The Inhibitory Effect of Kakkonto, Japanese Traditional (Kampo) Medicine, on Brain Penetration of Oseltamivir Carboxylate in Mice with Reduced Blood-Brain Barrier Function

Oseltamivir phosphate (OP) is used to treat influenza virus infections. However, its use may result in central nervous system (CNS) adverse effects. In Japan, OP is used with Kampo formulations to improve clinical effectiveness. We evaluated the potential for using Kampo formulations to reduce CNS adverse effects by quantifying the CNS distribution of oseltamivir and its active metabolite oseltamivir carboxylate (OC) when administered with maoto and kakkonto. We administered lipopolysaccharide (LPS) by intraperitoneal injection to C57BL/6 mice to reduce blood-brain barrier function. Saline, maoto, and kakkonto were administered orally at the same time as LPS. OP was orally administered 4 hours after the last LPS injection and the migration of oseltamivir and OC was examined. Additionally, we examined the brain distribution of OC following intravenous administration. Changes in OC concentrations in the brain suggest that, in comparison to LPS-treated control mice, both Kampo formulations increased plasma levels of OC, thereby enhancing its therapeutic effect. Additionally, our findings suggest kakkonto may not only improve the therapeutic effect of oseltamivir but also reduce the risk of CNS-based adverse effects. Considering these findings, it should be noted that administration of kakkonto during periods of inflammation has led to increased OAT3 expression

Nuclear Wobbling Motion and Electromagnetic Transitions

The nuclear wobbling motion is studied from a microscopic viewpoint. It is shown that the expressions not only of the excitation energy but also of the electromagnetic transition rate in the microscopic RPA framework can be cast into the corresponding forms of the macroscopic rotor model. Criteria to identify the rotational band associated with the wobbling motion are given, based on which examples of realistic calculations are investigated and some theoretical predictions are presented.Comment: 39 pages, plain TeX, figures not included, available via conventional mai

Reliability and Validity of the Nursing Student Competency Assessment Instrument and Related Factors

The purpose of this study was to confirm the reliability and validity of the competency assessment index of nursing students and to identify the factors associated with competency. An anonymous self-administered questionnaire survey was conducted on nursing students enrolled from April 2021 to March 2022. Principal component analysis and Cronbach’s alpha coefficient were used to examine the reliability and validity of the competency factor structure. Multiple regression analysis was used to analyze related factors. As a result, the reliability and validity of the factor structure of competency were statistically clarified. As related factors of competency, “grade level” and “thinking that learning in university education gives students confidence” and “cognitive regulation strategies” were identified. In the analysis by competency sub-factors, other than grade level,［ relationship building］ was affected by “being immersed in university education,” ［ethical care］ and ［cooperation and collaboration］ by “thinking that learning in university education gives students confidence”, and［ health problem-solving］ and［ professional development］ by “cognitive regulation strategies”. The importance of recommending experiential education in clinical practice, strengthening self-regulated learning strategies, and education to increase students’ self-confidence were suggested. The results of this study contribute to the reconstruction of education in which competencies are shared with students

Dielectric collapse at the LaAlO₃/SrTiO₃ (001) heterointerface under applied electric field

Abstract The fascinating interfacial transport properties at the LaAlO3/SrTiO3 heterointerface have led to intense investigations of this oxide system. Exploiting the large dielectric constant of SrTiO3 at low temperatures, tunability in the interfacial conductivity over a wide range has been demonstrated using a back-gate device geometry. In order to understand the effect of back-gating, it is crucial to assess the interface band structure and its evolution with external bias. In this study, we report measurements of the gate-bias dependent interface band alignment, especially the confining potential profile, at the conducting LaAlO3/SrTiO3 (001) heterointerface using soft and hard x-ray photoemission spectroscopy in conjunction with detailed model simulations. Depth-profiling analysis incorporating the electric field dependent dielectric constant in SrTiO3 reveals that a significant potential drop on the SrTiO3 side of the interface occurs within ~2 nm of the interface under negative gate-bias. These results demonstrate gate control of the collapse of the dielectric permittivity at the interface, and explain the dramatic loss of electron mobility with back-gate depletion

Structural aging of human neurons is the opposite of the changes in schizophrenia

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson's r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 x 10^(-4)). The neurite curvature also showed a correlation with a hallucination score (Pearson's r = 0.80, p = 1.8 x 10^(-4)), indicating that neurite structure is relevant to brain function. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia. This nano-CT paper is the result of our decade-long analysis and is unprecedented in terms of number of cases.Comment: 24 pages, 5 figures. arXiv admin note: text overlap with arXiv:2007.0021

Detection of viral RNA in diverse body fluids in an SFTS patient with encephalopathy, gastrointestinal bleeding and pneumonia: a case report and literature review

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. CASE PRESENTATION: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted. CONCLUSIONS: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed

Технологічні рішення і технічні засоби підвищення екологічної безпеки проведення бурових робіт

Рассмотрено влияние проведения буровых работ на окружающую среду. Приведены рекомендации для повышения экологической безопасности проведения буровых работ. Описаны технологические решения и технические средства уменьшения неблагоприятного влияния бурения нефтегазовых скважин на окружающую среду. В комплексе решены и эффективно внедрены на практике вопросы экологической безопасности проведения буровых работ, утилизации, размещения и захоронения отходов бурения. Дказано, что безамбарное бурение на месторождениях возможно при наличии шламонакопителя и нагнетательной скважины.The environmental impacts of drilling works are considered. A range of recommendations for environmental safety enhancement of drilling works is given. Technological solutions and technical means to reduce adverse environmental impacts of oil and gas wells drilling are described. The issues of drilling works environmental safety, utilization, disposal and burial of waste are jointly solved and successfully implemented. The pit less drilling is proved to be possible for any field under the condition of slurry pond and injection well use

Temporal regulation of Drosophila IAP1 determines caspase functions in sensory organ development

Caspase activation is regulated by the turnover of E3 ubiquitin ligase, DIAP1, and depends on cell type and maturity