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Shunsuke Kiuchi,1 Shinji Hisatake,1 Muneyasu Kawasaki,2 Osamu Hirashima,2 Takayuki Kabuki,1 Junichi Yamazaki,1 Takanori Ikeda1 1Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, 2Division of Cardiology and Cardiovascular Surgery, Misato Central General Hospital, Saitama, JapanBackground: The aim of controlling hypertension is to protect against arteriosclerosis. Calcium channel blockers (CCBs) and renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to have antihypertensive effects, but their effect on the progression of arteriosclerosis is not fully understood. The cardio-ankle vascular index (CAVI) was developed to estimate arterial stiffness, which reflects arteriosclerosis. In this study, we investigated the longer term effects of CCBs and RAAS inhibitors on the progression of arteriosclerosis by monitoring the CAVI.Methods: Our subjects were 115 consecutive, non-smoking hypertensive patients on oral treatment with a CCB and/or RAAS inhibitor for at least 3 years in whom the CAVI was measured on two occasions approximately 1 year apart during the period from January 2009 to December 2011. Changes in CAVI were evaluated in patients administered a CCB alone (group C), an RAAS inhibitor (group R) alone, or both drugs together (group B). Changes in laboratory findings, blood pressure, and ankle-brachial index were similarly evaluated.Results: No significant change in laboratory findings, blood pressure, or ankle-brachial index was noted in any of the groups. The CAVI decreased slightly in group R (first recording 8.80±1.03, second recording 8.57±0.97, P=0.517) and increased significantly in group C (first 8.45±0.92, second 8.95±1.04, P=0.038), but showed no significant change in group B (first 9.01±1.26, second 9.05±1.35, P=0.851).Conclusion: Long-term administration of a CCB alone increased the CAVI, but this effect was offset by the concomitant use of a RAAS inhibitor, indicating that a RAAS inhibitor might protect against arteriosclerosis. Keywords: cardio-ankle vascular index, renin-angiotensin-aldosterone system inhibitor, calcium channel blocker

Evidence suggests a longitudinal association between tooth loss and cognitive function. However, the temporality of this association is not well understood. We investigated the effect of several emulated tooth loss prevention scenarios on cognitive function. We used data from 3 waves (baseline: 2009, second wave: 2011–2012, and third wave: 2015) of the Panel on Health and Ageing of Singaporean Elderly (PHASE). PHASE targeted older adults, aged ≥60 y, in Singapore. Number of teeth was used as a time-varying exposure (baseline, second wave). Cognitive function (Short Portable Mental Status Questionnaire score) in the third wave was assessed as the outcome. Multiple time-invariant (baseline) and time-varying (baseline and second wave) covariates were included. The "longitudinal modified treatment policy approach" combined with targeted minimum loss–based estimation was used to define and estimate additive effects of emulated tooth loss prevention scenarios. Emulated scenarios were the following: what if edentate people retained 1 to 4 teeth (scenario 1), what if those with <5 teeth retained 5 to 9 teeth (scenario 2), what if those with <10 teeth retained 10 to 19 teeth (scenario 3), and what if everyone retained ≥20 teeth (scenario 4)? A total of 1,516 participants, excluding those with severe cognitive impairment, were included (male: 41.6%). The mean age at baseline was 70.6 y (SD = 7.1). The mean SPMSQ score at baseline was 2.06 (SD = 0.02) for edentulous, 1.55 (SD = 0.04) for 1 to 4 teeth, 1.61 (SD = 0.03) for 5 to 9 teeth, 1.73 (SD = 0.02) for 10 to 19 teeth, and 1.71 (SD = 0.02) for ≥20 teeth. Additive effect of hypothetical intervention gradually increased with intensity of prevention from scenario 1 to scenario 4 (scenario 1: −0.02 [95% CI, −0.08 to 0.04], scenario 2: −0.05 [95% CI, −0.11 to −0.00], scenario 3: −0.07 [95% CI, −0.14 to −0.00], scenario 4: −0.15 [95% CI, −0.23 to −0.06]). Emulated tooth loss prevention interventions were associated with better cognitive function score. Therefore, preventing tooth loss could potentially benefit maintenance of cognitive function among older adults. [ABSTRACT FROM AUTHOR]

Tooth loss is a risk factor for increased mortality; however, the underlying mechanism remains unclear. This study aimed to evaluate the mediating effect of weight change on the relationship between tooth loss and mortality risk. This was a 10-y follow-up prospective cohort study using the data from the Japan Gerontological Evaluation Study (JAGES). The participants were independent older adults aged ≥65 y at baseline and were followed up from 2010 to 2020. The incidence of death in 2013 and 2020, incidence of >5% weight loss/gain in 2010 and 2013, and the number of remaining teeth in 2010 were used as the outcome, mediator, and explanatory variables, respectively. We conducted causal mediation analysis by fitting the Cox proportional hazard model, including possible confounders. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the total effect (TE), natural indirect effect (NIE), and proportion mediated (PM) were estimated. Among the 34,510 participants, the mean age was 72.6 (SD = 5.4) y, and 47.6% were men. From 2013 to 2020, 14.0% of the participants (n = 4,825) died, 60.5% (n = 20,871) had 0 to 19 remaining teeth, and 17.2% (n = 5,927) and 8.4% (n = 2,907) experienced >5% weight loss and gain, respectively. The mortality rate was 0.016 per person-year among those with ≥20 remaining teeth and 0.027 per person-year among those with 0 to 19 remaining teeth. Weight loss of >5% significantly mediated the association between tooth loss and higher mortality risk (TE: HR, 1.28 [95% CI, 1.16 to 1.40]; NIE: HR, 1.03 [95% CI, 1.02 to 1.04]; PM, 13.1%); however, we observed a slight mediating effect for >5% weight gain (NIE: HR, 1.003 [95%CI, 1.0001 to 1.01]; PM, 1.3%). The present study suggests that a clinically meaningful level of weight loss mediated the association between tooth loss and increased risk of mortality among independent older adults. [ABSTRACT FROM AUTHOR]

Some modifiable risk factors for dementia are closely related to oral health. Although eating and speaking abilities are fundamental oral functions, limited studies have focused on the effect of malnutrition and lack of social interaction between oral health and dementia. We investigated the mediating effects of nutritional and social factors on the association between the number of teeth and the incidence of dementia. This 6-y cohort study used data from the Japan Gerontological Evaluation Study targeting older adults aged 65 y and above. The number of teeth (exposure) and covariates in 2010 (baseline survey), mediators (weight loss, vegetable and fruit intake, homeboundness, social network) in 2013, and the onset of dementia (outcome) between 2013 and 2016 were obtained. The Karlson–Holm–Breen mediation method was applied. A total of 35,744 participants were included (54.0% women). The mean age at baseline was 73.1 ± 5.5 y for men and 73.2 ± 5.5 y for women. A total of 1,776 participants (5.0%) had dementia during the follow-up period. There was a significant total effect of the number of teeth on the onset of dementia (hazard ratio, 1.14; 95% CI, 1.01–1.28). Controlling for nutritional and social mediators, the effect of the number of teeth was reduced to 1.10 (95% CI, 0.98–1.25), leaving an indirect effect of 1.03 (95% CI, 1.02–1.04). In the sex-stratified analysis, the proportion mediated by weight loss was 6.35% for men and 4.07% for women. The proportions mediated by vegetable and fruit intake and homeboundness were 4.44% and 4.83% for men and 8.45% and 0.93% for women, respectively. Furthermore, the proportion mediated by social networks was 13.79% for men and 4.00% for women. Tooth loss was associated with the onset of dementia. Nutritional and social factors partially mediated this association. [ABSTRACT FROM AUTHOR]

Despite their prevalence and burdens, oral diseases are neglected in universal health coverage. In Japan, a 30% copayment (out of pocket) by the user and a 70% contribution by Japan's universal health insurance (JUHI) are required for dental and medical services. From the age of 70 y, an additional 10% is offered by JUHI (copayment, 20%; JUHI, 80%). This study aimed to investigate the effect of cost on dental service use among older adults under the current JUHI system. A regression discontinuity quasi-experimental method was used to investigate the causal effect of the JUHI discount policy on dental visits based on cross-sectional data. Data were derived from the 2016 Japan Gerontological Evaluation Study. This analysis contained 7,161 participants who used JUHI, were aged 68 to 73 y, and responded to questions regarding past dental visits. Analyses were controlled for age, sex, number of teeth, and equalized household income. Mean ± SD age was 72.1 ± 0.79 y for the discount-eligible group and 68.9 ± 0.78 y for the noneligible group. During the past 12 mo, significantly more discount-eligible participants had visited dental services than noneligible participants (66.0% vs. 62.1% for treatment visits, 57.7% vs. 53.1% for checkups). After controlling for covariates, the effect of discount eligibility was significant on dental treatment visits (odds ratio [OR], 1.36; 95% CI, 1.32 to 1.40) and dental checkups (OR, 1.49; 95% CI, 1.44 to 1.54) in the regression discontinuity analysis. Similar findings were observed in triangular kernel-weighted models (OR, 1.38 [95% CI, 1.34 to 1.44]; OR, 1.52 [95% CI, 1.47 to 1.56], respectively). JUHI copayment discount policy increases oral health service utilization among older Japanese. The price elasticity for dental checkup visits appears to be higher than for dental treatment visits. Hence, reforming the universal health coverage system to improve the affordability of relatively inexpensive preventive care could increase dental service utilization in Japan. [ABSTRACT FROM AUTHOR]

Taste receptor family 1 member 3, TAS1R3, is shown to be involved in sweet and umami tastes in mouse, and the nucleotide sequence of the gene has been reported in rat, gorilla, and human. Pigs are frequently used as models for human diseases, and are also considered to be source animals for xenotransplantation to humans due to their anatomical and physiological similarities to humans. Therefore, in the present study, the genomic structure of the swine TAS1R3 gene was determined, and TAS1R3 expression was studied in various swine tissues. The gene was shown to reside on swine chromosome 6q22→q23, from which three types of mRNAs were generated: 3,752 bp derived from six exons in tongue, 3,704 bp from six exons and 3,630 bp from seven exons in testis. The 6 exons/5 introns were structurally similar to those of humans and mice, but the 7 exons/6 introns structure of TAS1R3 was first observed in swine. High expressions of TAS1R3 were revealed in tongue, kidney, and testis by real-time PCR. The expression profile of the tissues except for kidney was similar to that of mouse. When in situ hybridization using an RNA probe for TAS1R3 was performed on swine tongue and testis tissues, TAS1R3 expressions were revealed in tongue circumvallate papillae, fungiform papillae, mucosal epithelium, follicular B lymphocytes, lymphocytes in submucosal tissues of lingual tonsil, and spermatogenic cells. Using peripheral mature B lymphocytes, the expression of TAS1R3 in B lymphocytes was further confirmed by real-time PCR and sequencing of the real-time PCR product. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Economically important traits such as growth and backfat in pigs have been shown to be influenced by genes in swine chromosome (SSC) 10q12→qter corresponding to human chromosome (HSA) 10p. However, since gene information in the swine chromosomal region was limited, we attempted to generate a dense comparative map between SSC10 and HSA10 by mapping the 115 genes of HSA10 to a swine RH map (IMpRH map). In the mapping ten genes were assigned to SSC10, 88 to SSC14, and one to SSC3. One gene was suggested to link to SSC3, and another to SSC9. The correspondences between HSA10 and SSC10 and between HSA10 and SSC14 were essentially consistent with the observations obtained from bi/uni-directional chromosome painting or other results. This study further indicated that a large number of intrachromosomal rearrangements occurred in the synteny-conserved regions following species separation. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Bi- and uni-directional chromosome painting (ZOO-FISH) and gene mapping have revealed correspondences between human chromosome (HSA) 17 and porcine chromosome (SSC) 12 harboring economically important quantitative trait loci. In the present study, we have assigned 204 genes localized on HSA17 to SSC12 to generate a comprehensive comparative map between HSA17 and SSC12. Two hundred fifty-five primer pairs were designed using porcine sequences orthologous with human genes. Of the 255 primer pairs, 208 (81.6%) were used to assign the corresponding genes to porcine chromosomes using the INRA-Minnesota 7000-rad porcine × Chinese hamster whole genome radiation hybrid (IMpRH) panel. Two hundred three genes were integrated into the SSC12 IMpRH linkage maps; and one gene, PPARBP, was found to link to THRA1 located in SSC12 but not incorporated into the linkage maps. Three genes (GIT1, SLC25A11, and HT008) were suggested to link to SSC12 markers, and the remaining gene (RPL26) did not link to any genes/expressed sequence tags/markers registered, including those in the present study. A comparison of the gene orders among SSC12, HSA17, and mouse chromosome 11 indicates that intra-chromosomal rearrangements occurred frequently in this ancestral mammalian chromosome during speciation. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The human chromosome (HSA)19q region has been shown to correspond to swine chromosome (SSC) 6q11→q21 by bi-directional chromosomal painting and gene mapping. However, since the precise correspondence has not been determined, 26 genes localized in HSA19q13.3→q13.4 were assigned to the SSC6 region mainly by radiation hybrid (RH) mapping, and additionally, by somatic cell hybrid panel (SCHP) mapping, and fluorescent in situ hybridization (FISH). Out of the 26 genes, 24 were assigned to a swine RH map with LOD scores greater than 6 (threshold of significance). The most likely order of the 24 genes along SSC6 was calculated by CarthaGene, revealing that the order is essentially the same as that in HSA19q13.3→q13.4. For AURKC and RPS5 giving LOD scores not greater than 6, SCHP mapping and FISH were additionally performed; SCHP mapping assigned AURKC and RPS5 to SSC6q22→q23 and SSC6q21, respectively, which is consistent with the observation of FISH. Consequently, all the genes (26 genes) examined in the present study were shown to localize in SSC6q12→q23, and the order of the genes along the chromosomes was shown to be essentially the same in swine and human, though several intrachromosomal rearrangements were observed between the species. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A comprehensive and comparative map was constructed for the porcine chromosome (SSC) 6q11→q21 region, where the gene(s) responsible for the maldevelopment of embryos are localized using swine populations of the National Institute of Animal Industry, Japan (NIAI). Since the chromosomal region corresponds to a region of human chromosome (HSA) 19q13.1→q13.3 based on bi-directional chromosome painting, primer pairs were designed from porcine cDNA sequences identified, on a sequence comparison basis, as being transcripts from genes orthologous to those in the HSA region. Fifty-one genes were successfully assigned to a swine radiation hybrid (RH) map with LOD scores greater than 6. ERF and PSMD8 genes were assigned to SSC4 and SSC1, respectively. The remaining 49 genes were assigned to SSC6, demonstrating that the synteny between the SSC6 and HSA19 chromosomal regions is essentially conserved, therefore confirming, the results of bi-directional chromosome painting. However, when examined precisely, rearrangements have apparently occurred within the region of conserved synteny. For the ERF and PSMD8 genes assigned to SSCs other than SSC6, additional mapping using somatic cell hybrid (SCH) panels was performed to confirm the results of RH-mapping. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Interleukin 7 (IL7) is a cytokine that has many immunological functions, including regulation of hematopoiesis and peripheral lymphocytes. cDNA and a genomic DNA segment containing the porcine IL7 gene were isolated and sequenced, showing that porcine IL7 consists of 176 amino acids and that its gene spans over about 13 kb of genomic DNA. Porcine IL7 has 85% and 73% homology with human IL7 in terms of the nucleotide and amino acid sequences, respectively. Whereas the murine IL7 gene does not have an exon corresponding to human exon 5 (Lupton et al., 1990), the porcine IL7 gene was found to contain the same exon-intron structure as the human gene. These findings, together with the upstream structure of the cDNA elucidated in the present study, indicate that the relationship between swine and human IL7 is closer than that between mouse and human IL7. The IL7 gene was mapped to swine chromosome 4q11→q13 by fluorescence in situ hybridization and, using a radiation hybrid panel, was localized between microsatellite markers Sw1336 and Sw1073 on the same chromosome. Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Using the cDNA sequence of porcine T-cell receptor (TCR) α-, β-, γ-, and δ-chain genes, we screened a porcine BAC library to isolate clones containing these genes. The isolated BAC clones were confirmed to carry these TCR genes by partial nucleotide sequencing. Among the clones obtained in the present screening, two clones carried both the TCR α-chain gene (TRA) and the TCR δ-chain gene (TRD) while one clone each carried only the sequence of either TRA or TRD. This observation demonstrated that TRA and TRD are localized in close proximity on a swine chromosome. Also two clones contained the sequence of the TCR β-chain gene (TRB), and two clones contained the sequence of TCR γ-chain gene (TRG). Fluorescence in situ hybridization using the above BAC clones as probes revealed that TRA and TRD, TRB, and TRG loci reside on swine chromosomes 7q15.3→q21, 18q11.3→q12, and 9q21→q22, respectively. The chromosome positions of TRA and TRB are consistent with those determined by somatic cell hybrid analysis (Rettenberger et al., 1996). In addition, RH mapping of these genes was performed using the INRA-University of Minnesota RH panel DNA. The result confirmed the position of TRA and TRB reported earlier (http://imprh.toulouse.inra.fr/), and further demonstrated that TRG was located 11 cR away from genetic marker SW989 toward the marker S0019. Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents a study that mapped the gene DNMT1 to porcine chromosome 2 using somatic cell hybrid cells and a radiation hybrid panel. Rationale and significance; Materials and methods; Results.

Presents a study that mapped gene MBD3 to porcine chromosome 2 using somatic cell hybrid cells and a radiation hybrid panel. Rationale and significance; Materials and methods; Results.

Background and Aims: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients., Methods: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels., Results: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident., Conclusions: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America., Clinical Trial Registration: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Previous studies have reported that tooth loss is associated with an increased risk of dementia; however, few have explored the association between number of teeth and dementia-free and total life expectancies. We investigated whether having more teeth is associated with longer dementia-free and total life expectancies., Design: A 10-year follow-up prospective cohort study from 2010 to 2020., Setting and Participants: Functionally independent older adults aged ≥65 years living in 9 municipalities in Japan., Methods: The exposure was the number of teeth (≥20, 10-19, 1-9, and 0). Dementia onset and mortality within the 10-year follow-up were used as the outcome. Dementia-free and total life expectancies according to the number of teeth were derived from multistate modeling estimates., Results: A total of 44,083 participants were included (men: 46.8%). The mean age was 73.7 years [standard deviation (SD) = 6.0]. During follow-up, 17.3% and 21.4% of the participants experienced the onset of dementia and death, respectively. Having fewer teeth was associated with dementia [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.07-1.22, 10-19 teeth; HR, 1.15; 95% CI, 1.08-1.22, 1-9 teeth; HR, 1.13; 95% CI, 1.05-1.21, 0 teeth] and death (HR, 1.13; 95% CI, 1.05-1.22, 10-19 teeth; HR, 1.27; 95% CI, 1.19-1.37, 1-9 teeth; HR, 1.47; 95% CI, 1.36-1.59, 0 teeth) compared with having ≥20 teeth. Dementia-free life expectancies at the age of 65 years were 16.43 years and 18.88 years with ≥20 teeth, and 14.40 years and 17.12 years with 0 teeth for men and women, respectively. The total life expectancies at the age of 65 were 17.84 years and 22.03 years with ≥20 teeth, and 15.42 years and 19.79 years with 0 teeth for men and women, respectively., Conclusions and Implications: Having more teeth was associated with longer dementia-free and total life expectancies., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Although there are reports on the recurrence prevention in the chronic phase using direct oral anticoagulants (DOACs) for deep vein thrombosis (DVT) in patients with cancer, acute thrombus regression effect using DOACs has not been assessed. This study aimed to assess the thrombus regression effect of initial treatment using edoxaban for acute lower-extremity DVT in patients with active cancer., Methods and Results: In this observational study, among the inpatients with cancer and lower-extremity DVT who underwent initial treatment with edoxaban at our hospital from November 2019 to December 2021, 34 consenting patients were recruited in this study. The quantitative ultrasound thrombus (QUT) score of thrombus volume was calculated at baseline (before administration) and 7-14 days after the start of edoxaban administration, using lower-extremity venous ultrasound to evaluate changes in thrombus volume. The primary and secondary endpoints were the acute thrombus regression effect of edoxaban and the impact of patients' clinical frailty on the thrombus regression effect, respectively. Anticoagulant therapy with edoxaban significantly reduced QUT score (p < 0.001). In addition, regardless of the Clinical Frailty Scale scores, QUT score decreased significantly., Conclusion: Initial treatment with edoxaban was effective for lower-extremity DVT in patients with cancer. In addition, the effect was the same independent of the degree of frailty., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Purpose: Depression is a leading cause of disability. Although tooth loss increases the risk of depressive symptoms, it is unclear whether dental prosthesis use moderates this risk. This study aimed to investigate whether dental prosthesis use moderates the association between tooth loss and new depressive symptoms in older adults., Methods: This cohort study used data from the 2016 and 2019 Japan Gerontological Evaluation Study (JAGES). The participants were independent older adults aged ≥65 years without depressive symptoms in 2016. The onset of depressive symptoms in 2019 was the outcome variable. The exposure variables were dental status (≥20 teeth, 10-19 teeth with or without dental prostheses, and 0-9 teeth with or without dental prostheses) in 2016. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression models with potential confounders as covariates., Results: The analysis included 50,169 participants (mean age: 72.8 [standard deviation, 5.4] years). During follow-up, the incidence of depressive symptoms was 11.3%. Compared to those who had ≥20 teeth, the RR of depressive symptom onset was highest among those who had 0-9 teeth without dental prostheses (RR, 1.27; 95% CI, 1.04-1.56), after the adjustment for confounders. However, this risk was lower in those with 0-9 teeth and dental prostheses (RR, 1.08; 95% CI, 1.01-1.15)., Conclusions: These data highlight the potential of dental prostheses as an important factor in reducing the risk of depressive symptoms among individuals with severe tooth loss.

Objectives: Lower socioeconomic status (SES) is associated with increased dental pain among children. Lower SES in childhood may also contribute to the experience of dental pain among older adults, regardless of the SES in later life. However, this association is still unclear., Methods: We used cross-sectional data from the 2019 Japan Gerontological Evaluation Study using self-administrated questionnaires to investigate the causal mediating pathways between childhood SES and dental pain in later life using several SES variables collected at older age as potential mediators. A total of 21,212 physically and cognitively independent participants aged 65 y or older were included in the analysis. The dependent variable was experiencing dental pain during the past 6 mo. The independent variable was the SES at the age of 15 y (low/middle/high). Ten covariates were selected covering demographics and other domains. Education, subjective current income, objective current income, objective current property ownership, and the number of remaining teeth were used as mediators. Prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for dental pain by childhood SES were calculated using a modified Poisson regression model., Results: The mean age of the study participants was 74.5 ± 6.2 y, and 47.5% were men. Of these, 6,222 participants (29.3%) experienced dental pain during the past 6 mo, and 8,537 participants (40.2%) were of low childhood SES. Adjusted for covariates and mediators, the participants with middle and high childhood SES had a lower PR of dental pain (PR = 0.93 [95%, CI 0.89-0.98], PR = 0.79 [95% CI, 0.73-0.85], respectively). Almost 40% of the association between childhood SES and dental pain at older age was mediated via SES in later life and the number of teeth., Conclusions: This study reemphasizes the importance of support for early-life SES to maintain favorable oral health outcomes at an older age., Knowledge Transfer Statement: The results of this study can be used by policymakers to promote policies based on a life-course approach that supports children living in communities with low SES and helps them maintain favorable oral health outcomes into their older age., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Capillary electrophoresis coupled with tandem mass spectrometry (CE-MS/MS) offers advantages in peak capacity and sensitivity for metabolic profiling owing to the electroosmotic flow-based separation. However, the utilization of data-independent MS/MS acquisition (DIA) is restricted due to the absence of an optimal procedure for analytical chemistry and its related informatics framework. We assessed the mass spectral quality using two DIA techniques, namely, all-ion fragmentation (AIF) and variable DIA (vDIA), to isolate 60-800 Da precursor ions with respect to annotation rates. Our findings indicate that vDIA, coupled with the updated MS-DIAL chromatogram deconvolution algorithm, yields higher spectral matching scores and annotation rates compared to AIF. Additionally, we evaluated a linear migration time (MT) correction method using internal standards to accurately align chromatographic peaks in a data set. Postcorrection, the data set exhibited less than 0.1 min MT drifts, a difference mostly equivalent to that of conventional reverse-phase liquid chromatography techniques. Moreover, we conducted MT prediction for metabolites recorded in mass spectral libraries and metabolite structure databases containing a total of 469,870 compounds, achieving an accuracy of less than 1.5 min root mean squares. Our platform provides a peak annotation platform utilizing MT information, accurate precursor m / z , and the MS/MS spectrum recommended by the metabolomics standards initiative. Applying this procedure, we investigated metabolic alterations in lipopolysaccharide (LPS)-induced macrophages, characterizing 170 metabolites. Furthermore, we assigned metabolite information to unannotated peaks using an in silico structure elucidation tool, MS-FINDER. The results were integrated into the nodes in the molecular spectrum network based on the MS/MS similarity score. Consequently, we identified significantly altered metabolites in the LPS-administration group, where glycinamide ribonucleotide, not present in any spectral libraries, was newly characterized. Additionally, we retrieved metabolites of false-negative hits during the initial spectral annotation procedure. Overall, our study underscores the potential of CE-MS/MS with DIA and computational mass spectrometry techniques for metabolic profiling.

Background: Long-term care (LTC) costs create burdens on aging societies. Maintaining oral health through dental visits may result in shorter LTC periods, thereby decreasing LTC costs; however, this remains unverified. We examined whether dental visits in the past 6 months were associated with cumulative LTC insurance (LTCI) costs., Methods: This cohort study of the Japan Gerontological Evaluation Study targeted independent adults aged≥65 years in 2010 over an 8-year follow-up. We used data from a self-reported questionnaire and LTCI records from the municipalities. The outcome was cumulative LTCI costs, and exposure was dental visits within 6 months for prevention, treatment, and prevention or treatment. A 2-part model was used to estimate the differences in the predicted cumulative LTCI costs and 95% confidence intervals (CIs) for each dental visit., Results: The mean age of the 8 429 participants was 73.7 years (standard deviation [SD] = 6.0), and 46.1% were men. During the follow-up period, 17.6% started using LTCI services. The mean cumulative LTCI cost was USD 4 877.0 (SD = 19 082.1). The predicted cumulative LTCI costs were lower among those had dental visits than among those who did not. The differences in predicted cumulative LTCI cost were -USD 1 089.9 (95% CI = -1 888.5 to -291.2) for dental preventive visits, -USD 806.7 (95% CI = -1 647.4 to 34.0) for treatment visits, and -USD 980.6 (95% CI = -1 835.7 to -125.5) for preventive or treatment visits., Conclusions: Dental visits, particularly preventive visits, were associated with lower cumulative LTCI costs. Maintaining oral health through dental visits may effectively reduce LTCI costs., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objective: The most important aspect of managing heart failure (HF) is preventing rehospitalization. Bundle branch block (BBB), particularly left BBB (LBBB), has been a known risk factor for worsening prognosis, whereas no such consideration has been made for right BBB (RBBB). However, recent research has shown that RBBB was associated with increased mortality. This study evaluated the effects of RBBB on prognosis, especially rehospitalization, in patients with HF., Materials: This study included 698 patients admitted for HF. Those who died in the hospital (n = 31) and dropped out during observation (n = 143) were excluded. After one year of observation, the patients were divided into a control group (n = 361) and a major adverse cardiovascular event (MACE) group (n = 163). After further excluding according to electrocardiography findings, patients were categorized as having no BBB (n = 307), pure RBBB (n = 37), and LBBB (n = 56), and then the characteristics, clinical data, and prognosis of the remaining patients were evaluated., Results: Patients were compared to no BBB, pure RBBB, and LBBB was associated with a risk for HF rehospitalization (p = 0.007). Furthermore, pure RBBB was independently associated with HF rehospitalization even after adjusting for confounders (hazard ratio: 2.40 (95% confidence interval: 1.26-4.58; p = 0.008)., Conclusion: Pure RBBB was independently associated with HF rehospitalization, highlighting the need for vigilance against the risk of HF rehospitalization among those with pure RBBB., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sano et al.)

Background: Although aesthetic treatments can rejuvenate the skin, they often cause specific forms of tissue damage. Unlike wounding, which typically results in fibrotic scar tissue, damage from aesthetic treatments induces a distinct histological rejuvenation. The mechanisms that drive this rejuvenation are not yet fully understood. Here, we were interested in cellular responses following aesthetic treatments injecting adipose-derived stem cells (ASCs) subcutaneously. Through investigation with an ex vivo experimental model, a key gene was identified that orchestrates fibrous structural changes and tissue remodeling., Methods: Using fresh human subcutaneous adipose tissue co-cultured with ASCs, the changes in the fibrous architecture of the tissue were sequentially mapped. The key regulatory genes involved in remodeling were identified using gene expression and computational analyses., Results: We identified the regulatory elements that are crucial for tissue remodeling. Among those, we found that tumor necrosis factor-stimulated gene-6 (TSG-6) is a paracrine mediator essential for the collagen activity. It not only alleviates tissue inflammation but also promotes collagen replacement ex vivo. This is primarily achieved by inhibiting the formation of neutrophil extracellular traps, which are known to promote fibrosis., Conclusions: TSG-6 is a key factor modulating tissue inflammation. As our results demonstrate, after ASCs treatment, this factor directs skin healing away from fibrosis by reducing neutrophil extracellular trap formation in subcutaneous adipose tissue and promotes fibrous rejuvenation., Competing Interests: Kiuchi is an author on a patent applied for by POLA Chemical Industries that relates to this study. All the other authors have no financial interest to declare in relation to the content of this article. This study was funded by POLA Chemical Industries, Inc., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

BackgroundDementia is the leading cause of disability and imposes a significant burden on society. Previous studies have suggested an association between metabolites and cognitive decline. Although the metabolite composition differs between Western and Asian populations, studies targeting Asian populations remain scarce.MethodsThis cross-sectional study used data from a cohort survey of community-dwelling older adults aged ≥ 60 years living in Miyagi, Japan, conducted by Tohoku Medical Megabank Organization between 2013 and 2016. Forty-three metabolite variables quantified using nuclear magnetic resonance spectroscopy were used as explanatory variables. Dependent variable was the presence of cognitive decline (≤ 23 points), assessed by the Mini-Mental State Examination. Principal component (PC) analysis was performed to reduce the dimensionality of metabolite variables, followed by logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive decline.ResultsA total of 2,940 participants were included (men: 49.0%, mean age: 67.6 years). Among them, 1.9% showed cognitive decline. The first 12 PC components (PC1-PC12) accounted for 71.7% of the total variance. Multivariate analysis showed that PC1, which mainly represented essential amino acids, was associated with lower odds of cognitive decline (OR = 0.89; 95% CI, 0.80-0.98). PC2, which mainly included ketone bodies, was associated with cognitive decline (OR = 1.29; 95% CI, 1.11-1.51). PC3, which included amino acids, was associated with lower odds of cognitive decline (OR = 0.81; 95% CI, 0.66-0.99).ConclusionAmino acids are protectively associated with cognitive decline, whereas ketone metabolites are associated with higher odds of cognitive decline.

Anorexia of aging is a risk factor for malnutrition among older adults. This study aimed to evaluate the association between objective and subjective oral health and anorexia among independent older adults. This cross-sectional study targeted independent older adults aged ≥65 years who participated in the Japan Gerontological Evaluation Study conducted in 2022. The outcome variable was the presence of anorexia, as assessed by the Simplified Nutritional Appetite Questionnaire. Exposure variables were dental status (≥20 teeth, 10-19 teeth with/without dentures, and 0-9 teeth with/without dentures) as objective oral health and oral health-related quality of life measured by five items of the short version of the Oral Impacts on Daily Performances (OIDP) (eating, speaking, smiling, emotional stability, and enjoying with others) as subjective oral health. We fitted the Poisson regression model, including possible confounders, and estimated prevalence ratios (PRs) and 95% confidence intervals. Among 19,787 participants (mean age: 74.6 years [1SD = 6.2], male: 48.5%), 9.0% were classified as having anorexia. After adjusting possible confounders, those with ≤19 teeth had a higher proportion of experiencing anorexia compared to those with ≥20 teeth; however, the association was less pronounced among those with dentures (0-9 teeth with dentures: PR = 1.48 [1.31-1.68], and 0-9 teeth without dentures: PR = 2.08 [1.65-2.63]). Even after adjusting for dental status, each item of OIDP was significantly associated with the presence of anorexia (all p < 0.05). The results showed that both objective and subjective poor oral health were significantly associated with a higher probability of developing anorexia of aging. Therefore, improving both objective and subjective oral health through appropriate dental care could contribute to maintaining appetite in later life., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Serum retinol (ROH) is commonly used for population level assessment of vitamin A status. High-performance liquid chromatography (HPLC) is considered most accurate method for measuring ROH. However, with the technical difficulty of using HPLC for routine assays, serum retinol-binding protein (RBP) measured by immunological assays is expected to be a surrogate marker for ROH, with reports of a close correlation between serum RBP and ROH. Nevertheless, RBP is not commonly tested to assess vitamin A status with concerns over RBP alterations under various physiopathological conditions. Thus, we reappraised the extent to which RBP could be used as a surrogate marker in representative disorders that alter serum RBP levels. As a related marker, diagnostic utility of transthyretin (TTR) was also evaluated., Methods: To evaluate the reliability of ROH and RBP assays, specimen stability was assessed in terms of (1) storage at 25, 4, -20, and -80 °C for 1-28 days, (2) five-cycle freeze-thawing, and (3) fluorescent light exposure for 1-14 days. Sources of variation (sex, age, body mass index [BMI], and drinking habits) and reference intervals for ROH, RBP, and TTR were determined in 617 well-defined healthy individuals. To investigate the influence of disorders that affect serum RBP, patients with five diagnostic groups were enrolled: 26 with chronic kidney disease (CKD); 13 with various malignancies in advanced stages (AdM), 12 with acute bacterial infections (ABI), 6 with liver cirrhosis (LC), and 26 with simple obesity (BMI ≥ 27 kg/m 2 )., Results: The stability of RBP and ROH in serum was confirmed under all conditions. In healthy individuals, serum ROH, RBP, and TTR were appreciably high in males with a slight increase in proportion to age and BMI. The major-axis regression line between RBP (x) and ROH (y) in healthy individuals was y = x, with a correlation coefficient of 0.986. In the LC, AdM, and ABI groups, similar strong correlations were observed; however, the regression lines were shifted slightly rightward from the healthy group line, indicating a positive bias in estimating ROH. Interestingly, the same analyses between TTR and ROH revealed similar strong linear relationships in all groups; however, the regression line of each group showed a leftward (opposite) shift from the healthy group line. Based on these observations, we developed a novel regression model composed of RBP and TTR, which gave much improved accuracy in estimating ROH, even under these pathological conditions., Conclusions: The perfect RBP-ROH correlation in healthy individuals indicates the utility of RPB as a surrogate marker for ROH. Nevertheless, under RBP-altered conditions, a slight overestimation of ROH is inevitable. However, when the TTR was tested together, the bias can be corrected almost perfectly using the novel ROH estimation formula comprising RBP and TTR., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Blood vessels have the Windkessel effect and are involved in blood circulation. The breakdown of this mechanism is also involved in the pathogenesis of heart failure (HF); however, the relationship between vascular dysfunction and HF prognosis is not fully understood. Methods : We evaluated 214 patients hospitalized for HF at our institution who underwent a cardio-ankle vascular index (CAVI), which evaluates vascular function, between January 2012 and July 2018. To investigate factors (including CAVI) associated with major adverse cardiac events (MACE) during 1 year after patients with HF were discharged, we evaluated clinical profiles, blood tests, chest X-P, 12-lead electrocardiography, and transthoracic echocardiographic findings. MACE was defined as cardiovascular death or readmission for HF. Results : The severity of HF between the MACE and non-MACE was not significantly different. Previous HF and chronic kidney disease were significantly more common in the MACE group. CAVI and % mean atrial pressure in the MACE group were statistically higher than those in the non-MACE group. The cardiac shadow as shown by chest X-P and left ventricular size in the MACE group were significantly bigger, and HF preserved ejection fraction (EF) (EF > 50%) was significantly more common in the MACE group. In multivariate analysis, CAVI was an independent predictive factor for the occurrence of MACE (model 1; hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.05-1.68, p = 0.018; model 2; HR: 1.31, 95% CI: 1.07-1.60, p = 0.009). Conclusions : Because high CAVI is associated with poor prognosis of HF, these patients require more careful treatment.

Background: Dental caries are a common non-communicable disease among children. As a public health measure at the prefectural level, school-based fluoride mouth-rinse (S-FMR) program, medical/dental expense subsidy policies, and other factors may reduce the incidence of dental caries and tooth loss. Prefectures focusing on promoting oral health policies may promote both, but the interaction effect of implementing both subsidy policies and S-FMR at the prefectural level on caries prevention has not yet been examined., Methods: We conducted an ecological study using two-wave panel data, prefecture-level aggregated data in Japan for 2016 and 2018. Coefficient and 95% confidence intervals (CI) were calculated for the dependent variables for oral health using mixed-effects linear regression analysis adjusted for possible confounders. Two dependent variables were used; the standardized claim ratio (SCR) of deciduous tooth extraction and 12-year-olds' decayed, missing, or filled permanent teeth (DMFT). Four independent variables were S-FMR, the SCR of dental sealants, prefectural income per person, and subsidy policy in three models: co-payment until children enter elementary school (n = 23), no co-payment until children enter elementary school (n = 7), and co-payment continuing beyond elementary school (n = 17). The effects of six interaction terms, each representing a unique pairing from the four independent variables, were individually calculated., Results: S-FMR was negatively associated with the SCR of deciduous tooth extractions and DMFT (coefficient = -0.11, 95% CI -0.20; -0.01 and coefficient = -0.003, 95% CI -0.005; -0.001, respectively). No co-payment until children enter elementary school was positively associated with the SCR of deciduous tooth extraction compared to co-payment until children enter elementary school(coefficient = 11.42, 95% CI 3.29; 19.55). SCR of dental sealants was positively associated with the SCR of deciduous tooth extractions (coefficient = 0.12, 95% CI 0.06; 0.19) but negatively associated with DMFT (coefficient = -0.001, 95% CI -0.003; -0.0001). Per capita prefectural income was positively associated with the SCR of deciduous tooth extractions(coefficient = 0.01, 95% CI 0.001; 0.02). No interaction was found between S-FMR and the subsidy policy at both outcomes., Conclusion: High S-FMR utilization and no co-payment until children enter elementary school were associated with fewer deciduous tooth extractions. Also, S-FMR and dental sealant were associated with decreased DMFT., (© 2024. The Author(s).)

Background: Bidirectional association between oral health, including tooth loss and oral hypofunction, and cognitive impairment can induce time-varying confounding in association with dementia. This study aimed to investigate the association between oral health and the development of dementia among older adults, considering cognitive impairment as a time-varying confounder., Methods: This nine-year follow-up cohort study targeted independent older adults aged ≥65 years who participated in the Japan Gerontological Evaluation Study. The exposure variables were self-reported poor oral health (≤19 remaining teeth, edentulousness, chewing difficulty, swallowing problems, and xerostomia), which were assessed in 2010 and 2013. The outcome variable was the incidence of dementia between 2013 and 2019, which was obtained from the municipalities' administrative database. Furthermore, in 2010 and 2013, we considered cognitive impairment as a time-varying confounder and treated it based on a marginal structural model (MSM), including possible baseline confounders. Oral health and cognitive impairment were assessed using the items of Kihon checklist. We employed a Cox proportional hazards model with a stabilized inverse probability weight and estimated hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Among 37,556 participants (mean age: 72.8 years [1 SD = 5.5], males: 46.8%), the dementia incidence rate was 2.2/100 person-year. The proportions of those with ≤19 remaining teeth, edentulousness, chewing difficulty, swallowing problems, and xerostomia were 61.3%, 11.0%, 24.4%, 14.7%, and 19.2%, respectively. From the regression analysis based on MSM, ≤19 remaining teeth (HR = 1.12, 95% CI = 1.03-1.23), edentulousness (HR = 1.20, 95% CI = 1.09-1.32), chewing difficulty (HR = 1.11, 95% CI = 1.02-1.21), and xerostomia (HR = 1.10, 95% CI = 1.01-1.20) were significantly associated with an increased risk of dementia; however, swallowing problems were not significantly associated with dementia onset (p > 0.05)., Conclusions: Even after considering time-varying confounding by cognitive function at baseline and follow-up, we observed significant associations between poor oral health and increased risk of dementia among older adults., (© 2023 The American Geriatrics Society.)

Aim: Tooth loss has various causes; however, its cause-specific effects on health outcomes remain unclear. This study evaluated whether the association between past/current smoking and risk of dementia was mediated by tooth loss., Materials and Methods: This 9-year-follow-up prospective cohort study targeted adults aged ≥65 years. Dementia incidence during 2013-2019, smoking status (never, past/current) in 2010 and the number of remaining teeth (≤19, ≥20) in 2013 were the outcome, exposure and mediator, respectively. We used causal mediation analysis to fit the Cox proportional hazards model and estimated the hazard ratio (HR) and 95% confidence interval (CI) of the natural indirect effect (NIE) of smoking on dementia incidence through tooth loss and their mediated proportions., Results: Among 32,986 participants (mean age 72.6 years [1 SD = 5.4]; men 48.4%), the dementia incidence during follow-up was 2.11/100 person-years. Tooth loss significantly mediated the association between past/current smoking and dementia incidence; the NIE of fewer remaining teeth for past/current smokers compared to never smokers was HR = 1.03 (95% CI: 1.02-1.05), and the mediated proportion was 18.0%., Conclusions: Tooth loss significantly mediates the association between past/current smoking and an increased risk of dementia among older adults., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

In 2014, Japan was estimated to have approximately 27 million patients with hypertension (HT), and the ultimate goal of treatment is to prevent complications of HT, including heart failure (HF). The major structural changes in the heart that cause HF are left ventricular (LV) hypertrophy (LVH) and the resulting LV diastolic dysfunction. However, in patients with HT with well-controlled blood pressure (BP), whether they are in HF stage A (only HT) or B (with organic heart disease) is often unclear. It has been reported that strict BP control suppresses LVH, and the improvement of LVH leads to the suppression of cardiovascular complications. Thus, detecting HF stage B HT and providing appropriate treatment lead to the suppression of HF onset. This review focuses on the detection and treatment of organic heart disease in HT.

Background: The evaluation of arteriosclerosis (vascular function) is important when treating heart failure (HF). Vascular dysfunction is associated with anemia through renal function and endothelial nitric oxide synthase. Additionally, blood pressure (BP) variability (BPV) caused by vascular dysfunction is also associated with HF prognosis. However, how anemia and BPV may affect HF prognosis is unclear., Methods: Between January 2012 and July 2018, 214 patients with HF were hospitalized. The cardio-ankle vascular index (CAVI) as an index of arteriosclerosis of these patients was measured. The patients were divided into the elevated and preserved CAVI groups. We investigated the factors related to major adverse cardiovascular events (MACEs) as cardiovascular death or rehospitalization within 1 year after discharge., Results: In the elevated CAVI group, significant differences in body mass index (BMI), BPV, left ventricular dimension, and hemoglobin levels were observed between patients with and without MACEs. In the preserved CAVI group, significant differences in BMI, diastolic/mean BP, and hemoglobin levels were observed between those with and without MACEs. The multivariate analysis showed an independent association between hemoglobin levels and MACE occurrence in both the elevated and preserved CAVI groups (elevated CAVI group: hazard ratio [HR] = 0.800, p = .045 [model 1], HR = 0.802, p = .035 [model 2]; preserved CAVI group: HR = 0.783, p = .049 [model 1], HR = 0.752, p = .023 [model 2], and HR = 0.754, p = .024 [model 3])., Conclusions: Anemia was independently associated with HF prognosis with or without arteriosclerosis., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)