Structure of antiviral drug bulevirtide bound to hepatitis B and D virus receptor protein NTCP.

Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding of the viral surface polypeptide preS1 to the hepatobiliary transporter Na+-taurocholate co-transporting polypeptide (NTCP). This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a preS1 derivative and approved drug for treating HDV infection. Here, to elucidate the basis of this inhibitory function, we determined a cryo-EM structure of BLV-bound human NTCP. BLV forms two domains, a plug lodged in the bile salt transport tunnel of NTCP and a string that covers the receptor's extracellular surface. The N-terminally attached myristoyl group of BLV interacts with the lipid-exposed surface of NTCP. Our structure reveals how BLV inhibits bile salt transport, rationalizes NTCP mutations that decrease the risk of HBV/HDV infection, and provides a basis for understanding the host specificity of HBV/HDV. Our results provide opportunities for structure-guided development of inhibitors that target HBV/HDV docking to NTCP.

Homicide Manner-of-Death Classification in Arrest-Related Death.

ABSTRACT: Multiple studies have documented various factors that influence or determine forensic pathologist classification of manner of death. There do not appear to be any published studies on manner of death classification specifically regarding arrest-related deaths (ARDs). The goal of this study was to consider a large body of cases of nonfirearm ARDs to analyze the homicide classification with regards to numerous decedent and practitioner (medical examiner/coroner [ME/C]) variables. We analyzed 1145 US autopsy reports from the years 2006-2020, inclusive, and considered decedent variables of age, ethnicity, height, weight, body mass index, toxicology, and mention of a conducted electrical weapon and ME/C influence variables of gender, country region, and year. We found that the homicide classification likelihood increased by a factor of 1.04-1.05 per year, 1.34-1.37 for a female medical examiner, and 1.4-1.5 going from Southern states to Western states. There is an increasing trend for ME/C to label nonfirearm ARDs as homicides in the United States. The homicide classification is more common in Western states and less common in Southern states, and it was more common with a female ME/C.

Comparison of massively parallel sequencing to capillary electrophoresis for short tandem repeat genotyping of trace DNA.

In forensic genetics, massively parallel sequencing (MPS) offers several advantages over the current golden standard, capillary electrophoresis (CE): additional sequence information, shorter amplicon lengths, and the simultaneous analysis of many markers. These benefits result in a reduced number of reactions necessary while improving the amount of data obtained, thereby conserving valuable sample extracts. This proves particularly advantageous for the analysis of trace DNA. This study assessed the suitability of MPS for short tandem repeat (STR) typing of low template samples compared with results obtained through CE. The MPS genotypes showed higher concordance to reference genotypes, with donor alleles being more frequently assigned to be the major contributor, meeting the requirements for database entry. However, the MPS workflow is more time-consuming and associated with higher costs.

Emergence of SARS-CoV-2 spike protein at the vaccination site.

BACKGROUND: The anti-coronavirus disease 2019 (COVID-19) vaccines are of paramount importance in the fight against the COVID-19 pandemic. Both viral vector- and nucleic acid-based vaccines are known to effectively induce protection against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus by generating high antibody titers and effective T-cell responses to the spike protein they encode. Although these vaccines are being applied worldwide and have been extensively investigated, the immunomorphological events at the vaccination site with respect to SARS-CoV-2 spike protein expression have not yet been described. METHODS: We had the opportunity to examine the deltoid muscles of three men who died shortly after vaccination for unrelated reasons. We examined the vaccination sites histologically and immunohistochemically with various antibodies. Furthermore we incubated two different cell lines with one vaccine and examined the expression of the spike protein. RESULTS: The vaccination sites show a dense lymphohistiocytic interstitial infiltrate which surrounds the small vessels and extends into the perimysium. The spike protein is expressed by histiocytic cells with a dendritic shape that are CD68-positive and CD207-negative, fibrocytes, and very rare S100-positive cells. Interestingly, the skeletal muscle, being constitutively human leukocyte antigen (HLA)-A,B,C-negative, is induced at different levels in each specimen. In a cell culture experiment, we confirmed the ability of fibroblasts and interdigitating dendritic sarcoma cells to express spike protein in vitro after incubation with the Comirnaty vaccine. CONCLUSIONS: Histiocytic cells and fibrocytes are the heralds of spike protein synthesis at the vaccination site. The underlying cause of this apparent cell specifity is unknown. This needs to be investigated in future experiments, for example in an animal model.

Development of a multiplex assay for detection of autosomal and Y-chromosomal STRs, assessment of the degradation state of mitochondrial DNA and presence of mitochondrial length heteroplasmies.

The current focus in most routine forensic casework is detection of autosomal or gonosomal Short Tandem Repeats (STRs). With increasing degradation, STR analysis tends to be less successful up to complete failure. For challenging samples such as telogen hair roots and shafts, touch DNA samples or skeletal remains, mitochondrial DNA (mtDNA) analysis provides a powerful tool. Determination of DNA quantity is an important part in the casework workflow. Several ready-to-use kits are commercially available for nuclear DNA targets. However, quantification of mtDNA targets requires the establishment of an in-house method. Some assays even contain assessment of degradation, which alleviates the choice of target enrichment for sequencing through medium or small amplicons. As Sanger-type Sequencing (STS) still remains the golden standard in many laboratories, identification of heteroplasmies in C-tract regions prior to the sequencing reaction is advantageous. Firstly, primer selection can be expanded with primers binding near the C-tract and secondly, determination of the dominant variant is straightforward. All those quantity (nuclear and mtDNA) and quality (degradation and length heteroplasmies) evaluations usually require at least two separate reactions. Therefore, the aim of this project was the combination of all these targets in one multiplex assay using capillary electrophoresis to spare valuable sample extract. Amplification of representative autosomal and Y-chromosomal STRs allows estimate of success of (Y-)STR analysis. Simultaneously, five length heteroplasmies in the mitochondrial control region are targeted as well as three conservative regions of differing fragment lengths for assessment of the mitochondrial degradation state. Based on the outcome of this assay, forensic examiners can decide if STR analysis may be suitable. In case of absent STR peaks, appropriate proceeding of mtDNA sequencing can be determined.

Mapping SNOMED CT Codes to Semi-Structured Texts via an NLP Pipeline.

In the project presented here, we used NLP tools for annotating German medical trainings documents with SNOMED CT codes. Following research question was addressed: Is it possible to automate the annotation of training documents with an NLP pipeline especially designed for this task but requiring translation into English? The goal of our stakeholder, an institution responsible for the continuing education of physicians, was to facilitate the switch between different medical trainings programs by coding the same requirement with the same SNOMED CT code, even if the wording is different. We first describe how we chose the concrete NLP tools, after which the concrete steps for implementing our prototype are outlined: the NLP pipeline construction, the implementation, and the validation. We infer three important lessons from our results: (i) self-supervision is no free lunch and should be based on a sophisticated task, (ii) the translation via DeepL can be too context-dependent for a peculiar use case, and (iii) ontology extraction can increase efficiency as well as accuracy.

Tyrosine 146 of the Human Na+/Taurocholate Cotransporting Polypeptide (NTCP) Is Essential for Its Hepatitis B Virus (HBV) Receptor Function and HBV Entry into Hepatocytes.

Na+/taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1) is a hepatic bile acid uptake carrier participating in the enterohepatic circulation of bile acids. Apart from its transporter function, NTCP acts as the high-affinity liver-specific receptor for the hepatitis B virus (HBV), which attaches via its preS1-peptide domain of the large surface protein to NTCP, subsequently leading to endocytosis of the virus/NTCP-receptor complex. Although the process of NTCP-dependent HBV infection of hepatocytes has received much attention over the last decade, the precise molecular sites of the virus/NTCP interaction have not been fully identified. Inspection of the primary protein sequence of human NTCP revealed 139YIYSRGIY146 as a highly conserved tyrosine-rich motif. To study the role of Y139, Y141 and Y146 amino acids in NTCP biology, the aforementioned residues were substituted with alanine, phenylalanine or glutamate (mimicking phosphorylation) using site-directed mutagenesis. Similar to wt NTCP, the Y139A, Y141A, Y146A, Y141F, Y146F, and Y146E mutants were expressed at the plasma membrane of HEK293 cells and exhibited intact bile acid transport function. Y146A, Y146E, and Y146F demonstrated transport kinetics comparable to wild-type NTCP with Km values of 57.3-112.4 µM and Vmax values of 6683-7579 pmol/mg protein/min. Only Y141E was transport deficient, most likely due to an intracellular accumulation of the mutant protein. Most importantly, Y146A and Y146E mutation completely abrogated binding of the viral preS1-peptide to NTCP, while the Y146F mutant of NTCP showed some residual binding competence for preS1. Consequently, the NTCP mutants Y146A and Y146E, when expressed in HepG2 hepatoma cells, showed complete loss of susceptibility for in vitro HBV infection. In conclusion, tyrosine 146, and to some extent tyrosine 141, both belonging to the tyrosine-rich motif 139YIYSRGIY146 of human NTCP, are newly identified amino acid residues that play an essential role in the interaction of HBV with its receptor NTCP and, thus, in the process of virus entry into hepatocytes.

Best of both: A simultaneous analysis of mRNA and miRNA markers for body fluid identification.

The body fluid identification of traces found at crime scenes is crucial in relation of the circumstance of crime. For this reason, the body fluid identification (BFI) by molecular biological methods has been increasingly investigated in recent decades. Especially the use of messenger RNA (mRNA) has been established and validated by various studies. mRNAs can resist degradation for several decades under dry and dark environmental conditions, but degradation increases greatly e.g., in humid environments and UV radiation. In contrast, the shorter and protein-protected micro RNAs (miRNAs) are less susceptible to degradation, but not all potential markers are tissue-specific. The aim of this study was to develop a simultaneous mRNA/miRNA multiplex assay to take advantage of both types of RNA. The final assay was tested for various body fluids, dilutions, and mixtures. To demonstrate the advantage of a combined mRNA/miRNA assay, older and mostly degraded samples were examined and compared to an established mRNA assay. Initial results from degraded samples show that tissue-specific miRNAs expected could be detected for 93% of the degraded samples compared to mRNA markers with 25% of the mRNA assay. The result is a simultaneous mRNA/miRNA multiplex assay on capillary electrophoresis (CE) for the first time.

[Suicidal gas embolism in hospital]. / Suizidale Gasembolie im Krankenhaus.

Air embolisms are a common entity seen in clinical practice after traumatic or iatrogenic events. Cases of a suicidally induced air embolism are rare. The connectivity of air-carrying and fluid-carrying tubing systems allow large gas volumes to be infused in a short period of time, usually with fatal outcome. In such cases, the use of computed tomography prior to autopsy is mandatory and provides a comprehensive visualization of introduced gas volumes. We present an unusual case of a suicidal gas embolism, in which a man in hospital connected a tube supplying oxygen to a venous catheter.

Casework-related DNA transfer on footwear in consideration of the shedder status.

DNA evidence on shoes can play an important role in solving a variety of crimes. We investigated the transfer, persistence, prevalence and recovery of DNA (DNAtppr) on shoes (sneakers) and their soles in realistic handling scenarios taking into account the shedder status. This study aims to increase the understanding of the expected composition of DNA profiles and their probative value, providing a basis for activity level assessments. Samples were analyzed using a direct lysis method, suggesting its versatility and increasing the DNA typing success compared to previous studies on footwear. The data showed surface-dependent background DNA (bDNA) levels on shoe soles and prevalence of bDNA on the upper parts of the shoe. The owner of the shoe was allocatable to the mixture for almost every shoe and sampling location. Alternating scenarios of shoe handling were simulated through different pairs of shedders to distinguish shoe owner and subsequent user. Secondary users were attributable to DNA mixtures regardless of shedder status after wearing shoes a single time. The influence of the shedder status follows specific trends in this context. However, particularly intermediate shedders show inconsistent results. The prevalence of bDNA appears to have a greater effect on the impact of the shedder status on DNA profile composition than previously reported. The data help researchers to better resolve suspect statements and determine if a person of interest wore the shoes relevant to the investigation.

Persistence of blood (DNA/RNA) on shoe soles under varying casework related conditions.

Blunt force traumas by footwear can result in severe and even fatal head and upper body injuries. Oftentimes, footwear impressions are only partially available and evidential value is limited. DNA evidence on shoe soles could provide crucial evidence helping to solve crimes by linking target DNA to the activity of interest. Little is known about the persistence and detectability of biological material post such offenses and the interplay of factors affecting the analytical success. In this study, we assessed the persistence of blood on shoe soles under varying parameters such as blood location, different sneakers, weather condition, gait, amount of blood, underground and step count. We applied an optimized DNA/RNA workflow adapted to micro-traces without constraints for the primary DNA pipeline. There is a high probability to link donor DNA to the shoe sole for up to 300-400 steps, regardless of the underground, blood location, and amount of blood. Depending on the sole material and the degree of abrasion of the sole, a longer blood persistence can be observed. Considering blood, 98.2% of the initial DNA amount (1 µl initial blood volume) was lost after 100 steps walked on sole areas that are in constant contact with the ground. Proportion of foreign DNA was marginal (avg. 4.4 alleles), minimizing the probability of unintentional DNA transfer in this context. RNA typing showed high specificity but lower sensitivity than presumptive tests used for body fluid identification (BFI). Luminol is essential for targeted sampling on shoe soles, as latent blood traces (>100-200 steps) provided sufficient biological material for DNA/RNA typing. The generated data help to address the activity of interest and evaluate probabilities about prevalence of target DNA important for casework implications and assessments on activity level.

Anion Dependent Particle Size Control of Platinum Nanoparticles Synthesized in Ethylene Glycol.

The polyol synthesis is a well-established method to form so-called "surfactant-free" nanoparticles (NPs). In the present study, the NP size resulting from the thermal reduction of the precursors H2PtCl6, H2Pt(OH)6, or Pt(acac)2 in presence of the bases NaOH or Na(acac) at different concentrations is studied. It is shown that the size control depends more strongly on the nature of the precursor (metal salt) than on the anion present in the base. The latter is surprising as the concentration of the base anion is often an important factor to achieve a size control. The reduction of H2PtCl6 or H2Pt(OH)6 in presence of NaOH and Na(acac) confirm the observation that the NP size is determined by the OH-/Pt molar ratio and expands it to the base anion/Pt molar ratio. In contrast, the reduction of Pt(acac)2 in presence of the bases NaOH (previous reports) or Na(acac) (shown in the present work) leads to larger NPs of ca. 3 nm, independent of the concentration of the base anions. Hence, the anion effect observed here seems to originate predominantly from the nature of the precursor (precursor anion dependence) and only for certain precursors as H2PtCl6 or H2Pt(OH)6 the size control depends on the base anion/Pt molar ratio.

Synthesis and Characterization of Ligand-Linked Pt Nanoparticles: Tunable, Three-Dimensional, Porous Networks for Catalytic Hydrogen Sensing.

Porous networks of Pt nanoparticles interlinked by bifunctional organic ligands have shown high potential as catalysts in micro-machined hydrogen gas sensors. By varying the ligand among p-phenylenediamine, benzidine, 4,4''-diamino-p-terphenyl, 1,5-diaminonaphthalene, and trans-1,4-diaminocyclohexane, new variants of such networks were synthesized. Inter-particle distances within the networks, determined via transmission electron microscopy tomography, varied from 0.8 to 1.4 nm in accordance with the nominal length of the respective ligand. While stable structures with intact and coordinatively bonded diamines were formed with all ligands, aromatic diamines showed superior thermal stability. The networks exhibited mesoporous structures depending on ligand and synthesis strategy and performed well as catalysts in hydrogen gas microsensors. They demonstrate the possibility of deliberately tuning micro- and mesoporosity and thereby transport properties and steric demands by choice of the right ligand also for other applications in heterogeneous catalysis.

Development and validation of an mRNA-based multiplex body fluid identification workflow and a rectal mucosa marker pilot study.

Molecular identification of body fluids and tissues is crucial in order to understand the circumstances of crimes. For that reason, molecular investigations used to identify body fluids/tissues have increasingly been examined recently. Various studies have proved that messenger RNA (mRNA) profiling is a sensitive and robust method for body fluid/tissue identification. The forensically relevant body fluids/tissues blood, semen, saliva, vaginal secretion, menstrual blood and skin have all been detected successfully by applying suitable mRNA assay. However, rectal mucosa, which can be found as evidence in sexual assault cases, has been neglected in forensic investigations. So far there is no mRNA marker to detect rectal mucosa, although anal penetration occurs in a large number of sexual assaults (23.2% of female victims and 50% of male victims). In this study, specific and sensitive mRNA markers for forensically relevant body fluids were adapted and validated in an mRNA multiplex assay for routine casework. This included the implementation of a DNA/RNA re-extraction method for automated extraction that can be integrated into casework without loss of DNA. This re-extraction method and the mRNA multiplex assay were tested using casework samples. PCR-primers were designed for the identification of rectal mucosa and the more effective marker MUC12 was integrated into an extended multiplex assay. The result of our study is a highly specific and sensitive mRNA multiplex assay plus an automated DNA/RNA re-extraction method, that can be integrated into casework and identify rectal mucosa for the first time.

Crowdsourcing for Creating a Dataset for Training a Medication Chatbot.

To facilitate interaction with mobile health applications, chatbots are increasingly used. They realize the interaction as a dialog where users can ask questions and get answers from the chatbot. A big challenge is to create a comprehensive knowledge base comprising patterns and rules for representing possible user queries the chatbot has to understand and interpret. In this work, we assess how crowdsourcing can be used for generating examples of possible user queries for a medication chatbot. Within one week, the crowdworker generated 2'738 user questions. The examples provide a large variety of possible formulations and information needs. As a next step, these examples for user queries will be used to train our medication chatbot.

The diversity of shedder tests and a novel factor that affects DNA transfer.

Since the first shedder test was formulated almost 20 years ago, a plethora of different test strategies has emerged. The amount of data generated so far is considerable. However, because of the limited reproducibility of its results, the reliability of the shedder concept is frequently questioned. This study provides a literature overview of applied shedder tests that capture the diversity of the concept. It is pointed out to what extent different classification criteria, workflows, and trace evaluation can impair the classification outcome. The robustness of shedder status was assessed by applying a promising approach established by Fonneløp et al. (Forensic Sci Int Genet 29:48-60, 21). Data provide similar results to those in recent studies but also ambiguous shedder classifications. The applied shedder test was adapted based on our own as well as the reviewed data. With novel classification parameters, promising results were achieved. This study reveals uncertainties and inconsistencies of the shedder concept. Recommendations for harmonization and transparency are proposed. Implementation of the recommendations may result in an increased impact on casework and transfer studies, including activity-level assessments. Furthermore, this study shows that moisturizers affect participants' shedder status as well as DNA transfer. The impact appears to remain relevant even 60 min post ointment application but depends greatly on the type of moisturizer applied.

Electrical weapons and rhabdomyolysis.

It has been suggested that an application of a conducted electrical weapon (CEW) might cause muscle injury such as rhabdomyolysis and an acute inflammatory response. We explored this hypothesis by testing the effects of electrical weapons on circulating markers of inflammation and muscle damage. In a prospective study, 29 volunteers received a full-trunk 5-s TASER® X26(E) CEW exposure. Venous blood samples were taken before, 5 min after, and at 24 h following the discharge. We tested for changes in serum levels of C-reactive protein (CRP), alkaline phosphatase (ALP), myoglobin, albumin, globulin, albumin/globulin ratio, aspartate and alanine aminotransferase, creatine kinase, total protein, bilirubin, and lactic acid dehydrogenase. Uncorrected CRP and myoglobin levels were lower in the immediate post exposure period (CRP levels 1.44 ± 1.39 v 1.43 ± 1.32 mg/L; p = 0.046 and myoglobin 36.8 ± 11.9 v 36.1 ± 13.9 µg/L; p = 0.0019) but these changes were not significant after correction for multiple comparisons. There were no changes in other biomarkers. At 24 h, CRP levels had decreased by 30% to 1.01 ± 0.80 mg/L (p = 0.001 from baseline). ALP was unchanged immediately after the CEW application but was reduced by 5% from baseline (66.2 ± 16.1 to 62.7 ± 16.1 IU/L; p = 0.0003) at 24 h. No other biomarkers were different from baseline at 24 h. A full-trunk electrical weapon exposure did not lead to clinically significant changes in the acute phase protein levels or changes in measures of muscle cellular injury. We found no biomarker evidence of rhabdomyolysis.

A comparative study of conducted electrical weapon incapacitation during a goal-directed task.

Conducted electrical weapons (CEW) are ubiquitous in law enforcement given their unique ability to physically incapacitate violently resisting subjects. Early use of animal models to study CEW incapacitation effectiveness (e.g. porcine model with 4-limb strain gauges) proved to be poorly predictive of human incapacitation effectiveness. In a previously published human study, we developed a methodology for the prospective assessment of the incapacitation effectiveness of CEWs in highly motivated human subjects. Here we use this methodology in Part 1 to compare the incapacitation effectiveness of the newly released Axon® (formerly TASER® International) T(ASER) 7 to the TASER X26E, the "gold standard", and the TASER X2, a current model. The T7 has a new "adaptive cross-connect" technology that may improve incapacitation effectiveness in the scenario of small spreads between probe pairs, a common cause of weapon "failure" in the field. In Part 2, we use our methodology to test the functionality of the T7 cross-connect technology by comparing different bay and probe configurations. This is the first published study in the literature comparing different CEW models using this human model. For Part 1, 29 subjects completed the study and had data available for analysis. For Part 2, 21 subjects completed the study and had data available for analysis. The subjects were motivated to complete the task of reaching a suspended martial arts dummy 3.4 m (11 ft) away while being exposed "under power" to the CEW. In Part 1, subjects were assigned to 1 of 6 groups with probe spreads of 10, 20, and 30 cm (4, 8, 12 in). Subjects were exposed to a "control" CEW (either the X2 or X26E) and the T7 on alternating sides. Exposures with the X2 and T7 included 2 bay-exposures. In Part 2, 21 subjects were assigned to 1 of 5 groups of different T7 bay and probe configurations all with a theoretical effective spread of 30 cm (12 in). Subjects were rated on their progress towards successfully reaching the dummy and on the extent of limb incapacitation using a quasi-blinded expert-observer scoring panel based on high-speed video review. In Part 1, all CEW models achieved maximal or near-maximal subject control with the 30 cm probe spread. With probe spreads of 10 and 20 cm the pooled data showed the T7 to be superior to the X2 for goal achievement (p < 0.001) and limb incapacitation (p = 0.002) mostly driven by differences seen with the 10 cm spread (2-bay exposures). The T7 was non-inferior to the X26E. In Part 2, there was no statistical significance between the limb capture scores, but there was a statistically significant difference in goal scores. The results overall validate that the T7 CEW cross-connect feature performed as expected. The T7 adaptive cross-connect feature with two simultaneous deployed probe pairs demonstrated a significant improvement in incapacitation effectiveness compared to the current X2 CEW with two simultaneously deployed probe pairs. Small probe spreads are a common reason for limited incapacitation effectiveness in the field and this study suggests the T7 may offer an improvement in this scenario. The T7, with single-bay exposures, was non-inferior to the single-bay X26E.

Electrical weapons, hematocytes, and ischemic cardiovascular accidents.

BACKGROUND: There have been case reports following the use of a conducted electrical weapon (CEW) suggesting that these devices might affect coagulation or thrombosis in at-risk individuals. The aim of this manuscript therefore is firstly to explore this hypothesis by reviewing each of these cases and secondly to report the results of a prospective study exploring a priori the effects of electrical weapons on hematocytes in a group of human volunteers. METHODS: First, we systematically reviewed all cases of adverse outcomes following CEW discharge that could be due to an effect on coagulation or thrombosis, with particular focus on the clinical scenario and its relationship with the weapon discharge. Second, we assessed hematocyte levels in venous blood from 29 volunteers before, 5 min after, and 24 h after receiving a full-trunk 5-s TASER® X26(E) CEW exposure. RESULTS: Following extensive review of the literature, we found 3 relevant case reports of possible vascular thromboembolic clinical events after CEW exposure, specifically a case of ischemic stroke, and 2 cases of ST-segment elevation myocardial infarctions. Review of these published cases failed to establish a plausible linkage to the CEW beyond a temporal association with significant emotional and physiological stress from a violent struggle. Our prospective study of biomarker change following CEW discharge revealed acutely increased values for WBC (white blood cells), specifically lymphocytes and monocytes, and a raised platelet count. Neutrophil levels decreased as a percentage of WBC. While these changes were statistically significant at 5 min, all results remained within established reference ranges. At 24 h, all values had returned to baseline except total WBC which decreased to slightly below baseline but was still within the normal reference range. CONCLUSIONS: A review of clinical cases, of ischemic or thrombotic events revealed no direct association with the CEW discharge. A full-trunk electrical weapon exposure did not lead to hematocyte changes beyond normal clinically expected variations in similar acute response scenarios. The case report and biomarker data do not support the hypothesis that a CEW discharge is associated with changes likely to promote coagulation or thrombus formation.