Human Brain Injury and miRNAs: An Experimental Study.

Brain damage is a complex dysfunction that involves a variety of conditions whose pathogenesis involves a number of mediators that lead to clinical sequelae. For this reason, the identification of specific circulating and/or tissue biomarkers which could indicate brain injury is challenging. This experimental study focused on microRNAs (miRNAs), a well-known diagnostic tool both in the clinical setting and in medico-legal investigation. Previous studies demonstrated that specific miRNAs (miR-21, miR-34, miR-124, miR-132, and miR-200b) control important target genes involved in neuronal apoptosis and neuronal stress-induced adaptation. Thus, in this experimental setting, their expression was evaluated in three selected groups of cadavers: drug abusers (cocaine), ischemic-stroke-related deaths, and aging damage in elder people who died from other neurological causes. The results demonstrated that the drug abuser group showed a higher expression of miR-132 and miR-34, suggesting a specific pathway in consumption-induced neurodegeneration. Instead, miR-200b and miR-21 dysregulation was linked to age-related cognitive impairment, and finally, stroke events and consequences were associated with an alteration in miR-200b, miR-21, and miR-124; significantly higher levels of this last expression are strongly sensitive for ischemic damage. Moreover, these results suggest that these expression patterns could be studied in other biological samples (plasma, urine) in subjects with brain injury linked to aging, drug abuse, and stroke to identify reliable biomarkers that could be applied in clinical practice. Further studies with larger samples are needed to confirm these interesting findings.

Immunodeficiency as a side effect of anabolic androgenic steroid abuse: a case of necrotizing myofasciitis.

Even if there are well-known consequences of anabolic androgenic steroid (AAS) abuse, their full pathway of action is still being investigated. In this context, the presented case report aims to discuss and provide evidence of unusual adverse effects linked to immunodeficiency in an AAS abuser. In fact, this kind of chronic complication, even if not usually considered, may lead sudden death. In this case a 31-year-old aesthetic weightlifter, who presented to the emergency department due to an accidental fall that resulted in left thigh trauma. This subsequently developed into left thigh necrotizing myofasciitis in the following few days. Although surgery and hyperbaric therapy were carried out, the man died. An autopsy with complete biological sampling for toxicological studies was performed. This case highlights the close relationship between AAS abuse and immunodeficiency and highlights it's importance for further studies. However, it should be considered that of all the dangerous effects produced by AAS use, necrotizing fasciitis is not such an unusual consequence.

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells.

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real-time PCR. The results obtained show that testosterone levels increase at a 3.9 µM concentration of nandrolone and return to the basal level a 15.6 µM dose of nandrolone. Nandrolone-induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a-hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down-regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects.

Morpho-radiological and brain endocast analysis in the study of Hyperostosis Frontalis Interna (HFI): A combined approach.

The purpose of this study is to anatomically evaluate the impact on the patient intra vitam of an endocranial condition on a late 20th century skull housed in the Section of Legal Medicine of the University of Foggia (Foggia, Apulia, Italy). After performing a retrospective diagnosis, the condition is framed in the broader context of studies on this pathology. An anthropological and radiological analysis (X-ray and CT scan imaging) made it possible to confirm the preliminary information and to detail the osteological diagnosis of HFI. In order to assess the impact on the cerebral surface of the endocranial growth a 3D endocast was obtained using the Software OrtogOnBlender. The skull is demonstrated to have belonged to a female senile individual known, from limited documentary evidence, to have suffered from a psychiatric condition during her life. The final diagnosis is hyperostosis frontalis interna (HFI), Type D. Although a direct correlation between the demonstrated intracranial bony growth and the onset of the patient's psychiatric condition is difficult to retrospectively ascertain, the pressure exerted on this female individual's frontal lobe may have contributed to further degenerative behavioural changes in the last years of her life. This case adds to previous knowledge, especially from the palaeopathological literature, on this condition and, for the first time, presents a neuroanatomical approach to assess the global impact of the disease.

Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review.

Anabolic-androgenic steroids (AASs) are a large group of molecules including endogenously 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.

Traumatic Brain Injury: A Forensic Approach: A Literature Review.

Traumatic brain injury (TBI) is the principal cause of invalidity and death in the population under 45 years of age worldwide. This mini-review aims to systematize the forensic approach in neuropathological studies, highlighting the proper elements to be noted during external, radiological, autoptical, and histological examinations with particular attention paid to immunohistochemistry and molecular biology. In the light of the results of this mini-review, an accurate forensic approach can be considered mandatory in the examination of suspected TBI with medico-legal importance, in order to gather all the possible evidence to corroborate the diagnosis of a lesion that may have caused, or contributed to, death. From this point of view, only the use of an evidence-based protocol can reach a suitable diagnosis, especially in those cases in which there are other neuropathological conditions (ischemia, neurodegeneration, neuro-inflammation, dementia) that may have played a role in death. This is even more relevant when corpses, in an advanced state of decomposition, are studied, where the radiological, macroscopic and histological analyses fail to give meaningful answers. In these cases, immune-histochemical and molecular biology diagnostics are of fundamental importance and a forensic neuropathologist has to know them. Particularly, MiRNAs are promising biomarkers for TBI both for brain damage identification and for medico-legal aspects, even if further investigations are required to validate the first experimental studies. In the same way, the genetic substrate should be examined during any forensic examination, considering its importance in the outcome of TBI.

Mistrial or Misdiagnosis: The Importance of Autopsy and Histopathological Examination in Cases of Sudden Infant Bronchiolitis-Related Death.

Pediatrics, among all the branches of medicine, is a sector not particularly affected by a high number of claims. Nevertheless, the economic value of the compensation is significantly high, for example, in cases of children who suffered multiple disabilities following perinatal lesions with a long life expectancy. In Italy, most of the claims for compensation concern surgical pathologies and infections. Among these latter, the dominant role is taken by respiratory tract infections. In this context, the purpose of this manuscript is to present a case series of infant deaths in different emergency-related facilities (ambulances, emergency rooms) denounced by relatives. Following these complaints, the autopsy was performed, and subsequent histological examinations revealed the presence of typical and pathognomonic histological findings of acute viral bronchiolitis, whose morphological appearance is poorly reported in the literature. The analysis of these cases made it possible to highlight the following conclusions: the main problems in diagnosing sudden death causes, especially in childhood, are the rapidity of death and the scarce correlation between the preexistent diseases and of the cause of death itself. For all these reasons, the autopsy, either clinical or medicolegal, is mandatory in cases of sudden unexpected infant death to manage claim requests because only the histological examinations performed on samples collected during the autopsy can reveal the real cause of death.

Dog-bite-related attacks: A new forensic approach.

Dog attacks today represent a health hazard considering that prevention strategies have not always been successful. The identification of the dog that attacked the victim is necessary, considering the civil or criminal consequences for the animal's owner. An accurate scene analysis must be performed collecting a series of important information. Forensic investigations in dog attacks involve different methods, such as the evaluating of the canine Short Tandem Repeat (STR) typing in saliva traces on wounds or bite mark analysis, however, these techniques cannot always be applied. The effort to find new methods to identify the dog that attacked the victim represents a very interesting field for the forensic community. This study aims to propose an innovative approach, based on the identification of the victim's profile in the dog's mouth, using a buccal swab on the suspected aggressor dog, to find the victim's genetic profile. In addition, a further goal of this study is to determine the persistence time of hexogen DNA in the dog's mouth to define a timeframe for performing this particular technique. For this purpose, ten different dogs were used to aggressively bite a bovine sample (reference sample) to simulate the victim. For each dog two buccal swabs were taken at different time intervals: 30', 45', 60', 90', 120', 150', 180' and 240'. The typing of the swabs provided an interpretable profile after 45' while traces of bovine profile were found until 150' after the dog attack simulation. These results could be improved using the human identification kit, which is more sensitive. In the light of this experimental study, the forensic community should consider using this approach in real casework studies with the aim of collecting new data, validating this technique for forensic use.

Homicide or car accident: The case of the 'guilty' fibre.

Crime scene investigation should be carried out using a critical forensic approach by an expert team. This provides essential tools in the research and collection of evidence and samples which must be integrated with the autopsy and the police officers' investigations. This paper aims to highlight the importance of a multidisciplinary approach to crime scene investigation and describes a very interesting criminal case. As demonstrated by this case, the evidence obtained from the crime scene analysis sheds light on difficult cases, such as murders staged as suicides or accidents.

First report of Heleomyzidae (Diptera) recovered from the inner cavity of an intact human femur.

One of the main characteristics of the Mafia of Gargano is their use of ritual murders: they shoot their victims in the face and then conceal the corpses in the numerous natural ravines present in the Gargano area. Skeletal remains are often recovered in a poor state of preservation under particular conditions related to the environmental situation. Humidity, temperature and environmental contaminants could be considered very important for forensic examinations and are strictly related to the bone preservation status. One of the most important analyses is the identification of the victim: the success rate is linked to the condition of the bones. During military investigations in the Gargano area, several bones were recovered and analyzed in a karst ravine about 30 m deep. The forensic examination highlighted the presence of fly puparia from an intact human femur. The colonization of the inner bone cavity by a species of the Heleomyzidae family is described for the first time. Puparia, despite not being identified at the species level, are described and illustrated and their potential role in the degradation of the victim's DNA is discussed. This work increases our knowledge about the effects of Diptera in the taphonomic process underlying the need of a multidisciplinary approach to skeletal investigations.

Medical Records Quality as Prevention Tool for Healthcare-Associated Infections (HAIs) Related Litigation: a Case Series.

BACKGROUND: Healthcare-associated infections are one of the most serious Public Health concern, as they prolong the length of hospitalization, reduce the quality of life, and increase morbidity and mortality. Despite they are not completely avoidable, the number of healthcare-associated infections related to negligence claims has risen over the last years, contributing to remarkable economic and reputation losses of Healthcare System. METHODS: In this regard, several studies suggested a key role of medical records quality in determining medical care process, risk management and preventing liability. Clinical documentation should be able to demonstrate that clinicians met their duty of care and did not compromise patient's safety. RESULTS: Therefore, it has a key role in assessing healthcare workers' liability in malpractice litigation. Our risk management experience has confirmed the role of medical records accuracy in preventing hospital liability and improving the quality of medical care. CONCLUSION: In the presented healthcare-associated infections cases, evidence-based and guidelinesbased practice, as well as a complete/incomplete medical record, have shown to significantly affect the verdict of the judicial court and inclusion/exclusion of hospital liability in healthcare-associated infections related claims.

Anabolic Androgenic Steroids: Searching New Molecular Biomarkers.

Even if anabolic androgenic steroid (AAS) abuse is clearly associated with a wide spectrum of collateral effects, adolescents and athletes frequently use a large group of synthetic derivatives of testosterone, both for aesthetic uses and for improving performance. Over the last few years, the development of MicroRNA (miRNA) technologies has become an essential part of research projects and their role as potential molecular biomarkers is being investigated by the scientific community. The circulating miRNAs detection as a diagnostic or prognostic tool for the diagnosis and treatment of several diseases is very useful, because with a minimal quantity of sample (peripheral blood), miRNAs are very sensitive. Even more, miRNAs remain stable both at room temperature and during freeze-thaw cycles. These characteristics highlight the important role of miRNAs in the near future as new tools for anti-doping. The article provides a systematic review and meta-analysis on the role of miRNAs as new potential molecular biomarkers of AAS use/abuse. Particularly, this paper analyzed the "miRNA signature" use as biomarkers for health disorders, focusing on the organ damages which are related to ASS use/abuse. Moreover, this review aims to provide a future prospect for less invasive or non-invasive procedures for the detection of circulating miRNA biomarkers as doping assumption signaling.

The Role of Anabolic Androgenic Steroids in Disruption of the Physiological Function in Discrete Areas of the Central Nervous System.

Anabolic-androgenic steroids (AAS) abuse is often associated with a wide spectrum of adverse effects. These drugs are frequently abused by adolescents and athletes for esthetic purposes, as well as for improvement of their endurance and performances. In this literature review, we evaluated the correlation between AAS and anxiety or aggression. Two pathways are thought to be involved in AAS-induced behavioral disorders. Direct pathway via the amygdalo-fugal pathway, which connects the central nucleus of the amygdala to the brainstem, is involved in cognitive-emotive and homeostatic processes. The latter is modified by chronic AAS use, which subsequently leads to increased anxiety. Indirect pathways via the serotonergic, dopaminergic, and glutamatergic signals which are modified by AAS abuse in latero-anterior hypothalamus and can mediate the aggressive behavior. In conclusion, the molecular mechanisms underlying the behavioral alterations following AAS abuse is unclear and remains ambiguous as additional long-term studies aimed to understand the precise mechanisms are required.

Heart rate variability as predictive factor for sudden cardiac death.

Sudden cardiac death (SCD) represents about 25% of deaths in clinical cardiology. The identification of risk factors for SCD is the philosopher's stone of cardiology and the identification of non-invasive markers of risk of SCD remains one of the most important goals for the scientific community.The aim of this review is to analyze the state of the art around the heart rate variability (HRV) as a predictor factor for SCD.HRV is probably the most analyzed index in cardiovascular risk stratification technical literature, therefore an important number of models and methods have been developed.Nowadays, low HRV has been shown to be independently predictive of increased mortality in post- myocardial infarction patients, heart failure patients, in contrast with the data of the general population.Contrariwise, the relationship between HRV and SCD has received scarce attention in low-risk cohorts. Furthermore, in general population the attributable risk is modest and the cost/benefit ratio is not always convenient.The HRV evaluation could become an important tool for health status in risks population, even though the use of HRV alone for risk stratification of SCD is limited and further studies are needed.

Hematopoietic Stem Cell Transplantation: A Bioethical Lens.

Hematopoietic stem cell transplantation (HSCT) is one of a range of therapeutic options available to patients suffering from various diseases. HSCT procedure involves important ethical and legal aspects that can occur at every phase of the procedure: the clinical choice of whether to perform the procedure, pretransplantation preparation regimens, donor selection, stem cell harvest procedure, transplantation phase, and short-term and long-term follow-up care. In this discussion paper, we outline the ethical issue-facing physicians involved in HSCT. Currently, HSCT is a widely accepted treatment for many life-threatening diseases. It thus represents a real therapeutic hope for many patients. It does, however, carry a burden of possible morbidity and mortality. Consequently, there are substantial information and communication issues involved in the consent process for HSCT. In the final decision, the judgements of different parties, such as patients, family members, and healthcare professionals, intersect and overlap and this is particularly true when the patient is a minor. Finally, HSCT is a very expensive procedure. The social and economic concerns of HSCT are discussed within the actual contextual framework of the dramatic increase in healthcare costs and inequalities in healthcare in relation to socioeconomic status, educational status, and ethnicity.

"Lupara Bianca" a way to hide cadavers after Mafia homicides. A cemetery of Italian Mafia. A case study.

The Gargano, also known as the 'Spur of Italy', is a sub-region of Italy which is located in North of Puglia, in the Province of Foggia. A ravine located in this area was used as a dumping ground in past. During a clearing operation, a team of speleologists discovered human skeletal remains, which led to an official investigation by the local prosecutor's office. The prosecutor called a team of forensic specialist for a scene investigation to recover and identify the human skeletal remains. Four different human skeletal remains located at four different levels of depth underground were found and were in different conditions. A complete forensic investigation was initiated and comprised of radiological imaging with DNA profiling. Three of the four human skeletal remains that were found were identified as those belonging to men who vanished mysteriously in the nineties. The studies conducted have demonstrated that the victims found were murdered and the murders were attributed to the "Mafia of Gargano". The Mafia of Gargano was officially recognized as a criminal organization dating back to 2009 and their criminal activities included the smuggling of firearms and cigarettes, human trafficking, and smuggling of undocumented immigrants. Murders in which corpses are made to disappear is common practice in criminal activities including that of the Italian Mafia. The "Lupara Bianca" is a colloquial term commonly used in Sicily to refer to concealed murders. To the best of our knowledge, this is the first reported study describing the discovery of one of the locations used extensively by the local Mafia as a "cemetery" for victims of "Lupara Bianca" homicides. Based on evidences collected at the site, an explanation of this homicidal modality will be provided.