カンゴシ ノ タイショク ト ショクギョウ ケイゾク シエン ニ カンスル チョウサ ケンキュウ

The aims of this study are to clear the reasons why nurses resign or continue their jobs, and to investigate the actual conditions of support system for continuing jobs of nursing

Treatment Strategy for Recurrent and Refractory Epithelial Ovarian Cancer: Efficacy of High-Dose Chemotherapy with Hematopoietic Stem Cell Transplantation

According to population statistics in Japan, approximately 3,800 women die of ovarian ­cancer annually, and approximately 6,000 are affected by this disease. Ovarian cancer is ­referred to as a “silent tumor”, since patients have few subjective symptoms and by the time symptoms are observed, the cancer has progressed to Stage III or IV in about half of the patients. The basic treatment for advanced epithelial ovarian cancer is to remove as much of the tumor as possible, and subsequently to perform anticancer therapy using drugs such as cisplatin, carboplatin and paclitaxel, all of which have been shown to be effective for epi­thelial ovarian cancer. However, the 5-year survival rate in advanced ovarian cancer patients is still only about 20%, and a treatment that leads to long-term survival has yet to be developed. Here, we review the available treatments for ovarian cancer, and present the results of high-dose chemotherapy (HDC) performed in our hospital for recurrent and refractory ­ovarian cancer

Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids

International audienceThe amniote middle ear is a classical example of the evolutionary novelty. Although paleontological evidence supports the view that mammals and diapsids (modern reptiles and birds) independently acquired the middle ear after divergence from their common ancestor, the developmental bases of these transformations remain unknown. Here we show that lower-to-upper jaw transformation induced by inactivation of the Endothelin1-Dlx5/6 cascade involving Goosecoid results in loss of the tympanic membrane in mouse, but causes duplication of the tympanic membrane in chicken. Detailed anatomical analysis indicates that the relative positions of the primary jaw joint and first pharyngeal pouch led to the coupling of tympanic membrane formation with the lower jaw in mammals, but with the upper jaw in diapsids. We propose that differences in connection and release by various pharyngeal skeletal elements resulted in structural diversity, leading to the acquisition of the tympanic membrane in two distinct manners during amniote evolution

Thermostabilization by the Improvement of Intertrimeric Residues in Thermus thermophilus Inorganic Pyrophosphatase.

Inorganic pyrophosphatase (EC. 3.6.1.1) from Thermus thermophilus (Tth PPase)is a thermostable homohexamer of 174 amino acids，and its intertrimer interface is formed mainly by the symmetric α-helix A between subunits. Amino acids and their interactions composing intertrimer interface are different in hexameric Family I PPases，and then it was deduced that Tth PPase showed high thermostability because of stabilizing this interface by interactions of these residues. In this study，we focused on Thr138 and Ala141 residues in intertrimer interface of Tth PPase to confirm the relationship between intertrimeric residues and thermostability， and then improved their combination to His and Asp/Glu (HD or HE variant). As results，the HD variant showed the highest thermostability of enzyme activity，fluorescence spectra, and quaternary structure in the wild type Tth PPase and all variants. Especially，about 38% of hexamer and almost 40% of enzyme activity were observed in HD variant after heating even at 85℃. Therefore，we suggested that the conversion to a set of ionic His138 and Asp141 at intertrimer interface had increased the thermostability of Tth PPase，and then suppressed its thermal aggregation

Brexpiprazole II: Antipsychotic-Like and Procognitive Effects of a Novel Serotonin-Dopamine Activity Modulator

ABSTRACT Brexpiprazole piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel serotonin-dopamine activity modulator with partial agonist activity at serotonin 1A (5-HT 1A ) and D 2/3 receptors, combined with potent antagonist effects on 5-HT 2A , a 1B -, and a 2C -adrenergic receptors. Brexpiprazole inhibited conditioned avoidance response (ED 50 = 6.0 mg/kg), apomorphine-or D-amphetamine-induced hyperactivity (ED 50 = 2.3 and 0.90, respectively), and apomorphine-induced stereotypy (ED 50 = 2.9) in rats at clinically relevant D 2 receptor occupancies. Brexpiprazole also potently inhibited apomorphine-induced eye blinking in monkeys. The results suggest that brexpiprazole has antipsychotic potential. Brexpiprazole induced catalepsy (ED 50 = 20) well above clinically relevant D 2 receptor occupancies, suggesting a low risk for extrapyramidal side effects. Subchronic treatment with phencyclidine (PCP) induced cognitive impairment in both novel object recognition (NOR) and attentional set-shifting (ID-ED) tests in rats. Brexpiprazole reversed the PCP-induced cognitive impairment in the NOR test at 1.0 and 3.0 mg/kg, and in the ID-ED test at 1.0 mg/kg. However, aripiprazole (10 mg/kg) was ineffective in both tests, despite achieving relevant D 2 occupancies. In the NOR test

Expression of TRPV1 channels after nerve injury provides an essential delivery tool for neuropathic pain attenuation.

Increased expression of the transient receptor potential vanilloid 1 (TRPV1) channels, following nerve injury, may facilitate the entry of QX-314 into nociceptive neurons in order to achieve effective and selective pain relief. In this study we hypothesized that the level of QX-314/capsaicin (QX-CAP) - induced blockade of nocifensive behavior could be used as an indirect in-vivo measurement of functional expression of TRPV1 channels. We used the QX-CAP combination to monitor the functional expression of TRPV1 in regenerated neurons after inferior alveolar nerve (IAN) transection in rats. We evaluated the effect of this combination on pain threshold at different time points after IAN transection by analyzing the escape thresholds to mechanical stimulation of lateral mental skin. At 2 weeks after IAN transection, there was no QX-CAP mediated block of mechanical hyperalgesia, implying that there was no functional expression of TRPV1 channels. These results were confirmed immunohistochemically by staining of regenerated trigeminal ganglion (TG) neurons. This suggests that TRPV1 channel expression is an essential necessity for the QX-CAP mediated blockade. Furthermore, we show that 3 and 4 weeks after IAN transection, application of QX-CAP produced a gradual increase in escape threshold, which paralleled the increased levels of TRPV1 channels that were detected in regenerated TG neurons. Immunohistochemical analysis also revealed that non-myelinated neurons regenerated slowly compared to myelinated neurons following IAN transection. We also show that TRPV1 expression shifted towards myelinated neurons. Our findings suggest that nerve injury modulates the TRPV1 expression pattern in regenerated neurons and that the effectiveness of QX-CAP induced blockade depends on the availability of functional TRPV1 receptors in regenerated neurons. The results of this study also suggest that the QX-CAP based approach can be used as a new behavioral tool to detect dynamic changes in TRPV1 expression, in various pathological conditions

MondoA and AKI and AKI-to-CKD Transition

Maeda S., Sakai S., Takabatake Y., et al. MondoA and AKI and AKI-to-CKD Transition. Journal of the American Society of Nephrology , (2024); https://doi.org/10.1681/ASN.0000000000000414.Key PointsThe expression of MondoA was decreased in the renal tubules of patients with CKD.Genetic ablation of MondoA in proximal tubules inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon.MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the transcription factor EB-peroxisome proliferator-activated receptor-γ coactivator-1α axis.BackgroundElderly individuals and patients with CKD are at a higher risk of AKI. The transcription factor MondoA is downregulated in the kidneys of aged individuals or patients with AKI; however, its roles in AKI development and the AKI-to-CKD transition remain unknown.MethodsWe investigated the expression of MondoA in human kidney biopsy samples, ischemia-reperfusion-injured (IRI) mouse kidneys, and cultured proximal tubular epithelial cells under hypoxia/reoxygenation. The role of MondoA during the initial and recovery phases after IRI was evaluated using proximal tubule-specific MondoA knockout mice and MondoA-deficient proximal tubular epithelial cells. Furthermore, we explored the involvement of Rubicon and transcription factor EB (TFEB), both of which are downstream factors of MondoA.ResultsMONDOA expression was decreased in the renal tubules of patients with CKD. In mouse kidneys, MondoA expression was decreased under ischemia, whereas its expression was increased during reperfusion. Genetic ablation of MondoA in proximal tubular epithelial cells inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon. Ablation of Rubicon in MondoA-deficient IRI kidneys activated autophagy and protected mitochondrial function. MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the TFEB-peroxisome proliferator-activated receptor-γ coactivator-1α axis. Pharmacological upregulation of TFEB contributed to maintaining mitochondrial biogenesis and increased peroxisome proliferator-activated receptor-γ coactivator-1α transcription.ConclusionsOur findings demonstrate that MondoA protected against vulnerability to AKI by maintaining autophagy and subsequently supporting mitochondrial function to prevent progression to CKD

[その他] 地域包括ケアを担う医療従事者を対象とした 感染症対策研修会の有効性と課題

地域包括ケアを担う医療関係者が、地域で発生する感染症の実態と予防策を理解し、自施設での感染症対策に役立てることをねらいとして２日間の感染症対策研修会を企画・実施した。本稿ではその研修会の有効性と課題について検討する。訪問看護ステーション、診療所、高齢者施設の延べ70名の研修参加者に対し、研修終了後に質問紙調査を行った結果、58名から回答を得た。受講目的は「感染症対策の最新の知識や正しい知識の習得」が多く、職場における感染予防上の問題は「手指衛生、標準予防策の不徹底」や「針廃棄方法の危険性」等であった。感染症対策研修会について、役立ったと回答した者は96.6％で、感染症に対する知識の習得や針刺し予防対策、標準予防策の再認識の機会となっていた。“職場で活かせる”、“感染管理の情報が得られにくいので今回のような研修会を行ってほしい” 等の記述があったことから本研修会の有効性が示唆された。しかし、看護職者の中には、介護職者の感染予防行動や意識の低さに危機感を示した者もおり、今後対象者別の研修について検討する必要がある