Access to high-quality care at the end-of-life is a fundamental human right; therefore, it is necessary to examine how end-of-life care should be taught in nursing education to prepare for a super-aging society. Japan and Hong Kong are both in the East Asian region and are facing similar super-aging challenges, such as increased mortality and declining birth rates. This paper explores the literature on this topic and discusses how end-of-life care is taught in undergraduate nursing education in both Japan and Hong Kong. A comprehensive literature search was performed using end-of-life care keywords. Subsequently, the authors engaged in a discourse on expert perspectives, insights, and results from the literature. It is necessary to bridge the gap between the desired manner of spending oneʼs final days and the practical reality of considering patientsʼ best interests by referring to the existing policies, laws, guidelines, and frameworks of healthcare systems. This study suggests the importance of understanding patientsʼ views on life, death, values, and cultural backgrounds and educating healthcare personnel to apply these principles flexibly in their practice.

I, Professor Nobuaki Tanaka, gave a Farewell Lecture on February 29, 2024. First, I talked about the episode that led me to start researching aortic stenosis, and reflected on my own lectures on this topic to students aiming to become medical laboratory scientist. Lastly, I spoke to students majoring in medical laboratory scientist about the importance of practical clinical training.

Dementia, a leading cause of death, often initiates with spatial cognitive impairment. Assisting spatial cognition may not only address challenges faced by individuals with spatial cognitive impairment but also facilitate the prevention of dementia. While previous studies have explored voice navigation for the visually impaired, its utility for those without visual impairment remains unexamined. To provide insights for spatial navigation in the elderly, in the present study, we evaluated the usefulness of voice navigation in healthy university students. In a randomized controlled trial, forty students were assigned to either a paper map only group or a paper map and Google Maps voice navigation group and instructed to navigate a predetermined 800-meter route in a park. The effectiveness of voice navigation was evaluated through various means, including time taken to reach the destination, accuracy of the route followed, and participantsʼ experience. The results show that the two groups did not differ in terms of goal completion and time consumed. Nor did they differ in feelings of drowsiness, instability, uneasiness, pleasure, and relaxation. However, participants in the paper map only group demonstrated a decrease in local pain and eyestrains together with improved feelings of vigor at the goal compared to the start, which was absent in participants using both paper map and voice navigation. Although the effectiveness of the voice navigation was not confirmed, our study did provide important insights regarding in what ways voice navigation can be improved. Moreover, we were able to observe mood improvements in participants with a paper map only, which may indicate the effect of physical activity and exposure to the natural environment.

Purpose: We investigated sex differences in heart rate variability (HRV; a non-invasive indicator of autonomic nervous system) and its frequency-specific responses to whole-body vibration (WBV) at three distinct frequencies among elderly subjects. Methods: Data from 11 males and 13 females were analyzed across four randomized sessions of exposure: WBV at 15, 20, or 25 Hz with a 4 mm peak-to-peak displacement, or control (0 Hz) condition comprising three bouts of 1-minute exposure with 1-minute between-bout rests. HRV measurements were taken before and during the exposure. Results: At baseline, low-frequency power/LF (ms^{2}) were significantly lower in females than males (P < 0.05). During exposure, LF (ms^{2}), high-frequency power (ms^{2}), standard deviation of normal-to-normal intervals, root mean square of successive differences between RR intervals, standard deviation of the Poincaré plot perpendicular to the line-of-identity, and standard deviation of the Poincaré plot along the line-of-identity significantly increased at 20 Hz for males and 25 Hz for females (P < 0.05 to 0.005) compared to respective baselines. Conclusions: Elderly females tend to exhibit reduced autonomic nervous system function compared to males. Furthermore, our results indicate that WBV at 20 Hz for males and 25 Hz for females may be considered beneficial for enhancing HRV in the elderly.

This study investigated the potential of adalimumab (ADA), a monoclonal antibody targeting TNF-alfa, to protect the inner ear from intense sound exposure, given that inflammatory cytokines, including TNF-alfa, are linked to hearing loss in acoustic disorders. In this study, adalimumab was administered to mice, and its effect on the inner ear was assessed. We examined the translocation of ADA to the inner ear and its ototoxicity and impact on acoustic exposure. The results showed that adalimumab partially reached the cochlea after administration but increased the susceptibility to acoustic exposure, resulting in higher hair cell loss in the inner ear. While TNF-alfa had been considered a potential therapeutic target, the results suggested that excessive TNF-alfa suppression could harm the inner ear. We acknowledged some limitations, such as the use of adalimumab instead of an anti-mouse TNF-alfa antibody and the need to explore the suppression of other cytokines for better inner ear protection. In conclusion, adalimumab administration was found to increase the inner earʼs susceptibility to acoustic exposure, potentially leading to more significant hair cell damage, possibly due to excessive TNF-alfa suppression.

Vestibular hair cells are susceptible to damage from various stimuli such as infections, ischemia, and certain therapeutic drugs, including aminoglycoside antibiotics and the antineoplastic agent cisplatin. In mammals, damage to the vestibular hair cells is permanent. This study aimed to evaluate the protective effects of nobiletin (NOB) against aminoglycoside-induced hair cell death using utricles collected from adult mice. The utricles removed from CBA/N mice were assigned to eight groups according to the dose of NOB and the administration or not of neomycin. Hair cells in the utricles were counted by double labeling with calmodulin and calbindin. NOB inhibited hair cell death in utricles exposed to neomycin. The protective effect of NOB on hair cells in the utricles was also suggested to have resulted from the inhibition of the production and accumulation of 4-hydroxy-2-nonenal, the final product of lipid peroxide aldehyde. NOB suppressed neomycin-induced hair cell death. The principle of hair cell protection from aminoglycoside-induced hair cell death suggests that NOB inhibits reactive oxygen species formation in the utricles exposed to neomycin.

Objective: The objective was to explore the potential existence and nature of the relationship between serum of uric acid (SUA) and serum uric acid to serum creatinine ratio (SUA/SCr) with reduced estimated glomerular filtration rate (eGFR) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: A cross-sectional study was conducted among apparently healthy subjects with NAFLD (n=485). The association between tertiles of SUA and SUA/SCr with reduced eGFR (n=56) were investigated after adjustments for potentially relevant confounders. Also, the diagnostic performances of SUA and SUA/SCr were evaluated with the receiver operating characteristic (ROC) curve analysis. Results: In the adjusted models, SUA showed a significant positive association with reduced eGFR in the highest tertile (OR 5.65, 95% CI 2.48-12.86, p<0.001), and SUA/SCr, in the lowest tertile (4.21, 95% CI 1.76-10.07, p=0.001). The ROC curve analysis did not reveal any significant difference between the corresponding values of area under the curve for SUA and SUA/SCr (0.70 and 0.67, respectively; p=0.521). Conclusions: We revealed significant and independent associations of elevated SUA and reduced SUA/SCr with kidney function decline in NAFLD. However, the clinical utility of these two biomarkers seemed to be limited for the mentioned purpose and needs further investigations.

Benign paroxysmal positional vertigo (BPPV) is the most common vertigo disease and is more likely to occur in perimenopausal women, suggesting an association with osteoporosis. Since otoconia are primarily composed of calcium carbonate, abnormal calcium metabolism may lead to otoconia dislocation. However, the detailed mechanism is currently unknown. In this study, we investigated the effects of drugs (cadmium and dexamethasone) that cause abnormal calcium metabolism on otolith formation in zebrafish larvae. Here, otolith size was clearly reduced in the cadmium group, and the calcium content of the larvae was also markedly reduced. In contrast, in the dexamethasone group, which also had a lower calcium content than the control group, otolith size increased. Our results suggest that, as in bone, calcium metabolism influences the repeated dissolution and recrystallization of otoliths and maintains homeostasis in response to calcium concentrations in the endolymphatic fluid.

Native English scholarly writers use interactional metadiscourse markers in their research articles to indicate their stance and negotiate their claims with readers. Hedges are a type of interactional metadiscourse marker often used in scientific research articles to soften writers’ claims and protect themselves from criticism (Hyland, 2005a). When Japanese researchers write research articles in English, they tend to use fewer English hedges than native English writers. Although hedges are used in research articles written in Japanese, their usage appears to differ from that of English hedges. This study analyses the use of hedges in research articles by Japanese writers in both English and Japanese in comparison with English hedges employed by native English writers in order to reveal the differences in the use of hedges between the two languages. The analysis focuses not only on the discrepancies in usage between native English and Japanese writers, but also on the characteristics of hedges used in academic articles written in English and Japanese. Furthermore, this study investigates the impact of Japanese writers’ first language on their use of English hedges in articles written in English. A total of 30 published empirical research articles in soft science disciplines in English and Japanese were used for the quantitative and qualitative analyses of the use of hedges, revealing both the writing and linguistic differences between the two languages. Thus, this study aims to offer pedagogical suggestions for Japanese learners of English to use hedges more effectively in their research papers written in English.

Right ventricular (RV) dysfunction and its linked arrhythmias play a crucial role in determining the prognosis of pulmonary arterial hypertension (PAH). Our paper aimed to explore the potential protective effects of direct pharmacological intervention in the RV muscle using dantrolene (DAN), a stabilizer of the cardiac ryanodine receptor (RyR2), against RV dysfunction and arrhythmia in a rat model of monocrotaline (MCT)-induced PAH. To induce PAH, male 8-week-old Sprague-Dawley rats received MCT injections. The study also assessed the induction of ventricular tachycardia (VT) by catecholamines, examining RyR2-mediated Ca^{2+} release properties in isolated cardiomyocytes. Additionally, a pulmonary artery-banding model was established to evaluate the independent effects of chronic pressure overload on RV morphology and function. In the MCT-induced PAH rat model, findings revealed RV hypertrophy, dilation, and functional decline, resulting in 0% survival rate two months post-MCT induction. Conversely, chronic DAN treatment demonstrated improvements in these RV parameters and an 80% increase in survival. Furthermore, chronic DAN treatment prevented the dissociation of calmodulin from RyR2, inhibiting Ca^{2+} sparks and spontaneous Ca^{2+} transients in MCT-induced hypertrophied RV cardiomyocytes. Epinephrine induced VT in over 50% of rats with MCT-induced PAH, while chronic DAN treatment achieved complete suppression of VT. The paper concludes that stabilizing RyR2 with DAN holds promise as a novel therapeutic approach against the development of RV dysfunction and fatal arrhythmias associated with PAH.

To investigate whether dantrolene (DAN), cardiac ryanodine receptor (RyR2) stabilizer, improves impaired diastolic function in an early pressure-overloaded hypertrophied heart, pressure-overload hypertrophy was induced by transverse aortic constriction (TAC) in mice. Wild-type (WT) mice were divided into four groups: sham-operated mice (Sham), sham-operated mice treated with DAN (DAN+Sham), TAC mice (TAC), and TAC mice treated with DAN (DAN+TAC). The mice were then followed up for 2 weeks. Left ventricular (LV) hypertrophy was induced in TAC, but not DAN+TAC mice, 2 weeks after TAC. There were no differences in LV fractional shortening among the four groups. Catheter tip micromanometer showed that the time constant of LV pressure decay, an index of diastolic function, was significantly prolonged in TAC but not in DAN+TAC mice. Diastolic function was significantly impaired in TAC, but not in DAN+TAC mice as determined by cell shortening and Ca^{2+} transients. An increase in diastolic Ca^{2+} leakage and a decrease in calmodulin (CaM) binding affinity to RyR2 were observed in TAC mice, while diastolic Ca^{2+} leakage improved in DAN+TAC mice. Thus, DAN prevented the progression of hypertrophy and improved the impairment of LV relaxation by inhibiting diastolic Ca^{2+} leakage through RyR2 and the dissociation of CaM from RyR2.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in the cardiac type 2 ryanodine receptor (RyR2). Using knock-in mouse (KI) model (R2474S/+), we previously reported that a single point mutation within the RyR2 sensitized the channel to agonists, primarily mediated by defective inter-domain interaction within the RyR2 and subsequent dissociation of calmodulin (CaM) from the RyR2. Here, we examined whether CPVT can be genetically rescued by enhancing the binding affinity of CaM to the RyR2. We first determined whether there was a possible amino-acid substitution within the CaM-binding domain in the RyR2 (3584-3603) that can enhance its binding affinity to CaM, and found that V3599K substitution showed the highest binding affinity of CaM to CaM-binding domain. Hence, we generated a heterozygous KI mouse model (V3599K/+) with a single amino acid substitution in the CaM-binding domain of the RyR2, and crossbred it with the heterozygous CPVT –associated R2474S/+ KI mouse to obtain a double heterozygous R2474S/V3599K KI mouse model. The CPVT phenotypes, bidirectional or polymorphic ventricular tachycardia, were inhibited in the R2474S/V3599K mice. Thus, enhancement of the CaM binding affinity of the RyR2 is essential to prevent CPVT-associated arrhythmogenesis.

Abstract Background: Expanding nursing workload is a worldwide problem. However, any nursing workload assessment (NWA) tool requires complicated analyses of the nursing job profile. To determine the imbalance in time assignments across all nursing operations and to reduce nursing workload, a nursing job survey was conducted. Methods: A total of 25 major job categories, common to all hospital wards, were identified, and an NWA tool was developed for efficient analyses to feature easy/flexible entry of the time spent for each job category and real-time visual profiling of job time allocation. The profile could be divided by job categories, wards, shifts, and years. Results: From the preliminary analyses, undesirable time allocation was revealed in several job categories, especially the time for recording and other nonessential nursing operations. Using the analytical functions of the NWA tool between 2014 and 2016, a series of corrective measures were successfully taken to many job categories, and they were found to be effective. Consequently, excessive overtime workload was reduced from 125 min/day/nurse in 2014 to 100 and 100 min/day/ nurse in 2015 and 2016, respectively. Conclusion: Notable improvements in nursing workload and time allocation for attentive patient care could be achieved employing the novel user-aimed NWA tool.

Abstract Purpose: The purpose of this study was to investigate the effects of two different postures (sitting and standing) and three different ambient temperatures (10℃, 20℃, and 30℃) on heart rate variability (HRV) among healthy young adults. Methods: Twelve young adult volunteers (males 6, females 6) were recruited. Following acclimatization to any the room temperature (10℃, 20℃ or 30℃), 5-min measurements of HRV were conducted in sitting and standing postures of the subjects. Results: Compared to the sitting posture, measurements obtained in the standing posture revealed a significant decrease in high-frequency power/HF, root mean square of successive differences between RR intervals, standard deviation of Poincaré plot perpendicular to the line-of-identity or SD1 and SD1/standard deviation of Poincaré plot along the line-of-identity or SD2, and a significant increase in lowfrequency power/LF and LF/HF under all experimental conditions (p<0.05 to 0.005). Majority of HRV parameters showed significant differences while the values obtained under 10℃ were compared with 20℃ and 30℃ conditions, respectively (p<0.05 to 0.001). Conclusions: Our findings suggest the predominance of sympathetic tone in the standing compared with sitting posture. Furthermore, colder conditions caused a predominance of the parasympathetic activity in both sitting and standing postures, and such effects of ambient temperature on the sympathovagal balance were stronger in the latter posture.

Abstract Background: Recently, the importance of nutritional management in pressure ulcer control has been pointed out. In this study, we analyzed the relationship between nutritional indicators and the presence or absence of pressure ulcers in order to reveal the importance of nutritional management in pressure ulcer control. Method: We investigated 407 inpatients for blood tests, height, weight, BMI, the Ohura-Hotta (OH) scale, nutrition method, living independence, and the presence or absence of pressure ulcers. Results: In the comparison of patients with and without pressure ulcer, significant differences were found in gender, nutrition method, serum total protein, serum albumin, hemoglobin concentration, and the OH scales. Multiple logistic regression analysis showed that gender, intravenous nutrition, serum albumin levels, and the OH scale were associated with the presence or absence of pressure ulcers. The results suggest that not only the OH scale, but the nutritional support was also important in the prediction of the pressure ulcer. It was suggested that shifting from intravenous feeding to tube feeding or oral feeding is important. Conclusion: we found that pressure ulcer was related to gender, intravenous nutrition, serum albumin level and the OH scale. The importance of nutritional management for pressure ulcer prevention was confirmed.

Abstract Objectives: This study examined the short-term outcomes of endovascular therapy (EVT) with the GORE VIABAHN VBX (VBX) which is a balloon-expandable covered stent in patients with aortoiliac occlusive disease (AIOD) and acute limb ischemia (ALI). Methods: This was a single-center retrospective review of patients with AIOD and ALI who underwent EVT with the VBX between December 2018 and January 2021. Primary, assisted, and secondary patency rates were assessed, along with 30-day mortality rates. Results: Twenty-two patients underwent EVT with the VBX; 18 patients had AIOD, whereas 4 had ALI. The incidence of TransAtlantic Intersociety Classification II D lesions was 50% (n=9). Technical success was 100%. One patient with unilateral common iliac artery stenosis developed an intraoperative dissection of the distal edge of the VBX, which required an additional self-expanding VIABAHN stent on the distal edge of the VBX. The primary patency rate at 24 months was 100%. No patients required additional target vessel treatment at a median follow-up of 10 months (range, 1-27). EVT was also successful in the four patients with ALI, who had no complications of the target vessel. Conclusion: The present study demonstrated that EVT with the VBX is effective for AIOD and ALI.

Incontinentia pigmenti (IP; OMIM# 308300) is a rare inherited disease caused by a mutation of IKBKG, which is also known as NEMO, located on Xq28. IP patients usually present with abnormalities of skin, eyes, nails and central nervous system. The neurological damege, which occur usually from neonatal through the early infantile period, leads to neulogical complication such as development retardation, motor paralysis and epilepsy. However, there has been little study done concerning the effect of therapy for the neural abnormalities. We have investigated the clinical findings in a female IP case with a novel mutation of IKBKG for six years due to disclosing the neurological prognosis and the immunological features. It is hoped that the present study will contribute to a better management of IP patients.

The hippocampal dentate gyrus has been identified to play a critical role in maintaining contextual memory in many mammalian species. To evaluate learninginduced synaptic plasticity of granule cells, we subjected male rats to an inhibitory avoidance (IA) task and prepared acute hippocampal slices. In the presence of 0.5 μM tetrodotoxin, we recorded miniature excitatory post synaptic currents (mEPSCs) and inhibitory post synaptic currents (mIPSCs) in male rats experiencing four groups: untrained, IA-trained, unpaired, and walk-through. Compared with the untrained, IA-trained, unpaired, and walk-through groups, the unpaired group significantly enhanced mean mEPSC amplitudes, suggesting the experience-induced plasticity at AMPA receptor-mediated excitatory synapses. For inhibitory synapses, both unpaired and walk-through groups significantly decreased mean mIPSC amplitudes, showing the experience-induced reduction of postsynaptic GAB A_{A} receptor-mediated currents. Unlike the plasticity at CA1 synapses, it was difficult to explain the learning- specific plasticity at the synapses. However, overall multivariate analysis using four variables of mE(I)PSC responses revealed experience-specific changes in the diversity, suggesting that the diversity of excitatory/inhibitory synapses onto granule cells differs among the past experience of animals include the learning. In comparison with CA1 pyramidal neurons, granule cells consistently showed greater amplitude and frequency of mE(I)PSCs. Fluctuation analysis further revealed that granule cells provide more postsynaptic AMPA receptor channels and greater single-channel current of GABA_{A} receptors of than CA1 pyramidal neurons. These findings show functional differences between two types of principal cells in the hippocampus.

Androgen receptor (AR)-signaling plays an important role in promoting tumor cell survival and the development of castration-resistant prostate cancer (CRPC). Androgen deprivation therapy is the basic therapeutic strategy for AR signaling blockade, but that effects wonʼt last long and most of metastatic prostate cancer show castration resistance. Recently, new agents, AR Axis Targeted agents (ARAT), have been developed. We have been developing our bench-to-bedside translational research to elucidate the mechanisms of drug resistance in prostate cancer. This review describes our investigational results and recent advances in CRPC with ARAT treatment strategy.