Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Pharmacoacupuncture for the Treatment of Frozen Shoulder: protocol for a systematic review and meta-analysis.

Objectives: Frozen shoulder (FS) is one of the most challenging shoulder disorders for patients and clinicians. Its symptoms mainly include any combination of stiffness, nocturnal pain, and limitation of active and passive glenohumeral joint movement. Conventional treatment options for FS are physical therapy, nonsteroidal anti-inflammatory drugs, injection therapy, and arthroscopic capsular release, but adverse and limited effects continue to present problems. As a result, pharmacoacupuncture (PA) is getting attention as an alternative therapy for patients with FS. PA is a new form of acupuncture treatment in traditional Korean medicine (TKM) that is mainly used for musculoskeletal diseases. It has similarity and specificity compared to corticosteroid injection and hydrodilatation, making it a potential alternative injection therapy for FS. However, no systematic reviews investigating the utilization of PA for FS have been published. Therefore, this review aims to standardize the clinical use of PA for FS and validate its therapeutic effect. Methods: The protocol was registered in Prospero (CRD42023445708) on 18 July 2023. Until Aug. 31, 2023, seven electronic databases will be searched for randomized controlled trials of PA for FS. Authors will be contacted, and manual searches will also be performed. Two reviewers will independently screen and collect data from retrieved articles according to predefined criteria. The primary outcome will be pain intensity, and secondary outcomes will be effective rate, Constant-Murley Score, Shoulder Pain and Disability Index, range of motion, quality of life, and adverse events. Bias and quality of the included trials will be assessed using the Cochrane handbook's risk-of-bias tool for randomized trials. Meta analyses will be conducted using Review Manager V.5.3 software. GRADE will be used to evaluate the level of evidence for each outcome. Results: This systematic review and meta-analysis will be conducted following PRISMA statement. The results will be published in a peer-reviewed journal. Conclusion: This review will provide scientific evidence to support health insurance policy as well as the standardization of PA in clinical practice.

Incidence, Prevalence, and Mortality of Eosinophilic Granulomatosis With Polyangiitis in Korea: A Nationwide Population-Based Study.

PURPOSE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis with multiorgan involvement. The incidence and prevalence of EGPA vary geographically and ethnically. This study investigated the incidence, prevalence, and mortality of EGPA in a nationwide population-based cohort in Korea. METHODS: This retrospective cohort study used data from the National Health Insurance database that covers almost all Korean residents. EGPA was identified using relevant diagnostic codes from 2007 to 2018. Newly diagnosed EGPA cases since 2007 and patients who visited outpatient clinics for EGPA at least three times were included. Age- and sex-adjusted standardized incidence and prevalence rates were analyzed. RESULTS: A total of 843 patients with EGPA were identified. The mean annual standardized incidence between 2007 and 2018 was 1.2 (per 1,000,000 individuals). The incidence of EGPA has increased from 1.1 (per 1,000,000 individuals) in 2007 to 1.6 (per 1,000,000 individuals) in 2017. The standardized prevalence of EGPA has increased from 1.1(per 1,000,000 individuals) in 2007 to 11.2 (per 1,000,000 individuals) in 2018. The incidence and prevalence of EGPA were higher in women than in men. The standardized mortality rate was 1.61 (95% confidence interval [CI], 1.34-1.93) in total population, 1.59 (95% CI, 1.23-2.02) in males, and 1.63 (95% CI, 1.22-2.13) in females. CONCLUSIONS: The incidence of EGPA has increased over the past decade. Incidence and prevalence rates were higher in females than in males. The overall mortality rate associated with EGPA was higher than that in the general population.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Inhaled Corticosteroids May Not Affect the Clinical Outcomes of Pneumonia in Patients with Chronic Obstructive Pulmonary Disease.

Background: Although inhaled corticosteroids (ICS) is reportedly associated with a higher risk of pneumonia in chronic obstructive pulmonary disease (COPD), the clinical implications of ICS have not been sufficiently verified to determine their effect on the prognosis of pneumonia. Methods: The electronic health records of patients hospitalized for pneumonia with underlying COPD were retrospectively reviewed. Pneumonia was confirmed using chest radiography or computed tomography. The clinical outcomes of pneumonia in patients with COPD who received ICS and those who received long-acting bronchodilators other than ICS were compared. Results: Among the 255 hospitalized patients, 89 met the inclusion criteria. The numbers of ICS and non-ICS users were 46 and 43, respectively. The CURB-65 scores at the initial presentation of pneumonia were comparable between the two groups. The proportions of patients with multilobar infiltration, pleural effusion, and complicated pneumonia in the radiological studies did not vary between the two groups. Additionally, the defervescence time, proportion of mechanical ventilation, intensive care unit admission, length of hospital stays, and mortality rate at 30 and 90 days were not significantly different between the two groups. ICS use and blood eosinophils count were not associated with all pneumonia outcomes and mortality in multivariate analyses. Conclusion: The clinical outcomes of pneumonia following ICS use in patients with COPD did not differ from those in patients treated without ICS. Thus, ICS may not contribute to the severity and outcomes of pneumonia in patients with COPD.

Changes in Neurodegeneration and Visual Prognosis in Branch Retinal Vein Occlusion after Resolution of Macular Edema.

This study aimed to examine the thicknesses of the ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (RNFL) in eyes with resolved macular edema (ME) in branch retinal vein occlusion (BRVO) and determine their relationship with visual acuity (VA). This retrospective observational case-control study included 57 eyes of BRVO patients with resolved ME after treatment. The macular GCL thickness, peripapillary RNFL thickness, and central macular thickness (CMT) measured on swept-source optical coherence tomography scans with the contralateral eyes used as controls were evaluated. The mean CMT was 270.48 ± 32.7 µm; the mean RNFL thickness was 105.46 ± 25.94 µm in BRVO eyes. Although the average RNFL thickness was decreased in BRVO eyes compared to unaffected eyes, there was no significant difference between the groups. However, the temporal and nasal RNFL thicknesses were significantly different between the groups. The mean affected quadrant had a significantly thinner GCL compared to the corresponding opposite unaffected quadrant (p = 0.02). Final VA was significantly correlated with nasal and middle GCL thicknesses in the affected area (r = -0.512, p = 0.003 and r = -0.537, p = 0.001, respectively); no correlation was found between the average RNFL thickness and mean CMT. The peripapillary RNFL and GCL thicknesses of the affected area were reduced in BRVO eyes compared to unaffected eyes. VA significantly correlated with nasal and middle GCL thicknesses in the affected area. Inner retinal damage occurring in patients with ME secondary to BRVO may be related to the visual prognosis.

Urinary Metabolomic Differentiation of Infants Fed on Human Breastmilk and Formulated Milk.

Human breastmilk is an invaluable nutritional and pharmacological resource with a highly diverse metabolite profile, which can directly affect the metabolism of infants. Application of metabolomics can discriminate the complex relationship between such nutrients and infant health. As the most common biological fluid in metabolomic study, infant urinary metabolomics may provide the physiological impacts of different nutritional resources, namely human breastmilk and formulated milk. In this study, we aimed to identify possible differences in the urine metabolome of 30 infants (1-14 days after birth) fed with breast milk (n = 15) or formulated milk (n = 15). From metabolomic analysis with gas chromatography-mass spectrometry, 163 metabolites from single mass spectrometry (GC-MS), and 383 metabolites from tandem mass spectrometry (GC-MS/MS) were confirmed in urinary samples. Various multivariate statistical analysis were performed to discriminate the differences originating from physiological/nutritional variables, including human breastmilk/formulate milk feeding, sex, and duration of feeding. Both unsupervised and supervised discriminant analyses indicated that feeding resources (human breastmilk/formulated milk) gave marginal but significant differences in urinary metabolomes, while other factors (sex, duration of feeding) did not show notable discrimination between groups. According to the biomarker analyses, several organic acid and amino acids showed statistically significant differences between different feeding resources, such as 2-hydroxyhippurate.

Is fractional exhaled nitric oxide a treatable trait in chronic cough: a narrative review.

Background and Objective: Current management of chronic cough is largely based on sequential therapeutic trials. The concept of treatable traits was first introduced for individualized treatment of chronic airway diseases; however, it has emerged as a potentially useful strategy in revising the management of chronic cough. This narrative review aimed to analyze the literature to determine if fractional exhaled nitric oxide (FeNO) is a treatable trait in chronic cough, compared to other type 2 biomarkers, and to summarize current knowledge and gaps in the clinical application. Methods: An online electronic search was performed on PubMed, Web of Science, and Scopus of English-language literature with following keywords: cough, nitric oxide (NO), eosinophils, biomarker, and treatable trait. Relevance and eligibility of each article were assessed by one or more of the authors and a narrative review was composed. Key Content and Findings: Eosinophilic or type 2 airway inflammation is a major treatable trait in patients with chronic cough. Induced sputum tests are regarded as the gold standard for defining inflammatory phenotype, however, technically demanding and cannot be widely applied in clinical practice. FeNO, a practical biomarker, has emerged as an alternative to induced sputum analyses. Mechanistic and clinical evidence indicated that FeNO had a potential for diagnostic utility and treatment response predictability. Conclusions: FeNO measurement may help to identify patients with chronic cough that will benefit from corticosteroid treatment. Further studies are warranted to determine the diagnostic roles of FeNO in the management of patients with chronic cough.

Quantitative Profiling of Carotenoids, Tocopherols, Phytosterols, and Fatty Acids in the Flower Petals of Ten Marigold (Tagetes spp. L.) Cultivars.

Marigold (Tagetes spp.) flower petals are the most vital sources of carotenoids, especially lutein esters, for the production of natural lutein to use for food, feed, and pharmaceutical industries. Several marigold cultivars are cultivated globally; however, their lutein ester composition and contents have not been widely investigated. Considering this, this study aimed to identify and quantify prominent carotenoid esters from the flower petals of ten marigold cultivars by liquid chromatography (LC)-diode-array detection (DAD)-mass spectrometry (MS). In addition, tocopherols, phytosterols, and fatty acids were analyzed by gas chromatography (GC)-flame ionization detection (FID) and GC-MS. Furthermore, the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) and 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging abilities of lipophilic extracts were determined. The total carotenoid contents varied significantly (p < 0. 05, Tukey HSD) among cultivars, ranging from 25.62 (cv. Alaska)-2723.11 µg/g fresh weight (cv. Superboy Orange). Among the five major lutein-diesters, (all-E)-lutein-3-O-myristate-3'-O-palmitate and lutein dipalmitate were predominant. Among the studied cultivars, α-tocopherol was recorded, ranging from 167.91 (cv. Superboy Yellow) to 338.50 µg/g FW (cv. Taishan Orange). Among phytosterols, ß-sitosterol was the most prevalent phytosterol, ranging between 127.08 (cv. Superboy Yellow) and 191.99 µg/g FW (cv. Taishan Yellow). Palmitic acid (C16:0; 33.36-47.43%) was the most dominant among the fatty acids. In this study, the highest contents of lutein were recorded from cv. Superboy Orange; however, due to the substantially higher flower petal yield, the cv. Durango Red can produce the highest lutein yield of 94.45 kg/ha. These observations suggest that cv. Durango Red and cv. Superboy Orange are the ideal candidates for lutein fortification in foods and also for commercial lutein extraction.

Changes in Nutrient Components and Digestive Enzymatic Inhibition Activities in Soy Leaves by Ethephon Treatment.

In this study, the high isoflavone-enriched soy leaves (IESLs) were manufactured by treating with the chemical inducer ethephon, a plant growth regulator, to confirm changes in the properties of soy leaves (SLs), which are underutilized. Ethephon treatment concentrations consisted of 0 (SL1), 150 (SL2), and 300 (SL3) µg/mL. The composition analysis and physiological activity were conducted according to the ethephon treatment concentration of SLs. There was no significant difference in the proximate composition and fatty acids, except for an increase with increasing ethephon treatment concentrations. Depending on the ethephon treatment concentration, free amino acids increased to 1413.0, 1569.8, and 2100.4 mg/100 g, and water-soluble vitamins increased to 246.7, 244.7, and 501.6 mg/100 g. In particular, the functional substance isoflavone increased significantly to 1430.11, 7806.42, and 14,968.00 µg/g. Through this study, it was confirmed that the nutritional components and isoflavones of SLs increased according to the ethephon treatment concentration, a chemical inducer treatment agent. This can be used as a high-value-added biosubstance for raw materials for functional foods, cosmetics, and for natural drugs.

Baseline Cohort Profile of the Korean Chronic Cough Registry: A Multicenter, Prospective, Observational Study.

PURPOSE: The Korean Chronic Cough Registry study was initiated to characterize patients with chronic cough (CC) and investigate their outcomes in real-world clinical practice. This report aims to describe the baseline cohort profile and study protocols. METHODS: This multicenter, prospective observational cohort study included newly referred CC patients and those already being treated for refractory or unexplained chronic cough (RUCC). Cough status was assessed using a visual analog scale, the Leicester Cough Questionnaire (LCQ), and the Cough Hypersensitivity Questionnaire (CHQ). RESULTS: A total of 610 patients (66.9% women; median age 59.0 years) were recruited from 18 centers, with 176 being RUCC patients (28.9%). The median age at CC onset was 50.1 years, and 94.4% had adult-onset CC (≥ 19 years). The median cough duration was 4 years. Compared to newly referred CC patients, RUCC patients had a longer cough duration (6.0 years vs. 3.0 years) but had fewer symptoms and signs suggesting asthma, rhinosinusitis, or gastroesophageal acid reflux disease. Subjects with RUCC had lower LCQ scores (10.3 ± 3.3 vs. 11.6 ± 3.6; P < 0.001) and higher CHQ scores (9.1 ± 3.9 vs. 8.4 ± 4.1; P = 0.024). There were no marked differences in the characteristics of cough between refractory chronic cough and unexplained chronic cough. CONCLUSIONS: Chronic cough typically develops in adulthood, lasting for years. Cough severity and quality of life impairment indicate the presence of unmet clinical needs and insufficient cough control in real-world clinical practice. Longitudinal follow-up is warranted to investigate the natural history and treatment outcomes.

Dissipation Kinetics and Risk Assessment of Diniconazole, Dinotefuran, Metconazole, and Tebuconazole in Raphanus sativus L.

This study investigated the degradation characteristics and conducted a risk assessment of four pesticides (Diniconazole, Dinotefuran, Metconazole, and Tebuconazole) in the leaves and roots of radish. Radish was cultivated in two greenhouse fields, and samples were collected at 0, 1, 2, 3, 5, 7, and 10 days after pesticide application. Sample analysis was performed using LC-MS/MS, and the recovery rates ranged from 70.1% to 118.6%. The biological half-life of Diniconazole was found to be 6.2 days (leaf and root), Dinotefuran was 5.3 days (leaf) and 4.6 days (root), Metconazole was 9.3 days (leaf) and 3.2 days (root), and Tebuconazole was 8.0 days (leaf) and 5.1 days (root). After comparing the maximum residue limits (MRL) of each pesticide in Korea with the residues during the pre-harvest interval (PHI), Diniconazole showed a Hazard quotient (HQ) exceeding 1, indicating potential risks for true consumers. Furthermore, Tebuconazole showed an HQ of 0.3 or higher, indicating a significant level of risk.

The association between lactate to albumin ratio and outcomes at early phase in patients with traumatic brain injury.

BACKGROUND: The majority of traumatic brain injury (TBI) cases result in death in the early phase; predicting short-term progno-sis of affected patients is necessary to prevent this. This study aimed to examine the association between the lactate-to-albumin ratio (LAR) on admission and outcomes in the early phase of TBI. METHODS: This retrospective observational study included patients with TBI who visited our emergency department between January 2018 and December 2020. TBI was considered as an head abbreviated injury scale (AIS) score of 3 or higher and other AIS of 2 or lower. The primary and secondary outcomes were 24-h mortality and massive transfusion (MT), respectively. RESULTS: In total, 460 patients were included. The 24-h mortality was 12.6% (n=28) and MT was performed in 31 (6.7%) patients. In the multivariable analysis, LAR was associated with 24-h mortality (odds ratio [OR], 2.021; 95% confidence interval [CI], 1.301-3.139) and MT (OR, 1.898; 95% CI, 1.288-2.797). The areas under the curve of LAR for 24-h mortality and MT were 0.805 (95% CI, 0.766-0.841) and 0.735 (95% CI, 0.693-0.775), respectively. CONCLUSION: LAR was associated with early-phase outcomes in patients with TBI, including 24-h mortality and MT. LAR may help predict these outcomes within 24 h in patients with TBI.

Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Pulmonary Disease in Chronic Obstructive Pulmonary Disease: Findings from a Nationwide Population-Based Study.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (2005-2018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio (HR), 1.121; 95% confidence interval (CI), 0.950-1.323; p = 0.176). However, in a subgroup analysis, the highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.950-1.323, p = 0.050). Medium (1.229, 1.008-1.499, p = 0.041) and high daily doses of ICS (1.637, 1.241-2.160, p < 0.001) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may increase the risk of developing NTM disease in patients with COPD. Physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

Dynamic modeling of pesticide residue in proso millet under multiple application situations.

Proso millet (Panicum miliaceum L.) is a cereal crop with potential resistance to drought and heat stress, making it a promising alternative crop for regions with hot and dry climates. Because of its importance, it is crucial to investigate pesticide residues in proso millet and assess their potential risks to the environment and human health to protect it from insects or pathogens. This study aimed to develop a model for predicting pesticide residues in proso millet using dynamiCROP. The field trials consisted of four plots, with each plot containing three replicates of 10 m2. The applications of pesticides were conducted two or three times for each pesticide. The residual concentrations of the pesticides in the millet grains were quantitatively analyzed using gas and liquid chromatography-tandem mass spectrometry. The dynamiCROP simulation model, which calculates the residual kinetics of pesticides in plant-environment systems, was employed for predicting pesticide residues in proso millet. Crop-specific, environment-specific, and pesticide-specific parameters were utilized to optimize the model. Half-lives of pesticides in grain of proso millet, which were needed to input for dynamiCROP, were estimated using a modified first-order equation. Proso millet-specific parameters were obtained from previous studies. The accuracy of the dynamiCROP model was assessed using statistical criteria, including the coefficient of correlation (R), coefficient of determination (R2), mean absolute error (MAE), relative root mean square error (RRMSE), and root mean square logarithmic error (RMSLE). The model was then validated using additional field trial data, which showed that it could accurately predict pesticide residues in proso millet grain under different environmental conditions. The results demonstrated the accuracy of the model in predicting pesticide residues in proso millet after multiple applications.

Outstanding Characteristics of Birt-Hogg-Dube Syndrome in Korea.

Birt-Hogg-Dube (BHD) is a rare genetic disorder characterized by multiple lung cysts, typical skin manifestations, and renal tumors. We prospectively enrolled thirty-one subjects from four South Korean institutions with typical lung cysts, and next-generation sequencing was conducted. We prospectively enrolled thirty-one subjects from four Korean institutions with typical lung cysts. Next-generation sequencing was performed to investigate mutations in the following genes: FLCN, TSC1, TSC2, CFTR, EFEMP2, ELN, FBLN5, LTBP4, and SERPINA1. BHD was diagnosed in 11 of the 31 enrolled subjects (35.5%; FLCN mutations). Notably, we identified three novel mutations (c.1098G>A, c.139G>T, and c.1335del) that have not been previously reported. In addition to FLCN mutations, we also observed mutations in CFTR (16.1%), LTBP4 (9.7%), TSC2 (9.7%), TSC1 (3.2%), ELN (3.2%), and SERPINA1 (3.2%). According to a systematic review of 45 South Korean patients with BHD, the prevalence of pneumothorax (72.7%) was greater in South Korea than in the rest of the world (50.9%; p = 0.003). The prevalence of skin manifestations (13.6%) and renal tumors (9.1%) was lower in Korea than in the rest of the world, at 47.9% [p < 0.001] and 22.5% [p = 0.027], respectively). This study confirmed a significant prediction model for BHD based on age, number of lung cysts (>40), and maximal diameter of lung cysts (>2 cm) regardless of skin manifestations and renal tumors. Importantly, three novel mutations (c.1098G>A, c.139G>T, and c.1335del) were identified. In conclusion, South Korean patients with BHD display characteristics that are different from those observed in patients of other nationalities. Detailed characterization of lung cysts is needed to define BHD, especially in South Korea, even if patients do not present with skin or renal lesions.

Inoculation Effect of Methanotrophs on Rhizoremediation Performance and Methane Emission in Diesel-Contaminated Soil.

During the rhizoremediation of diesel-contaminated soil, methane (CH4), a representative greenhouse gas, is emitted as a result of anaerobic metabolism of diesel. The application of methantrophs is one of solutions for the mitigation CH4 emissions during the rhizoremediation of diesel-contaminated soil. In this study, CH4-oxidizing rhizobacteria, Methylocystis sp. JHTF4 and Methyloversatilis sp. JHM8, were isolated from rhizosphere soils of tall fescue and maize, respectively. The maximum CH4 oxidation rates for the strains JHTF4 and JHM8 were 65.8 and 33.8 mmol·g-DCW-1·h-1, respectively. The isolates JHTF4 and JHM8 couldn't degrade diesel. The inoculation of the isolate JHTF4 or JHM8 significantly enhanced diesel removal during rhizoremediation of diesel-contaminated soil planted with maize for 63 days. Diesel removal in the tall fescue-planting soil was enhanced by inoculating the isolates until 50 days, while there was no significant difference in removal efficiency regardless of inoculation at day 63. In both the maize and tall fescue planting soils, the CH4 oxidation potentials of the inoculated soils were significantly higher than the potentials of the non-inoculated soils. In addition, the gene copy numbers of pmoA, responsible for CH4 oxidation, in the inoculated soils were significantly higher than those in the non-inoculated soils. The gene copy numbers ratio of pmoA to 16S rDNA (the ratio of methanotrophs to total bacteria) in soil increased during rhizoremediation. These results indicate that the inoculation of Methylocystis sp. JHTF4 and Methyloversatilis sp. JHM8, is a promising strategy to minimize CH4 emissions during the rhizoremediation of diesel-contaminated soil using maize or tall fescue.

Cinnamaldehyde-Rich Cinnamon Extract Induces Cell Death in Colon Cancer Cell Lines HCT 116 and HT-29.

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10-60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G1-phase cells was observed with arrest at the G2 phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation.

Roles of real-world evidence in severe asthma treatment: challenges and opportunities.

Recent advances in asthma research have led to the development of novel biologicals that hinder the pathological actions of key molecules in severe asthma. Traditional randomised controlled studies (RCTs), the gold standard for evaluating the efficacy and safety of medical interventions with excellent internal validity, have proven the clinical benefits and favourable safety profiles of type 2 biologicals in severe asthma. However, RCTs are not always ideal because of shortcomings such as limited external validity and practical issues in the management of severe asthma that cannot be solved through strictly designed clinical trials. Thus, the applicability of their findings may be questioned because treatment adherence is frequently poor in the real world. Real-world evidence includes a wide range of real-world data (RWD) collected from multiple sources in clinical practice, such as electronic medical records, healthcare insurance claims and retrospective or prospective patient registries. RWD may help clinicians decide how to manage patients with severe asthma. Real-world evidence is also gaining attention in addressing clinical questions not answered by traditional RCTs. Because there are various types of RWD with different possibilities and limitations, it is important to decide which type of RWD could be "fit for purpose" to address a specific question. This narrative review discusses the challenges and opportunities of RWD for evaluating the effectiveness and clinical outcomes of biological treatments for severe asthma.

Comparisons of Physicochemical Properties, Bacterial Diversities, Isoflavone Profiles and Antioxidant Activities on Household and Commercial doenjang.

In this study, the physicochemical properties (pH, acidity, salinity, and soluble protein), bacterial diversities, isoflavone contents, and antioxidant activities of doenjang (fermented soy paste), household doenjang (HDJ), and commercial doenjang (CDJ), were assessed and compared. The values of pH 5.14-5.94 and acidity 1.36-3.03%, indicated a similar level in all doenjang. The salinity was high in CDJ at 12.8-14.6%, and the protein contents (25.69-37.54 mg/g) were generally high in HDJ. Forty-three species were identified from the HDJ and CDJ. The main species were verified to be Bacillus amyloliquefaciens (B. amyloliquefaciens), B. amyloliquefaciens subsp. plantarum, Bacillus licheniformis, Bacillus sp. and Bacillus subtilis. Comparing the ratios of isoflavone types, the HDJ has an aglycone ratio of >80%, and 3HDJ indicates a ratio of isoflavone to aglycone of 100%. In the CDJ, except 4CDJ, glycosides account for a high proportion of more than 50%. The results of antioxidant activities and DNA protection effects were variedly confirmed regardless of HDJs and CDJs. Through these results, it is judged that HDJs have a variety of bacterial species compared to CDJs, and these are biologically active and converted from glycoside to aglycone. Bacterial distribution and isoflavone contents could be used as basic data.