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The temperature measurement of material inside of an object is one of the key technologies for control of dynamical processes. For this purpose, various techniques such as laser-based thermography and phase-contrast imaging thermography have been studied. However, it is, in principle, impossible to measure the temperature of an element inside of an object using these techniques. One of the possible solutions is measurements of Doppler brooding effect in neutron resonance absorption (NRA). Here we present a method to measure the temperature of an element or an isotope inside of an object using NRA with a single neutron pulse of approximately 100 ns width provided from a high-power laser. We demonstrate temperature measurements of a tantalum (Ta) metallic foil heated from the room temperature up to 617 K. Although the neutron energy resolution is fluctuated from shot to shot, we obtain the temperature dependence of resonance Doppler broadening using a reference of a silver (Ag) foil kept to the room temperature. A free gas model well reproduces the results. This method enables element(isotope)-sensitive thermometry to detect the instantaneous temperature rise in dynamical processes.
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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted routine childhood vaccination worldwide, especially at the beginning of the pandemic. After the emergence of variants of concern, particularly the Omicron variants, the number of COVID-19 cases significantly increased, especially in children. However, the impact of the Omicron variants on routine childhood vaccination is unknown. METHODS: This retrospective observational study collected data on vaccines included in the Japanese national immunization program (NIP) of children 15 years or younger between 2016 and 2022 in Niigata, Japan. During the study period, hepatitis B virus vaccine and rotavirus vaccines were introduced to the NIP in October 2016 and October 2020, respectively. The monthly number of vaccine doses per eligible child population between 2020 and 2022 (pandemic period) was compared to the average number of vaccine doses in the corresponding month between 2016 and 2019 (pre-pandemic period). The effect of 8 surges of COVID-19 patients on trends in routine childhood vaccination was also analyzed. RESULTS: The numbers of doses during the pre-Omicron pandemic period were comparable to the values administered before the pandemic. However, after the emergence of the Omicron variants, and especially after the surge of Omicron variant BA.5 in 2022, the number of vaccine doses declined. The decline was notable in second doses of MR vaccine at age 5-6 years by - 9.6 % and diphtheria-tetanus vaccine at ages 11-12 years by - 14.1 %. CONCLUSIONS: Routine childhood immunization was significantly affected by the emergence of the Omicron variants most likely due to the facts that more candidates and their guardians contracted COVID-19, or were required isolation for close contacts. The findings highlight the importance of continued monitoring to maintain high coverage of routine childhood immunizations for controlling vaccine preventable diseases. A follow-up study should investigate changes in the number of declined vaccine doses during Omicron variant predominance.
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Physical reservoir computing is a promising solution for accelerating artificial intelligence (AI) computations. Various physical systems that exhibit nonlinear and fading-memory properties have been proposed as physical reservoirs. Highly-integrable physical reservoirs, particularly for edge AI computing, has a strong demand. However, realizing a practical physical reservoir with high performance and integrability remains challenging. Herein, we present an analogue circuit reservoir with a simple cycle architecture suitable for complementary metal-oxide-semiconductor (CMOS) chip integration. In several benchmarks and demonstrations using synthetic and real-world data, our developed hardware prototype and its simulator exhibit a high prediction performance and sufficient memory capacity for practical applications, showing promise for future applications in highly integrated AI accelerators.
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Chronic stress has been implicated in mental illnesses and depressive behaviors. Somatostatin 4 receptor (SSTR4) has been shown to mediate anxiolytic and depression-like effects. Here, we aimed to explore the potential of SSTR4 as a diagnostic marker for chronic stress in mice. The mice were divided into single stress, chronic restraint stress, and control groups, and Sstr4 mRNA expression in the pituitary, lungs, and thymus, its protein expression in the thymus, were analyzed. Compared to controls, Sstr4 mRNA expression decreased significantly in the pituitary gland of the chronic and single-stress groups (P = 0.0181 and 0.0022, respectively) and lungs of the single-stress group (P = 0.0124), whereas it significantly increased in the thymus of the chronic-stress group (P = 0.0313). Thymic SSTR4 expression did not decrease significantly in stress groups compared to that in the control group (P = 0.0963). These results suggest that SSTR4 expression fluctuates in response to stress. Furthermore, Sstr4 mRNA expression dynamics in each organ differed based on single or chronic restraint stress-loading periods. In conclusion, this study suggests that investigating SSTR4 expression in each organ could allow for its use as a stress marker to estimate the stress-loading period and aid in diagnosing chronic stress.
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Biomarcadores , Receptores de Somatostatina , Estresse Psicológico , Timo , Animais , Receptores de Somatostatina/metabolismo , Receptores de Somatostatina/genética , Camundongos , Estresse Psicológico/metabolismo , Masculino , Biomarcadores/metabolismo , Timo/metabolismo , Hipófise/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Pulmão/metabolismo , Doença Crônica , Estresse Fisiológico , Restrição FísicaRESUMO
Cluster of differentiation 36 (CD36) is a scavenger receptor (SR), recognizing diverse extracellular ligands in various types of mammalian cells. Long-chain fatty acids (FAs), which are important constituents of phospholipids and triglycerides, also utilize CD36 as a predominant membrane transporter, being incorporated from the circulation across the plasma membrane in several cell types, including cardiac and skeletal myocytes and adipocytes. CD36 is localized in intracellular vesicles as well as the plasma membrane, and its distribution is modulated by extracellular stimuli. Herein, we aimed to clarify the molecular basis of insulin-stimulated translocation of CD36, which leads to the enhanced uptake of long-chain FAs, in adipocytes. To this end, we developed a novel exofacial epitope-tagged reporter to specifically detect cell surface-localized CD36. By employing this reporter, we demonstrate that the small GTPase Rac1 plays a pivotal role in insulin-stimulated translocation of CD36 to the plasma membrane in 3T3-L1 adipocytes. Additionally, phosphoinositide 3-kinase and the protein kinase Akt2 are shown to be involved in the regulation of Rac1. Downstream of Rac1, another small GTPase RalA directs CD36 translocation. Collectively, these results suggest that CD36 is translocated to the plasma membrane by insulin through mechanisms similar to those for the glucose transporter GLUT4 in adipocytes.
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Insulina , Proteínas Monoméricas de Ligação ao GTP , Animais , Adipócitos/metabolismo , Antígenos CD36/metabolismo , Membrana Celular/metabolismo , Ácidos Graxos/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/farmacologia , Insulina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transporte Proteico , Transdução de Sinais , CamundongosRESUMO
Cadherin-6 (CDH6) is expressed in several cancer types, but no CDH6-targeted therapy is currently clinically available. Here, we generated raludotatug deruxtecan (R-DXd; DS-6000), a novel CDH6-targeting antibody-drug conjugate with a potent DNA topoisomerase I inhibitor, and evaluated its properties, pharmacologic activities, and safety profile. In vitro pharmacologic activities and the mechanisms of action of R-DXd were assessed in serous-type ovarian cancer and renal cell carcinoma cell lines. In vivo pharmacologic activities were evaluated with several human cancer cell lines and patient-derived xenograft mouse models. The safety profile in cynomolgus monkeys was also assessed. R-DXd exhibited CDH6 expression-dependent cell growth-inhibitory activity and induced tumor regression in xenograft models. In this process, R-DXd specifically bound to CDH6, was internalized into cancer cells, and then translocated to the lysosome. The DXd released from R-DXd induced the phosphorylation of Chk1, a DNA damage marker, and cleaved caspase-3, an apoptosis marker, in cancer cells. It was also confirmed that the DXd payload had a bystander effect, passing through the cell membrane and impacting surrounding cells. The safety profile of R-DXd was favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys. R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting.
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Caderinas , Carcinoma de Células Renais , Imunoconjugados , Neoplasias Renais , Neoplasias Ovarianas , Feminino , Humanos , Camundongos , Animais , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/uso terapêutico , Camptotecina/farmacologia , Imunoconjugados/efeitos adversos , Macaca fascicularis/metabolismo , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/tratamento farmacológico , Trastuzumab , Receptor ErbB-2/metabolismoRESUMO
BACKGROUND: Real-time asthma exacerbation prediction and acute asthma attack detection are essential for patients with severe asthma. Peak expiratory flow (PEF) exhibits a potential for use in long-term asthma self-monitoring. However, the method for processing PEF calculations remains to be clarified. OBJECTIVE: To develop clinically applicable novel exacerbation predictors calculated using PEF records. METHODS: Previously proposed exacerbation predictors, including the slope of PEF, percentage predicted PEF, percentage best PEF, the highest PEF over the lowest PEF within specific periods, and PEF coefficient of variation, in addition to a novel indicator delta PEF moving average (ΔMA), defined as the difference between 14-day and 3-day average PEF values, along with moving average (MA) adjusted for PEF reference (%ΔMA), were verified using the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma data of 127 patients with severe asthma from whom 73,503 PEF observations were obtained. Receiver operating characteristic curves for all predictors were drawn, and the corresponding areas under the curve (AUCs) were computed. Regression analysis for MA and percentage MA were conducted. RESULTS: The most outstanding performance was shown by ΔMA and %ΔMA, with AUC values of 0.659 and 0.665 in the univariate model, respectively. When multivariate models were incorporated with random intercepts for individual participants, the AUC for ΔMA and %ΔMA increased to 0.907 and 0.919, respectively. CONCLUSION: The MA and percentage MA are valuable indicators that should be considered when deriving predictors from the PEF trajectory for monitoring exacerbations in patients with severe asthma. TRIAL REGISTRATION: The Hokkaido-based Investigative Cohort Analysis for Refractory Asthma was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN ID: 000003254). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003917.
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Asma , Humanos , Asma/diagnóstico , Asma/tratamento farmacológico , Pico do Fluxo ExpiratórioRESUMO
Although previous studies have demonstrated that royal jelly (RJ) may have estrogenic properties and prevent postmenopausal bone loss, the underlying mechanisms are not fully understood. This animal study aimed to investigate the effects of specific fatty acids of RJ, 10-hydroxy-2-decenoic acid (10H2DA) and 10-hydroxydecanoic acid (10HDAA), in ovariectomized rats. Ten-week-old female Wistar rats were divided into the Baseline, Sham, Ovx, Ovx + 10H2DA, and Ovx + 10HDAA groups. Rats in the Baseline group were sacrificed immediately, whereas those in the other groups were subjected to either a sham operation or bilateral ovariectomy. The animals in the Ovx + 10H2DA and Ovx + 10HDAA groups were fed diets containing 10H2DA and 10HDAA, respectively. Twelve weeks after surgery, the rats were sacrificed, and indices of bone mass and bone mechanics were analyzed. Femoral bone mineral density was significantly lower in the Ovx group than in the Sham group (p < 0.01). Administration of 10H2DA or 10HDAA did not ameliorate bone loss after ovariectomy. In addition, administration of these fatty acids diminished femur bone stiffness in ovariectomized rats (p < 0.01 and p < 0.05, respectively). These findings suggest that the favorable effects of RJ may not be exerted solely by 10H2DA or 10HDAA. However, these effects may be exhibited in combination with other RJ constituents.
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BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.
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COVID-19 , Diabetes Mellitus , Humanos , Masculino , Idoso , COVID-19/epidemiologia , Estudos Retrospectivos , Progressão da Doença , Diabetes Mellitus/epidemiologia , Obesidade/epidemiologiaRESUMO
A woman in her 70s presented to our hospital with complaints of cough and dyspnea. Computed tomography(CT) images showed a large amount of left pleural effusion, pleural tumors, and mediastinal lymphadenopathy. Left thoracic drainage was performed, and high-grade fetal lung adenocarcinoma was suspected upon pleural effusion-cell block immunostaining. Pathological evaluation of the CT-guided biopsy specimen provided a diagnosis of carcinoma with high-grade fetal lung adenocarcinoma. Although the tumor progressed rapidly, chemotherapy with atezolizumab/bevacizumab/carboplatin/ paclitaxel was highly effective. However, subsequent maintenance therapy with atezolizumab/bevacizumab led to disease progression.
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Adenocarcinoma de Pulmão , Carcinoma , Neoplasias Pulmonares , Derrame Pleural , Humanos , Feminino , Bevacizumab , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma de Pulmão/tratamento farmacológico , Progressão da DoençaRESUMO
Prevention of hypoglycemia is an important strategy for glycemic management in patients with type 1 diabetes mellitus (T1D). Hypoglycemia is difficult to recognize at night while sleeping, particularly when using multiple daily injection (MDI) insulin therapy rather than sensor-augmented insulin-pump therapy. Therefore, it is possible that patients with T1D are at higher risk of nocturnal hypoglycemia when insulin is administered using an MDI regimen. We investigated nocturnal hypoglycemia in 50 pediatric patients with T1D on MDI insulin therapy using data from an intermittently scanned continuous glucose monitoring (isCGM) system. Hypoglycemia was observed on 446 of the 1,270 nights studied. Most of the hypoglycemic episodes were severe (blood glucose <54 mg/dL). On nights when hypoglycemia occurred, the blood glucose concentrations measured using finger-stick blood glucose monitoring (FSGM) before sleep and the next morning were lower than nights when hypoglycemia did not occur. However, few values were below the normal blood glucose range, suggesting that FSGM alone may be insufficient to detect nocturnal hypoglycemia. Approximately 7% of time was spent below the normal glucose range during the 10 hours from 21:00 to 7:00 the next morning. This result suggests that the patients on MDI insulin therapy could end up spending more time in hypoglycemia than is recommended by the American Diabetes Association (time below range <4.0% of time per day). Monitoring glucose levels overnight using an isCGM sensor may improve glycemic management via automatic detection of blood glucose peaks and troughs.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Criança , Glicemia , Automonitorização da Glicemia , Hipoglicemiantes/efeitos adversos , População do Leste Asiático , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversosRESUMO
Background: The mechanism of high transfer coefficients of the lungs for carbon monoxide (Kco) in non-smokers with asthma is explained by the redistribution of blood flow to the area with preserved ventilation, to match the ventilation perfusion. Objectives: To examine whether ventilation heterogeneity, assessed by pulmonary function tests, is associated with computed tomography (CT)-based vascular indices and Kco in patients with asthma. Methods: Participants were enrolled from the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) study that included a prospective asthmatic cohort. Pulmonary function tests including Kco, using single breath methods; total lung capacity (TLC), using multiple breath methods; and CT, were performed on the same day. The ratio of the lung volume assessed using single breath methods (alveolar volume; VA) to that using multiple breath methods (TLC) was calculated as an index of ventilation heterogeneity. The volume of the pulmonary small vessels <5 mm2 in the whole lung (BV5 volume), and number of BV5 at a theoretical surface area of the lungs from the plural surface (BV5 number) were evaluated using chest CT images. Results: The low VA/TLC group (the lowest quartile) had significantly lower BV5 number, BV5 volume, higher BV5 volume/BV5 number, and higher Kco compared to the high VA/TLC group (the highest quartile) in 117 non-smokers, but not in 67 smokers. Multivariable analysis showed that low VA/TLC was associated with low BV5 number, after adjusting for age, sex, weight, lung volume on CT, and CT emphysema index in non-smokers (not in smokers). Conclusion: Ventilation heterogeneity may be associated with low BV5 number and high Kco in non-smokers (not in smokers). Future studies need to determine the dynamic regional system in ventilation, perfusion, and diffusion in asthma.
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BACKGROUND: Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients respond poorly to currently available treatments and there is a need to develop more effective therapies directly disrupting the MeninâMLL1 complex. Small-molecule-mediated inhibition of the proteinâprotein interaction between Menin and MLL1 fusion proteins is a potential therapeutic strategy for patients with MLL1-r or mutated-nucleophosmin 1 (NPM1c) acute leukemia. In this study, we preclinically evaluated the new compound DS-1594a and its salts. METHODS: We evaluated the preclinical efficacy of DS-1594a as well as DS-1594a·HCl (the HCl salt of DS-1594a) and DS-1594a·succinate (the succinic acid salt of DS-1594a, DS-1594b) in vitro and in vivo using acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) models. RESULTS: Our results showed that MLL1-r or NPM1c human leukemic cell lines were selectively and highly sensitive to DS-1594a·HCl, with 50% growth inhibition values < 30 nM. Compared with cytrabine, the standard chemotherapy drug as AML therapy, both DS-1594a·HCl and DS-1594a·succinate mediated the eradication of potential leukemia-initiating cells by enhancing differentiation and reducing serial colony-forming potential in MLL1-r AML cells in vitro. The results were confirmed by flow cytometry, RNA sequencing, RTâqPCR and chromatin immunoprecipitation sequencing analyses. DS-1594a·HCl and DS-1594a·succinate exhibited significant antitumor efficacy and survival benefit in MOLM-13 cell and patient-derived xenograft models of MLL1-r or NPM1c acute leukemia in vivo. CONCLUSION: We have generated a novel, potent, orally available small-molecule inhibitor of the Menin-MLL1 interaction, DS-1594a. Our results suggest that DS-1594a has medicinal properties distinct from those of cytarabine and that DS-1594a has the potential to be a new anticancer therapy and support oral dosing regimen for clinical studies (NCT04752163).
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In forensic practice, the presence of chicken fat clots (CFCs) in the heart and/or large blood vessels of cadavers has been empirically used to estimate the time from the onset of fatal events to death. However, little scientific evidence of its significance exists, and the mechanism of its formation has not been elucidated. CFCs contain large amounts of leukocytes; thus, we hypothesized that leukocytes might contribute to their formation. Since leukocytes, especially neutrophils, are considered to be involved in blood coagulation through the formation of neutrophil extracellular traps (NETs), we aimed to investigate whether NETs are related to the formation of CFCs through immunohistochemistry. Most cells in the CFCs were myeloperoxidase- and neutrophil elastase-positive, strongly suggesting that they were neutrophils. Since chromatin is released extracellularly during NET formation, immunostaining was performed against some types of histones in CFCs. A certain number of neutrophils in CFCs showed positive extra-nuclear and extracellular signals of histones. In addition, citrullination of histone H3, which is considered important for histone release, was immunohistochemically detected in some neutrophils. These results suggest that neutrophils may affect the formation of CFCs through histone release. Although it was not clear how and when citrullination and extracellular release of histones in CFCs occur in this study, our findings provide insights into the events occurring at the time of death in a human body.
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Armadilhas Extracelulares , Histonas , Animais , Humanos , Galinhas , Neutrófilos , Coagulação SanguíneaRESUMO
BACKGROUND: Blood eosinophils are essential biomarkers that vary substantially over time in patients with COPD and asthma. However, no study has identified the changes and effects in the changes of the blood eosinophil counts over time in both diseases. This study aimed to demonstrate blood eosinophil variability in patients with COPD and severe asthma based on these backgrounds. METHODS: A total of 172 patients with COPD from the Hokkaido COPD cohort study and 96 patients with severe asthma from the Hokkaido Severe Asthma Cohort Study, whose blood eosinophil counts were measured annually over a 3-year period, were analyzed. The factors contributing to consistently high or low blood eosinophil counts were examined in each cohort. The stability of the eosinophil classification (<150, 150-299, ≥300 cells/µL) was compared based on the number of asthma-like features in patients with COPD and the smoking status in patients with severe asthma. RESULTS: Among all the patients, the most stable range of baseline blood eosinophil counts differed between the two diseases, with <150 cells/µL in COPD and ≥300 cells/µL in severe asthma. In COPD, the number of asthma-like features (bronchodilator reversibility, blood eosinophilia, and atopy) affects the blood eosinophil count variation patterns. In severe asthma, smoking status did not affect the blood eosinophil count variation patterns. CONCLUSIONS: We identified variations in the blood eosinophil counts and their contributing factors in patients with COPD and severe asthma.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Eosinófilos , Estudos de Coortes , Asma/diagnóstico , Contagem de LeucócitosRESUMO
BACKGROUND: There are knowledge gaps in the potential role of Club cell 16-kDa secretory protein (CC16) in severe asthma phenotypes and type 2 inflammation, as well as the longitudinal effect of CC16 on pulmonary function tests and exacerbation risk in epidemiological studies. OBJECTIVE AND METHODS: To assess whether serum CC16 is associated with eosinophilic inflammation in patients with severe asthma. We also examined the effect of this protein on the annual decline in forced expiratory volume in the first second (FEV1) and the risk of exacerbation using a longitudinal approach. We recruited 127 patients with severe asthma from 30 hospitals/pulmonary clinics in Hokkaido, Japan. The least square means and standard error were calculated for T-helper 2 (Th2) biomarkers and pulmonary function test across CC16 tertiles at baseline. We did the same for asthma exacerbation and annual decline in FEV1 with 3 and 5 years' follow-up, respectively. RESULTS: We found that serum CC16 was inversely associated with sputum eosinophils and blood periostin in a dose-response manner. Baseline CC16 and FEV1/forced vital capacity ratio were positively associated in adjusted models (p for trend = 0.008). Patients with the lowest tertile of serum CC16 levels at baseline had a -14.3 mL decline in FEV1 than those with the highest tertile over 5 years of follow-up (p for trend = 0.031, fully adjusted model). We did not find any association of CC16 with exacerbation risk. CONCLUSION: Patients with severe asthma with lower circulatory CC16 had enhanced eosinophilic inflammation with rapid FEV1 decline over time.
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Asma , Eosinofilia , Humanos , Pulmão , Volume Expiratório Forçado , Eosinófilos , Eosinofilia/complicações , InflamaçãoRESUMO
BACKGROUND: The physiological importance of mucus plugs in computed tomography (CT) imaging is being increasingly recognized. However, whether airway inflammation and smoking affect the association between mucus plugs and clinical-physiological outcomes in asthma remains to be elucidated. The objective of this study is to examine how airway inflammation and/or smoking affect the correlation of CT-based mucus plug scores with exacerbation frequency and airflow limitation indices in asthma. METHODS: A total of 168 patients with asthma who underwent chest CT and sputum evaluation were enrolled and classified in eosinophilic asthma (EA; n = 103) and non-eosinophilic asthma (NEA; n = 65) groups based on sputum eosinophil percentage (cut-off: 3%). The mucus plug score was defined as the number of lung segments with mucus plugs seen on CT. RESULTS: More mucus plugs were detected on CT scans in the EA group than in the NEA group, regardless of smoking status. Mucus plug score and exacerbation frequency during one year after enrollment were significantly associated in the EA group but not in the NEA group after adjusting for demographics, blood eosinophil count, and fractional exhaled nitric oxide. Mucus plug score was associated with percentage of predicted forced expiratory volume in 1 s in non-smoking individuals in the EA and NEA group and in smoking individuals in the EA group but not in the NEA group after adjusting for demographics. CONCLUSIONS: The association of mucus plug score with exacerbation frequency and reduced lung function may vary due to airway inflammatory profile and smoking status in asthma.
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Asma , Fumar , Humanos , Fumar/efeitos adversos , Eosinófilos/fisiologia , Inflamação , Pulmão , Escarro , MucoRESUMO
A counter-propagating laser-beam platform using a spherical plasma mirror was developed for the kilojoule-class petawatt LFEX laser. The temporal and spatial overlaps of the incoming and redirected beams were measured with an optical interferometer and an x-ray pinhole camera. The plasma mirror performance was evaluated by measuring fast electrons, ions, and neutrons generated in the counter-propagating laser interaction with a Cu-doped deuterated film on both sides. The reflectivity and peak intensity were estimated as â¼50% and â¼5 × 1018 W/cm2, respectively. The platform could enable studies of counter-streaming charged particles in high-energy-density plasmas for fundamental and inertial confinement fusion research.
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In forensic practice, wound age estimation is essential for making assessments of injuries; however, it remains challenging, and markers which correctly indicate wound age are required. Since our previous study showed that chitinase 3-like protein 3 (CHI3L3) expression changed chronologically in murine skin wounds, we hypothesized that other proteins of chitinase and chitinase-like protein (C/CLP) family, which CHI3L3 belongs to, might also have varied expression in wound healing. Therefore, we considered that some proteins of the C/CLP family could be used as markers of wound age estimation, and we aimed to test this hypothesis. Examinations of murine skin wounds revealed that the expression of chitinase 3-like protein 1 (CHI3L1) changed chronologically. CHI3L1 expression in human cadaver skin wounds, which was immunohistochemically analyzed by the average ratio of CHI3L1-expressed cells/total cells in 10 microscopic fields, was weak in wounds from days 0 to 1 after injury (0.11 ± 0.024; mean ± standard error of the mean); however, CHI3L1-positive cells appeared in wounds from days 2 to 3 (1.65 ± 0.19). The number of CHI3L1-expressed cells increased in wounds from days 4 to 6 (5.35 ± 0.35) but dropped from days 7 to 13 (1.53 ± 0.24). Receiver operating characteristic curve analysis indicated that wounds from days 4 to 6 after injury could be clearly distinguished from other wounds based on a cutoff value of 2.75, sensitivity of 92.31%, and specificity of 85.14%. Our findings suggest that CHI3L1 could be a reliable marker for wound age estimation in forensic practice.
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Quitinases , Animais , Humanos , Camundongos , Biomarcadores/metabolismo , Quitinases/genética , Quitinases/metabolismo , Curva ROC , Pele/lesõesRESUMO
BACKGROUND: The chitinase-like protein YKL-40 is associated with airflow limitation on spirometry and airway remodeling in patients with asthma. It remains unclear whether YKL-40 is associated with morphologic changes in the airways and parenchyma or with future progression of airflow limitation in severe asthma. OBJECTIVE: To evaluate the association of circulating YKL-40 levels with morphologic changes in the airways and parenchyma and with longitudinal progression of airflow limitation. METHODS: The patients were participants in the Hokkaido Severe Asthma Cohort Study (n = 127), including smokers. This study consisted of 2 parts. In analysis 1, we analyzed associations between circulating YKL-40 levels and several asthma-related indices, including computed tomography-derived indices of proximal wall area percentage, the complexity of the airways (airway fractal dimension), and the parenchyma (exponent D) cross-sectionally (n = 97). In analysis 2, we evaluated the impact of circulating YKL-40 levels on forced expiratory volume in 1 second (FEV1) decline longitudinally for a 5-year follow-up (n = 103). RESULTS: Circulating YKL-40 levels were significantly associated with proximal wall area percentage and airway fractal dimension (r = 0.25, P = .01; r = -0.22, P = .04, respectively), but not with exponent D. The mean annual change in FEV1 was -33.7 (± 23.3) mL/y, and the circulating YKL-40 level was a significant independent factor associated with annual FEV1 decline (ß = -0.24, P = .02), even after controlling for exponent D (ß = -0.26, P = .01). CONCLUSION: These results provide further evidence for the association of YKL-40 with the pathogenesis of airway remodeling in severe asthma.