Application and limitation of a biological clock-based method for estimating time of death in forensic practices.

Estimating time of death is one of the most important problems in forensics. Here, we evaluated the applicability, limitations and reliability of the developed biological clock-based method. We analyzed the expression of the clock genes, BMAL1 and NR1D1, in 318 dead hearts with defined time of death by real-time RT-PCR. For estimating the time of death, we chose two parameters, the NR1D1/BMAL1 ratio and BMAL1/NR1D1 ratio for morning and evening deaths, respectively. The NR1D1/BMAL1 ratio was significantly higher in morning deaths and the BMAL1/NR1D1 ratio was significantly higher in evening deaths. Sex, age, postmortem interval, and most causes of death had no significant effect on the two parameters, except for infants and the elderly, and severe brain injury. Although our method may not work in all cases, our method is useful for forensic practice in that it complements classical methods that are strongly influenced by the environment in which the corpse is placed. However, this method should be applied with caution in infants, the elderly, and patients with severe brain injury.

Localized mesospheric ozone destruction corresponding to isolated proton aurora coming from Earth's radiation belt.

Relativistic electron precipitation (REP) from the Earth's radiation belt plays an important role in mesospheric ozone loss as a connection between space weather and the climate system. However, the rapid (tens of minutes) destruction of mesospheric ozone directly caused by REP has remained poorly understood due to the difficulty of recognizing its location and duration. Here we show a compelling rapid correspondence between localized REP and ozone destruction during a specific auroral phenomenon, the called an isolated proton aurora (IPA). The IPA from the Earth's radiation belt becomes an important spatial and temporal proxy of REP, distinct from other auroral phenomena, and allowing visualizing micro-ozone holes. We found ozone destruction of as much as 10-60% within 1.5 h of the initiation of IPA. Electromagnetic ion cyclotron waves in the oxygen ion band observed as the driver of REP likely affect through resonance with mainly ultra-relativistic (> 2 mega-electron-volts) energy electrons. The rapid REP impact demonstrates its crucial role and direct effect on regulating the atmospheric chemical balance.

Forensic significance of intracardiac heme oxygenase-1 expression in acute myocardial ischemia.

Heme oxygenase-1 (HO-1), an inducible stress-response protein, exerts anti-oxidant and anti-apoptotic effects. However, its significance in forensic diagnosis of acute ischemic heart diseases (AIHD) such as myocardial infarction (MI) is still unknown. We examined the immunohistochemical expression of HO-1 in the heart samples to discuss their forensic significance to determine acute cardiac ischemia. The heart samples were obtained from 23 AIHD cases and 33 non-AIHD cases as controls. HO-1 positive signals in cardiomyocyte nuclear were detected in 78.2% of AIHD cases, however, that were detected in only 24.2% control cases with statistical difference between AIHD and non-AIHD groups. In contrast to HO-1 protein expression, there was no significant difference in the appearance of myoglobin pallor regions and leukocyte infiltration in the hearts between AIHD and non-AIHD groups. From the viewpoints of forensic pathology, intracardiac HO-1 expression would be considered a valuable marker to diagnose AIHD as the cause of death.

Aphasic status epilepticus of frontal origin treated by resective surgery.

Aphasic status epilepticus (SE) is a clinical entity of SE, but it has not been well recognized. We report a 43-year-old female with a chronic drug-resistant epilepsy with aphasic SE, treated by resective surgery. The patient showed long-lasting weekly episodes of hypokinesia, slow verbal response, and dysphasia, which were diagnosed as symptoms of aphasic SE. Magnetic resonance imaging showed encephalomalacia in the left frontal lobe with a hemosiderin rim. Intracranial electroencephalography revealed continuous spikes, predominantly on the left superior frontal gyrus with hemosiderin deposit. The aphasic symptoms were seen when ictal discharges gradually spread to the wide area of the left anterior frontal lobe, including the language area. The episodes of recurrent aphasic SE had disappeared by one year after the left anterior frontal resection. We should consider aphasic SE when language impairment is episodic, and consider surgical intervention in cases where it repeatedly occurs despite appropriate medical therapy.

Quantitative evaluation for cervical foraminal bony stenosis based on angled sagittal slices along a nerve root on computed tomography.

Cervical foraminal canal stenosis is a common disease, but any relationships between the measurement values of cervical foraminal canals and clinical symptoms have yet to be explored. We aim to determine a numerical cutoff point of cervical foraminal bony canal size that does not lead to radiculopathy so as to establish criteria for the surgical indication. We reconstructed angled sagittal slices along a nerve root on computed tomography (CT) on a workstation from pre-operative CT data and measured 1152 cervical foraminal canals (144 patients) from Cervical (C) 4/5 to C7/Thoracic (Th) 1. We evaluated the relationship between the size of foraminal canals and clinical manifestations. Receiver operating characteristic (ROC) analysis was used to calculate cutoff points of each foraminal canal size with positive neurologic manifestations. Of the 144 patients' 1152 nerve roots, 286 nerve roots (24.8%) were diagnosed as radiculopathy by neurological examinations. The mean measured value of all foraminal canals on angled sagittal CT imagery was 3.39 ±â€¯1.37 mm. The cutoff point of foraminal canal sizes without radiculopathy was 2.7 mm (sensitivity 0.680, specificity 0.591) overall. A cutoff point ascertained by quantitative evaluation of cervical foraminal canal size is useful for making diagnosis of cervical foraminal canal bony stenosis.

Forensic pathological study on temporal appearance of dendritic cells in skin wounds.

Dendritic cells (DCs) can essentially contribute to innate and adaptive immune system in various organs. A double-color immunofluorescence analysis was carried out with anti-CD11c and -HLA-DRα antibodies to detect DCs in 53 skin wounds (their postinfliction intervals: group I, 0-3 days; group II, 4-7 days; group III, 9-14 days; and group IV, 17-21 days). CD11c+HLA-DRα+ DCs were first observed in skin wounds with postinfliction intervals of 3 days, and the DC numbers were found to be elevated in skin wounds with the subsequent increase in postinfliction intervals. Semi-quantitative morphometric analyses showed that the DC number was the highest in the 12-day-old wound. More than 50 DCs were present in 8 of 10 samples (80%) in group II and 14 of 16 samples (87.5%) in group III, and there was no difference between the two groups. Thus, the presence of DCs in a skin wound was possibly estimated as postinfliction intervals of at least 3 days. Furthermore, when a skin wound contained > 50 DCs, its age would be judged as 4-14 days. Collectively, the appearance of DCs in human skin wounds may provide useful information in determining the age of a wound.

A case of complex suicide due to acute nicotine intoxication caused by cigarette ingestion.

This paper presents an unusual complex suicide case that died of nicotine addiction. The deceased was a 40-year-old male who was found lying dead on the floor in his room. In external findings, many incision wounds on his forearms and skin discoloration with epidermolysis on his cervical region could be seen. In the room, a blood-stained scissors and electric cord hanged on the exercise bike were found. Moreover, nine cigarette residues which were only the filter part and empty bottle of coffee were found on his side. At autopsy, we found that those injuries were not serious enough to lead him to the death. Toxicologically, caffeine, nicotine, cotinine, mirtazapine, and olanzapine could be detected, and the concentrations of nicotine were 3.740, 2.140, 3.100, and 451.100 µg/ml in cardiac blood, peripheral blood, urine, and stomach contents, respectively. These concentrations were evaluated as the fatal levels, and the cause of his death was diagnosed as acute nicotine intoxication.

Visualization of rapid electron precipitation via chorus element wave-particle interactions.

Chorus waves, among the most intense electromagnetic emissions in the Earth's magnetosphere, magnetized planets, and laboratory plasmas, play an important role in the acceleration and loss of energetic electrons in the plasma universe through resonant interactions with electrons. However, the spatial evolution of the electron resonant interactions with electromagnetic waves remains poorly understood owing to imaging difficulties. Here we provide a compelling visualization of chorus element wave-particle interactions in the Earth's magnetosphere. Through in-situ measurements of chorus waveforms with the Arase satellite and transient auroral flashes from electron precipitation events as detected by 100-Hz video sampling from the ground, Earth's aurora becomes a display for the resonant interactions. Our observations capture an asymmetric spatial development, correlated strongly with the amplitude variation of discrete chorus elements. This finding is not theoretically predicted but helps in understanding the rapid scattering processes of energetic electrons near the Earth and other magnetized planets.

Crucial Involvement of IL-6 in Thrombus Resolution in Mice via Macrophage Recruitment and the Induction of Proteolytic Enzymes.

After the ligation of the inferior vena cava (IVC) of wild-type (WT) mice, venous thrombi formed and grew progressively until 5 days and resolved thereafter. Concomitantly, intrathrombotic gene expression of Il6 was enhanced later than 5 days after IVC ligation. IL-6 protein expression was detected mainly in F4/80-positive macrophages in thrombus. When Il6-deficient (Il6-/-) mice were treated in the same manner, thrombus mass was significantly larger than in WT mice. Moreover, the recovery of thrombosed IVC blood flow was markedly delayed in Il6-/- compared with WT mice. F4/80-positive macrophages in thrombus expressed proteolytic enzymes such as matrix metalloproteinase (Mmp) 2, Mmp9, and urokinase-type plasminogen activator (Plau); and their mRNA expression was significantly reduced in Il6-/- mice. Consistently, the administration of anti-IL-6 antibody delayed the thrombus resolution in WT mice, whereas IL-6 administration accelerated thrombus resolution in WT and Il6-/- mice. Moreover, IL-6 in vitro enhanced Mmp2, Mmp9, and Plau mRNA expression in WT-derived peritoneal macrophages in a dose-dependent manner; and the enhancement was abrogated by a specific Stat3 inhibitor, Stattic. Thus, IL-6/Stat3 signaling pathway can promote thrombus resolution by enhancing Mmp2, Mmp9, and Plau expression in macrophages.

Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and Global Excitatory" Inputs to the Basal Ganglia.

To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information.

Activation of the arachidonic acid metabolic pathway and induction of sleep disturbance by sacral osteoblastoma: A case report.

Osteoblastomas are benign bone tumors that produce prostaglandin and promote inflammation. The aim of the present study was to describe the clinical and radiological characteristics of a pediatric osteoblastoma case over an 8-month postoperative follow-up. The case involved an 11-year-old female patient with normal somatic development, presenting with a chief complaint of sleep disturbance. The patient had no spontaneous pain or other readily evident possible causes. Magnetic resonance imaging (MRI) revealed a neoplastic lesion in the sacrum, with peritumoral edema. Intraoperative fast-frozen biopsy raised the suspicion of osteosarcoma. However, the final diagnosis was osteoblastoma and a second operation was performed for total resection. The edematous peritumoral bone and muscle tissues were preserved. Following total removal of the tumor, the sleep disturbance resolved. Eight months after the surgery, MRI revealed no recurrence of the tumor and reduction of the peritumoral edema. On immunohistochemical examination, cyclooxygenase (COX)-1 and COX-2 were strongly positive, indicating that the tumor activated the arachidonic acid metabolic pathway and produced prostaglandin. The inflammatory process subsequently promoted the development of peritumoral edema and induced the sleep disturbance.

[The efficiency of cilostazol for cerebral vasospasm following subarachnoid hemorrhage].

Delayed ischemic deficit following subarachnoid hemorrhage(SAH)is a major source of morbidity and mortality after rupture of an intracranial aneurysm. Once symptomatic cerebral vasospasm has occured, available treatments do not provide good outcomes for all patients. Symptomatic vasospasm results in serious sequelae for 10-15% of patients and the etiology and pathogenesis remain unclear. Cilostazol is a specific inhibitor of cAMP(cyclic adenosine monophosphate)phosphodiesterase, and is used for treating ischemic symptoms of peripheral vascular disease. Cilostazol has various actions, such as inhibiting vascular smooth muscle proliferation, and increasing nitric oxide(NO)levels derived from endothelial cells. The present study included 81 patients with SAH caused by ruptured cerebral aneurysms treated in two hospitals between June, 2008 and September, 2009. All patients were treated with clipping surgery, and were classified into two groups: 25 patients who received cilostazol from postoperative day 1 to 14 or 28; and 56 control patients. Clinical symptoms due to cerebral vasospasm and frequency of severe spasm were compared between each of the groups. The frequencies of severe spasm appearing on angiography(age>65)and symptomatic cerebral vasospasm were lower in the cilostazol group than in controls. These findings suggest that cilostazol may prevent symptomatic cerebral vasospasm after subarachnoid hemorrhage.

Displays of paternal mouse pup retrieval following communicative interaction with maternal mates.

Compared with the knowledge of maternal care, much less is known about the factors required for paternal parental care. Here we report that new sires of laboratory mice, though not spontaneously parental, can be induced to show maternal-like parental care (pup retrieval) using signals from dams separated from their pups. During this interaction, the maternal mates emit 38-kHz ultrasonic vocalizations to their male partners, which are equivalent to vocalizations that occur following pheromone stimulation. Without these signals or in the absence of maternal mates, the sires do not retrieve their pups within 5 min. These results show that, in mice, the maternal parent communicates to the paternal parent to encourage pup care. This new paradigm may be useful in the analysis of the parental brain during paternal care induced by interactive communication.