X-ray pumping of the 229Th nuclear clock isomer.

The metastable first excited state of thorium-229, 229mTh, is just a few electronvolts above the nuclear ground state1-4 and is accessible by vacuum ultraviolet lasers. The ability to manipulate the 229Th nuclear states with the precision of atomic laser spectroscopy5 opens up several prospects6, from studies of fundamental interactions in physics7,8 to applications such as a compact and robust nuclear clock5,9,10. However, direct optical excitation of the isomer and its radiative decay to the ground state have not yet been observed, and several key nuclear structure parameters-such as the exact energies and half-lives of the low-lying nuclear levels of 229Th-remain unknown11. Here we present active optical pumping into 229mTh, achieved using narrow-band 29-kiloelectronvolt synchrotron radiation to resonantly excite the second excited state of 229Th, which then decays predominantly into the isomer. We determine the resonance energy with an accuracy of 0.07 electronvolts, measure a half-life of 82.2 picoseconds and an excitation linewidth of 1.70 nanoelectronvolts, and extract the branching ratio of the second excited state into the ground and isomeric state. These measurements allow us to constrain the 229mTh isomer energy by combining them with γ-spectroscopy data collected over the past 40 years.

Vertical gradient of needle ozone uptake within the canopy of Cryptomeria japonica.

Leaf ozone uptake through the stomata is an important index for the ozone risk assessments on trees. Stomatal conductance (gs) and ozone concentration ([O3]), determinants of the leaf ozone uptake, are known to show vertical gradients within a tree canopy. However, less is known about the within-canopy vertical gradient of leaf ozone uptake. This study was aimed to elucidate how the vertical gradient of [O3] and gs affect needle ozone uptake within a canopy of mature Cryptomeria japonica trees in a suburban forest at Tokyo, Japan. For this purpose, a multilayer gas exchange model was applied to estimate the vertical gradient of needle gs and the accumulated ozone uptake during the study period (POD1, Phytotoxic Ozone Dose above a threshold of 1 nmol m-2 s-1). In addition, we also tested several scenarios of vertical gradient of [O3] within the canopy for sensitivity analysis. The POD1 was declined from the top to the bottom of the canopy. This tendency strongly depended on the vertical gradient of gs and was hardly affected by the changes in simulated vertical reductions of the [O3]. We further assessed the photosynthesis of sunlit needles (needles absorbing both direct and diffuse light) and shaded needles (needles only absorbing diffuse light). The photosynthesis of shaded needles in the upper half of the canopy made a great contribution to the entire canopy photosynthesis. In addition, given that their POD1 was lower than that of sunlit needles, ozone may affect sunlit and shaded needles differently. We concluded that these considerations should be incorporated into modeling of the calculation of ozone uptake for mature trees to make accurate predictions of the ozone effects on trees at the canopy scale.

Differences in the feasibility, anatomical parameters predicting procedural difficulty, and isolation area of a left atrial posterior wall isolation using radiofrequency versus cryoballoon catheters.

BACKGROUNDS: The difficulty and outcome of the adjunctive left atrial posterior wall isolation (LAPWI) in patients with persistent atrial fibrillation (PersAF) may be affected by the ablation energy used. This study aimed to compare the completion rate, anatomical parameters predicting procedural difficulty, and the isolation area of a LAPWI between the use of radiofrequency (RFA) and cryoballoon ablation (CBA). METHODS: We enrolled 95 and 93 patients with PersAF who underwent pulmonary vein isolation (PVI)+LAPWI using RFA (RF group) and CBA (CB group), respectively. Preoperative computed tomography was used to evaluate the anatomical features associated with an incomplete LAPWI. Post-ablation 3-dimensional maps were analyzed to quantify the isolation area. RESULTS: The completion rate of the LAPWI was significantly higher in the RF group than the CB group without touch-up RFA (88.4% vs. 72.0%; p = .005). Predictors of incomplete LAPWI were a longer left inferior pulmonary vein (LIPV)-esophageal distance (p < .001) for RFA and a steeper angle of the LAPW (p < .001) and longer transverse LAPW diameter (p = .016) for CBA. The isolated non-PV area with RFA or CBA alone was significantly greater in the CB group than the RF group (27.5 ± 9.5 cm2 vs. 22.9 ± 6.9 cm2 ; p < .001). CONCLUSION: The position of the esophagus at a distance from the LIPV was associated with an incomplete LAPWI using RFA, while a steeper angle of the LAPW and transverse enlargement of the LAPW were associated with that using CBA. The completion rate of the LAPWI was higher with RFA, but the isolation area outside of the PVs was greater with CBA.

Effect of ozone stress on crop productivity: A threat to food security.

Tropospheric ozone (O3), the most important phytotoxic air pollutant, can deteriorate crop quality and productivity. Notably, satellite and ground-level observations-based multimodel simulations demonstrate that the present and future predicted O3 exposures could threaten food security. Hence, the present study aims at reviewing the phytotoxicity caused by O3 pollution, which threatens the food security. The present review encompasses three major aspects; wherein the past and prevailing O3 concentrations in various regions were compiled at first, followed by discussing the physiological, biochemical and yield responses of economically important crop species, and considering the potential of O3 protectants to alleviate O3-induced phytotoxicity. Finally, the empirical data reported in the literature were quantitatively analysed to show that O3 causes detrimental effect on physiological traits, photosynthetic pigments, growth and yield attributes. The review on prevailing O3 concentrations over various regions, where economically important crop are grown, and their negative impact would support policy makers to implement air pollution regulations and the scientific community to develop countermeasures against O3 phytotoxicity for maintaining food security.

Relationship between carotid intima-media thickness and periodontal disease in a Japanese urban population with and without hypertension: The Suita Study.

AIM: To investigate the association between periodontal disease and atherosclerosis and to examine whether the association is modified by hypertension status. MATERIALS AND METHODS: In this cross-sectional study, 1472 Japanese individuals aged 50-79 years who underwent a medical check-up, dental examination, and carotid ultrasonography were studied. Carotid atherosclerosis was expressed as the maximum and mean carotid intima-media thickness (max-IMT, mean-IMT) and the presence of stenosis (≥75%). Periodontal status was examined by the Community Periodontal Index (CPI, codes 0-4). The participants were divided into three groups according to the periodontal status (CPI0-2, CPI3, CPI4). RESULTS: A positive correlation was found between mean-IMT and periodontal disease after adjustment for cardiovascular risk factors in the entire cohort (mean-IMT in hypertensives: CPI0-2: 0.848 mm, CPI3: 0.857 mm, CPI4: 0.877 mm; normotensives: 0.782, 0.802, 0.826). In the entire cohort, the multivariable-adjusted odds ratio of stenosis based on mean-IMT significantly increased according to periodontal status in normotensives (odds ratio; CPI0-2: 1, CPI3: 1.39, CPI4: 2.53; p-value for trend = .004) but showed only marginal significant increase in hypertensives (1, 1.15, 1.55; p-value for trend = .063). No significant relationships were observed for max-IMT in all analyses. CONCLUSION: We observed an association between periodontal disease and atherosclerosis in normotensive and hypertensive participants.

Seasonal variations in the amount of black carbon particles deposited on the leaf surfaces of nine Japanese urban greening tree species and their related factors.

As black carbon (BC) particles can be deposited on the leaf surfaces, urban greening is considered to be effective in purifying urban air. However, little information on the seasonal variations in the amount of BC particles deposited on the leaf surfaces (BC amount on the leaves) is available in Japanese urban greening tree species. Therefore, we investigated seasonal variations in the BC amount on the leaves of evergreen (Quercus glauca, Quercus myrsinaefolia, Osmanthus fragrans and Ilex rotunda) and deciduous (Zelkova serrata, Styrax japonica, Magnolia kobus, Cornus kousa and Cornus florida) broad-leaved tree species. The BC amount on the leaves tended to increase from April for different periods, and then reached a saturated state in the tree species, excluding M. kobus. In the 4 evergreen broad-leaved trees, the seasonal variation was positively correlated with the atmospheric concentration of BC particle. In the 5 deciduous broad-leaved trees, the seasonal variation was negatively and positively correlated with the water-repellence (water droplet contact angle) and the amount of epicuticular wax on the leaf surface, respectively. Therefore, the BC amounts on the leaves of evergreen and deciduous broad-leaved urban tree species are considered to be mainly regulated by environmental factors and leaf surface characteristics, respectively.

This is the first paper that reports the seasonal variations in the amount of BC particles deposited on the leaves of Japanese urban greening tree species and their related factors such as environmental conditions and leaf surface characteristics. This study will provide the basic and novel information for the phytoremediation of urban air pollution induced by BC particles in Asia.

Relationship between the amount of black carbon particles deposited on the leaf surface and leaf surface traits in nine urban greening tree species.

To select urban greening tree species suitable for the purification of the atmosphere polluted by black carbon (BC) particles, it is necessary to clarify the determinants of the amount of BC particles deposited on the tree leaves. In the present study, we investigated the relationship between the amount of BC particles that were deposited from the atmosphere and firmly adhered to the leaf epicuticular wax, and leaf surface traits in seedlings of nine tree species grown for two years under natural conditions (Fuchu, Tokyo, Japan). There was a significant interspecific difference in the maximum amount of BC particles deposited on the leaf surface, and the order was as follows: Ilex rotunda > Cornus florida > Osmanthus fragrans > Cornus kousa > Quercus glauca ≒ Quercus myrsinifolia > Magnolia kobus ≒ Zelkova serrata ≒ Styrax japonicus. In the nine tree species, significant highly positive correlations were observed between the amount of BC particles deposited on the leaf surface, and the hydrophobicity of leaf epicuticular wax determined by its chemical composition. Therefore, we concluded that the hydrophobicity of leaf epicuticular wax is an important determinant of the amount of BC particles deposited on the leaf surface of urban greening tree species.

This is the first paper that shows that the hydrophobicity of leaf epicuticular wax is an important determinant of the amount of BC particles deposited on the leaf surface of urban greening tree species. This study will provide the basic and novel information for the selection of urban greening tree species suitable for the purification of the air polluted by BC particles.

Effect of scan strategy on the formation of a pure nickel single-crystal structure using a flat-top laser beam via laser powder bed fusion.

In this study, the role of a scan strategy in the fabrication of a single crystal (SX) structure of face-centered cubic (fcc) pure Ni using a flat-top laser profile by a laser powder bed fusion (LPBF) process was investigated. A flat-top laser with a uniform heat intensity across the beam profile was employed to fabricate the SX structure with a <001> texture parallel to the build direction (║BD). A meander scan strategy with an XY-90° scan rotation was required to achieve the flat-top-derived SX structure. The meander scanning strategy promoted the epitaxial <001> fcc growth along the direction ║BD, leading to the <001>║BD texture formation. Meanwhile, the XY-90° scan rotation induced the epitaxial growth of <001> fcc phase on the hatch direction (HD)-scan direction (SD) plane in the direction deviated by approximately 45° relative to the SD. This 45° deviation relative to the SD occurred to accommodate the beam movement and the circular beam geometry on the HD - SD plane, resulting in the preferred configurations of <011>║SD and HD. Thus, this paper reports the importance of meander scanning with a 90° scan-rotation strategy to yield a flat-top-LPBF-derived SX structure with <001>║BD and <011>║SD and HD textures.

The First Case in Japan of Fulminant Myocarditis Due to Multisystem Inflammatory Syndrome in Children (MIS-C) That Required Mechanical Circulatory Support.

Multisystem inflammatory syndrome in children (MIS-C) is a novel hyperinflammatory syndrome that is associated with severe acute respiratory syndrome coronavirus 2 infections. Reports describing the mechanical circulatory support (MCS) and myocardial biopsy for fulminant myocarditis due to MIS-C are limited.A 13-year-old male patient with MIS-C underwent treatment, including immunosuppressive therapy and MCS devices, and managed to recover from pulseless electrical activity cardiac arrest.This is the first patient in Japan with MIS-C who required MCS devices in Japan. Appropriate and immediate treatment with immunosuppressive therapy and MCS devices is important.

Varicella-zoster virus meningitis coincident with bacteremia caused by liver abscess: a case report.

Varicella-zoster virus (VZV) meningitis is sometimes associated with herpes zoster, which is also associated with various other infectious diseases. However, there are limited case reports of VZV meningitis with concomitant infectious diseases. Herein, we report a unique case of VZV meningitis concomitant with a pyogenic liver abscess. VZV meningitis was associated with herpes zoster ophthalmicus, Klebsiella pneumoniae bacteremia, and liver abscess. When VZV meningitis is suspected, clinicians should be aware of its relatively rare epidemiology, nonspecific presentation, and many background risks shared with other infections and should never omit thorough examinations to rule out other infectious causes.

Strategic roadmap to assess forest vulnerability under air pollution and climate change.

Although it is an integral part of global change, most of the research addressing the effects of climate change on forests have overlooked the role of environmental pollution. Similarly, most studies investigating the effects of air pollutants on forests have generally neglected the impacts of climate change. We review the current knowledge on combined air pollution and climate change effects on global forest ecosystems and identify several key research priorities as a roadmap for the future. Specifically, we recommend (1) the establishment of much denser array of monitoring sites, particularly in the South Hemisphere; (2) further integration of ground and satellite monitoring; (3) generation of flux-based standards and critical levels taking into account the sensitivity of dominant forest tree species; (4) long-term monitoring of N, S, P cycles and base cations deposition together at global scale; (5) intensification of experimental studies, addressing the combined effects of different abiotic factors on forests by assuring a better representation of taxonomic and functional diversity across the ~73,000 tree species on Earth; (6) more experimental focus on phenomics and genomics; (7) improved knowledge on key processes regulating the dynamics of radionuclides in forest systems; and (8) development of models integrating air pollution and climate change data from long-term monitoring programs.

New Conversion Formula Between B-Type Natriuretic Peptide and N-Terminal-Pro-B-Type Natriuretic Peptide　- Analysis From a Multicenter Study.

BACKGROUND: Although B-type natriuretic peptide (BNP) and N-terminal (NT)-proBNP are commonly used markers of heart failure, a simple conversion formula between these peptides has not yet been developed for clinical use.Methods and Results: A total of 9,394 samples were obtained from Nara Medical University, Jichi Medical University, and Osaka University. We randomly selected 70% for a derivation set to investigate a conversion formula from BNP to NT-proBNP using estimated glomerular filtration rate (eGFR) and body mass index (BMI); the remaining 30% was used as the internal validation set and we used a cohort study from Nara Medical University as an external validation set. Multivariate linear regression analysis revealed a new conversion formula: log NT-proBNP = 1.21 + 1.03 × log BNP - 0.009 × BMI - 0.007 × eGFR (r2=0.900, P<0.0001). The correlation coefficients between the actual and converted values of log NT-proBNP in the internal and external validation sets were 0.942 (P<0.0001) and 0.891 (P<0.0001), respectively. We applied this formula to samples obtained from patients administered with sacubitril/valsartan. After treatment initiation, NT-proBNP levels decreased and actual BNP levels increased. However, the calculated BNP levels decreased roughly parallel to the NT-proBNP levels. CONCLUSIONS: This new and simple conversion formula of BNP and NT-proBNP with eGFR and BMI is potentially useful in clinical practice.

Prevention of Contrast-Induced Nephropathy After Cardiovascular Catheterization and Intervention With High-Dose Strong Statin Therapy in Japan　- The PREVENT CINC-J Study.

BACKGROUND: Previous studies have reported that high-dose strong statin therapy reduces the incidence of contrast-induced nephropathy (CIN) in statin naïve patients; however, the efficacy of high-dose strong statins for preventing CIN in real-world clinical practice remains unclear. The aim of this study was to evaluate the efficacy of strong statin therapy in addition to fluid hydration for preventing CIN after cardiovascular catheterization.Methods and Results: This prospective, multicenter, randomized controlled trial included 420 patients with chronic kidney disease who underwent cardiovascular catheterization. They were assigned to receive high-dose pitavastatin (4 mg/day × 4 days) on the day before and of the procedure and 2 days after the procedure (Statin group, n=213) or no pitavastatin (Control group, n=207). Isotonic saline hydration combined with a single bolus of sodium bicarbonate (20 mEq) was scheduled for administration to all patients. In the control group, statin therapy was continued at the same dose as that before randomization. CIN was defined as a ≥0.5 mg/dL increase in serum creatinine or ≥25% above baseline at 48 h after contrast exposure. Before randomization, 83% of study participants were receiving statin treatment. The statin group had a higher incidence of CIN than the control group (3.0% vs. 0%, P=0.01). The 12-month rate of major adverse cardiovascular events was similar between the 2 groups. CONCLUSIONS: High-dose pitavastatin increases the incidence of CIN in this study population.

The impact of different targeted temperatures on out-of-hospital cardiac arrest outcomes in patients receiving extracorporeal membrane oxygenation: a nationwide cohort study.

BACKGROUND: Targeted temperature management (TTM) is recommended in the management of out-of-hospital cardiac arrest (OHCA) when coma persists after the return of spontaneous circulation. In the setting of extracorporeal membrane oxygenation (ECMO) for OHCA patients, TTM is associated with good neurological outcomes and is recommended in the Extracorporeal Life Support Organization guidelines. However, the optimal targeted temperature for these patients has not yet been adequately investigated. This study aimed to compare the impact of different targeted temperatures on the outcomes in OHCA patients receiving ECMO. METHODS: This was a retrospective analysis of data from the Japanese Association for Acute Medicine (JAAM)-OHCA Registry, a multicentre nationwide prospective database in Japan in which 103 institutions providing emergency care participated. OHCA patients aged ≥ 18 years who required ECMO with TTM between June 2014 and December 2019 were included in our analysis. The primary outcome was 30-day survival with favourable neurological outcomes, defined as a Glasgow-Pittsburgh cerebral performance category score of 1 or 2. Patients were divided into two groups according to their targeted temperature: normothermic TTM (n-TTM) (35-36 °C) and hypothermic TTM (h-TTM) (32-34 °C). We compared the outcomes between the two targeted temperature groups using multivariable logistic regression and inverse probability weighting (IPW). RESULTS: A total of 890 adult OHCA patients who received ECMO and TTM were eligible for our analysis. Of these patients, 249 (28%) and 641 (72%) were treated with n-TTM and h-TTM, respectively. The proportions of patients with 30-day favourable neurological outcomes were 16.5% (41/249) and 15.9% (102/641), in the n-TTM and h-TTM groups, respectively. No difference in neurological outcomes was observed in the multiple regression analysis [adjusted odds ratio 0.91, 95% confidence interval (CI) 0.58-1.43], and the result was constant in the IPW (odds ratio 1.01, 95% CI 0.67-1.54). CONCLUSION: No difference was observed between n-TTM and h-TTM in OHCA patients receiving TTM with ECMO. The current understanding that changes to the targeted temperature have little impact on the outcome of patients may remain true regardless of ECMO use.

Incidence and prognostic impact of the calcified nodule in coronary artery disease patients with end-stage renal disease on dialysis.

Coronary artery calcification is frequently observed in coronary artery disease (CAD) patients with end-stage renal disease (ESRD). Calcified nodule (CN) is recognized as one of the vulnerable plaque characteristics responsible for acute coronary syndrome (ACS). Although CN is a cause of ACS in only 10%, its prevalence may be higher in elderly patients and/or ESRD. The aim of this study is to investigate incidence, clinical characteristics, and prognostic impact of CN in CAD patients with ESRD on dialysis. A total of 51 vessels from 49 CAD patients with ESRD on dialysis were enrolled in this study. CN was defined as a high-backscattering mass protruding into the lumen with a strong signal attenuation and an irregular surface by optical coherence tomography. Incidence, clinical characteristics and prognosis of patients with CN were studied. Major adverse cardiac events (MACE) were defined as a composite of all-cause death, non-fatal myocardial infarction, target vessel revascularization (TVR) and stroke. CNs were observed in 30 vessels from 29 patients (59.2%). Duration of dialysis was significantly longer in CN group than in non-CN group (P = 0.03). Overall, all-cause death, cardiac death, TVR and MACE occurred in 7 (14.3%), 3 (6.1%), 11 (22.4%) and 16 (32.7%) patients during follow-up (median 826 days), respectively. Kaplan-Meier survival analysis revealed that MACE-free survival was significantly lower in patients with CN compared with those without CN (Log-rank, P = 0.036).In conclusion, CN was observed in about 60% of the CAD patients with ESRD and was associated with duration of dialysis and worse prognosis.

Catheter ablation of ganglionated plexi in patients with adenosine triphosphate-induced atrial fibrillation after pulmonary vein isolation.

Intravenous ATP may induce atrial fibrillation (AF). ATP shares similar receptor-effector coupling systems with acetylcholine. However, the association between an ATP injection and the hyperactivity of the intrinsic cardiac autonomic nervous system, known as ganglionated plexi (GPs), is not well understood. We describe a series of patients with non-pulmonary vein (PV) trigger sites provoked by an ATP injection, and assess the feasibility of a ganglionated plexus (GP) ablation. We retrospectively analyzed 547 patients (69% male; mean age 67.4 ± 10.4 years; 38.5% non-paroxysmal AF) who underwent a total of 604 ablation procedures. Intravenous ATP was administered with an isoproterenol infusion during sinus rhythm after a pulmonary vein isolation in 21.3%, Box isolation in 78.6%, and SVC isolation in 52.0% of the procedures, respectively. We reviewed the incidence, the distribution of the foci, and the ablation outcomes in patients with ATP-induced AF. A total of seven patients (1.3%) had ATP-induced AF. Foci were identified in the coronary sinus (CS) in six patients, right atrial posterior wall (RAPW) adjacent to the interatrial groove in two, mitral annulus in two, ligament of Marshall in one, right septum below the foramen ovale in one and left atrial posterior wall in one, respectively. Among these trigger foci, we confirmed the vagal response by high-frequency stimulation in the CS and RAPW in six and two patients, respectively. After a median RF time of 2.9 min (range 2.5-11.3) targeting these foci, in five of six patients who received a repeat ATP injection, the AF became non-inducible. ATP-provoked trigger foci were distributed among certain sites that overlapped with the distribution of the GPs. The GP ablation was effective for this rare, but challenging situation.

Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-like Vasculitis Mouse Model.

Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE-) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD.

The Sympathetic Nervous System Contributes to the Establishment of Pre-Metastatic Pulmonary Microenvironments.

Emerging evidence suggests that neural activity contributes to tumor initiation and its acquisition of metastatic properties. More specifically, it has been reported that the sympathetic nervous system regulates tumor angiogenesis, tumor growth, and metastasis. The function of the sympathetic nervous system in primary tumors has been gradually elucidated. However, its functions in pre-metastatic environments and/or the preparation of metastatic environments far from the primary sites are still unknown. To investigate the role of the sympathetic nervous system in pre-metastatic environments, we performed chemical sympathectomy using 6-OHDA in mice and observed a decrease in lung metastasis by attenuating the recruitment of myeloid-derived suppressor cells. Furthermore, we note that neuro-immune cell interactions could be observed in tumor-bearing mouse lungs in conjunction with the decreased expression of Sema3A. These data indicate that the sympathetic nervous system contributes to the preparation of pre-metastatic microenvironments in the lungs, which are mediated by neuro-immune cell interactions.

Oral health-related quality of life is associated with the prevalence and development of depressive symptoms in older Japanese individuals: The Ohasama Study.

OBJECTIVE: This prospective study investigated the cross-sectional association between impaired oral health-related quality of life (OHRQoL) and the prevalence of depressive symptoms, and the longitudinal association between impaired OHRQoL and development of depressive symptoms among older adults. BACKGROUND: Previous studies have shown a relationship between poor oral health and depression among older adults; however, findings are inconsistent. MATERIALS AND METHODS: Participants were 669 community-dwelling older Japanese individuals aged≥55 years (mean: 67.8 ± 7.2 years). Data of 296 participants were used for longitudinal analyses. OHRQoL was evaluated using the Oral Impacts on Daily Performances scale. Impaired OHRQoL was defined as the presence of at least one impact on the scale. Depressive symptoms were assessed using the Japanese version of the Zung self-rating depression scale with a cut-off score of 40. RESULTS: The cross-sectional logistic regression model demonstrated that impaired OHRQoL was significantly associated with depressive symptoms (odds ratio [OR], 5.17; 95% confidence interval [CI], 2.99-8.95) independent of age, sex, body mass index, hypertension, cerebrovascular/cardiovascular disease, smoking, drinking alcohol, education, cognitive function, objective oral health (dentition status) and oral health behaviour (dental visit within 1 year). Similarly, impaired OHRQoL predicted the development of depressive symptoms within 4 years in a fully adjusted longitudinal model (OR, 6.00; 95% CI, 1.38-26.09). CONCLUSION: Impaired OHRQoL was identified as a potential comorbidity of depressive symptoms and a predictor for depressive disorder later in life. OHRQoL may be a useful clinical outcome for elder patients with regard to their mental and oral health.

The liposome of trehalose dimycolate extracted from M. bovis BCG induces antitumor immunity via the activation of dendritic cells and CD8+ T cells.

Intravesical Bovis bacillus Calmette-Guérin (BCG) therapy is the most effective immunotherapy for bladder cancer, but it sometime causes serious side effects because of its inclusion of live bacteria. It is necessary to develop a more active but less toxic immunotherapeutic agent. Trehalose 6,6'-dimycolate (TDM), the most abundant hydrophobic glycolipid of the BCG cell wall, has been reported to show various immunostimulatory activities such as granulomagenesis and adjuvant activity. Here, we developed cationic liposomes incorporating TDM purified from Mycobacterium bovis BCG Connaught, and we investigated the antitumor effect of the cationic liposome TDM (Lip-TDM). Lip-TDM exerted an antitumor effect in bladder cancer, colon cancer, and melanoma-bearing mouse models that was comparable or even superior to that of BCG, with no body weight loss or granuloma formation. The antitumor effect of Lip-TDM disappeared in two types of mice: those with depletion of CD8+ T cells, and those with knockout of macrophage-inducible C-type lectin (Mincle) which recognize TDM. Lip-TDM treatment enhanced the maturation and migration of dendritic cells in the tumor microenvironment in a Mincle-dependent manner. Our results elucidate mechanisms that underlie Lip-TDM treatment and suggest that Lip-TDM has potential as a safe and effective treatment for various cancers.