Authentic role of ATP signaling in micturition reflex

Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2 -/- and P2X3 -/- mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex

Granulovacuolar Degenerations Appear in Relation to Hippocampal Phosphorylated Tau Accumulation in Various Neurodegenerative Disorders

BACKGROUND: Granulovacuolar degeneration (GVD) is one of the pathological hallmarks of Alzheimer's disease (AD), and it is defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. Several lines of evidence have suggested that GVDs appear within hippocampal pyramidal neurons in AD when phosphorylated tau begins to aggregate into early-stage neurofibrillary tangles. The aim of this study is to investigate the association of GVDs with phosphorylated tau pathology to determine whether GVDs and phosphorylated tau coexist among different non-AD neurodegenerative disorders. METHODS: An autopsied series of 28 patients with a variety of neurodegenerative disorders and 9 control patients were evaluated. Standard histological stains along with immunohistochemistry using protein markers for GVD and confocal microscopy were utilized. RESULTS: The number of neurons with GVDs significantly increased with the level of phosphorylated tau accumulation in the hippocampal regions in non-AD neurodegenerative disorders. At the cellular level, diffuse staining for phosphorylated tau was detected in neurons with GVDs. CONCLUSIONS: Our data suggest that GVDs appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders, while the presence of phosphorylated tau in GVD-harbouring neurons in non-AD neurodegenerative disorders was indistinguishable from age-related accumulation of phosphorylated tau. Although GVDs in non-AD neurodegenerative disorders have not been studied thoroughly, our results suggest that they are not incidental findings, but rather they appear in relation to phosphorylated tau accumulation, further highlighting the role of GVD in the process of phosphorylated tau accumulation

The in-depth accident study to evaluate the advanced automatic collision notification system in Japan

In Japan, an automatic collision notification service called “HELPNET” has been in operation since 2000. In addition to HELPNET, the pilot study on Advanced Automatic Collision Notification (AACN) and Helicopter Emergency Medical Service (HEMS) system, so-called D-Call Net, had started in several prefectures of Japan by the D-Call Net committee in affiliation with Emergency Medical Network of Helicopter and Hospital (HEM-Net) since November 2015. Regarding D-Call Net pilot system, HELPNET infrastructures already developed for existing Japanese ACN service were used for sending vehicle data to HELPNET center. In the case of accident, Event Data Recorder (EDR) data was added on usual HELPNET data and transmitted from a vehicle to HELPNET server at HELPNET center. D-Call Net server got vehicle data such as Delta V and seatbelt status, etc. and input them to the algorithm. The algorithm result was transmitted to “iPad” at the Trauma Center nearby the crash spot. Simultaneously, an operator of HELPNET made Emergency Call to the fire department. In case of severe injury, “iPad” indicated the serious situation and a doctor rushed to the accident spot by a helicopter. After the helicopter with a doctor and a nurse took off, verbal communications between the helicopter pilot and the fire department were started to decide a rendezvous point nearby the crash spot. After landing, the doctor and the nurse contacted the injured occupant who was curried by an ambulance there. This system is operated at about 30 trauma centers with Helicopter Emergency Medical Service in Japan, as of 17 November 2017. This paper is focusing on the in-depth accident study to evaluate the Advanced Automatic Collision Notification and Helicopter Emergency Medical Service system (D-Call Net) in Japan. For this system, the Occupant Injury Predict Algorithm newly developed by Nihon University was utilized. About 2.8 million of Japanese accident data, so called ITARDA Macro Data, were calculated to define logistic regression risk curves of fatal and severe injured drivers and front passengers. During the pilot study, accident cases should be collected and accident database should be established in order to evaluate D-Call Net algorithm and D-Call Net Helicopter Emergency Medical Service operation at both fire departments and trauma centers. The results will be feedback on the actual service planned to start in spring 2018