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 of stomatal ozone uptake in leaves of mature trees and seedlings of Zelkova serrata.

Ozone uptake through the stomata in tree leaves is an important process for improving air quality by urban trees. Stomatal conductance (gs) is a key determinant of stomatal ozone uptake. The parameterization of gs models for estimating stomatal ozone uptake of trees has mainly been carried out using gs data measured in seedling leaves although the leaf traits may differ between mature trees and seedlings. In the present study, we compared stomatal ozone uptake estimated by gs models parameterised with data from mature trees and seedlings of Zelkova serrata. We measured gs in leaves of mature trees and seedlings of Z. serrata using a leaf porometer for 3-4 growing seasons. The Jarvis-type gs model was parameterised with data from mature trees and seedlings, separately. The maximum gs, and the functions of the seedling gs estimation model regarding the response to air temperature, vapour pressure deficit and atmospheric ozone concentration were the factors inducing lower stomatal ozone uptake. In contrast, the function of the seedling gs estimation model regarding the response to irradiance resulted in a higher estimated stomatal ozone uptake. The estimated stomatal ozone uptake for one growing season (April-September) by the seedling gs estimation model was 27% lower than that by the mature tree gs estimation model. These results indicate that leaf gas exchange traits of Z. serrata were different between mature trees and seedlings, and that estimating ozone uptake in mature tree leaves using a model based on seedling gs measurements results in an underestimation.

Number of teeth and functional disability in community-dwelling older adults.

INTRODUCTION: This study determined whether tooth loss was associated with the development of functional disability and estimated the population attributable fraction (PAF) of functional disability due to tooth loss, along with risk factors for functional disability such as physical function and cognitive impairment. METHODS: The participants were 838 community-dwelling older adults aged ≥70 years living in the Tsurugaya district in Japan in 2003. The exposure variable was the number of remaining teeth (counted by trained dentists). Other variables were age, sex, depressive symptoms, cognitive impairment, educational attainment, physical function and social support. The Cox proportional hazards model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the incidence of functional disability for each risk factor, such as tooth loss. The functional disability PAF due to tooth loss was estimated, and risk factors for functional disability were identified. RESULTS: In total, 619 (73.9%) participants developed functional disability during follow-up. A multivariable model showed that those with <20 teeth (HR, 1.28; 95% CI, 1.08-1.53) were more likely to develop functional disability than those with 20 teeth or more. PAF estimation for functional disability was shown to have decreasing values in the following order: age, female sex, tooth loss and reduced physical function. CONCLUSIONS: Tooth loss was associated with the development of functional disability in community-dwelling older Japanese adults. While retaining teeth may be a potential strategy for avoiding functional disability, clinical studies on the effect of dental treatment on preventing functional disability are warranted.

Acute alcohol intoxication presenting acquired lesion of the corpus callosum in a young healthy woman: A case of possible Marchiafava-Bignami disease.

Background: Marchiafava-Bignami disease is a rare neurological disease characterized by acquired lesions of the corpus callosum. Although the major causative etiology is chronic alcoholism, a case caused by acute alcohol intoxication has not yet been reported. Case Presentation: A 19-year-old female with no known medical history or a history of chronic alcohol consumption was brought to the emergency department in a coma after binge alcohol consumption. Even after an overnight observation, she remained comatose. After a thorough examination including magnetic resonance imaging, which showed lesions of the corpus callosum, she was treated with thiamine for Marchiafava-Bignami disease. She recovered completely and at the follow-up, the callosum lesion had resolved. Conclusion: This is a rare case within the spectrum of Marchiafava-Bignami disease caused by acute consumption of alcohol. Clinicians should be aware of this potentially devastating critical condition among patients with severe alcohol intoxication, which might have been overlooked.

Candesartan Attenuates Vasculitis in a Mouse Model of Kawasaki Disease Induced by Candida albicans Water-Soluble Fraction.

BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFß receptors. Measurement of the inflammatory cytokines IL-1ß, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

Evaluation of Coronary Circulation by 13N-Ammonia Myocardial Perfusion Positron Emission Tomography in Patients with Right Coronary Artery Occlusion Due to Kawasaki Disease.

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.

Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva.

Heterotopic ossification (HO) is a non-physiological bone formation where soft tissue progenitor cells differentiate into chondrogenic cells. In fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated ACVR1/mTORC1 cascade induces HO in progenitors in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however. RNA-sequencing analyses revealed the enrichment of genes involved in oxidative phosphorylation (OXPHOS) during Activin A-induced chondrogenesis of mesenchymal stem cells derived from FOP patient-specific induced pluripotent stem cells. Functional analyses showed a metabolic transition from glycolysis to OXPHOS during chondrogenesis, along with increased mitochondrial biogenesis. mTORC1 inhibition by rapamycin suppressed OXPHOS, whereas OXPHOS inhibitor IACS-010759 inhibited cartilage matrix formation in vitro, indicating that OXPHOS is principally involved in mTORC1-induced chondrogenesis. Furthermore, IACS-010759 inhibited the muscle injury-induced enrichment of fibro/adipogenic progenitor genes and HO in transgenic mice carrying the mutated human ACVR1. These data indicated that OXPHOS is a critical downstream mediator of mTORC1 signaling in chondrogenesis and therefore is a potential FOP therapeutic target.

Prognostic impact and predictors of persistent renal dysfunction in acute kidney injury after percutaneous coronary intervention for acute myocardial infarction.

This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3 mg/dL or ≥ 50% from baseline 1 month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30-10.8; P < 0.001). Age > 75 years, left ventricular ejection fraction < 40%, a high maximum creatinine phosphokinase MB level, and bleeding after PCI were independently associated with persistent AKI. Persistent AKI was independently associated with worse clinical outcomes in patients who underwent emergency PCI for AMI. Advanced age, poor cardiac function, large myocardial necrosis, and bleeding were predictors of persistent AKI.

Association between the severity of hypothermia and in-hospital mortality in patients with infectious diseases: The J-Point registry.

Aim: Hypothermia is associated with poor prognosis in patients with sepsis. However, no studies have explored the correlation between the severity of hypothermia and prognosis. Methods: Using data from the Japanese accidental hypothermia network registry (J-Point registry), we examined adult patients aged ≥18 years with infectious diseases whose initial body temperature was ≤35°C from April 1, 2011 to March 31, 2016, in 12 centers. Patients were divided into three groups according to their body temperature: Tertile 1 (T1) (32.0-35.0°C), Tertile 2 (T2) (28.0-31.9°C), and Tertile 3 (T3) (<28.0°C). In-hospital mortality was employed as a metric to assess outcomes. We conducted a multivariate logistic regression analysis to investigate the relationship between the three categories and the occurrence of in-hospital mortality. Results: A total of 572 patients were registered, and 170 eligible patients were identified. Of these patients, 55 were in T1 (32.0-35.0°C), 76 in T2 (28.0-31.9°C), and 39 in T3 (<28.0°C) groups. The overall in-hospital mortality rate in accidental hypothermia (AH) patients with infectious diseases was 34.1%. The in-hospital mortality rates in the T1, T2, and T3 groups were 34.5%, 36.8%, and 28.2%, respectively. The multivariable analysis demonstrated no significant differences regarding in-hospital mortality among the three groups (T2 vs. T1, adjusted odds ratio [OR]: 1.29; 95% confidence interval [CI]: 0.58-2.89 and T3 vs. T1, adjusted OR: 0.83; 95% CI: 0.30-2.31). Conclusion: In this multicenter retrospective observational study, hypothermia severity was not associated with in-hospital mortality in AH patients with infectious diseases.

Non-classical Monocytes Enhance the Efficacy of Immune Checkpoint Inhibitors on Colon Cancer in a Syngeneic Mouse Model.

BACKGROUND/AIM: The response rate to immune checkpoint inhibitors (ICIs) is approximately 10%-30% and only in a few cancer types. In the present study, we determined whether non-classical monocytes (NCMs) could enhance ICI efficacy in colon cancer using a syngeneic mouse model. MATERIALS AND METHODS: The MC38 C57BL/6 mouse colon cancer model was used. Cells collected from the bone marrow of C57BL/6 mice were cultured, and NCMs were fractionated by cell sorting and administered via the tail veins to the mice implanted with MC38 cells. The anti-mouse PD-L1 antibody was administered three times, and tumor volume and overall survival were observed. RESULTS: More tumors were eradicated and more complete response occurred, after cotreatment with ICIs and NCMs than after treatment with ICIs alone. Moreover, no efficacy was observed when NCMs were administered alone. CONCLUSION: NCMs enhance ICI efficacy. The underlying mechanisms and clinical applications will be studied in the future.