing upon the main databases (Scopus, PubMed, Google Scholar and LILACS) to evaluate biological and clinical characteristics possibly relatable to forensic issues. All the collected data were summarized and elaborated on for the purpose of this article. A patient underwent extraction of the right upper first molar and auto-transplantation of the unerupted ipsilateral third molar. Many biologic and clinical factors are involved in the success of this clinical procedure. Knowledge of third molar anatomy, of its development and viable surgical approaches are all essential elements; just as important are the treatment of the tooth before and after transplantation and the integrity of the periodontal ligament. Follow-up of the clinical case for 5 years made it possible to verify the stability of the procedure over time. Third molar auto-transplantation is feasible and cost-effective. However, the use of third molars as donor teeth in auto-transplantation may have medico-legal implications. The lack of official protocols and consistent evidence-based guidelines for operators still prevent such a procedure from becoming mainstream; therefore, it is viewed with suspicion by clinicians and patients, even though the biological factors herein detected point to a reasonably high degree of safety. The understanding of many specific biological and clinical factors involved in the stability of third molar auto-transplantation allows for a thorough understanding of the forensic implications relevant to clinical practice. Effective communication and information provision are therefore of utmost importance, in the interest of both patients and doctors.

Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer-Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects.

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and-as much as possible-minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

Type I Dentin Dysplasia: The Literature Review and Case Report of a Family Affected by Misrecognition and Late Diagnosis.

Background and Objectives: Type I dentin dysplasia (DD-I) is a rare genetic disorder with autosomal dominant or recessive inheritance at risk of late or long-misunderstood diagnosis because the teeth, compared to other degenerative dentin diseases, do not have coronal defects and/or alterations but only at the root level (absent, conical, pointed roots, and obliterated pulp canals). The first radiographic suspicion often occurs only in case of sudden mobility and/or abscesses of the permanent teeth. Genetic tests confirm the diagnosis. Case Presentation: This case report describes the oral and radiographic characteristics of two siblings, 12 and 10 years old, a male and a female, at an early age affected by DD-I, whose diagnosis was made for a first orthodontic visit. The father and the older child had already undergone dental and orthodontic treatments, respectively, without the disease being suspected by the dentist. Results: Genetic tests support the diagnosis of DD-I. Following the diagnosis, the patients began a process of close periodic checks every 3-4 months to monitor their situation. The male child lost upper lateral incisors, which were then replaced with a light nylon removable prosthesis. Conclusions: The ability to recognize the radiographic features characteristic of DD-I is very important to avoid prejudicial diagnostic delays and to be able to plan the long-term treatment of these patients better, especially when the pathology was primarily misrecognized in the family.

Using ncRNAs as Tools in Cancer Diagnosis and Treatment-The Way towards Personalized Medicine to Improve Patients' Health.

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular network of crossed interactions (competing endogenous RNA networks, or ceRNET) that fine-tune the gene expression in both health and disease. The alteration of the equilibrium among such interactions can be enough to cause a transition from health to disease, but the opposite is equally true, leading to the possibility of intervening based on these mechanisms to cure human conditions. In this review, we summarize the present knowledge on these mechanisms, illustrating how they can be used for disease treatment, the current challenges and pitfalls, and the roles of environmental and lifestyle-related contributing factors, in addition to the ethical, legal, and social issues arising from their (improper) use.

Fertility preservation in female cancer sufferers: (only) a moral obligation?

PURPOSE: Advances in cancer diagnostics and therapeutics have thankfully led to high numbers of young cancer survivors, although some interventions may sometimes threaten fertility. The authors aimed to assess how evidence-based oncofertility counselling can be adequately fulfilled for the sake of female cancer patients, in light of its complexities and multidisciplinary nature, which require thorough counselling and consent pathways. MATERIALS AND METHODS: A search has been conducted in the databases PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Google Scholar via search strings such as fertility preservation, reproductive counselling, oncofertility, cancer survivors, in order to identify relevant meaningful sources spanning the 2010-2021 period. RESULTS: Counselling needs to be implemented in compliance with international guidelines, so as to avoid medicolegal repercussions. Albeit fertility preservation is supported by most health care institutions, actual conditions at health care facilities often reflect several lingering difficulties in the oncofertility process. Oncofertility counselling should foster access to fertility preservation procedures. To best serve that purpose, it should be implemented in a manner consistent with ethical and legal standards, so that patients can make an informed decision based on comprehensive and relevant data. CONCLUSIONS: Counselling needs to be rooted in a close cooperation of oncologists, reproductive endocrinologists, mental health counsellors and clinical researchers. The provision of oncofertility services is grounded in the moral obligation to uphold individual autonomy, which is essential in a free society, unless the exercise thereof could pose a risk to the children conceived or to others.

Neonatal Outcomes and Long-Term Follow-Up of Children Born from Frozen Embryo, a Narrative Review of Latest Research Findings.

In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.

Catchment-wide validated assessment of combined sewer overflows (CSOs) in a mediterranean coastal area and possible disinfection methods to mitigate microbial contamination.

The first phase of this study aimed to evaluate the environmental impact of combined sewer overflow (CSO) events originated from 35 spillways on the Rio Vallescura catchment (Central Italy) and to understand their contribution to the deterioration of the coastal bathing water quality. A specific analytical campaign was carried out in the sewer system and a dynamic rainfall-runoff simulation model was developed and integrated with a water quality model and further validated. The simulations led to identify the most critical spills in terms of flow rate and selected pollutant loads (i.e. suspended solids, biochemical oxygen demand, chemical oxygen demand, total Kjeldahl nitrogen, Escherichia coli). Specifically, the E. coli release in the water body due to CSO events represented almost 100% of the different pollutant sources considered. In the second phase, the applicability of various disinfection methods was investigated on the CSOs introduced into the catchment. On site physical (UV) and lab-scale chemical (peracetic acid (PAA), performic acid (PFA), ozone) disinfectant agents were tested on microbial indicators including E. coli and intestinal enterococci. PFA and ozone were more effective on the removal of both bacteria (above 3.5 log units) even at low concentration and with short contact time; whereas, PAA showed a moderate removal efficiency (around 2.5 log units) only for E. coli. The highest removal efficiency was achieved in the on-site UV unit and none of the indicator bacteria was detected in the final effluent after the sand filtration and UV treatment. Finally, potential scenarios were developed in comparison to the baseline scenario for the management and treatment of CSOs where a mitigation of E. coli loads from 28% to 73% was achieved on the receiving water body, and a comparative cost assessment of the disinfection methods was provided for in situ treatment of the most critical spillway.

Non-Coding RNAs as Prognostic Markers for Endometrial Cancer.

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

Does the EU COVID Digital Certificate Strike a Reasonable Balance between Mobility Needs and Public Health?

The need to fight a highly aggressive virus such as SARS-CoV-2 has compelled governments to put in place measures, which, in the name of health protection, have constrained many freedoms we all enjoy, including freedom of movement, both nationally and within the European Union. In order to encourage and facilitate the return to free movement, the European Parliament has launched a "COVID-19 digital certificate". A spirited debate centered around the use of this certificate is still ongoing among scholars, many of whom have pointed out the uncertainties relative to COVID-19 immunity, privacy issues and the risk of discriminatory effects. The authors, while highlighting some critical aspects, argue that the COVID digital certificate in its current approved version can effectively help prevent the spread of the infection and promote free movement, while upholding the right to health as much as possible. However, they also stress the need for a thorough information campaign to illustrate the advantages and limitations of this document in order to avoid creating a false sense of security in the public opinion, who may wrongly assume that the emergency has been overcome for good.

The rise of new psychoactive substances and psychiatric implications: A wide-ranging, multifaceted challenge that needs far-reaching common legislative strategies.

The ever-growing number of novel psychoactive substances (NPS) that have been surfacing globally, as well as related changes in drug abuse trends, undoubtedly constitute a difficult and multifaceted challenge for psychiatry. The intake and abuse of such substances has been linked to a risk of psychopathological disturbances, which stem from imbalances of a range of neurotransmitter pathways and receptors. Through an analysis of relevant research articles and reviews (particularly those outlining NPS neurological and cerebral mechanisms of action and psychopathological consequences arising from NPS abuse; research papers more closely focused on chemical/pharmacological aspects have been ruled out), through a systematic analysis of Pubmed, Medline, PsycLIT and EMBASE literature, as well as data released by health care institutions and drug enforcement agencies (among which the World Health Organization, the United Nations Office on Drugs and Crime, the European Monitoring Centre for Drugs and Drug Addiction, Eurojust, the Novel Psychoactive Treatment UK Network, the Court of Justice of the European Union), the authors aimed to elaborate on the most relevant data relative to NPS-related psychiatric effects, focusing on the conceptual and definition-related complexities inherent to NPS, clinical management and motivations for NPS use; moreover, an effort has been made to highlight the possible measures in order to tackle the unremitting rise of such elusive and potentially harmful substances.

Medicolegal Issues in Power Morcellation: Cautionary Rules for Gynecologists to Avoid Unfavorable Outcomes.

Power morcellation in laparoscopic surgery enables specialists to carry out minimally invasive procedures such as hysterectomies and myomectomies by cutting specimens into smaller pieces using a rotating blade and removing pieces through a laparoscope. Unexpected uterine sarcoma treated by surgery involving tumor disruption could be associated with poor prognosis. The current study aims to shed light on power morcellation from a medicolegal perspective: the procedure has resulted in adverse outcomes and litigation, and compensation for plaintiffs, as published in various journals cited in PubMed and MEDLINE, Cochrane Library, EMBASE, and GyneWeb. Considering the claims after the US Food and Drug Administration warnings on morcellation, the current study broadens the scope of research by including search engines, legal databases, and court filings (DeJure, Lexis Nexis, Justia, superior court of New Jersey, and US district court of Minnesota) between 1995 and 2019. Legal records show that courts determine professional responsibility regarding complications, making it essential to document adherence to safety protocols and specific guidelines, when available. Sound medical practices and clearly stated institute best practices result in better patient outcomes and are important when unfavorable clinical outcomes occur; adverse legal decisions can be avoided if there are grounds to prove professional conformity with specific guidelines and the unpredictability of an event.

Intensive and pharmacological care in times of COVID-19: A "special ethics" for emergency?

BACKGROUND: The Authors have laid out an analysis of Italian COVID-19 confirmed data and fatality rates, pointing out how a dearth of health care resources in northern regions has resulted in hard, ethically challenging decisions in terms of granting patient access to intensive care units (ICU). MAIN TEXT: Having to make such decisions certainly entails substantial difficulties, and that has led many health care professional to seek ethical guidance. The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) has attempted to meet that growing need by a set of recommendations, applying "clinical soundness" as a beacon standard; that approach tends to prioritize patients with higher life expectancy, which could be characterized as a "moderately utilitarian" approach. Yet, such a selection has engendered daunting ethical quandaries. The authors believe it can only be warranted and acceptable if rooted in a transparent decision-making process and verifiable, reviewed criteria. Moreover, the authors have stressed how clinical experimentation in a pandemic setting is a subtext of great interest from an ethical perspective. In Italy, no drug therapy and trials were undertaken for COVID-19 patients for a rather long period of time. When the epidemic was already circulating, an intervention proved necessary on the system of administrative procedures, aimed at expediting the authorization and validation of protocols, then bogged down by bureaucracy. A new system has since been instituted by a government decree that was signed about one month after the first Covid-19 case was officially recorded in the country. Such a swift implementation, which took just a few weeks, is noteworthy and proves that clinical trials can be initiated in a timely fashion, even with a pandemic unfolding. The concerted, action of supportive care and RCTs is the only way to attain effective forms of treatments for COVID-19 and any other future outbreak. CONCLUSIONS: The authors have arrived at the conclusion that the most effective and ethically sound response on the part of any national health care system would be to adequately reconfigure its organizational mechanisms, by making clinical trials and all related administrative procedures consistent with the current state of emergency.

Cardiovascular Outcomes in Advanced Maternal Age Delivering Women. Clinical Review and Medico-Legal Issues.

Background and objecives: Adverse cardiovascular outcomes during pregnancy have increased over the past few decades, with increased numbers of women delivering later in their reproductive life. Other factors include higher rates of female obesity, diabetes, hypertension, cardiovascular diseases and assisted reproductive technology, which has extended fertility. Those at risk require extensive prenatal maternal screening, constant pregnancy supervising, monitoring during labor, delivery and puerperium and careful anesthetic evaluation during delivery. Materials and Methods: The present review reports the relevant information available on cardiovascular outcomes in advanced maternal age delivering women and related medico-legal issues. The search was performed on Pubmed, Cochrane, Semantic Scholar, Medline and Embase databases, accessed by Ovid, including among others the terms "cardiomyopathy", "ischaemic heart disease", "arrhythmias", "hypertension", "peripartum period", "diabetes", "advanced maternal age" "anesthesia", "maternal morbidity and mortality" and "litigation". Results: To the extent that underestimating risk factors for peripartum cardiomyopathy (PPCM) can adversely impact maternal and fetal outcomes, the legal implications of misdiagnosis or mismanagement can result in high compensatory damages. Substantial indemnity payments drive up costs of insurance coverage. Conclusions: Multidisciplinary approaches are necessary from obstetricians, cardiologists, anesthesiologists and perinatologists for pregnancy monitoring and delivery outcomes.

Determination of oxycodone and its major metabolites noroxycodone and oxymorphone by ultra-high-performance liquid chromatography tandem mass spectrometry in plasma and urine: application to real cases.

BACKGROUND: Oxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma concentrations of parent drug and its active metabolite, oxymorphone. To evaluate patient compliance and to set up therapeutic drug monitoring (TDM), an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay was developed and validated for the parent drug and its major metabolites noroxycodone and oxymorphone. METHODS: Extraction of analytes from plasma and urine samples was obtained by simple liquid-liquid extraction. The chromatographic separation was achieved with a reversed phase column using a linear gradient elution with two solvents: acetic acid 1% in water and methanol. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). RESULTS: Separation of analytes was obtained in less than 5 min. Linear calibration curves for all the analytes under investigation in urine and plasma samples showed determination coefficients (r2) equal or higher than 0.990. Mean absolute analytical recoveries were always above 86%. Intra- and inter-assay precision (measured as coefficient of variation, CV%) and accuracy (measured as % error) values were always better than 13%. Limit of detection at 0.06 and 0.15 ng/mL and limit of quantification at 0.2 and 0.5 ng/mL for plasma and urine samples, respectively, were adequate for the purpose of the present study. CONCLUSIONS: Rapid extraction, identification and quantification of oxycodone and its metabolites both in urine and plasma by UHPLC-MS/MS assay was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in patients under oxycodone treatment.

Hepatotoxicity Induced by "the 3Ks": Kava, Kratom and Khat.

The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by "the 3Ks", while trying to clarify the numerous aspects that still need to be addressed.

Accuracy of MRI skeletal age estimation for subjects 12-19. Potential use for subjects of unknown age.

INTRODUCTION: In forensic practice, there is a growing need for accurate methods of age estimation, especially in the cases of young individuals of unknown age. Age can be estimated through somatic features that are universally considered associated with chronological age. Unfortunately, these features do not always coincide with the real chronological age: for these reasons that age determination is often very difficult. Our aim is to evaluate accuracy of skeletal age estimation using Tomei's MRI method in subjects between 12 and 19 years old for forensic purposes. MATERIAL AND METHODS: Two investigators analyzed MRI images of the left hand and wrist of 77 male and 74 female caucasian subjects, without chronic diseases or developmental disorders, whose age ranged from 12 to 19 years. Skeletal maturation was determined by two operators, who analyzed all MRI images separately, in blinded fashion to the chronological age. Inter-rater agreement was measured with Pearson (R (2)) coefficient. One of the examiners repeated the evaluation after 6 months, and intraobserver variation was analyzed. Bland-Altman plots were used to determine mean differences between skeletal and chronological age. RESULTS: Inter-rater agreement Pearson coefficient showed a good linear correlation, respectively, 0.98 and 0.97 in males and females. Bland-Altman analysis demonstrated that the differences between chronological and skeletal age are not significant. Spearman's correlation coefficient showed good correlation between skeletal and chronological age both in females (R (2) = 0.96) and in males (R (2) = 0.94). CONCLUSIONS: Our results show that MRI skeletal age is a reproducible method and has good correlation with chronological age.

Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology.

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined.

Sudden death due to butane abuse - An overview.

Volatile Solvents Abuse (VSA) poses major health risks, especially for young people and those living in precarious socio-economic conditions. Such substances can in fact bring about psychoactive effects such as euphoria, and even lead to sudden death from cardiac arrhythmias, respiratory depression, myocardial infarction, laryngospasm, encephalopathy, and rhabdomyolysis. The present case report is centered around a 23-year-old man who died in prison due to inhalation of a cooker gas mixture (n-butane, propane, and isobutane) inside a plastic bag. External examination and autopsy showed non-specific signs of asphyxia associated with edema and brain swelling. Histological signs of early myocardial damage and hypoxic-ischemic injury (HII) were highlighted in the brain and cerebellum, as well as activated macrophages and anthracotic-like material in the lungs. Toxicological investigations revealed the presence of propane, isobutane and n-butane in liquids and biological samples. Besides the cardiotoxic effect, there was an asphyctic component due to the plastic bag that may have facilitated death. The assessment of cerebral HII and cardiopulmonary damage in acute cases is very important to prove death by butane inhalation. In the forensic field, it may be useful to shed more light on intoxications, deaths, and butane encephalopathies, as the latter can be mistaken for a hypoxic-ischemic encephalopathy.

A Journey into the Evolution of Human Host-Oral Microbiome Relationship through Ancient Dental Calculus: A Scoping Review.

One of the most promising areas of research in palaeomicrobiology is the study of the human microbiome. In particular, ancient dental calculus helps to reconstruct a substantial share of oral microbiome composition by mapping together human evolution with its state of health/oral disease. This review aims to trace microbial characteristics in ancient dental calculus to describe the evolution of the human host-oral microbiome relationship in oral health or disease in children and adults. Following the PRISMA-Extension for Scoping Reviews guidelines, the main scientific databases (PubMed, Scopus, Lilacs, Cochrane Library) have been drawn upon. Eligibility criteria were established, and all the data collected on a purpose-oriented collection form were analysed descriptively. From the initial 340 records, only 19 studies were deemed comprehensive enough for the purpose of this review. The knowledge of the composition of ancient oral microbiomes has broadened over the past few years thanks to increasingly well-performing decontamination protocols and additional analytical avenues. Above all, metagenomic sequencing, also implemented by state-of-the-art bioinformatics tools, allows for the determination of the qualitative-quantitative composition of microbial species associated with health status and caries/periodontal disease. Some microbial species, especially periodontal pathogens, do not appear to have changed in history, while others that support caries disease or oral health could be connected to human evolution through lifestyle and environmental contributing factors.

miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine.

Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to tumor development and angiogenesis in different types of cancer. Recently, complex interactions among coding and non-coding RNA have been elucidated, further shedding light on the complexity of the roles these molecules fulfill in cancer formation. In this context, knowledge about the role of miR in BC has significantly improved, highlighting the deregulation of these molecules as additional factors influencing BC occurrence, development and classification. A considerable number of papers has been published over the past few years regarding the role of miR-125 in human pathology in general and in several types of cancer formation in particular. Interestingly, miR-125 family members have been recently linked to BC formation as well, and complex interactions (competing endogenous RNA networks, or ceRNET) between this molecule and target mRNA have been described. In this review, we summarize the state-of-the-art about research on this topic.