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Background: Although depressive symptoms are associated with an increased risk of readmission after left ventricular assist device (LVAD) implantation, it is unclear whether they affect the efficacy of exercise-based cardiac rehabilitation (EBCR). This study aimed to investigate the effect of depressive symptoms on EBCR efficacy., Methods: We analyzed 48 patients who participated in EBCR after LVAD implantation (mean age 45 ± 12 years; 60% male). Patients were classified into two groups using the Zung Self-Rating Depression Scale (SDS): depressive group (SDS ≥40, n = 27) and non-depressive group (SDS <40, n = 21). We examined changes in peak oxygen uptake (VO 2 ), knee extensor muscular strength (KEMS), and quality of life (QOL) during EBCR using analysis of covariance., Results: Although baseline characteristics were similar between the two groups, the non-depressive group was less likely to receive diuretics (22% vs. 52%, p = 0.030). Peak VO 2 , KEMS, and QOL significantly increased over time in both groups (all p < 0.05). The depressive group had a significantly lower change in peak VO 2 than the non-depressive group (2.7 vs. 1.6 ml/kg/min; mean difference: -1.1 ml/kg/min, 95% confidence interval [CI]: -0.045 to -2.17; p = 0.041, d = 0.59). There was no between-group difference regarding the change in KEMS or QOL. Adjusting for the baseline value, a significant difference between groups was observed only in peak VO 2 (p = 0.045)., Conclusions: Although EBCR significantly improved exercise capacity after LVAD implantation, depressive symptoms interfered with this improvement. Further studies are needed to determine whether psychological interventions for depression, in addition to EBCR, would improve the response to EBCR after LVAD implantation., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Objective: Although immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an important component of mucosal barriers against luminal pathogens, its precise function remains unclear. Therefore, we tried to elucidate the effect of IgA on gut homeostasis maintenance and its mechanism., Design: We generated various IgA mutant mouse lines using the CRISPR/Cas9 genome editing system. Then, we evaluated the effect on the small intestinal homeostasis, pathology, intestinal microbiota, cytokine production, and immune cell activation using intravital imaging., Results: We obtained two lines, with one that contained a <50 base pair deletion in the cytoplasmic region of the IgA allele (IgA tail-mutant; IgA tm/tm ) and the other that lacked the most constant region of the IgH α chain, which resulted in the deficiency of IgA production (IgA -/- ). IgA -/- exhibited spontaneous inflammation in the ileum but not the other parts of the gastrointestinal tract. Associated with this, there were significantly increased lamina propria CD4 + T cells, elevated productions of IFN-γ and IL-17, increased ileal segmented filamentous bacteria and skewed intestinal microflora composition. Intravital imaging using Ca 2+ biosensor showed that IgA -/- had elevated Ca 2+ signalling in Peyer's patch B cells. On the other hand, IgA tm/tm seemed to be normal, suggesting that the IgA cytoplasmic tail is dispensable for the prevention of the intestinal disorder., Conclusion: IgA plays an important role in the mucosal homeostasis associated with the regulation of intestinal microbiota and protection against mucosal inflammation especially in the ileum., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Primary myelofibrosis (PMF) is a clonal stem cell disorder characterized by myeloid dominant hematopoiesis and dysregulated proliferation of fibroblasts in the bone marrow. However, how these aberrant myeloid cells and fibroblasts are produced remains unclear., Aim and Methods: In this study, we examined in vivo engraftment kinetics of PMF patient-derived CD34+ cells in immunecompromised NOD/SCID/IL2rgKO (NSG) mice. Engrafted human cells were analyzed with flow cytometry, and proliferation of fibroblastic cells and bone marrow fibrosis were assessed with the histo-pathological examination., Results: Transplantation of PMF patient-derived circulating CD34+ fractions into NSG newborns recapitulates clinical features of human PMF. Engraftment of human CD45+ leukocytes resulted in anemia and myeloid hyperplasia accompanied by bone marrow fibrosis by six months post-transplantation. Fibrotic bone marrow contained CD45-vimentin+ cells of both human and mouse origin, suggesting that circulating malignant CD34+ subsets contribute to myelofibrotic changes in PMF through direct and indirect mechanisms., Conclusion: A patient-derived xenotransplantation (PDX) model of PMF allows in vivo examination of disease onset and propagation originating from immature CD34+ cells and will support the investigation of pathogenesis and development of therapeutic modalities for the disorder., (© 2021. Japanese Society of Hematology.)

Apixaban is used to treat venous thromboembolism (VTE) at 10 mg twice daily (BID) for 7 days, followed by 5 mg BID without dose adjustment, and non-valvular atrial fibrillation (NVAF) at 5 mg BID or 2.5 mg BID with dose adjustment criteria (DAC) including age, body weight, and renal function. The anti-factor Xa activity (AXA), prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients with VTE receiving 10 mg BID of apixaban remains unclear. Twenty-six patients (70.8±15.4 years, 10 males) with VTE receiving 10 mg BID of apixaban were enrolled. The patients were divided into two groups based on whether they met the DAC of NVAF: DAC group (n=8) and non-DAC group (n=18). Trough and peak AXA values, PT, and APTT were measured at 10 mg BID dosage and then at 5 mg BID dosage. Coagulation markers in recipients of 10 mg BID therapy were significantly higher than those of 5 mg BID recipients. A significant and strong positive correlation was observed between AXA and PT at trough and peak times. The AXA values and PT in the DAC group were significantly higher than those in the non-DAC group. No significant inter-group differences were seen in APTT. This study provides the first report of AXA distribution in VTE patients receiving 10 mg BID of apixaban. Our findings indicate that coagulation markers may differ in patients with VTE-prescribed higher doses of apixaban and a DAC may be warranted in such patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Japanese indigenous chickens include approximately 50 breeds exhibiting various morphological traits, such as a long tail. These genetic resources will be important for revealing the genetic basis of morphological traits in the future. However, little is known about the phenotypic characteristics of each breed during the growth stages. To understand age-dependent changes in growth and morphological traits, we investigated tail length, tail number, body weight, and shank length at several time points using three genetically distinct Japanese indigenous chicken breeds. A total of 155 birds from the Tosa-jidori, Chabo, and Minohikichabo breeds were used for trait measurements from 1 to 36 weeks of age to reveal breed and sex effects. Significant sex differences through the growth stages were observed for all traits except for tail number. Although there were no clear breed differences in tail length traits at the 6- and 20-week stages, Minohikichabo ultimately had a significantly longer tail due to extended tail feather growth at later stages (28 and 36 weeks). By measuring two tail length variables (central and maximum), it was revealed that the shape of the tail feathers varies with the growth stage. Minohikichabo's tail number was higher than that of Tosajidori and Chabo at earlier ages (8 and 16 weeks), which leads to an elegant visual in Minohikichabo. Tosa-jidori's body weight was higher than that of Chabo and Minohikichabo, whereas the shank lengths of Chabo and Minohikichabo were shorter than those of Tosa-jidori. These differences in body weight and shank length were consistent from the early to late growth stages. These results revealed the age-dependency of growth and morphological trait breed characteristics., Competing Interests: The authors declare no conflicts of interest.

Background: Some organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats., Methods: Male F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO 2 nanoparticles were used as comparators., Results: Persistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5), which correlated with lung tissue gene expression, were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO 2 nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure., Conclusion: Our results suggested that CL-PAA potentially causes strong neutrophil inflammation in the rat and human lung., (© 2022. The Author(s).)

The winking earlobe sign is a sign of tricuspid regurgitation, characterized by the movement of the earlobe coincident with the pulse., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: The 6-minute walk distance (6MWD) is a simple way of assessing exercise capacity. The purpose of this study was to investigate the relationship between preoperative 6MWD and long-term prognosis after esophagectomy., Methods: This retrospective cohort study involved 108 patients who underwent radical esophagectomy for esophageal cancer between 2013 and 2020. The patients were classified into the short group (SG: 6MWD < 480 m) or the long group (LG: 6MWD  ≥  480 m). To adjust for the background characteristics of both groups, propensity score matching (PSM) analysis was performed and 32 patients were matched from each group. Five-year overall survival (OS) and relapse-free survival (RFS) were analyzed by the Kaplan-Meier method. The log-rank test was used to evaluate differences in survival between the groups. After adjusting for other prognostic factors, the Cox proportional hazards model was used to investigate the impact of preoperative 6MWD on long-term prognosis., Results: The median follow-up period was 923 days. Thirty-three deaths were recorded during the study period. After PSM, 5-year OS following surgery was 29.2 and 66.1% (p = 0.003) and 5-year RFS was 27.9 and 58.6% (p  =  0.021) in the SG and LG, respectively. In Cox proportional hazards analysis, the SG was a significant independent risk factor for OS (hazard ratio 3.33; 95% confidence interval 1.37-8.11, p = 0.008) and RFS (hazard ratio 2.30; 95% confidence interval 1.08-4.88, p = 0.030)., Conclusion: The preoperative 6MWD is useful for evaluating exercise capacity and predicting the long-term outcome in patients undergoing esophagectomy., (© 2021. The Japan Esophageal Society.)

Objectives: The benefit of using a noncontact eye-tracking system is its low a burden on individuals for measuring biological signals. The goal of this study was to develop a visually induced motion sickness (VIMS) evaluation index using data collected with a noncontact eye-tracking system for driving simulator (DS) experiments., Methods: The participants included nine elderly people with visual and balance functions that did not interfere with their daily life. The gaze data of the participants were measured at rest-both before and after DS trials. The participants answered followed up the simulator sickness questionnaire (SSQ) before and after each trial. The participants were divided into two groups on the basis of their SSQ results. One group experienced VIMS during the DS trial (four people; average age, 79.0 years), whereas the other group did not experience it (five people; average age, 71.2 years)., Results: The results of VIMS symptoms were confirmed: data concerning the locus of eye-tracking were lengthened, the eye-tracking data were diffused. This experiment demonstrated the usefulness of sparse density as a quantification index based on eye-tracking data in the evaluation of VIMS., Conclusions: Regarding the application of the findings of this study, it is believed that it will be easier to detect VIMS symptoms induced by DS operations if the index can be used for an eye-tracking data-based evaluation of VIMS.

Objectives : The aims of this study were to examine the biomechanics of StandTS movements in older adults and to identify their optimal StandTS motion by measuring sitting impact forces. Methods : Healthy older women (n = 17) and healthy young women (n = 18) were asked to perform SitTS and StandTS motions at a natural speed using a chair. We measured the ground reaction forces from the participants' feet and the chair, the angle of the trunk and ankle, vertical velocity, and postural muscle activities using a force plate, motion analyzer, and electromyography, respectively. Results : Sitting impact force was significantly greater in the older women than in the young women during the StandTS motion. There was a significant difference between the trunk angle and the ankle angle during the StandTS motion and sitting impact force had a significant negative correlation with the ankle joint motion in the older women. Conclusions : The ankle joint strategy was characterized by body sway resembling a single-segment-inverted pendulum and suggests that this response is less developed in the older adult. These results indicate that the ankle joint strategy may be an important factor involved in the sitting impact force. J. Med. Invest. 69 : 278-286, August, 2022.

Objectives: These days, developments in graphical technology have resulted in an increase in the chance to view 3D video clips. Visually induced motion sickness (VIMS) has been widely reported as a negative result of viewing these clips. The onset of VIMS is explained by some hypotheses. However, the root causes of VIMS have not been elucidated yet, whereas dizziness and nausea are regarded as symptoms of VIMS. In this study, we focus on the difference in the pattern of body sway among age groups and examine whether the consistency between the background and the viewpoint motion depends on the severity of VIMS., Methods: This experiment was conducted with 116 subjects aged 15-89 years. They peripherally viewed a 3D video clip showing a sphere whose motion was consistent with their viewpoint (VC-I) and another 3D video clip of a sphere whose motion was inconsistent with their viewpoint (VC-II). Statokinesigrams (SKGs) were recorded with their eyes open and with their eyes closed for 60 s. The amount of sway was calculated from the SKGs., Results: Results showed that for all age groups, sway values were significantly higher when viewing the 3D video clip (VC-II) than in the Pre. However, for the elderly, there was no significant difference between the sway values while viewing the VC-I and those in the Pre., Conclusions: Results suggest that VIMS might not occur in the elderly because of the deterioration of their visual function, such as visual acuity and accommodation, with advancing age.

Objectives: As more countries are implementing measures to address Alzheimer's disease (AD), it is essential to update the available knowledge on the relationship between economic status and mortality in patients with AD. This study examined the influence of economic status on mortality in Japanese individuals with AD using a medical claims dataset., Design: This was a retrospective cohort study., Setting and Participants: Medical claims data from April 2014 to March 2019 were obtained from 13 local cities participating in the Longevity Improvement and Fair Evidence study. The inclusion criteria were patients aged 65 years and older who were newly diagnosed with AD during the study period., Methods: The outcome was death during the follow-up period. We assessed economic status by household income (middle to high income and low income); data were obtained from the use of the Medical Expenditure Ceiling Application and Standard Copayment Reduction Card (fee reduction card) when receiving an AD diagnosis, as an indicator of low-income status. We performed multivariate Cox proportional hazards analyses to examine the relationship between economic status and mortality; the model was adjusted for age, sex, the Charlson comorbidity index, and antidementia drug use., Results: We identified 39,081 newly diagnosed patients with AD from the Longevity Improvement and Fair Evidence study database (mean age, 83.6 years; female, 67.1%). Of these, 3189 individuals were identified as having a low-income status. After adjusting for possible confounders, low-income status was associated with mortality (hazard ratio, 1.95; 95% confidence interval, 1.84-2.07)., Conclusions and Implications: Low-income status was associated with substantially poorer prognoses in new AD cases, indicating a need for a thorough examination of medical and nursing care services utilized by low-income individuals with AD and to explore improvement strategies., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Social participation is an essential component of active aging. Physical dysfunction is restriction of social participation, but it is inconclusive that improvement of physical function contributes to promote social participation. Therefore, understanding the other factor that moderates the association between physical dysfunction and social participation is important, and social network (i.e., ties with family and friends) may be a key factor. The aims of this study were to investigate the association between physical function and frequency of social participation, with social network as a moderator, and to examine the gender differences on the relationships., Methods: We conducted a cross-sectional study among 287 community-dwelling older adults. We asked how often they participated in social groups in a week to measure frequency of social participation. Physical function and social network were measured by using the modified version of Short Physical Performance Battery for community-dwelling older adults and the abbreviated Lubben Social Network Scale, respectively. To investigate the association, we performed a linear regression analysis., Results: After adjustment, a linear regression analysis showed interactions between physical function and social network on frequent social participation (β: -0.20, 95% confidence interval [CI]: -0.40 to -0.01). Furthermore, the same association was observed only in women (adjusted β: -0.33, 95% CI: -0.65 to -0.02)., Conclusion: Our results suggested that social network moderates the association between physical function and social participation, and observed gender differences on the relationships. The findings of this study indicated the importance of multidimensional assessment and measures for improving social participation, not only physical function but also social network., (©2022 Japanese Society of Physical Therapy.)

Objectives: Organic polymers are materials widely used in our daily lives, such as daily necessities, foods, and medicines. There have been reports recently that cross-linked polyacrylic acid (CL-PAA) can possibly cause serious lung disease. We investigated whether intratracheal instillation of CL-PAA causes pulmonary disorder in rats., Methods: Male F344 rats were administered low (0.2 mg/rat) and high (1.0 mg/rat) doses of CL-PAA intratracheally and were dissected 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses in the lungs. Only the high-dose specimens were subjected to ultrasonic dispersion treatment of the administered material., Results: There was a dose-dependent increase in the total cell count, neutrophil count, neutrophil percentage, lactate dehydrogenase (LDH), surfactant protein D (SP-D), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 values in bronchoalveolar lavage fluid (BALF) from 3 days to at least 3 months after intratracheal administration of CL-PAA. Heme oxygenase-1 (HO-1) in lung tissue was also persistently elevated from 3 days to 6 months after exposure. Alkaline phosphatase (ALP) in BALF was elevated at 3 days and 1 month after exposure only in the high-dose group. Histopathological findings in lung tissue showed inflammatory and fibrotic changes from 3 days after administration, and we observed obvious inflammatory changes for up to 3 months and fibrotic changes for up to 6 months., Conclusion: Intratracheal administration of CL-PAA induced persistent neutrophilic inflammation and fibrosis in the rats' lungs, suggesting that CL-PAA may have inflammogenic and fibrogenic effects., (© 2022 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

We are constructing the "Percellome Database" containing many transcriptomes of mice exposed to a series of chemicals to elucidate the molecular mechanism of toxicity and to develop toxicity prediction technology. Acute toxicity of a chemical can be predicted to a certain extent by searching the similarity of the transcriptomes obtained by the single-dose exposure experiments. In addition, we are analyzing the relation between the transcriptome and the epigenome i.e. histone modification and genomic DNA methylation to understand the molecular mechanism of the repeated dose toxicity. We are attempting to expand the scale and improve the efficiency of the analysis by introducing artificial intelligence technologies. This approach should maximize the use of toxicogenomics technology for optimizing the experimental protocols for repeated dose toxicity studies towards 3Rs principle, and optimizing the process of in silico toxicity prediction by combining the available big data.

In this article, we present the following: a background of visually induced motion sickness (VIMS), the goal of our study, and descriptions of three recent studies conducted by our group on the measurement and analysis of eye movement while viewing movies and the relationship of eye movement with VIMS. First, this study focuses on the relationship between eye movement and motion sickness susceptibility. We investigated the relationship between the motion sickness susceptibility and the frequency of optokinetic nystagmus (OKN) with peripheral viewing. It was revealed that susceptible participants showed a lower OKN frequency under conditions that strongly support the occurrence of OKN than insusceptible participants. Second, this study focuses on the relationship between visual information and postural variation such as visually evoked postural responses (VEPRs). In this study, both eye movement and the center of gravity while viewing a movie were measured. Additionally, we evaluated the difference in the transfer gain of the transfer function (vision as input and equilibrium function as output) due to the type of movie content or way of viewing. The gain for the three-dimensional movie with peripheral viewing exceeded that for the two-dimensional movie with central viewing. Third, this study focuses on eye movement and the application of deep-learning technology. In this study, we classified the eye movement as peripheral or central using a convolutional deep neural network with supervised learning. Then, cross validation was performed to test the classification accuracy. The use of >1-s eye movement data yielded an accuracy of >90%.

Objective: This study aimed to investigate whether longitudinal changes in exercise capacity in patients with acute myocardial infarction (AMI) differ by sex and clarified what contributed to these differences., Methods: We retrospectively examined the differences in each variable between men and women in 156 patients with AMI (mean age: 65 ± 12 years; 82.0% male) who participated in a 3-month cardiac rehabilitation (CR) program and could be followed-up for exercise capacity 12-months after AMI onset. Sex-related differences in the change in peak oxygen uptake (peak VO 2 ) at baseline, 3-months, and 12-months after AMI were analyzed., Results: Male patients with AMI were younger and had higher body mass index and employment rate than women. The attendance of the CR program was higher in women (men vs. women; 10 [3-15] vs. 14 [11-24] sessions, p = 0.0002). Women showed a significant lower %change in peak VO 2 after 12 months (men vs. women; 7.8% [-0.49% to 14.6%] vs. 1.3% [-5.7% to 7.5%], p = 0.013). In multiple linear regression analysis, age (β = -0.76, 95% confidence interval [CI] = -1.0 to -0.50, p <0.0001) and female sex (β = -6.3, 95% CI = -9.1 to -3.5, p <0.0001) were negative independent predictors of change in peak VO 2 over 12 months, while CR attendance (β = 0.21, 95% CI = 0.0032-0.42, p = 0.047) and recommended exercise habit after the CR program (β = 2.1, 95% CI = 0.095-4.1, p = 0.040) were positive independent predictors of change in peak VO 2 over 12 months., Conclusion: In female patients, exercise capacity improved during the CR program but decreased to AMI onset levels after 12 months., (©2022 Japanese Society of Physical Therapy.)

Background: Since the start of the COVID-19 pandemic, the number of people working at home has grown significantly., Objective: This cohort study aimed to investigate whether the frequency of working at home was associated with changes in body mass index (BMI) and productivity from 2018 to 2020., Method: Frequency of working at home was self-reported. Participants were classified into three groups based on mean frequency of working at home per week (no working at home: ≦ 0.5 days, low frequency: 0.5 to 2.5 days, and high frequency: >2.5 days). Productivity was measured using a numerical rating scale, and BMI was calculated using height and weight. Changes in BMI and productivity were calculated by subtracting 2018 data from 2020 data. Linear regression analysis was performed by considering BMI and productivity change as outcomes and frequency of working at home as explanatory variable., Results: BMI change in the high frequency group was significantly smaller than in the group that did not work at home (crude; coefficient: -0.27; 95% CI: -0.55--0.01, adjusted; coefficient: -0.30; 95% CI: -0.60--0.01). Frequency of working at home was not associated with productivity change., Conclusion: Working at home may be a solution for preventing BMI from increasing significantly.

Depressive symptoms have a strong effect on appetite decline in older adults. There is also an association between social activity and decreased depressive symptoms, but the mechanism between appetite and social activity with respect to depressive symptoms is unclear. This cross-sectional study examined the direct and indirect effects of social activity on appetite, via depressive symptoms. A total of 259 community-dwelling older adults (mean age 75.1 ± 5.3 years; 55% female) completed the Council on Nutrition Appetite Questionnaire (CNAQ) and the 15-item version of the Geriatric Depression Scale (GDS). We used a cutoff score of 6 on the GDS-15 to determine whether participants displayed depressive symptoms. Social activity was assessed based on the number of activities participated in at least 1-3 times per month. The types of social activity consisted of local community, hobby, sports, citizen, industry, religion, volunteer, and others. Other assessed factors included age, sex, education, financial status, living situation, and comorbidities. To examine the relationships among social activity, depressive symptoms, and appetite, structural equation modeling (SEM) was used, adjusting for variables associated with depressive symptoms or appetite in multivariate analyses. SEM revealed that participation in more types of social activity had a significant indirect effect on higher appetite score via less having depressive symptoms (β = 0.04, p = 0.018). Our findings suggest that active participation in social activities may have a positive effect on good appetite via not having depressive symptoms among older adults. Further longitudinal or intervention studies are needed to confirm our findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Muscle strength decline is reported to predict mortality in many cancers. However, there is little knowledge of the relation between muscle strength decline and clinical outcomes of allogeneic haematopoietic stem cell transplantation (allo-HSCT). This study aimed to determine the impact of pre-transplant lower extremity muscle strength (LEMS) on post-transplant overall survival (OS) and non-relapse mortality (NRM)., Methods: In this retrospective cohort study, 97 adult patients underwent allo-HSCT during 2012-2020. LEMS was defined as knee extension force divided by patient's body weight. The patients were divided into low and high LEMS groups based on pre-transplant LEMS. OS was measured using the Kaplan-Meier method and the Cox proportional hazards model. The cumulative incidence of NRM was evaluated using the Fine and Gray method, with relapse considered as a competing risk event., Results: Probability of OS was significantly lower in the low LEMS groups (HR 2.48, 95% CI 1.20 to 5.12, p=0.014) than in the high LEMS group on multivariate analysis. Five-year OS was 25.8% and 66.4% in the low and high LEMS groups, respectively. Risk of NRM was significantly higher in the low LEMS group (HR 4.49, 95% CI 1.28 to 15.68, p=0.019) than in the high LEMS group. The cumulative incidence of NRM was 41.4% and 11.1% in the low and high LEMS groups, respectively., Conclusions: Pre-transplant LEMS was a significant factor in predicting OS and NRM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We developed an intranasal vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the replication-incompetent human parainfluenza virus type 2 (hPIV2) vector BC-PIV, which can deliver ectopic gene as stable RNA and ectopic protein on the envelope. BC-PIV expressing the full-length prefusion-stabilized spike gene (K986P/V987P) of SARS-CoV-2, S-2PM, possessed a corona-like viral envelope. Intranasal vaccination of mice with BC-PIV/S-2PM induced high levels of neutralizing immunoglobulin G (IgG) and mucosal IgA antibodies against the spike protein. Although BC-PIV showed hemagglutinating activity, BC-PIV/S-2PM lacked such activity, in accordance with the presence of the massive spike protein on the viral surface. Furthermore, single-dose intranasal vaccination of hamsters with BC-PIV/S-2PM completely protected the lungs from SARS-CoV-2 at 11-week post-immunization, and boost vaccination two weeks before the challenge conferred virtually complete protection of the nasal turbinates against SARS-CoV-2. Thus, this chimeric hPIV2/spike intranasal vaccine is a promising vaccine candidate for SARS-CoV-2 to curtail virus transmission., Competing Interests: J.O., M.Im., M.F., R.O., S.Y., Y.Kaw., and T.N. are patent applicants for recombinant BC-PIV vaccine against SARS-CoV-2. M.F. is a founder of BioComo, Inc., and J.O. is an employee of BioComo, Inc. J.O., M.F., M.M., and T.N. have shares of stock in BioComo, Inc. M.M. is a scientific advisor of JEOL Ltd. The other authors declare no competing interests., (© 2021 The Author(s).)

Background: Few studies have examined patient satisfaction with playing pre-injury sports after anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to investigate patient satisfaction with playing pre-injury sport and identify factors associated with satisfaction., Methods: A total of 97 patients underwent unilateral ACL reconstruction using a hamstring autograft and returned to pre-injury sports 1 year after surgery. Patient satisfaction with playing pre-injury sport was assessed by a visual analog scale (VAS) and an ordinal four-grade scale. Problems related to the operated knee were also assessed. Knee muscle strength, single leg hop distance, knee laxity, subjective knee pain, and fear of movement/reinjury using Tampa Scale for Kinesiophobia-11 (TSK-11) were measured. Multivariate linear regression analysis was performed to determine the factors associated with patient satisfaction with playing pre-injury sport 1 year after surgery., Results: The average VAS score for patient satisfaction with playing pre-injury sports 1 year after surgery was 77.8 ± 20.2. Of the 97 patients, 87 patients (89.7%) answered "satisfied" or "mostly satisfied", whereas 51 patients (52.6%) had one or more problems. Multivariate linear regression analysis identified that the TSK-11 score was associated with patient satisfaction with playing a pre-injury sport 1 year after surgery., Conclusion: Most of the patients who returned to pre-injury sports were satisfied with their outcomes. In contrast, approximately half of the patients had one or more problems after returning to play pre-injury sports. In particular, fear of movement/reinjury was significantly associated with patient satisfaction with playing pre-injury sport 1 year after surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: A substantial number of women have postpartum lumbopelvic pain (LBPP). Additionally, many postpartum women stay for long inactivity. Therefore, we examined the impact of sedentary behavior on persistent postpartum LBPP and the difference in this impact due to parity. Materials and Methods: This cohort study followed up women who had reported LBPP at 4 months postpartum and divided them into the presence or absence of LBPP at 10 months postpartum. Sedentary time and physical activity were assessed at 4 months postpartum using the International Physical Activity Questionnaire short form. Univariate and multivariate logistic regression analysis was used to calculate persistent LBPP odds ratios (ORs) according to sedentary times, followed by stratification analysis by parity. The institutional review board approval was obtained. Results: A total of 182 women (32.1 ± 5.1 years old) were included for analysis and 112 (61.5%) participants had persistent LBPP at 10 months postpartum. Those with persistent LBPP at 10 months postpartum had increased sedentary time (5.0 [3.0-7.0] hours vs. 3.5 [2.0-6.0] hours, p  = 0.05) at 4 months compared with those without LBPP. Even after adjusting for confounding factors, longer sedentary time at 4 months postpartum affected persistent LBPP at 10 months postpartum in primiparas (adjusted OR [95% confidence interval, CI] = 1.28 [1.05-1.55]), but longer sedentary time at 4 months postpartum did not affect persistent LBPP at 10 months postpartum in multiparas (adjusted OR [95% CI] = 0.96 [0.86-1.07]). Conclusion: Sedentary behavior after childbirth is associated with persistent postpartum LBPP in primiparas, but not multiparas. Reducing sedentary time might be beneficial to prevent persistent postpartum LBPP for primiparas.

Objectives: This study aimed to assess the effect of home-based preoperative pulmonary rehabilitation (HBPPR) on the incidence of postoperative complications, length of stay (LOS), and duration of intercostal catheterization in non-small cell lung cancer (NSCLC) patients who underwent lung resection., Materials and Methods: In this retrospective cohort study, 144 patients who underwent lung resection were recruited, 51 of whom received HBPPR, comprising respiratory muscle training and was supervised (for patients undergoing it for the first time). Patients continued these programs for 2-4 weeks during the preoperative waiting period, in their homes. Data on postoperative complications graded according to the Clavien-Dindo classification, LOS, and intercostal catheterization duration were collected from medical records. These outcomes were compared between the HBPPR and non-HBPPR groups using Fisher's exact test and Wilcoxon rank sum test, after 1:1 propensity score matching to avoid selection bias., Results: Forty-nine matched pairs were extracted using propensity score matching. HBPPR reduced the onset of postoperative complications (p = 0.04), with the relative ratio (RR) for Clavien-Dindo Class I postoperative complications showing a significant difference (RR 0.55, 95% CI 0.30-1.02; p = 0.05), whereas RRs for the other Clavien-Dindo classes were not statistically significant. There was no significant difference in LOS or the duration of intercostal catheterization., Conclusion: HBPPR reduced the incidence of Clavien-Dindo Class I postoperative complications after lung resection. Implementing HBPPR practices in a clinical setting would benefit patients unable to receive supervised preoperative pulmonary rehabilitation due to access barriers, time, and financial constraints., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hypereosinophilic syndrome (HES) is defined by persistently elevated blood eosinophil levels and is associated with evidence of organ damage. Cardiovascular involvement in HES is most commonly associated with Loffler endocarditis (cardiac HES). Cardiac HES is typically characterized by progressive subendocardial fibrosis with overlying mural thrombus formation, leading to restrictive dysfunction of the left ventricle. The thrombus from cardiac HES could result in cardiogenic stroke; however, most of the stroke cases with HES were not associated with huge thromboembolism rather multiple infarcts in the watershed area. The major clinical features of 97 previously reported cases of stroke with HES are as follows: the median age was 52 years, of which 61 (63%) were men; the initial presenting symptoms were neurological (73%), followed by headache (16%), respiratory symptoms (9%), and visual symptoms (9%). Almost half of the cases were diagnosed with cardiac HES. The characteristics of cardiac findings were mural thrombi, endomyocardial fibrosis, and a restrictive pattern of heart failure. Cerebral findings revealed 78 cases (80%) were described as multiple infarctions and 55 cases (57 %) were involved with watershed areas, whereas 11 cases (11％) were described as embolic stroke for one proximal large-vessel occlusion. Regarding treatment, 71 (73%), 28 (29%), and 16 (16%) patients were treated with steroids, anticoagulants, and antiplatelets, respectively. The overall mortality and recovery rates were 11% and 89%, respectively. Physicians should know most cases of stroke with HES are characterized by multiple infarctions in the watershed area, and cardiac HES is not always associated with stroke., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Rationale: Paraganglioma (PGL), an extra-adrenal pheochromocytoma, is a rare tumor, especially in children. While hypersecretion of catecholamines causes the classic triad of headaches, palpitations, and profuse sweating, prompt diagnosis is still challenging., Patient Concerns: For 7 months, an 8-year-old boy complained of polyuria and weight loss, followed by proteinuria and headache for 1 month prior to admission. He was admitted to our hospital due to an afebrile seizure., Diagnosis: His blood pressure remained markedly elevated even after cessation of the convulsion. Magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Abdominal computed tomography showed a mass lesion encasing the left renal artery, measuring 41 mm in length along its major axis. The plasma and urine levels of normetanephrine were elevated. Additionally, iodine-123-metaiodobenzylguanidine scintigraphy showed an abnormal uptake in the abdominal mass with no evidence of metastasis. Based on these findings, we tentatively diagnosed him with PGL., Intervention: Substantial alpha- and beta-blocking procedures were performed, followed by a tumor resection and an extended left nephrectomy on day 31 of hospitalization. Pathological findings confirmed the diagnosis of PGL., Outcome: The postoperative course was uneventful, and his blood pressure normalized without the use of antihypertensive agents. Genetic testing revealed a known SDHB germline mutation. The same mutation was also detected on his father and paternal grandfather without any history of hypertension or malignant tumor., Lesson: It remains challenging to diagnose pheochromocytoma/paraganglioma (PPGL) promptly because PPGL can present with a variety of symptoms. Preceding symptoms of the presented case might be caused by PGL. Although PPGL is a rare disease, especially in children, it should be considered in differential diagnosis when various unexplained symptoms persist., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Dynamic regulation in molecular networks including cell cycle regulation and DNA damage response play an important role in cancer. To reveal the feature of cancer malignancy, gene expression and network regulation were profiled in diffuse- and intestinal-type gastric cancer (GC). The results of the network analysis with Ingenuity Pathway Analysis (IPA) showed that the activation states of several canonical pathways related to cell cycle regulation were altered. The G 1 /S checkpoint regulation pathway was activated in diffuse-type GC compared to intestinal-type GC, while canonical pathways of the cell cycle control of chromosomal replication, and the cyclin and cell cycle regulation, were activated in intestinal-type GC compared to diffuse-type GC. A canonical pathway on the role of BRCA1 in the DNA damage response was activated in intestinal-type GC compared to diffuse-type GC, where gene expression of BRCA1, which is related to G 1 /S phase transition, was upregulated in intestinal-type GC compared to diffuse-type GC. Several microRNAs (miRNAs), such as mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451 and mir-605, were identified to have direct relationships in the G 1 /S cell cycle checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in epithelial-mesenchymal transition (EMT) conditions. The alterations in the activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC highlighted the significance of cell cycle regulation in EMT.

Esaxerenone, a mineralocorticoid receptor blocker (MRB), is a new antihypertensive agent. However, esaxerenone-related data with respect to hypertension with heart failure are limited. We investigated the safety and efficacy of esaxerenone in hypertensive patients with heart failure with reduced ejection fraction (HFrEF). Hypertensive patients with HFrEF treated with esaxerenone were retrospectively analyzed at two timepoints (short-term: 35±15 days; mid-term: 167±45 days). Adverse events including hyperkalemia (K+ >5.5 mEq/L), worsening renal function (WRF; estimated glomerular filtration rate (eGFR) reduction by ≥20%), and hypotension (systolic blood pressure <90 mmHg) were evaluated. eGFR and K+, serum creatinine, and brain natriuretic peptide (BNP) levels at baseline, short-term, and mid-term assessments were compared. Patients administered esaxerenone as their first MRB (first-MRB cohort) and those who converted from another MRB (conversion cohort) were separately analyzed. There were 50 (56±10 years old, 26% female) patients. At the short-term assessment, hyperkalemia or hypotension was not observed at a dose of 2.0±0.9 mg/day. Seven patients (14%) showed WRF. K+ was slightly elevated (4.12±0.41 to 4.25±0.39 mmol/L, p = 0.07) and eGFR was significantly reduced (66.9±19.6 mL/min/1.73 m2 to 62.4±19.7 mL/min/1.73 m2, p = 0.006). In the conversion cohort, significant changes in K+ and eGFR from baseline were not observed at the short-term assessment. BNP levels were consistently improved regardless of the cohorts (first-MRB cohort, 310 [110-370] pg/mL to 137 [47-152] pg/mL, p = 0.001; conversion cohort, 181 [30-203] pg/mL to 108 [26-146] pg/mL, p = 0.028). At the mid-term assessment, there were no significant changes in K+ and eGFR compared with the short-term assessment. In conclusion, esaxerenone was safe for hypertensive patients with HFrEF. Hyperkalemia and hypotension were rarely noted, while eGFR was marginally reduced. Moreover, esaxerenone might be beneficial for HFrEF in terms of BNP level reduction., Competing Interests: We declared that YK received lecture fees and research grant from Daiichi Sankyo Co., Ltd. YK does not have any other relation with this funder, including employment, consultancy, patents, products in development, or marketed products. This does not influence our adherence to PLOS ONE policies on sharing data and materials.

Aim: Adiponectin (APN) exhibits different atheroprotective effects, and we have previously reported that APN function is modulated by its binding proteins, E-selectin ligand 1, Mac-2 binding protein, and cystatin C. In the present study, we aimed to identify a novel atheroprotective mechanism of APN via C-C motif chemokine 2 (CCL2)., Methods: We conducted iMAP ® -intravascular ultrasound (IVUS) in 111 Japanese male patients with stable angina. The plaque characteristics were determined where "plaque burden" [(EEM CSA - lumen CSA)/(EEM CSA)×100 (%)] ＞50%, and their correlation with serum CCL2 and APN levels was analyzed. Using western blot analysis, the effects of APN on the biological effects of CCL2 were examined in their mutual binding by co-immunoprecipitation assay, the monocyte migration, and the phosphorylation of MAP kinases., Results: In a clinical study, we found that the percentage of plaque in the culprit lesion was correlated positively with serum CCL2 and negatively with serum APN levels, with significance. We identified CCL2 as a novel APN-binding serum protein using immunoprecipitation and western blot analysis. CCL2-induced phosphorylation of MAP kinases and monocyte migration was significantly attenuated by APN in vitro., Conclusion: The opposite association of APN and CCL2 on the percentage of coronary plaque might be caused by their direct interaction and competitive functions on monocyte migration.

Aim: States of vulnerability are multidimensional and become more prevalent with advancing age. These states and the causal relationships between them, merit thorough investigation. This study aimed to understand the reciprocal relationship between the constructs of the locomotive syndrome and social frailty among a community of older adults., Methods: This 2-year cohort study examined a community of older adults (≥75 years) consisting of 1177 members. Using Makizako's method, social frailty was deemed to be present if more than two out of five questions were answered negatively. Locomotive syndrome was measured with the Geriatric Locomotive Function Scale-25, which consists of 25 items measuring an individual's risk of developing locomotive syndrome; a total score of ≥16 identified the presence of locomotive syndrome. Possible reciprocal associations between locomotive syndrome and social frailty were assessed using Cox proportional hazards analyses., Results: A total of 748 older adults were analyzed in the following subgroups. Among 574 participants without social frailty at the baseline, the presence of locomotive syndrome at the baseline was associated with new-onset social frailty during the next 2 years, after adjusting for confounding factors (hazard ratio 1.76, 95% confidence interval 1.17-2.65). Conversely, the presence of social frailty among participants without locomotive syndrome in the baseline was not associated with new-onset locomotive syndrome., Conclusion: The presence of locomotive syndrome was determined to be a risk factor for the onset of social frailty. Therefore, interventions that address the negative impact of locomotive syndrome are a first step toward addressing these vulnerable conditions. Geriatr Gerontol Int 2021; 21: 981-984., (© 2021 Japan Geriatrics Society.)

We reveal the microscopic origin of electric polarization P[over →] induced by noncollinear magnetic order. We show that in Mott insulators, such P[over →] is given by all possible combinations of position operators r[over →][over ^]&#95;{ij}=(r[over →]&#95;{ij}^{0},r[over →]&#95;{ij}) and transfer integrals t[over ^]&#95;{ij}=(t&#95;{ij}^{0},t&#95;{ij}) in the bonds, where r[over →]&#95;{ij}^{0} and t&#95;{ij}^{0} are spin-independent contributions in the basis of Kramers doublet states, while r[over →]&#95;{ij} and t&#95;{ij} stem solely from the spin-orbit interaction. Among them, the combination t&#95;{ij}^{0}r[over →]&#95;{ij}, which couples to the spin current, remains finite in the centrosymmetric bonds, thus yielding finite P[over →] in the case of noncollinear arrangement of spins. The form of the magnetoelectric coupling, which is controlled by r[over →]&#95;{ij}, appears to be rich and is not limited to the phenomenological law P[over →]∼ε&#95;{ij}×[e&#95;{i}×e&#95;{j}] with ε&#95;{ij} being the bond vector connecting the spins e&#95;{i} and e&#95;{j}. Using density-functional theory, we illustrate how the proposed mechanism works in the spiral magnets CuCl&#95;{2}, CuBr&#95;{2}, CuO, and α-Li&#95;{2}IrO&#95;{3}, providing a consistent explanation for the available experimental data.

Purpose: Persistent low back and pelvic pain (LBPP) is a postpartum-specific health problem. Sleep disturbances' association with persistent LBPP is not yet clear. We aimed to examine the cross-sectional association between sleep disturbance and persistent LBPP at 4 months postpartum., Methods: We enrolled 120 women with LBPP during pregnancy (mean age, 31.8; standard deviation, 4.9 years). The primary outcome was persistent LBPP. We assessed LBPP severity at 4 months postpartum using the Numerical Rating Scale (NRS), where women with an NRS score of ≥ 4 at 4 months postpartum were allocated to the persistent LBPP group. We assessed sleep disturbance at 4 months postpartum using the Japanese version of the Pittsburgh Sleep Quality Index with a total score of ≥ 6 indicating sleep disturbance. Moreover, we performed univariate and multiple logistic regression analyses to examine the cross-sectional association of sleep disturbance with persistent LBPP. The relevant confounding variables were age, body mass index, parity, and history of LBPP before pregnancy., Results: Among the 120 women, 45 women had persistent LBPP (37.5%) with 32 (71.1%) of them reporting sleep disturbance. There was a significant association of sleep disturbance with persistent LBPP (odds ratio [OR], 2.81; 95% confidence interval [95% CI], 1.28-6.19), which remained after adjustments for confounding variables (OR, 2.98; 95% CI, 1.31-6.75)., Conclusion: Our findings indicate that sleep disturbance is associated with persistent LBPP at 4 months postpartum; therefore, it should be taken into consideration in postpartum women with persistent LBPP., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The therian-specific gene paternally expressed 10 (Peg10) plays an essential role in placenta formation: Peg10 knockout mice exhibit early embryonic lethality as a result of severe placental defects. The PEG10 protein exhibits homology with long terminal repeat (LTR) retrotransposon GAG and POL proteins; therefore, we generated mice harboring a mutation in the highly conserved viral aspartic protease motif in the POL-like region of PEG10 because this motif is essential for the life cycle of LTR retrotransposons/retroviruses. Intriguingly, frequent perinatal lethality, not early embryonic lethality, was observed with fetal and placental growth retardation starting mid-gestation. In the mutant placentas, severe defects were observed in the fetal vasculature, where PEG10 is expressed in the three trophoblast cell layers that surround fetal capillary endothelial cells. Thus, Peg10 has essential roles, not only in early placenta formation, but also in placental vasculature maintenance from mid- to late-gestation. This implies that along the feto-maternal placenta interface an interaction occurs between two retrovirus-derived genes, Peg10 and retrotransposon Gag like 1 (Rtl1, also called Peg11), that is essential for the maintenance of fetal capillary endothelial cells., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Lions (Panthera leo) breed well under captivity, so contraception has been commonly conducted for population management, leading to a demand for a less invasive and reversible contraceptive approach in lions. In this study, we examined the efficacy of a commercial gonadotropin-releasing hormone vaccine as a method of suppressing reproductive activity in a sexually matured female lion. Under behavioral restraint, the vaccine was injected twice (days 0 and 109). After the initial vaccination, ovarian activity is still observed. After the second vaccination, contraceptive effect was confirmed for 246 days until restart of estrous cycles. We confirmed only a slight swelling around the injection site after the second vaccination. This study may suggest an alternative option for a contraceptive method in lions.

AkaLumine hydrochloride, named TokeOni, is one of the firefly luciferin analogs, and its reaction with firefly luciferase produces near-infrared (NIR) bioluminescence. Prior to studying the bioluminescence mechanism, basic knowledge about the chemical structures, electronic states, and absorption properties of TokeOni at various pH values of solution has to be acquired. In this paper, the absorption spectra for TokeOni and AkaLumine at pH 2-10 were measured. Density functional theory (DFT) calculations, time-dependent DFT calculations, and the vibrational analyses were carried out. The absorption spectra indicate that the chemical forms of TokeOni in solutions are same as those of AkaLumine. The peaks at pH 7-10 in the absorption spectra correspond to the excitation from the ground state of a carboxylate anion of AkaLumine, the peak at pH 2 corresponds to the excitation from the ground state of a carboxylate anion with an N-protonated thiazoline ring and N-protonated dimethylamino group of AkaLumine, and the peak at pH 4 corresponds to the excitation from the ground state of a carboxylate anion with an N-protonated thiazoline ring of AkaLumine., (© 2021 American Society for Photobiology.)

Objectives: Irreversible morphological regressions of the teeth or related structures in older people can diminish their overall health. However, research on human aging in dentistry is complicated by several confounding factors. In this study, we conducted a morphometric analysis of the mandibular second molars and surrounding alveolar bone in C57BL/6 mice to evaluate age-related changes in the oral cavity., Methods: The animals were divided into five groups based on their age: 4 weeks (juvenile mice; n = 5); 20 weeks (n = 7), 50 weeks (n = 5), 77 weeks (n = 7), and 100 weeks (n = 5); changes were evaluated using micro-computed tomography., Results: The molars of juvenile mice had sharp and pointed cusps and presented maximum heights. With age and occlusal wear, the cusp heights demonstrated a significant decrease (up to 75%) until the last stage of life. Conversely, apparent lesions were not observed on the basal portion of the crown, even in the most heavily worn teeth. The roots of the molars continued to grow in length at 4 weeks of age. Alveolar bone resorption begins to occur in middle age and continues throughout life. The proportion of vertical bone loss reached approximately 40% of the entire root length, demonstrating a remarkable increase between weeks 77 and 100., Conclusions: Overall, these morphological changes were similar to those observed in humans. Therefore, it might be appropriate to use aged mice as an experimental model for basic and clinical research in geriatric dentistry., Competing Interests: Conflicts of interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Objectives: Frailty is a multidimensional syndrome. However, typical frailty scales used in oncology clinics assess physical impairment and/or malnutrition but do not consider the social domain. Our study aimed to clarify the relationship between preoperative social frailty and overall survival (OS) and cancer-specific survival (CSS) among older patients with gastrointestinal cancer., Design: This was a prospective cohort study., Setting and Participants: This single-center study recruited 195 patients with gastrointestinal cancer scheduled for curative surgery and aged >60 years., Methods: The outcomes considered were the OS and CSS of surgery. Primary associated factors included frailty defined as a Geriatric 8 score ≤14; social frailty defined as 2 or more of the following-going out less frequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not talking with someone daily, and combinations therein [no frailty without social frailty (-/-), frailty without social frailty (+/-), no frailty with social frailty (-/+), and frailty with social frailty (+/+)]. We used the Cox proportional hazards model and the Fine and Gray proportional subdistribution hazard model adjusting for confounding factors., Results: Of the 195 patients, 181 (mean age, 72.0 years) were included for analysis. The median follow-up time was 994 days. Social frailty (hazard ratio 3.10) and their combinations [6.35; frailty with social frailty (+/+) vs no frailty without social frailty (-/-)] were significant predictors of OS. Social frailty (subdistribution hazard ratio 3.23) and their combinations (7.57) were significant predictors of CSS., Conclusions and Implications: Preoperative social frailty is a predictor of OS and CSS in older patients with gastrointestinal cancer. Screening for social frailty, frailty, and their combinations in older patients with cancer is important., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern with long-term administration of lenvatinib. The long-term effects of lenvatinib on renal function in patients with advanced differentiated thyroid carcinoma (DTC) were analyzed., Method: This study involved 40 DTC patients who continued lenvatinib therapy for ≥6 months. Estimated glomerular filtration rate (eGFR) was calculated as an indicator of renal function. The temporal course of eGFR, effects of baseline eGFR on eGFR changes, and factors affecting renal impairment were investigated., Results: The overall cohort showed sustainable decreases in eGFR, with decreased values of 11.4, 18.3, and 21.0 mL/min/1.73 m 2 at 24, 36, and 48 months after starting treatment, respectively. No differences in eGFR decrease every 6 months were seen for three groups classified by baseline eGFR ≥90 mL/min/1.73 m 2 (n = 6), < 90 but ≥60 mL/min/1.73 m 2 (n = 26), or < 60 but ≥45 mL/min/1.73 m 2 (n = 8). Grade 3 proteinuria was associated with declines in eGFR (p = 0.0283). Long observation period was also associated with decreases in eGFR (p = 0.0115), indicating that eGFR may decrease in a time-dependent manner., Conclusion: Lenvatinib can induce declines in eGFR, particularly with treatment duration > 2 years, regardless of baseline eGFR. Proteinuria is a risk factor for declines in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making protocols must balance the benefits of lenvatinib continuation with acceptable risks of harm., (© 2021. The Author(s).)