The identification of gunshot residue (GSR) on wounds enables the differentiation of entry and exit wounds. Unfortunately, studies analyzing GSR on degraded bodies have been poorly documented, and no ...data exist regarding GSR detection after stagnant water immersion. The aim of this preliminary experimental study was to detect GSR on wounds altered in stagnant water, using scanning electron microscopy coupled with energy‐dispersive X (SEM‐EDX) and inductively coupled plasma mass spectrometry (ICP‐MS). Shots were performed on sheep limbs with a 22LR at a distance of 20 cm. The limbs were then submerged in stagnant water and analyzed on days 0, 6, and 14. SEM‐EDX was performed on previously dehydrated wounds. For ICP‐MS analysis, the wounds were rubbed with a cotton swab that was then analyzed. In the SEM studies, a higher number of particles were detected in entry wounds compared to exit wounds under every set of experimental conditions. Unfortunately, SEM‐EDX failed to detect GSR particles, even on day 0. ICP‐MS enabled the detection of Pb, Sb, and Ba at every stage with higher quantities on entry than in exit. These elements remained detectable following limb immersion. ICP‐MS enabled differentiate entry from exit wounds, even after immersion in stagnant water. Nevertheless, when manually swabbing the wounds, quantities of matter collected is highly variable. ICP‐MS is a more suitable technique than SEM‐EDX for GSR identification of wounds after decomposition in stagnant water; however, standardization is needed.
Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries. Few data regarding genotype 3 HEV extrahepatic manifestations exist.
We assessed kidney function and histology in ...solid-organ transplant patients during HEV infection. In all, 51 cases of genotype 3 HEV infections were diagnosed (34 kidney, 14 liver, and 3 kidney-pancreas transplant patients). Of these, 43.2% were cleared of the virus spontaneously within 6 months of infection, whereas 56.8% evolved to chronic hepatitis. Twelve of these patients completed a 3-month antiviral therapy and were followed up for 6 months posttreatment. Kidney function (estimated glomerular filtration rate eGFR obtained by the Modification of Diet in Renal Disease equation) and proteinuria were assessed before infection, during HEV infection and during follow-up. Kidney biopsies were obtained from patients with high proteinuria and decreased eGFR levels.
During HEV infection, there was a significant decrease in eGFR in both kidney- and liver-transplant patients. Glomerular diseases were observed in kidney biopsies obtained during the acute and chronic phases. This included membranoproliferative glomerulonephritis and relapses in IgA nephropathy. The majority of patients had cryoglobulinemia that became negative after HEV clearance. Kidney function improved and proteinuria decreased after HEV clearance.
HEV-associated glomerulonephritis seems to be an HEV-related extrahepatic manifestation. Further studies are required to confirm these observations.
In heart failure (HF), mitochondrial quality control and autophagy are progressively impaired, but the role of oxidative stress in this process and its underlying mechanism remain to be defined. By ...degrading norepinephrine and serotonin, the mitochondrial enzyme, monoamine oxidase-A (MAO-A), is a potent source of reactive oxygen species (ROS) in the heart and its activation leads to the persistence of mitochondrial damage. In this study, we analyzed the consequences of ROS generation by MAO-A on the autophagy-lysosome pathway in the heart.
Cardiomyocyte-driven expression of MAO-A in mice led to mitochondrial fission and translocation of Drp1 and Parkin in the mitochondrial compartment. Ventricles from MAO-A transgenic mice displayed accumulation of LC3-positive autophagosomes, together with p62 and ubiquitylated proteins, indicating impairment of autophagy. In vitro adenoviral delivery of MAO-A in cardiomyocytes and the consequent generation of ROS blocked autophagic flux with accumulation of LC3II, p62, and ubiquitylated proteins, leading to mitochondrial fission and cell necrosis. In addition, MAO-A activation induced accumulation of lysosomal proteins, cathepsin D and Lamp1, reduced lysosomal acidification, and blocked the nuclear translocation of transcription factor-EB (TFEB), a master regulator of autophagy and lysosome biogenesis. Most interestingly, overexpression of TFEB attenuated autophagosome buildup, mitochondrial fission, cardiomyocyte death, and HF associated with MAO-A activation.
This study unravels a new link between MAO-dependent H2O2 production and lysosomal dysfunction. Altogether, our findings demonstrate that the MAO-A/H2O2 axis has a negative impact on the elimination and recycling of mitochondria through the autophagy-lysosome pathway, which participates in cardiomyocyte death and HF. Antioxid. Redox Signal. 25, 10-27.
Sudden Death Due to Coronary Arteritis Gabarrou, Gabrielle; Guilbeau‐Frugier, Céline; Blanc, Anthony ...
Journal of forensic sciences,
March 2018, Letnik:
63, Številka:
2
Journal Article
Recenzirano
We report the case of a middle‐aged man, without medical history, who suddenly died at his workplace. The autopsy highlighted a pathological heart macroscopically, with multiple small white areas on ...the left myocardium. Coronary dissection revealed a pseudotumoural fibromyxoid aspect within the anterior interventricular artery (AIVA) and the left main coronary trunk, including reduction in their diameter with tight stenosis. Microscopic examination of these arteries showed fibroinflammatory wall destruction. In the left myocardium, there were multiple focal ischemic areas at different stages of recovery. Our case is an illustration of primary ischemic heart disease due to coronary arteritis, with a pseudotumoural presentation, which was revealed by sudden death. We discuss the cause of death and the etiological diagnosis preceding coronary arteritis.
Hyperostosis frontalis interna is a common phenomenon, which may have been overrated in its significance in the past, and may, currently be underrated in its significance. We present three cases of ...hyperostosis frontalis interna found during medicolegal autopsies and discuss their forensic considerations. The patients were all middle‐aged women with metabolic and endocrine manifestations and psychiatric ailments; thickening of the inner table of the frontal bone of the skull was found during each autopsy. We describe the relationship between hyperostosis frontalis interna, metabolic manifestations, and neuropsychiatric symptoms as part of Morgagni‐Stewart‐Morel syndrome. There is still considerable disagreement in the scientific community as to whether this syndrome is a clinical entity. Nonetheless, awareness of Morgagni‐Stewart‐Morel syndrome can be of help in understanding the circumstances surrounding death. In some other cases, hyperostosis frontalis interna could be used by forensic pathologists as criteria for sexing and aging a skeleton.
Abstract
Aims
Correlations between malignant ventricular arrhythmias and the COVID waves have never been investigated.
Methods and results
Prevalence of malignant ventricular arrhythmias/sudden ...cardiac death has been correlated to the four COVID waves between the onset of pandemic and end 2021. No significant correlation was present in the temporal evolution of both COVID patients/positive tests and incidence of malignant ventricular arrhythmias, which tended to decrease after vaccination onset.
Conclusion
We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.
Adipose tissue secretes a variety of bioactive factors, which can regulate cardiomyocyte hypertrophy via reactive oxygen species (ROS). In the present study we investigated whether apelin affects ...ROS-dependent cardiac hypertrophy. In cardiomyocytes apelin inhibited the hypertrophic response to 5-HT and oxidative stress induced by 5-HT- or H2O2 in a dose-dependent manner. These effects were concomitant to the increase in mRNA expression and activity of catalase. Chronic treatment of mice with apelin attenuated pressure-overload-induced left ventricular hypertrophy. The prevention of hypertrophy by apelin was associated with increased myocardial catalase activity and decreased plasma lipid hydroperoxide, as an index of oxidative stress. These results show that apelin behaves as a catalase activator and prevents cardiac ROS-dependent hypertrophy.
Summary
The incidence and consequences of de novo donor‐specific anti‐HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and ...complications associated with de novo DSAs in this setting. A total of 152 de novo liver‐transplant patients, without preformed anti‐HLA DSAs, were tested for anti‐HLA antibodies, with single‐antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver‐enzyme levels until the last follow‐up, that is, 34 (1.5–77) months. Twenty‐one patients (14%) developed de novo DSAs. Of these, five patients had C1q‐binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody‐mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B‐cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient‐ and graft‐survival rates did not differ between patients with and without DSAs. In conclusion, liver‐transplant patients with liver abnormalities should be screened for DSAs and AMR.
Rhabdomyolysis can be life threatening if complicated by AKI. Macrophage infiltration has been observed in rat kidneys after glycerol-induced rhabdomyolysis, but the role of macrophages in ...rhabdomyolysis-induced AKI remains unknown. Here, in a patient diagnosed with rhabdomyolysis, we detected substantial macrophage infiltration in the kidney. In a mouse model of rhabdomyolysis-induced AKI, diverse renal macrophage phenotypes were observed depending on the stage of the disease. Two days after rhabdomyolysis, F4/80(low)CD11b(high)Ly6b(high)CD206(low) kidney macrophages were dominant, whereas by day 8, F4/80(high)CD11b(+)Ly6b(low)CD206(high) cells became the most abundant. Single-cell gene expression analyses of FACS-sorted macrophages revealed that these subpopulations were heterogeneous and that individual cells simultaneously expressed both M1 and M2 markers. Liposomal clodronate-mediated macrophage depletion significantly reduced the early infiltration of F4/80(low)CD11b(high)Ly6b(high)CD206(low) macrophages. Furthermore, transcriptionally regulated targets potentially involved in disease progression, including fibronectin, collagen III, and chemoattractants that were identified via single-cell analysis, were verified as macrophage-dependent in situ. In vitro, myoglobin treatment induced proximal tubular cells to secrete chemoattractants and macrophages to express proinflammatory markers. At day 30, liposomal clodronate-mediated macrophage depletion reduced fibrosis and improved both kidney repair and mouse survival. Seven months after rhabdomyolysis, histologic lesions were still present but were substantially reduced with prior depletion of macrophages. These results suggest an important role for macrophages in rhabdomyolysis-induced AKI progression and advocate the utility of long-term follow-up for patients with this disease.
Objectives To assess the long term outcomes of transplantation using expanded criteria donors (ECD; donors aged ≥60 years or aged 50-59 years with vascular comorbidities) and assess the main ...determinants of its prognosis. Design Prospective, population based cohort study.Setting Four French referral centres.Participants Consecutive patients who underwent kidney transplantation between January 2004 and January 2011, and were followed up to May 2014. A validation cohort included patients from another four referral centres in France who underwent kidney transplantation between January 2002 and December 2011. Main outcome measures Long term kidney allograft survival, based on systematic assessment of donor, recipient, and transplant clinical characteristics; preimplantation biopsy; and circulating levels of donor specific anti-HLA (human leucocyte antigen) antibody (DSA) at baseline.Results The study included 6891 patients (2763 in the principal cohort, 4128 in the validation cohort). Of 2763 transplantations performed, 916 (33.2%) used ECD kidneys. Overall, patients receiving ECD transplants had lower allograft survival after seven years than patients receiving transplants from standard criteria donors (SCD; 80% v 88%, P<0.001). Patients receiving ECD transplants who presented with circulating DSA at the time of transplantation had worse allograft survival after seven years than patients receiving ECD kidneys without circulating DSA at transplantation (44% v 85%, P<0.001). After adjusting for donor, recipient, and transplant characteristics, as well as preimplantation biopsy findings and baseline immunological parameters, the main independent determinants of long term allograft loss were identified as allocation of ECDs (hazard ratio 1.84 (95% confidence interval 1.5 to 2.3); P<0.001), presence of circulating DSA on the day of transplantation (3.00 (2.3 to 3.9); P<0.001), and longer cold ischaemia time (>12 h; 1.53 (1.1 to 2.1); P=0.011). Recipients of ECD kidneys with circulating DSA showed a 5.6-fold increased risk of graft loss compared with all other transplant therapies (P<0.001). ECD allograft survival at seven years significantly improved with screening and transplantation in the absence of circulating DSA (P<0.001) and with shorter (<12 h) cold ischaemia time (P=0.030), respectively. This strategy achieved ECD graft survival comparable to that of patients receiving an SCD transplant overall, translating to a 544.6 allograft life years saved during the nine years of study inclusion time.Conclusions Circulating DSA and cold ischaemia time are the main independent determinants of outcome from ECD transplantation. Allocation policies to avoid DSA and reduction of cold ischaemia time to increase efficacy could promote wider implement of ECD transplantation in the context of organ shortage and improve its prognosis.
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