Rosa Maria Gaudio

Quadruple immunofluorescence: a direct visualization method.

We describe fluorescence immunostaining of four different antigens in the same section. The fluorochrome conjugates used show highest emission in the blue, green, yellow, and red regions of the visible light spectrum, respectively. Specially designed single fluorochrome filter combinations allow selective visualization of each fluorochrome label in turn, without visible crosstalk with the others.

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 worlds 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.

Experimental ββ′-iminodipropionitrile (IDPN) neuropathy: neurofilament profile of sensory, motor and autonomic nerves as seen by immunocytochemistry on whole-mount preparations

IDPN-induced changes in a variety of sensory, motor and autonomic nerves were studied by whole-mount immunocytochemistry. A full range of proximo-distal accumulations of neurofilament-like material was found, from paranuclear round bodies in perikarya to distal and preterminal axonal dilations. Conversely, both terminal areas and nodal-paranodal regions of myelinated axons showed striking, sharply localized loss of neurofilament-immunostaining. The latter change, when transport of neurofilaments is halted by IDPN, may indicate their local processing and/or differential transport at nodal-paranodal regions.

Evaluation of the placenta in a stillborn fetus to estimate the time of death.

The authors present a case of a presumably unknown pregnancy, in which the newborn was found dead in the bathroom. The child was considered stillborn and the death due to natural causes. The literature on estimation of the time of fetal death is reviewed. It has been reported that certain placental histological changes are useful in predicting the time of death in stillborn fetuses, but little has been published about their potential role. Furthermore, parameters evaluated by literature in examining the placenta for determining time of fetal demise in cases of stillbirth are not uniform in the few studies that have been published. We emphasize that any attempt to estimate the time of fetal death without an adequate knowledge of placental morphological changes is futile and forensically unjustifiable, and that a comprehensive placental, external, and histological examination of the fetus is still the method of choice to gain a reliable forensic answer.

The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study.

Objectives Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. Methods 133 OAT patients were recruited and assessed for warfarin/3’-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups Results In the whole OAT group both warfarin and 3’-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3’-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3’-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001). Interestingly, 3’-hydroxywarfarin reached a strong correlation at c4 respect to warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3’-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and that the combination of VKORC1 and CYP2C9 yielded a warfarin responsive index (WRI) inversely related to the number variant alleles Conclusion Our results overall suggest that 3’-hydroxywarfarin monitoring could be of great advantage in INR monitoring respect to classical warfarin assessment showing significant contribution also in multivariate analysis. Therefore, additional active metabolites should be recognized and investigated as novel useful indicators.

Unusual Displacement of a Mobilised Dental Bridge during Orotracheal Intubation

Dental trauma during tracheal intubation mostly happens in case of poor dentition, restricted mouth opening, and/or difficult laryngoscopy. 57-year-old man undergoing laparoscopic radiofrequency ablation of unresectable hepatocellular carcinoma had his dental work detached at induction of anesthesia. Oropharyngeal direct view, manual inspection, fibreoptic nosendoscopy, tracheobronchoscopy, and fiberoptic inspection of the esophagus and stomach were unsuccessful in locating the dislodged bridge. While other possible exams were considered, such as lateral and AP x-ray of head and neck, further meticulous manual “sweepings” of the mouth were performed, and by moving the first and second fingers below the soft palate deep towards the posterolateral wall of the pharynx, feeling consistent with a dental prosthesis was detected in the right pharyngeal recess. Only after pulling the palatopharyngeal arch upward was it possible to grasp it and extract it out with the aid of a Magill Catheter Forceps. Even though the preexisting root and bridge deficits were well reported by the consultant dentist, the patient was fully reimbursed. The lack of appropriate documentation of the advanced periodontal disease in the anesthesia records, no mention of potential risks on anesthesia consent, and insufficient protective measures during airway instrumentation reinforced the reimbursement claim.

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.

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.

Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice

ABSTRACT Novel psychoactive substances are intoxicating compounds developed to mimic the effects of well‐established drugs of abuse. They are not controlled by the United Nations drug convention and pose serious health concerns worldwide. Among them, the dissociative drug methoxetamine (MXE) is structurally similar to ketamine (KET) and phencyclidine (PCP) and was created to purposely mimic the psychotropic effects of its “parent” compounds. Recent animal studies show that MXE is able to stimulate the mesolimbic dopaminergic transmission and to induce KET‐like discriminative and rewarding effects. In light of the renewed interest in KET and PCP analogs, we decided to deepen the investigation of MXE‐induced effects by a battery of behavioral tests widely used in studies of “safety‐pharmacology” for the preclinical characterization of new molecules. To this purpose, the acute effects of MXE on neurological and sensorimotor functions in mice, including visual, acoustic and tactile responses, thermal and mechanical pain, motor activity and acoustic startle reactivity were evaluated in comparisons with KET and PCP to better appreciate its specificity of action. Cardiorespiratory parameters and blood pressure were also monitored in awake and freely moving animals. Acute systemic administrations of MXE, KET and PCP (0.01–30 mg/kg i.p.) differentially alter neurological and sensorimotor functions in mice depending in a dose‐dependent manner specific for each parameter examined. MXE and KET (1 and 30 mg/kg i.p.) and PCP (1 and 10 mg/kg i.p.) also affect significantly cardiorespiratory parameters, systolic and diastolic blood pressure in mice. HighlightsMethoxetamine (MXE) is a ketamine (KET) ‐ like novel psychoactive substance (NPS).Number of MXE‐induced acute toxicity are increasing at an alarming rate.MXE induces significant neurological, sensorimotor, cardiorespiratory alterations.MXE effects were qualitatively but not quantitatively similar to KET and phencyclidine.

Novel Synthetic Opioids: The Pathologist’s Point of View

Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.