Hair toxicological analysis of infants and their mothers: a 5-year retrospective study focusing on cocaine.

Prenatal and infant exposure to drugs of abuse is an emerging social and public health problem affecting children health and which may relate to child abuse and neglect. Exposure to drugs of abuse may occur through different routes, including intrauterine, breastfeeding, accidental intake, passive inhalation, and intentional administration. Currently, cases of suspected exposure can be investigated by hair toxicological analysis, the interpretation of which is, however, often difficult, leading to consequent difficulties in the management of such cases. In order to provide a contribution in terms of interpretation of the analytical results, this study aimed to search for the possible existence of elements, from a toxicological point of view, indicative towards the route of exposure. A retrospective study was performed on cases of suspected exposure to drugs of abuse in children aged 0-1 year, evaluated at a University Hospital between 2018 and 2022. Data of children hair toxicological analysis were analyzed and then compared with those of their mothers, when available; 41.6% children tested positive for cocaine. The study found a significant correlation between cocaine and benzoylecgonine concentrations, and a benzoylecgonine/cocaine ratio that tends to decrease as the age of children increases. From the comparison with mothers, a child/mother cocaine concentration ratio lower than 1 was found in all cases of hair sampled within the first week of life, and a ratio greater than or equal to 1 in all cases in which the sampling was performed later. These results, if confirmed in a larger cohort, could represent a contribution in the interpretation of cases of infant exposure to drugs of abuse and be integrated in the context of their multidisciplinary evaluation.

The Precision, Inter-Rater Reliability, and Accuracy of a Handheld Scanner Equipped with a Light Detection and Ranging Sensor in Measuring Parts of the Body-A Preliminary Validation Study.

BACKGROUND: Anthropometric measurements play a crucial role in medico-legal practices. Actually, several scanning technologies are employed in post-mortem investigations for forensic anthropological measurements. This study aims to evaluate the precision, inter-rater reliability, and accuracy of a handheld scanner in measuring various body parts. METHODS: Three independent raters measured seven longitudinal distances using an iPad Pro equipped with a LiDAR sensor and specific software. These measurements were statistically compared to manual measurements conducted by an operator using a laser level and a meterstick (considered the gold standard). RESULTS: The Friedman test revealed minimal intra-rater variability in digital measurements. Inter-rater variability analysis yielded an ICC = 1, signifying high agreement among the three independent raters. Additionally, the accuracy of digital measurements displayed errors below 1.5%. CONCLUSIONS: Preliminary findings demonstrate that the pairing of LiDAR technology with the Polycam app (ver. 3.2.11) and subsequent digital measurements with the MeshLab software (ver. 2022.02) exhibits high precision, inter-rater agreement, and accuracy. Handheld scanners show potential in forensic anthropology due to their simplicity, affordability, and portability. However, further validation studies under real-world conditions are essential to establish the reliability and effectiveness of handheld scanners in medico-legal settings.

Phosphatidylethanol (PEth) in Blood as a Marker of Unhealthy Alcohol Use: A Systematic Review with Novel Molecular Insights.

The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of unhealthy alcohol use. This systematic review aims to investigate the molecular characteristics of PEth and summarize the last ten years of published literature and its use compared to structured questionnaires. A systematic search was performed, adhering to PRISMA guidelines, through "MeSH" and "free-text" protocols in the databases PubMed, SCOPUS, and Web of Science. The inclusion criteria were as follows: PEth was used for detecting unhealthy alcohol consumption in the general population and quantified in blood through liquid chromatography coupled to mass spectrometry, with full texts in the English language. Quality assessment was performed using the JBI critical appraisal checklist. Twelve papers were included (0.79% of total retrieved records), comprising nine cross-sectional studies and three cohort studies. All studies stratified alcohol exposure and quantified PEth 16:0/18:1 through liquid chromatography coupled to mass spectrometry (LC-MS) in liquid blood or dried blood spots (DBS) with lower limits of quantitation (LLOQ) ranging from 1.7 ng/mL to 20 ng/mL. A correlation between blood PEth level and the amount of alcohol ingested in the previous two weeks was generally observed. PEth interpretative cut-offs varied greatly among the included records, ranging from 4.2 ng/mL to 250 ng/mL, with sensitivity and specificity in the ranges of 58-100% and 64-100%, respectively. Although the biomarker seems promising, further research elucidating the variability in PEth formation and degradation, as well as the molecular mechanisms behind that variability, are necessary.

Entrapment within an ottoman storage bed: an unusual accidental asphyxial death.

Herein, we present an uncommon forensic case of death by asphyxia. The victim was a woman whose body at death scene investigation (DSI) was discovered beside an ottoman storage bed. According to the rescue team, who had moved the body before our arrival, the body was originally found in the prone position and stuck with the neck, thorax and arms within the bed. Examination of the body showed hypostasis that was mainly distributed to the face and the lower chest while sparing the neck and the upper chest. The face was markedly swollen, and the eyes were congested with blood. Dissection and histology revealed pulmonary oedema and emphysema of both lungs. Integrating circumstantial, radiology and autopsy data, it was established that the victim, while trapped between the mattress and the edge of the ottoman storage bed, died by mechanical asphyxia due to cervical-thoracic compression and postural asphyxia acting simultaneously.

Homicide and concealment of the corpse. Autopsy case series and review of the literature.

INTRODUCTION: The concealment of the body following a homicide undermines different moments of the forensic and medico-legal investigations. The aim of the present study is to provide an overview of the literature and the forensic casuistry of the Institute of Legal Medicine of Padova for analyzing and discussing diverse methodological approaches for the forensic pathologist dealing with covered-up homicides. MATERIAL AND METHODS: A literature review, updated until September 2019, was performed, and a literature pool of forensic cases was built. In-house cases were included by conducting a retrospective analysis of the forensic caseworks of Padova of the last 20 years. Data regarding epidemiology, methodology of assessment, methods of concealment, and answers to medico-legal issues were extracted for both data sets. RESULTS AND DISCUSSION: Seventy-eight papers were included in the literature review (78.2% being case reports or case series, 17% retrospective studies, and 6% experimental studies or reviews). Literature and in-house data sets consisted of 145 and 13 cases, respectively. Death scene investigation, radiology, toxicology, and additional analyses were performed in 20-54% of literature and 62-77% of in-house cases. Cover-up by multiple methods prevailed. Death was caused by head trauma in about 40% of cases (both data sets), strangulation in 21% of literature, and 7% of in-house cases, and was undetermined in 17% of literature and 7% of in-house cases. CONCLUSIONS: The methodology of ascertainment should be case-specific and based on a multidisciplinary and multimodal evaluation of all data, including those gained through novel radiological and/or analytical techniques.

Intra-class and inter-class tool discrimination through micro-CT analysis of false starts on bone.

Micro-CT has successfully been applied to the characterization of false starts (FSs) and, among several parameters, kerf width seems to correlate to the tool blade. The aim of the present study was to evaluate the diagnostic value of micro-CT for the differentiation of saw marks produced by different classes of saws and by saws belonging to the same class and differing only in number of teeth per inches (TPI). A morphological and morphometric analysis of 84 marks, produced by 6 saws belonging to 3 morphological classes, was performed. In the experimental cohort, for each parameter, statistically significant differences in intra- and inter-class analysis were searched for and cut-offs were established. The diagnostic accuracy of cut-offs was assessed through statistical analyses on the validation cohort. The morphological assessment did not allow to differentiate saws differing only in TPI. Angle 1 and top kerf width, respectively for cross-cut and rip-cut saws with alternating set, allowed a good discrimination between FSs produced by tools belonging to the same morphological class. High positive predictive values were found in intra-class analyses, while results in inter-class analyses were less encouraging. In cases of dismemberment, a micro-CT-based analysis of FSs is strongly suggested as a part of a multistep and multimodal methodology of assessment, which includes scanning electron microscopy and stereomicroscopy. A morphological assessment should be followed by an experimental trial and by a morphometric analysis. Further studies are needed to evaluate hampering factors, such as damage by physico-chemical agents.

The importance of sex as a risk factor for hospital readmissions due to pulmonary diseases.

BACKGROUND: Pulmonary diseases are a common and costly cause of 30-day readmissions. Few studies have focused on the difference in risk for rehospitalization between men and women in older patients. In this study we analyzed the association between sex and the risk of readmission in a cohort of patients admitted to the hospital for chronic obstructive pulmonary disease (COPD) exacerbation and other major pulmonary diseases. METHODS: This was a retrospective cohort study based on administrative data collected in the Veneto Region in 2016. We included 14,869 hospital admissions among residents aged ≥65 years for diagnosis related groups (DRGs) of the most common disorders of the respiratory system: bronchitis and asthma, pneumonia, pulmonary edema, respiratory failure, and COPD. Multilevel logistic regressions were performed to test the association between 30-day hospital readmission and sex, adjusting for confounding factors. RESULTS: For bronchitis and asthma, male patients had significantly higher odds of 30-day readmission than female patients (adjusted odds ratio (aOR), 2.07; 95% confidence interval (CI), 1.11-3.87). The odds of readmission for men were also significantly higher for pneumonia (aOR, 1.40; 95% CI, 1.13-1.72), for pulmonary edema and respiratory failure (aOR, 1.28; 95% CI, 1.05-1.55), and for COPD (aOR, 1.34; 95% CI, 1.00-1.81). CONCLUSIONS: This study found that male sex is a major risk factors for readmission in patients aged more than 65 years with a primary pulmonary diagnosis. More studies are needed to understand the underlying determinants of this phenomena and to provide targets for future interventions.

Education level and hospitalization for ambulatory care sensitive conditions: an education approach is required.

BACKGROUND: Studies in several different countries and settings suggest that ambulatory care-sensitive conditions (ACSCs)-related hospitalizations could be associated more with socioeconomic variables than with the quality of primary healthcare services. The aim of the present study was to analyze the potential links between education levels or other social determinants and ACSC-related hospitalization rates. METHODS: We analyzed a total of 467 504 records of ordinary discharges after acute hospitalization in 2015-16 for patients 20-74 years old residing in the Veneto Region. We calculated the prevention quality indicators (PQIs) developed by the Agency for Healthcare Research and Quality. Rate ratios (RRs) and 95% confidence intervals (95% CIs) were estimated with a set of Poisson regressions to measure the relative risk by sociodemographic level. RESULTS: Hospitalizations for ACSCs accounted for 3.9% of all hospital admissions (18 436 discharges), and the crude hospitalization rate for ACSCs among 20- to 74-year-olds was 26.6 per 10 000 inhabitants (95% CI, 25.8-27.4). For all conditions, we found a significant association with formal education. In the case of the overall composite PQI#90, e.g. poorly educated people (primary school or no schooling) were at significantly higher risk of hospitalization for ACSCs than the better educated (RR, 4.50; 95% CI, 4.13-4.91). CONCLUSIONS: Currently available administrative data regarding ACSCs may be used effectively for reveal equity issues in the provision of health care. Our results indicate that an educational approach inside Primary Health Care could address the extra risk for preventable healthcare demands associated with poorly educated patients.

Radiological investigation of gunshot wounds: a systematic review of published evidence.

INTRODUCTION: Despite the constantly growing popularity of radiological imaging in forensic pathology, a systematic review investigating the efficiency and limits of radiological techniques, in comparison to forensic autopsy, was still missing. AIM: The present review aims at providing an overview on the current role of radiology in the forensic investigation of fatal gunshot wounds without any restriction to specific radiological techniques. MATERIAL AND METHODS: A systematic literature search on three databases (PubMed, Web of Science, and Science Direct) was performed until December 2017. The Oxford Centre for Evidence Based Medicine (OCEBM) grading system for levels of evidence was applied, in order to weigh published evidence. RESULTS AND DISCUSSION: Eighty-six papers (1.64% of the records) were included. Despite the quite limited general level of evidence, which contrasts with the abundance of the scientific literature on this topic, several recommendations/statements, coupled to their OCEBM grade, were distilled as for the identification of retained bullets, gunshot wounds detection, diagnosis of entrance and exit wounds, trajectories and internal injury detection and estimation of the firing distance. CONCLUSIONS: Imaging radiological technologies represent the present and future of wound ballistics. However, traditional, micro and molecular imaging techniques require further validation through blinded cross-sectional studies with appropriate reference standards (e.g. forensic autopsy).

Post-mortem thermal angiography: a pilot study on swine coronary circulation.

Thermal imaging (TI) allows the detection of thermal patterns emitted from objects as a function of their temperature in the long-infrared spectrum and produces visible images displaying temperature differences. The aim of this pilot study was to test TI to visualize the coronary circulation of swine hearts. Thirty swine hearts were prepared for ex situ coronarography, and thermal images were acquired through a FlirOne thermal camera (FLIR Systems®) paired with a Google Android Smartphone. Coronary arteries were cannulated, namely the anterior interventricular artery, the circumflex branch of the left coronary artery, and the right coronary artery. The heart was cooled, and contrast medium (CM) consisting of distilled water heated to 40 °C was injected in a coronary vessel, while thermal images were captured. These steps were repeated for each coronary vessel and under experimentally simulated coronary heart disease. Thermal imaging coronarography (TIC) allowed a clear representation of the morphology and course of the coronary vessels and of experimentally simulated coronary heart disease, moreover, demonstrated to be easy to perform during or after autopsies on ex situ hearts, non-destructive, reproducible, and cheap. On the basis of these preliminary results, TIC might allow a subsequent more focused and comprehensive cardiopathological examination of the heart, which remains mandatory for the definitive diagnosis of coronary heart disease. Although these preliminary results seem encouraging, further systematic studies on human hearts, both normal and pathological, are necessary for estimating the sensitivity and specificity of the proposed method and to draw any definitive conclusion.

Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

[Personalized medicine and medical malpractice.] / Medicina personalizzata e mala praxis sanitaria.

OBJECTIVES: The manuscript deals with personalized medicine and medical liability in Europe and Italy, addressing the importance of synergistic collaboration between clinical and medico-legal professionals in order to appropriately investigate medical errors and prevent any future adverse event. METHODS: Following a rapid epidemiological overview of mala praxis in Europe, the manuscript presents and discusses the International Guidelines developed and adopted by the International Academy of Legal Medicine (IALM), which guide the work of the medical experts under both criminal and/or civil law. RESULTS: Finally, the manuscript proposes the indispensability of a quality assurance and accreditation system for clinical and medico-legal reports along with a shared and integrated methodology for managing health claims in order to prevent adverse events.

Micro-CT features of intermediate gunshot wounds covered by textiles.

The analysis of gunshot residue (GSR) on the clothing and the underlying skin of the victim may play an important role in the reconstruction of the shooting incident. The aim of the present study was to test micro-computed tomography (micro-CT) for the analysis of firearm wounds experimentally produced on human skin covered by textiles. Firing trials were performed on 60 sections of human calves enveloped by a single layer of fabric (cotton or jeans or leather or nylon) and 15 controls consisting of bare calves. Experimental firings were conducted in a ballistic laboratory at three different muzzle-to-target distances (5, 15, and 30 cm), using a .32 ACP pistol (Beretta Mod. 81) loaded with full-jacketed bullets coming from the same production lot (7.65 × 17 mm, Browning SR). The visual inspection revealed the classic pattern of GSR distribution on the fabrics and the skin of control samples, while only a dark ring around the entrance lesion was identified on the skin beneath the fabrics. Micro-CT analysis showed the presence of radiopaque material on all entrance wounds, with a statistically significant difference between cases and controls. No differences were found among specimens covered by fabrics, with regard to the firing distance and the type of clothing. No GSR-like deposits were detected in exit wounds. Our results suggest that micro-CT analysis may be a useful screening tool for differentiating entry from exit gunshot wounds when the covering textiles are contaminated, damaged, or missing.

A novel methodology for the objective ascertainment of psychic and existential damage.

Personal injury is a legal term for a physical or psychic injury suffered by the plaintiff under civil and/or tort law. With reference to non-pecuniary damages, the evidence itself of physical and/or psychic injury is not sufficient for damage compensation. The process of ascertaining impairments and/or disabilities which pertain to the "personal sphere" of the individual, such as pain and suffering, loss of amenity, and/or psycho-existential damage, poses particular difficulties in relation to the obtainment of scientific evidence. The "immateriality" and the subjective connotation of the personal sphere are, in themselves, critical issues. The clinical data obtained from the neuropsychological ascertainment find their essential prerequisite in the active participation of the examinee who, in legally relevant contexts (criminal law, civil law, insurance), may be "affected" by personal interests. The present manuscript presents a novel interdisciplinary methodology, experimented on a series of judicial and extra-judicial cases, aimed at the attainment of objectivity and accuracy eligible in relation to the judicial settlement of cases and other matters involving the ascertainment of peculiar aspects of non-pecuniary damage.

Padova Charter on personal injury and damage under civil-tort law : Medico-legal guidelines on methods of ascertainment and criteria of evaluation.

Compensation for personal damage, defined as any pecuniary or non-pecuniary loss causally related to a personal injury under civil-tort law, is strictly based on the local jurisdiction and therefore varies significantly across the world. This manuscript presents the first "International Guidelines on Medico-Legal Methods of Ascertainment and Criteria of Evaluation of Personal Injury and Damage under Civil-Tort Law". This consensus document, which includes a step-by-step illustrated explanation of flow charts articulated in eight sequential steps and a comprehensive description of the ascertainment methodology and the criteria of evaluation, has been developed by an International Working Group composed of juridical and medico-legal experts and adopted as Guidelines by the International Academy of Legal Medicine (IALM).

Morphometric analysis of stab wounds by MSCT and MRI after the instillation of contrast medium.

OBJECTIVE: To analyze the morphology and depth of stab wounds experimentally produced on human legs amputated for medical reasons using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) after the instillation of a single contrast medium solution (CMS). MATERIALS AND METHODS: For morphological analysis, MSCT and MRI scans were performed before and after the instillation of CMS into the wound cavity. Depth measurements were performed on the sagittal view only after CMS instillation. Subsequently, each wound was dissected using the layer-by-layer technique and the depth was measured by a ruler. One-way between-groups pairwise analysis of variance (ANOVA) and Bland-Altman plot analysis were used for comparing radiological and anatomical measurements. RESULTS: Unenhanced MSCT images did not identify the wound channels, whereas unenhanced MRI evidenced the wound cavity in 50 % of cases. After the instillation of CMS, both MSCT and MRI depicted the wound channel in all the investigated stabbings, although the morphology of the cavity was irregular and did not resemble the shape of the blade. The radiological measurements of the wounds' depth, after the application of CMS, exhibited a high level of agreement (about 95 % at Bland-Altman plot analysis) with the anatomical measurements at dissection. A similar systematic underestimation, however, has been evidenced for MSCT (average 11.4 %; 95 % CI 7-17) and MRI (average 9.6 %; 95 % CI 6-13) data after the instillation of CMS with respect to wound dissection measurements. CONCLUSION: MSCT and MRI after the instillation of CMS can be used for depicting the morphometric features of stab wounds, although depth measurements are affected by a slight systematic underestimation compared to layer-by-layer dissection.

Sensitivity and specificity of EtG in hair as a marker of chronic excessive drinking: pooled analysis of raw data and meta-analysis of diagnostic accuracy studies.

BACKGROUND: To assess the debated diagnostic performance of ethyl glucuronide in the 3-cm proximal scalp hair fraction (HEtG) as a marker of chronic excessive drinking. METHODS: In July 2012/May 2013, after a systematic search through the MEDLINE, OVID/EMBASE, WEB OF SCIENCE, and SCOPUS databases, 8 studies were included in the pooled analysis that report raw single data on HEtG concentration and self-reported daily alcohol intake (SDAI). A receiver operating characteristic curve analysis and a Spearman rank-order correlation test were used. A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane recommendations, comprising quality and bias assessments. RESULTS: The pooled analysis showed that 30 pg/mg could be a useful cutoff value for HEtG to detect an SDAI >60 g/d and demonstrated a parabolic direct correlation between HEtG and SDAI data [rho 0.79; 95% confidence interval (CI), 0.69-0.87; P < 0.001]. The meta-analysis found an overall HEtG sensitivity of 0.96 (95% CI, 0.72-1.00) and a specificity of 0.99 (95% CI, 0.92-1.00); a nomogram to predict the posttest probability of exhibiting the targeted condition in the general population was built. Significant variability among the included studies was detected, which was mainly explained by true heterogeneity in the presence of publication bias. CONCLUSIONS: With the available data, we conclude that HEtG is a promising marker for identifying chronic excessive drinking. Nonetheless, larger and well-designed population studies are required to draw any definitive conclusions on the significance and appropriateness of its application in the forensic setting.

Can immunohistochemistry quantification of Cathepsin-D be useful in the differential diagnosis between vital and post-mortem wounds in humans?

Markers of skin wound vitality and the research methodology used for their determination are still matters of debate in forensic pathology. Cathepsin-D, a lysosomal enzyme, is the most expressed cathepsin in human skin, and although it seems to have the necessary requirements to be utilized as a vitality marker, past research has provided no definitive and clear response on its potential usefulness. Immunohistochemistry with monoclonal antibodies and image analysis has been employed to detect and quantify the expression of Cathepsin-D in human skin wounds. We analyzed skin fragments obtained from 20 living individuals (group A) and 20 persons deceased from natural causes (group B). For each case, five skin fragments were withdrawn at 0', 5', 10', 30', and 90' after abdominal incision. Once the samples were formalin-fixed and paraffin-embedded, we analyzed the expression of Cathepsin-D through the quantification of the immunohistochemistry signal by image analysis. Immunoreactivity was displayed in Pixels of positive area measured by image analysis and converted in micrometer squares. The average levels of Cathepsin-D were higher in group B than in group A, except in three cases which showed a lower expression, with a statistically significant difference of Cathepsin-D expression between the two groups (p < 0.0001). Group B showed unvaried levels among the progressive samples and group A revealed an increasing predominant trend at 30'. Due to the high levels of expression of Cathepsin-D found in the post-mortem injuries, our study definitively excludes any usefulness of immunohistochemistry quantification of this enzyme in the differentiation between vital and post-mortem injuries.

Dying at home during the SARS-CoV-2 endemic: The importance of defining the exact mechanism of death.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) has become endemic in Europe thanks to the presence of less deadly and more infectious variants and to the existence of a significant portion of unvaccinated people among the general population. SARS-Cov-2 related deaths are probably going to fade in the next years, but Covid-19 should still be considered a potential cause of death in the out-of-hospital setting in the next future. MATERIAL AND METHODS: Three (3) cases of unexpected death at home are here presented. Each case has been investigated with the same methodological approach: death scene investigation (DSI), complete autopsy with histology, immunohistochemistry, RNA in situ hybridization for SARS-CoV-2 spike protein in lung tissue, toxicology and microbiology. RESULTS AND DISCUSSION: All three cases had a COVID + post-mortem nasopharyngeal swab. Histology and immunohistochemistry revealed a SARS-CoV-2 lung involvement in only two of the cases (Cases 2 and 3), while a septic bacterial pneumonia was found in Case 1, where RNA-in situ hybridization for viral spike protein showed no reactivity in pneumocytes. The integration of all postmortem evidence allowed to attribute a different role of SARS-Cov-2 in the determinism of the death. CONCLUSION: In the current post-pandemic context, SARS-CoV-2 remains a possible cause of death when investigating out-of-hospital unexpected deaths. Since a positive post-mortem swab does not automatically imply a COVID-19-related death, histology and immunohistochemistry are helpful for identifying SARS-CoV-2 lung involvement and, therefore, its potential active role in the determinism of death.