In recent years, microglia have attracted attention owing to their roles in various neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Microglia, which are brain-resident macrophages, not only act as immune cells but also perform other functions in the body. Interestingly, they exert contrasting effects on different neurodegenerative diseases. In addition to the previously reported M1 (toxic) and M2 (protective) types, microglia now also include disease-associated microglia owing to a more elaborate classification. Understanding this detailed classification is necessary to elucidate the association between microglia and neurodegenerative diseases. In this review, we discuss the diverse roles of microglia in neurodegenerative diseases and highlight their potential as therapeutic targets.
Background Clinical nursing competence includes ethics, cooperation with other professionals, and management, in addition to nursing abilities and responding per situation. Therefore, it may vary depending on one’s experience and the work environment. However, there is a lack of studies exploring the competence for different experience levels. Therefore, this study aimed to clarify the association between clinical nursing competence and the work environment by experience groups.
Methods Anonymous self-administered questionnaire surveys were conducted on 717 nurses in regional core hospitals from December 2017 to March 2018. Clinical nursing competence was measured using the Clinical Nursing Competence Self-Assessment Scale (CNCSS). Association of CNCSS with experience and work environment was examined.
Results Responses from 231 nurses with 1–10 years of experience were analyzed. Compared with those in the 2-year experience group, those in the 3–5- and 6–10-year experience groups assessed their “planned development of nursing care” and “assessment of care” competencies to be higher. Additionally, compared with those in the 2-year experience group, those in the 6–10-year experience group assessed their “clinical judgment” and “care coordination” competencies to be higher. Nurses with 1 year of experience showed significant positive correlations between clinical nursing competence and “good interpersonal relationship,” “clarity about the organization’s vision,” and “ease of taking time off”; and those with 6–10 years of experience showed significant positive correlations between clinical nursing competence and “support from superiors and senior coworkers” and “established and easily accessible support system for taking time off for childcare and caregiving.”
Conclusion The relationship between clinical nursing competence and the work environment differed according to years of experience. Interventions to improve clinical nursing competence should be developed for each experience group considering the associations.
Background This study aimed to evaluate the effect of chitin nanofibers (CNF) produced from crab shells as a medical material for the knee in an osteoarthritic rat model.
Methods The effect of intra-articular CNF injection was evaluated histologically among three groups: saline, hyaluronic acid (HA), and CNF injection groups. The Osteoarthritis Research Society International (OARSI) cartilage, subchondral bone, synovial, and meniscus scores were used for scoring.
Results At 4 weeks, the CNF group had significantly lower scores than the saline group. The Synovial score was lower in HA and CNF groups at 4 weeks than in the saline group. At 4 weeks post-treatment, the thickening of the subchondral bone plate and angiogenesis were significantly reduced in the CNF treatment group compared to those in the saline treatment group (P = 0.02).
Conclusion The anti-inflammatory effects of CNF on knee osteoarthritis were comparable to that of HA in the early stages.
Background Voriconazole is an antifungal drug for which therapeutic monitoring is recommended to prevent side effects. Temporary administration of the antiemetic drug fosaprepitant remarkably decreases the plasma concentration of voriconazole from the therapeutic range. The ratio of the major metabolite voriconazole N-oxide to voriconazole exceeded that at any other time for a patient who started chemotherapy during voriconazole therapy. We attributed this unpredictable result to cytochrome P450 3A4 induced by aprepitant that was converted from fosaprepitant in vivo.
Methods Concentrations of voriconazole and voriconazole N-oxide were measured using liquid chromatography-mass spectrometry/mass spectrometry in primary human hepatocytes after incubation with aprepitant. Aprepitant suppressed voriconazole N-oxide formation within 24 h, followed by a continuous increase. Levels of drug-metabolizing cytochrome P450 mRNA were measured using real-time PCR in primary human hepatocytes incubated with aprepitant.
Results Cytochrome P450 3A4 and 2C9 mRNA levels increased ~4- and 2-fold, respectively, over time. Cytochrome P450 3A4 induction was confirmed using reporter assays. We also assessed L-755446, a major metabolite of aprepitant that lacks a triazole ring. Both compounds dose-dependently increased reporter activity; however, induction by L-755446 was stronger than that by aprepitant.
Conclusion These results indicate that aprepitant initially inhibited voriconazole metabolism via its triazole ring and increased cytochrome P450 3A4 induction following L-755446 formation. The decrease in plasma voriconazole concentration 7 days after fosaprepitant administration was mainly attributed to cytochrome P450 3A4 induction by L-755446.
Background Doxorubicin (Dox) is effective against different types of cancers, but it poses cardiotoxic side effects, frequently resulting in irreversible heart failure. However, the complexities surrounding this cardiotoxicity, especially at sublethal dosages, remain to be fully elucidated. We investigated early cellular disruptions in response to sublethal Dox, with a specific emphasis on the role of phosphorylated calcium/calmodulin-dependent protein kinase II (CaMKII) in initiating mitochondrial dysfunction.
Methods This study utilized the H9c2 cardiomyocyte model to identify a sublethal concentration of Dox and investigate its impact on mitochondrial health using markers such as mitochondrial membrane potential (MMP), mitophagy initiation, and mitochondrial calcium dynamics. We examined the roles of and interactions between CaMKII, dynamin-related protein 1 (Drp1), and the mitochondrial calcium uniporter (MCU) in Dox-induced mitochondrial disruption using specific inhibitors, such as KN-93, Mdivi-1, and Ru360, respectively.
Results Exposure to a sublethal dose of Dox reduced the MMP red-to-green fluorescence ratio in H9c2 cells by 40.6% compared with vehicle, and increased the proportion of cells undergoing mitophagy from negligible levels compared with vehicle to 62.2%. Mitochondrial calcium levels also increased by 8.7-fold compared with the vehicle group. Notably, the activation of CaMKII, particularly its phosphorylated form, was pivotal in driving these mitochondrial changes, as inhibition using KN-93 restored MMP and decreased mitophagy. However, inhibition of Drp1 and MCU functions had a limited impact on the observed mitochondrial disruptions.
Conclusion Sublethal administration of Dox is closely linked to CaMKII activation through phosphorylation, emphasizing its pivotal role in early mitochondrial disruption. These findings present a promising direction for developing therapeutic strategies that may alleviate the cardiotoxic effects of Dox, potentially increasing its clinical efficacy.
Background Cardiovascular changes during exercise are regulated by a motor volitional signal, called central command, which originates in the rostral portions of the brain and simultaneously regulates somatomotor and autonomic nervous systems. Whereas we recently elucidated mesencephalic locomotor region (MLR) neurons projecting to the rostral ventrolateral medulla as a crucial component of the central circuit responsible for transmitting central command signals, upstream circuits that regulate the MLR neurons remain unknown. Orexinergic neurons, which primarily originate from the perifornical area (PeFA) of the hypothalamus and reportedly play roles in eliciting locomotion and elevating sympathetic activity, send axonal projection to the MLR. The knowledge led us to investigate whether central command signals are relayed through orexinergic neurons projecting to the MLR.
Methods We performed anterograde transsynaptic tagging with AAV1 encoding Cre to confirm the presence of MLR neurons postsynaptic to the PeFA in rats. We also conducted retrograde neural tracing with retrograde AAV, combined with immunohistochemical staining, to examine the excitability of MLR-projecting orexinergic neurons in rats that were allowed to freely run on the wheel for 90 min.
Results A significant number of MLR neurons were labeled with Cre, indicating that PeFA neurons make synaptic contacts with MLR neurons. Moreover, immunoreactivities of Fos, a marker of neuronal excitation, were found in many MLR-projecting orexinergic neurons by voluntary wheel running exercise, compared to non-exercising control rats, especially in the intermediate-posterior, rather than anterior, and medial, rather than lateral, portions within the orexinergic neuron-distributing domain.
Conclusion The findings suggest that specifically located orexinergic neurons transmit central command signals onto the MLR for running exercise. Elucidating the role of these MLR-projecting orexinergic neurons in somatomotor control and autonomic cardiovascular control deserves further study to unveil central circuit mechanisms responsible for central command function.
Background This study aimed to evaluate the efficacy of subtraction computed tomography arteriography (s-CTA) during preoperative embolization in spinal tumors.
Methods The study analyzed 17 vertebrae in 13 patients who underwent preoperative embolization before spinal fixation surgery for malignant spinal tumors to decrease blood loss at our hospital from 2019 to 2021. Their ages ranged from 56 to 88 years (average, 73.5 years). Metastatic bone tumors were most common, including five cases originating as lung carcinomas and three as renal cancers. After digital subtraction angiography of selected tumor-feeding arteries and non-subtraction CTA (ns-CTA) were performed, s-CTA was conducted using data obtained from both procedures. A clarity score of the boundary between the normal bone and tumor was derived for each patient, which was then classified into four grades (good, 3 points; fair, 2 points; faint, 1 point; poor, 0 points) by two experienced radiologists, followed by a comparison between the s-CTA and ns-CTA groups using the Wilcoxon signed-rank test.
Results Clarity scores were significantly higher in the s-CTA group than in the ns-CTA group (P < 0.001). The agreement of Cohen’s coefficients between the two radiologists was κ = 0.724 in s-CTA scoring and κ = 0.622 in ns-CTA scoring, which were moderately matched. Seven arteries were not embolized due to insufficient tumor contrast enhancement and their poor relation to the surgical invasion zone. No complications were observed during or after embolization.
Conclusion S-CTA successfully distinguished between tumor and normal bone and may help avoid unnecessary embolization.
Isolated superior mesenteric artery dissection (ISMAD) is a rare cause of acute abdominal conditions. Most cases of ISMAD have a favorable prognosis, and only a few cases of ISMAD-associated intestinal necrosis have been reported. A 75-year-old male was referred to our department because of abdominal pain and portal venous gas detected on imaging. Computed tomography suggested ileal necrosis, necessitating emergency surgery. Indocyanine green was used for blood flow assessment; however, no fluorescence was observed in the ileum proximal to the Bauhin valve, leading to the decision for ileocecal resection. On postoperative day 6, abdominal pain recurred when meals were resumed. As a surgical intervention for ISMAD, a bypass was created using the left great saphenous vein as a graft between the superior mesenteric artery and the right external iliac artery. This case highlights a rare occurrence where intestinal necrosis recurred due to ISMAD. We propose that in cases of ISMAD with concomitant intestinal necrosis, a more aggressive revascularization strategy for the dissected segment of the superior mesenteric artery may be required.
Background Japan is reviewing how physicians operate and plans to implement a work-style reform for physicians in 2024. This study examined how outsourcing housework cleaning tasks changed the daily lives of university hospital physicians.
Methods A total of 18 physicians participated in the study, outsourcing cleaning tasks either once or thrice.
Results Fourteen out of 18 respondents reported a decrease in the burden of household chores. Additionally, 10 respondents reported having more time for family contact, and nine respondents reported having more time for their own hobbies and diversions. Meanwhile, only five respondents reported that they had more time to work.
Conclusion Outsourcing housework cleaning tasks and using the newly created time for family and self may improve work performance.