Forensic significance of postmortem pink teeth: A narrative review.

OBJECTIVE: To review the phenomenon of postmortem pink teeth, exploring its etiology, correlation with the cause of death, and the potential forensic significance of this medico-legal finding. METHODS: A comprehensive literature search was conducted using databases such as PubMed, Scopus, and B-on, employing keywords like "Forensic Pathology," "Forensic Dentistry," "Pink Teeth," and "Medico-legal aspects." The search included studies without temporal limits to gather extensive data on the postmortem pink teeth phenomenon. RESULTS: The postmortem pink teeth phenomenon is characterized by a red-pink discoloration of the dentin, typically sparing the enamel. It is most often observed in moist environments and cases involving water immersion, strangulation, and carbon monoxide poisoning. The study found no consistent relationship between the pink discoloration and specific causes of death, suggesting the phenomenon is more closely related to environmental conditions and the state of decomposition. The pink coloration is more prevalent in anterior, single-rooted teeth and younger individuals. CONCLUSION: The postmortem pink teeth phenomenon remains a complex and enigmatic finding in forensic science. While it does not conclusively indicate a specific cause of death, understanding its occurrence can aid forensic investigations. Further research is needed to elucidate this phenomenon's mechanisms and validate its forensic relevance.

"Not everything that can be counted counts" in ethanol toxicological results: an antemortem and postmortem technical interpretation focusing on driving under the influence.

Ethanol blood analysis is the most common request in forensic toxicology, and some studies point to positive results in approximately one-third of all unnatural deaths. However, distinguishing sober deaths from drunk deaths is not as simple as it may seem. This technical, clinical, and forensic interpretation is proposed to interpret the ethanol toxicological results, discussing several artefacts and pitfalls that must be considered, namely focusing on driving under the influence. This work is presented with a practical and objective approach, aiming to alleviate the complexities associated with clinical, physiological, pathophysiological, and toxicological aspects to enhance comprehension, practicality, and applicability of its content, especially to courts. Particularly the physical integrity of the body, the postmortem interval, putrefactive signs, anatomic place of blood collection, alternative samples such as vitreous humour and urine, the possibility of postmortem redistribution, the inclusion of preservatives in containers, and optimal temperature conditions of shipment are among some of the aspects to pay attention. Although several biomarkers related to postmortem microbial ethanol production have been proposed, their translation into forensic routine is slow to be implemented due to the uncertainties of their application and analytical difficulties. Specifically, in the interpretation of ethanol toxicological results, "not everything that can be counted counts and not everything that counts can be counted" (attributed to Albert Einstein).

Ovarian cancer ascites proteomic profile reflects metabolic changes during disease progression.

Ovarian cancer (OC) patients develop ascites, an accumulation of ascitic fluid in the peritoneal cavity anda sign of tumour dissemination within the peritoneal cavity. This body fluid is under-researched, mainly regarding the ascites formed during tumour progression that have no diagnostic value and, therefore, are discarded. We performed a discovery proteomics study to identify new biomarkers in the ascites supernatant of OC patients. In this preliminary study, we analyzed a small amount of OC ascites to highlight the importance of not discarding such biological material during treatment, which could be valuable for OC management. Our findings reveal that OC malignant ascitic fluid (MAF) displays a proliferative environment that promotes the growth of OC cells that shift the metabolic pathway using alternative sources of nutrients, such as the cholesterol pathway. Also, OC ascites drained from patients during treatment showed an immunosuppressive environment, with up-regulation of proteins from the signaling pathways of IL-4 and IL-13 and down-regulation from the MHC-II. This preliminary study pinpointed a new protein (Transmembrane Protein 132A) in the OC context that deserves to be better explored in a more extensive cohort of patients' samples. The proteomic profile of MAF from OC patients provides a unique insight into the metabolic kinetics of cancer cells during disease progression, and this information can be used to develop more effective treatment strategies.

Single-camera photogrammetry using a mobile phone for low-cost documentation of corpses.

Photogrammetry is a technique for studying and defining objects' shape, dimension, and position in a three-dimensional space using measurements obtained from two-dimensional photographs. It has gained popularity following the development of computer graphics technologies and has been applied to various branches of medicine. In this study, the authors present a method for low-cost photorealistic documentation of corpses during autopsy using single-camera photogrammetry with a mobile phone. Besides representing the body by demonstrating the injured and non-injured body parts as control, evidencing the body parts on a 3D reconstruction allows easy explanation to nonmedical experts such as lawyers.

Clinical and forensic aspects of potassium iodide: Suddenly in high demand across Europe due to fears of radiation poisoning from a nuclear attack in Ukraine.

Potassium iodide has demonstrated several therapeutic applications over time, being the choice for shielding the thyroid during radiation emergencies involving radioiodine release. Amidst the ongoing military conflict between Ukraine and Russia and the growing concern regarding the potential deployment of nuclear weapons, there has been a surge in the demand for potassium iodide across Europe. This work aimed to comprehensively review the current knowledge regarding the pharmacology, physiology, adverse effects, the protective role in reducing the risk of thyroid cancer and recommendations for potassium iodide use during radiation emergencies. Evidence on adverse effects is scarce, as potassium iodide is generally well-tolerated. Guidelines for thyroid blocking with potassium iodide during radiation emergencies suggest that, among populations vulnerable to radioiodine exposure, the benefits of potassium iodide outweigh the risks of adverse effects. Controversial topics surrounding the utilization of potassium iodide in radiation emergencies include the prophylaxis in iodine-deficient regions and following the detonation of dirty bombs, whether granule formulations versus tablets should be used and mental health concerns. Although the rise in demand seems to be a justified security measure, it is essential to recognize that potassium iodide protects the thyroid from radioiodine and does not impact the body's absorption of other radioactive materials or defend against external radiation exposure.

Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity.

Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. The hippocampal formation is known to participate in memory and learning processes and has been documented to contribute to opioid dependence. Accordingly, the present study assessed molecular and cellular alterations in the hippocampal formation of Wistar rats intraperitoneally administered with 50 mg/kg tramadol or tapentadol for eight alternate days. Alterations were found in serum hydrogen peroxide, cysteine, homocysteine, and dopamine concentrations upon exposure to one or both opioids, as well as in hippocampal 8-hydroxydeoxyguanosine and gene expression levels of a panel of neurotoxicity, neuroinflammation, and neuromodulation biomarkers, assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of hippocampal formation sections showed increased glial fibrillary acidic protein (GFAP) and decreased cluster of differentiation 11b (CD11b) protein expression, suggesting opioid-induced astrogliosis and microgliosis. Collectively, the results emphasize the hippocampal neuromodulator effects of tramadol and tapentadol, with potential behavioral implications, underlining the need to prescribe and use both opioids cautiously.

The Future Is Now: Unraveling the Expanding Potential of Human (Necro)Microbiome in Forensic Investigations.

The relevance of postmortem microbiological examinations has been controversial for decades, but the boom in advanced sequencing techniques over the last decade is increasingly demonstrating their usefulness, namely for the estimation of the postmortem interval. This comprehensive review aims to present the current knowledge about the human postmortem microbiome (the necrobiome), highlighting the main factors influencing this complex process and discussing the principal applications in the field of forensic sciences. Several limitations still hindering the implementation of forensic microbiology, such as small-scale studies, the lack of a universal/harmonized workflow for DNA extraction and sequencing technology, variability in the human microbiome, and limited access to human cadavers, are discussed. Future research in the field should focus on identifying stable biomarkers within the dominant Bacillota and Pseudomonadota phyla, which are prevalent during postmortem periods and for which standardization, method consolidation, and establishment of a forensic microbial bank are crucial for consistency and comparability. Given the complexity of identifying unique postmortem microbial signatures for robust databases, a promising future approach may involve deepening our understanding of specific bacterial species/strains that can serve as reliable postmortem interval indicators during the process of body decomposition. Microorganisms might have the potential to complement routine forensic tests in judicial processes, requiring robust investigations and machine-learning models to bridge knowledge gaps and adhere to Locard's principle of trace evidence.

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis.

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+ CD11b+ CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies.

Bisphosphonates and osteonecrosis of the jaws: Clinical and forensic aspects.

OBJECTIVE: This manuscript aims to provide a comprehensive review of the current knowledge in the pathophysiology, diagnosis, prevention, and other relevant clinical and forensic aspects of a potentially severe complication known as medication-related osteonecrosis of the jaw (MRONJ) while synthesizing state-of-the-art information on bisphosphonates and introducing a possible differential diagnosis. DESIGN: An extensive search was conducted in PubMed (U.S. National Library of Medicine) without a time or language constraint, focusing on the epidemiology, pathophysiology, risk factors, site specificity, signs and symptoms, differential diagnosis, prevention, and forensic aspects of MRONJ. All types of original articles, reviews, case reports, short communications, opinion articles, guidelines, and letters to editors were considered to produce a complete review on this subject. RESULTS: MRONJ prevention relies on a multidisciplinary approach and is critical since truly effective treatments are lacking. This therapeutic challenge is partly due to uncertainty regarding this condition's pathophysiology. Differential diagnosis of osteonecrosis of the jaws associated with krokodil abuse, one of the most dangerous and homemade psychoactive illicit substances, should be considered. CONCLUSIONS: Further research into the etiology and site specificity of MRONJ is encouraged, aiming to develop novel treatment prospects. Indeed, comprehending this would allow for increased efficacy and therapeutic options while emphasizing the importance of prevention. In addition, we advocate for greater consensus among the various societies regarding MRONJ's treatment and management.

No Boundaries for Toxicology in Clinical Medicine: One Health, One Society and One Planet for All of Us.

The concept of One Health is not new; it can be traced back for at least two hundred years [...].

Clinical and Forensic Signs Resulting from Exposure to Heavy Metals and Other Chemical Elements of the Periodic Table.

Several heavy metals and other chemical elements are natural components of the Earth's crust and their properties and toxicity have been recognized for thousands of years. Moreover, their use in industries presents a major source of environmental and occupational pollution. Therefore, this ubiquity in daily life may result in several potential exposures coming from natural sources (e.g., through food and water contamination), industrial processes, and commercial products, among others. The toxicity of most chemical elements of the periodic table accrues from their highly reactive nature, resulting in the formation of complexes with intracellular compounds that impair cellular pathways, leading to dysfunction, necrosis, and apoptosis. Nervous, gastrointestinal, hematopoietic, renal, and dermatological systems are the main targets. This manuscript aims to collect the clinical and forensic signs related to poisoning from heavy metals, such as thallium, lead, copper, mercury, iron, cadmium, and bismuth, as well as other chemical elements such as arsenic, selenium, and fluorine. Furthermore, their main sources of occupational and environmental exposure are highlighted in this review. The importance of rapid recognition is related to the fact that, through a high degree of suspicion, the clinician could rapidly initiate treatment even before the toxicological results are available, which can make a huge difference in these patients' outcomes.

Twenty years of real-world data to estimate chronic kidney disease prevalence and staging in an unselected population.

Chronic kidney disease (CKD) represents a global public health burden, but its true prevalence is not fully characterized in the majority of countries. We studied the CKD prevalence in adult users of the primary, secondary and tertiary healthcare units of an integrated health region in northern Portugal (n = 136 993; representing ∼90% of the region's adult population). Of these, 45 983 (33.6%) had at least two estimated glomerular filtration rate (eGFR) assessments and 30 534 (22.2%) had at least two urinary albumin:creatinine ratio (UACR) assessments separated by at least 3 months. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as a persistent decrease in eGFR (<60 ml/min/1.73 m2) and/or an increase in UACR (≥30 mg/g). The estimated overall prevalence of CKD was 9.8% and was higher in females (5.5%) than males (4.2%). From these, it was possible to stratify 4.7% according to KDIGO guidelines. The prevalence of CKD was higher in older patients (especially in patients >70 years old) and in patients with comorbidities. This is the first real-world-based study to characterize CKD prevalence in a large, unselected Portuguese population. It probably provides the nearest estimate of the true CKD prevalence and may help healthcare providers to guide CKD-related policies and strategies focused on prevention and on the improvement of cardiovascular disease and other outcomes.

Tramadol and Tapentadol Induce Conditioned Place Preference with a Differential Impact on Rewarding Memory and Incubation of Craving.

Tramadol and tapentadol, synthetic opioids commonly prescribed for moderate-to-severe pain, have a unique pharmacology that optimizes their analgesia and safety. However, they are not devoid of risks, presenting addictive, abuse, and dependence potential. While tramadol-reinforcing properties have been documented by various studies with human and animal models, including conditioned place preference (CPP) assays, no similar studies have been performed with tapentadol. In the present study, we performed CPP assays by intraperitoneally administering Wistar rats with a tramadol/tapentadol therapeutic dose. Animal permanence and the number of entries in the CPP compartments were recorded in the preconditioning phase and then 1 (T1), 7 (T7), and 14 (T14) days after conditioning. Both opioids induced a change in place preference (T1), suggesting that they have short-term reinforcing properties. However, only tramadol was associated with place preference retention (T7 and T14), with an increase in the number of entries in the opioid-paired compartment (T1 and T7), showing that it causes rewarding memory and incubation of craving. The results indicate that at therapeutic doses: (1) both drugs cause short-term rewarding effects and (2) as opposed to tramadol, tapentadol does not cause CPP retention, despite its higher central nervous system activity and stricter scheduling.

Toxicological Analysis of Drugs in Human Mummified Bodies and Proposed Guidelines.

From palaeopathology to forensic taphonomy, mummified human bodies constitute biological archives of paramount importance. Toxicology analysis of endobiotics and xenobiotics has already shown value to archaeological mummies research with detecting heavy metals, sedative-hypnotic drugs, and stimulants. Thanks to the large window of drug detection in hair and nails, the information from such studies has increased the scientific community's knowledge regarding past populations' lifestyles. Still, few bibliographic references exist regarding toxicology reports in mummified bodies from forensic settings. Here, the authors aim to draw attention to the valuable contribution of toxicology analysis, taking into account previously conducted studies and their findings. Given that sample collection on mummified bodies from forensic scenarios may not always happen in laboratories or autopsy rooms, the authors also suggest guidelines for in situ sampling of forensic mummies. It is expected that the present technical note will encourage experts to perform toxicology analysis in mummified bodies and publish their case reports more often.

Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins.

Ovarian cancer metastization is accompanied by the development of malignant ascites, which are associated with poor prognosis. The acellular fraction of this ascitic fluid contains tumor-promoting soluble factors, bioactive lipids, cytokines, and extracellular vesicles, all of which communicate with the tumor cells within this peritoneal fluid. Metabolomic profiling of ovarian cancer ascites has revealed significant differences in the pathways of fatty acids, cholesterol, glucose, and insulin. The proteins involved in these pathways promote tumor growth, resistance to chemotherapy, and immune evasion. Unveiling the key role of this liquid tumor microenvironment is crucial for discovering more efficient treatment options. This review focuses on the cholesterol and insulin pathways in ovarian cancer, identifying statins and metformin as viable treatment options when combined with standard chemotherapy. These findings are supported by clinical trials showing improved overall survival with these combinations. Additionally, statins and metformin are associated with the reversal of T-cell exhaustion, positioning these drugs as potential combinatory strategies to improve immunotherapy outcomes in ovarian cancer patients.

Health Outcomes in Women Victims of Intimate Partner Violence: A 20-Year Real-World Study.

Intimate partner violence is characterized by violent actions against a person perpetrated by his or her former or current partner, regardless of cohabitation. It most frequently affects women, and one of its most relevant outcomes is the health problems associated with the experience of repeated violence. Thus, the main objective of this study is to analyse the prevalence of health problems among women for whom there was a medical suspicion of being victims of intimate partner violence. The specific objectives are to analyse the prevalence of (a) health risk behaviours; (b) traumatic injuries and intoxications; (c) mental health conditions; and (d) somatic diseases. We conducted a real-world, retrospective, observational, cross-sectional and multicentric study based on secondary data analyses of electronic health records and health care register data in patients of the Local Healthcare Unit of Matosinhos (between 2001 and 2021). The identified data were extracted from electronic health records corresponding to the Health Insurance Portability and Accountability Act Safe Harbor Standard. Information was obtained considering the International Classification of Diseases, the International Classification of Primary Care, and the Anatomical Therapeutic Chemical Classification System, as well as clinical notes (according to previously defined keywords). Considering all information sources, 1676 cases were obtained. This number means that just 2% of the women observed at this health care unit were suspected of being victims of intimate partner violence, which is far from the known statistics. However, we found much higher rates of all health risk behaviours, trauma and intoxication cases, mental health conditions, and somatic disorders we looked for, when compared to the general population. Early detection of these cases is mandatory to prevent or minimize their related health outcomes.

Cardiovascular Risk Profile and Lipid Management in the Population-Based Cohort Study LATINO: 20 Years of Real-World Data.

The rising prevalence of cardiovascular (CV) risk factors in Portugal has translated into more than 35,000 annual deaths due to CV diseases. We performed a multicenter observational cohort study encompassing clinical activities performed between 2000 and 2019 to characterize the CV risk profile and LDL-C management of patients in every CV risk category using electronic health records of a regional population in Portugal. We analyzed data from 14 health centers and 1 central hospital in the north of Portugal of patients between 40 and 80 years that had at least 1 family medicine appointment at these institutions. Living patients were characterized on 31 December 2019. CV risk assessment was computed according to the 2019 ESC/EAS Guidelines. Lipid-lowering therapy (LLT) and achievement of LDL-C targets were assessed. In total, the analysis included 78,459 patients. Patient proportions were 33%, 29%, 22%, and 17% for low, intermediate, high, and very high CV risk, respectively. Moderate-intensity statins were the most frequently used medication across all CV risk categories. High-intensity statins were used in 5% and 10% of high and very high CV risk patients, respectively. Ezetimibe was used in 6% and 10% of high and very high CV risk patients, respectively. LDL-C targets were achieved in 44%, 27%, 7%, and 3% of low, intermediate, high, and very high CV risk patients, respectively. For uncontrolled patients in the high and very high CV risk categories, a median LDL-C reduction of 44% and 53%, respectively, would be required to meet LDL-C targets. There are clear opportunities to optimize LDL-C management in routine clinical practice. The prescription of LLT according to CV risk represents an important missed treatment opportunity.

Immune Tumor Microenvironment in Ovarian Cancer Ascites.

Ovarian cancer (OC) has a specific type of metastasis, via transcoelomic, and most of the patients are diagnosed at advanced stages with multiple tumors spread within the peritoneal cavity. The role of Malignant Ascites (MA) is to serve as a transporter of tumor cells from the primary location to the peritoneal wall or to the surface of the peritoneal organs. MA comprise cellular components with tumor and non-tumor cells and acellular components, creating a unique microenvironment capable of modifying the tumor behavior. These microenvironment factors influence tumor cell proliferation, progression, chemoresistance, and immune evasion, suggesting that MA play an active role in OC progression. Tumor cells induce a complex immune suppression that neutralizes antitumor immunity, leading to disease progression and treatment failure, provoking a tumor-promoting environment. In this review, we will focus on the High-Grade Serous Carcinoma (HGSC) microenvironment with special attention to the tumor microenvironment immunology.

Raising Awareness on the Clinical and Forensic Aspects of Jellyfish Stings: A Worldwide Increasing Threat.

Jellyfish are ubiquitous animals registering a high and increasing number of contacts with humans in coastal areas. These encounters result in a multitude of symptoms, ranging from mild erythema to death. This work aims to review the state-of-the-art regarding pathophysiology, diagnosis, treatment, and relevant clinical and forensic aspects of jellyfish stings. There are three major classes of jellyfish, causing various clinical scenarios. Most envenomations result in an erythematous lesion with morphological characteristics that may help identify the class of jellyfish responsible. In rare cases, the sting may result in delayed, persistent, or systemic symptoms. Lethal encounters have been described, but most of those cases happened in the Indo-Pacific region, where cubozoans, the deadliest jellyfish class, can be found. The diagnosis is mostly clinical but can be aided by dermoscopy, skin scrapings/sticky tape, confocal reflectance microscopy, immunological essays, among others. Treatment is currently based on preventing further envenomation, inactivating the venom, and alleviating local and systemic symptoms. However, the strategy used to achieve these effects remains under debate. Only one antivenom is currently used and covers merely one species (Chironex fleckeri). Other antivenoms have been produced experimentally but were not tested on human envenomation settings. The increased number of cases, especially due to climate changes, justifies further research in the study of clinical aspects of jellyfish envenoming.