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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 1H 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 1H 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 1H 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.

Questo lavoro e il risultato delle ricerche portate avanti sullo studio dei fondi in lingua italiana relativi al Supremo Consiglio del Rito Scozzese Antico ed Accettato, guidato da Saverio Fera dal 1908, dopo la scissione dentro al RSAA del Grande Oriente d’Italia. I documenti, sono unici, testimoniano sia i primi anni di vita dell’organismo massonico e portato avanti da Saverio Fera per inserirlo nel novero degli organismi massonici riconosciuti e operanti nel sistema mondiale del Rito Scozzese Antico e Accettato, sia le forti relazioni con l’omologo spagnolo. L’arco cronologico inizia dal 1908, per terminare nel 1925.

IntroductionDue 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.ObjectivesWe applied a metabolomic approach based on1H 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.MethodsPericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 hours 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 of1H Nuclear Magnetic Resonance and multivariate statistical data analysis.ResultsThe 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 hours depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 hours, the prediction power of the model was significantly improved with an error of 13-15 hours depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model.ConclusionThe 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.

The topic of tourism is gaining more and more importance from the scientific point of view, there are now several papers dealing with it, so it seemed appropriate to present an essay on the history of tourism in Sardinia. Therefore, this contribution aims to describe the phenomenon of tourism, its birth and development in the south of the island particularly in the southwest coast, that of Santa Margherita di Pula. The study has been carried out through the analysis of existing literature, trade, custom and society newspapers – which offer a glimpse of life on the Island between 1960 and 1980 – documents preserved in the few historical archives of the Autonomous Region of Sardinia, and also through the use of oral sources, used to make up for the dearth of certain sources.

The combined use of multiple omics methods to answer complex system biology questions is growing in biological and medical sciences, as the importance of studying interrelated biological processes in their entirety is increasingly recognized. We applied a combination of metabolomics, lipidomics and proteomics to human bone to investigate the potential of this multi-omics approach to estimate the time elapsed since death (i.e., the post-mortem interval, PMI). This “ForensOMICS” approach has the potential to improve accuracy and precision of PMI estimation of skeletonized human remains, thereby helping forensic investigators to establish the timeline of events surrounding death. Anterior midshaft tibial bone was collected from four female body donors in a fresh stage of decomposition before placement of the bodies to decompose outdoors at the human taphonomy facility managed by the Forensic Anthropological Center at Texas State (FACTS). Bone samples were again collected at selected PMIs (219, 790, 834 and 872 days). Liquid chromatography mass spectrometry (LC-MS) was used to obtain untargeted metabolomic, lipidomic and proteomic profiles from the pre- and post-placement bone samples. Multivariate analysis was used to investigate the three omics blocks by means of Data Integration Analysis for Biomarker discovery using Latent variable approaches for Omics studies (DIABLO), to identify the reduced number of markers that could effectively describe post-mortem changes and classify the individuals based on their PMI. The resulting model showed that pre-placement bone metabolome, lipidome and proteome profiles were clearly distinguishable from post-placement profiles. Metabolites associated with the pre-placement samples, suggested an extinction of the energetic metabolism and a switch towards another source of fuelling (e.g., structural proteins). We were able to identify certain biomolecules from the three groups that show excellent potential for estimation of the PMI, predominantly the biomolecules from the metabolomics block. Our findings suggest that, by targeting a combination of compounds with different post-mortem stability, in future studies we could be able to estimate both short PMIs, by using metabolites and lipids, and longer PMIs, by including more stable proteins.

Cadaveric rigidity-also referred to as rigor mortis-is a valuable source of information for estimating the time of death, which is a fundamental and challenging task in forensic sciences. Despite its relevance, assessing the level of cadaveric rigidity still relies on qualitative and often subjective observations, and the development of a more quantitative approach is highly demanded. In this context, ultrasound shear wave elastography (US SWE) appears to be a particularly well-suited technique for grading cadaveric rigidity, as it allows non-invasive quantification of muscle stiffness in terms of Young's modulus (E), which is a widely used parameter in tissue biomechanics. In this pilot study, we measured, for the first time in the literature, changes in the mechanical response of muscular tissues from 0 to 60 h post-mortem (hpm) using SWE, with the aim of investigating its applicability to forensic practice. For this purpose, 26 corpses were included in the study, and the muscle mechanical response was measured at random times in the 0-60 hpm range. Despite the preliminary nature of this study, our data indicate a promising role of SWE in the quantitative determination of cadaveric rigidity, which is still currently based on qualitative and semiquantitative methods. A more in-depth study is required to confirm SWE applicability in this field in order to overcome some of the inherent limitations of the present work, such as the rather low number of cases and the non-systematic approach of the measurements.

Resumen El Gran Oriente de Italia (GOI) ha mantenido y mantiene relaciones con algunas de las obediencias más importantes del mundo. En este caso, se investigó las relaciones entre el Gran Oriente de Italia y la Gran Logia de Cuba, mediante el estudio y el análisis de las fuentes que se encuentran en el Archivo Histórico del Gran Oriente de Italia y, para el período más reciente, en el Gran Secretariado. El archivo histórico del GOI conserva algunos documentos y números de las Revista de la Masonería Italiana que atestiguan las relaciones entre las dos Obediencias desde finales del siglo XIX. Abstract The present paper shows the relations Italian Freemasonry – the Grand Orient of Italy (GOI) – has been keeping with some of the most relevant Obediences in the world. Between G.O.I. and the Grand Lodge of Cuba. the research was carried out mostly through the analysis of documents and periodicals in the Historical Archive of the Grand Orient of Italy and, for more recent information, in the Grand Secretariat. The GOI historical archive preserves some documents and numbers from Rivista della Massoneria Italiana that witness the relations between the two Obediences since the end of the 19th century.

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 1H 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.

Objectives: Arsenic is a toxic metal ubiquitous in the environment and in daily life items. Long-term arsenic exposure is associated with severe adverse health effects involving various tar...

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; I2 = 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; I2 = 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.

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.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.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).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.

BackgroundPolymyxin B remains an important antimicrobial against multi-drug resistant bacteria; however, kidney injury is often a treatment limiting event with kidney failure rates that range from 5-13%.MethodsSamples were obtained from a previously conducted study of male Sprague-Dawley rats that received dose fractionated polymyxin B (12 mg/kg/day subcutaneously) once daily (QD), twice daily (BID), and thrice daily (TID) for three days. In the original study, urinary biomarkers and kidney histopathology scores were determined. Urine was sampled daily and analyzed for urinary metabolites via 1H NMR analysis.Unsupervised Principal Components Analysis was applied for exploratory data analysis to identify trends and outliers in the spectral data. Then, supervised Orthogonal Partial Least Square Discriminant Analysis was applied to classify the samples collected in different days and identify metabolic differences during the treatment. Metabolomes were compared across study 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.ResultsA total of 27 rats contributed 77 urinary samples; n=25 rats were included that were treated with Polymyxin B and n=2 received saline. Pre-dosing samples clustered well and were characterized by higher amounts of citrate, 2-oxoglutarate, and Hippurate. On day 1 post treatment, day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite significantly increased in both BID and TID compared to QD group. Taurine on day 1 correlated with increasing histopathology scores (Spearman’s rho = 0.4167, P=0.038) and KIM-1 (Spearman’s rho =0.4052, P=0.036); whereas KIM-1 on day one and day 3 did not reach significance with histopathology (Spearman’s rho = 0.3248, P=0.11 and Spearman’s rho = 0.3739, P=0.066).ConclusionPolymyxin 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.

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 1H 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.

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.

Brain damage related to perinatal asphyxia is the second cause of neuro-disability worldwide. Its incidence was estimated in 2010 as 8.5 cases per 1000 live births worldwide, with no further recent improvement even in more industrialized countries. If so, hypoxic-ischemic encephalopathy is still an issue of global health concern. It is thought that a consistent number of cases may be avoided, and its sequelae may be preventable by a prompt and efficient physical and therapeutic treatment. The lack of early, reliable, and specific biomarkers has up to now hampered a more effective use of hypothermia, which represents the only validated therapy for this condition. The urge to unravel the biological modifications underlying perinatal asphyxia and hypoxic-ischemic encephalopathy needs new diagnostic and therapeutic tools. Metabolomics for its own features is a powerful approach that may help for the identification of specific metabolic profiles related to the pathological mechanism and foreseeable outcome. The metabolomic profiles of animal and human infants exposed to perinatal asphyxia or developing hypoxic-ischemic encephalopathy have so far been investigated by means of 1H nuclear magnetic resonance spectroscopy and mass spectrometry coupled with gas or liquid chromatography, leading to the identification of promising metabolomic signatures. In this work, an extensive review of the relevant literature was performed.

Cardiac arrest (CA) is not a uniform condition and its pathophysiology strongly depends on its cause. In this work we have used a metabolomics approach to study the dynamic metabolic changes occurring in the plasma samples of a swine model following two different causes of CA, namely asphyxia (ACA) and ventricular fibrillation (VFCA). Plasma samples were collected at baseline and every minute during the experimental phases. In order to identify the metabolomics profiles characterizing the two pathological entities, all samples were analysed by 1H NMR spectroscopy and LC-MS/MS spectrometry.The metabolomics fingerprints of ACA and VFCA significantly differed during the peri-arrest period and the resuscitation phase. Major alterations were observed in plasma concentrations of metabolites related to tricarboxylic acid (TCA) cycle, urea cycle, and anaplerotic replenishing of TCA. ACA animals showed significant metabolic disturbances during the asphyxial and CA phases, while for VFCA animals this phenomenon resulted shifted at the resuscitation phase. Interestingly, starting from the asphyxial phase, the ACA animals were stratified in two groups based on their metabolomics profiles that resulted to be correlated with the clinical outcome. Succinate overproduction was observed in the animals with the worse outcome, suggesting a potential prognostic role for this metabolite.

Pulmonary arterial hypertension (PAH) in systemic sclerosis (SS) identifies a poor prognosis subset of patients. Recent studies suggested a "metabolic theory" on the development of pulmonary arterial hypertension. On this basis we performed a metabolomic study in order to evaluate whether differences in pulmonary arterial blood metabolites were identifiable in SS patients with increased pulmonary vascular resistance (PVR).We studied 18 SS patients (age 58.7±15.6years) free of pulmonary fibrosis who underwent a right heart catheterization (RHC). A blood sample was collected during the RHC in the distal peripheral circulation of the pulmonary arteries to perform the metabolomic analysis.Based on PVR we divided the population into Group A (n=8; PVR=1.16±0.23WU) and Group B (n=10; PVR=2.67±0.67WU; p0.001 vs Group A). No significant differences were identified in terms of anthropometric, clinical, echo and therapeutic characteristics. At RHC the 2 groups showed a difference in mean pulmonary pressure values (Group A: 20±4mmHg; Group B: 27±3.4mmHg; p=0.03), with mild PAH in Group B. We applied an OSC-PLS-DA with a clear clusterization; SSc patients with PAH showed an increase in acetate, alanine, lactate, and lipoprotein levels and a decrease in γ-aminobutyrate, arginine, betaine, choline, creatine, creatinine, glucose, glutamate, glutamine, glycine, histidine, phenylalanine, and tyrosine levels CONCLUSIONS: Our results suggest that, despite similar clinical and disease-related parameters, SSc patients who develop PAH have an unfavorable metabolic profile able to cause an impaired production of metabolites with protective effects on endothelial cells.

Background Vancomycin and piperacillin/tazobactam are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated synergistic toxicity, only that serum creatinine increases. Objectives To clarify the potential for synergistic toxicity between vancomycin, piperacillin/tazobactam and vancomycin + piperacillin/tazobactam treatments by quantifying kidney injury in a translational rat model of AKI and using cell studies. Methods (i) Male Sprague–Dawley rats (n = 32) received saline, vancomycin 150 mg/kg/day intravenously, piperacillin/tazobactam 1400 mg/kg/day intraperitoneally or vancomycin + piperacillin/tazobactam for 3 days. Urinary biomarkers and histopathology were analysed. (ii) Cellular injury was assessed in NRK-52E cells using alamarBlue®. Results Urinary output increased from Day −1 to Day 1 with vancomycin but only after Day 2 for vancomycin + piperacillin/tazobactam-treated rats. Plasma creatinine was elevated from baseline with vancomycin by Day 2 and only by Day 4 for vancomycin + piperacillin/tazobactam. Urinary KIM-1 and clusterin were increased with vancomycin from Day 1 versus controls (P Conclusions All groups treated with vancomycin demonstrated AKI; however, vancomycin + piperacillin/tazobactam was not worse than vancomycin. Histopathology suggested that piperacillin/tazobactam did not worsen vancomycin-induced AKI and may even be protective.

The estimation of the time since death, or post-mortem interval (PMI), still remains a main conundrum in forensic science. Several approaches have been so far proposed from either a qualitative or a quantitative point of view, but they still lack reliability and robustness. Recently, metabolomics has shown to be a potential tool to investigate the time-related post-mortem metabolite modifications in animal models. Here we propose, for the first time, the use of a 1H NMR metabolomic approach for the estimation of PMI from aqueous humour (AH) in an ovine model. AH samples were collected at different times after death (from 118 to 1429 min). 1H NMR experiments were performed and spectral data analysed by multivariate statistical tools. A multivariate calibration model was built to estimate PMI on the basis of the metabolite content of the samples. The model was validated with an independent test set, obtaining a prediction error of 59 min for PMI 1000 min. Moreover, the metabolomic approach suggested a picture of the mechanisms underlying the post-mortem biological modifications, highlighting the role played by taurine, choline, and succinate. The time-related modifications of the 1H NMR AH metabolomic profile seem to be encouraging in addressing the issue of a reproducible and robust model to be employed for the estimation of the time since death.

IntroductionVancomycin and piperacillin tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic toxicity occurs, only that serum creatinine (SCr) increases with VAN+TZP. The purpose of this study was to assess biologic plausibility by quantifying kidney injury between VAN, TZP, and VAN+TZP treatments using a translational rat model of AKI and rat kidney epithelial cell studies.Methods(i) Male Sprague-Dawley rats (n=32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1400 mg/kg/day via intraperitoneal injection, or VAN+TZP. Animals were placed in metabolic cages pre-study and on drug dosing days 1-3. Urinary biomarkers and histopathology were analyzed. (ii) Cellular injury of VAN+TZP was assessed in serum-deprived rat kidney cells (NRK-52E) using an alamarBlue® viability assay. Cells were incubated with antibiotics VAN, TZP, cefepime, and gentamicin alone or combined with the same drugs plus VAN 1 mg/mL.ResultsIn the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared to controls (P5048.76 mg/mL). TZP alone did not cause cellular death under the same conditions. VAN+TZP was not different from VAN alone in NRK-52E cells (P>0.2).ConclusionsVAN+TZP does not cause more kidney injury than VAN alone in a rat model of VIKI or in rat kidney epithelial cells.

We used field-emission scanning electron microscopy (FESEM) coupled with energy dispersive X-ray spectroscopy (EDS) microanalysis to determine size, shape, and elemental composition of particles in the liver and kidney autopsy of 35 subjects living in Sardinia. Particles were detected in 94% of livers and in 97% of kidney samples as aggregates, ranging between 50 nm and 100 μm. A total of 513 particle aggregates were observed in all tissues (276 in the liver and 237 in the kidney samples). Aggregates consisted of single elements (As, Ba, Cu, F, Fe, Ge, Hg, Ni, P, Pb, S, Si, Ti) or multiple association of elements, up to six. Silicon and Fe were the main element constituents (presence in 61% and 23% of the total Pags) followed by Al, Hg, Ni, Pb, and Ti (

The estimation of the time since death, or post-mortem interval (PMI), still remains a main conundrum in forensic science. Several approaches have been so far proposed from either a qualitative or a quantitative point of view, but they still lack reliability and robustness. Recently, metabolomics has shown to be a potential tool to investigate the time-related post-mortem metabolite modifications in animal models.Here we propose, for the first time, the use of aAH samples were collected at different times after death (from 118 to 1429 min).A multivariate calibration model was built to estimate PMI on the basis of the metabolite content of the samples. The model was validated with an independent test set, obtaining a prediction error of 59 min for PMI 500 min, 104 min for PMI from 500 to 1000 min, and 118 min for PMI 1000 min. Moreover, the metabolomic approach suggested a picture of the mechanisms underlying the post-mortem biological modifications, highlighting the role played by taurine, choline, and succinate.The time-related modifications of the

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

Introduction: A disease or disorder is defined rare when it affects less than 1 in 2000 subjects. 400 million people worldwide are living with a rare disease; approximately 50% of these patients are children, and 30% of them die within the first 5 years of life. The wide aetiology diversity leads to high variability in symptomatology, and clinical manifestations and consequently to challenging diagnosis. New experimental approaches are therefore recommended to improve diagnosis, and for the development of new therapeutic strategies. In the last years, metabolomics have allowed to better understand the metabolic processes associated with several rare diseases.Areas covered: This review describes the use of metabolomics for the study of the metabolic alterations related to some of the most studied pediatric rare disorders. Metabolomics, by means of 1H NMR spectroscopy and MS spectrometry, allows the identification and the quantification of a large number of metabolites (biomarkers) in different biof...

Background The endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that the endothelial status can be regarded as an integrated index of individual atherogenic and anti-atherogenic properties, and that the interaction between circulating factors and the arterial wall might be critical for atherogenesis. In organism-level investigations, a functional view is provided by metabolomics, the study of the metabolic profile of small molecules. We sought to verify whether metabolomic analysis can reveal the presence of coronary microenvironment peculiarities associated with distinct manifestations of CAD. Methods Thirty-two coronary blood samples were analyzed using 1H-NMR-based metabolomics. Samples collected from patients with evidence of myocardial ischemia formed the case group, and were further divided into the stenotic-disease (SD) group (N = 13) and absence of stenosis (microvascular disease; “Micro”) group (N = 8); specimens of patients presenting no evidence of ischemic heart disease (dilated cardiomyopathy, valvular diseases) constituted the control group (N = 11). Results Application of an orthogonal partial least squares discriminant analysis (OPLS-DA) model to the entire dataset clearly separated the samples into 3 groups, indicating 3 distinct metabolic fingerprints. Relative to control-group members, Micro patients showed a higher content of 2-hydroxybutirate, alanine, leucine, isoleucine, and N-acetyl groups and lower levels of creatine/phosphocreatine, creatinine, and glucose, whereas SD patients showed higher levels of 3-hydroxybutirate and acetate and a lower content of 2-hydroxybutirate. Moreover, relative to SD patients, Micro patients showed higher levels of 2-hydroxybutirate, alanine, leucine, and N-acetyl groups and lower levels of 3-hydroxybutirate and acetate. Conclusions Specific coronary microenvironments are likely associated with distinct development and pathological expression of CAD. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1215-7) contains supplementary material, which is available to authorized users.

1H NMR spectroscopy was used to investigate changes in the low molecular weight metabolic profile of raw mullet (Mugil spp.) roes during frozen storage and upon processing. NMR data were analysed by Principal Component Analyses (PCA). In the model constructed using frozen roes, no statistical significant metabolic modifications were observed in the first six months of storage, while choline derivatives, dimethylamine, lactate, and most of the free amino acids were identified as changing with statistical significance (p

Background Vancomycin and piperacillin–tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic AKI occurs, only that serum creatinine increases with VAN+TZP. Previous preclinical work demonstrated that novel urinary biomarkers and histopathologic scores were not increased in the VAN+TZP group compared with VAN alone. The purpose of this study was to assess changes in urinary output and plasma creatinine between VAN, TZP, and VAN+TZP treatments. Methods Male Sprague–Dawley rats (n = 32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1,400 mg/kg/day intraperitoneally, or VAN+TZP for 3 days. Animals were placed in metabolic cages pre-study and on drug dosing days 1–3. Urinary output, plasma creatinine, urinary biomarkers were compared daily and kidney histopathology was compared at the end of therapy between the groups. Mixed-effects, repeated-measures models were employed to assess differences between the groups. Results In the VAN-treated rats, urinary output was increased on days 1, 2 and 3 compared with baseline and saline (P < 0.01 for all), whereas it increased later for VAN+TZP (i.e., day 2 and 3 compared with saline, P < 0.001). No changes in urinary output were observed with saline and TZP alone. Plasma creatinine rose for VAN on days 1, 2, and 3 from baseline and VAN+TZP on day 3 (P < 0.02 for all), but no treatment group was different from saline. In the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared with controls (P < 0.001). Elevations were seen only after 3 days of treatment with VAN+TZP (P < 0.001 KIM-1, P < 0.05 clusterin). No changes in urinary biomarkers output were observed with saline and TZP alone. Histopathology was only elevated in the VAN group compared with saline (P < 0.002). No histopathology changes were noted with VAN+TZP. Conclusion All groups with VAN demonstrated kidney injury; however, VAN+TZP did not cause more kidney injury than VAN alone in a rat model of VIKI when using plasma creatinine, urinary output, or urinary biomarkers as outcomes. Histopathology data suggest that adding TZP did not worsen VAN-induced AKI and may even be protective. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.

In this feasibility study, we propose, for the first time, (1)H NMR spectroscopy coupled with mathematical strategies as a valid tool for body fluid (BF) trace identification in forensic science. In order to assess the ability of this approach to identify traces composed either by a single or by two different BFs, samples of blood, urine, saliva, and semen were collected from different donors, and binary mixtures were prepared. (1)H NMR analyses were carried out for all samples. Spectral data of the whole set were firstly submitted to unsupervised principal component analysis (PCA); it showed that samples of the same BF cluster well on the basis of their characterizing molecular components and that mixtures exhibit intermediate characteristics among BF typologies. Furthermore, samples were divided into a training set and a test set. An average NMR spectral profile for each typology of BF was obtained from the training set and validated as representative of each BF class. Finally, a fitting procedure, based on a system of linear equations with the four obtained average spectral profiles, was applied to the test set and the mixture samples; it showed that BFs can be unambiguously identified, even as components of a mixture. The successful use of this mathematical procedure has the advantage, in forensics, of overcoming bias due to the analyst's personal judgment. We therefore propose this combined approach as a valid, fast, and non-destructive tool for addressing the challenges in the identification of composite traces in forensics.

Objectives: 1H NMR-metabolomic approach was used to investigate QTc interval correlation with plasma metabolic profiles in shiftworkers. Methods: Socio-demographic data, electrocardiographic QTc interval and plasma metabolic profiles from 32 male shiftworkers, were correlated by multivariate regression analysis. Results: We found a positive correlation between QTc interval values, body mass index, glycemia and lactate level and a negative correlation between QTc interval and both pyroglutamate and 3-hydroxybutyrate plasma level. Conclusions: Our analysis provides evidence of the association between clinical, metabolic profiles and QTc interval values. This could be used to identify markers of early effects and/or susceptibility in shiftworkers.

This paper will examine the role women played within the vast system of reforms carried out by Mustafa Kemal, during the very first Republic. Gender issues, fundamental rights - voting, open access to education and the ensuing way in the work world - were but a few of the main pillars of the Kemalist reforms. The Kemalist ideology built a new paradigm of liberated woman, as well as devising a new model of the nation. The spillover on a very traditional Islamic society was pretty much high; thus, the aim of the present study is to explain the dynamics that led - earlier than elsewhere - the Turkish female world to become the global player of its time