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Single-molecule fluorescence imaging of DNA origami-based transporters showed shorter run lengths in dence layouts of kinesin motors.

Purpose For patients with aortic dissection (AD) and intramural hematoma (IMH), the optimal cardiac phase to detect intimal tears (IT) and ulcer-like projections (ULP) on retrospective electrocardiogram (ECG)-gated computed tomography angiography (CTA) remains unclear. The purpose of this study was to compare the accuracy of retrospective ECG-gated CTA for detecting IT in AD and ULP in IMH between each cardiac phase. Materials and methods A total of 75 consecutive patients with AD and IMH of the thoracic aorta were enrolled in this single-center retrospective study. The diagnostic performance to detect IT and ULP in the thoracic aortic regions (including the ascending aorta, aortic arch, and proximal and distal descending aorta) was compared in each cardiac phase on retrospective ECG-gated CTA. Results In the systolic phase (20%), the accuracy, sensitivity, and specificity to detect IT in AD was 64% (95% confidence interval [CI] 56–72%), 69% (95%CI 60–78%), and 25% (95%CI 3.3–45%), respectively. In the diastolic phase (70%), the accuracy, sensitivity, and specificity to detect IT in AD was 52% (95%CI 43–60%), 52% (95%CI 42–61%), and 50% (95%CI 25–75%), respectively. The accuracy to detect IT in AD on ECG-gated CTA was significantly higher in the systolic phase than that in the diastolic phase (P = 0.025). However, there were no differences in the accuracy (83%; 95%CI 78–89%), sensitivity (71%; 95%CI 62–80%), or specificity (100%; 95%CI 100%) to detect ULP in IMH between the cardiac cycle phases. Conclusion Although it is currently recommended for routine diagnosis of AD and IMH, single-diastolic-phase ECG-gated CTA has risk to miss some IT in AD that are detectable in the systolic phase on full-phase ECG-gated CTA. This information is critical for determining the optimal treatment strategy for AD.

pUC18 and pUC19 are well-known high copy-number plasmid vectors routinely used for DNA cloning purposes. We show here that, in Escherichia coli transformed by native pUC18, the α-complementation of β-galactosidase (i.e., mediated by the peptide LacZα18) is intrinsically weak and slow, but is greatly stimulated by the DnaK/DnaJ/GrpE chaperone system. In contrast, the α-complementation mediated by the peptide LacZα19 (in E. coli transformed by the native pUC19) is much more efficient and therefore does not require the assistance of the DnaK chaperone machinery. The marked difference between these two LacZα peptides is reproduced in a cell-free protein expression system coupled with α-complementation. We conclude that: (i) α-complementation of β-galactosidase is DnaK-mediated depending upon the LacZα peptide donor; (ii) DnaK, sensu stricto, is not necessary for α-complementation, but can enhance it to a great extent; (iii) this observation could be used to establish an easy and inexpensive method for screening small molecules libraries in search of DnaK inhibitors and also for deciphering the DnaK-mediated protein quality control mechanism.

Objectives To assess whether systemic-pulmonary collaterals are associated with clinical severity and extent of pulmonary perfusion defects in chronic thromboembolic pulmonary hypertension (CTEPH). Methods This prospective study was approved by a local ethics committee. Twenty-four patients diagnosed with inoperable CTEPH were enrolled between July 2014 and February 2017. Systemic-pulmonary collaterals were detected using pulmonary vascular enhancement on intra-aortic computed tomography (CT) angiography. The pulmonary enhancement parameters were calculated, including (1) Hounsfield unit differences (HUdiff) between pulmonary trunks and pulmonary arteries (PAs) or veins (PVs), namely HUdiff-PA and HUdiff-PV, on the segmental base; (2) the mean HUdiff-PA, mean HUdiff-PV, numbers of significantly enhanced PAs and PVs, on the patient base. Pulmonary perfusion defects were recorded and scored using the lung perfused blood volume (PBV) based on intravenous dual-energy CT (DECT) angiography. Pearson’s or Spearman’s correlation coefficients were used to evaluate correlations between the following: (1) segment-based intra-aortic CT and intravenous DECT parameters (2) patient-based intra-aortic CT parameters and clinical severity parameters or lung PBV scores. Statistical significance was set at p < 0.05. Results Segmental HUdiff-PV was correlated with the segmental perfusion defect score (r = 0.45, p < 0.01). The mean HUdiff-PV was correlated with the mean pulmonary arterial pressure (PAP) (r = 0.52, p < 0.01), cardiac output (rho = − 0.41, p = 0.05), and lung PBV score (rho = 0.43, p = 0.04). And the number of significantly enhanced PVs was correlated with the mean PAP (r = 0.54, p < 0.01), pulmonary vascular resistance (r = 0.54, p < 0.01), and lung PBV score (rho = 0.50, p = 0.01). Conclusions PV enhancement measured by intra-aortic CT angiography reflects clinical severity and pulmonary perfusion defects in CTEPH. Key Points • Intra-aortic CT angiography demonstrated heterogeneous enhancement within the pulmonary vasculature, showing collaterals from the systemic arteries to the pulmonary circulation in CTEPH. • The degree of systemic-pulmonary collateral development was significantly correlated with the clinical severity of CTEPH and may be used to evaluate disease progression. • The distribution of systemic-pulmonary collaterals is positively correlated with perfusion defects in the lung segments in CTEPH.

Many studies of the reconstitution of the Escherichia coli small ribosomal subunit from its individual molecular parts have been reported, but contrastingly, similar studies of the large ribosomal subunit have not been well performed to date. Here, we describe protocols for preparing the 33 ribosomal proteins of the E. coli 50S subunit and demonstrate successful reconstitution of a functionally active 50S particle that can perform protein synthesis in vitro. We also successfully reconstituted both ribosomal subunits (30S and 50S) and 70S ribosomes using a full set of recombinant ribosomal proteins by integrating our developed method with the previously developed fully recombinant-based integrated synthesis, assembly and translation. The approach described here makes a major contribution to the field of ribosome engineering and could be fundamental to the future studies of ribosome assembly processes.

Background The mortality rates of coronavirus disease 2019 (COVID-19) have been changed across the epidemiological waves. The aim was to investigate the differences in mortality rates of COVID-19 patients in Japan across the 6 epidemiological waves stratified by age group and Coronavirus Clinical Characterisation Consortium (4C) mortality score risk group. Methods A total of 56 986 COVID-19 patients in the COVID-19 Registry Japan from 2 March 2020 to 1 February 2022 were enrolled. These patients were categorized into 4 risk groups based on their 4C mortality score. Mortality rates of each risk group were calculated separately for different age groups: 18–64, 65–74, 75–89, and ≥90 years. In addition, mortality rates across the wave periods were calculated separately in 2 age groups: Results The mortality rates of patients in Japan were significantly lower than in the UK across the board, with the exception of patients aged ≥90 years at very high risk. The mortality rates of patients aged ≥75 years at very high risk in the fourth and fifth wave periods showed no significant differences from those in the UK, whereas those in the sixth wave period were significantly lower in all age groups and in all risk groups. Conclusions The present analysis showed that COVID-19 patients had a lower mortality rate in the most recent sixth wave period, even among patients ≥75 years old at very high risk.

IntroductionFew clinical trials have examined the effects of home-based exercise programmes on health-related quality of life (HR-QoL) in older adults with frailty. Radio-Taiso is the most famous exercise programme in Japan. A home-based Radio-Taiso exercise programme may serve as an accessible, scalable and sustainable care intervention for older adults with frailty. The primary aim of this trial is to test whether older adults with frailty who are prescribed our home-based Radio-Taiso exercise programme will receive greater benefits for HR-QoL compared with those who are not prescribed the exercise programme. Potential mechanisms underlying the effectiveness of the programme and the effects of the programme on daily lifestyle will also be investigated.Methods and analysisThis assessor-blind randomised controlled trial will be conducted at the Tokyo Metropolitan Institute of Gerontology (TMIG) in Itabashi-ku, Tokyo, Japan. From April to May 2022, 226 older adults with prefrailty or frailty according to the revised Japanese version of the Cardiovascular Health Study criteria will be included from a large database. After a baseline assessment in June 2022, participants will be randomly assigned to the intervention (home-based Radio-Taiso exercise and nutrition programme) or control (nutrition programme) groups at a 1:1 ratio. After intervention completion, a follow-up assessment will be conducted in September 2022. The primary outcome is the change in the mental domain of HR-QoL assessed using SF-36. Secondary outcomes include physical and role/social domains and subscales of HR-QoL, frailty phenotype, physical fitness, posture, cognition, exercise self-efficacy, depressive symptoms, brain-derived neurotrophic factor, social network, habitual energy intake, physical activity and sleep conditions.Ethics and disseminationThe Research Ethics Committee of TMIG has approved the research protocol. This trial will be conducted in accordance with the principles of the Declaration of Helsinki. The findings will be presented at international academic conferences and published in peer-reviewed international journals.Trial registration numberUMIN000047229.

Arsenic (As) and heavy metals (Cd, Hg, Pb, and Cu) and pesticide residues in 14 edible insects were investigated. The maximum levels of elements were 6.15 for As, 0.82 for Cd, 0.50 for Hg, 0.67 for Pb, and 297.7 ppm for Cu. Fenobucarb (or BPMC) has been quantified through GC- and LC-MS/MS analysis at a concentration of approximately 3 ppm. Further studies of the contaminants may help ensure the safety of edible insect consumption.

Purpose:To develop a deep learning (DL)-based algorithm to predict the presence of stromal invasion of breast cancer on digital breast tomosynthesis (DBT).Materials and Methods:The institutional review board approved this retrospective study and waived the requisite to obtain the informed consent from the patients. Initially, 499 patients (mean age of 50.5 years, ranging from 29 to 90 years) who were referred to our hospital suggestive of breast cancer and performed DBT between March 1, 2019 and August 31, 2019, were enrolled in this study. Out of the 499 patients, 140 patients who were performed surgery with diagnosed breast cancer were finally selected. Based on the pathological reports, 140 patients were divided to be categorized as 20 patients with non-invasive cancer and 120 patients with invasive cancer. Xception architecture was used for the DL model to differentiate non-invasive cancer and invasive cancer. Diagnostic performance of the DL model was assessed by accuracy, sensitivity, specificity, and areas under the receiver operating characteristic curve (AUC).Results:The average accuracy, sensitivity, specificity, and AUC were 0.897, 0.909, 0.758, and 0.749, respectively.Conclusion:The proposed DL model trained on DBT images is useful to predict the presence of stromal invasion of breast cancer.Secondary abstractThe proposed deep learning (DL) model trained on digital breast tomosynthesis (DBT) images is useful to predict the presence of stromal invasion of breast cancer.

Background: High-resolution medical images often need to be downsampled because of the memory limitations of the hardware used for machine learning. Although various image interpolation methods are applicable to downsampling, the effect of data preprocessing on the learning performance of convolutional neural networks (CNNs) has not been fully investigated. Methods: In this study, five different pixel interpolation algorithms (nearest neighbor, bilinear, Hamming window, bicubic, and Lanczos interpolation) were used for image downsampling to investigate their effects on the prediction accuracy of a CNN. Chest X-ray images from the NIH public dataset were examined by downsampling 10 patterns. Results: The accuracy improved with a decreasing image size, and the best accuracy was achieved at 64 × 64 pixels. Among the interpolation methods, bicubic interpolation obtained the highest accuracy, followed by the Hamming window.

Objectives When local governments and community nurses provide support for community-based activities led by older residents, it is imperative to reduce the burden of participants in leadership positions. This study aimed to identify the issues associated with the activities by social position, such as leadership, support, and regular participation, to discuss effective support for community-based activities and to examine the association between social position, relating issues, and psychosocial health.Methods Participants in community-based activities were recruited by the local government in Tokyo, Japan. Overall, 2,367 people from 155 activity groups from 40 municipalities responded. Social positions in the groups were defined as leaders who manage activities; supporters who support leaders; and regular members who do not have any specific role. The participants chose the issues of community-based activities from 10 items. Psychosocial health was measured by the WHO-5 well-being index (WHO-5) and Lubben social network scale-6 (LSNS-6). The relationship between recognition of issues and social positions were examined by the chi-square test. Interaction effects of social positions and issues (with or without) on the WHO-5 and LSNS-6 were investigated using a two-way analysis of covariance.Results The final sample comprised 2,096 respondents: 174 leaders, 296 supporters, and 1,626 regular members. There was a significant association between recognition of social positions and issues in the groups: respondents who reported no issues in the activities comprised 8.6% of the leaders, 27.7% of the supporters, and 53.6% of the regular members (P0.001). There was a large difference in recognition between roles for issues related to group management, such as the lack of management members. There was no significant interaction between these issues and social positions in either WHO-5 or LSNS-6 (P=0.729, P=0.171, respectively). The main effect of the social positions was significant in both analyses (P0.001). The leaders and supporters showed significantly higher WHO-5 and LSNS-6 scores than regular members.Conclusion The issues that the participants reported differed by social positions in activities. It may be effective to provide support according to the difficulty of sharing issues within the group. Regardless of whether or not the participants report issues, leaders and supporters had improved psychosocial health than regular members. The study concludes that organizational position in community-based activities may offer health benefits for older adults.

The purpose of this study was to develop a deep learning model to diagnose breast cancer by embedding a diagnostic algorithm that examines the asymmetry of bilateral breast tissue. This retrospective study was approved by the institutional review board. A total of 115 patients who underwent breast surgery and had pathologically confirmed breast cancer were enrolled in this study. Two image pairs [230 pairs of bilateral breast digital breast tomosynthesis (DBT) images with 115 malignant tumors and contralateral tissue (M/N), and 115 bilateral normal areas (N/N)] were generated from each patient enrolled in this study. The proposed deep learning model is called bilateral asymmetrical detection (BilAD), which is a modified convolutional neural network (CNN) model of Xception with two-dimensional tensors for bilateral breast images. BilAD was trained to classify the differences between pairs of M/N and N/N datasets. The results of the BilAD model were compared to those of the unilateral control CNN model (uCNN). The results of BilAD and the uCNN were as follows: accuracy, 0.84 and 0.75; sensitivity, 0.73 and 0.58; and specificity, 0.93 and 0.92, respectively. The mean area under the receiver operating characteristic curve of BilAD was significantly higher than that of the uCNN (p = 0.02): 0.90 and 0.84, respectively. The proposed deep learning model trained by embedding a diagnostic algorithm to examine the asymmetry of bilateral breast tissue improves the diagnostic accuracy for breast cancer.

Objectives A recent long-term care insurance policy encourages the promotion of various types of "Kayoi-no-ba," or places to go, not limited to those focusing on functional training, as resident activities are expected to keep older adults from needing care. In this study, Kayoi-no-ba were voluntary groups in which older adults participated, and their attributes were examined in terms of "diversity of participants" and "autonomy of community residents," based on the type of group.Methods The staff from the preventing long-term care division in each of the 38 municipalities in Tokyo selected 175 voluntary groups that met three criteria: (1) more than three community residents participate in activities at least once a month, (2) participants are primarily older adults or multi-generational residents including older adults, and (3) community residents participate in group management. Representatives from 165 groups responded to the questionnaire. For the group categorization, a latent class analysis was performed using the goals and activities of the group. Participants' age, gender, and health status were used to assess diversity. The number of residents who managed and/or supported group activities and the precise role the residents played in the activities were used to assess autonomy.Results The groups were categorized into four types: "Physical Exercises," where the primary activity was physical exercise; "Multi-purpose," which included various purposes and activities; "Social Interaction Oriented," where interaction with others was the goal, but physical exercise was not; and "Non-Interaction," where social interaction was not the goal. Participants in the Multi-purpose group ranged in age and were more likely to have health problems, such as mobility limitations, dementia, and frailty, than those in the Physical Exercises and Social Interaction Oriented groups. Moreover, the Multi-purpose group had more resident managers and supporters involved in various roles.Conclusion The Multi-purpose group had the most diverse participants and autonomy of residents. However, the type of Kayoi-no-ba should not be considered fixed. The support system should encourage flexible changes such as adding a new activity depending on the situation and the varying needs of the residents.

Mammalian mitochondria have their own dedicated protein synthesis system, which produces 13 essential subunits of the oxidative phosphorylation complexes. We have reconstituted an in vitro translation system from mammalian mitochondria, utilizing purified recombinant mitochondrial translation factors, 55S ribosomes from pig liver mitochondria, and a tRNA mixture from either Escherichia coli or yeast. The system is capable of translating leaderless mRNAs encoding model proteins (DHFR and nanoLuciferase) or some mtDNA-encoded proteins. We show that a leaderless mRNA, encoding nanoLuciferase, is faithfully initiated without the need for any auxiliary factors other than IF-2mt and IF-3mt. We found that the ribosome-dependent GTPase activities of both the translocase EF-G1mt and the recycling factor EF-G2mt are insensitive to fusidic acid (FA), the translation inhibitor that targets bacterial EF-G homologs, and consequently the system is resistant to FA. Moreover, we demonstrate that a polyproline sequence in the protein causes 55S mitochondrial ribosome stalling, yielding ribosome nascent chain complexes. Analyses of the effects of the Mg concentration on the polyproline-mediated ribosome stalling suggested the unique regulation of peptide elongation by the mitoribosome. This system will be useful for analyzing the mechanism of translation initiation, and the interactions between the nascent peptide chain and the mitochondrial ribosome.

The dissemination of antimicrobial-resistant bacteria in environmental water is an emerging concern in medical and industrial settings. Here, we analysed the antimicrobial resistance of Escherichia coli isolates from river water and sewage by the use of a combined experimental phenotypic and whole-genome-based genetic approach. Among the 283 tested strains, 52 were phenotypically resistant to one or more antimicrobial agents. The E. coli isolates from the river and sewage samples were phylogenetically indistinguishable, and the antimicrobial-resistant strains were dispersedly distributed in a whole-genome-based phylogenetic tree. The prevalence of antimicrobial-resistant strains as well as the number of antimicrobials to which they were resistant were higher in sewage samples than in river samples. Antimicrobial resistance genes were more frequently detected in strains from sewage samples than in those from river samples. We also found that 16 river isolates that were classified as Escherichia cryptic clade V were susceptible to all the antimicrobials tested and were negative for antimicrobial resistance genes. Our results suggest that E. coli strains may acquire antimicrobial resistance genes more frequently and/or antimicrobial-resistant E. coli strains may have higher rates of accumulation and positive selection in sewage than in rivers, irrespective of their phylogenetic distribution.

Purpose To compare the accuracy of non-electrocardiogram (ECG)-gated CT angiography (CTA), single-diastolic-phase ECG-gated CTA, and full-phase ECG-gated CTA in detecting the intimal tear (IT) in aortic dissection (AD) and ulcer-like projection (ULP) in intramural hematoma (IMH). Materials and methods A total of 81 consecutive patients with AD and IMH of the thoracic aorta were included in this single-center retrospective study. Non-ECG-gated CTA, single-diastolic-phase ECG-gated CTA, and full-phase ECG-gated CTA were used to detect the presence of the IT and ULP in thoracic aortic regions including the ascending aorta, aortic arch, and proximal and distal descending aorta. Results The accuracy of detecting the IT and ULP was significantly greater using full-phase ECG-gated CTA (88% [95% CI: 100%, 75%]) than non-ECG-gated CTA (72% [95% CI: 90%, 54%], P = 0.001) and single-diastolic-phase ECG-gated CTA (76% [95% CI: 93%, 60%], P = 0.008). Conclusion Full-phase ECG-gated CTA is more accurate in detecting the IT in AD and ULP in IMH, than non-ECG-gated CTA and single-diastolic-phase ECG-gated CTA.

In vitro reconstitution is a powerful tool for investigating ribosome functions and biogenesis, as well as discovering new ribosomal features. In this study, we integrated all of the processes required for Escherichia coli small ribosomal subunit assembly. In our method, termed fully Recombinant-based integrated Synthesis, Assembly, and Translation (R-iSAT), assembly and evaluation of the small ribosomal subunits are coupled with ribosomal RNA (rRNA) synthesis in a reconstituted cell-free protein synthesis system. By changing the components of R-iSAT, including recombinant ribosomal protein composition, we coupled ribosomal assembly with ribosomal protein synthesis, enabling functional synthesis of ribosomal proteins and subsequent subunit assembly. In addition, we assembled and evaluated subunits with mutations in both rRNA and ribosomal proteins. The study demonstrated that our scheme provides new ways to comprehensively analyze any elements of the small ribosomal subunit, with the goal of improving our understanding of ribosomal biogenesis, function, and engineering., Shimojo et al. demonstrate the use of individually purified ribosomal proteins added into iSAT (integrated ribosomal synthesis, assembly, and translation) system to enable assembly of functional 30S subunits. They further show that while some 30S r-proteins must be full synthesized before transcription, others may be co-transcriptionally produced, to enable the assembly of 30S particles.

[Purpose] We aimed to evaluate the risk to clarify the seasonal variations in the circulatory dynamics of community-dwelling older people performing early morning outdoor exercises. [Participants and Methods] This study included 76 community-dwelling older adults (42 men, mean age: 76.9 ± 5.0 years; 34 women, mean age: 74.0 ± 4.2 years) who perform early morning exercises. The prevalence of hypertension among these adults was assessed, and their blood pressure and pulse rate were obtained before and after performing a 30-minute exercise using automatic and aneroid type sphygmomanometers while sitting on a chair. Further, we calculated the double product by multiplying systolic blood pressure and pulse rate. We analyzed the changes in the pre- and post-exercise systolic blood pressure, diastolic blood pressure, pulse rate, double product, diagnosis of hypertension, and seasonal factors (moderate-temperature season/low-temperature season). [Results] Thirty-five participants were assigned in the hypertension diagnosis group, while 40 participants were in the non-hypertension group. There was no significant difference in the mean age between the two groups. The main effects and interactions were not confirmed in relation to systolic blood pressure, diastolic blood pressure, pulse rate, and double product. [Conclusion] Essentially, blood pressure should be obtained before exercise, as individuals with hypertension are more likely to have an increase in baseline systolic blood pressure while exercising in the early morning during the low-temperature seasons.

Numerical simulations for blood flows related to cardiovascular diseases are presented. Differences in vessel morphologies produce different flow characteristics, stress distributions, and ultimately different outcomes. Some examples illustrating the effects of curvature and torsion on blood flows are presented both for simplified and patient-specific simulations. The goal of this study is to understand relationships between geometrical characteristics of blood vessels and blood flow behaviors.

Invasive mucinous adenocarcinoma (IMA) is a newly classified variant of lung adenocarcinoma. The aim of this study was to examine the correlation between the proportion of goblet cells and the clinicopathological characteristics of IMA. Ninety-nine patients with stage I IMA were included in this study. We estimated prognostic impact of goblet cell proportion. We classified them into two groups: the cases with a high goblet cell proportion (HGP, goblet cell proportion ≥80%) and the cases with a low goblet cell proportion (LGP, goblet cell proportion ≤30%), and compared the expression levels of five cancer progression markers and the number of tumor-promoting stromal cells between the two groups. Univariate and multivariate analysis revealed that the goblet cell proportion was a prognostic factor for recurrence free survival (P < 0.01) and overall survival (P = 0.01). The expression levels of the cancer stem cell-related marker, ALDH-1, and proliferation-related marker, geminin were significantly higher in the LGP group than in the HGP group. CD204+ tumor-associated macrophages were significantly more in the LGP stroma than the HGP stroma. Our current study indicated that the proportion of goblet cells was correlated with the malignant potential in surgically resected IMA.

MPIase is a glycolipid that is involved in membrane protein integration. Despite evaluation of its functions in vitro, the lack of information on MPIase biosynthesis hampered verification of its involvement in vivo. In this study, we found that depletion of CdsA, a CDP-diacylglycerol synthase, caused not only a defect in phospholipid biosynthesis but also MPIase depletion with accumulation of the precursors of both membrane protein M13 coat protein and secretory protein OmpA. Yeast Tam41p, a mitochondrial CDP-diacylglycerol synthase, suppressed the defect in phospholipid biosynthesis, but restored neither MPIase biosynthesis, precursor processing, nor cell growth, indicating that MPIase is essential for membrane protein integration and therefore for cell growth. Consistently, we observed a severe defect in protein integration into MPIase-depleted membrane vesicles in vitro. Thus, the function of MPIase as a factor involved in protein integration was proven in vivo as well as in vitro. Moreover, Cds1p, a eukaryotic CdsA homologue, showed a potential for MPIase biosynthesis. From these results, we speculate the presence of a eukaryotic MPIase homologue.

Interferon β (IFN-β) is considered a signaling molecule with important therapeutic potential in cancer since IFN-β-induced gene transcription mediates antiproliferation and cell death induction. Whereas, TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) has emerged as a promising anticancer agent because it induces apoptosis specifically in cancer cells. In this study, we elucidated that IFN-β augments TRAIL-induced apoptosis synergistically using five human malignant melanoma cells. All of these cells were induced apoptosis by TRAIL. Whereas, the response against IFN-β was different in amelanotic cells (A375 and CRL1579) and melanotic cells (G361, SK-MEL-28, and MeWo). The responsibility of amelanotic cells against IFN-β was higher than those of melanotic cells. The synergism of IFN-β and TRAIL were correlated with the responsibilities of the cells against IFN-β. The synergistic interaction was confirmed by a combination index based on the Chou-Talalay method. The upregulation of apoptosis in amelanotic cells was caused by very low doses of IFN-β (over 0.1 IU/ml). Both of p53-mediated intrinsic pathway and Fas-related extrinsic pathway were activated by IFN-β alone and combination with TRAIL. Further, TRAIL death receptors (DR4 and DR5) were upregulated by a low-dose IFN-β (over 0.1 IU/ml) and the expression was more promoted by the combination with TRAIL. It was clarified that the upregulation of DR5 is associated with the declination of viability.

Objectives Community-based activities led by older residents are important in preventing long-term care and enhancing social participation among older persons in Japan. Local governments and community nurses are required to support these activities. However, there is no knowledge about the issues of residents who participate in community-based activities, which is essential for the effective support of community-based activities. We aimed to examine the association between the length of participation and recognized issues among community-based activities.Methods Through the local governments in Tokyo, we recruited participants from community-based activity groups; 2,367 people from 155 activity groups from 40 municipalities responded. The presence or absence of 10 items of recognized issues, such as lack of management members and lack of teachers, were examined. The number of years of participation in the activity was divided into four groups: "less than 1 year," "more than 1 year and less than 2 years," "more than 2 years and less than 4 years," and "more than 4 years." Logistic regression analysis was conducted to examine the association between the length of participation and recognized issues.Results The number of analyzed respondents was 2,194 (14.5% were male and the average age was 76.9 years). Compared to "less than 1 year" group, the "more than 2 years and less than 4 year" group recognized "aging of group" (OR=1.92), "lack of management members" (OR=1.61), and "health condition of participants" (OR=1.47) as issues. In the "more than 4 years" group, "aging of group" (OR=3.24), "lack of management members" (OR=2.63), "lack of participants" (OR=2.12), "health condition of participants" (OR=1.95), "mannerism of activities" (OR=1.62), and "lack of place" (OR=1.48) were recognized as issues.Conclusion Issues recognized by participants in community-based activities differed depending on the number of years they had been participating in the activity. This suggests that it is necessary to provide appropriate support taking the length of participation into account. For example, the issue of the "health condition of participants" was recognized by participants who had been participating in the activity for approximately two years. Consequently, "lack of participants" may have occurred in participants who have been participating in the activity for four years. Therefore, promoting the health management of participants from the early phase of community-based activity would be effective in preventing dropout.