Anti-Inflammatory Effects of Paraprobiotic Lactiplantibacillus plantarum KU15122 in LPS-Induced RAW 264.7 Cells.

Inflammation is a biodefense mechanism that provides protection against painful conditions such as inflammatory bowel disease, other gastrointestinal problems, and irritable bowel syndrome. Paraprobiotics have probiotic characteristics of intestinal modulation along with merits of safety and stability. In this study, heat-killed Lactiplantibacillus plantarum KU15122 (KU15122) was investigated for its anti-inflammatory properties. KU15122 was subjected to heat-killed treatment for enhancement of its safety, and its concentration was set at 8 log CFU/mL for conducting different experiments. Nitric oxide production was most remarkably reduced in the KU15122 group, whereas it was increased in the LPS-treated group. In RAW 264.7 cells, KU15122 inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. ELISA revealed that among the tested strains, KU15122 exhibited the most significant reduction in PGE2, IL-1ß, and IL-6. Moreover, KU15122 inhibited various factors involved in the nuclear factor-kappa B, activator protein-1, and mitogen-activated protein kinase pathways. In addition, KU15122 reduced the generation of reactive oxygen species. The anti-inflammatory effect of KU15122 was likely attributable to the bacterial exopolysaccharides. Conclusively, KU15122 exhibits anti-inflammatory potential against inflammatory diseases.

Multiparametric myocardial mapping using cardiac magnetic resonance imaging in healthy dogs: Reproducibility, repeatability, and differences across slices, segments, and sequences.

Myocardial mapping in humans has been widely studied and applied to understand heart disease, facilitate early diagnosis, and determine therapeutic targets; however, the reproducibility, repeatability, and protocol-dependent differences in myocardial mapping in dogs remain unknown, which limits its application in dogs. This study investigated the reproducibility and test-retest repeatability of myocardial mapping in dogs and evaluated the differences according to slice, segment, and sequence. Precontrast T1 (native T1), T2 (T2), and T2* relaxation time (T2*), and extracellular volume (ECV) were measured at the base, midventricle, and apex of the left ventricle in six healthy beagles. To compare the sequences, the saturation recovery-based (SMART1) and inversion recovery-based (MOLLI) sequences were used for native T1 and ECV mapping. The intraclass correlation coefficient was measured to evaluate reproducibility and repeatability using the coefficient of variation and Bland-Altman analysis. All parameters showed good to excellent intra- and interobserver reproducibility and test-retest repeatability. The apex slice showed the lowest repeatability among the slices, whereas ECV had the lowest repeatability among the parameters. Native T1, ECV, and T2* did not differ according to slice, but T2 significantly increased from the base to the apex. Native T1 was significantly higher in SMART1 than in MOLLI, whereas ECV did not differ between the two sequences. Our results suggest that myocardial mapping is applicable in dogs with high reproducibility and repeatability, although slice and sequence differences should be considered. This study can serve as a guide for myocardial mapping studies in dogs with heart disease.

Ibulocydine Inhibits Migration and Invasion of TNBC Cells via MMP-9 Regulation.

Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.

Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Infection in Chronic Airway Disease: A Nationwide Population-Based Study.

BACKGROUND: Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroids (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases. METHODS: We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability treatment weighting (IPTW) to ensure a balanced analysis of covariates. RESULTS: Of the 57,553 patients (mean age: 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including 9 among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI]: 7.48-15.58). Higher risks were significant for patients ≥65 years (adjusted HR: 6.40, 95% CI: 1.28-31.94), females (adjusted HR: 10.91, 95% CI: 2.24-53.20), never-smokers (adjusted HR: 6.31, 95% CI: 1.49-26.64), systemic steroid users (adjusted HR: 50.19, 95% CI: 8.07-312.19), and those with higher comorbidity scores (adjusted HR: 6.64, 95% CI: 1.19-37.03). CONCLUSION: ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.

Treatment expectations and clinical outcomes following repetitive transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Patient expectations, including both positive (placebo) and negative (nocebo) effects, influence treatment outcomes, yet their impact on acute repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) is unclear. METHODS: In this single-center retrospective chart review, 208 TRD patients completed the Stanford Expectation of Treatment Scale (SETS) before starting open-label rTMS treatment. Patients were offered two excitatory rTMS protocols (deep TMS or intermittent theta-burst stimulation), which stimulated the left dorsolateral prefrontal cortex. A minimum of 20 once daily treatments were provided, delivered over 4-6 weeks. Primary outcomes were 1) remission, measured by a post-treatment score of <8 on the Hamilton Depression Rating Scale (HAMD-17), and 2) premature discontinuation. The change in HAMD-17 scores over time was used as a secondary outcome. Physicians were blinded to SETS scores. Logistic and linear regression, adjusting for covariates, assessed SETS and HAMD-17 relationships. RESULTS: Of 208 patients, 177 had baseline and covariate data available. The mean positivity bias score (positive expectancy minus negative expectancy subscale averages) was 0.48 ± 2.21, indicating the cohort was neutral regarding the expectations of their treatment on average. Higher positive expectancy scores were significantly associated with greater odds of remission (OR = 1.90, p = 0.003) and greater reduction in HAMD-17 scores (ß = 1.30, p = 0.005) at the end of acute treatment, after adjusting for covariates. Negative expectancy was not associated with decreased odds of remission (p = 0.2) or treatment discontinuation (p = 0.8). CONCLUSIONS: Higher pre-treatment positive expectations were associated with greater remission rates with open-label rTMS in a naturalistic cohort of patients with TRD.

Acute myocardial infarction prognosis prediction with reliable and interpretable artificial intelligence system.

OBJECTIVE: Predicting mortality after acute myocardial infarction (AMI) is crucial for timely prescription and treatment of AMI patients, but there are no appropriate AI systems for clinicians. Our primary goal is to develop a reliable and interpretable AI system and provide some valuable insights regarding short, and long-term mortality. MATERIALS AND METHODS: We propose the RIAS framework, an end-to-end framework that is designed with reliability and interpretability at its core and automatically optimizes the given model. Using RIAS, clinicians get accurate and reliable predictions which can be used as likelihood, with global and local explanations, and "what if" scenarios to achieve desired outcomes as well. RESULTS: We apply RIAS to AMI prognosis prediction data which comes from the Korean Acute Myocardial Infarction Registry. We compared FT-Transformer with XGBoost and MLP and found that FT-Transformer has superiority in sensitivity and comparable performance in AUROC and F1 score to XGBoost. Furthermore, RIAS reveals the significance of statin-based medications, beta-blockers, and age on mortality regardless of time period. Lastly, we showcase reliable and interpretable results of RIAS with local explanations and counterfactual examples for several realistic scenarios. DISCUSSION: RIAS addresses the "black-box" issue in AI by providing both global and local explanations based on SHAP values and reliable predictions, interpretable as actual likelihoods. The system's "what if" counterfactual explanations enable clinicians to simulate patient-specific scenarios under various conditions, enhancing its practical utility. CONCLUSION: The proposed framework provides reliable and interpretable predictions along with counterfactual examples.

Maternal and child oral health barriers and solutions: Case studies from South Africa, Brazil, and Indonesia.

The World Federation of Public Health Associations (WFPHA) has introduced a maternal oral health framework and launched its Global Maternal and Child Oral Health Initiative, advocating for maternal and child health as a strategic entry point for oral health to be integrated into primary healthcare systems. This article delves into maternal oral health initiatives in South Africa, Brazil, and Indonesia, exploring challenges and proposing context-specific solutions aligned with the WFPHA maternal oral health framework and its Global Maternal and Child Oral Health Initiative. The apartheid legacy in South Africa has led to the gross health inequalities, including oral health disparities characterized by maldistribution of dental facilities and dental professionals in the public sector. The proposed objectives focus on effective leadership, human resource capacity building, and integration of maternal and child oral health policy into existing health policies. Brazil faces challenges in reaching pregnant women, especially pregnant teens, due to workforce shortages. Brazil's Oral Health National Program mandates all pregnant women undergo at least one dental appointment, but a shortage of oral health teams persists and impedes timely access to dental care during pregnancy. Dental students' outreach to vulnerable pregnant teens can enhance the future oral health workforce's sensitivity to maternal oral health matters. In Indonesia, the Antenatal Care Innovative (iANC) Project has introduced a co-training model for midwives and oral health professionals addressing oral health needs of mothers and their spouses and fostering a comprehensive understanding of the interplay between oral health and maternal well-being. These country cases demonstrate the importance of tailored policies, health promotion, and care delivery interventions in maternal oral health. All cases highlight the importance of workforce training and distribution, fostering cross-disciplinary collaboration and future oral health workforce who can promote health beyond treatment delivery.

Performance of the galactomannan test for the diagnosis of invasive pulmonary aspergillosis using non-invasive proximal airway samples.

OBJECTIVE: To diagnose invasive pulmonary aspergillosis (IPA), galactomannan (GM) detection in serum or bronchoalveolar lavage fluid (BALF) is widely used. However, the utility of proximal airway GM test (from induced sputum or tracheal aspirate) has not been well elucidated. METHODS: In this retrospective cohort study, we evaluated the diagnostic performance of proximal airway GM in diagnosis of IPA including COVID-19 associated pulmonary aspergillosis (CAPA). Between January 2022 and January 2023, patients who had been tested for GM with clinical suspicion or for surveillance from any specimen (serum, induced sputum, tracheal aspirate, and BALF) were screened. IPA was diagnosed using EORTC/MSGERC criteria, and CAPA was diagnosed following the 2020 ECMM/ISHAM consensus criteria. RESULTS: Of 624 patients with GM results, 70 met the criteria for proven/probable IPA and 427 had no IPA. The others included possible IPA and chronic form of aspergillosis. The sensitivities and specificities of serum, proximal airway, and BALF GM for proven/probable IPA versus no IPA were 78.9% and 70.6%, 93.1% and 78.7%, and 78.6% and 91.0%, respectively. Areas under the receiver operating characteristic curve (AUCs) were 0.742 for serum GM, 0.935 for proximal airway GM, and 0.849 for BALF GM (serum GM vs proximal airway GM, p = 0.014; proximal airway GM vs BALF GM, p = 0.334; serum GM vs BALF GM, p = 0.286). CONCLUSION: This study demonstrates that the performance of GM test from non-invasive proximal airway samples is comparable or even better than those from serum and distal airway sample (BALF).

Race, Ethnicity, and Other Barriers to Access Dental Care During Pregnancy.

BACKGROUND: Historically, women of color showed poorer oral health and lower dental service utilization in the USA. These barriers to dental care during pregnancy included dental coverage, primary language, dental provider availability, safety concerns, affordability of dental care, and perceived oral health benefits during pregnancy. METHODS: The purpose of this study is to examine whether race/ethnicity modified the associations between barriers to accessing dental care and dental service utilization during pregnancy. This cross-sectional study sample included 62,189 women aged 20 and older with a recent birth history in 21 states from the Pregnancy Risk Assessment Monitoring System (PRAMS) data from 2016 to 2019. We introduced a race/ethnicity by barrier interaction term to our multiple logistic regression models. RESULTS: After adjusting for other confounders, dental insurance during pregnancy and perceived oral health benefits were associated with 4.0- and 5.6-fold higher odds, respectively, of dental service utilization during pregnancy. Statistically significant effect modification by race/ethnicity was observed in crude and adjusted analyses of the relationship between dental service utilization for all barriers included in the interaction analyses with all adjusted p-values < 0.001. CONCLUSION: The interaction analysis found that racial/ethnic disparity in visiting dentists during pregnancy was significant among women who reported these dental barriers. In contrast, such racial/ethnic disparity was substantially attenuated among women who did not report such barriers. PRACTICAL IMPLICATIONS: The observed racial/ethnic disparities could be mitigated by such supporting mechanisms: dental coverage, provider availability and willingness to treat pregnant women, oral health education on the safety of dental care during pregnancy, and affordable dental care costs.

Unlocking synergies: Harnessing the potential of biological methane sequestration through metabolic coupling between Methylomicrobium alcaliphilum 20Z and Chlorella sp. HS2.

A halotolerant consortium between microalgae and methanotrophic bacteria could effectively remediate in situ CH4 and CO2, particularly using saline wastewater sources. Herein, Methylomicrobium alcaliphilum 20Z was demonstrated to form a mutualistic association with Chlorella sp. HS2 at a salinity level above 3.0%. Co-culture significantly enhanced the growth of both microbes, independent of initial inoculum ratios. Additionally, increased methane provision in enclosed serum bottles led to saturated methane removal. Subsequent analyses suggested nearly an order of magnitude increase in the amount of carbon sequestered in biomass in methane-fed co-cultures, conditions that also maintained a suitable cultural pH suitable for methanotrophic growth. Collectively, these results suggest a robust metabolic coupling between the two microbes and the influence of the factors other than gaseous exchange on the assembled consortium. Therefore, multi-faceted investigations are needed to harness the significant methane removal potential of the identified halotolerant consortium under conditions relevant to real-world operation scenarios.

Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes.

ABSTRACT: Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes, with a limit of detection of 0.2%. Seventy mutations were detected in 57 diagnostic samples (22.4%), whereas 64 mutations were detected in 39 of the follow-up samples (27.9%). Carrying any mutation at initial diagnosis was associated with worse outcomes after TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with imatinib showed higher risks of treatment failure (hazard ratio, 2.53; 95% confidence interval, 1.13-5.66; P = .0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs. The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival, and progression risk. Additionally, there was an observable nonsignificant trend indicating a heightened risk of progression to advanced disease and worse overall survival. In conclusion, mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression and may help upfront TKI selection.

Knee Measurement System with Osteoarthritis Levels Using Artificial Cartilage and Skeletons.

Knee osteoarthritis (OA), also known as degenerative arthritis, is a disease characterized by irreversible changes in the cartilage and bones comprising the joints, resulting in pain, impaired function, and deformity. Furthermore, independent of natural aging, the rate of change in joint cartilage has increased in recent years, which is mainly attributed to environmental factors. The rising incidence of knee-related disorders emphasizes the importance of analyzing the morphology and kinematics of knee structure. This study introduces a knee measurement system designed to replicate the motions of knee using 3D-printing technology, providing insights into knee mechanics with OA level. The research explores the stages of OA using the Kellgren-Lawrence (KL) grade scale, highlighting the variations in the force applied to the knee bone according to movement. The developed knee-simulation system, utilizing the four-bar-link theory, presents a novel approach to studying OA levels 0 to 4. As OA progresses, the cartilage deteriorates, affecting the movement of OA. The OA-based knee measurement system that incorporates soft tissues and skeletons can assist in developing a personalized diagnostic approach for knee disease. This will also help to enhance surgical effectiveness by facilitating the creation of personalized prosthetic joints for individual patients and offering a customized surgical simulation.

A Comparison of Health Risks from PM2.5 and Heavy Metal Exposure in Industrial Complexes in Dangjin and Yeosu·Gwangyang.

Particulate matter (PM) can cause illness, including respiratory diseases, and PM2.5 compositions are likely to vary according to the emission profiles of industrial complexes. This study analyzed and compared the concentrations and distributions of PM2.5 and heavy metals in two regions of Republic of Korea: Yeosu·Gwangyang, which houses a massive national industrial complex, and Dangjin, which houses power plants. Further, we conducted a health risk assessment on the residents of the areas near these industrial complexes. Measurements were taken at five different points in each setting over a two-year period from August 2020 to August 2022. We found differences in PM2.5 concentrations and heavy metal composition ratios across the sites. Specifically, PM2.5 concentrations exceeded the standard of 1 at all measurement sites, while the specific heavy metals exceeding the standard varied across the sites. Ultimately, we observed regional differences in PM2.5 composition across measurement sites across and within the two regions and variations in health risks and according health effects due to the absence of PM2.5 toxicity values, and compared the health risks of two industrial complexes with different characteristics. These findings underscore the importance of considering not only PM2.5 but also its composition in exposure and health risk assessments.

Impact of ambient temperature on respiratory disease: a case-crossover study in Seoul.

BACKGROUND: Respiratory diseases contribute to global morbidity and mortality, and temperature is a significant factor. We investigated the association between ambient temperature and emergency department (ED) visits for various respiratory diseases in Seoul, South Korea. METHODS: Using data from the National Emergency Department Information System (2008-2017), we analysed 1,616,644 ED visits for respiratory diseases, categorised according to the Korean Standard Classification of Diseases 7th revision codes (J00-J99). Using a time-stratified case-crossover design and a distributed lag nonlinear model, we investigated the effect of temperature exposure on ED visits for respiratory diseases, calculating the relative risk (RR) for the maximum risk temperature (MaxRT) of both cold and hot extremes compared to the minimum risk temperature (MinRT). RESULTS: Cold temperatures (MaxRT: -9.0 °C) resulted in a 2.68-fold increase (RR = 2.68, 95% CI = 2.26-3.14) in ED visits for total respiratory diseases, while hot temperatures (MaxRT: 29.4 °C) led to a 1.26-fold increase (RR = 1.26, 95% CI = 1.11-1.42) compared to the MinRT (24.8 °C). Cold temperatures increased the risk of most respiratory diseases, except interstitial lung disease, whereas hot temperatures increased ED visits for acute upper respiratory infections and influenza. Cold temperatures increased ED visits for all age groups, especially those aged 18-64 (RR = 3.54, 95% CI = 2.90-4.33), while hot temperatures significantly affected those < 18 (RR = 1.45, 95% CI = 1.27-1.66). The risk levels were similar in both males and females, regardless of hot and cold temperatures. CONCLUSION: Our findings underscore the significant impact of both cold and heat exposure on ED visits for respiratory diseases, with varying intensities and risk profiles across different population groups.

The online promotion strategies of e-cigarette and heated tobacco product retailers in South Korea following the COVID-19 pandemic: Implications for regulation.

INTRODUCTION: The surge in popularity of e-cigarettes and heated tobacco products (HTPs) in South Korea, driven by perceived health benefits and COVID-19-related concerns, has led to increased advertising claims about their safety despite ongoing debates about their health effects. This study explores the marketing strategies of online e-cigarette and HTP retailers in South Korea pre- and post-COVID-19, examining potential misleading claims and providing a foundation for future regulatory measures. METHODS: We conducted a comprehensive study of eight major e-commerce platforms and three dominant search engines in South Korea to analyze the marketing and advertising strategies of e-cigarettes and heated tobacco products (HTPs) (n=774). Using specific keywords, promotional strategies were identified and categorized, after which statistical analysis was conducted to understand the frequency and proportion of these strategies, highlighting differences between HTP and e-cigarette sellers. RESULTS: Our analysis reveals a significant rise in the number of online retailers selling e-cigarettes and HTPs following the COVID-19 pandemic, with the promotional strategies 'Stay home and vape' and 'Trendy' being the most prevalent. Trends also indicate a shift in promotional strategies over the years, with a marked increase in health reassurance themes and appeals to trendiness, particularly targeting female consumers, which were used significantly more at HTPs stores. CONCLUSIONS: The study highlights the need for stricter regulation due to the potential health risks posed by the aggressive marketing strategies of e-cigarette and HTP online retailers in South Korea, amplified by the COVID-19 pandemic.

Probiotic Lactiplantibacillus plantarum KU210152 and its fermented soy milk attenuates oxidative stress in neuroblastoma cells.

We evaluated the probiotic properties and neuroprotective effects of Lactiplantibacillus plantarum KU210152 and its application in soy milk. L. plantarum KU210152 exhibited high tolerance to artificial gastrointestinal conditions, high adhesion to intestinal cells (HT-29), and safe enzyme production. Conditioned medium acquired from HT-29 cells treated with heat-killed lactic acid bacteria (LAB-CM) was used to evaluate the neuroprotective effects. The CM exhibited neuroprotective effects via cell viability assay, morphological observations, and suppression of ROS production. Heat-killed L. plantarum KU210152 increased brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase (TH) expression in HT-29 cells. In SH-SY5Y cells, pretreatment with L. plantarum KU210152 CM decreased Bax/Bcl-2 ratio and upregulated BDNF and TH expression. The CM inhibited caspase-9 and caspase-3 activities. The neuroprotective effects of L. plantarum KU210152 were also confirmed in fermented soy milk. Therefore, both L. plantarum KU210152 and the fermented soy milk can be used as functional ingredients with neuroprotective effects against oxidative stress.

Novel Signal Peptides and Episomal Plasmid System for Enhanced Protein Secretion in Engineered Bacteroides Species.

The genus Bacteroides, a predominant group in the human gut microbiome, presents significant potential for microbiome engineering and the development of live biotherapeutics aimed at treating gut diseases. Despite its promising capabilities, tools for effectively engineering Bacteroides species have been limited. In our study, we have made a breakthrough by identifying novel signal peptides in Bacteroides thetaiotaomicron and Akkermansia muciniphila. These peptides facilitate efficient protein transport across cellular membranes in Bacteroides, a critical step for therapeutic applications. Additionally, we have developed an advanced episomal plasmid system. This system demonstrates superior protein secretion capabilities compared to traditional chromosomal integration plasmids, making it a vital tool for enhancing the delivery of therapeutic proteins in Bacteroides species. Initially, the stability of this episomal plasmid posed a challenge; however, we have overcome this by incorporating an essential gene-based selection system. This novel strategy not only ensures plasmid stability but also aligns with the growing need for antibiotic-free selection methods in clinical settings. Our work, therefore, not only provides a more robust secretion system for Bacteroides but also sets a new standard for the development of live biotherapeutics.