Mitigation of acute lung injury by human bronchial epithelial cell-derived extracellular vesicles via ANXA1-mediated FPR signaling.

Acute lung injury (ALI) is characterized by respiratory failure resulting from the disruption of the epithelial and endothelial barriers as well as immune system. In this study, we evaluated the therapeutic potential of airway epithelial cell-derived extracellular vesicles (EVs) in maintaining lung homeostasis. We isolated human bronchial epithelial cell-derived EVs (HBEC-EVs), which endogenously express various immune-related surface markers and investigated their immunomodulatory potential in ALI. In ALI cellular models, HBEC-EVs demonstrated immunosuppressive effects by reducing the secretion of proinflammatory cytokines in both THP-1 macrophages and HBECs. Mechanistically, these effects were partially ascribed to nine of the top 10 miRNAs enriched in HBEC-EVs, governing toll-like receptor-NF-κB signaling pathways. Proteomic analysis revealed the presence of proteins in HBEC-EVs involved in WNT and NF-κB signaling pathways, pivotal in inflammation regulation. ANXA1, a constituent of HBEC-EVs, interacts with formyl peptide receptor (FPR)2, eliciting anti-inflammatory responses by suppressing NF-κB signaling in inflamed epithelium, including type II alveolar epithelial cells. In a mouse model of ALI, intratracheal administration of HBEC-EVs reduced lung injury, inflammatory cell infiltration, and cytokine levels. Collectively, these findings suggest the therapeutic potential of HBEC-EVs, through their miRNAs and ANXA1 cargo, in mitigating lung injury and inflammation in ALI patients.

Validity and Reliability of the Japanese Version of the Dyspnea-12 Questionnaire in Patients With Lung Cancer.

CONTEXT: The Dyspnea-12 questionnaire is a simple tool to assess dyspnea using qualitative descriptors that include both physical and emotional domains. However, the reliability and validity of the Japanese version in patients with lung cancer have not been assessed. OBJECTIVE: To determine the reliability and validity of the Japanese version of the Dyspnea-12 questionnaire in patients with lung cancer. METHODS: The assessment was based on the numerical rating scale (NRS), cancer dyspnea scale (CDS), and hospital anxiety and depression scale (HADS). Spearman's correlation assessed the convergent validity of Dyspnea-12 using these three scales. Exploratory factor analysis examined the construct validity. The reliability was verified using Cronbach's alpha. Anxiety, depression, clinical dyspnea, presence of chronic obstructive pulmonary disease (COPD), and patient status were identified by discriminating performance. RESULTS: The analysis included 113 patients with lung cancer. A significant positive correlation was found between Dyspnea-12 and NRS, CDS, and HADS scores. Similar to the original version, factor analysis clearly classified Dyspnea-12 into two components (physical and emotional), thereby confirming its construct validity. Cronbach's alpha values for the total Dyspnea-12 and its physical and emotional components were 0.97, 0.95, and 0.96, respectively. Patients with anxiety, depression, and clinical dyspnea and those in the palliative phase had significantly higher Dyspnea-12 scores than their respective counterparts. The Dyspnea-12 scores of patients with and without COPD were similar. CONCLUSION: The Japanese version of the Dyspnea-12 questionnaire is a useful and reliable tool to assess the multi-dimensional aspects of dyspnea in patients with lung cancer.

Iliopsoas gravity abscess secondary to a tuberculous empyema.

A 29-year-old Japanese man with a history of right-sided tuberculous pleurisy presented with fever and right flank pain. Computed tomography images revealed a right pleural effusion and an area of low attenuation in the right iliopsoas muscle. Percutaneous drainage of the iliopsoas lesion resulted in a bloody pyogenic discharge that tested positive for Mycobacterium tuberculosis by both acid-fast staining and polymerase chain reaction. Enhanced fluoroscopy revealed a perforation of the diaphragm between the thoracic region and the psoas muscle. The patient was diagnosed with an iliopsoas abscess secondary to tuberculous empyema.

Mediastinal metastasis from ovarian serous carcinoma 29 years after initial treatment.

Ovarian cancer is a critically lethal gynecologic malignancy. More than 80% of patients with ovarian cancer have relapses within 5 years after initial treatment. However, recurrence from ovarian cancer more than 20 years later is extremely rare. We report a case of a 67-year-old female with mediastinal metastasis from ovarian cancer 29 years after initial gynecologic surgery and chemotherapy.

The benefit of stool mycobacterial examination to diagnose pulmonary tuberculosis for adult and elderly patients.

BACKGROUND: In patients with suspected pulmonary tuberculosis, who have difficulty in expectorating sputum, alternative specimens by invasive procedures, gastric aspirate or sputum suction, are not always available in the feeble elderly. Several studies report the benefit of stool test for pediatric or HIV infected patients, but few in adult patients. OBJECTIVE: To evaluate the benefit of stool examination as non-invasive alternative test to detect Mycobacterium tuberculosis (MTB) infection. METHODS: Stool specimens were examined for mycobacteria in 187 cases of microbiologically-diagnosed pulmonary tuberculosis between September 2013 and August 2017. We retrospectively reviewed the medical records to determine the positive detection rate of MTB with stool specimens and investigated factors related to MTB detection. RESULTS: Among 187 patients included, positive rate of MTB in stool was 12.8% (24/187) by stool acid-fast bacilli smear, 68.1% (98/144) by TRC Rapid®, and 40.6% (76/187) by culture. Multivariate logistic regression analysis revealed two contributing factors to MTB detection in stool; cavitation and male. The adjusted odds ratio with 95% confidence interval (CI) for cavitation was 2.9 (95%CI 1.48-5.69) and 2.1 (95%CI 1.08-3.93) for male. CONCLUSION: We recommend stool examination for those who are unable to give sputum and have risks for invasive procedures.

Effects of Manufacturing Processing Conditions on Retronasal-Aroma Odorants from a Milk Coffee Drink.

To develop a ready-to-drink (RTD) milk coffee that retains the original coffee flavor, the effects of manufacturing processing conditions on retronasal-aroma (RA) odorants were investigated by gas chromatography-olfactometry (CharmAnalysis™) using an RA simulator (RAS). Twenty-nine of 33 odorants detected in the RAS effluent (RAS odorants) were identified. The detected odorants were classified into 19 odor-description groups. The total odor intensity (charm value, CMV) of all coffee RAS odorants decreased approximately 68% following pH adjustment, whereas the total CMV increased 6% to 7% following ultra-high-temperature sterilization. The total CMV ratio (about 83%) of the milk coffee produced using a new blending-after-sterilization (BAS) process without pH adjustment of the coffee was greater than that (approximately 56%) prepared using a conventional blending-before-sterilization (BBS) process with pH adjustment. In BAS-processed milk coffees, the total CMV ratio (91%) with infusion (INF)-sterilized reconstituted milk (r-milk) was greater than that (83%) of plate (PLT)-sterilized r-milk. Principal component analysis of odor-description CMVs indicated that the effect of coffee pH adjustment on odor characteristics was greater than that of sterilization, that BAS and BBS samples differed, and that BAS milk coffee prepared using INF sterilization was more similar to homemade milk coffee (blending unsterilized coffee without pH adjustment with PLT-sterilized milk) than milk coffee prepared using PLT sterilization. In conclusion, the BAS process using INF sterilization is superior for manufacturing RTD milk coffee that retains odor characteristics similar to targeted homemade milk coffee. PRACTICAL APPLICATION: Ready-to-drink milk coffee beverages produced using conventional blending-before-sterilization methods do not retain their original coffee flavor following adjustment of the pH of the coffee during manufacturing. The use of newly developed blending-after-sterilization methods, by contrast, produces ready-to-drink milk coffee with an aroma more similar to that of homemade milk coffee, as demonstrated using an analytical system for characterizing food product aromas. The blending-after-sterilization process is now being used in Japan to produce ready-to-drink milk coffee beverages.

Effects of Processing Conditions During Manufacture on Retronasal-Aroma Compounds from a Milk Coffee Drink.

To develop a ready-to-drink (RTD) milk coffee retaining the original coffee flavor, the effects of processing conditions during manufacture on retronasal-arma (RA) compounds from the milk coffee were investigated by gas chromatography-mass spectrometry using an RA simulator (RAS). Thirteen of 46 detected compounds in the RAS effluent (RAS compounds) decreased significantly following pH adjustment of coffee (from pH 5.1 to 6.8) and 5 compounds increased. RAS compounds from coffee tended to decrease through the pH adjustment and subsequent sterilization. Significantly higher amounts of 13 RAS compounds were released from the milk coffee produced using a blending-after-sterilization (BAS) process without the pH adjustment than from that using a blending-before-sterilization (BBS) process with the pH adjustment. In BAS-processed milk coffee, significantly lower amounts of 8 high-volatility compounds and 1H-pyrrole were released from coffee containing infusion-sterilized (INF) milk than from coffee containing plate-sterilized (PLT) milk, whereas 3 low-volatility compounds were released significantly more from coffee using PLT milk. Principal component analysis revealed that the effect of the manufacturing process (BAS, BBS, or homemade (blending unsterilized coffee without pH adjustment with sterilized milk)) on milk coffee volatiles was larger than that of the sterilization method (INF or PLT) for milk, and that the sterilization method could result in different RAS volatile characteristics in BAS and homemade processes. In conclusion, a BAS process was found to be superior to a BBS process for the manufacture of an RTD milk coffee that retains volatile characteristics similar to that of a homemade milk coffee. PRACTICAL APPLICATION: Ready-to-drink (RTD) milk coffee manufactured using the conventional blending-before-sterilization process does not retain its original coffee flavor due to pH adjustment of the coffee during the process. The new blending-after-sterilization (BAS) process enabled the production of RTD milk coffee whose volatiles are closer to that of homemade milk coffee, as demonstrated by the results of RAS-GC-MS analysis. The BAS process has already been applied to the manufacture of RTD milk coffees in Japan.

The role of α4 integrin in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease: an infectious animal model for multiple sclerosis (MS).

Natalizumab, which is an antibody against α4 integrin, has been used for the treatment of multiple sclerosis. In the present study, we investigated both the role of α4 integrin and the therapeutic effect of HCA3551, a newly synthesized orally active small molecule α4 integrin antagonist, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). The mRNA levels of α4 integrins were significantly up-regulated in the central nervous system (CNS) of mice with TMEV-IDD as compared with naive mice (*P < 0.05). HCA3551 treatment in the effector phase significantly suppressed both the clinical and histological development of TMEV-IDD. The number of infiltrating mononuclear inflammatory cells in the CNS was significantly decreased in the mice treated with HCA3551 (**P < 0.01). The labeling indices for CD68 antigen and the absolute cell numbers of TNF-α-producing CD4+ T cells and IFN-γ-producing CD8+ T cells were significantly decreased in the CNS of mice treated with HCA3551 (*P < 0.05). HCA3551 treatment in the effector phase might inhibit the binding of α4 integrin to vascular cell adhesion molecule-1, thereby decreasing the number of mononuclear cells in the CNS.

Prognostic markers for patient outcome following vaccination with multiple MHC Class I/II-restricted WT1 peptide-pulsed dendritic cells plus chemotherapy for pancreatic cancer.

BACKGROUND/AIM: Treatment combining dendritic cells (DCs) pulsed with three types of major histocompatibility complex (MHC) class I and II (DC/WT1-I/II)-restricted Wilms' tumor 1 (WT1) peptides with chemotherapy may stabilize disease in pancreatic cancer patients. MATERIALS AND METHODS: Laboratory data from seven patients with pancreatic cancer who underwent combined DC/WT1-I/II vaccination and chemotherapy were analyzed. The DC phenotypes and plasma cytokine profiles were analyzed via flow cytometry. RESULTS: The post-treatment neutrophil to lymphocyte (N/L) ratio was a treatment-related prognostic factor for better survival. Moreover, the mean fluorescence intensities (MFIs) of human leukocyte antigen (HLA)-DR and cluster of differentiation (CD)83 on DCs were significantly increased after chemoimmunotherapy. Interestingly, interleukin (IL)-6 level in plasma was significantly increased after chemoimmunotherapy in non-super-responders. CONCLUSION: An increased N/L ratio, as well as HLA-DR and CD83 MFI levels may be prognostic markers of longer survival in patients with advanced pancreatic cancer who undergo chemoimmunotherapy.

Ultraslow relaxation of the structure at the ionic liquid|gold electrode interface to a potential step probed by electrochemical surface plasmon resonance measurements: asymmetry of the relaxation time to the potential-step direction.

The relaxation of the structure in the electrical double layer at the ionic liquid|gold interface to the steps of the electrode potential has been studied using surface plasmon resonance (SPR) measurements. The relaxation of the SPR resonance angle occurs on the order of 100 s, which is distinctively slower than the RC time constant of the cell, about 0.1 s. A relaxation model considering the distribution of the time constants well reproduces the SPR curves. The potential steps to the positive direction lead to two orders of magnitude slower relaxation of the SPR resonance angle than those to the negative direction. The ultraslow relaxation and its asymmetry to the potential-step directions are likely to be caused by slow inter-layer dynamics of ions in the ionic multilayers and interaction of ions with gold, respectively.

Gas chromatography/olfactometry and electronic nose analyses of retronasal aroma of espresso and correlation with sensory evaluation by an artificial neural network.

To develop a method for evaluating and designing the retronasal aroma of espresso, sensory evaluation data was correlated with data obtained from gas chromatography/olfactometry (GC/O, CharmAnalysis™) and from an electronic nose system αFOX4000 (E-nose). The volatile compounds of various kinds of espresso (arabica coffee beans from 6 production countries: Brazil, Ethiopia, Guatemala, Colombia, Indonesia, and Tanzania; 3 roasting degrees for each country: L values, 18, 23, and 26) were collected with a retronasal aroma simulator (RAS) and examined by GC/O and E-nose. In addition, sensory descriptive analysis using a 7-point scale for RAS effluent gas was performed by 5 trained flavorists using sensory descriptors selected based on the frequency in use and coefficient of correlation. The charm values of 10 odor descriptions obtained from GC/O analysis exhibited the significant (P < 0.05) differences among both roasting degrees and origins. Also, linear discriminant analysis (LDA) on the E-nose-sensor resistances and factor analysis on the sensory evaluation scores showed that the differences of aroma characteristics among the roasting degrees were larger than those among the origins. Based on an artificial neural network (ANN) model applied to the data from GC/O analyses and sensory evaluations, the perceptual factor of the RAS aroma was predicted to be mainly affected by sweet-caramel, smoke-roast, and acidic odors. Also, 3 metal oxide semiconductor sensors (LY2/Gh, P30/1, and T40/1) of E-nose were selected for analyses of RAS aroma and correlated with the sensory descriptive scores by the ANN to support sensory evaluation.