Association between Smoking Habit Changes and the Risk of Myocardial Infarction in Ischemic Stroke Patients: a Nationwide cohort study.

INTRODUCTION: Smoking is a well-known risk factor for cardiovascular diseases, including myocardial infarction (MI) and ischemic stroke (IS). While the relationship between smoking and the risk of cardiovascular diseases is established, the impact of changing smoking habits post-IS on the risk of subsequent MI remains unclear. This study aims to elucidate the effects of alterations in smoking behavior following an IS diagnosis on the likelihood of experiencing an MI. METHODS: Utilizing data from the Korean National Health Insurance Services Database, this nationwide population-based cohort study included 199,051 participants diagnosed with IS between January 2010 and December 2016. Smoking status was categorized based on changes in smoking habits before and after IS diagnosis. The association between changes in smoking behavior and the risk of subsequent MI was analyzed using multivariable Cox proportional hazard regression models. RESULTS: During a median follow-up of 4.17 person-years, a total of 5,734 (2.88%) patients were diagnosed with MI after IS. Smoking quitters (2.93%) or former smokers (2.47%) have a similar or lower rate of MI than the average, even if they have smoked cigarettes, while sustained smokers (3.46%) or new smokers (3.81%) have much higher rates of MI. Among sustained and new smokers, the risk of incident MI were significantly higher than never smokers (new smoker adjusted HR [aHR]: 1.496, 95% CI 1.262-1.774; sustained smoker aHR 1.494, 95% CI 1.361-1.641). Also, among the study participants, approximately two-thirds continued smoking after their IS diagnosis. CONCLUSION: Changing smoking habits after an IS diagnosis significantly influences the risk of subsequent MI. Specifically, continuing or starting to smoke after an IS diagnosis is associated with a higher risk of MI. These results underscore the importance of targeted smoking cessation interventions for stroke patients to reduce the risk of subsequent myocardial infarction.

Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Association between physical activity changes and incident myocardial infarction after ischemic stroke: a nationwide population-based study.

BACKGROUND: The impact of changes in physical activity after ischemic stroke (IS) on the subsequent myocardial infarction (MI) risk is not fully understood. We aimed to investigate the effects of changes in physical activity on the risk of MI after acute IS using data from the Korean National Health Insurance Services Database. METHODS: 224,764 patients newly diagnosed with IS between 2010 and 2016 who underwent two serial biannual health checkups were included. The participants were divided into four categories according to changes in their physical activity: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was a new diagnosis of incident MI. Multivariable Cox proportional models were used to assess the effects of changes in exercise habits on the risk of MI. RESULTS: After a median of 4.25 years of follow-up, 6,611 (2.94%) MI cases were observed. After adjusting for confounders, new exercisers and exercise maintainers were significantly associated with a lower risk of incident MI than persistent non-exercisers (aHR, 0.849; 95% CI, 0.792-0.911; P-value < 0.001; and aHR, 0.746; 95% CI, 0.696-0.801; P-value < 0.001, respectively). Effects were consistent across sexes, more pronounced in those > 65 years. Notably, any level of physical activity after stroke was associated with a reduced MI risk compared to no exercise. CONCLUSIONS: In this nationwide cohort study, commencing or sustaining physical activity after an IS corresponded to a diminished likelihood of subsequent MI development. Advocating physical activity in ambulatory stroke survivors could potentially attenuate the prospective risk of MI.

Anticancer Activity of Astaxanthin-Incorporated Chitosan Nanoparticles.

Astaxanthin (AST)-encapsulated nanoparticles were fabricated using glycol chitosan (Chito) through electrostatic interaction (abbreviated as ChitoAST) to solve the aqueous solubility of astaxanthin and improve its biological activity. AST was dissolved in organic solvents and then mixed with chitosan solution, followed by a dialysis procedure. All formulations of ChitoAST nanoparticles showed small diameters (less than 400 nm) with monomodal distributions. Analysis with Fourier transform infrared (FT-IR) spectroscopy confirmed the specific peaks of AST and Chito. Furthermore, ChitoAST nanoparticles were formed through electrostatic interactions between Chito and AST. In addition, ChitoAST nanoparticles showed superior antioxidant activity, as good as AST itself; the half maximal radical scavenging concentrations (RC50) of AST and ChitoAST nanoparticles were 11.8 and 29.3 µg/mL, respectively. In vitro, AST and ChitoAST nanoparticles at 10 and 20 µg/mL properly inhibited the production of intracellular reactive oxygen species (ROSs), nitric oxide (NO), and inducible nitric oxide synthase (iNOS). ChitoAST nanoparticles had no significant cytotoxicity against RAW264.7 cells or B16F10 melanoma cells, whereas AST and ChitoAST nanoparticles inhibited the growth of cancer cells. Furthermore, AST itself and ChitoAST nanoparticles (20 µg/mL) efficiently inhibited the migration of cancer cells in a wound healing assay. An in vivo study using mice and a pulmonary metastasis model showed that ChitoAST nanoparticles were efficiently delivered to a lung with B16F10 cell metastasis; i.e., fluorescence intensity in the lung was significantly higher than in other organs. We suggest that ChitoAST nanoparticles are promising candidates for antioxidative and anticancer therapies of B16F10 cells.

A Comparative Study of Endoscopic versus Percutaneous Epidural Neuroplasty in Lower Back Pain: Outcomes at Six-Month Follow Up.

Background and Objectives: Endoscopic epidural neuroplasty (EEN) facilitates adhesiolysis through direct epiduroscopic visualization, offering more precise neural decompression than that exhibited by percutaneous epidural neuroplasty (PEN). We aimed to compare the effects of EEN and PEN for 6 months after treatment with lower back and radicular pain in patients. Methods: This retrospective study compared the visual analog scale (VAS) and Oswestry disability index (ODI) scores in patients with low back and radicular pain who underwent EEN or PEN with a steering catheter. The medical records of 107 patients were analyzed, with 73 and 34 undergoing EEN and PEN, respectively. Results: The VAS and ODI scores decreased at all time points after EEN and PEN. VAS and ODI scores decreased more in the EEN group than those in the PEN group at 1 day and 1- and 6-months post-procedure, indicating superior pain relief for both lower back and radicular pain through EEN. Conclusions: EEN is a superior treatment of pain control than PEN in lower back and radicular pain patients.

Dynamic altruistic cooperation within breast tumors.

BACKGROUND: Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism's survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance. METHODS: MicroRNA profiling was performed on circulating tumor cells collected from the blood of treated breast cancer patients. Cancer cell lines ectopically expressing candidate miRNA were used in co-culture experiments and treated with docetaxel. Ecological parameters like relative survival and relative fitness were assessed using flow cytometry. Functional studies and characterization performed in vitro and in vivo include proliferation, iTRAQ-mass spectrometry, RNA sequencing, inhibition by small molecules and antibodies, siRNA knockdown, CRISPR/dCas9 inhibition and fluorescence imaging of promoter reporter-expressing cells. Mathematical modeling based on evolutionary game theory was performed to simulate spatial organization of cancer cells. RESULTS: Opposing cancer processes underlie altruism: an oncogenic process involving secretion of IGFBP2 and CCL28 by the altruists to induce survival benefits in neighboring cells under taxane exposure, and a self-sacrificial tumor suppressive process impeding proliferation of altruists via cell cycle arrest. Both processes are regulated concurrently in the altruists by miR-125b, via differential NF-κB signaling specifically through IKKß. Altruistic cells persist in the tumor despite their self-sacrifice, as they can regenerate epigenetically from non-altruists via a KLF2/PCAF-mediated mechanism. The altruists maintain a sparse spatial organization by inhibiting surrounding cells from adopting the altruistic fate via a lateral inhibition mechanism involving a GAB1-PI3K-AKT-miR-125b signaling circuit. CONCLUSIONS: Our data reveal molecular mechanisms underlying manifestation, persistence and spatial spread of cancer cell altruism. A minor population behave altruistically at a cost to itself producing a collective benefit for the tumor, suggesting tumors to be dynamic social systems governed by the same rules of cooperation in social organisms. Understanding cancer cell altruism may lead to more holistic models of tumor evolution and drug response, as well as therapeutic paradigms that account for social interactions. Cancer cells constitute tractable experimental models for fields beyond oncology, like evolutionary ecology and game theory.

Role of IL-22 in acute asthma mouse model.

Introduction: Allergic asthma is often associated with eosinophilic inflammation, which is related to the T-helper cell type 2 (Th2) cytokines and responsive to corticosteroids. However, there are also phenotypes of non-Th2-mediated asthma, which have poor responsivity to corticosteroids. The leading phenotype of non-Th2-mediated asthma is neutrophilic asthma, which is considered difficult to treat. Recently, IL-22 has been found to be involved in neutrophilic inflammation in asthma. However, studies on the role of IL-22 in asthma are still controversial as IL-22 has both pro-inflammatory and anti-inflammatory roles in asthma. This study examined whether the IL-22 level increased in acute neutrophilic asthma in the mouse model. Herein, we aimed to demonstrate increased IL-22 levels in neutrophilic asthma and elucidate the pathways leading to elevated neutrophil counts.Methods: Six-week old female BALB/c mice were sensitized and challenged with PBS, ovalbumin (OVA) or OVA + lipopolysaccharide (LPS). The mice were then assigned to one of the following five groups: (1) control (PBS/ PBS), (2) OVA/PBS, (3) OVA/OVA, (4) OVA+LPS/PBS, (5) OVA+LPS/OVA+LPS.Results: The levels of Th2 cytokines, IL-17, and IL-22 were assessed, with investigation of the neutrophil chemokines. This study showed that in the acute neutrophilic asthma, the levels of IL-17 and IL-22 were significantly higher than those in the OVA/OVA group, which represents acute eosinophilic asthma. Moreover, the level of CCL20 increased in the neutrophilic asthma group.Conclusion: Thus, this study suggests that in the acute neutrophilic asthma mouse model, IL-17 and IL-22 may increase with CCL20, resulting in neutrophilic inflammation.

Healthcare usage and cost for plantar fasciitis: a retrospective observational analysis of the 2010-2018 health insurance review and assessment service national patient sample data.

BACKGROUND: Plantar fasciitis (PF) is the most common cause of heel pain in adults, and the number of patients and medical expenses are increasing annually. However, studies on this condition are lacking. There is a need to investigate universally administered PF treatment and the associated costs. Therefore we analyzed the South Korean Health Insurance Review and Assessment Service data to investigate the distribution and healthcare usage of patients with PF. METHODS: A cross-sectional retrospective observational design was used in this study. Patients diagnosed with PF (ICD-10 code M72.2) between January 2010 and December 2018 in South Korea, of whom 60,079 had used healthcare at least once, were included in the study. We assessed healthcare usage and cost due to PF, treatment method, and visit route. All statistical analyses were performed with descriptive statistics using SAS 9.4 version. RESULTS: The number of treated cases of PF and patients with PF was 11,627 cases and 3,571 patients in 2010, respectively, which increased annually to 38,515 cases and 10,125 patients by 2018, respectively. The 45-54-year-old age group had the highest number of patients; the patient population was predominantly women. Physical therapy was used frequently in Western medicine (WM) institutions, where > 50% of the medicines prescribed to outpatients were analgesics. In contrast, acupuncture therapy was most commonly used in Korean medicine (KM) institutions. A high percentage of patients who visited a KM institution, followed by a WM institution, and then returned to the same KM institution had visited the WM institution for radiological diagnostic examination. CONCLUSION: This study analyzed nine years of period data from a patient sample of claims data from the Health Insurance Review and Assessment Service to examine the current status of health service use for PF in Korea. We obtained information on the status of WM/KM institution visits for PF treatment, which could be useful for health policymakers. Study findings regarding treatments often used in WM/KM, the frequency of treatments, and their costs could be used as basic data by clinicians and researchers.

Effectiveness of Chuna (or Tuina) Manual Therapy for Temporomandibular Disorder: A Systematic Review.

Background: Temporomandibular disorder (TMD) affects patients' quality of life (QoL) because of the resulting structural and functional impairment and pain. Objective: This study aimed to evaluate the evidence regarding the effectiveness, safety and improvement in QoL in patients who underwent Chuna manual therapy (CMT) for TMD. Methods: We searched 11 databases and included randomized controlled trials (RCT) on CMT for TMD published before March 2020. A meta-analysis was conducted, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was used to evaluate the evidence level. We included 12 RCTs that compared CMT and conventional care. Results: CMT showed significantly better patient pain reduction, functional improvement and QoL. A superior result was seen in the use of CMT in conjunction with Traditional Chinese Medicine (TCM) or conventional care. CMT showed no minor or serious adverse events compared with medical treatments. The evidence level was low for all outcomes, except QoL. Conclusions: We found that CMT for TMD resulted in functional improvement, pain reduction and improvement in QoL, with fewer adverse events. However, since the evidence level varied from very low to moderate due to imprecision and the risk of bias with the included studies, we are limited in determining the efficacy of Chuna therapy using these studies. High-quality, well-designed and large-scale RCTs are needed to conclusively determine the clinical efficacy of CMT in TMD.

Casein kinase I inhibitor D4476 influences autophagy and apoptosis in chloroquine-induced adult retinal pigment epithelial-19 cells.

The antimalarial drug chloroquine (CQ) induces retinopathy, a disorder characterized by lysosomotropic alteration. In this study, we examined whether D4476 (4-(4-(2,3-dihydrobenzo [1,4] dioxin-6-yl)-5-pyridin-2-yl-1H-imidazole-2-yl) benzamide), a specific casein kinase 1 inhibitor, alleviate CQ-induced retinopathy in adult retinal pigment epithelial (ARPE-19) cells. Cultured ARPE-19 cells were exposed to CQ with or without D4476 and cell death was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To examine autophagy flux, ARPE-19 cells were transfected with green fluorescence protein light chain 3 (GFP-LC3)-red fluorescence protein (RFP)-LC3ΔG plasmid DNA and co-stained with the lysosomal-associated membrane protein (LAMP)-1 antibody. Western blotting and fluorescence-activated cell sorting (FACS) showed apoptosis, whereas the fluorescence intensity of 2'-7'-dichlorofluorescein diacetate revealed levels of cellular oxidative stress. We then confirmed the effect of D4476 on the interaction between Beclin 1 and B-cell lymphoma-2 (Bcl-2) through immunoprecipitation with an anti-Bcl-2 antibody. Following CQ exposure, ARPE-19 cells accumulated autophagosomes because of defective lysosomal degradation. Furthermore, CQ trapped Beclin 1 with Bcl-2, disturbing autophagy initiation and autolysosome formation. However, D4476 alleviated CQ-induced effects by rescuing ARPE-19 cells from CQ-induced toxicity by modulating the association between Beclin 1 and Bcl-2. Therefore, D4476 controls autophagy and apoptosis simultaneously by upregulating autophagy flux, decreasing ROS formation, and triggering the expression of anti-apoptotic proteins through inhibition of mTOR, JNK, and p38 MAPK signals. We conclude that D4476 is a promising treatment strategy for CQ-mediated retinopathy.

Platycodin D attenuates airway inflammation via suppression Th2 transcription factor in a murine model of acute asthma.

Introduction: Bronchial asthma is a common chronic inflammatory condition of the airway tissue. Platycodin D (PLD) has antiinflammatory effects in a mouse model of allergic asthma. In this work, the anti-asthma potential of PLD was studied by investigation of its effect to suppress airway inflammation and mucin production, a murine model of asthma and the possible mechanisms.Methods: Mice were randomly assigned to five experimental groups: control, ovalbumin (OVA), OVA+ICS (intranasal fluticasone), OVA+PLD and OVA+PLD/ICS. Airway histological studies were evaluated by the H&E staining; IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid were evaluated by ELISA; GATA3 and IRF4 mRNA of airway were measured by RT-PCR and their protein level were measured by Western blotting.Results: Our study showed that PLD suppressed eosinophilic inflammation and mucin production in bronchial mucosa. Moreover, PLD inhibited production of Th2 cytokines such as IL-4, IL-5, and IL-13. Protein production of GATA3 and IRF4, were also decreased in PLD treated OVA asthma model. Taken together, our results provided evidence that PLD inhibits the airway inflammation via suppression of Th2 transcription factor production.Conclusion: These findings suggest that PLD may effectively ameliorate the progression of asthma. These results suggest that PLD could be used as a therapy for allergic asthma.

Evidence to guide ethical decision-making in the management of older people living in squalor: a narrative review.

Older people living in squalor present healthcare providers with a set of complex issues because squalor occurs alongside a variety of medical and psychiatric conditions, and older people living in squalor frequently decline intervention. To synthesise empirical evidence on squalor to inform ethical decision-making in the management of squalor using the bioethical framework of principlism. A systematic literature search was conducted using Medline, Embase, PsycINFO and CINAHL databases for empirical research on squalor in older people. Given the limited evidence base to date, an interpretive approach to synthesis was used. Sixty-seven articles that met the inclusion criteria were included in the review. Our synthesis of the research evidence indicates that: (i) older people living in squalor have a high prevalence of frontal executive dysfunction, medical comorbidities and premature deaths; (ii) interventions are complex and require interagency involvement, with further evaluations needed to determine the effectiveness and potential harm of interventions; and (iii) older people living in squalor utilise more medical and social resources, and may negatively impact others around them. These results suggest that autonomous decision-making capacity should be determined rather than assumed. The harm associated with squalid living for the older person, and for others around them, means a non-interventional approach is likely to contravene the principles of non-maleficence, beneficence and justice. Adequate assessment of decision-making capacity is of particular importance. To be ethical, any intervention undertaken must balance benefits, harms, resource utilisation and impact on others.

Clinical evaluation of usefulness and effectiveness of sitting type continuous passive motion machines in patients with total knee arthroplasty: a study protocol for a single-blinded randomized controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is an important management strategy for patients with knee osteoarthritis (OA) refractory to conservative management. Postoperative range of motion (ROM) exercise is important to recover patients' activities of daily living. Continuous passive motion (CPM) is a machine that provides passive ROM exercises of the knee joint in a pre-defined arc of motion. The short- and long-term effects of CPM exercise are controversial. We hypothesized that the inconsistent results of the CPM exercise are due to poor fitting of CPM machines and measurement errors. This study aims to present a protocol for investigating a new type of CPM machine that could be applied in a sitting position in comparison with the conventional type of CPM machine for patients with unilateral TKAs. METHODS: This study presents the protocol of a prospective, multicenter, single-blinded, three-armed randomized controlled trial (RCT). One hundred and twenty-six patients receiving unilateral TKAs will be recruited at the physical medicine and rehabilitation clinics of two urban tertiary medical hospitals. The patients were randomly divided into three groups with a 1:1:1 allocation. The intervention group will receive two weeks of post-operative rehabilitation using a new type of CPM machine. The control group will receive 2 weeks of post-operative rehabilitation using conventional CPM machines. The third group will receive post-operative rehabilitation with both types of CPM machines. The primary outcome will be the change in the passive ROM of the affected knee joint from baseline to 2 weeks after baseline assessment. The secondary outcomes will be pain and functional measurements, and will include patient-reported outcomes and performance tests surveyed at multiple time points up to 3 months after TKA. DISCUSSION: This is the first RCT to investigate the effect of a new type of CPM machine. The results of this RCT will determine whether the position of the patients during CPM exercise is important in post-operative rehabilitation protocols after TKAs and will provide evidence for the development of proper rehabilitation guidelines after TKAs. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea, KCT0005520, Registered on 21 October 2020, https://cris.nih.go.kr/cris/search/detailSearch.do/21750.

Association of temporomandibular disorders and tinnitus with health-related quality of life: A cross-sectional study using the Fifth Korea National Health and Nutrition Examination Survey.

BACKGROUND: Few studies have examined the associations of temporomandibular disorders (TMDs) and tinnitus with health-related quality of life on a national level. OBJECTIVE: We aimed to investigate the associations of TMDs, tinnitus and quality of life among the Korean population, aged 19 years or older. METHODS: Data were obtained from the fifth Korea National Health and Nutrition Examination Survey (2012; N = 5786). TMDs, tinnitus and health-related quality of life were assessed using self-report data from EuroQol-5 Dimension. Participants were divided into four groups: no TMD and no tinnitus, TMD present but no tinnitus, no TMD but tinnitus present and both TMD and tinnitus present. RESULTS: Among the participants, 21.88% had TMD, 24.93% had tinnitus, and 7.74% had both. The prevalence of most TMD and all types of tinnitus was higher among females than among males. The group with both TMD and tinnitus reported the highest percentage of problems in the usual activity, pain/discomfort and anxiety/depression dimensions. Moreover, the odds ratio (OR) for lower quality of life was significantly higher in the group with both TMD and tinnitus compared to the group without TMD and tinnitus: mobility (OR = 1.527, 95% confidence interval [CI]: 1.014-2.300), pain/discomfort (OR = 2.072, 95% CI: 1.570-2.735), anxiety/depression (OR = 1.692, 95% CI: 1.034-2.767), EQ-5D score (OR = 1.651, 95% CI: 1.121-2.431) and EQ-VAS (OR = 1.682, 95% CI: 1.246-2.269). CONCLUSION: The presence of both TMD and tinnitus has a considerable impact on HRQoL in the Korean population. In our study, the group with both TMD and tinnitus showed lower HRQoL than without TMD and tinnitus group. These results emphasise the need for a multilateral and comprehensive approach to address these disorders and provide baseline data for developing appropriate interventions.

Glucagon-like peptide 1 receptor (GLP-1R) agonist relieved asthmatic airway inflammation via suppression of NLRP3 inflammasome activation in obese asthma mice model.

BACKGROUND: Obesity is a correctable factor for uncontrolled bronchial asthma. However, the effects of glucagon-like peptide-1 receptor (GLP-1R) agonist, a recently approved antiobestic drug, on airway hyperresponsiveness (AHR) and immune responses are not known. METHODS: Mice were fed with high-fat diet (HFD, 60% fat) for 8 weeks to induce obesity. Ovalbumin (OVA) sensitization and challenges were performed for 7 weeks. The mice were injected intraperitoneally with GLP-1R agonist 5 times a week for 4 weeks after OVA sensitization. After AHR measurement, expression of Th2, Th17 cytokines, and interleukin (IL)-33 were measured in BALF and lung tissues. Moreover, IL-1ß and activity level of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were analyzed to investigate the mechanism of GLP-1R agonist on asthmatic airway inflammation. RESULTS: HFD induced significant weight gain, OVA sensitization and challenge in obese mice made eosinophilic airway inflammation, and increased AHR. Treatment with GLP-1R agonist-induced weight loss suppressed eosinophilic airway inflammation and decreased AHR. Expression of IL-4, 5, and 33 was increased in BALF of obese asthma mice followed by a decrease in response to GLP-1R agonist treatment. Moreover, lung tissue H&E stain revealed that peribronchial inflammation induced by obesity and OVA was effectively suppressed by GLP-1R agonist. Expressions of NLRP3, activated caspase-1, and IL-1ß were increased in lung tissues of obese asthma mice and demonstrated a decrease in response to GLP-1R agonist treatment. CONCLUSIONS: GLP-1R agonist effectively induced weight loss, suppressed eosinophilic bronchial airway inflammation, and AHR in obese asthma mice. These effects were mediated by suppression of NLRP3 inflammasome activity and IL-1ß. GLP-1R agonist is proposed as a novel anti-asthmatic agent targeting the obese asthmatics.

Cyclo-VEGI inhibits bronchial artery remodeling in a murine model of chronic asthma.

Purpose/Aim: In the context of asthma, airway bronchial remodeling and angiogenesis in the bronchial mucosa are well established. Cyclopeptidic-vascular endothelial growth inhibitor (cyclo-VEGI) is an inhibitor of the vascular endothelial growth factor (VEGF) receptor that increases the proliferation of endothelial cells and the formation of new vessels. However, changes in the bronchial arteries of patients with asthma have not been clearly elucidated. We investigated whether structural changes occurred in bronchial arteries, as well as the effects of cyclo-VEGI in a mouse model of chronic asthma (in vivo) and human fibroblasts (in vitro). Materials and Methods: A validated mouse model of allergic airway inflammation with ovalbumin (OVA) as the causative allergen was used for the study. Mice were treated with cyclo-VEGI or fluticasone during OVA challenge. In vitro experiments were conducted to determine whether fibroblasts proliferated following elastin exposure and the effects of cyclo-VEGI on them. Results: OVA sensitization and challenge led to greater perivascular smooth muscle area, more elastic fibers, and elevated expression of vascular cell adhesion molecule (VCAM)-1 antigen. These phenomena indicated changes to bronchial arteries. Cyclo-VEGI and fluticasone treatment both inhibited airway hyper-responsiveness and inflammation. Cyclo-VEGI-treated mice exhibited decreased perivascular smooth muscle area, elastin fibers, and VCAM-1 expression. Fluticasone-treated mice exhibited reductions in perivascular smooth muscle but not in perivascular elastin or VCAM-1 expression. In vitro, fibroblast proliferation was enhanced by elastin treatment, which was inhibited by cyclo-VEGI treatment. Eotaxin expression was elevated in elastin-treated fibroblasts and decreased with cyclo-VEGI treatment. Conclusions: Vascular remodeling occurred in our mouse model of chronic asthma. Cyclo-VEGI could reduce airway inflammation and hyper-responsiveness by inhibiting VCAM-1 expression and elastin deposition around the bronchial arteries.

Association between diabetes mellitus and anemia among Korean adults according to sex: a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey (2010-2016).

BACKGROUND: There are many conflicting opinions regarding the association between anemia and diabetes mellitus (DM), and the mechanism by which DM influences anemia remains uncertain. Therefore, we aimed to investigate the association between anemia and DM in Korean adults and to analyze the risk factors for anemia among these patients according to sex. METHODS: This retrospective cross-sectional survey was conducted using data from the Korea National Health and Nutrition Examination Survey V, VI, and VII between January 2010 and December 2016. In total, 25,597 Korean adults aged ≥19 years (10,117 men, 15,480 women) were included. Patients with a fasting blood sugar level of ≥126 mg/dL or who have been diagnosed with DM were classified as the DM group. Anemia was defined as hemoglobin levels of < 13 g/dL in men and < 12 g/dL in women. Logistic regression analysis was used to adjust for demographic characteristics and lifestyle-, disease-, and health-related factors. RESULTS: Approximately 11.3% of patients had DM. The prevalence of anemia was significantly higher in the DM group than in the non-DM group. After adjusting for confounding factors, the odds of the prevalence of anemia in men were higher in the DM group than in the non-DM group (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.42-2.50, p < 0.0001). When investigated according to the serum creatinine level, the association was significantly stronger among women (OR 42.63, 95% CI 17.25-105.36, p < 0.0001) than among men (OR 6.30, 95% CI 3.08-12.90, p < 0.0001). CONCLUSIONS: We found a strong association between DM and anemia that was more prominent among men than among women. We also determined that the serum creatinine level had a greater influence on DM and anemia in women than in men.

Effect of Cognitive Training in Fully Immersive Virtual Reality on Visuospatial Function and Frontal-Occipital Functional Connectivity in Predementia: Randomized Controlled Trial.

BACKGROUND: Cognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent. OBJECTIVE: We aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia. METHODS: Participants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel-based analyses were used to identify the cognitive improvement-related functional connectivity in the visual network of the brain. RESULTS: After VR cognitive training, significant improvement was found in the total score (F1,39=14.69, P=.001) and basic components score of the RCFT copy task (F1,39=9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F1,39=3.55, P=.07), verbal memory delayed recall (F1,39=3.03, P=.09), and phonemic fluency (F1,39=3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F1,39=7.02, P=.01), affect (F1,39=14.40, P=.001 for positive affect; F1,39=4.23, P=.047 for negative affect), and quality of life (F1,39=4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group. CONCLUSIONS: Fully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity. TRIAL REGISTRATION: Clinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa.

Intergenic recombination in feline calicivirus associated with a hemorrhagic-like disease in the Republic of Korea.

Feline calicivirus (FCV) is a common cause of upper respiratory tract disease in cats. In this study, the complete genome sequence of FCV 14Q315, which was detected from a dead domestic cat with a hemorrhagic-like disease, was analyzed to identify the genetic characteristics. The FCV 14Q315 genome was 7,684 bp. Phylogenetic analyses based on the ORF1, ORF2, and ORF3 sequences indicated that FCV 14Q315 is more closely related to FCV 15D022 than to other FCV strains. ORF1 of FCV 14Q315 shared high sequence similarity with ORF1 of FCVs 15D022 and UTCVM-H1. We further evaluated genetic recombination in ORF1 of FCV 14Q315 and detected intergenic recombination between p30 and the ORF1/ORF2 junction with high significance. Particularly, the non-recombination region in ORF1 of FCV 14Q315 showed high sequence similarity with FCVs GX2019, CH-JL2, and 15D022. The recombination region in ORF1 of FCV 14Q315 showed the highest similarity with FCV UTCVM-H1, which is associated with a hemorrhagic-like disease. The results suggest that the UTCVM-H1-like FCV was introduced into the Republic of Korea and presumably recombined with Korean FCVs by occasional mixed infections. In addition, the Korean FCV strains were located in several phylogenetic clusters with marked genetic diversity in the ORF2 region. These results imply that Korean FCVs possess high genetic diversity owing to mutations and recombination. Furthermore, it is possible that certain FCVs caused cyclical infections in the Korean cat population based on a phylogenetic analysis of FCVs isolated at different time points. Keywords: calicivirus; virulent systemic feline calicivirus; recombination; hemorrhagic-like disease.

Metabolic profiling and antioxidant activity during flower development in Agastache rugosa.

Our previous study showed that flowers of Agastache rugosa had higher phenolic levels and higher antibacterial and antioxidant capacity compared to those of the leaves and stems. The aim of this study was to provide information on the variation in primary and secondary metabolites during flower development in A. rugosa by using high performance liquid chromatography (HPLC) and assays of total anthocyanin (TAC), flavonoid (TFC), and phenolic content (TPC), as well as gas chromatography time-of-flight mass spectrometry (GC-TOFMS) analysis. Assays of TPC, TAC, and TFC showed that the floral bud (stage I) contained higher TPC than did the partially open flower (stage II) and fully open flower (stage III). However, the TFC was the highest at stage II, and the highest TAC was observed at stage III. Furthermore, HPLC analysis revealed that the level of total phenylpropanoids, including rosmarinic acid, tilianin, acacetin, 4-hydroxybenzoic acid, caffeic acid, chlorogenic acid, trans-cinnamic acid, rutin, (-)-epicatechin, quercetin, and kaempferol, was higher in stages I and II, but the concentrations of rutin and rosmarinic acid were highest in stage III. A total of 43 compounds, including amino acids, organic acids, phenolic compounds, sugars, photorespiration-related compounds, and intermediates of the tricarboxylic acid cycle, were identified through GC-TOFMS analysis. Of these compounds, most amino acids decreased during flower development. In contrast, the increase in concentrations of glucose and sucrose were observed from stages I to III. In this study, health-beneficial compounds were identified and quantified in flowers of A. rugosa. Accordingly, our results suggests that A. rugosa flowers can potentially be used as biomaterials for pharmaceuticals, cosmetics, food, and related industries. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s12298-021-00945-z).