One autopsy case of an elderly traffic accident victim with Tetralogy of Fallot

The case of a61-year-old male traffic accident victem with Tetralogy of Fallot (TOF) is reported. The autopsy revealed massive hemorrhages in the subcutaneous tissue, muscle, and subarachnoidal space. Furthermore, multiple fractures of ribs, sternum and thoracic vertebrae were observed. Histopathological examination revealed changes characteristic of trauma, such as acute lung congestion, acute renal cortical necrosis, and embolization in the lungs and kidney. These autopsy and histological observations indi-cated that traumatic shock was cause of his death. Moreover, histologically, we observed changes due to his congenital heart disease, such as right ventricular hypertrophy, heart failure cells in the lungs, sclerosis of the liver, and hyaline degeneration in the kidney. Furthermore, ischemic changes, shrinkage or loss of neurons, were seen in hippocampus, and swelling of astrocytes in both cortex and hippocampus were also observed. These observations lead us to speculate that a hypoxic episode may have caused his accidental death while driving

PACAP centrally mediates emotional stress-induced corticosterone responses in mice

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide widely distributed in the nervous system. Recently, PACAP was shown to be involved in restraint stress-induced corticosterone release and concomitant expression of the genes involved in hypothalamic–pituitary–adrenal (HPA) axis activation. Therefore, in this study, we have addressed the types of stressors and the levels of the HPA axis in which PACAP signaling is involved using mice lacking PACAP (PACAP−/−). Among four different types of stressors, open-field exposure, cold exposure, ether inhalation, and restraint, the corticosterone response to open-field exposure and restraint, which are categorized as emotional stressors, but not the other two, was markedly attenuated in PACAP−/− mice. Peripheral administration of corticotropin releasing factor (CRF) or adrenocorticotropic hormone induced corticosterone increase similarly in PACAP and wild-type mice. In addition, the restraint stress-induced c-Fos expression was significantly decreased in the paraventricular nucleus (PVN) and medial amygdala (MeA), but not the medial prefrontal cortex, in PACAP−/− mice. In the PVN of PACAP−/− mice, the stress-induced c-Fos expression was blunted in the CRF neurons. These results suggest that PACAP is critically involved in activation of the MeA and PVN CRF neurons to centrally regulate the HPA axis response to emotional stressors

Lower-dose prescriptions in the post-marketing situation and the influencing factors thereon.

The dosage of pharmaceuticals is determined through the process of clinical development and approval review based on clinical trial results; however, the information obtained from clinical trials before approval is limited. Some pharmaceutical products are used at doses lower than those approved for post-marketing use. The aim of this study was to reveal the actual state of lower-dose prescriptions for post-marketing clinical use of pharmaceuticals. We investigated the factors related to the deviation based on therapeutic area, detailed statement of the approved dosage, clinical data package, and post-marketing requirement. Among the new molecular entities approved in Japan between January 2005 and December 2014, we identified products that are orally administered and have the same daily dose for different indications, if any. For these products, we collected information on the actual daily dose from the medical information databases of Medical Data Vision Co., LTD. and JammNet Co., LTD. Products whose dose was lower than the approved dose (maintenance dose excluding the initial dose) in ≥ 30% prescriptions in 2015 were defined here as "lower-dose prescription drugs." We identified 27 lower-dose prescription drugs out of 113 products investigated. The results of the multivariate analysis revealed that factors related to the Anatomical Therapeutic Chemical classification and the detailed statement of the approved dosage significantly influenced the occurrence of lower-dose prescription, whereas the factors related to clinical data package and post-marketing requirements did not. These results suggest the limitation in determining an optimal dosage for the actual clinical use of a drug based on the information obtained from clinical trials conducted before approval, emphasizing the importance of reexamining the optimal dosage that is applicable to a greater number of patients after marketing, if necessary. We believe that the utilization of real-world data could be of help in this regard

Modeling the shearing behavior of discontinuous rock mass incorporating dilation of joint aperture

The shearing characteristics of rock joints govern the mechanical performance of discontinuous rock masses. The present study investigated the normal compression and shear behavior of rock joints through cyclic compression tests and direct shear tests. The irreversible relationship between the normal stress and the normal closure was confirmed by cyclic compression tests on rock joints. An elastoplastic model was proposed incorporating the aperture variation. A modified version of the critical state framework was developed for modeling the shearing and dilation behavior. Specifically, the initial state of the rock joints was determined according to the stress history. The proposed model for the mechanical behavior of rock joints was validated by predicting the experimental results. A parameter analysis was also performed to highlight the difference in the shear behavior of the rock joints due to the difference in the initial apertures