Search

Abstract Although serum uric acid (UA) has been reported to be positively associated with increased arterial stiffness as evaluated by cardio-ankle vascular index (CAVI), UA also has an antioxidative effect that prevents endothelial damage. Therefore, the status of endothelial repair induced by endothelial damage might affect the correlation between UA and CAVI. To clarify the correlation between UA and CAVI in relation to endothelial repair activity, we performed a cross-sectional study with 246 Japanese men aged 60–69 years undergoing a general health check-up. The analysis was stratified by the median circulating level of CD34-positive cells because circulating levels of CD34-positive cells could indicate the degree of endothelial repair activity. Independent of known cardiovascular risk factors, among participants with high circulating levels of CD34-positive cells (0.95 cells/μL ≤), UA was significantly positively correlated with CAVI (standardized parameter estimate β = 0.23, p = 0.009), but not among participants with low circulating levels of CD34-positive cells (

Abstract Although fast eating speed has been associated with cardiovascular risk factors, no studies have reported an association between fast eating speed and atherosclerosis as evaluated by carotid intima–media thickness (CIMT). Rapid glucose ingestion is known to cause glucose spikes, which may accelerate atherogenesis and increase levels of growth differentiation factor 15 (GDF-15). Therefore, GDF-15 levels may influence the association between fast eating speed and atherosclerosis. To evaluate the association between eating speed and atherosclerosis in relation to GDF-15, this cross-sectional study analyzed 742 Japanese aged 60–69 years. They were required to have normal thyroid hormone levels, because both GDF-15 levels and atherosclerosis (CIMT ≥ 1.1 mm) can be influenced by thyroid dysfunction. Participants were stratified by the median GDF-15 level. A significant positive association was observed between fast eating speed and atherosclerosis, but only among participants with a high GDF-15 level: the sex- and age-adjusted odds ratios (95% confidence intervals) were 1.95 (1.09, 3.48) in participants with a high GDF-15 level, and 0.83 (0.37, 1.88) in those with a low GDF-15 level. This association remained even after further adjustment for thyroid function and metabolic factors. Serum concentrations of GDF-15 may mediate the association between fast eating speed and atherosclerosis.

Abstract A detailed understanding of the ultrafast dynamics of halogen-bonded materials is desired for designing supramolecular materials and tuning various electronic properties by external stimuli. Here, a prototypical halogen-bonded multifunctional material containing spin crossover (SCO) cations and paramagnetic radical anions is studied as a model system of photo-switchable SCO hybrid systems using ultrafast electron diffraction and two complementary optical spectroscopic techniques. Our results reveal a sequential dynamics from SCO to radical dimer softening, uncovering a key transient intermediate state. In combination with quantum chemistry calculations, we demonstrate the presence of halogen bonds in the low- and high-temperature phases and propose their role during the photoinduced sequential dynamics, underscoring the significance of exploring ultrafast dynamics. Our research highlights the promising utility of halogen bonds in finely tuning functional properties across diverse photoactive multifunctional materials.

Abstract Electron transfer is a fundamental energy conversion process widely present in synthetic, industrial, and natural systems. Understanding the electron transfer process is important to exploit the uniqueness of the low-dimensional van der Waals (vdW) heterostructures because interlayer electron transfer produces the function of this class of material. Here, we show the occurrence of an electron transfer process in one-dimensional layer-stacking of carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs). This observation makes use of femtosecond broadband optical spectroscopy, ultrafast time-resolved electron diffraction, and first-principles theoretical calculations. These results reveal that near-ultraviolet photoexcitation induces an electron transfer from the conduction bands of CNT to BNNT layers via electronic decay channels. This physical process subsequently generates radial phonons in the one-dimensional vdW heterostructure material. The gathered insights unveil the fundamentals physics of interfacial interactions in low dimensional vdW heterostructures and their photoinduced dynamics, pushing their limits for photoactive multifunctional applications.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow them for vital status (death), migration, and occurrence of diseases, such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1)-associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014–2016, secondary surveys during 2017–2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed; 3,594 and 3,364 residents (aged 27–96 and 28–98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.

Abstract Atherosclerosis and height loss are each reportedly associated with cardiovascular disease. However, no studies have found an association between atherosclerosis and height loss. A retrospective study of 2435 individuals aged 60–89 years who underwent annual health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. Height loss was defined as being in the highest quintile of height decrease per year, as in our previous studies. Among study participants, 555 were diagnosed as having atherosclerosis. Independent of known cardiovascular risk factors, atherosclerosis was positively associated with height loss. The adjusted odds ratio (OR) was 1.46 (95% confidence interval, 1.15, 1.83). Essentially the same associations were observed for men and women. The adjusted OR (95% CI) was 1.43 (1.01, 2.04) for men and 1.46 (1.07, 1.99) for women. Among older individuals, atherosclerosis is associated with height loss. This result can help clarify the mechanism underlying the association between height loss and cardiovascular disease.

Abstract Background Dengue has become a major health issue in tropical regions as the numbers of reported cases and estimated infections continuously increase. In the Philippines, many challenges remain in preventing and controlling the disease amidst all the mitigation efforts of the government. This study sought to measure the health literacy of Filipino teachers and determine the associations among teachers’ knowledge, attitudes, and selected practices (KAP) against dengue. Methods Elementary and secondary school teachers from the consistently declared dengue hotspots in the City of San Fernando, Pampanga, Philippines, from the years 2017 to 2019 were selected as target participants in this cross-sectional study. A self-administered online survey tool was used in this study for both screening of participants and the KAP survey proper. STATA, descriptive statistics, and multiple logistic regression were used for the data analysis. Odds Ratios (ORs) and 95% confidence intervals (CIs) were reported. Results The study comprised 604 participants whose mean age was 38.4 years. Television was determined as the top media source of information, and various health staff were the most trusted and common source of information. Good knowledge on dengue treatment (OR = 1.81; 95% CI 1.18–2.78) and dengue prevention (OR = 1.85; 95% CI 1.26–2.71) were positively associated with having good practices on protection against mosquito bites. Good knowledge on dengue signs and symptoms (OR = 1.56; 95% CI 1.02–2.37) and dengue prevention (OR = 2.38; 95% CI 1.59–3.58) were positively associated with having good practices on preventing breeding sites. Those with positive perceived susceptibility to dengue had lower odds of having good practices on protection against mosquito bites (OR = 0.64; 95% CI 0.41–0.99) and of having good practices on preventing breeding sites (OR = 0.46; 95% CI 0.26–0.81). Conclusion Even with the existing dengue policies, programs, and strategies, and the high disease literacy rate of Filipinos, dengue remains a struggle with an increasing case rate. Therefore, specific concepts should be emphasized, and interventions should be fine-tuned to better reach and influence the target population to attain a dengue-free Philippines.

Abstract Background Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. Methods The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan’s Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. Results The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34–55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30–60 mg/day], and the SDI at registration was 1 [IQR = 0–2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74–1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42–3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47–2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41–4.66). Conclusions The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.

Abstract To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH.

Abstract Background Administration of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs has dramatically improved even the clinical outcomes in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Dysregulation of JAK-STAT pathways via overproduction of cytokines, such as interleukin-6, is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor pending approval for use in RA. By inhibition of the JAK-STAT pathway, filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction. Similarly, interleukin-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways by inhibition of interleukin-6 signaling. We present the protocol for a study that will evaluate whether the effectiveness of filgotinib monotherapy is non-inferior to that of tocilizumab monotherapy in RA patients with an inadequate response to MTX. Methods This study is an interventional, multicenter, randomized, open-label, parallel-group, and non-inferiority clinical trial with a 52-week follow-up. Study participants will be 400 RA patients with at least moderate disease activity during treatment with MTX. Participants will be randomized in a 1:1 ratio to administer filgotinib monotherapy or subcutaneous tocilizumab monotherapy switched from MTX. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who achieve an American College of Rheumatology 50 response at week 12. Secondary endpoints are changes from baseline in the MSUS scores. We will also comprehensively analyze serum levels of multiple biomarkers, such as cytokines and chemokines. Discussion The study results are expected to show the non-inferiority of the effectiveness of filgotinib monotherapy to that of tocilizumab monotherapy in RA patients with inadequate response to MTX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices, but also MSUS, which accurately and objectively evaluates disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will evaluate the effectiveness of both drugs by integrating multilateral assessments—clinical disease activity indices, MSUS findings, and serum biomarkers. Trial registration Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ) jRCTs071200107. Registered on March 3, 2021. ClinicalTrials.gov NCT05090410. Registered on October 22, 2021.

Abstract Background This exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods In this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety. Results In total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2–3 metacarpal heads at 6 months was − 0.57 mm (− 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs − 0.22 mm (− 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: − 0.35 mm [− 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2–3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%). Conclusions Although the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. Japan Registry for Clinical Trials, jRCTs071180018

Axons are equipped with the digital signaling capacity by which they generate and faithfully propagate action potentials (APs), and also with the analogue signaling capacity by which subthreshold activity in dendrites and soma is transmitted down the axon. Despite intense work, the extent and physiological role for subthreshold synaptic activity reaching the presynaptic boutons has remained elusive because of the technical limitation to record from them. To address this issue, we made simultaneous patch-clamp recordings from the presynaptic varicosities of cerebellar GABAergic interneurons together with their parent soma or postsynaptic target cells in young rat slices and/or primary cultures. Our tour-de-force direct functional dissection indicates that the somatodendritic spontaneous excitatory synaptic potentials are transmitted down the axon for significant distances, depolarizing presynaptic boutons. These analogously transmitted excitatory synaptic potentials augment presynaptic Ca++ influx upon arrival of an immediately following AP through a mechanism that involves a voltage-dependent priming of the Ca++ channels, leading to an increase in GABA release, without any modification in the presynaptic AP waveform or residual Ca++. Our work highlights the role of the axon in synaptic integration.

IntroductionTo allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study.MethodsThis study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels.ResultsSerum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63–77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5–59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation.ConclusionIn this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels.

Abstract Height loss starting in middle age is reportedly significantly associated with death due to cardiovascular disease. Impaired blood flow is the main pathology in cardiovascular disease. Hematopoietic stem cells such as CD34-positive cells play an important role in maintaining the microcirculation and preventing impaired blood flow by activating endothelial repair and angiogenesis. Therefore, circulating CD34-positive cell count could be associated with height loss. To clarify the association between circulating CD34-positive cell count and height loss, we conducted a follow-up study of 363 Japanese men aged 60–69 years over 2 years. Height loss was defined as being in the highest quartile of height decrease per year. Independent of known cardiovascular risk factors, circulating CD34-positive cell count was significantly inversely associated with height loss. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) of height loss for circulating CD34-positive cell count (logarithmic values) was 0.49 (0.32, 0.74). This study suggests that a lower capacity to maintain the microcirculation due to a fewer CD34-positive cells might affect height loss.

Remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE), a rheumatic disease affecting the elderly, responds well to corticosteroids; however, our RS3PE patients' corticosteroid therapy is longer than expected. Elderly-onset rheumatoid arthritis (EORA) patients are reported to be at a significantly increased risk for steroid-related side effects including cardiovascular diseases (CVDs). To clarify the complications during a 1-year follow-up in corticosteroid-treated RS3PE patients compared to EORA patients. We retrospectively analyzed the records of 47 RS3PE patients (28 men, 19 women, age 78.4 ± 7.5 years) and 46 EORA patients (10 men, 36 women; 77.0 ± 6.8 yrs) to compare the complications over a 1-year follow-up. The RS3PE and EORA groups' average initial PSL doses were 16.5 ± 7.2 mg/day and 7.3 ± 4.6 mg/day, respectively. During the 1-year follow-up after treatment, there was no significant increase in CVDs in both groups. However, infections occurred in nine RS3PE patients, which is a significantly higher incidence compared to the EORA patients with infections (n = 3). The initial PSL dose was the independent variable associated with the incidence of infection. Infections were significantly increased during elderly RS3PE patients' steroid therapy. The initial corticosteroid dose was an infection-risk factor.Key messagesInfections are increased during steroid therapy in elderly patients with RS3PE syndrome.The initial dose of corticosteroids was one of the risk factors for infections.

Abstract Angiogenesis inhibition therapy causes hypertension by increasing peripheral vascular resistance. Vasa vasorum angiogenesis plays a crucial role in the development of atherosclerosis. Since vascular endothelial growth factor (VEGF), which contributes to the progress of angiogenesis, is reported to be inversely associated with the minor allele of polymorphism rs3025039, the minor allele of rs3025039 could be inversely associated with atherosclerosis among individuals with hypertension. A cross-sectional study of 1793 older Japanese adults aged 60–89 years with hypertension who participated in general health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. The minor allele of polymorphism rs3025020 was positively associated with VEGF. Therefore, in addition to known cardiovascular risk factors, rs3025020 genotype acted as a confounding factor in the present study. Independent of known confounding factors, the minor allele of rs3025039 was inversely associated with atherosclerosis among older Japanese adults with hypertension. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) for atherosclerosis with the minor allele of rs3025039 was 0.78 (0.64, 0.96). The angiogenesis-related polymorphism rs3025039 was associated with the development of atherosclerosis among older Japanese individuals. This study indicates that the development of atherosclerosis among older individuals might partly indicate a capacity for angiogenesis.

Abstract Background High normal levels of thyroid-stimulating hormone (TSH) have been reported to be associated with chronic kidney disease (CKD) among euthyroid individuals. However, there has been only limited research on the association between TSH and proteinuria, a major risk factor for the progression of renal disease. Methods A cross-sectional study of 1595 euthyroid individuals was conducted. All participants were within the normal range for free triiodothyronine (T3), free thyroxine (T4), and TSH. Analyses were stratified by thyroid cyst status to test the hypothesis that the absence of thyroid cysts, an indicator of latent thyroid damage, is associated with declining ability to synthesis thyroid hormone. Results For participants with thyroid cysts, a significant inverse association between TSH and proteinuria was observed (adjusted odds ratio (95% confidence intervals) of log-transformed TSH for proteinuria 0.40 (0.18, 0.89)). In participants without thyroid cysts, a significant positive association between those two factors was observed (2.06 (1.09, 3.90)). Conclusions Among euthyroid individuals in the general population, being in the normal range of TSH was found to have an ambivalent association with proteinuria. Thyroid cyst status could be an effect modifier for those associations.

Abstract Objective To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis. Method We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis. Results Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%). Conclusion Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines.

Abstract Background Physical frailty is related to adverse outcomes, and poor oral health has been linked to malnourishment. Subjective measures of oral health‐related quality of life (OHRQoL) have been used as indicators of the oral health problems of older adults, and they have been associated with malnourishment. This study aimed to assess OHRQoL's association with physical frailty. Methods Cross‐sectional study was conducted using data from the Nagasaki Islands Study that enrolled participants aged ≥60 years at Japanese national medical check‐ups from 2014 to 2019. Physical frailty phenotype criteria were determined using the modified Fried frailty phenotype model. OHRQoL was assessed using the Geriatric Oral Health Assessment Index (GOHAI). Dentists conducted clinical dental examinations. Simple correlation and linear regression analyses were performed to investigate the associations of number of physical frailty phenotype criteria with GOHAI and other oral health indicators. Results Among 1341 participants with a mean age of 72 years, GOHAI score was significantly associated with number of physical frailty phenotype criteria (B = −0.01, 95% confidence interval: −0.02 to −0.01, p

We investigated the ultrafast photo-response of a ferroelectric co-crystal of Hdppz–Hca composed of protonated 2,3-di (2-pyridinyl)pyrazine (Hdppz) and deprotonated chloranilic acid (Hca). Whereas the intermolecular proton transfer triggers the ferroelectricity in Hdppz–Hca, the majority of the large spontaneous polarization has a quantum mechanical origin from the highly polarizable π-electron system. In this study, we prepared a carrier-envelope phase-stable mid-infrared pulse tuned to the proton vibration of this system and investigated the time dependence of the subsequent change in the second harmonic generation (SHG) yield. By exciting the proton vibration, the relative change in SHG yield increased by about 100%, and the enhancement was only observed within the duration of the applied electric field. The huge enhancement and ultrafast response of the SHG, which is not seen in usual ferroelectrics, is attributed to the fact that the photoexcitation dynamically changes the stable position of protons and π-electrons, resulting in an ultrafast increase in the value of χ(2) of Hdppz–Hca. The phenomena observed here indicate a new property of this system as a quantum material with nonlinearity and can be regarded as opto-protonics in proton-mediated ferroelectrics.

Abstract Objective To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. Methods A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. Results The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, −0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. Conclusions Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.

Abstract Our recent studies indicate that thyroid cysts have clinical implications. Thyroid cysts could have a positive effect on the supply of thyroid hormones. Both hyperthyroidism and hypothyroidism cause hypertension. Hypothyroidism, but not hyperthyroidism, is a risk factor for atherosclerosis. Therefore, thyroid cysts could be associated with hypertension, and atherosclerosis might influence the association between thyroid cysts and hypertension. To evaluate the clinical significance of thyroid cysts, a cross-sectional study was conducted with 1801 Japanese aged 40–74 years. Thyroid cysts were significantly positively associated with hypertension in participants without atherosclerosis. However, there was a significant inverse association in those with atherosclerosis. The potential confounding factor adjusted odd ratios and 95% confidence intervals (95% CIs) were 1.49 (95% CI 1.17–1.90) for participants without atherosclerosis and 0.49 (95% CI 0.24–0.98) for those with atherosclerosis. The present study demonstrates that thyroid cysts have clinical implications because thyroid cysts support thyroid hormone activity. Our findings provide sufficient evidence to develop a risk assessment for hypertension for the general population, even though further research is required.

Abstract Background To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. Methods We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients’ clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. ‘Power Doppler (PD) responder’ was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. Results Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23–0.91, p = 0.043) was an independent predictor of PD responder status. Conclusion Serum levels of bone biomarkers may be useful for predicting RA patients’ therapeutic responses to abatacept. Trial registration Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657

Abstract Background A positive association between handgrip strength and blood pressure has been reported. Since these factors are linked to the condition of the endothelium, the activity of endothelial repair might influence the association between handgrip strength and hypertension. Methods A cross-sectional study was conducted with 257 Japanese men aged 60–69 years who underwent an annual health checkup. As individuals with high level of circulating CD34-positive cells might show active endothelial repair, which plays an important role in vascular homeostasis, participants were stratified by circulating CD34-positive cell levels, using the median value of this population (0.96 cells/μL) as the cutoff. Results Independent of known cardiovascular risk factors, for participants with a high CD34-positive cell, handgrip strength is significantly positively associated with hypertension (odds ratio and 95% confidence interval of hypertension for 1 standard deviation increment of handgrip strength were 1.85 (1.19, 2.88) but not for participants with a low CD34-positive cell (0.91 (0.61, 1.37)). Conclusion The positive association between handgrip strength and hypertension is limited to high CD34-positive cells. This result may help clarify the role of vascular homeostasis in maintaining muscle strength.

Growth differentiation factor 15 (GDF-15), which modulates cellular energy balance, is reported to be positively associated with cardiovascular disease. However, there have been no reports about the association between serum GDF-15 concentration and atherosclerosis as evaluated by carotid intima-media thickness (CIMT) among the general population. A cross-sectional study of 536 Japanese individuals aged 60 to 69 years was conducted. To avoid the influence of abnormal cellular energy balance, this study only included participants who had a normal body mass index (BMI) and normal thyroid hormone (free thyroxine and free triiodothyronine) levels. A significant positive association between serum GDF-15 concentration and atherosclerosis was observed. In the sex- and age-adjusted model (Model 1), the odds ratio (OR) (95% confidence interval (CI)) for the logarithmic value of GDF-15 and atherosclerosis was 2.62 (1.67, 5.87). This association remained after adjusting for thyroid function and renal function (Model 2) and further adjusting for known cardiovascular risk factors (Model 3). The corresponding values were 2.61 (1.15, 5.93) for Model 2 and 2.49 (1.08, 5.71) for Model 3, respectively. Serum GDF-15 concentrations could help us to estimate the risk of atherosclerosis by indicating the status of cellular energy balance, which is related to mitochondrial activity among comparative healthy older individuals.

Abstract Background Recently, short stature has been revealed to be positively associated with hypertension, possibly because this indicates lower activity of vascular maintenance, such as angiogenesis. Vascular endothelial growth factor (VEGF) polymorphism (rs3025020) plays an important role in the progression of angiogenesis and may be associated with both hypertension and hypertension-associated short stature. Methods A cross-sectional study of 1377 elderly Japanese individuals aged 60–89 years was conducted. Short stature was defined as the lowest tertile of height (

Abstract Background Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60–99 years participating in a general health check-up. Methods Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway. Results HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]). Conclusion Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.

Abstract Serum sodium concentration within the normal range could act as an indicator of age-related changes such as decrease in muscle strength and impairment of capillary function. Since endothelial injury stimulates endothelial repair by enhancing CD34-positive cell production, the level of serum sodium may be inversely associated with that of circulating CD34-positive cells, thus indicating the degree of age-related endothelial injury. We conducted a cross-sectional study of 246 elderly Japanese men aged 60–69 years. Subjects were stratified by hypertension status because hypertension should act as a strong confounding factor for the analyses performed in this study. Serum sodium concentration was positively associated with handgrip strength in non-hypertensive subjects [standardized parameter estimate (β) = 0.29; p = 0.003], but not for hypertensive subjects (β = 0.01; p = 0.878), while it was inversely associated with circulating CD34-positive cell levels in non-hypertensive subjects [simple correlation coefficient (r) = − 0.28; p = 0.002] but not for hypertensive subjects (r = − 0.07; p = 0.454). For non-hypertensive elderly subjects, serum sodium concentration within the normal range is positively associated with handgrip strength and inversely associated with CD34-positive cells, thus partly indicating the degree of age-related endothelium injury. These associations could prove to be an efficient tool for clarifying the background mechanism governing the decrease in age-related muscle strength.

Abstract Background We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people. Methods We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women) has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ≥5 points on the K6 as high psychological distress (high-K6 group). Results The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (≥ 5) was a substantial contributing factor of the GOHAI (β = − 0.23, 95% Cl − 2.31 to −1.41, p < 0.0001). Conclusions It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population.

Abstract Background The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status. Methods We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40–74 years who participated in an annual health checkup in 2014. Results In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = − 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = − 0.03, p = 0.525). Conclusions TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.

Abstract Background Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. Design; cross-sectional study Setting and Participants; The survey population included 1008 postmenopausal women 50–92 years of age residing in rural communities. Methods Self-reported walking speed was ascertained by asking the participants: “Is your walking speed faster than others of the same age and sex?” to which participants responded “yes (faster)” or “no (moderate/slower).” Calcaneal stiffness index was measured. Results Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p

To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p

Abstract Background Most patients with systemic lupus erythematosus (SLE) progress to lupus nephritis (LN) within 5 years of their SLE diagnosis, although it is not uncommon for LN to develop at later time points. Here we evaluated the clinical features of early- and late-onset LN. Patients and methods We retrospectively analyzed the cases of 184 of the 201 patients who underwent a renal biopsy at Nagasaki University Hospital and associated community hospitals between 1990 and 2016 and were diagnosed as having LN. Early onset was defined as the development of LN within the first 5 years after the patient’s SLE diagnosis, and late onset was defined as LN development > 5 years post-diagnosis. We analyzed the complete renal response (CR) at 6 and 12 months after induction therapy, the classification of renal pathology, and the mortality of the early- and late-onset LN groups. Results The mean follow-up duration after the renal biopsy was 123 ± 85 months. There were 113 (61.4%) early-onset patients and 71 (38.6%) late-onset patients. A multivariate analysis revealed that the following factors were predictive of CR: at 6 months: female sex (odds ratio [OR] 3.93, 95% confidence interval [CI] 1.31–11.77, p = 0.010), proteinuria (OR 0.83, 95% CI 0.71–0.97, p = 0.009), index of activity (0–24) (OR 0.83, 95% CI 0.70–0.99, p = 0.030), and early-onset LN (OR 2.39, 95% CI 1.15–4.98, p = 0.018); at 12 months: female sex (OR 3.60, 95% CI 1.32–9.83, p = 0.013), mixed LN (OR 0.18, 95% CI 0.04–0.80, p = 0.024), index of activity (0–24) (OR 0.80, 95% CI 0.68–0.94, p = 0.007), and early-onset LN (OR 2.10, 95% CI 1.05–4.23, p = 0.035). In a Cox proportional hazards and Fine-Gray regression model, the early-onset LN group had a significantly better mortality rate than the late-onset LN group (p = 0.038 and p = 0.043, respectively). Conclusions In our cohort, early-onset LN was a better predictor of CR at 6 and 12 months than late-onset LN. Our results suggest that early-onset LN patients had lower mortality than late-onset LN patients.

Abstract Objective To identify potential biomarkers to distinguish adult-onset Still’s disease (AOSD) from sepsis. Method We recruited 70 patients diagnosed with AOSD according to the Yamaguchi criteria, 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the AOSD and sepsis groups in order to identify specific molecular networks. Further, multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by their importance and determine specific biomarkers for distinguishing AOSD from sepsis. Results Seventeen of the 40 cytokines were found to be suitable for further analyses. The serum levels of eleven were significantly higher in patients with AOSD than healthy controls. Levels of serum fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and interleukin (IL)-18 were significantly elevated in patients with AOSD compared with those with sepsis, and cytokine clustering patterns differed between these two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both FGF-2 and IL-18 could distinguish AOSD from sepsis with high accuracy (cutoff value for FGF-2 = 36 pg/mL; IL-18 = 543 pg/mL, sensitivity 100%, specificity 72.2%, accuracy 93.8%). Conclusion Determination of FGF-2 and IL-18 levels in combination may represent a biomarker for the differential diagnosis of AOSD from sepsis, based on the measurement of multiple cytokines.

Abstract Background An increase in serum undercarboxylated osteocalcin concentrations suggests vitamin K deficiency. Clinical intervention studies suggested that the vitamin K supplementation might contribute to preventing bone loss in postmenopausal women. Evidence on the relationship between serum undercarboxylated osteocalcin (ucOC) levels and bone parameters of quantitative ultrasound (QUS) is limited. We examined the correlation between serum ucOC concentrations and bone status as measured by QUS among middle-aged and older Japanese men and women. Methods The subjects were community-dwelling men (n = 358) and women (n = 503) aged ≥ 40 years in Japan. Heel QUS parameters, including the stiffness index, speed of sound, and broadband ultrasound attenuation, were measured. Serum ucOC concentrations were measured by electrochemiluminescence immunoassay. Grip strength was measured in the dominant hand. Information on alcohol drinking, current smoking, exercise, and menopause in women was collected. Results Serum ucOC concentrations were significantly associated with age in both sexes. Serum ucOC concentrations in men were higher at ≥ 80 years than those in the age groups of 40–49, 50–59, and 60–69 years. Serum ucOC concentrations in women were higher in the age groups of 50–59 and 60–69 years than those at 40–49 years. Partial correlation analysis adjusting for covariates (age, body mass index, grip strength, alcohol drinking, current smoking, and exercise in men; age, body mass index, grip strength, alcohol drinking, current smoking, exercise, and menopause in women) showed that serum ucOC concentrations were negatively significantly correlated with all QUS parameters in women. Serum ucOC concentrations were not correlated with them in men. Conclusions Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women.

Abstract Background Patients with systemic sclerosis (SSc) complicated by gastrointestinal dysmotility are difficult to treat and have high mortality. To clarify the pathogenesis of gastrointestinal manifestations, we aimed to demonstrate the association among the clinical features of SSc, the serological markers, the autoantibodies against nicotinic acetylcholine receptor at autonomic ganglia (gAChR). Methods Fifty patients were enrolled and divided into two groups according to the presence or absence of gastrointestinal manifestations, and the characteristics were analyzed between these two groups. We measured biomarkers and the autoantibodies against two gAChRα3 and β4 subunits to test sera samples. Furthermore, patients were classified based on the presence or absence of anti-gAChR autoantibodies, and their clinical features were compared. Results In patients with SSc and gastrointestinal manifestations, digital ulcers were more frequent (p = 0.050) and VEGF expression was significantly higher (p = 0.038). Seven subjects with SSc were seropositive for α3 subunit, whereas one patient was seropositive for β4 subunit. The mean level of anti-gAChRα3 autoantibodies in SSc patients with gastrointestinal manifestations was significantly higher than that in SSc patients without gastrointestinal manifestations (p = 0.001). The group of patients with SSc and gAChR autoantibodies had significantly higher endostatin levels (p = 0.046). Conclusions This study is the first to demonstrate that clinical characteristics of SSc patients with seropositivity for gAChR autoantibodies. Patients with SSc have circulating autoantibodies against gAChR, which may contribute to gastrointestinal manifestations associated with this disease, suggesting that gAChR-mediated autonomic neurotransmission may provide a pathomechanism for gastrointestinal dysmotility in SSc.

Abstract Background Anti-thyroid peroxidase antibody (TPO-Ab) has been shown to cause autoimmune thyroiditis by inducing a deleterious influence on thyroid hormone synthesis. Further, thyroglobulin, which has an important role in thyroid hormone synthesis, is reported to be high in the fluid from thyroid cysts. Therefore, TPO-Ab could be associated with the presence of thyroid cyst, partly by affecting the activity of thyroid hormone synthesis. Methods To investigate the association between TPO-Ab and thyroid cysts, we conducted a cross-sectional study of 1432 Japanese with normal thyroid function [i.e., normal range of free triiodothyronine (free T3) and free thyroxine (free T4)] between the ages of 40 and 74 years, who participated in an annual health check-up. Results In men, the statistical power did not reach a statistical significance value. Additionally, subjects with TPO-Ab showed lower odds ratios (ORs) of thyroid cysts than those without TPO-Ab. In women, subjects with TPO-Ab showed significantly lower ORs of thyroid cysts than those without TPO-Ab. The fully adjusted ORs were 0.68 (0.40, 1.18) for men and 0.40 (0.27, 0.60) for women. When evaluating the association between logarithmic values of TPO-Ab titer and thyroid cysts in both men and women, a notable inverse correlation was observed. The fully adjusted ORs were 0.68 (0.50, 0.92) for men and 0.68 (0.57, 0.81) for women. Conclusion TPO-Ab titer revealed to be inversely associated with thyroid cysts among Japanese with normal thyroid function. The presence of a thyroid cyst could indicate a lower risk of having TPO-Ab among the general population with normal thyroid function.

An epitaxial film of YbFe2O4, a candidate for oxide electronic ferroelectrics, was fabricated on yttrium-stabilized zirconia (YSZ) substrate by magnetron sputtering technique. For the film, second harmonic generation (SHG), and a terahertz radiation signal were observed at room temperature, confirming a polar structure of the film. The azimuth angle dependence of SHG shows four leaves-like profiles and is almost identical to that in a bulk single crystal. Based on tensor analyses of the SHG profiles, we could reveal the polarization structure and the relationship between the film structure of YbFe2O4 and the crystal axes of the YSZ substrate. The observed terahertz pulse showed anisotropic polarization dependence consistent with the SHG measurement, and the intensity of the emitted terahertz pulse reached about 9.2% of that emitted from ZnTe, a typical nonlinear crystal, implying that YbFe2O4 can be applied as a terahertz wave generator in which the direction of the electric field can be easily switched.

Abstract Background Human T cell leukemia virus type-1 (HTLV-1) stimulates inflammation activity. Our previous study revealed a positive association between asymptomatic HTLV-1 infection and advanced periodontitis among elderly Japanese individuals with low levels of hematopoietic activity (reflected by reticulocyte levels). Since low hematopoietic activity has been correlated with low-grade inflammation and low-grade inflammation is associated with atherosclerosis, the status of atherosclerosis could, in turn, determine the nature of this association. Methods To this end, a cross-sectional study of 907 elderly Japanese individuals (aged 60–99 years), who had participated in dental health check-up during the period 2016–2018, was conducted. Advanced periodontitis was defined as periodontal pocket ≥ 6.0 mm. Results Among the study population, 295 (32.5%) were found to have atherosclerosis defined as a carotid intima-media thickness (CIMT) of ≥ 1.1 mm. HTLV-1 infection was positively associated with advanced periodontitis in participants with atherosclerosis, but no significant associations were observed among the participants without atherosclerosis. The known risk factors’ (including reticulocyte and CIMT) adjusted odds ratio (OR) and 95% confidence interval (CI) of advanced periodontitis were OR 2.01 and 95% CI 1.06–3.81 for participants with atherosclerosis and OR 0.61 and 95% CI 0.34–1.12 for participants without atherosclerosis. Conclusion This study found a significant association between HTLV-1 infection and advanced periodontitis among elderly Japanese with atherosclerosis. However, this association is absent in individuals without atherosclerosis, suggesting that atherosclerosis might act as a determinant in the association between HTLV-1 infection and advanced periodontitis among elderly Japanese.

Height is inversely associated with inflammation that stimulates endothelial repair. In our previous study involving elderly men aged 60–69 years, we found that active arterial wall thickening, which is known as the process of endothelial repair, requires CD34-positive cells. As thyroid hormone regulates CD34-positive cell production and as the absence of thyroid cysts might indicate latent damage in the thyroid, the status of thyroid cysts possibly influences the association between height and active arterial wall thickening. We conducted a 2-year follow-up study of Japanese aged 60–69 years. For participants with thyroid cysts, height was significantly inversely associated with active arterial wall thickening (thyroid function and baseline CIMT adjusted odds ratio of active arterial wall thickening for one increment of standard deviation of height (5.7 cm for men and 4.8 cm for women), 0.66 [0.49, 0.89]), while for those without thyroid cysts, a positive tendency between the two parameters was observed (1.19 [0.96, 1.50]). An inverse association between height and active arterial wall thickening was observed only for elderly participants with thyroid cysts possibly because of a supportive role of thyroid hormone, as the absence of thyroid cysts might indicate latent damage in the thyroid.

Aggressive endothelial repair results in the progression of both structural and functional atherosclerosis, while insufficient endothelial repair worsens functional but not structural atherosclerosis. Aging increases the risk of inadequate endothelial repair. Since low-density lipoprotein cholesterol (LDLc) activates endothelial repair, LDLc may be positively associated with structural atherosclerosis but inversely associated with functional atherosclerosis in older individuals. This cross-sectional study analyzed 1458 participants aged 60 to 79 years. We defined structural atherosclerosis as a carotid intima-media thickness (CIMT) of at least 1.1 mm and functional atherosclerosis as a cardio-ankle vascular index (CAVI) of at least 9.0. LDLc was significantly positively associated with structural atherosclerosis and significantly inversely associated with functional atherosclerosis, independently of known cardiovascular risk factors. For 1 standard increment of LDLc (28 mg/dL for men and 29 mg/dL for women), the odds ratios and 95% confidence intervals after adjustment for known cardiovascular risk factors were 1.28 (1.10, 1.50) for structural atherosclerosis and 0.85 (0.75, 0.96) for functional atherosclerosis. LDLc activates endothelial repair, which results in the development of structural atherosclerosis but maintains endothelial function in older individuals. To evaluate atherosclerosis in clinical practice, the combination of structural and functional assessment of atherosclerosis could be informative.