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Abstract Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer’s disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus. Here, we demonstrate that HCNP-precursor protein (pp) knockout (KO) mice electrophysiologically presented with glutamatergic dysfunction in the hippocampus with age. The impairment of cholinergic function via a decrease in vesicular acetylcholine transporter in the pre-synapse with reactive upregulation of the muscarinic M1 receptor may be partly involved in glutamatergic dysfunction in the hippocampus of HCNP-pp KO mice. The results, in combination with our previous reports that show the reduction of hippocampal theta power through a decrease of a region-specific choline acetyltransferase in the stratum oriens of CA1 and the decrease of acetylcholine concentration in the hippocampus, may indicate the defined cholinergic dysfunction in HCNP-pp KO mice. This may also support that HCNP-pp KO mice are appropriate genetic models for cholinergic functional impairment in septo-hippocampal interactions. Therefore, according to the cholinergic hypothesis, the model mice might are potential partial pathological animal models for Alzheimer’s disease.

Abstract The cholinergic efferent network from the medial septal nucleus to the hippocampus plays an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine (Ach) synthesis in the medial septal nuclei of an explant culture system, was purified from the soluble fraction of postnatal rat hippocampus. HCNP is processed from the N-terminal region of a 186-amino acid, 21-kDa HCNP precursor protein, also known as Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein 1. Here, we confirmed direct reduction of Ach release in the hippocampus of freely moving HCNP-pp knockout mice under an arousal state by the microdialysis method. The levels of vesicular acetylcholine transporter were also decreased in the hippocampus of these mice in comparison with those in control mice, suggesting there was decreased incorporation of Ach into the synaptic vesicle. These results potently indicate that HCNP may be a cholinergic regulator in the septo-hippocampal network.

The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer’s disease and Lewy body dementia.

The population density of cities has been increasing with time and the development of industry. Building fires in large cities with high population density cause extensive human and property damage. To prevent such damage, the characteristics of flames such as the thermal radiation and intensity of the fire source must be considered when designing building structures. However, the consideration of these factors is practically inadequate. Accordingly, in this study, when a mattress was ignited in an open environment at a different installation height (0–515 mm), the measurements from a heat flux meter and the calculated thermal radiation were compared, and a comparative analysis was conducted using the existing prediction formulas by researchers described in ISO 24678-7. We examined the fire risk of mattresses according to the mattress installation height. As a result, the fire risk of the mattress was confirmed according to the mattress installation height; upon comparing the experimental and calculated values for radiant heat, it was found to be necessary to estimate the radiant heat using a calculation method that applies the configuration factor differently depending on the change in the flame shape. In addition, as a result of substituting the experimental value into the calculation method of ISO 24678-7 (a method for estimating the radiant heat of liquid combustibles), the experimental value and the calculated value were found to be significantly different. Therefore, similar to ISO 24678-7 for the radiation heat estimation method for “liquid combustibles”, an international standard for establishing the radiation heat estimation method for “solid combustible materials” as a standard was also required for a reasonable analysis of the fire safety phenomenon of solid materials, such as bed mattresses.

Bed mattresses are rated as products to cause a fire hazard because of their very high heat release rate among indoor combustibles. In this study, fire growth rate and flame height were measured through a series of combustion experiments on a full scale in order to provide information regarding mattress fire characteristics. The experiments were conducted in an open space, and bed mattresses as the test samples were installed at different installation heights (0~515 mm). The experiment results revealed that the higher the bed mattress was installed, the higher the fire growth rate, the heat release rate, and the flame height. Additionally, the time of the mattress to reach 1 MW was evaluated as the category “medium” in the NFPA 72 standards. The flame heights showed a good coincidence compared to the existing flame height model equations, proving the applicability of the model to the mattress combustion.

The prevention of post-operative bleeding is currently a critical issue associated with endoscopic submucosal dissection (ESD), where combined anti-thrombotic therapy is the standard in a super-aged society. Post-ESD coagulation (PEC) is widely performed to prevent post-operative bleeding; nonetheless, post-operative bleeding rates associated with gastric ESD continue to be reported in 3.1-5.5% of cases. The present study aimed to examine the effectiveness of a novel technique, the modified coagulation and clipping (MCC) method, in preventing post-operative bleeding associated with ESD. Overall, 481 patients were treated between April, 2007 and July, 2020. Between July, 2010 and June, 2020, the MCC method was adopted. The incidence of post-operative bleeding was assessed following gastric ESD and the clinical conditions affecting post-operative bleeding during this period were analyzed retrospectively. In addition, the incidence of postoperative bleeding associated with gastric ESD and the clinical conditions in the 3-year period from April, 2007 to June, 2010 were assessed, during which PEC was employed, as a historical control. The bleeding rates for these two periods were compared using propensity score matching (PSM). Of the 481 included patients, 160 and 321 patients underwent the PEC and MCC method, respectively. In total, 9 patients (5.6%) in the PEC group developed post-operative bleeding, whereas no patient (0.0%) in the MCC group developed post-operative bleeding. The PSM analysis revealed that the MCC method was significantly associated with the prevention of post-operative bleeding. On the whole, the findings of the present study indicate that the MCC method is a promising technique for preventing post-operative bleeding associated with ESD. However, further studies are required to identify the optimal indications. [ABSTRACT FROM AUTHOR]