Agonal Stage Research Articles

Metabolic perturbations and bacterial communities dysbiosis associated with skin ulcer disease progression in Sepia pharaonis

Skin ulcer disease causes massive mortalities during the culture of the cuttlefish Sepia pharaonis. In the present study, metabolomic and 16S rRNA sequence were used to investigate the variation in metabolites and bacterial communities in the skin tissue of S. pharaonis with skin ulcer symptom. S. pharaonis were collected at the undiseased stage (UDS), early diseased stage (EDS), and agonal stage (AS) during a severe and highly contagious skin ulcer disease on the fin. Significantly lysis of the epidermal cells in the skin tissue at both the AS and EDS groups were observed under microscope. Specific metabolic changes responding to disease were identified using metabolomic analysis. Choline continually increased while osmotic chemicals including betaine, homotaurine, and trehalose, decreased; variable levels of phosphocholine and AMP related to energy, and decreased GSH/GSSG ratio related to intense oxidative stress disturbed the balance of osmoregulators, energy and redox equilibrium. 16S rRNA sequence showed a significant decrease in Pseudomonas spp. and Acinetobacter spp., but an increase in Vibrio spp. as the disease progressed. Gammaproteobacteria and Bacillus spp. can be used as biomarkers for the skin ulcer disease, while Pseudomonas spp. and Acinetobacter spp. were the potential probiotics for S. pharaonis culturing. Our present results indicated the characteristic changes in metabolic profile and bacterial community as the disease progressed, which would offer basic information for the further understanding of the disease occurrence in S. pharaonis culturing.

Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

BackgroundThe current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death.Methods and findingsWe examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings.ConclusionsIncluding conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

Non-Contact Vital States Identification of Trapped Living Bodies Using Ultra-Wideband Bio-Radar

Identifying the vital states of trapped survivors during post-disaster rescue missions can result in improved rescue strategies and provide injury pre-diagnosis information. The most effective rescue method is the use of bio-radar based non-contact measurements. Presently, bio-radar techniques focus on detecting and locating. Herein, a method to identify vital states with an ultra-wideband bio-radar is proposed, while simulating a trapped condition with Beagle dogs. This investigation revealed three vital stages under the trapped condition: normal, transitioning, and agonal stages. Upon entering the transitioning stage, the heartrates were apparently high, and the respiratory rates increased sharply. The temperatures dropped rapidly once passing this stage. In particular, the respiratory waveforms from the bio-radar frequently change from a normal sine like curve to an “M” like curve within the transitioning stage. The accurate beginning and ending of the transitioning stage are defined by a newly proposed indicator of relative occurrence frequency. Pathological observations indicated that the fragmentation of lamellar bodies within type II alveolar cells caused the insufficiency of the lung surfactant, and further resulted in the occurrence of the “M” like curves. This pioneering work realizes the vital states identification only using a non-contact ultra-wideband bio-radar, thereby enables to infer the health conditions, life expectancy, and appropriate subsequent treatment of victims in the trapped condition. Therefore, it has the potential to promote the welfare of post-disaster trapped human victims.

Death as a Process: Early Postmortem Changes Observed in the Agonal Stage of Terminal Patients

Agony can be defined as the preciding stage to death, in those situations where life is gradually extinguished. So that, agony is characterized by the cese of the vital functions. From the moment of death and throughout the decomposition process, a series of observable postmortem changes occur in the corpse. Early postmortem changes are rigor mortis, livor mortis, algor mortis and cornea drying.

Variable tau accumulation in murine models with abnormal prion protein deposits

The conversion of cellular prion protein (PrP) into a misfolded isoform is central to the development of prion diseases. However, the heterogeneous phenotypes observed in prion disease may be linked with the presence of other misfolded proteins in the brain. While hyperphosphorylated tau (p.tau) is characteristic of Alzheimer's disease (AD), p.tau is also observed in human prion diseases. To explore this association in the absence of potential effects due to aging, drug treatment, agonal stage and postmortem delay we analyzed p.tau and PrP immunopositivity in mouse models. Analyses were performed on mice inoculated with prion agents, and mice with PrP amyloid in the absence of prion disease. We observed that p.tau was consistently present in animals with prion infectivity (models that transmit disease upon serial passage). In contrast, p.tau was very rarely observed or absent in mice with PrP amyloid plaques in the absence of prion replication. These data indicate that the formation of p.tau is not linked to deposition of misfolded PrP, but suggest that the interaction between replication of infectivity and host factors regulate the formation of p.tau and may contribute to the heterogeneous phenotype of prion diseases.

Qualitative study on cancer patients agonal judge of medical staff

Objective To explore what symptoms which medical staff judged from determination of agonal symptoms in cancer patients. Methods Focus group interview was conducted by 3 groups, 5 people in each group in appropriate time and place at May 2015. The interview was conducted around theme of how to judge advanced cancer patients in . Results Agonal patients often showed changes in 7 aspects by content analyzing included pain, the last radiance of setting sun , consciousness, breathing patterns, blood circulation, intake and output volume and functional status. Besides, instinct and experience of medical staff was another determinant. Conclusions Medical staff members have their qualitative understanding on evaluating when cancer patients are agonal. Changes in some symptoms before death can provide references for evaluating survival time. Key words: Cancer patients; Agonal stage; Hospice care; Qualitative research; Symptoms of dying

HOW TO LIVE WHEN DEATH KNOCKS YOUR DOOR

The main goal of this work is to show the best way of treating people who are under palliative care. It should point out the attention of medical staff, nurses and the whole environment on inner experiences and feelings of person in agonal stage. At the same time it should change perception and the way of thinking about death itself. This work assigns special role to realizing dying person in what condition he is and making him familiar about what is to come from the moment he receives information to the moment of death. In simple language it recognizes medical experiences of palliative care so it is very accessible and easy to understand for professional medical staff and for the loved ones. What is more, it shows phases which experiences terminally ill person in physiological aspect and aspect of experiences which is not always properly understood and even neglected in care activities undertaken by nurses. Delving into the content reader should discover precisely described methods and techniques of treating patient in unknown so far look - the psychological state - in order to understand the needs of the dying and establish empathy that will make death a concept less unpleasant and incomprehensible for both patient and his family.

Ebola in children: epidemiology, clinical features, diagnosis and outcomes.

Ebola virus disease is caused by a highly contagious and pathogenic threadlike RNA virus of the Filoviridae family. The index human case is usually a zoonosis that launches human-to-human transmission interface with varying levels of sustainability of the epidemic depending on the level of public health preparedness of the affected country and the Ebola virus strain. The disease affects all age groups in the population. Clinical diagnosis is challenging in index cases especially in the early stages of the disease when the presenting features are usually nonspecific and only similar to a flu-like illness. However, in the agonal stages, hemorrhage frequently occurs in a high proportion of cases. The diagnostic gold standard is by detecting the antigen using reverse transcription-polymerase chain reaction. Mortality rates in the past 28 outbreaks since 1976 have ranged from 30% to 100% in different settings among adults, but lower mortality rates have been documented in children. This review aims to describe Ebola virus infection, clinical presentation, diagnosis and outcomes in children.

Early postmortem volume reduction of adrenal gland: initial longitudinal computed tomographic study.

We aimed to confirm whether postmortem adrenal volumetric changes occur by measuring adrenal volumes on computed tomography (CT). Fifty-five adrenal glands from 28 subjects who died were included. All subjects underwent antemortem CT (AMCT) and postmortem CT (PMCT) within 94-1,191min after death, followed by conventional autopsy. CT volumetry was performed using freely-available software. Differences between AMCT and PMCT adrenal volumes were evaluated statistically along with differences in the degree of volume change, elapsed time to PMCT, and presence of underlying malignant disease. The mean volume of the right adrenal gland decreased from 3.8cm(3) on AMCT to 2.6cm(3) on PMCT (P<0.001); the left adrenal gland decreased from 4.2cm(3) on AMCT to 3.1cm(3) on PMCT (P<0.001). Conventional autopsy revealed decreased intracellular lipid components in portions of the adrenal glands. No correlation between the adrenal gland reduction rate and the elapsed time from AMCT to death or from death to PMCT was observed (P=0.99 and 0.79; P=0.28 and 0.59 for the right and left adrenal glands, respectively). Significant differences in both the bilateral adrenal gland reduction rates and underlying malignant disease were found for the left adrenal gland (P=0.015), but not for the right (P=0.74). Adrenal volume reduction was observed on PMCT compared to AMCT. This highlights the need to further elucidate the mechanism of adrenal shrinkage during the agonal stage and after death. This may be explained by pathological findings of intracellular lipid depletion.

Is acute subdural hematoma reduced during the agonal stage and postmortem?

The issue of proper use of postmortem computed tomography (PMCT) in forensic fields is currently being actively discussed. The PMCT image has specific findings that differ from the antemortem image, and it is essential to understand and interpret postmortem changes in order to utilize PMCT properly. In this article, we present two cases of acute subdural hematoma (ASDH) in which images were obtained both ante- and postmortem. These images showed marked reduction of hematoma and diminishing midline shift between the agonal and postmortem periods, without evacuation of the hematoma. Attention should be paid to this phenomenon because key findings in determining cause of death could disappear if investigating the cause of death takes too long in cases that prove to be ASDH. In other words, this phenomenon potentially becomes a risk for misdiagnosis when we decide the cause of death without knowing the details of the circumstances of death.

Recombinant Human Soluble Thrombomodulin (ART-123) Prevents Warm Ischemia-Reperfusion Injury in Liver Grafts from Non–Heart-Beating Donors

BackgroundLiver transplantation is an established treatment for end-stage liver disease. However, an ongoing problem worldwide concerning this treatment is the shortage of grafts. Although transplantation using grafts from non–heart-beating donors (NHBDs) is considered a promising solution, some researchers have reported that these liver grafts are associated with primary graft nonfunction and biliary complications. The purpose of this study was to establish a safe technique procuring liver grafts from marginal donors such as NHBDs. Materials and methodsMale Wistar rats were divided into three groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the non-HB (NHB) group, whose livers were retrieved from NHBDs that had experienced an apnea-induced agonal condition (for this group, livers were subjected to warm ischemia for 30 minutes after cardiac arrest); and (3) the recombinant human soluble thrombomodulin (ART-123) group, whose livers were retrieved in the same manner as the NHB group but pretreated with ART-123 (1 mg/kg) at the agonal stage. The livers were reperfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. ResultsBile production and portal flow volume in the ART-123 group were significantly higher than those in the NHB group. Alanine aminotransferase levels in the ART-123 group were significantly lower than those in the NHB group. Histological findings showed the narrowing of sinusoidal spaces and necroses in the NHB group were more severe than those in the ART-123 group. ConclusionsThese results suggest that thrombomodulin may improve the viability of liver grafts from NHBDs.

Renal Protective Effects of Erythropoietin on Ischemic Reperfusion Injury

While the problem of organ shortage has not yet been solved, the number of patients who need to be treated with dialysis due to end-stage renal disease (ESRD) is increasing each year. With the aim of eliminating dialytic therapy as much as possible, the opportunities for organ donation from expansive criteria donor (ECD) or marginal donors due to cardiac death have been increasing. With the purpose of extracting organs in a state in which the function is preserved as much as possible, we reexamined the conditions of tissue disorders resulting from temporary ischemia of the organs as well as changes in tissue function and the effects on the preservation of renal function over time by using rat models in order to clinically utilize erythropoietin, which has inhibitory effects on ischemia-reperfusion disorder, as has been conventionally reported. With 8- to 9-week-old Wister male rats, after the right kidney had been resected under general anesthesia, the left renal artery was clamped to inhibit the blood flow for 45 min. At 30 min before inhibiting the blood flow and after releasing the inhibited blood flow, 100 U/kg of recombinant human erythropoietin (rhEPO) was administered via the inferior vena cava and the abdominal cavity, and then the tissues and blood samples were extracted at 6 and 24 h after the release. The renal tissue specimens were evaluated using H&E staining and TUNEL staining in order to observe differences in the expression of apoptosis as well as the renal function and changes in the emergence of active oxygen were investigated by using samples that had been obtained from drawn blood. Moreover, we examined the degree of renal dysfunction by means of neutrophil gelatinase-associated lipocalin (NGAL) in the spot urine samples. The changes in renal function, which were observed according to the serum creatinine level, showed that the renal function was preserved with a significant difference in the rhEPO administration group. The liver deviation enzymes, which had also shown increases in the serum as well as the occurrence of renal dysfunction, showed clear decreases in the serum, even though changes with a significant difference were not observed in the rhEPO administration group. The active oxygen did not show changes before and after ischemia-reperfusion nor changes due to the rhEPO administration. When examining the status of apoptosis in the tissues, apoptosis was shown to be inhibited due to the rhEPO administration. It is believed that the main preservation effects of rhEPO are the elimination of cytopathy/cell death, as derived from the resulting ischemic condition that extends to the target organ before ischemia occurs. In this examination, no direct effects of rhEPO administration on the emergence of active oxygen were observed. It is therefore suggested that there is a possibility of preserving the renal function in marginal donors with a longer agonal stage by effectively using rhEPO.

Recording movement and activity pattern of a White-tailed Sea Eagle (Haliaeetus albicilla) by a GPS datalogger

For the first time, we measured the home range size and activity pattern of a White-tailed Sea Eagle (WTSE) by GPS telemetry. Positions were recorded three times a day and the activity pattern were continuously recorded by two acceleration sensors. From July to January, we obtained 475 positions and calculated a 95% kernel home range of 4.53 km2 and a 95% minimum convex polygon of 8.22 km2, indicating a rather small area explained by an optimal habitat and by the much more precise location method used here compared to reports in the literature. Biorhythmic analysis of activity data revealed nearly no night-activity, high day-activity with no fixed daily pattern and a strong 24-h period of activity. The stability and synchronisation between the eagle's activity and the environmental 24-h period was evaluated by calculating the degrees of functional coupling (DFC) and the harmonic part (HP). Mostly, DFC was 100% (meaning that the different physiological and behavioural functions are completely synchronised to each other and to the environmental 24-h period) and the few incursions of the DFC we assumed to be caused by clinically relevant lead intoxications. The agonal stage of the WTSE was indicated by a daily decreasing activity level and HPs and highly modified day–night relationship, and decreasing DFCs at the beginning and at the end of dying process, representing changes in the activity structure. The underlying reason for the behavioural changes was found to be a lethal lead intoxication due to an oral ingestion of particles of rifle ammunition. The new technology of a combined GPS receiver and an acceleration sensor allows the automatic measuring of positions and activity of wild animals at a very precise level over prolonged periods which cannot be achieved by manpower.

Machine perfusion preservation for liver transplantation from non-heart-beating donors with agonal stage

Machine perfusion preservation for liver transplantation from non-heart-beating donors with agonal stage

Neuropathology of progressive supranuclear palsy

The fundamental neuropathological findings of progressive supranuclear palsy (PSP) are presented, based on 14 autopsied cases of PSP. The blunt pathologies of PSP are degeneration in the substantia nigra, globus pallidus, subthalamic nuclei, dentate nucleus of the cerebellum and red nucleus, where there are neuronal loss, gliosis and neurofibrillary changes, to varying degree. In addition, the atrophy of the midbrain, especially the characteristic pattern of tegmental atrophy of the pons exhibiting a hand‐bag profile, is an important finding. Hypertrophy of inferior olivary nucleus is frequently observed, suggesting the existence of lesions in the dentato‐olivary system. Hypoxemic affects at the agonal stage should be noted because death of Purkinje cells of the cerebellum leads to degeneration of their axons and subsequently to the decrease of grumose degeneration in the dentate nucleus. Familial PSP have been reported by several authors but all case in the present study were sporadic.

Perturbations of cerebral hemodynamics in Kenyans with cerebral malaria

The mechanisms of death and neurologic sequelae in African children with cerebral malaria are undetermined. Because pathologic features are confined to the cerebral vasculature, perturbations in cerebral hemodynamics may be responsible. We compared the transcranial Doppler findings in 50 children with cerebral malaria with those of 115 conscious Kenyan children. In addition, 10 children with cerebral malaria were studied during intracranial pressure monitoring and nine children were studied during the agonal stages. In the children with cerebral malaria, cerebral blood flow velocity was increased in 30%, usually associated with seizures. Of the 11 children who developed neurologic sequelae, six had sonographic abnormalities associated with lateralizing deficits, including four children with hemiparesis (in two children the contralateral middle cerebral artery could not be insonated and two had transient increases in blood flow velocity associated with seizures). In the children with severe intracranial hypertension, there was a significant linear relationship between the cerebral perfusion pressure and blood flow velocity, suggesting that autoregulation was impaired. Sonographic features of progressive intracranial hypertension, were observed in three children with cerebral malaria who died. Perturbations of cerebral hemodynamics are associated with a poor outcome in Kenyan children with cerebral malaria.

Enzyme-linked immunoabsorbent assay for plasma thyroglobulin following compression of the neck

A highly sensitive enzyme-linked immunosorbent assay (ELISA) for determination of plasma thyroglobulin (Tg) which we devised was applied to the postmortem diagnosis of external compression of the neck. The coefficients of variation within and between assays were 2.4–6.6% and 6.8–12.0%, respectively. A significant correlation was observed between Tg levels measured by our ELISA and those measured by radioimmunoassay ( r = 0.996, P < 0.001). Plasma Tg levels in all 36 cadavers without external compression of the neck or neck injuries were lower than 200 ng/ml (73.6 ± 51.9 ng/ml, M ± S.D.) although these levels were a little higher than those in living bodies (16.7 ± 11.8 ng/ml). On the other hand, plasma Tg levels in most of 42 victims of asphyxia due to external compression of the neck were higher than 200 ng/ml (2190 ± 4300 ng/ml), and the highest one was 24 600 ng/ml. Plasma levels of the other thyroid hormones and thyroid-stimulating hormone were determined in some cases, and the cervical conditions in certain cases of strangulation were analyzed. Present results suggest that Tg was released by mechanical force on the thyroid gland added at the agonal stage. The determination of plasma Tg level in a cadaver using our ELISA would seem to be useful for the postmortem diagnosis of the presence of external compression of the neck. Although thyroid diseases causing elevated Tg levels are rare in forensic cases, they should be excluded by routine histology of the thyroid at autopsy, so that the finding of a high Tg level would thus carry more weight when given in evidence.

Simultaneous elevation of plasma insulin and catecholamines during endotoxicosis in the conscious and anesthetized rat

Plasma levels of glucose, insulin and catecholamines were assessed during the early phase of sub-lethal endotoxicosis in fasted male rats which were either conscious or continuously anesthetized with sodium pentobarbital. Exogenous glucose challenge was administered during endotoxicosis to probe insulin release at a time when plasma catecholamines were elevated. An endogenous hyperglycemia occurred following endotoxin but was moderated by continuous pentobarbital anesthesia. Plasma insulin was elevated in the conscious but not anesthetized rats during endogenous hyperglycemia following endotoxin. Hyperglycemia with exogenous glucose elevated plasma insulin levels in both conscious and anesthetized groups and occurred in the presence of elevated levels of norepinephrine, epinephrine and dopamine. Simultaneous elevation of plasma catecholamine and insulin levels during endotoxicosis suggests that glucose utilization may be promoted at the same time that glucose is mobilized through adrenergic mechanisms. These events may contribute to the rapid depletion of carbohydrate stores leading to the hypoglycemia of the agonal stage of endotoxic shock.

A hypothesis concerning Clostridium perfringens type A enterotoxin (CPE) and Sudden Infant Death Syndrome (SIDS)

This study identifies the presence of Clostridium perfringens type A enterotoxin (CPE) in some gastrointestinal and serum samples from babies who had died of the Sudden Infant Death Syndrome (SIDS) and other causes. On occasion antibodies to this toxin were identified in sera. CPE is parasympathomimetic in its action. In the adult food poisoning model it is produced when the organism sporulates in vivo . This leads to speculation as to whether this toxin may play an ante-mortem role in the dying process of infants, either in the agonal stages or as a causative factor in SIDS.

Characteristics of myocardial beta-adrenergic receptors during endotoxicosis in the rat.

The effects of in vivo endotoxin administration on beta-adrenergic receptors in rat ventricle membranes were studied using [3H]dihydroalprenolol as a radioligand. Nonlinear regression analysis of saturation binding indicated one-site binding of antagonist in both control and endotoxic tissues. There was no change in maximum binding or dissociation constant of [3H]dihydroalprenolol at 0.5 or 3 h after endotoxin administration or when the rats were in the agonal stage of shock. Isoproterenol competition studies revealed that there was an increase in the slope of the curve from endotoxic tissues at the agonal stages (0.6 +/- 0.06 vs. 0.91 +/- 0.12, control and endotoxic, respectively, P less than 0.05) and that there was a decrease in affinity for isoproterenol binding. Control binding modeled to a two-state fit, whereas binding to endotoxin-exposed membranes modeled to one state of lower affinity. These data suggest that there is an alteration in receptor-adenylate cyclase coupling, which may account for an attenuation of agonist-stimulated cyclase activity. A modification in the beta-adrenergic receptor may contribute to the decrease in myocardial performance during shock.