Necrotizing Scleritis, Conjunctivitis, and Other Pathologic Findings in the Left Eye and Brain of an Ebola Virus-Infected Rhesus Macaque (Macaca mulatta) With Apparent Recovery and a Delayed Time of Death.

A 3.5-year-old adult female rhesus macaque (Macaca mulatta) manifested swelling of the left upper eyelid and conjunctiva and a decline in clinical condition 18 days following intramuscular challenge with Ebola virus (EBOV; Kikwit-1995), after apparent clinical recovery. Histologic lesions with strong EBOV antigen staining were noted in the left eye (scleritis, conjunctivitis, and peri-optic neuritis), brain (choriomeningoencephalitis), stomach, proximal duodenum, and pancreas. Spleen, liver, and adrenal glands, common targets for acute infection, appeared histologically normal with no evidence of EBOV immunoreactivity. These findings may provide important insight for understanding sequelae seen in West African survivors of Ebola virus disease.

A case of a motor vehicle collision suspected as associated with development of angiosarcoma.

Trauma has been suspected as a factor leading to development of angiosarcoma, a malignant soft-tissue tumor. We conducted a forensic autopsy to investigate a putative relation between a motor vehicle collision and the driver's later death from angiosarcoma. A vehicle operated by a man in his 60 s collided with an oncoming vehicle at a curve. The victim noticed no injury at the scene. However, 45 days later, he was transferred to an emergency room with dyspnea and bloody sputum. After diagnosis of angiosarcoma, he died of respiratory failure 132 days later. The bereaved family speculated about a relation between the collision and angiosarcoma onset. At autopsy, tumor cells of the scalp had metastasized to the lung, pleura, liver, and spleen. Histopathological examinations revealed characteristic features of angiosarcoma with positive immune-staining for CD31, CD34, and factor VIII. When a person dies some time after a collision, it is designated as a delayed death. In such cases, the relevance of trauma to the person's death is often an issue of concern. Because the interval between trauma and angiosarcoma development was short, only 45 days, the angiosarcoma might be coincidental. Therefore, we rejected the relation. Forensic experts sometimes need to investigate such inquiries.

Delayed death of a child from chlorfenapyr poisoning: A case report and literature review.

This was the first article reported a fatal case of chlorfenapyr poisoning in a child, and the typical symptoms before death include high fever, severe sweating, coma, and limb stiffness, and elevation of myocardial enzymes and myoglobin; neurological symptoms tend to appear earlier in children than in adults.

Post-obstructive Pulmonary Oedema in Delayed Death by Hanging: A Case Report.

Hanging is a common method to attempt suicide, which is highly lethal and results in immediate death. Near-hanging refers to those who survive a hanging injury and are able to reach a hospital. Only a few survive such episodes if they are promptly rescued, but they usually die later, which is called delayed death by hanging. Post-obstructive pulmonary oedema is a fatal complication that occurs after the removal of severe upper respiratory tract obstruction. Post-obstructive pulmonary oedema developing in delayed hanging death is not widely reported in the literature. Herein, we describe a case of post-obstructive pulmonary oedema in a 16-year-old girl with a history of attempted suicide by hanging.

Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum.

Boromycin is a boron-containing macrolide antibiotic produced by Streptomyces antibioticus with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug. Despite the success of artemisinin combination therapies, the current gold standard treatment, new alternatives are constantly needed due to the ability of malaria parasites to become resistant to almost all drugs that are in heavy clinical use. In vitro antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against Plasmodium falciparum and the zoonotic Plasmodium knowlesi. In contrast to tetracyclines, boromycin rapidly killed asexual stages of both Plasmodium species already at low concentrations (~ 1 nM) including multidrug resistant P. falciparum strains (Dd2, K1, 7G8). In addition, boromycin was active against P. falciparum stage V gametocytes at a low nanomolar range (IC50: 8.5 ± 3.6 nM). Assessment of the mode of action excluded the apicoplast as the main target. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite.

Delayed Death by Plastid Inhibition in Apicomplexan Parasites.

The discovery of a plastid in apicomplexan parasites was hoped to be a watershed moment in the treatment of parasitic diseases as it revealed drug targets that are implicitly divergent from host molecular processes. Indeed, this organelle, known as the apicoplast, has since been a productive therapeutic target for pharmaceutical interventions against infections by Plasmodium, Toxoplasma, Babesia, and Theileria. However, some inhibitors of the apicoplast are restricted in their treatment utility because of their slow-kill kinetics, and this characteristic is called the delayed death effect. Here we review the recent genetic and pharmacological experiments that interrogate the causes of delayed death and explore the foundation of this phenomenon in Plasmodium and Toxoplasma parasites.

Delayed death due to traumatic dissection of the common carotid artery after attempted suicide by hanging.

Traumatic dissection of the carotid arteries is a rare cause of delayed death due to hanging. We report a case of delayed death two and a half months following attempted suicide by hanging where the patient was able to talk after being released from neck compression. The cause of death was aspiration pneumonia due to cerebral infarction secondary to traumatic dissection of the left common carotid artery due to attempted suicide by hanging. Carotid artery injuries should be examined in patients who were able to talk after an unsuccessful suicide attempt by hanging but who later died.

To Test or Not To Test?: The Value of Toxicology in a Delayed Overdose Death.

A case demonstrating the necessity of thorough death investigation processes where toxicology plays an active role is presented. A 33-year-old white man presented to the emergency room in respiratory distress after an overdose episode where he was revived on the scene by fire rescue. His condition continued to deteriorate and he expired 6 days after the initial incident. No admission specimens were available for testing; however, there were specimens drawn 4 and 5 days after the incident. Drug paraphernalia from the scene was obtained by the laboratory through collaboration with local law enforcement. Drug paraphernalia was initially tested in the laboratory and after obtaining the results, the antemortem and postmortem specimens were tested identifying mitragynine and U-47700, among other drugs. These results indicate the value in obtaining and testing drug paraphernalia, and the value of testing antemortem specimens even in the event of a delay.

Exploiting the apicoplast: apicoplast-targeting drugs and malaria vaccine development.

The apicoplast, a relic plastid found in most Apicomplexan parasites, is a notable drug target. Certain antibiotics elicit a delayed death phenotype by targeting this organelle. Here, we review apicoplast-targeting drugs and their targets, particularly those that cause delayed death, and highlight its potential uses in malaria vaccine development.

Regionally Impaired Redox Homeostasis in the Brain of Rats Subjected to Global Perinatal Asphyxia: Sustained Effect up to 14 Postnatal Days.

The present report evaluates the effect of global perinatal asphyxia on several parameters of oxidative stress and cell viability in rat brain tissue sampled at an extended neonatal period up to 14 days, a period characterised by intensive neuritogenesis, synaptogenesis, synaptic consolidation, pruning and delayed cell death. Perinatal asphyxia was induced by immersing foetus-containing uterine horns removed by a caesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling caesarean-delivered foetuses were manually resucitated and nurtured by surrogate dams for 1 to 14 postnatal (P) days. Brain samples (mesencephalon, telencephalon and hippocampus) were assayed for glutathione (reduced and oxidated levels; spectrophotometry), tissue reducing capacity (potassium ferricyanide reducing assay, FRAP), catalase (the key enzyme protecting against oxidative stress and reactive oxygen species, Western blots and ELISA) and cleaved caspase-3 (the key executioner of apoptosis, Western blots) levels. It was found that global PA produced a regionally specific and sustained increase in GSSG/GSH ratio, a regionally specific decrease in tissue reducing capacity and a regionally and time specific decrease of catalase activity and increase of cleaved caspase-3 levels. The present study provides evidence for regionally impaired redox homeostasis in the brain of rats subjected to global PA, an effect observed up to P14, mainly affecting mesencephalon and hippocampus, suggesting a sustained oxidative stress after the posthypoxia period. The oxidative stress observed postnatally can in part be associated to a respiratory apneic-like deficit, since there was a statistically significant decrease in respiration frequency in AS compared to CS neonates, also up to P14, together with the signs of a decreased peripheral blood perfusion (pink-blue skin colour in AS, compared to the pink colour observed in all CS neonates). It is proposed that PA implies a long-term metabolic insult, triggered by the length of hypoxia, the resuscitation/reoxigenation manoevres, but also by the developmental stage of the affected brain regions, and the integrity of cardiovascular and respiratory physiological functions, which are fundamental for warrantying a proper development.

Delayed In-Custody Death Involving Excited Delirium.

This case study presents a 37-year-old male who was experiencing excited delirium (ExD) and died in a county jail 4 days after being taken into custody. The male died in a jail observation cell without having been restrained and was not under the influence of a drug stimulant. The subject had a documented psychiatric history of bipolar disorder and schizophrenia and was known to consume marijuana, cocaine, and methamphetamines. This case illustrates the pernicious effects of ExD and how its lethality can be delayed when many cases involve drug use and use of force where subjects die shortly thereafter. Implications of ExD for correctional agencies and efforts of responding to it in correctional and law enforcement contexts are discussed.