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In nature, various types of animals will form self-organised large-scale structures. Through designing wireless actuation methods, microrobots can emulate natural swarm behaviours, which have drawn extensive attention due to their great potential in biomedical applications. However, as the prerequisite for their in-vivo applications, whether microrobotic swarms can take effect in bio-fluids with complex components has yet to be fully investigated. In this work, we first categorise magnetic active swarms into three types, and individually investigate the generation and navigation behaviours of two types of the swarms in bio-fluids. The influences of viscosities, ionic strengths and mesh-like structures are studied. A strategy is then proposed to select the optimised swarms in different fluidic environments based on their physical properties, and the results are further validated in various bio-fluids. Moreover, we also realise the swarm generation and navigation in bovine eyeballs, which also validates the proposed prediction in the ex-vivo environment. Although microrobotic swarms are attractive for biomedical applications, controlling their collective movement in specific bio-fluids is difficult. Here, the authors report navigated locomotion and collective behaviors of magnetic field- and medium-induced micro-robotic swarms in various bio-fluids.

Aims/hypothesisProliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR.MethodsWe analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27–80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration.ResultsWe identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024).Conclusions/interpretationThese results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR.

To characterize the biophysical properties of an artificial vitreous body substitute (VBS), which consists of a biocompatible, cross-linked, hyaluronic acid (HA)-based hydrogel, by analysing the VBS's influence on intraocular pressure (IOP) and retinal integrity in distinct ex vivo eye models in order to evaluate the its potential for in vivo biocompatibility testing. Pig eyes were obtained immediately postmortem, and VBS was injected after core-vitrectomy. IOP was followed for 24 h (n = 5). VBS influence on retinal integrity was investigated using isolated bovine retinas superfused with an oxygen saturated nutrient solution. An electroretinogram (ERG) was recorded on explanted bovine retinae using silver/silver chloride electrodes; after application of VBS for 2 min, a washout period of 70 min was employed. The percentage of a-and b-wave reduction at the end of the washout phase was compared to baseline values (n = 5). Data were calculated throughout as the mean and the standard deviation. qRT-PCR (Bax/Bcl-2-ratio, GFAP- and PGP9.5-levels) or western blot analysis was used to test for toxicity of Princess Volume after 24 h (and β-3 tubulin with GAPDH as a control gene). Significance was estimated by Student´s t-test; p ≤0.05 was considered to be statistically significant. The IOP increased non-significantly by 10% after 24 h. Short-term biocompatibility testing using isolated superfused bovine retinas showed neither significant reductions of the b-wave nor the a-wave amplitudes (b-wave reduction 14.2%, p>0.05; a-wave reduction 23.9%, p>0.05). qRT-PCR and western blot analysis did not reveal significant toxicity after 24 h. The manufactured HA-based hydrogel showed highly favourable biophysical characteristics in the explored ex vivo models, justifying in vivo studies enabling the assessment of biocompatibility.

Ethanol (ethylic alcohol) represents the most commonly used drug worldwide and is often involved in clinical and forensic toxicology. Based on several reports, excessive alcohol consumption is the main contributing factor in traffic accidents, drownings, suicides, and other crimes. For these reasons, it becomes essential to analyze the alcohol concentration during autopsy. Although blood is usually used for alcohol analysis in post-mortem cases, it could suffer alterations, putrefaction, and microbial contaminations. As an alternative to whole blood, vitreous humor has been successfully used in medico-legal studies. In this work, post-mortem specimens were analyzed for ethanol determination. The analysis of blood and vitreous humor were carried-out using gas chromatography-flame ionized detector (GC-FID) with a total run time of 6 min. The method was validated in terms of limit of detection, limit of quantification, dynamic range, sensibility, recovery, precision and trueness. A linear regression analysis indicated a coefficient of determination (R2) of 0.9981. The study confirmed no statistically differences between alcohol concentration in blood and vitreous humor, leading vitreous humor as an excellent matrix that could be used as an alternative to whole blood in toxicological analysis in cases where blood is not available.

This review will focus on the molecular organisation of the adult vitreous and how it undergoes ageing changes throughout life that result in vitreous liquefaction and a predisposition towards posterior vitreous detachment and retinal break formation. At birth, the vitreous humour is in a gel state due to the presence of a network of fine collagen fibrils. With ageing, these collagen fibrils progressively aggregate due to a loss of type IX collagen from their surfaces. The aggregation of collagen fibrils may cause vitreous liquefaction which, when combined with an age-related weakening of postbasal vitreoretinal adhesion, predisposes to posterior vitreous detachment. Throughout postnatal life, the posterior border of the vitreous base migrates posteriorly from the ora serrata into the peripheral retina. This is due to new collagen synthesis by the peripheral retina. This new collagen intertwines with pre-existing cortical vitreous collagen to create new adhesions and thereby extends the vitreous base posteriorly. If irregularities in the posterior border of the vitreous base arise from this process, there is a predisposition towards retinal break formation during posterior vitreous detachment and subsequent rhegmatogenous retinal detachment.

[Display omitted] •The estimation of the PMI is of paramount importance in the field of forensic sciences.•Traditionally, the methodology for its estimation is based on physical variables.•Introducing chemical variables and GAM methodology reduces the error when estimating the PMI.•PMI estimation can be performed in an easy, fast and reliable way using software designed for this purpose. The estimation of the time elapsed since death is of paramount importance in the field of forensic sciences and criminal investigation, owing, among other factors, to the possible legal repercussions. Over the past few years various formulae have been developed to calculate this interval using a combination of different statistical methods and the concentrations of substances found in the vitreous humor. Corrective factors, such as ambient temperature, cause of death or age, which can modify the concentration of these substances and therefore the estimation of the postmortem interval, have been incorporated into models. In this paper five simple and reliable models to estimate PMI based the on the analysis of potassium, hypoxanthine and urea in the vitreous humor are presented. Corrective factors, such as body weight, rectal temperature and ambient temperature, which can influence the estimation of this interval have been incorporated into the formulae. Finally, the R2 and the mean squared error have been calculated for each model in order to select the best of the five. A free software program which calculates the PMI from the model and parameters used is available from the authors. It provides quick and reliable results as well as the error committed and R2 for each case.

Determination of the time of death and post-mortem interval (PMI) is a major task for Legal and Forensic Medicine, given the implications it entails. In this respect, depending on the proximity to the moment of death, this PMI estimation will be simpler or more complex. Traditionally, the estimation of the PMI has centred upon the analysis of corporeal rigidity, body temperature and the concentration of potassium within the vitreous humour. However, in recent years, innovative methodologies that facilitate an increasingly precise prediction of the PMI have been developed. Therefore, this article aims to compile and present a comprehensive overview of these PMI estimation techniques, in order to serve as a basic guide and reference point to understand the latest advances in this area, as well as to identify their limitations and to explore the potential future directions of this discipline. •The estimation of the time of death is a highly complex task in Forensic Medicine.•Classical methods, such as cadaveric stiffness, have wide variations with respect to death data.•In recent years, novel techniques for estimating the time of death have been developed.•These techniques focus, among others, on immunohistochemical or protein degradation methods.•It is essential to validate and replicate these techniques to gain certainty and reliability

Ketone bodies, like β-hydroxybutyrate (BHB), derived from fatty acid breakdown, can cause fatal ketoacidosis if levels are excessively high. Postmortem diagnosis of ketoacidosis is challenging due to non-specificity of rapid chromogenic tests and the time required for LC-MS/MS analysis. This study investigates the feasibility of using point-of-care (POC) BHB and glucose testing to diagnose ketoacidosis-related deaths and distinguish between diabetic and other types of ketoacidosis, post-mortem. This study evaluated the Nova StatStrip meter’s analytical and post-mortem performance for measuring BHB and glucose in decedent whole blood and vitreous humor. Precision, linearity, and recovery were assessed. BHB and glucose were measured in whole blood and vitreous humor from 100 autopsy cases (both ketoacidosis and non-ketoacidosis deaths). Results were compared quantitatively and qualitatively with standard laboratory methods to determine the meter's accuracy and reliability in predicting ketoacidosis-related deaths. Receiver operating characteristic (ROC) curves were constructed for each matrix/analyte combination to evaluate screening capabilities for ketoacidosis- and diabetic ketoacidosis-related deaths. Imprecision was highest in decedent vitreous humor samples for both BHB and glucose and both assays exhibited acceptable linearity. ROC curve analysis indicated comparable post-mortem performance between methods and matrices. Whole blood BHB showed the best performance for predicting all-cause ketoacidosis on the meter, despite exhibiting a higher device error messages than vitreous humor. Glucose in vitreous humor exhibited the most optimal performance (100 % sensitivity and specificity) but showed the highest rate of error messages (64 %). Thus, whole blood glucose (80 % sensitivity, 98 % specificity) would be the preferred matrix to identify potential DKA-related deaths. Agreement between meter and laboratory methods was excellent despite differing thresholds (96–100 %). This study suggests that post-mortem BHB levels in whole blood and vitreous humor can be conveniently obtained using the StatStrip meter and have comparable performance to current standards, making it suitable as a screening tool for ketoacidosis-related death. Screening thresholds recommended are vitreous humor (≥ 0.9 mmol/L) or whole blood (≥ 1.6 mmol/L) BHB for ketoacidosis-related death, followed by whole blood glucose (≥ 27.3 mmol/L) for DKA-related death. •Post-mortem β-hydroxybutyrate can be obtained via a point-of-care device•Potential suitability as a screening tool for ketoacidosis-mediated deaths•Point-of-care glucose may identify diabetic ketoacidosis via a reflexive algorithm•Screening by point-of-care devices may reduce additional testing, time, and cost•Provides answers sooner to death investigation stakeholders and loved ones

IntroductionThe 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.ObjectivesWe applied 1H NMR metabolomics to estimate PMI on ovine vitreous humour comparing the results with the actual scientific gold standard, namely vitreous potassium concentrations.MethodsVitreous 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.ResultsA 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.ConclusionThe 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.

•A method for the determination of 9 antidepressants and metabolites was developed.•The method was validated and applied to blood and vitreous humor samples.•The vitreous humor/blood concentration ratios were calculated.•In all cases antidepressants were detected in blood and vitreous humor.•Vitreous humor can be used alternatively for antidepressants determination. Vitreous humor has become in recent years an important alternative biological fluid in forensic toxicological analysis especially for the investigation of cases where alcohol and drugs of abuse are involved but there is limited scientific information regarding the distribution of antidepressant drugs in this material. This work aimed to study the distribution of antidepressant drugs in vitreous humor and to estimate the blood/vitreous humor concentration ratios of these drugs. For this purpose, a GC/MS method for the simultaneous determination of 9 antidepressant drugs, namely amitriptyline, nortriptyline, citalopram, clomipramine, fluoxetine, maprotiline, mirtazapine, sertraline and venlafaxine, and 4 of their metabolites, namely desmethylmaprotiline, desmethylmirtazapine, desmethylsertraline, O-desmethylvenlafaxine, was developed and validated. The developed method includes solid-phase extraction followed by derivatization with Heptafluorobutyric Anhydride. For all analytes, LOD and LOQ were 1.50 and 5.00ng/mL, respectively, and the calibration curves were linear within the dynamic range of 5.00–500.0ng/mL (R2≥0.990). The absolute recovery was found to be ≥86.3 % for all analytes. The accuracy (%Er) was found to range between -6.58 and 6.18 %, whereas the precision (%RSD) was less than 10.9 % for all analytes. The developed method was successfully applied to vitreous humor samples from 43 blood positive cases for antidepressant drugs. Whenever antidepressant drugs were detected in blood, they were also detected in the respective vitreous humor samples. The vitreous humor/blood concentration ratios were also calculated and were found to range from 0.04–7.07. Citalopram, mirtazapine, and its metabolite desmethylmirtazapine as well as venlafaxine and its metabolite O-desmethylvenlafaxine were the most identified substances in these samples (n≥4) and their results were better statistically evaluated. Our results suggest that vitreous humor could be an appropriate matrix for the determination of antidepressants in postmortem toxicology.