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Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modi- fied wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The ongoing Coronavirus pandemic (COVID-19) showed similar characteristics with the severe acute respiratory syndrome (SARS). In the most compromised cases, COVID-19 infection leads to death due to severe respiratory complications. COVID-19-related acute respiratory distress syndrome (ARDS) is the primary cause of death in these patients. In the present study, we show an ultrastructural analysis on the lungs of a patient affected by COVID-19. PATIENTS AND METHODS: Lung specimens obtained at autopsy from a 63-years old patient affected by COVID-19 were fixed in 1% paraformaldehyde. Slices of 300 µm thickness were dehydrated and dried by Critical Point Drying in CO2. Slices were covered with a conductive gold film approximately 30 nm thick and observed at a Zeiss Sigma 300 SEM FEG in the secondary electron (SE) and backscattered electron (BSE) modes. As case control a lung biopsy from a 60-year-old man was considered. RESULTS: At low power in all COVID-19 lung specimens severe changes in the pulmonary architecture were found, due to the collapse of air spaces. Moreover, alveolar cavities were covered by large membranes. At high power, alveolar membranes showed a fibrillar structure, suggestive of a loose network of fibrin. It has been also found that intra-alveolar red blood cells were frequently present in the alveolar spaces, surrounded by a reticular fibrin network, suggestive for fibrin-hemorrhagic alveolitis. Alveolar changes were constantly associated with pathological features related to the pulmonary vessels. Vascular changes were prominent, including endothelial damage and thrombosis of large pulmonary vessels. Fibrinous microthrombi were frequently detected in the inter-alveolar septal capillaries. In addition, it has been frequently detected capillary proliferation in the alveolar septa with finding suggestive for intussusceptive neo-angiogenesis. CONCLUSIONS: In conclusion, our electron microscopy analysis showed that COVID-19-related lung disease is characterized by a substantial architectural distortion, with the interactions between alveolar and vascular changes. Intra-alveolar hyaline membranes are associated with macroand micro-thrombotic angiopathy, ending with capillary proliferation. The new blood vessel formation originates from the septa and extends into the surrounding parenchyma. Our findings confirm previous reports on the specificity of the multiple and complex morphological pattern typical, and apparently specific, of COVID-19-related lung disease. [ABSTRACT FROM AUTHOR]

Arterial thromboembolic complications reported in patients with COVID-19 infection suggested that SARS-CoV-2 can trigger atherosclerotic plaque vulnerability. While endothelial cells in healthy subjects protect against thrombus formation, after injury they show prothrombotic activity. In addition, it has been hypothesized that "cytokine storm" might stimulate the production of neo-platelets triggering an abnormal "immunothrombosis" responsible for the hypercoagulable state induced in COVID-19 patients. The aim of this study is to report a case of severe COVID-19 infection characterized by the occurrence of microthrombosis in the vasa vasorum of the aorta. A 67-year-old male patient, in good health status and without comorbidities, who underwent a severe COVID-19 infection with fatal outcome, showed scattered aortic atherosclerotic plaques, characterized by multiple occlusive micro-thromboses in the vasa vasorum, spread out lymphocytic infiltrates and foci of endotheliitis and endothelial detachment. This case report confirms the previously described thrombotic involvement of vasa vasorum in COVID-19. The occurrence of the synchronous damage involving both the lumen surface (endothelial dysfunction, endotheliitis and endothelial detachment) and the adventitia (inflammation and occlusive thrombosis of vasa vasorum) could be the key points related to the fatal outcome of the SARS-CoV-2 patients. In our opinion, vasa vasorum thrombosis may thus initiate an atherogenic process that could be characterized by a much more rapid development. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Vaccine-induced immune thrombocytopenia (VITT) is a new syndrome occurring primarily in healthy young adults, with a female predominance, after receiving the first dose of ChAdOx1 nCoV-19 vaccine. We describe VITT syndrome characterized by severe thrombosis and thrombocytopenia found in our patient, with fatal outcome. CASE REPORT: A 5 8-year-old m an, a fter 13 days from the first administration of ChAdOx1 nCoV-19 vaccine (AstraZeneca), presented with abdominal pain, diarrhea and vomitus. Laboratory tests revealed a severe thrombocytopenia, low fibrinogen serum levels and marked increase of D-dimer serum levels. The patient quickly developed a multiple organ failure, till death, three days after the hospital admission. RESULTS: At histology, in the lungs, interalveolar septa appeared thickened with microthrombi in the capillaries and veins. Interalveolar septa appeared thickened and showed vascular proliferation. Thrombi were detected in the capillaries of glomerular tufts. In the hearth, thrombi were observed in veins and capillaries. In the liver, voluminous fibrin thrombi were diffusely observed in the branches of the portal vein. Microthrombi were also found in the vasa vasorum of the wall of abdominal aorta. In the brain, microthrombi were observed in the capillaries of the choroid plexuses. Diffuse hemorrhagic necrosis was observed in the intestinal wall with marked congestion of the venous vessels. CONCLUSIONS: In our patient, the majority of data necessary for a VITT final diagnosis were present: thrombocytopenia and thrombosis in pulmonary, portal, hepatic, renal and mesenteric veins, associated with a marked increase of D-dimer serum levels. The finding of cerebral thrombosis in choroid plexuses, is a new finding in VITT. These features are suggestive for a very aggressive form of VITT. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is characterized by quantitative and qualitative changes in surfactant composition, leading to surfactant dysregulation with alveolar collapse and acute respiratory hypoxic failure. Recently, surfactant has been hypothesized to play a relevant role in COVID-19, representing a strong defender against SARSCoV- 2 infection. The aim of our work was the study of immunohistochemical surfactant expression in the lungs of patients died following SARS-CoV-2 ARDS, in order to shed light on a possible therapeutic surfactant administration. PATIENTS AND METHODS: We investigated four patients who died due to ARDS following SARS-COV-2 infection and four patients submitted to lung biopsy, in the absence of SARSCoV- 2 infection. In all 8 cases, lung specimens were immunostained with anti-surfactant protein A (SP-A) and B (SP-B). RESULTS: In control subjects, reactivity for SP-B was restricted to type II alveolar cells. Immunostaining for SP-A was observed on the surface of alveolar spaces. In the COVID-19 positive lungs, immunoreactivity for SP-B was similar to that observed in control lungs; SP-A was strongly expressed along the alveolar wall. Moreover, dense aggregates of SP-A positive material were observed in the alveolar spaces. CONCLUSIONS: Our immunohistochemical data show the dysregulation of surfactant production in COVID-19 patients, particularly regarding SP-A expression. The increased presence of SP-A in condensed masses inside alveolar spaces could invalidate the therapeutic efficacy of the treatment with exogenous surfactant. [ABSTRACT FROM AUTHOR]

Introduction: Due to its peculiar anatomy and physiology, the pericardial fluid is a biological matrix of particular interest in the forensic field. Despite this, the available literature has mainly focused on post-mortem biochemistry and forensic toxicology, while to the best of authors' knowledge post-mortem metabolomics has never been applied. Similarly, estimation of the time since death or post-mortem interval based on pericardial fluids has still rarely been attempted., Objectives: We applied a metabolomic approach based on 1 H nuclear magnetic resonance spectroscopy to ascertain the feasibility of monitoring post-mortem metabolite changes on human pericardial fluids with the aim of building a multivariate regression model for post-mortem interval estimation., Methods: Pericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 h after death. The only exclusion criterion was the quantitative and/or qualitative alteration of the sample. Two different extraction protocols were applied for low molecular weight metabolites selection, namely ultrafiltration and liquid-liquid extraction. Our metabolomic approach was based on the use of 1 H nuclear magnetic resonance and multivariate statistical data analysis., Results: The pericardial fluid samples treated with the two experimental protocols did not show significant differences in the distribution of the metabolites detected. A post-mortem interval estimation model based on 18 pericardial fluid samples was validated with an independent set of 6 samples, giving a prediction error of 33-34 h depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 h, the prediction power of the model was significantly improved with an error of 13-15 h depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model., Conclusion: The present study, although preliminary, shows that PF samples collected from a real forensic scenario represent a biofluid of interest for post-mortem metabolomics, with particular regard to the estimation of the time since death., (© 2023. The Author(s).)

Introduction: The estimation of post-mortem interval (PMI) remains a major challenge in forensic science. Most of the proposed approaches lack the reliability required to meet the rigorous forensic standards., Objectives: We applied 1 H NMR metabolomics to estimate PMI on ovine vitreous humour comparing the results with the actual scientific gold standard, namely vitreous potassium concentrations., Methods: Vitreous humour samples were collected in a time frame ranging from 6 to 86 h after death. Experiments were performed by using 1 H NMR metabolomics and ion capillary analysis. Data were submitted to multivariate statistical data analysis., Results: A multivariate calibration model was built to estimate PMI based on 47 vitreous humour samples. The model was validated with an independent test set of 24 samples, obtaining a prediction error on the entire range of 6.9 h for PMI < 24 h, 7.4 h for PMI between 24 and 48 h, and 10.3 h for PMI > 48 h. Time-related modifications of the 1 H NMR vitreous metabolomic profile could predict PMI better than potassium up to 48 h after death, whilst a combination of the two is better than the single approach for higher PMI estimation., Conclusion: The present study, although in a proof-of-concept animal model, shows that vitreous metabolomics can be a powerful tool to predict PMI providing a more accurate estimation compared to the widely studied approach based on vitreous potassium concentrations., (© 2023. The Author(s).)

The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison.

Most patients with idiopathic REM sleep behavior disorder (iRBD) will develop an overt α-synucleinopathy over time, with a rate of phenoconversion of 73.5% after 12 years from diagnosis. Several markers of phenoconversion were identified; however, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without standardized data collection methods. The risk FActoRs PREdictive of phenoconversion in idiopathic REM sleep behavior disorder: the Italian STudy (FARPRESTO) is a multicentric longitudinal retrospective and prospective study with a cohort of incident (prospective recruitment) and prevalent (retrospective recruitment) iRBD patients, whose primary aim is to stratify the risk of phenoconversion, through the systematic collection by means of electronic case report forms of different biomarkers. Secondary aims are to (1) describe the sociodemographic and clinical characteristics of patients with iRBD; (2) collect longitudinal data about the development of α-synucleinopathies; (3) monitor the impact of iRBD on quality of life and sleep quality; (4) assess the correlation between phenoconversion, cognitive performance, and loss of normal muscle atony during REM sleep; (5) identify RBD phenotypes through evaluating clinical, biological, neurophysiological, neuropsychological, and imaging biomarkers; and (6) validate vPSG criteria for RBD diagnosis. The FARPRESTO study will collect a large and harmonized dataset, assessing the role of different biomarkers providing a unique opportunity for a holistic, multidimensional, and personalized approach to iRBD, with several possible application and impact at different levels, from basic to clinical research, and from prevention to management. The FARPRESTO has been registered at clinicaltrials.gov (NCT05262543)., (© 2022. The Author(s).)

Background: Shared decision-making implies that patients and healthcare professionals make decisions together about clinical exams, available treatments, choice of options, and the benefit or downside of every choice. Patients involved in the shared decision-making process are more compliant with treatments and have a reduced risk of complications related to the pathology. In Italy, patient involvement in caring processes is still barely investigated., Aim: To investigate patients' perceptions about shared decision-making with physicians and nurses, respectively, and to examine the relationship between shared decision-making and patient satisfaction and perceived quality of care/treatment., Methods: The study was performed between March and June 2019 in two wards of one Italian hospital. A questionnaire was administered to inpatients at the time of admission and again at discharge, including demographic information and measurement scales regarding patient involvement in shared decision-making, patient satisfaction, and perceived quality of treatment/care., Results: A total of 151 out of 301 patients completed questionnaires at both admission and discharge. Patients' scores for shared decision-making (information, patient needs, treatment planning) were significantly different for physicians and nurses. At both admission and discharge, patients rated shared decision-making significantly higher for physicians compared to nurses, while there were no differences in their satisfaction ratings. Patient ratings of physicians did not change from admission (information: mean (M) = 3.50, standard deviation (SD) = 0.81; patient need: M = 3.05, SD = 1.05; treatment planning: M = 2.75, SD = 1.23) to discharge (information: M = 3.50, SD = 0.79; patient need: M = 3.17, SD = 1.02; treatment planning: M = 2.66, SD = 1.23) ( p = 0.924, p = 0.098, p = 0.293, respectively), but patients' ratings of nurses' behavior increased significantly from admission (information: M = 2.44, SD = 1.23; patient need: M = 2.27, SD = 1.17; treatment planning: M = 2.12, SD = 1.19) to discharge (information: M = 2.62, SD = 1.22; patient need: M = 2.53, SD = 1.24; treatment planning: M = 2.35, SD = 1.21) ( p = 0.019, p = 0.001, p = 0.003, respectively). Attention to patients' needs was the key determinant of both satisfaction with nurses (OR = 3.65, 95% CI = 1.31-10.14, p = 0.013) and perceived quality of care (OR = 3.97, 95% CI = 1.49-10.55, p = 0.006). Providing appropriate information about disease progress and treatments was a key determinant of both satisfaction with physicians (OR = 19.75, 95% CI = 7.29-53.55, p < 0.001) and perceived quality of treatment (OR = 8.03, 95% CI = 3.25-19.81, p < 0.001)., Discussion: Nurses should be sensitized to involving patients in the decision-making process, especially upon hospital admission. Specific training about effective communication techniques can be implemented to manage relationships with patients in different caring situations. Practical implications and future directions are discussed.

In the current study, using portable optical coherence tomography, we evaluated 46 corneas of 23 individuals in a multicenter setting during the first 17 h after death. Twenty-three eyes were kept open, and twenty three were kept closed. Furthermore, the experiment was carried out for 12 samples in summer and 11 in winter. Our data show that postmortem corneal alterations largely depend on the phenomena of dehydration (in particular in open eyes) and swelling of the stroma in closed eyes, probably due in the first phase to hypoxia/anoxia and subsequently to the passage by osmosis of the aqueous humor from the anterior chamber to the corneal tissue. Our findings could have significant repercussions in forensic pathology for estimating the postmortem interval and transplantation to optimize the conservation of the tissue before the explant.

Background: several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their prognostic value., Objective: this systematic review and meta-analysis was designed to investigate the role of blood biomarkers and metabolomic profiling as diagnostic and prognostic predictors in pre-clinical studies of VIKI., Methods: a systematic search of PubMed was conducted for relevant articles from January 2000 to May 2022. Animal studies that administered vancomycin and studied VIKI were eligible for inclusion. Clinical studies, reviews, and non-English literature were excluded. The primary outcome was to investigate the relationship between the extent of VIKI as measured by blood biomarkers and metabolomic profiling. Risk of bias was assessed with the CAMARADES checklist the SYRCLE's risk of bias tool. Standard meta-analysis methods (random-effects models) were used., Results: there were four studies for the same species, dosage, duration of vancomycin administration and measurement only for serum creatine and blood urea nitrogen in rats. A statistically significant increase was observed between serum creatinine in the vancomycin group compared to controls (pooled p = 0.037; Standardized Mean Difference: 2.93; 95% CI: 0.17 to 5.69; I 2 = 92.11%). Serum BUN levels were not significantly different between control and vancomycin groups (pooled p = 0.11; SMD: 3.05; 95% CI: 0.69 to 6.8; I 2 = 94.84%). We did not identify experimental studies using metabolomic analyses in animals with VIKI., Conclusions: a total of four studies in rodents only described outcomes of kidney injury as defined by blood biomarkers. Blood biomarkers represented included serum creatinine and BUN. Novel blood biomarkers have not been explored., Competing Interests: M.S. declares ongoing research contracts with Nevakar and SuperTrans Medical and has filed patent US10688195B2. The remaining authors declare no conflict of interest.

Background: Polymyxin B treatment is limited by kidney injury. This study sought to identify Polymyxin B-related urinary metabolomic profile modifications for early detection of polymyxin-associated nephrotoxicity., Methods: Samples were obtained from a previously conducted study. Male Sprague-Dawley rats received dose-fractionated polymyxin B (12 mg/kg/day) once daily (QD), twice daily (BID), and thrice daily (TID) for three days, with urinary biomarkers and kidney histopathology scores determined. Daily urine was analysed for metabolites via 1H nuclear magnetic resonance (NMR). Principal components analyses identified spectral data trends with orthogonal partial least square discriminant analysis applied to classify metabolic differences. Metabolomes were compared across groups (i.e., those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome., Results: A total of 25 rats were treated with Polymyxin B, and n = 2 received saline, contributing 77 urinary samples. Pre-dosing samples clustered well, characterised by higher amounts of citrate, 2-oxoglutarate, and hippurate. Day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite that significantly increased in both BID and TID compared with the QD group. Day 1 taurine correlated with increasing histopathology scores (rho = 0.4167, P = 0.038) and kidney injury molecule-1 (KIM-1) (rho = 0.4052, P = 0.036), whereas KIM-1 on day 1 and day 3 did not reach significance with histopathology (rho = 0.3248, P = 0.11 and rho = 0.3739, P = 0.066)., Conclusions: Polymyxin B causes increased amounts of urinary taurine on day 1, which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Human postmortem skeletal muscles are a unique source of satellite cells for skeletal muscle regenerative studies. Presomite and somite satellite cells obtained by postmortem muscles have been established as populations of human skeletal muscle precursor cells able to proliferate and differentiate in vitro . It is extremely interesting to have access to a large amount of postmortem human skeletal muscle precursor cells, especially from craniofacial as well as limb skeletal muscles in order to evaluate their potential application not only for the fundamental understanding of muscle physiology and diseases but also for drug testing in a challenging 3D-shaping muscles like skeletal muscle microphysiological systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pietrangelo, Demontis, Santangelo, Pini, Bonelli, Rosato, Roberti, Locatelli, Tartaglia, Marramiero, Verratti, Bondi, Fulle, D’Aloja and D’Ovidio.)

A case report suspicious for a Sudden Infant Death Syndrome is here described. Pathological findings were consistent with an acute respiratory failure while toxicological analysis revealed an elevated blood methadone concentration. Death was then ascribed to an acute methadone intoxication. In addition to the routinary approach, the urinary sample collected at autopsy was investigated with a 1 H NMR metabolomic approach and the identified metabolomic profile was challenged with the urinary metabolomic profiles previously obtained from 10 newborns who experienced perinatal asphyxia and 16 healthy control newborns. Intriguingly, the urinary profile of the methadone intoxicated infant was very similar to those belonging to the perinatal asphyxia newborns, especially to those belonging to the newborns characterised by the worst outcome. The results offer several hints on a shared metabolic derangement between different mechanisms of asphyxia/hypoxia. To the best of the authors' knowledge, this is the first report of the use of a metabolomic approach in a pathological case, in which metabolomics offers useful additional information regarding the mechanism and the cause of death., (© 2022. The Author(s).)

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.

A growing body of evidence suggests that the post-mortem interval exerts a strong effect on the metabolome, independently of the biological matrix or the cause of death. A sound and shared approach in standardization is mandatory.

There is still a lack of knowledge concerning the pathophysiology of death among COVID-19-deceased patients, and the question of whether a patient has died with or due to COVID-19 is still very much debated. In Italy, all deaths of patients who tested positive for SARS-CoV-2 are defined as COVID-19-related, without considering pre-existing diseases that may either contribute to or even cause death. Our study included nine subjects from two different nursing homes (Cases 1-4, Group A; Cases 5-9, Group B). The latter included patients who presumably died from CO poisoning due to a heating system malfunction. All subjects tested positive for COVID-19 both ante- and post-mortem and were examined using post-mortem computed tomography prior to autopsy. COVID-19 was determined to be a contributing cause in the deaths of four out of nine subjects (death due to COVID-19; i.e., pneumonia and sudden cardiac death). In the other five cases, for which CO poisoning was identified as the cause of death, the infection presumably had no role in exitus (death with COVID-19). In our attempt to classify our patients as dying with or due to COVID-19, we found the use of complete assessments (both histological analyses and computed tomography examination) fundamental.

Background: In times of global public health emergency, such as the COVID-19 pandemic, nurses stand at the front line, working in close contact with infected individuals. Being actively engaged in fighting against COVID-19 exposes nurses to a high risk of being infected but can also have a serious impact on their mental health, as they are faced with excessive workload and emotional burden in many front-line operating contexts. Purpose: The aim of the study is to analyze how risk factors such as perceived impact, preparedness to the pandemic, and worries were associated with mental health outcomes (crying, rumination and stress) in nurses. Methods: A cross-sectional study design was performed via an online questionnaire survey. Participants included 894 registered nurses from Italy. Participation was voluntary and anonymous. Multiple binary logistic regression was carried out to analyze the relationship between risk factors and health outcomes. Results: Increased job stress was related to higher levels of rumination about the pandemic (OR = 4.04, p < 0.001), job demand (OR = 2.00, p < 0.001), impact on job role (OR = 2.56, p < 0.001), watching coworkers crying at work (OR = 1.50, p < 0.05), non-work-related concerns (OR = 2.28, p < 0.001), and fear of getting infected (OR = 2.05, p < 0.001). Job stress (OR = 2.52, p < 0.01), rumination (OR = 2.28, p < 0.001), and watching colleagues crying (OR = 7.92, p < 0.001) were associated with crying at work. Rumination was associated with caring for patients who died of COVID-19 (OR = 1.54, p < 0.05), job demand (OR = 1.70, p < 0.01), watching colleagues crying (OR = 1.81, p < 0.001), non-work-related worries (OR = 1.57, p < 0.05), and fear of getting infected (OR = 2.02, p < 0.001). Conclusions: The psychological impact that this pandemic may cause in the medium/long term could be greater than the economical one. This is the main challenge that health organizations will have to face in the future. This study highlights that the perceived impact and worries about the pandemic affect nurses' mental health and can impact on their overall effectiveness during the pandemic. Measures to enhance nurses' protection and to lessen the risk of depressive symptoms and post-traumatic stress should be planned promptly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Galletta, Piras, Finco, Meloni, D'Aloja, Contu, Campagna and Portoghese.)

The diagnosis of mechanical asphyxia remains one of the most difficult issues in forensic pathology. Asphyxia ultimately results in cardiac arrest (CA) and, as there are no specific markers, the differential diagnosis of primitive CA and CA secondary to asphyxiation relies on circumstantial details and on the pathologist experience, lacking objective evidence. Histological examination is currently considered the gold standard for CA post-mortem diagnosis. Here we present the comparative results of histopathology versus those previously obtained by 1 H nuclear magnetic resonance (NMR) metabolomics in a swine model, originally designed for clinical purposes, exposed to two different CA causes, namely ventricular fibrillation and asphyxia. While heart and brain microscopical analysis could identify the damage induced by CA without providing any additional information on the CA cause, metabolomics allowed the identification of clearly different profiles between the two groups and showed major differences between asphyxiated animals with good and poor outcomes. Minute-by-minute plasma sampling allowed to associate these modifications to the pre-arrest asphyxial phase showing a clear correlation to the cellular effect of mechanical asphyxia reproduced in the experiment. The results suggest that metabolomics provides additional evidence beyond that obtained by histology and immunohistochemistry in the differential diagnosis of CA.

Estimation of the post-mortem interval (PMI) remains a matter of concern in the forensic scenario. Traditional and novel approaches are not yet able to fully address this issue, which relies on complex biological phenomena triggered by death. For this purpose, eye compartments may be chosen for experimental studies because they are more resistant to post-mortem modifications. Vitreous humour, in particular, has been extensively investigated, with potassium concentration ([K + ]) being the marker that is better correlated with PMI estimation. Recently, a 1 H nuclear magnetic resonance (NMR) metabolomic approach based on aqueous humour (AH) from an animal model was proposed for PMI estimation, resulting in a robust and validated regression model. Here we studied the variation in [K + ] in the same experimental setup. [K + ] was determined through capillary ion analysis (CIA) and a regression analysis was performed. Moreover, it was investigated whether the PMI information related to potassium could improve the metabolome predictive power in estimating the PMI. Interestingly, we found that a part of the metabolomic profile is able to explain most of the information carried by potassium, suggesting that the rise in both potassium and metabolite concentrations relies on a similar biological mechanism. In the first 24-h PMI window, the AH metabolomic profile shows greater predictive power than [K + ] behaviour, suggesting its potential use as an additional tool for estimating the time since death.

The forensics literature on the relationship between ocular changes and the postmortem interval (PMI) has traditionally focused on time-related variations in concentrations of metabolites and elements within the eye. However, structural changes within the eye over time deserve the same attention because there is significant evidence of their importance in determining the time since death. Therefore, we reviewed publications that provided substantial evidence on this issue. In light of our inclusion and exclusion criteria, 26 papers were eligible for review. On the basis of the ocular parameters considered, we grouped the reviewed evidence into eight thematic areas: corneal opacities, corneal thickness, drug-induced pupil diameter variations, retinal changes, segmentation of retinal vessels, intraocular pressure reduction, globe temperature and crystalline alterations. The most important and common limitations of the reviewed studies were small study populations (many were monocentric studies), absence of robust statistical methodology, use of mathematical models valid only in ideal conditions and validation only for short PMIs. Although many phenomena cannot be used to reliably estimate PMI, there is rigorous evidence suggesting that promising factors, including corneal thickness, require methodological innovations for application to forensics practice but could be used in the near future to reliably estimate the time since death., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions., Methods: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects., Results: Although always below the European Union limit of 5 μg/m 3 , airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area ( p = 0.026, p = 0.005, and p = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples ( p = 0.01 and p = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion., Conclusions: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children.

Postmortem analysis of the ocular globe is an important topic for forensic pathology and transplantology. Although crucial elements may be gathered from examining cadaveric eyes, the latter do not routinely undergo in-depth analysis. The paucity of quantitative and objective data that are obtainable using current, invasive necroscopic techniques is the main reason for the limited interest in this highly specialized procedure. The aim of the current study is to describe and to object for the first time the postmortem ocular changes by mean of portable optical coherence tomography for evaluating ocular tissues postmortem. The design involved the postmortem analysis (in situ, and without enucleation) of 12 eyes by portable spectral-domain Optical Coherence Tomography. The scans were performed, in corneal, retinal and angle modality at different intervals: <6 h, 6th, 12th, and 24th hour and after autopsy (25th-72nd hour). The morphological changes in the cornea, sclera, vitreous humor and aqueous humor were easy to explore and objectify in these tissues in first 72 h postmortem. On the other hand, the "in situ" observation of the retina was difficult due to the opacification of the lenses in the first 24 h after death.

Introduction: The COVID-19 pandemic is asking health care workers (HCWs) to meet extraordinary challenges. In turn, HCWs were experiencing tremendous psycho-social crisis as they have had to deal with unexpected emotional requirements (ERs) arising from caring for suffering and dying patients on a daily basis. In that context, recent studies have highlighted how HCWs working during the COVID-19 outbreak manifested extreme emotional and behavioral reactions that may have impacted their mental health, increasing the risk for developing post-traumatic stress symptoms. Purpose: The aim of the study was to investigate post-traumatic stress symptoms, such as intrusion symptoms, as a potential mediator of the link between ERs and crying at work, and whether rumination moderates the relationship between ERs and intrusion-based PTS symptoms among HCWs who have had to deal with patients dying from COVID-19. Methods: An online cross-sectional study design was performed. A total of 543 Italian HCWs (physicians and nurses) participated in the study. Participation was voluntary and anonymous. We used the SPSS version of bootstrap-based PROCESS macro for testing the moderated mediation model. Results: ERs had an indirect effect on crying at work through the mediating role of intrusion symptoms. Results from the moderated mediation model showed that rumination moderated the indirect effect of ERs on crying at work via intrusion symptoms, and this effect was significant only for high rumination. Furthermore, when we tested for an alternative model where rumination moderates the direct effect of ERs on crying at work, this moderation was not significant. Conclusions: As the second wave of the COVID-19 pandemic is ongoing, there is an urgent need for decision-makers to rapidly implement interventions aimed at offering timely psychological support to HCWs, especially in those contexts where the risk of emotional labor associated to patients dying from COVID-19 is higher., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Portoghese, Galletta, Meloni, Piras, Finco, D'Aloja and Campagna.)

On March 11, 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a pandemic. Simultaneously, in Italy, in which the first case had occurred on February 18, the rigid phase of the lockdown began. The country has attracted worldwide attention, becoming at the same time a field of study both concerning the spread of the pandemic and advanced assessments of the effectiveness of political, public health, and therapeutic measures. The protagonists of the Italian crisis were the healthcare workers (HCWs) who were exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without having any perception of what they were facing, courageously contributing to the containment of the epidemic to be defined by the media as "heroes." However, in the first phase of the pandemic (March-May 2020), the price that the Italian Public Health System had to pay both in terms of the number of positive virus cases and deaths among the HCWs was beyond and represented a peculiarity compared to what happened in other countries. In the current study, after a summary of the evolution of the pandemic in Italy, we offer an analysis of the statistical data concerning contagions and deaths among healthcare workers (physicians in particular). In conclusion, we describe the critical issues that still need to be resolved and the future challenges facing healthcare workers and the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nioi, Napoli, Lobina, Fossarello and d'Aloja.)

Background: Health care workers (HCWs) are among the professionals at serious risk for the impact of the COVID-19 pandemic on their mental health. In this sense, the next public health challenge globally will be to preserving healthy HCWs during this pandemic., Aim: The present study has the aim of investigating the relationship among concerns, perceived impact, preparedness for the COVID-19 pandemic and the mental health of Italian physicians., Methods: From March 29th to April 15th 2020, we conducted an online survey using snowball sampling techniques through Limesurvey platform. Data were analyzed using descriptive statistics and multiple binary logistic regressions., Results: Multivariate analysis showed that the risk factors for perceived job stress were concerns about catching COVID-19 (OR = 3.18 [95% CI = 2.00-5.05] P  < .001), perceived impact on job demands (OR = 1.63 [95% CI = 1.05-2.52] P  < .05), perceived impact on job role (OR = 2.50 [95% CI = 1.60-3.90] P  < .001), and non-working concerns (OR = 1.86 [95% CI = 1.15-3.03] P  < .05). With respect to the risk factors for rumination about the pandemic emerged concerns about catching COVID-19 (OR 1.74, [95% CI = 1.12-2.71] P  < .05), perceived impact on job role (OR = 1.68 [95% CI = 1.12-2.52] P  < .05), and impact on personal life (OR = 2.04 [95% CI = 1.08-3.86] P  < .05). Finally, the risk factors for crying at work were perceived impact on job role (OR = 2.47, [95% CI = 1.20-5.09] P  < .05), rumination about the pandemic (OR = 3.027 [95% CI = 1.27-7.19] P  < .01), watching colleagues crying at work (OR = 3.82 [95% CI = 1.88-7.77] P  < .01), and perceived job stress (OR = 3.53 [95% CI = 1.24-10.07] P  < .05)., Conclusion: In general, our results highlighted that being concerned about being infected/infecting other people, carrying out new and unusual tasks, and witnessing colleagues crying at work were important risk factors for physicians' well-being. Additional data are necessary to advance understanding of these risk factors in a long-term perspective.