CPMI: comprehensive neighborhood-based perturbed mutual information for identifying critical states of complex biological processes.

BACKGROUND: There exists a critical transition or tipping point during the complex biological process. Such critical transition is usually accompanied by the catastrophic consequences. Therefore, hunting for the tipping point or critical state is of significant importance to prevent or delay the occurrence of catastrophic consequences. However, predicting critical state based on the high-dimensional small sample data is a difficult problem, especially for single-cell expression data. RESULTS: In this study, we propose the comprehensive neighbourhood-based perturbed mutual information (CPMI) method to detect the critical states of complex biological processes. The CPMI method takes into account the relationship between genes and neighbours, so as to reduce the noise and enhance the robustness. This method is applied to a simulated dataset and six real datasets, including an influenza dataset, two single-cell expression datasets and three bulk datasets. The method can not only successfully detect the tipping points, but also identify their dynamic network biomarkers (DNBs). In addition, the discovery of transcription factors (TFs) which can regulate DNB genes and nondifferential 'dark genes' validates the effectiveness of our method. The numerical simulation verifies that the CPMI method is robust under different noise strengths and is superior to the existing methods on identifying the critical states. CONCLUSIONS: In conclusion, we propose a robust computational method, i.e., CPMI, which is applicable in both the bulk and single cell datasets. The CPMI method holds great potential in providing the early warning signals for complex biological processes and enabling early disease diagnosis.

Effects of population variations and temperature on Chrysomya megacephala (Diptera: Calliphoridae) development: implications for estimating the postmortem interval.

Forensic entomology requires knowledge of the developmental rates of the species that colonize a body after death to estimate the postmortem interval (PMI). These developmental rates may vary depending not only on the species but also on the geographic location due to population differences. Therefore, the objectives of this work were to determine the developmental duration of the forensically important fly Chrysomya megacephala under constant controlled and field condition temperatures and to compare these results, through a meta-analysis, with data reported by other authors on populations from different localities. For this, C. megacephala colonies were established in the laboratory, and the duration of the life cycle was studied at two controlled temperatures (25 °C and 27 °C) and field conditions (27.5 ± 3.2 °C). Analysis of variance was performed to determine differences in developmental time and larval length between constant laboratory temperatures and field conditions. A generalized linear model was performed with predictor variables extracted from the literature (diet, relative humidity, latitude, longitude) to evaluate the effect of population variation on developmental times. The results showed significant differences in developmental times between 25 and 27 °C. As expected, the complete life cycle of C. megacephala was shorter at 27 °C. Finally, the meta-analysis suggested differences between the developmental times of different populations, based on temperature and geographic location. The results of this study provide fundamental developmental data to use C. megacephala in PMI estimations. Finally, we suggest that, when making expert reports, information from local populations should be used to determine a more accurate and reliable PMI.

Bionomics, reproductive traits and assessment of forensic relevance of Peckia (Peckia) chrysostoma (Wiedemann, 1830) (Diptera: Sarcophagidae).

Peckia (Peckia) chrysostoma (Wiedemann, 1830) (Diptera: Sarcophagidae) is a colonizer of cadavers in the Neotropical Region. Nevertheless, data on development for the P. (P.) chrysostoma (e.g., instar duration) and behavioral strategies used by the species for locating and colonizing a corpse are scant. We aimed to explore bionomic and reproductive aspects of the flesh fly P. (P.) chrysostoma, and in this article we: (a) provide quantitative data on the life cycle of P. (P.) chrysostoma; (b) present bionomic measurements (length and weight) of larvae and pupae; (c) describe intrauterine egg and larvae development; and (d) analyze the ovo/larviposition behavior by gravid females. Females showed ovaries with discernible eggs and larvae between 8 and 10 days (x̅ = 23.3 eggs/female). This study reports the first observation of egg deposition, an atypical behavior for the species. The average development time for immature stages was 22.24 h and 21.36 h for 1st and 2nd respectively, and 3rd showed an average development time of 80.47 h. Pupa had the longest duration (x̅ = 295.69 h). A direct increase was observed in weight (P < 0.05) and length (P < 0.05) throughout time. The average survival time of males and females is approximately 30 days. This study expands the knowledge on P. (P.) chrysostoma, such as facultative ovoviviparity under laboratory conditions and the life cycle, which may benefit future studies for accuracy in entomology-based estimation of minimum post-mortem interval (min PMI).

Catch me if you can-emission patterns of human bodies in relation to postmortem changes.

The present study examines for the first time the emission patterns and olfactory signatures of 9 complete human corpses of different stages of decomposition. Air sampling was performed inside the body bags with solid sorbents and analysed by coupled gas chromatography-mass spectrometry after thermal desorption (TD-GC-MS). Furthermore, odour-related substances were detected by gas chromatography-olfactometry (GC-O). Sulfurous compounds (mainly dimethyl di- and trisulfide) were identified as most important to the odour perception. Around 350 individual organic substances were detected by TD-GC-MS, notably sulfurous and nitrogenous substances as well as branched alkanes, aldehydes, ketones, alcohols, carboxylic acids, carboxylic acid esters and ethers. A range of terpenes was detected for the first time in a characteristic emission pattern over all decomposition stages. Concentrations of the substances varied greatly, and no correlation between the emission patterns, the stage of decomposition and the cause of death could be found. While previous studies often analysed pig cadavers or only parts of human tissue, the present study shows the importance of analysing complete human corpses over a range of decomposition stages. Moreover, it is shown that using body bags as a kind of "emission test chamber" is a very promising approach, also because it is a realistic application considering the usual transport and store of a body before autopsy.

The impact of preoperative skeletal muscle loss on the completion of S-1 adjuvant chemotherapy for gastric cancer.

PURPOSE: Body weight loss after surgery for gastric cancer is related to S-1 compliance and it also affects the prognosis. However, it is unclear whether the preoperative skeletal muscle mass affects S-1 completion for gastric cancer. We investigated the impact of preoperative skeletal muscle mass loss on the completion of S-1 adjuvant chemotherapy for gastric cancer. METHODS: We retrospectively analyzed data from 53 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pStage II-III gastric cancer between 2012 and 2021 at our hospital. The psoas muscle mass index (PMI) was used as the index for preoperative skeletal muscle mass. RESULTS: Thirty-six patients completed S-1 treatment and 17 discontinued treatment. The patients who completed S-1 treatment had a longer overall survival than those who discontinued treatment (log-rank test, p = 0.043). According to a univariate analysis, the patients in the discontinuation group had a significantly lower preoperative body mass index (< 22.9 kg/m2, p = 0.005) and a higher rate of adverse events (grade 2 or higher, p < 0.001) than those in the completion group. According to a multivariate analysis, preoperative PMI (HR 3.563, p = 0.030) was an independent predictive factor for S-1 completion. CONCLUSION: Preoperative skeletal muscle loss might therefore prevent the completion of adjuvant chemotherapy S-1 in patients with gastric cancer.

Lipidomes in Cadaveric Decomposition and Determination of the Postmortem Interval: A Systematic Review.

Lipids are a large group of natural compounds, together with proteins and carbohydrates, and are essential for various processes in the body. After death, the organism's tissues undergo a series of reactions that generate changes in some molecules, including lipids. This means that determining the lipid change profile can be beneficial in estimating the postmortem interval (PMI). These changes can also help determine burial sites and advance the localization of graves. The aim was to explore and analyze the decomposition process of corpses, focusing on the transformation of lipids, especially triglycerides (TGs) and fatty acids (FAs), and the possible application of these compounds as markers to estimate PMI and detect burial sites. A systematic review of 24 scientific articles from the last 23 years (2000-2023) was conducted. The results show that membrane glycerophospholipids (such as phosphatidylcholine and phosphatidylglycerol, among others) are the most studied, and the most promising results are obtained, with decreasing patterns as PMI varies. Fatty acids (FAs) are also identified as potential biomarkers owing to the variations in their postmortem concentration. An increase in saturated fatty acids (SFAs), such as stearic acid and palmitic acid, and a decrease in unsaturated fatty acids (UFAs), such as oleic acid and linoleic acid, were observed. The importance of intrinsic and extrinsic factors in decomposition is also observed. Finally, as for the burial sites, the presence of fatty acids and some sterols in burial areas of animal and human remains can be verified. In conclusion, glycerophospholipids and fatty acids are good markers for estimating PMI. It has been observed that there are still no equations for estimating the PMI that can be applied to forensic practice, as intrinsic and extrinsic factors are seen to play a vital role in the decomposition process. As for determining burial sites, the importance of soil and textile samples has been demonstrated, showing a direct relationship between saturated fatty acids, hydroxy fatty acids, and some sterols with decomposing remains.

Proteomic Characterization of Changes in Mouse Brain Cortex Protein Expression at Different Post-Mortem Intervals: A Preliminary Study for Forensic Biomarker Identification.

Accuracy in the evaluation of death-induced tissue degradation for thanato-chronological purposes is strictly dependent on the condition of the biological source as well as on the precision of post-mortem interval (PMI) estimation. Thus, the optimization of tissue handling and identification of sensitive post-mortem biomarkers could help establish a timeline for post-mortem events. To this aim, we investigated the proteome changes in cortex samples of 6-week-old female SAMR1 mice over a post-mortem time course. After death, brain tissue was removed immediately (T0), and after 4, 8, 12, 24, and 32 h, four mice were used for each time period, and animals were maintained at 4 °C until brain removal. Dissected tissues were frozen at -80 °C until processed. Proteomic analysis, performed on samples related to early and late PMIs (<24 h and >24 h post-mortem, respectively) showed protein level changes as compared to T0 samples, with a remarkable increase in Calpain11 in the early PMI, as well as in Caspases 7 and 8 together with Gasdermin 3 in late PMI. These findings were confirmed by LIFT mass spectrometry technology and western blot analysis and, although requiring further investigation in other biological samples, suggest that these proteins could be considered as putative biomarkers of different PMIs.

Potential Role of mRNA in Estimating Postmortem Interval: A Systematic Review.

Although the postmortem interval estimation still represents one of the main goals of forensic medicine, there are still several limitations that weigh on the methods most used for its determination: for this reason, even today, precisely estimating the postmortem interval remains one of the most important challenges in the forensic pathology field. To try to overcome these limitations, in recent years, numerous studies have been conducted on the potential use of the mRNA degradation time for reaching a more precise post mortem interval (PMI) estimation. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of the knowledge focusing on the potential correlation between mRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed and Scopus. The analysis conducted made it possible to confirm the potential applicability of mRNA for reaching a more precise PMI estimation. The analysis of the results highlighted the usefulness of some mRNAs, such as ß-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, especially in short time frames, within a few hours or days of death. The matrices on which these analyses were conducted were also analyzed, resulting in less exposure to the external environment, including the heart, brain, and dental pulp. The major limitations were also reported, including the short time intervals analyzed in most of the articles, the lack of mathematical models, and the failure to report the error rate between the mRNA degradation time and PMI. Given the still small number of published articles, the lack of globally recognized standardized methods, and the numerous techniques used to evaluate the mRNA degradation times, numerous and larger studies are still necessary to reach more solid and shared evidence.

microRNAs as New Biomolecular Markers to Estimate Time since Death: A Systematic Review.

Estimating the post-mortem interval is still one of the most complex challenges in forensics. In fact, the main tools currently used are burdened by numerous limitations, which sometimes allow the time of death to be placed only within too large time intervals. In recent years, researchers have tried to identify new tools to try to narrow down the interval within which to place the time of death; among these, the analysis of microRNAs seems to be promising. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of knowledge, focusing on the potential correlation between miRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed, Scopus, and WOS. The results allowed us to highlight the usefulness of miRNAs both as markers for PMI estimation and for normalization, especially due to their stability. In fact, some miRNAs remain particularly stable for long periods and in different tissues, while others degrade faster. Furthermore, there are numerous factors capable of influencing the behavior of these molecules, among which the type of tissue, the cause of death, and the circadian rhythm appear to be the most relevant. Despite the promising results of the few articles present in the literature, because of the numerous limitations they are burdened by, further research is still necessary to achieve more solid and shareable results.

Dental DNA Mutations Occurring after Death: A Novel Method for Post-Mortem Interval (PMI) Estimation.

Post-mortem interval (PMI) estimation remains one of the major challenges in forensic practice, especially for late PMIs beyond 7-10 days after the death of the subject. In 2022, an innovative method to investigate the occurrence of mutations induced by the death of a subject in the DNA of post-mortem dental pulps at different PMIs was developed, applying a next-generation sequencing (NGS) analysis. The present study aims to apply the same method of analysis to a small sample of teeth belonging to the same subject and analyzed at different PMIs/accumulated degree days (ADDs), and of teeth extracted from different subjects but analyzed at the same PMI/ADD to verify the repeatability of the results obtained in relation to the time elapsed since death. A total of 10 teeth were collected from 6 patients (3 males and 3 females) with PMI varying from 8 to 35 days, and ADD from 157.4 to 753.8. We found 1754 mutations in 56 genes, with more than 700 mutations having a prevalence > 5% and more than 300 variants considered of interest for the purposes of the study. Mutations that were not present at lower PMIs but manifested in later PMIs in pulps belonging to the same subject demonstrate that they can only have been acquired by the subject after death and according to the time elapsed since death. In total, 67 somatic mutations in 29 out of the 56 genes of the used panel occurred in a fashion that allows an association with specific PMI/ADD ranges (within 8 days, between 17 and 28, and beyond 30 days after death). The results suggest that temperature and humidity could influence the rate of DNA degeneration in dental pulps, thus PMI should be estimated in ADD more than days. The preliminary validation supports the hypothesis that the innovative method could be a useful tool for estimating the post-mortem interval even beyond the first week after death, but further analyses are needed to customize a specific genetic panel for forensic investigations and verify the influence of degenerative processes of soft tissues surrounding dental elements on DNA degeneration of pulps.

Forensic entomology in homicide cases: study of a corpse found inside a buried vehicle.

Forensic entomology plays a crucial role in death investigations, particularly in estimating the postmortem interval (PMI). This study presents a forensic entomology case involving a corpse found in a buried utility vehicle. The victim was in an advanced state of decomposition, with autopsy findings revealing gunshot wounds. Cadaveric fauna was collected at the scene and during the autopsy. The analysis revealed a diverse insect community, with predominance of Compsomyiops fulvicrura and Piophila casei. The time of development of species like Dermestes maculatus and Necrobia rufipes was used to estimate the minimum PMI. The presence and low abundance of Calliphora vicina, a species preferring lower temperatures, shed light on the seasonal conditions at the time of death and suggested possible body concealment shortly after death. This research is the first to report insects as evidence in a corpse found in a buried vehicle and contributes to the body of knowledge in forensic entomology. The study also suggests that the use of entomological evidence can provide additional information about the season in which the body was concealed, making it a valuable tool in death investigation and crime scene reconstruction. Finally, it emphasizes the need for proper sampling, expert identification, and close collaboration between forensic entomologists and pathologists.

[Post-hospital support for families: current situation and outlook]. / L'accompagnement posthospitalier des familles : état des lieux et perspectives.

After neonatal hospitalization, our healthcare system offers multidisciplinary care for premature babies and their families during the first years of life. However, there are disparities and gaps, particularly in the case of medium prematurity. Maternal and child protection, a major player in early prevention and family follow-up, is a partner likely to be able to deploy post-hospital support perspectives in favor of child development and parenting support.

Protein familiarity is a fundamental but rarely operationalized concept in the safety assessment of genetically modified crops: example of phosphomannose isomerase (PMI).

Fundamental to the safety assessment of genetically modified (GM) crops is the concept of negligible risk for newly expressed proteins for which there is a history of safe use. Although this simple concept has been stated in international and regional guidance for assessing the risk of newly expressed proteins in GM crops, its full implementation by regulatory authorities has been lacking. As a result, safety studies are often repeated at a significant expenditure of resources by developers, study results are repeatedly reviewed by regulators, and animals are sacrificed needlessly to complete redundant animal toxicity studies. This situation is illustrated using the example of the selectable marker phosphomannose isomerase (PMI) for which familiarity has been established. Reviewed is the history of safe use for PMI and predictable results of newly conducted safety studies including bioinformatic comparisons, resistance to digestion, and acute toxicity that were repeated to gain regulatory reapproval of PMI expressed from constructs in recently developed GM maize. As expected, the results of these newly repeated hazard-identification and characterization studies for PMI indicate negligible risk. PMI expressed in recently developed GM crops provides an opportunity to use the concept of familiarity by regulatory authorities to reduce risk-disproportionate regulation of these new events and lessen the resulting waste of both developer and regulator resources, as well as eliminate unnecessary animal testing. This would also correctly imply that familiar proteins like PMI have negligible risk. Together, such modernization of regulations would benefit society through enabling broader and faster access to needed technologies.

Effect of temporary freezing on postmortem protein degradation patterns.

BACKGROUND: A precise determination of time since death plays a major role in forensic routine. Currently available techniques for estimating the postmortem interval (PMI) are restricted to specific time periods or cannot be applied for individual case-specific reasons. During recent years, it has been repeatedly demonstrated that Western blot analysis of postmortem muscle protein degradation can substantially contribute to overcome these limitations in cases with different background. Enabling to delimit time points at which certain marker proteins undergo distinct degradation events, the method has become a reasonable new tool for PMI delimitation under various forensic scenarios. However, additional research is yet required to improve our understanding of protein decomposition and how it is affected by intrinsic and extrinsic factors. Since there are temperature limits for proteolysis, and investigators are confronted with frozen corpses, investigation of the effects of freezing and thawing on postmortem protein decomposition in the muscle tissue is an important objective to firmly establish the new method. It is also important because freezing is often the only practical means to intermittently preserve tissue samples from both true cases and animal model research. METHODS: Sets of dismembered pig hind limbs, either freshly detached non-frozen, or thawed after 4 months of freeze-storage (n = 6 each), were left to decompose under controlled conditions at 30 °C for 7 days and 10 days, respectively. Samples of the M. biceps femoris were regularly collected at predefined time points. All samples were processed via SDS-PAGE and Western blotting to identify the degradation patterns of previously characterized muscle proteins. RESULTS: Western blots show that the proteins degrade predictably over time in precise patterns that are largely unaffected by the freeze-and-thaw process. Investigated proteins showed complete degradation of the native protein band, partly giving rise to degradation products present in distinct time phases of the decomposition process. CONCLUSION: This study provides substantial new information from a porcine model to assess the degree of bias that freezing and thawing induces on postmortem degradation of skeletal muscle proteins. Results support that a freeze-thaw cycle with prolonged storage in frozen state has no significant impact on the decomposition behavior. This will help to equip the protein degradation-based method for PMI determination with a robust applicability in the normal forensic setting.

A global perspective of forensic entomology case reports from 1935 to 2022.

Forensic entomology case reports are the product of rapid development in the field, the widespread acceptance of the science and the application of forensic entomological knowledge. In this study, we retrospectively summarized information derived from 307 forensic entomology case reports from 1935 to 2022 from a global perspective. Our checklist of relevant information included insect species, specific indoor or outdoor preferences, preferred temperatures, and stages of body decomposition. Finally, a concept and calculation method for postmortem interval (PMI) estimation accuracy was proposed. There were 232 cases using insect developmental data and 28 cases using succession patterns to estimate PMI. A total of 146 species of insects were involved in the cases, of which 62.3% were Diptera and 37.7% were Coleoptera. Postmortem intervals were estimated from eggs in 4 cases, larvae in 180 cases, pupae in 45 cases, and puparia in 38 cases. The majority of cases were from June to October, and the average number of species mentioned in the cases was more at 15-30 °C. Considering the standardization of application, in the majority of cases, insect evidence was collected by other personnel and sent to forensic entomologists, there was a delay in the sampling, and the scene or meteorological data were directly used without correcting. Our data shows that there are still many shortcomings in the universality and standardization of forensic entomology in its practical application.

PMI estimation through metabolomics and potassium analysis on animal vitreous humour.

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.

Initial laboratory validation of temperature development models for Necrodes littoralis L. (Staphylinidae: Silphinae).

Development models of necrophagous insects are applied in forensic entomology for post-mortem interval estimation. Such estimates may be used as scientific evidence in legal investigations. For this reason, it is important that the models are valid and that the expert witness is aware of their limitations. Necrodes littoralis L. (Staphylinidae: Silphinae) is a necrophagous beetle species that frequently colonizes human cadavers. Temperature models of development for the Central European population of these beetles were recently published. In this article, we present results of the laboratory validation study for these models. Errors of beetle age estimation differed significantly between the models. Thermal summation models yielded the most accurate estimates, and the isomegalen diagram least accurate estimates. Errors of the beetle age estimation varied across beetle developmental stages and rearing temperatures. In general, most development models of N. littoralis were satisfactorily accurate in estimating beetle age under laboratory conditions; therefore, the study provides initial evidence to support their validity in forensic cases.

Elastic fiber degradation as a possible indicator for PMI estimation on mummified and corified skin: a pilot study.

Mummified and corified bodies are particularly complex scenarios to investigate, starting from identifying the post-mortem interval (PMI), even more so in indoor environments. In these bodies, the skin has the peculiar feature to resist for a long time. Among its components, there are elastic fibers, which are characterized by intrinsic resistance to post-mortem degenerative phenomena. Starting from these considerations, we investigated microscopically the persistence, detectability, and changes of elastic fibers in the skin of mummified and corified bodies with different known PMI. The aim was to evaluate whether they could provide an additional tool to aid in PMI estimation in these cases. Therefore, we collected skin samples from mummified or corified bodies found in a domestic environment with different known PMI, as well as from corified bodies that had been exhumed after 11 years of burial. Histochemical staining specific for elastic fibers, namely, Weigert's resorcin fuchsin, showed their prolonged persistence and a progressive and different degradation between mummified and corified skin as a function of PMI. Moreover, on the whole, we observed greater preservation of elastic fibers in mummified skin than in corified one at the same PMI. Therefore, histological analysis of elastic fibers in mummified and corified skin may help to provide valuable aid in estimating PMI, especially in those particular cases where more reliable alternatives are lacking.

Metabolomics investigation of post-mortem human pericardial fluid.

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 1H 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 1H 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.

Vitamin C may reduce troponin and CKMB levels after PCI and CABG: a meta-analysis.

BACKGROUND: Ischemia/reperfusion injury contributes to periprocedural myocardial injury (PMI) in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PMI can be estimated by the elevation of troponin (Tn) and creatine kinase-MB (CKMB) plasma levels, and it is associated with increased risk of cardiovascular events and mortality. Vitamin C might have a beneficial effect on PMI by improving endothelial function, improving myocardial perfusion, and by reducing oxidative stress generated during/after reperfusion. In several small animal models of cardiac stress, vitamin C reduced the increase in Tn and CKMB levels. The aim of this meta-analysis was to investigate whether vitamin C administration may have an effect on Tn and CKMB levels in patients undergoing PCI or CABG. METHODS: We searched PubMed, Cochrane, Embase and Scopus databases for controlled clinical trials reporting on Tn and CKMB levels in adult patients who underwent PCI or CABG and received vitamin C. As secondary outcomes we collected data on biomarkers of oxidative stress in the included trials. In our meta-analysis, we used the relative scale and estimated the effect as the ratio of means. RESULTS: We found seven controlled trials which included 872 patients. All included trials administered vitamin C intravenously, with a range from 1 to 16 g/day, and all initiated vitamin administration prior to the procedure. Vitamin C decreased peak Tn plasma levels in four trials on average by 43% (95% CI: 13 to 63%, p = 0.01) and peak CKMB plasma levels in five trials by 14% (95% CI: 8 to 21%, p < 0.001). Vitamin C also significantly decreased the biomarkers of oxidative stress. CONCLUSIONS: Vitamin C may decrease cardiac enzyme levels in patients undergoing elective PCI or CABG. This may be explained partially by its antioxidant effects. Our findings encourage further research on vitamin C administration during cardiac procedures and in other clinical contexts that increase the level of cardiac enzymes. Future studies should search for an optimal dosing regimen, taking baseline and follow-up plasma vitamin C levels into account.