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.

The purpose of this study was to compare demographic trends in the aging of the Japanese and Brazilian populations on the basis of health indicator data collected by the statistics bureaus of the Japanese and Brazilian governments. The demographic and health indicator data from surveys by the Statistics Bureaus of the Japanese and Brazilian governments and other sources were obtained from websites. The data showed that Japan has an aging population, that the number of elderly persons in Japan is increasing and that the Government of Japan has a plan to address future demands for health resources by this aging population, whereas Brazil has a rapidly population aging but no plan for its future health services. Brazil may need to increase the number of hospitals and hospital beds and develop a medical care plan for the elderly within its Unified Health System.

Histopathological and immunohistochemical studies were conducted to investigate the local existence and distribution of mast cells, fibroblasts or dendritic cells, and myofibroblasts in scleroderma, while paying particular attention to the interstices around the adnexa. The skin tissues in 15 cases of systemic scleroderma were classified histopathologically into three stages: early, fully developed, and late stage. Mesenchymal cells were distinguished immunohistochemically by 6 markers: tryptase, CD34, factor XIIIa, alpha smooth muscle actin (αSMA), vimentin, and desmin. In scleroderma, there was an increase in the number of tryptase-positive mast cells in the interstices around the adnexa. With no relation to the interstitial sites, there was a significant decrease in the number of CD34-positive cells in the late stage, and a significant increase in αSMA-positive cells in the fully developed stage, but a decrease in the late stage. Results of the present study brought about the following new findings: it was only in the mast cells that there was a significant difference in the cell distribution between the interstices around the adnexa and the interstices in non-adnexal sites. Secondly, it was suggested that mast cells, CD34-positive dendritic cells, and αSMA-positive myofibroblasts were involved in the fibrosis and shrinkage or disappearance of the adnexa when scleroderma developed.

Hepatocellular carcinoma (HCC) has a poor prognosis even after curative surgery, due to the high frequency of early intrahepatic recurrence (IHR). Conventional staging systems are almost completely inadequate, and need to be complemented by novel tools. To this end, many investigators have performed DNA microarray analysis on the basis of genome-wide information. However, so far, few studies have been able to truly account for the clinical efficacy of DNA microarray analysis in HCC. To address this dilemma, we used a supervised learning method with information of 7070 genes from 33 HCC samples, to construct a 12-gene predictor for early IHR, and then evaluated its predictive performance in 27 independent HCC samples. Our 12-gene predictor correctly predicted early IHR or non-recurrence in 25 (93%) of the 27 independent samples. This predictive value is higher than that of any other system currently available, suggesting that our system can serve as a robust tool for accurate prediction of early IHR of HCC. I emphasize in this mini-review that, although there are some technical issues to resolve prior to clinical use, DNA microarray technology can provide molecular basis to initiate “bench to bedside” translation, which cannot be easily reached with other methods.

Application of cell therapy using stem cell into intractable diseases has been noted as the medicine in the next generation taking the place of organ transplantation. Bone marrow cells have been focused as a candidate of the source of this therapy. Liver failure is a terminal state of all advanced liver diseases and thousands of patients are dying of decompensated liver cirrhosis in every year in Japan. Liver transplantation must be the strongest weapon to relieve those patients. However, particularly in Japan, liver transplantation has not been popularized. In this sense, we thought of autologous bone marrow cells transplantation for decompensated liver cirrhosis. Basic studies using animal model revealed that transplanted bone marrow cells into syngenic mouse suffering from liver cirrhosis migrated into the damaged liver and transdifferentiated to the hepatocytes. Based upon the animal studies, clinical trial of this new cell therapy supported by the Ministry of Health, Labor and Welfare is ongoing. It is early to estimate this therapy. However, free from liver failure has been observed in some cases.

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.

Aim: To evaluate the efficacy of quantitative analysis for differentiating pancreatic ductal adenocarcinoma (PDAC) and inflammatory pancreatic masses (IPM) using time intensity curve (TIC) analysis based on contrast-enhanced endoscopic ultrasonography (CE-EUS). Methods: We reviewed 89 patients who had undergone CE-EUS for pancreatic solid lesions at our department between August 2012 and January 2016. CE-EUS images were recorded for 2 minutes after injection of the contrast agent. The diagnostic abilities of the enhanced patterns and TIC analysis were assessed. Results: The enhanced patterns of PDAC were mainly hypovascular and heterogeneous (66/77), while IPM were mainly isovascular and homogeneous (6/12). In PDAC, sensitivity was 77.9%, specificity 83.3%, and accuracy was 78.7%. In TIC analysis, the intensity reduction rate was significantly different at 10 and 30 seconds after peak intensity. After creating a cutoff value (49%) based on the receiver operating characteristic curve for the intensity reduction rate after 30 seconds, diagnosing PDAC with TIC analysis had a sensitivity of 67.5%, specificity of 100%, and accuracy of 71.9%. Combining enhanced pattern analysis with TIC analysis had a sensitivity of 90.9%, pecificity of 83.3%, and accuracy of 89.9%. Conclusion: Combining TIC analysis with CE-EUS improved diagnostic accuracy when differentiating between PDAC and IPM.