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Background Homeostasis of the vessel wall is cooperatively maintained by endothelial cells (ECs), smooth muscle cells, and adventitial fibroblasts. The genetic deletion of fibulin‐4 ( Fbln4 ) in smooth muscle cells ( SMKO ) leads to the formation of thoracic aortic aneurysms with the disruption of elastic fibers. Although Fbln4 is expressed in the entire vessel wall, its function in ECs and relevance to the maintenance of valvulo‐arterial integrity are not fully understood. Methods and Results Gene silencing of FBLN4 was conducted on human aortic ECs to evaluate morphological changes and gene expression profile. Fbln4 double knockout ( DKO ) mice in ECs and smooth muscle cells were generated and subjected to histological analysis, echocardiography, Western blotting, RNA sequencing, and immunostaining. An evaluation of the thoracic aortic aneurysm phenotype and screening of altered signaling pathways were performed. Knockdown of FBLN4 in human aortic ECs induced mesenchymal cell–like changes with the upregulation of mesenchymal genes, including TAGLN and MYL9 . DKO mice showed the exacerbation of thoracic aortic aneurysms when compared with those of SMKO and upregulated Thbs1, a mechanical stress–responsive molecule, throughout the aorta. DKO mice also showed progressive aortic valve thickening with collagen deposition from postnatal day 14, as well as turbulent flow in the ascending aorta. Furthermore, RNA sequencing and immunostaining of the aortic valve revealed the upregulation of genes involved in endothelial‐to‐mesenchymal transition, inflammatory response, and tissue fibrosis in DKO valves and the presence of activated valve interstitial cells. Conclusions The current study uncovers the pivotal role of endothelial fibulin‐4 in the maintenance of valvulo‐arterial integrity, which influences thoracic aortic aneurysm progression.

The cellular origins of cervical cancer and the histological differentiation of human papillomavirus (HPV)-infected cells remain unexplained. To gain new insights into the carcinogenesis and histological differentiation of HPV-associated cervical cancer, we focused on cervical cancer with mixed histological types. We conducted genomic and transcriptomic analyses of cervical cancers with mixed histological types. The commonality of cellular origins of these cancers was inferred using phylogenetic analysis and by assessing the HPV integration sites. Carcinogenesis was estimated by analyzing human gene expression profiles in different histological types. Among 42 cervical cancers with known HPV types, mixed histological types were detected in four cases, and three of them were HPV18-positive. Phylogenetic analysis of these three cases revealed that the different histological types had a common cell of origin. Moreover, the HPV-derived transcriptome and HPV integration sites were common among different histological types, suggesting that HPV integration could occur before differentiation into each histological type. Human gene expression profiles indicated that HPV18-positive cancer retained immunologically cold components with stem cell properties. Mixed cervical cancer has a common cellular origin among different histological types, and progenitor cells with stem-like properties may be associated with the development of HPV18-positive cervical cancer.

Recent studies have shown that mutation at Ser522 causes inhibition of collapsin response mediator protein 2 (CRMP2) phosphorylation and induces axon elongation and partial recovery of the lost sensorimotor function after spinal cord injury (SCI). We aimed to reveal the intracellular mechanism in axotomized neurons in the CRMP2 knock-in (CRMP2KI) mouse model by performing transcriptome analysis in mouse sensorimotor cortex using micro-dissection punching system. Prior to that, we analyzed the structural pathophysiology in axotomized or neighboring neurons after SCI and found that somatic atrophy and dendritic spine reduction in sensorimotor cortex were suppressed in CRMP2KI mice. Further analysis of the transcriptome has aided in the identification of four hemoglobin genes Hba-a1, Hba-a2, Hbb-bs, and Hbb-bt that are significantly upregulated in wild-type mice with concomitant upregulation of genes involved in the oxidative phosphorylation and ribosomal pathways after SCI. However, we observed substantial upregulation in channel activity genes and downregulation of genes regulating vesicles, synaptic function, glial cell differentiation in CRMP2KI mice. Moreover, the transcriptome profile of CRMP2KI mice has been discussed wherein energy metabolism and neuronal pathways were found to be differentially regulated. Our results showed that CRMP2KI mice displayed improved SCI pathophysiology not only via microtubule stabilization in neurons, but also possibly via the whole metabolic system in the central nervous system, response changes in glial cells, and synapses. Taken together, we reveal new insights on SCI pathophysiology and the regenerative mechanism of central nervous system by the inhibition of CRMP2 phosphorylation at Ser522. All these experiments were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee at Waseda University, Japan (2017-A027 approved on March 21, 2017; 2018-A003 approved on March 25, 2018; 2019-A026 approved on March 25, 2019).

Self-employed workers have a higher risk for adverse health outcomes than employed workers. However, the differences in health risk behaviors by employment status are largely unknown. This study examined differences in health risk behaviors between self-employed and employed (permanent/non-permanent) workers by sex and age (20-59 years, 60-79 years).This was a cross-sectional study involving community-dwelling adults living in urban cities in Japan.In 2019, we conducted a mail survey in Wako city, Saitama, and Fuchu city, Tokyo. In total, 30,315 adults aged ≥18 years were randomly selected, and 14,185 completed the survey (response rate: 46.8%). The participants for analysis were 8538 workers. Health risk behaviors included physical inactivity (150 min/wk of moderate-to-vigorous physical activity), prolonged sitting (480 min/d), high-frequency drinking (≥3 d/wk), tobacco use (current smoker), and overweight (body mass index ≥ 25 kg/mSelf-employed workers had more health risk behaviors than permanent and non-permanent employees, with this difference more significant among younger males. In younger males, compared with self-employment, permanent employment was associated with less tobacco use, and non-permanent employment was associated with less physical inactivity, prolonged sitting, high-frequency drinking, and overweight. In younger females, non-permanent employment was associated with less prolonged sitting and overweight than self-employment. In older males and females, the prevalence of physical inactivity was lower in non-permanent employed than in self-employed workers.Promoting health behaviors among self-employed may be beneficial for reducing health inequalities between self-employed and employed workers.

This study aims to identify the independent influence of face-to-face contact (FFC) and non-face-to-face contact (NFFC) on the subsequent decline in self-rated health and mental health status by age. A total of 12,000 participants were randomly selected among residents in the study area, and 1751 of them responded to both the 2016 and 2018 mail surveys. The participants were subsequently classified into three age groups (25–49: Young adults; 50–64: Mid-aged adults; and 65–84: Older adults). Social contact was assessed by computing the frequencies of FFC and NFFC. Multiple logistic regression analysis showed the risk of social contact on the decline in self-rated health and World Health Organization-Five Well-Being Index. Both FFC and NFFC were significantly associated with maintaining mental health; however, the impacts of FFC on mental health were more significant than that of NFFC among older adults and young adults. Compared with the no contact group, FFC was significantly associated with maintaining self-rated health in mid-aged adults. The influence of FFC and NFFC on health differed by age group.

The patient was a 62-year-old woman who had undergone mastectomy in August 2003 for cancer of the right breast. In addition to radiation therapy in the remaining breast, chemotherapy and endocrine therapy were subsequently performed. The patient had a 10-year recurrence-free postoperative course followed by annual surveillance. Beginning in 2016, an elevation in the serum level of tumor markers was detected; however, no accumulations were found in PET-CT over 2 consecutive years(2016 and 2017). Thereafter, serum levels of tumor markers continued to rise, and a PET-CT in 2018 revealed costal accumulations leading to a diagnosis of late-stage bone metastasis in postoperative year 15. Although hormone therapy was resumed, a continuing rise in the serum level of tumor markers led to a diagnosis of diffuse bone metastasis by MRI in 2019. Treatment with abemaciclib was initiated, and with effective radiotherapy, the PS was maintained at 0-1, serum levels of tumor markers decreased, and the lesions themselves continued at SD. However, in June 2020, multiple liver metastases appeared in an abdominothoracic CT scan. The patient refused chemotherapy; this, a BSC policy was adopted. Acute hemolytic anemia occurred immediately thereafter, and the PS gradually deteriorated. The patient died in September 2020, 17 years and 1 month after surgery.

The patient was an 80-year-old man, hospitalized with poor appetite, light-headedness, and black stool. Esophagogastroduodenoscopy showed an ulcerative lesion in cardia, and the tumor was diagnosed as gastric cancer using the biopsy specimens. The patient underwent a gastrectomy with D1-node dissection. Pathologically, the small tumor cells infiltrated the muscularis propria of the gastric wall, and these tumor cells immunohistochemically showed a positive reaction for synaptophysin. Therefore, the tumor was diagnosed as small cell-neuroendocrine carcinoma of the stomach. Metastasis was not observed in regional lymph nodes, and the TNM classification was defined as pStage ⅠB. After surgery, adjuvant chemotherapy was not performed. The patient is well without recurrence for more than 7 months after the surgery. We experienced and report a case of gastric endocrine cell carcinoma that underwent resection and provide a review of the literature.

Objective During a natural disaster, accessing appropriate information is essential to reduce damage to health. Information and community technology (ICT) devices can help in obtaining information. This study aimed to identify the characteristics of information tools commonly used by ICT device users during a natural disaster, and identify associations between sociodemographic factors and Internet-based information tools.Methods In 2019, 21,300 adults aged 18 years and above living in Fuchu city, Tokyo, were enrolled in our survey. Participants were asked which ICT devices (computer, smartphone, tablet, or mobile phone) they used. Those who used at least one device were classified as ICT device users. To evaluate the information tools commonly used during a natural disaster, participants were asked to select information resources they would use from a list provided (television, radio, Internet search, alert mail, administrative radio system, local government website, neighborhood, family, and friends). We classified Internet search, alert mail, and local government website as Internet-based tools. A Poisson regression model with robust variance was used to assess sex and age differences among ICT device users and clarify associations between sociodemographic factors and the use of Internet-based information tools.Results The respondents were 9,201 adults (response rate: 43.2%). Among the ICT device users, more than 95% were below 70 years. Moreover, 66.7% of women and 70.6% of men were 80 years or above. More than 80% preferred television to get information during a natural disaster. Over 70% of women below 60 years and men below 70 years preferred to use an Internet search, compared with 7.8% of women aged 80 years or above. Those who selected Internet search were more likely to be women, have a high household income and high educational attainment, be widowed/divorced/single, and be less likely to live alone or be older adults (especially older women). Participants who selected alert mail were more likely to be women and have high educational attainment, and less likely to be widowed/divorced/single and older adults. Those who selected government websites were more likely to be women, have high educational attainment and be widowed/divorced/single, and less likely to live alone, be widowed/divorced/single, and be older adults (especially older women).Conclusion There were differences by sex and age in information tools selected for use during a natural disaster among ICT device users. Sociodemographic factors were associated with Internet-based tools, and use differed by type of information tool.

Gene expression analysis at the single-cell scale by next generation sequencing has revealed the existence of clonal dissemination in cancer metastasis. The current spatial analysis technologies elucidate the heterogeneity of cell-cell interactions in situ; however, further analysis is needed to elucidate the nature of tumor heterogeneity. To reveal the expressional heterogeneity and cell-cell interactions in primary tumors and metastases, we performed transcriptomic analysis of microtissues dissected from a triple-negative breast cancer (TNBC) cell line MDA-MB-231 xenograft model by our automated tissue microdissection punching technology. This multiple-microtissue transcriptome analysis revealed that there were existed three cell-type clusters in the primary tumor and axillary lymph node metastasis, two of which were cancer stem cell-like clusters (CD44/MYC-high, HMGA1-high). The CD44/MYC-high cluster showed aggressive proliferation with MYC expression. The HMGA1-high cluster exhibited HIF1A activation and upregulation of ribosomal processes. Furthermore, we developed a cell-cell Interaction (CCI) analysis to investigate the ligand-receptor interactions (cancer cell to stroma and stroma to cancer cell) in each spot. The CCI analysis revealed the interaction dynamics generated by the combination of cancer cells and stromal cells in primary tumors and metastases. Two cancer stem cell-like populations were also detected by the scRNA-seq analysis of TNBC patients. In addition, the gene signature of the HMGA1-high cancer stem cell-like cluster has the potential to serve as a novel biomarker for diagnosis. The mixture of these multiple cancer stem cell-like populations may cause differential anticancer drug resistance, increasing the difficulty of curing this cancer.

This study aimed to verify the direction of providing and receiving intergenerational support and examine its effects on mental health among intergenerational non-relatives.In the initial survey (Time1), approximately 65,000 residents of Wako City in Saitama Prefecture, Japan, were considered, from which, a sample of 7,000 people was obtained. A total of 2,982 valid responses was received, and a follow-up survey was conducted two years later (Time2).Structural equation modeling with a cross-lagged effect model and a synchronous effect model showed that the direction of giving and receiving intergenerational support had changed with age; while the young and middle-aged groups shifted their direction from receiving support to giving support, the older adults shifted their direction from giving support to receiving support. Furthermore, in the young-adults group, receiving support from older adults positively influenced their mental health two years later. For the middle-aged group, giving support positively influenced their mental health at Time2. For the old-old group, receiving support from young and middle-aged people positively influenced the mental health at Time2.To facilitate intergenerational mutual help in the local community, it is necessary to create opportunities for older adults to provide support to young and middle-aged people and, in return, create a mechanism to prompt support from young and middle-aged people for older adults.

A simple and robust ultra-small four-color-fluorescence detection system was developed by integrating its components, namely, a four-capillary array, an injection-molded-plastic four-lens array, a four-dichroic-mirror array, and a CMOS sensor, as one device. The developed system was applied to a high-dynamic-range capillary-array electrophoresis (HiDy CE) to quantify a rare EGFR mutant (MT) of exon 19 deletion in a large excess of EGFR wild type (WT). Samples with serially diluted MT and constant-concentration WT were co-amplified by competitive PCR and subjected to HiDy CE. The MT peak in each electropherogram was then compared to the WT peak. As a result, MT was quantified with high-sensitivity (LOD of 0.004% MT/WT) and four-orders-of-magnitude dynamic range (0.01-100% MT/WT) by HiDy CE. Moreover, compared with existing methods, HiDy CE achieves higher speed, higher sample throughput, and lower consumable cost per sample. It has therefore great potential to be used in clinical practice.

Spatial transcriptomics is useful for understanding the molecular organization of a tissue and providing insights into cellular function in a morphological context. In order to obtain reproducible results in spatial transcriptomics, we have to maintain tissue morphology and RNA molecule stability during the image acquisition and biomolecule collection processes. Here, we developed a tissue processing method for robust and reproducible RNA-seq from tissue microdissection samples. In this method, we suppressed RNA degradation in fresh-frozen tissue specimens by dehydration fixation and effectively collected a small amount of RNA molecules from microdissection samples by magnetic beads. We demonstrated the spatial transcriptome analysis of the mouse liver and brain in serial microdissection samples (100 μm in a diameter and 10 μm in thickness) produced by a microdissection punching system. Using our method, we could prevent RNA degradation at room temperature and effectively produce a sequencing library with Smart-seq2. This resulted in reproducible sequence read mapping in exon regions and the detection of more than 2000 genes compared to non-fixed samples in the RNA-seq analysis. Our method would be applied to various transcriptome analyses, providing the information for region specific gene expression in tissue specimens.

A 67-year-old woman with a history of esophageal cancer(poorly-differentiated squamous cell carcinoma, pStageⅡ) was diagnosed with 2 liver tumors by regular checkup CT 10 years after her operation. We also observed elevated levels of tumor marker CEA. The tumors were suspected to be metastatic although no primary lesion was identified. We performed partial hepatectomy for diagnostic therapy. The pathological diagnosis was adenocarcinoma suggestive of metastatic tumors but the primary lesion remained unknown. Tumor marker levels were elevated 2 months after the operation and we detected a pancreatic tumor, multiple liver tumors, peritoneal dissemination, and para-aortic lymph node metastasis. Therefore, our clinical diagnosis was multiple metastases with primary pancreatic cancer and chemotherapy was performed. We conducted a thorough review of the diagnostic images and repeated the pathological analysis. Immunobiological staining showed that the tumor cells were positive for neuroendocrine markers such as chromogranin A, CD56, and Ki-67. We eventually diagnosed the liver tumors as metastasis from the pancreatic neuroendocrine carcinoma(Grade 3).

A 66-year-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass with bleeding. Triple-negative invasive ductal carcinoma of the breast was diagnosed by core needle biopsy. Computed tomogra- phy showed axillary and infraclavicular lymph node metastases. Epirubicin/cyclophosphamide(EC)therapy was started. We reduced the dose to 80%during courses 2-4. After 4 courses of treatment, CT showed a complete response. We reduced the dose to 50% during courses 5-12 and stopped chemotherapy. Five years have passed without recurrence since the first treatment.

Background:Social isolation and homebound statuses are possible risk factors for increased mortality among older adults. However, no study has addressed the impact of accumulation of these two factors on mortality. The aim of this study was to examine whether such accumulation increased the risk of all-cause mortality.Methods:The analyzed sample was drawn from a mail survey of 1,023 older adults without instrumental activities of daily living disability. Participants were classified into four groups according to the frequency of both face-to-face and non-face-to-face interactions with others (social isolation and non-social isolation) and the frequency of going outdoors (homebound and non-homebound). Social isolation and homebound statuses were defined as having a social interaction less than once a week and going outdoors either every few days or less, respectively. All-cause mortality information during a six-year follow-up was obtained.Results:In total, 78 (7.6%) participants were both socially isolated and homebound. During the follow-up period, 65 participants died, with an overall mortality rate of 10.6 per 1000 person-years. Cox proportional hazards regression analyses demonstrated that older adults who were socially isolated and homebound showed a significantly higher risk of subsequent all-cause mortality compared with healthy adults who were neither socially isolated nor homebound, independent of potential covariates (aHR, 2.19; 95% CI: 1.04–4.63).Conclusion:Our results suggest that the co-existence of social isolation and homebound statuses may synergistically increase risk of mortality. Both active and socially integrated lifestyle in later life might play a major role in maintaining a healthy status.

Aim Identifying factors that influence participation in social group activities in older adults might be helpful in promoting social participation in this population. We examined factors related to new or continuous participation in social group activities according to group type. Methods We carried out a community-based, longitudinal study with a 2-year follow-up period. Of 7608 older adults aged ≥65 years, 3380 completed the follow-up survey and were included in the analysis. We examined private group (hobbies, sports and volunteering; PrG) and public group (neighborhood associations and senior citizen clubs; PuG) activity. Results For PrG, 39.6% of the participants were engaged at baseline, 25.5% initiated participation and 9.5% withdrew during the study period. For PuG, 20.8% of the participants were engaged at baseline, 10.8% initiated participation and 31.5% withdrew during the study period. Logistic regression analysis showed mental health, self-rated health, employment, relationships with neighbors, subjective economic status, educational attainment and participation in PuG were related to new participation in PrG. Mental health, employment and relationships with neighbors were significantly related to continuous participation. For PuG, mental health, sex and relationships with neighbors were significantly related to new participation, whereas sex, relationships with neighbors and educational attainment were related to continuous participation. Conclusions The rate of new and continuous participation in PrG was higher than that in PuG, and different related factors were identified as existing between social group types. Geriatr Gerontol Int 2018; 18: 1259-1266.

Aim The health benefits of paid employment in late life are understood, but they might vary according to work motives. We examined the health effects of employment among older adults, focusing on motivation. Methods We carried out a 2-year longitudinal survey from 2013 (baseline) to 2015 (follow up). Among 7608 older adults, the analysis included 1069 who completed both surveys and were employed at baseline. Work motives were assessed using a questionnaire. Participants were assigned to groups based on their responses: (i) financial reasons; (ii) motivation other than financial reasons; and (iii) both financial and non-financial reasons. Self-rated health, mental health and higher-level functional capacity were evaluated as health outcomes. Results There were group differences in baseline demographic variables and health status; those with financial reasons had lower socioeconomic status and worse mental health. Multivariable logistic regression analysis showed that compared with older workers with non-financial reasons, those with financial reasons were more likely to decline in self-rated health (OR 1.42; 95% CI 1.00-2.03) and higher-level functional capacity (OR 1.55; 95% CI 1.16-2.07), which was independent of potential covariates, including socioeconomic status. However, no differences were evident between those with only non-financial reasons and those having both financial and non-financial reasons. Conclusions We found that the participants who worked only for financial rewards had reduced health benefits through working in old age. A prolonged working life among older workers can contribute to maintaining health and can be enhanced by non-financial reasons, such as finding meaning in life and social contact. Geriatr Gerontol Int 2020; 20: 745-751.

Background: Social contact leads to an increased likelihood of engaging in physical activity (PA). However, the influence of social contact on PA would be different depending on the social contact source. This study aimed to identify the association of changes in social contact with family and non-family members with the change in PA using a parallel latent growth curve modeling. Methods: Participants were randomly selected from among residents in the study area age ≥ 20 years (n = 7000). We conducted mail surveys in 2014, 2016, and 2019. The 1365 participants completed all surveys. PA was assessed with validated single-item physical activity measure. Social contact was assessed by summing frequencies of face-to-face and non-face-to-face contacts with family/relatives not living with the participant and friends/neighbors. Parallel latent growth curve modeling was used to assess the cross-sectional, prospective, and parallel associations of social contact with PA change. Results: There was a positive cross-sectional association between contact with friends/neighbors and PA, whereas prospective and parallel associations between contact with family/relatives and PA. Conclusion: Contacting friends/neighbors did not predict the change in PA, and a high frequency of contact with family/relatives at baseline and increasing contact with family/relatives was associated with increased PA over 5-year.

We have performed totally laparoscopic stomach-partitioning gastrojejunostomy for gastroduodenal outlet obstruction caused by advanced malignancies in 14 cases. We divided 14 patients into 2 groups according to age at surgery: those80 years of age and thoseB80 years of age. We compared these 2 groups regarding preoperative status, operative findings, and postoperative course. We found that the stage of cancer in the older group was lower than in the younger group, the number of unresectable factors in the older group were fewer than in the younger group, and the postoperative stay in the older group was shorter than in the younger group. There were no serious postoperative complications in either group and all 14 patients were able to drink or eat the day after surgery. These results suggest that palliative, totally laparoscopic stomachpartitioning gastrojejunostomy may be the best option for elderly cancer patients with gastroduodenal outlet obstruction caused by advanced malignancies, even when their general conditions is poor. We should consider this surgical procedure as soon as possible when the patient decides on palliative treatment.

A 57-year-old man visited our hospital with right hypochondralgia. Abdominal contrast CT showed a 10 cm sized mass in S6-7of the liver and abdominal hemorrhage areas. The tumor showed extrahepatic growth. Blood a-fetoprotein(AFP)was high at 4,447.9ng/mL. Hemostasis was performed through emergency transcatheter arterial embolization. At a later date, upper gastrointestinal endoscopy showed a 20 mm sized type 2 lesion in the gastric corpus. Therefore, we performed distal gastrectomy and right hepatic lobectomy. In histopathological findings, the gastric lesion showed identified as a hepatoid adenocarcinoma, which was positive for AFP protein. The liver lesion was negative for AFP protein, but was similar to hepatoid adenocarcinoma, and no fibrosis was observed in the background liver. Therefore, we diagnosed the tumor as a liver metastasis of AFP-producing gastric cancer. On postoperative day 31, CT showed a metastatic lesion in the S1 of the liver and ascites. Chemotherapy was not successful, and the patient died on postoperative day 75. The resection rate of metastatic liver tumor in AFP-producing gastric cancer is low. This is the second case in Japan, wherein a surgery was performed for a ruptured liver metastatic lesion.

Objective The purpose of this study was to examine the relationship between intra- and inter-generational exchange and mental health among young adults aged 25-49 years and older adults aged 65-84 years.Methods In 2016, a community-based, cross-sectional survey was conducted. A total of 3,334 young adults (valid response rate: 24.6%), and 3,116 older adults (valid response rate: 46.0%) completed the survey and were included in the analysis. Their mental health was evaluated using the World Health Organization-Five Well-Being Index (WHO-5), and those who scored under 13 or scored less than one on any item were considered to have poor mental health. To evaluate the intra- or inter-generational exchange, participants were asked about their frequency of interaction with people aged 20-49 years or aged ≥70, excluding family and co-workers. Young adults who interacted with people aged 20-49 years or older adults who interacted with people ≥70 were classified as "having intra-generational exchange," while young adults who interacted with people ≥70 years or older adults who interacted with people aged 20-49 years were classified as "having intergenerational exchange." Therefore, individuals who interacted with both generations were classified as "having multi-generational exchange," and those who did not interact with any generation were categorized as "no exchange." We conducted a logistic regression analysis that included mental health as a dependent variable, intra- and inter-generational exchange as independent variables, and gender, age, educational attainment, marital status, living situation, subjective economic status, social participation, employment, self-rated health, and Instrumental Activity of Daily Living as covariates.Results Of the 3,334 young adults, 61.5% were mentally healthy, 51.3% had intra-generational exchange, 21.9% had inter-generational exchange, 16.5% had multi-generational exchange, and 42.7% did not have any exchange. Of the 3,116 older adults, 65.8% were mentally healthy, 67.9% had intra-generational exchange, 34.3% had inter-generational exchange, 29.9% had multi-generational exchange, and 21.1% did not have any exchange. A logistic regression analysis revealed that "having intra-generational exchange" and "having intergenerational exchange" were significantly related to better mental health in both young adults (intra-generational; Odds ratios (OR) 1.19, 95% confidence intervals (CI) 1.10-1.30: inter-generational; OR 1.13, 95% CI 1.03-1.25) and older adults (intra-generational; OR 1.15, 95% CI 1.02-1.29: inter-generational; OR 1.46, 95% CI 1.30-1.65). Therefore, "having multi-generational exchange" was more strongly related to better mental health compared with "only having intra-generational exchange."Conclusion Among young and older adults, intra- and inter-generational exchange were related to better mental health, and multi-generational exchange showed the strongest relationship with better mental health.

Objectives Using the Community Child-Rearing Support Scale (CCRSS), which was developed for older adults, we examined 1) the reliability and validity of the scale for multiple generations, as well as the generational differences in the 2) degree and content of supportive behaviors for child rearing and 3) correlates of the behavior, in conjunction with gender differences.Methods A mail survey was conducted with residents aged 25-84 years who were randomly selected from two cities in Tokyo and the surrounding areas, and responses were obtained from 8918 residents (response rate: 33%). The respondents were grouped as follows: old-aged (65-84 years), middle-aged (50-64 years), and young-aged (25-49 years). We performed the following analyses by age group and gender: 1) Cronbach's reliability coefficient and a confirmatory factor analysis of the CCRSS, 2) analysis of variance of the total CCRSS scores and scores of the three subscales ("children's security and sound growth," "instrumental support to parents," and "emotional support to parents"), and 3) a multiple regression analysis of the total scores in which various individual characteristics were introduced as explanatory variables.Results The reliability coefficient was over 0.85 for each age group, and the factor analysis showed good model fitness. Compared to the middle- and young-aged groups, the old-aged group was more likely to provide support for "children's security and sound growth," and equally (for women) or more likely (for men) to provide "emotional support to parents," thereby resulting in the highest total score among the three generations. The mean score of "instrumental support to parents," such as taking care of a child, was the highest for young women, although the score was low overall. Having a child or grandchild under 13 years old and stronger generativity were positively associated with child-rearing support for all age groups; however, the degree of associations varied across the groups. While having a child was strongly associated with support among the young-aged group, the association between support and generativity was stronger for older groups. Moreover, participation in neighborhood associations or volunteer groups and high school or lower education were associated with more support among all age groups, whereas living in rental apartments was associated with less support among the young-aged group.Conclusion Our findings suggest that the CCRSS can be used for multiple generations and that old people play an important role in child rearing in the community. We found both differences and similarities between generations with respect to the correlates of child-rearing support.

We report a case of a 42-year-old man who underwent 3 times surgical resection for lymph nodes recurrence and multidisciplinary therapy for Stage IV b Barrett's esophageal adenocarcinoma, and was well 6 years and 3 months after the first resection. The prognosis of the recurrence cases after radical recection of the esophageal cancer is extremely poor. Long-term prognosis may be obtained in few patients, but the cases are squamous cell carcinoma in most of the reported cases. The number of Barrett's esophageal adenocarcinoma patients is increasing, but it is not many. There is little reports, and there is no fixed treatment policy.

Analyses of gene expressions in single cells are important for understanding detailed biological phenomena. Here, a highly sensitive and accurate method by sequencing (called “bead-seq”) to obtain a whole gene expression profile for a single cell is proposed. A key feature of the method is to use a complementary DNA (cDNA) library on magnetic beads, which enables adding washing steps to remove residual reagents in a sample preparation process. By adding the washing steps, the next steps can be carried out under the optimal conditions without losing cDNAs. Error sources were carefully evaluated to conclude that the first several steps were the key steps. It is demonstrated that bead-seq is superior to the conventional methods for single-cell gene expression analyses in terms of reproducibility, quantitative accuracy, and biases caused during sample preparation and sequencing processes.

Identifying factors that influence participation in social group activities in older adults might be helpful in promoting social participation in this population. We examined factors related to new or continuous participation in social group activities according to group type.We carried out a community-based, longitudinal study with a 2-year follow-up period. Of 7608 older adults aged ≥65 years, 3380 completed the follow-up survey and were included in the analysis. We examined private group (hobbies, sports and volunteering; PrG) and public group (neighborhood associations and senior citizen clubs; PuG) activity.For PrG, 39.6% of the participants were engaged at baseline, 25.5% initiated participation and 9.5% withdrew during the study period. For PuG, 20.8% of the participants were engaged at baseline, 10.8% initiated participation and 31.5% withdrew during the study period. Logistic regression analysis showed mental health, self-rated health, employment, relationships with neighbors, subjective economic status, educational attainment and participation in PuG were related to new participation in PrG. Mental health, employment and relationships with neighbors were significantly related to continuous participation. For PuG, mental health, sex and relationships with neighbors were significantly related to new participation, whereas sex, relationships with neighbors and educational attainment were related to continuous participation.The rate of new and continuous participation in PrG was higher than that in PuG, and different related factors were identified as existing between social group types. Geriatr Gerontol Int 2018; 18: 1259-1266.

Purpose We analyzed the data from a 2-year prospective-cohort survey to identify factors relating to new incidences of social isolation and recovery from social isolation in community-dwelling older people. Materials and methods We conducted a longitudinal study (2013–2015) involving 2657 older residents of Iriarai, Japan. A chi-square test, an independent t-test, and logistic regression analysis with imputed data were conducted to examine categorical data, continuous variables, and factors relating to social isolation, respectively. Principal results The results suggested that the factors that predicted future social isolation included being a man, being older, living with others, having a decline in mental health, having a lower frequency of going out, and not participating in community groups. On the other hand, being younger, having a higher level of mental health, having a higher frequency of going out, and participating in community groups were identified as factors that predicted participants’ recovery from social isolation. Major conclusions Some demographic, mental, and social factors could relate to new incidences of social isolation and recovery from social isolation in community-dwelling older people. As aging is an irreversible phenomenon, and there is a limit to preventing all disorders, either building a safety net or introducing exchange programs to prevent social isolation are important interventions for older people.

Effective therapeutic combinations targeting the oncogenic pathway still are unknown in human hepatocellular carcinoma (HCC). The authors previously identified aberrant expression of aurora B kinase as the independent predictor for the lethal recurrence of HCC, showing that AZD1152 induced in vitro and in vivo apoptosis with polyploidy in human HCC cells. In this preclinical study, the combined effects of molecular-targeted therapies were evaluated based on the cellular response of aurora B inhibition. This study analyzed the expression of Bcl-2 family proteins in polyploidization induced by AZD1152 and the in vitro synergistic effects of AZD1152 with control of the Bcl-2 family pathway in human HCC cells. The in vivo effects of the combination therapy targeting the specific molecules were evaluated using subcutaneous tumor xenograft models. The findings showed that Bcl-xL was specifically overexpressed in AZD1152-induced polyploid HCC cells. The combination of AZD1152 followed by Bcl-xL/2 inhibitor ABT263 induced synergistically cellular apoptosis (p

The prognosis of patients with Stage IV gastric cancer is generally poor. The 5-year overall survival rate is less than 10%. The patient was a 73-year-old man with Stage IV gastric cancer. Before chemotherapy, peritoneal dissemination was observed using staging laparoscopy. The patient received first-line chemotherapy with TS-1 plus CDDP. Renal function worsened and consequently the therapy was stopped. He received 3 courses of chemotherapy with weekly PTX. The peritoneal dissemination had disappeared by the second staging laparoscopy and he underwent distal gastrectomy. The final diagnosis was pT4a, ly2, v1, pN2(4/16),M0, fStage III B. The patient received adjuvant chemotherapy of TS-1 for 4 years and 8months after gastrectomy. More than 5 year after gastrectomy, the patient is alive without recurrence.