In Vivo Bio-Activation of JWH-175 to JWH-018: Pharmacodynamic and Pharmacokinetic Studies in Mice.

3-(1-Naphthalenylmethyl)-1-pentyl-1H-indole (JWH-175) is a synthetic cannabinoid illegally marketed for its psychoactive cannabis-like effects. This study aimed to investigate and compare in vitro and in vivo pharmacodynamic activity of JWH-175 with that of 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018), as well as evaluate the in vitro (human liver microsomes) and in vivo (urine and plasma of CD-1 male mice) metabolic profile of JWH-175. In vitro binding studies showed that JWH-175 is a cannabinoid receptor agonist less potent than JWH-018 on mouse and human CB1 and CB2 receptors. In agreement with in vitro data, JWH-175 reduced the fESPS in brain hippocampal slices of mice less effectively than JWH-018. Similarly, in vivo behavioral studies showed that JWH-175 impaired sensorimotor responses, reduced breath rate and motor activity, and increased pain threshold to mechanical stimuli less potently than JWH-018. Metabolic studies demonstrated that JWH-175 is rapidly bioactivated to JWH-018 in mice blood, suggesting that in vivo effects of JWH-175 are also due to JWH-018 formation. The pharmaco-toxicological profile of JWH-175 was characterized for the first time, proving its in vivo bio-activation to the more potent agonist JWH-018. Thus, it highlighted the great importance of investigating the in vivo metabolism of synthetic cannabinoids for both clinical toxicology and forensic purposes.

Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1ß, IL-6, IL-15 and TNF-α.

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1ß, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1ß in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice.

4,4'-Dimethylaminorex (4,4'-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1-60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4'-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers' co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.

Prosthetic joint infections and legal disputes: a threat to the future of prosthetic orthopedics.

Prosthetic joint infections (PJI) represent one of the major problems in orthopedic prosthetic surgery. The incidence of PJIs varies according to the site of intervention, and different published case studies report occurrence at 0.5 to 3.0% in the event of first implants, with a significant greater risk in the case of prosthesis revisions. The diagnosis of prosthetic infections is seldom simple, needing a multi-specialist approach, which includes the accurate collection of patient anamnesis, its clinical evaluation, the evaluation of inflammation biomarkers, and the use of imaging techniques. It is essential to identify the bacteria responsible for the infection not only for an accurate diagnosis, but also to select the correct antibiotic treatment. Failure to identify the bacteria involved makes it impossible to establish targeted systemic antibiotic therapy. In developed countries such as Italy, the right to health is guaranteed by the Constitution, where the institutions that provide health services must be staffed by a team of medical professionals that can guarantee the safest possible health pathways. Risk management represents the set of actions aimed at improving the quality of the care provided, the adherence to guidelines and good care practices with the final objective of guaranteeing patients' safety. All hospitals, including the ones where prosthetic orthopedic surgery is performed, must adopt clinical risk management procedures which, through prospective tools aimed at preventing errors and complications and by retrospective methods, permit the identification of critical points in the different phases of the process and propose actions for improvement. The constant increase in litigation for malpractice in Western countries, especially in Italy, calls for special attention to the problem of PJIs and the in-depth assessment of medico-legal problems, also considering the new legislative initiatives in the field of medical malpractice. Hospitals need to tackle the onset of PJIs in a transparent and linear fashion by constantly informing the patient on their progress.

A homemade furnace. Influence of occupational skills in a fire-related planned complex suicide.

The term "planned complex suicide" means the combination of more than one method of suicide, planned to prevent failure of the first method to ensure a fatal outcome. Professional skills and tools are sometimes used to plan and perpetrate the suicide. A case of planned complex suicide of a mechanical engineer working with furnaces in a tube factory is herein reported. The suicide was committed in a rudimental furnace set up in the victim's apartment using his professional skills, by assembling furniture, mattresses, books and flammable liquid present in the house. Three-dimensional models of the crime scene before and after the realization of the "homemade furnace" are proposed. The discussion will focus on the importance of a comprehensive analysis of the professional background of the victim to infer the manner of death for the identification of complex and occupation-related suicides.

Pedestrian Inattention Blindness While Playing Pokémon Go as an Emerging Health-Risk Behavior: A Case Report.

BACKGROUND: Cases of trauma resulting from the use of mobile phones while driving motor vehicles have become quite common in recent years. Road injuries incurred by people playing video games on mobile phones (or other media devices) while walking have also become a cause for concern. Pokémon Go has been the world's most popular game since it was launched in July 2016, with more than 15 million players trying to catch all Pokémon available in the game; however, the case detailed here is the first reported accident in the medical literature caused by a pedestrian distracted by the game while crossing a street. OBJECTIVE: We aim to provide additional information on the innovative nature of distractions that generate risks in road-users, and to explore the underreporting of pedestrian-motor vehicle collisions due to mobile device usage. METHODS: We included in this case report a 25-year-old male who suddenly crossed a road while playing Pokémon Go and was hit by a van, reporting several injuries and being assisted by the Emergency Medical Service of our hospital (Padova, Italy). The patient's history, the circumstances in which the collision happened, imaging data, and clinical course information were recorded per our hospital's privacy policy. RESULTS: The patient hit by the van was playing Pokémon Go on his mobile phone while crossing a street, despite red traffic lights, which he did not notice due to of the distraction induced by the game. CONCLUSIONS: Mobile videogames that imply movement (ie, walking, running, cycling) to play are an effective way to improve physical activity practice, especially in adolescents and young adults. Nevertheless, cases like the one presented here point out that these games could pose a significant risk to users who play while walking, cycling, or driving in unsafe areas such as city streets, because players become distracted and may ignore surrounding hazards. Comprehensive, multilevel interventions are needed to reduce accidents caused by distraction, and to stress findings on the positive and negative effects of video games, which are becoming a source of public health concern. Health care providers should be aware of their chief role in these possible prevention strategies, based on their direct interactions with road incident victims.

Sex-specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice.

BACKGROUND AND PURPOSE: AKB48 is a synthetic cannabinoid illegally sold for its psychoactive cannabis-like effects that have been associated with acute intoxication and whose effects are poorly known. EXPERIMENTAL APPROACH: Using a behavioural, neurochemical, and immunohistochemical approach, we investigated the pharmaco-toxicological effects, pharmacokinetics, and neuroplasticity at cannabinoid CB1 receptors in the cerebellum and cortex induced by repeated AKB48 administration in male and female mice. KEY RESULTS: The effects of AKB48 varied significantly depending on sex and treatment duration. The first injection impaired sensorimotor responses and reduced body temperature, analgesia, and breath rate to a greater extent in females than in males; the second injection induced stronger effects in males while the third injection of AKB48 induced weaker responses in both sexes, suggesting emergence of tolerance. The CB1 receptor antagonist NESS-0327 prevented the effects induced by repeated AKB48, confirming a CB1 receptor-mediated action. Blood AKB48 levels were higher in females than in males and repeated administration caused a progressive rise of AKB48 levels in both sexes, suggesting an inhibitory effect on cytochrome activity. Finally, immunohistochemical analysis revealed higher expression of CB1 receptors in the cerebellum and cortex of females, and a rapid CB1 receptor down-regulation in cerebellar and cortical areas following repeated AKB48 injections, with neuroadaptation occurring generally more rapidly in females than in males. CONCLUSION AND IMPLICATIONS: We have shown for the first time that AKB48 effects significantly vary with prolonged use and that sex affects the pharmacodynamic/pharmacokinetic responses to repeated administration, suggesting a sex-tailored approach in managing AKB48-induced intoxication.

The perils of dental vacation: possible anaesthetic and medicolegal consequences.

INTRODUCTION: The aim of this paper is to emphasize anaesthesiologists' difficulty in detecting poor dentition in cases of poorly applied prostheses and/or advanced periodontal disease, and to establish whether it is possible, and in which conditions, to calculate compensation in cases of dental damage postlaryngoscopy and/or intubation. The main complex problem here lies in trying to reconstruct exactly what the dental situation was before the teeth were damaged. For this reason the important preoperative factors (dental prostheses, crown fractures, parodontal disease, etc.) must be clearly shown before surgery on a dental chart. CLINICAL CASES: Two cases of interest, both to anaesthesiologists practising intubation and medicolegal physicians who have to deal with potential claims, are briefly reported. The first patient was a 55-year-old diabetic patient, who underwent emergency surgery for acute abdominal pathology. He had gone outside Italy for dental treatment three years previously and now presented with very poor pre-existing dentition, carefully noted on an anaesthetic chart. He now demanded compensation for dental damage due to intubation in Italy; the resulting dental treatment was very expensive because substantial remedial work was required. The second patient had received treatment outside Italy, work which involved cosmetic coating of the teeth. After surgery in Italy, she demanded compensation because one tooth, which had been coated and appeared to be healthy, was broken after emergency intubation. In both cases, the patients demanded very high compensation. COMMENT: Dental tourism alone accounts for more than 250,000 patients each year who combine a holiday with dental treatment in Eastern Europe. However, if prosthetic devices or conservative treatments are not applied correctly, it should be noted that durability may be poorer than expected, but iatrogenic damage may also be caused.

Insect Colonisation and the Decomposition Process in Aerated versus Watertight Burial Systems.

In recent years, burial systems have covered increasingly higher costs due to the pollution caused by decomposition products. These products are understood as chemicals and microorganisms in the surrounding soil and groundwater and represent a topical issue. The purpose of this research was to ascertain the extent of decomposition when pig carcasses are buried in two different burial systems ("aerated" vs. "watertight") and catalogue the arthropods associated with burials at different time-points of removal from niches (after 6, 12, 24, 36, and 60 months). Thirteen taxa were collected in aerated niches, whereas five were collected in watertight niches. The initial access or exclusion of insect colonisers affected overall functional activity. Two Diptera species, Hydrotaea capensis and Megaselia scalaris, were the most abundant, supporting the hypothesis that insects can colonise carcasses in aerated burial systems. Furthermore, some species of bacteria have been documented as facilitators of the initial decomposition process of the carcass. Most bacterial colonies develop only in aerated niches. The trial showed that the first enzymatic-bacterial and insect actions helped promote the process of cadaveric decomposition and later skeletonisation, mainly when associated with aeration modes of the tomb/mound. The results obtained provide essential information on the process of human decomposition and taphonomy in cemeteries. Moreover, these data could benefit forensic science by adding information on insect colonisation and body modification in medico-legal investigations concerning the post-mortem interval in exhumed bodies and illegal burials.

Application of Forensic DNA Phenotyping for Prediction of Eye, Hair and Skin Colour in Highly Decomposed Bodies.

In the last few years, predicting externally visible characteristics (EVCs) by adopting informative DNA molecular markers has become a method in forensic genetics that has increased its value, giving rise to an interesting field called "Forensic DNA Phenotyping" (FDP). The most meaningful forensic applications of EVCs prediction are those in which, having only a DNA sample isolated from highly decomposed remains, it is essential to reconstruct the physical appearance of a person. Through this approach, we set out to evaluate 20 skeletal remains of Italian provenance in order to associate them with as many cases of missing persons as possible. To achieve the intended goal, in this work we applied the HIrisPlex-S multiplex system through the conventional short tandem repeats (STR) method to confirm the expected identity of subjects by evaluating phenotypic features. To investigate the reliability and accuracy of the DNA-based EVCs prediction, pictures of the cases were compared as they were available to researchers. Results showed an overall prediction accuracy greater than 90% for all three phenotypic features-iris, hair, and skin colour-at a probability threshold of 0.7. The experimental analysis showed inconclusive results in only two cases; this is probably due to the characteristics of subjects who had an intermediate eye and hair colour, for which the DNA-based system needs to improve the prediction accuracy.

Pharmaco-Toxicological Effects of Atypical Synthetic Cathinone Mephtetramine (MTTA) in Mice: Possible Reasons for Its Brief Appearance over NPSs Scene.

Over the last year, NPSs have been steadily on the rise in the illicit drug market. Among these, synthetic cathinones seem to become increasingly popular among young adults, mainly because of their ability to replicate the effects of traditional psychostimulant drugs, such as cocaine, MDMA and amphetamines. However, scarce data are available about the in vivo pharmaco-toxicology of these new substances. To this end, this study focused on evaluation of effects induced by repeated administration of mephtetramine (MTTA 0.1-30 mg/kg i.p.) in mice. This atypical cathinone highlighted a sensorial (inhibition of visual and acoustic reflexes) and transient physiological parameter (decrease in breath rate and temperature) change in mice. Regarding motor activity, both a dose-dependent increase (accelerod test) and biphasic effect (drag and mobility time test) have been shown. In addition, blood and urine samples have been analysed to enrich the experimental featuring of the present study with reference to evaluation of potential toxicity related to consumption of MTTA. The latter analysis has particularly revealed important changes in blood cells count and blood and urine physicochemical profile after repeated treatment with this atypical cathinone. Moreover, MTTA induced histological changes in heart, kidney and liver samples, emphasizing its potential toxicity.

Epigenetic Studies for Evaluation of NPS Toxicity: Focus on Synthetic Cannabinoids and Cathinones.

In the recent decade, numerous new psychoactive substances (NPSs) have been added to the illicit drug market. These are synthetized to mimic the effects of classic drugs of abuse (i.e., cannabis, cocaine, etc.), with the purpose of bypassing substance legislations and increasing the pharmacotoxicological effects. To date, research into the acute pharmacological effects of new NPSs is ongoing and necessary in order to provide an appropriate contribution to public health. In fact, multiple examples of NPS-related acute intoxication and mortality have been recorded in the literature. Accordingly, several in vitro and in vivo studies have investigated the pharmacotoxicological profiles of these compounds, revealing that they can cause adverse effects involving various organ systems (i.e., cardiovascular, respiratory effects) and highlighting their potential increased consumption risks. In this sense, NPSs should be regarded as a complex issue that requires continuous monitoring. Moreover, knowledge of long-term NPS effects is lacking. Because genetic and environmental variables may impact NPS responses, epigenetics may aid in understanding the processes behind the harmful events induced by long-term NPS usage. Taken together, "pharmacoepigenomics" may provide a new field of combined study on genetic differences and epigenetic changes in drug reactions that might be predictive in forensic implications.

In vitro and in vivo pharmaco-dynamic study of the novel fentanyl derivatives: Acrylfentanyl, Ocfentanyl and Furanylfentanyl.

Fentanyl derivatives (FENS) belongs to the class of Novel Synthetic Opioids that emerged in the illegal drug market of New Psychoactive Substances (NPS). These substances have been implicated in many cases of intoxication and death with overdose worldwide. Therefore, the aim of this study is to investigate the pharmaco-dynamic profiles of three fentanyl (FENT) analogues: Acrylfentanyl (ACRYLF), Ocfentanyl (OCF) and Furanylfentanyl (FUF). In vitro, we measured FENS opioid receptor efficacy, potency, and selectivity in calcium mobilization studies performed in cells coexpressing opioid receptors and chimeric G proteins and their capability to promote the interaction of the mu receptor with G protein and ß-arrestin 2 in bioluminescence resonance energy transfer (BRET) studies. In vivo, we investigated the acute effects of the systemic administration of ACRYLF, OCF and FUF (0.01-15 mg/kg i.p.) on mechanical and thermal analgesia, motor impairment, grip strength and cardiorespiratory changes in CD-1 male mice. Opioid receptor specificity was investigated in vivo using naloxone (NLX; 6 mg/kg i.p) pre-treatment. In vitro, the three FENS were able to activate the mu opioid receptor in a concentration dependent manner with following rank order potency: FUF > FENT=OCF > ACRYLF. All compounds were able to elicit maximal effects similar to that of dermorphin, with the exception of FUF which displayed lower maximal effects thus behaving as a partial agonist. In the BRET G-protein assay, all compounds behaved as partial agonists for the ß-arrestin 2 pathway in comparison with dermorphin, whereas FUF did not promote ß-arrestin 2 recruitment, behaving as an antagonist. In vivo, all the compounds increased mechanical and thermal analgesia with following rank order potency ACRYLF = FENT > FUF > OCF and impaired motor and cardiorespiratory parameters. Among the substances tested, FUF showed lower potency for cardiorespiratory and motor effects. These findings reveal the risks associated with the use of FENS and the importance of studying the pharmaco-dynamic properties of these drugs to better understand possible therapeutic interventions in the case of toxicity.

Traumatic dental injuries during anaesthesia. Part II: medico-legal evaluation and liability.

INTRODUCTION: Claims for tooth damage following intubation are increasing. An anaesthetic chart (AC) has been proposed to describe patient's pre-existent dental diseases and any possible lesions caused during intubation and extubation. MATERIALS AND METHODS: We conducted a retrospective study of 235 cases of dental lesions reported in litigation files from January 2000 to June 2009. Based on preoperative oral inspection the anaesthetist decided whether or not to use a protective aid. Two different tooth protectors were applied: (i) a standard mouthguard and (ii) silicone impression putty. RESULTS: The study population consisted of 110 female (age 6-88 years) and 125 male patients (11-90 years) patients. In 66% of cases greater risk of perianesthetic dental injury was reported in the AC due to pre-existing poor dentition. In intubation procedures without protective devices dental subluxation/luxation occurred in 55% of patients, dental avulsion in 43%, exfoliation in 2%, and soft tissue damage in five patients. One patient suffered from transient facial nerve paralysis. The costs of treatments and of impression materials, as well as the total value of compensation for injuries are reported. DISCUSSION: Definition and demonstrability of damages on the AC is important in order to separate the cases worthy of compensation from the non-compensable ones, as to evaluate the possibility of solving the litigation by extrajudicial channels. There are cases in which, based on AC reporting and device adoption the damage resulted to be compensable, but the costs were defined on different estimates of lesions. The use of a protective device makes it possible to down-modulate the damage compensation. CONCLUSION: The analysis of litigation records and 'incident reports' has suggested that the choice of accurate proceeding and the use of protection aids could reduce the number of claims, insurance premiums and the costs of litigation process, thus improving physician-patient relationship.

Application of aquatic decomposition scores for the determination of the Post Mortem Submersion Interval on human bodies recovered from the Northern Adriatic Sea.

PURPOSE: The decomposition process of human bodies in marine environment is not well understood, and it is influenced by external variables related to the geographical area where the body is submerged. We report the application of two decomposition scores, the Heaton's score and the van Daalen's score, on a casuistry of human bodies recovered from the Northern Adriatic Sea. The aims of this study are to verify whether the marine environment of a Mediterranean climate area may affect the applicability of both scores and to develop a prediction model that can be applied on bodies recovered in salt water. METHODS: A retrospective study was performed on 61 human bodies recovered between 2005 and 2019 from coastal water of the Northern Adriatic Sea nearby the Italian regions Emilia-Romagna and Marche. For each of the 61 cases included, the Total Aquatic Decomposition Score (TADS) was calculated with the Heaton's score and the Van Daalen's score. The prediction model was assessed through multiple regression analyses, and the determination coefficients (r2) between TADS and PMSI (expressed in days) and between TADS and Accumulate Degrees Days (ADD) were studied. The prediction model was applied to the entire case sample, to bodies recovered during the warm season and to bodies recovered during the cold season. RESULTS: All bodies were recovered floating, and a very poor scavenging activity was observed. The regression analyses showed a strong correlation between the TADS and the total case sample using both scores and both independent variables (PMSI and ADD). The determination coefficients were greater than 0.95 also when considering the total case sample. DISCUSSION: The proposed prediction models are not significantly influenced by seasonality, contrarily to what observed on bodies recovered in fresh water in the same climate area. However, the ADD model, which also consider the water temperature, should be preferred for higher decomposition stages. This study helps increase the accuracy of PMSI estimation in bodies recovered from a marine environment of the Northern Adriatic Sea.

Illegal fishing with electrofishing devices in the Po river basin, Emilia Romagna, Italy.

Electric fishing is an illegal hunting method, unfortunately widely used by poachers to paralyze fish and to catch many animals in a short time. In Italy, it is authorized only for scientific and conservative purposes. Between 2014 and 2018, the Ferrara section of the Experimental Zooprophylactic Institute of Lombardy and Emilia Romagna, Italy, received nine cases of potentially illegal electric fishing in Po river and its tributary rivers. Necropsies were performed following standard protocols and samples of different tissues were collected and examined using histochemical and immunohistochemical techniques. Gross lesions frequently observed were circulatory alteration phenomena (i.e. multi-organ hyperemia, hemorrhages and congestion, hemopericardium), also found histologically, in addition to multifocal degenerative and necrotic muscular processes that could be attributed to injuries from electric current, as already reported in literature. Immunohistochemical investigations confirmed degenerative and necrotic lesions with myoglobin depletion and a corresponding fibrinogen accumulation. Myoglobin globules were also detected in the renal parenchyma, as consequent of rhabdomyolysis. The results of this study allowed to correlate electric fishing to gross, histologic and immunohistochemical lesions, which together constitute a pathognomonic picture to be considered a reference standard in this type of illegal controversy.

Traumatic dental injuries during anaesthesia: part I: clinical evaluation.

UNLABELLED: Dental injuries represent the most common claims against the anaesthesiologist. Dental lesions are frequent complications of oro-tracheal intubation and major causal factors are (i) poor dentition, (ii) aggressive laryngoscopy, (iii) insufficient anaesthesia and curarization, (iv) emergency interventions and (v) lack of experience by the anaesthesiologist. MATERIALS AND METHODS: We conducted a retrospective analysis of 83 cases of dental lesions occurring during elective, emergent and urgent surgery requiring general anaesthesia with tracheal tube placement in the years between 2000 and 2008. Preoperative evaluation of dental status was obtained from the anaesthesiology chart, filled by an experienced anaesthesiologist during the preoperative visit. Anaesthesiological records were inspected by physicians of Legal Medicine Department with the aim to attribute responsibility for the damage and manage potential reimbursements. Costs related to the required dental repair were also noted. RESULTS: Eighty-three patients of a total of 60.000 surgical procedures (no day surgery) under general anaesthesia were affected by dental lesions (0.13%). Seventy-five per cent of lesions occurred during intubation manoeuvres for elective major surgery, 15% occurred at tracheal intubation for minor surgery and 10% were related to emergency surgery. Teeth avulsions accounted for 50% of lesions, followed by damage to crowns and bridges (14%), luxations and fractures (>15%). DISCUSSION: The overall incidence of dental injury in our retrospective study was 1.38 per 1000 anaesthetics, which is slightly higher than those reported by some and lower with respect to others. Avulsion of a permanent tooth occurred in patients who were affected by severe mobility of native teeth while undergoing surgery. Even though the majority of anaesthesiologists were trained enough in the use of airway devices and aware of the potential damage while using excessive forces, some unexpected difficulties may have led to lesions. It is known that damage to teeth can occur even in the absence of negligence.

Postmortem submersion interval in human bodies recovered from fresh water in an area of Mediterranean climate. Application and comparison of preexisting models.

PURPOSE: The methods developed in recent years for the assessment of the Postmortem Submersion Interval (PMSI) have proven to be promising, but are strictly related to specific geographical areas or climates. The aim of this study is to assess the suitability of two of the most recent total aquatic decomposition scores (TADS) for the determination of the PMSI in bodies recovered from fresh water in an area of Mediterranean climate in the last 15 years. To do this, the correlation coefficient (r2) between PMSI and Accumulate Degrees Days (ADD) or PMSI and days was studied. METHODS: The correlation between PMSI (expressed in days or in ADD) and the TADS was evaluated considering: (a) bodies recovered during the entire period; (b) bodies recovered during the cold season; (c) bodies recovered during the warm season. A linear regression analysis was set comparing the statistical significance of a model plotting TADS versus ADD, and another model plotting TADS versus PMSI (expressed in days) for both scores. RESULTS: Scores were scarcely applicable when considering the entire casuistry, as regression models showed low r2 values, but both scores showed high correlations after dividing the cases into 2 groups. In fact, after performing the seasonal partition, we observed a strong correlation between PMSI and TADS, using either of the scores. CONCLUSION: This study helps increase the accuracy, reliability, and validity of PMI estimation in bodies recovered from freshwater in an area of temperate climate, such as Northern Italy, supporting the need to establish regionally-specific equations for estimating PMI in a forensic context.

Gabapentin affects the expression of inflammatory mediators on healthy gingival cells.

Gabapentin is one of the most used drugs to treat postoperative pain with antihyperalgesic properties and has a unique mechanism of action, which differentiates it from other commonly used drugs. Various studies have shown that the perioperative use of gabapentin reduces postoperative pain. In our study, fragments of gingival tissue of healthy volunteers were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblasts cell culture treated with gabapentin, compared with untreated cells. Of the different chemokines and interleukins studied, only 10 were statistically significant (CCL1, CCR1, CCR4, CCR5, CCR6, ILI1A, ILI1B, IL5, IL6R, TNFSF10). The overexpression of these cytokines, obtained in many studies, leads us to think that gabapentin can interact and cause post-inflammatory gingival hyperplasia, but, probably, in our study the gabapentin has not the same effect, because we used gingival fibroblasts of healthy people.