Respiratory microbiome and clinical course of carbapenem-resistant Acinetobacter baumannii pneumonia in critically Ill patients.

Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia has been a serious problem in the intensive care unit (ICU). However, defined characteristics of respiratory microbiome in CRAB pneumonia are lacking nowadays. This study aimed to analyze respiratory microbiome of CRAB pneumonia compared to non-CRAB pneumonia and reveal the clinical significance of respiratory microbiome data in these patients. Patients diagnosed with severe pneumonia with mechanical ventilation were enrolled in the ICU of a tertiary care hospital. Respiratory specimens were collected on days 1, 4, 7, and 14 in each participant via tracheal aspiration. Clinical data and outcomes of each enrolled patient were collected via electronic medical records. Microbiome analysis was conducted with collected respiratory specimens undergone by next-generation sequencing of microbial 16S ribosomal DNA. Six CRAB pneumonia, 4 non-CRAB pneumonia and 5 healthy controls were enrolled. In CRAB pneumonia, CRAB was detected in 3 patients by sputum culture at day 1, while it was negative at day 1 and detected later in the others by follow-up sputum culture. Beta diversity plot analysis showed differences between each group. Shannon index was decreased markedly at day 4 in CRAB pneumonia compared to the others. Among CRAB pneumonia cases, 3 respiratory specimens were culture-negative, but positive by microbiome analysis. Lower respiratory microbiome in CRAB pneumonia had distinct characteristics and early loss of diversity compared to non-CRAB pneumonia, which might be related to poor clinical course. Moreover, CRAB acquisition and colonization would be predicted by preemptive microbiome analysis, which will contribute to effective infection control in the ICU.

Biosolid Gasification Performance Prediction Using a Stoichiometric Thermodynamic Model.

The gasification process can recover energy from biosolids produced in wastewater treatment. This paper developed a stoichiometric thermodynamic equilibrium model for biosolid gasification based on the biosolid properties, thermodynamic database, and equilibrium constants. If the calculation result showed that the quantity of char was negative, the quantity of char was put to zero, and the simulation was carried out again. The model was first verified by woody gasification under isothermal conditions, and the influence of a given temperature on biosolid gasification was simulated. The model further investigated the effects of different feedstock types, moisture contents, equivalence ratios, and reaction extensions on the adiabatic temperature, exergy efficiency, and syngas properties under autothermal conditions. The four factors were all the main factors for adiabatic temperature. The exergy efficiency depended more on the operation conditions than on the feedstock type. The H2 concentration of the dry syngas in biosolid gasification exhibited a curve both against the given temperature under isothermal conditions and against the moisture content under autothermal conditions.

Impact of the Korea Early Childhood Home-visiting Intervention (KECHI) on child health and development and maternal health: a randomised controlled trial protocol.

INTRODUCTION: Randomised controlled trials (RCTs) of early childhood home-visiting interventions led by nurses have been conducted mainly in Western countries, whereas such trials have been limited in non-Western cultures, including Asia. In South Korea, a national nurse home visit programme (Korea Early Childhood Home-visiting Intervention (KECHI)) was developed in 2020 and launched throughout the country. We designed a pragmatic RCT to evaluate the effectiveness of KECHI on child health and development and maternal health. METHODS AND ANALYSIS: Eligible participants will be pregnant women at <37 weeks of gestation with risk factor scores of 2 or over, who are sufficiently fluent in Korean to read and answer the questionnaire written in Korean and live in districts where the KECHI services are available. Eight hundred participants will be recruited from the general community and through the District Public Health Centres. The participants will be randomised 1:1 to KECHI plus usual care or usual care. KECHI encompasses 25-29 home visits, group activities and community service linkage. Participants will complete assessments at baseline (<37 weeks gestation), 6 weeks, 6 months, 12 months, 18 months and 24 months post partum. The six primary outcomes will be (1) home environment (assessed by Infant/Toddler Home Observation for Measurement of the Environment), (2) emergency department visits due to injuries, (3) child development (assessed using Korean Bayley Scales of Infant and Toddler Development-III), (4) breastfeeding duration, (5) maternal self-rated health and (6) community service linkage. ETHICS AND DISSEMINATION: This trial has received full ethical approval from the Institutional Review Board of the Seoul National University Hospital. Written consent will be obtained from the participants. The results will be reported at conferences, disseminated through peer-reviewed publications and used by the Korean government to expand the KECHI services. TRIAL REGISTRATION NUMBER: NCT04749888.

Association of TP53 Mutation Status and Sex with Clinical Outcome in NSCLC Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of TCGA and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in disease control rate per the TP53 mutation status (p=0.503); however, female patients with TP53 mutated (MT) had a significantly prolonged median progression-free survival (PFS) compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). PD-L1 high (≥50%) expression was significantly enriched in female patients with TP53 MT (p=0.001). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p<0.001). In TCGA analysis, expression of immune-related genes, and TMB score in TP53 MT females were higher than in males without TP53 MT. Conclusion: Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Gd-EOB-DTPA enhanced MRI nomogram model to differentiate hepatocellular carcinoma and focal nodular hyperplasia both showing iso- or hyperintensity in the hepatobiliary phase.

BACKGROUND: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). METHODS: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. RESULTS: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. CONCLUSIONS: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery.

Virtual Supervision in Graduate Medical Education: A Systematic Review.

Background Despite the increased use of telemedicine, the evidence base on virtual supervision in graduate medical education (GME) is not well described. Objective To systematically review the impact of virtual supervision on trainee education, patient care, and patient satisfaction in Accreditation Council for Graduate Medical Education (ACGME)-accredited specialties. Methods Two databases (PubMed, EMBASE) were searched from database inception to December 2022. Inclusion criteria were peer-reviewed, full-text, English-language articles reporting the use of virtual supervision in GME in ACGME-accredited specialties. Exclusion criteria were studies involving direct supervision, supervisors who were not credentialed physicians, or non-GME trainees. Two investigators independently extracted data and appraised the methodological quality of each study using the Mixed Methods Appraisal Tool (MMAT). The reporting of this systematic review was guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Results Of 5278 records identified, 26 studies met the eligibility criteria. Virtual supervision was predominantly utilized in operating rooms and inpatient settings, facilitating clinical examinations or surgical procedures through videoconferencing software in specialties such as dermatology, neurosurgery, and orthopedics. However, some studies reported technical challenges that hindered effective teaching and communication. Based on self-reported surveys, supervisor and trainee satisfaction with virtual supervision was mixed, while patient satisfaction with the care was generally high. The MMAT ratings suggested limitations in sampling strategy, outcome measurement, and confounding factors. Conclusions Virtual supervision was applicable to various specialties and settings, facilitating communication between supervisors and trainees, although there were some technological challenges.

LIM-domain-only 4 (LMO4) enhances CD8+ T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling.

High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy trials. Herein, we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8+ T cells. Using IFN-γ production as a proxy for CD8+ T cell terminal differentiation, LMO4 emerged among the top hits inhibiting the development of effectors cells. Consistently, we found that Lmo4 was downregulated upon CD8+ T cell activation but maintained under culture conditions facilitating the formation of stem-like T cells. By employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8+ T cells, we enabled selective expansion and enhanced persistence of transduced cells, while limiting their terminal differentiation and senescence. LMO4 overexpression promoted transcriptional programs regulating stemness, increasing the numbers of stem-like CD8+ memory T cells and enhancing their polyfunctionality and recall capacity. When tested in syngeneic and xenograft tumor models, LMO4 overexpression boosted CD8+ T cell antitumor immunity, resulting in enhanced tumor regression. Rather than directly modulating gene transcription, LMO4 bound to JAK1 and potentiated STAT3 signaling in response to IL-21, inducing the expression of target genes (Tcf7, Socs3, Junb, and Zfp36) crucial for memory responses. CRISPR/Cas9-deletion of Stat3 nullified the enhanced memory signature conferred by LMO4, thereby abrogating the therapeutic benefit of LMO4 overexpression. These results establish LMO4 overexpression as an effective strategy to boost CD8+ T cell stemness, providing a new synthetic biology tool to bolster the efficacy of T cell-based immunotherapies.

Mukbang and Cookbang watching and dietary behavior in Korean adolescents.

BACKGROUND/OBJECTIVES: Given that adolescents watch Mukbang (eating broadcast) more frequently than other age groups, interest in the potential health effects of watching Mukbang and Cookbang (cooking broadcast) is growing. This study aimed to determine the status of watching Mukbang and Cookbang among Korean adolescents and its relationship with their dietary behaviors. SUBJECTS/METHODS: We used data from the 18th Korea Youth Risk Behavior Survey, conducted in 2022 (n = 51,850). The study included the frequency of watching Mukbang and Cookbang and the self-rated impact of watching them. Dietary behaviors included consumption of the following items: fruits (≥ once a day), vegetables (≥ 3 times a day), fast foods (≥ 3 times a week), late-night snacks (≥ 3 times a week), caffeinated drinks (≥ 3 times a week), and sweet-flavored drinks (≥ 3 times a week). Furthermore, obesity, weight loss attempts during the past 30 days, body image distortion, and inappropriate methods to control weight were also included. RESULTS: Among adolescents, 70.6% watched Mukbang and Cookbang, and 13.2% watched them more than 5 times a week. Approximately 27.6% of the adolescents responded that they were influenced by watching Mukbang and Cookbang. Adolescents who frequently watched Mukbang and Cookbang consumed less vegetable and fruit; however, the likelihood of consuming fast food, late-night snacks, sugary drinks, and caffeinated drinks increased. In addition, they were more likely to attempt inappropriate weight-loss methods and become obese. Adolescents who responded that their eating habits were influenced by watching Mukbang and Cookbang were more likely to have unhealthy eating behavior compared to the group who responded that their habits were not influenced by these shows. CONCLUSION: Watching Mukbang and Cookbang is common among Korean adolescents and is associated with unhealthy dietary behaviors. Prospective studies, including broadcasting content, should evaluate the impact of Mukbang and Cookbang on health.

Platycodon grandiflorum exhibits anti-neuroinflammatory potential against beta-amyloid-induced toxicity in microglia cells.

Background/objectives: Platycodon grandiflorum (PG) is used in traditional oriental medicine to treat several ailments. Methods: The study investigated the anti-inflammatory and neuroprotective effects of PGW (P. grandiflorum) extract in Aß25-35-induced inflammation in BV2 microglia cells. Result: PGW demonstrated significant inhibition of nitric oxide (NO) production, with reductions of 30.4, 36.7, and 61.2% at concentrations of 50, 100, and 200 µg/mL, respectively. Moreover, PGW effectively suppressed the production of pro-inflammatory cytokines IL-1ß and IL-6 and exhibited significant inhibitory activity against TNF-α at 200 µg/mL. Furthermore, PGW treatment mitigated apoptosis in Aß-induced BV2 cells by modulating the mitochondrial apoptosis pathway, regulating Bcl-2 family protein synthesis, and inhibiting caspase activation. Mechanistically, PGW attenuated the activation of the MAPK (JNK, ERK, p38) pathway induced by Aß, showing a concentration-dependent decrease in phosphorylation levels of these proteins. Additionally, PGW inhibited the NF-κB pathway activation by reducing the phosphorylation levels of p65 and IκBα in a concentration-dependent manner. Conclusion: PGW demonstrated anti-inflammatory and neuroprotective effects in Aß-induced neuronal cells, suggesting its potential as a therapeutic agent for neuroinflammatory associated with neurodegenerative diseases.

Novel Ag@NH2-UiO-66(Zr) photocatalyst with controllable charge transfer pathways for efficient Cr(VI) remediation.

Rational fabrication of core-shell photocatalysts to hamper the charge recombination is extraordinarily essential to enhance photocatalytic activity. In this work, core-shell Ag@NH2-UiO-66 (Ag@NU) Schottky heterojunctions with low Ag content (1 wt%) were constructed by a two-step solvothermal method and adopted for Cr(VI) reduction under LED light. Typically, the one with the Ag: NH2-UiO-66 mass ratio (1 : 100) led to 100% Cr(VI) removal within 1 h, superior to bare NH2-UiO-66 and Ag/NH2-UiO-66 (Ag was directly decorated on NH2-UiO-66 surface). The enhanced photocatalytic activity was related to the migration of the electrons on the CB of NH2-UiO-66 to Ag NPs through a Schottky barrier, and thus the undesired charge carriers recombination was avoided. This result was also evidenced by Density functional theory (DFT) calculations. The computational simulations indicate that the introduction of Ag effectively narrowed the band gap of NH2-UiO-66, facilitating the transfer of photo-generated electrons, expanding the light absorption area, and significantly enhancing photocatalytic efficiency. Most importantly, such a core-shell structure can inhibit the formation of •O2-, letting the direct Cr(VI) reduction by photo-excited e-. In addition, this structure can also protect Ag from being oxidized by O2. Ten cyclic tests evidenced the Ag@NU had excellent chemical and structural stability. This research offers a novel strategy for regulating the Cr(VI) reduction by establishing core-shell photocatalytic materials.

Characteristics of astigmatism in school-age children aged 5 to 13 years in northeast Sichuan: a cross-sectional school-based study.

Background: Astigmatism is closely associated with myopia progression, vision loss, eye fatigue and amblyopia, which seriously endangers children's eye health. This study aims to investigate the prevalence and characteristic distribution of astigmatism in children in Langzhong City, providing valuable insights for allocating resources and develop prevention and control strategies. Methods: A cross-sectional study and random sampling survey were conducted. Between January and November 2021, 21,415 students aged 5 to 13 years from 14 primary schools in Langzhong City underwent non-cycloplegic refractive testing using autorefraction. The data on myopia were analyzed using SPSS (Statistical Package for the Social Sciences) version 23.0. Results: The inclusion criterion was set at an absolute astigmatism value of ≥0.50D. Among the 21,415 children studied, 61.70% were found to have astigmatism. The prevalence of astigmatism varied significantly across different grades (χ2=501.414, P<0.001). The predominant types of astigmatism were mild astigmatism (0.50-1.00D) and with-the-rule astigmatism. Mixed astigmatism was primarily observed in children in grades 1 and 2, while compound myopic astigmatism was more common in children in grades 3 to 6. These differences were statistically significant. As the degree of astigmatism increased, the proportions of against-the-rule astigmatism, oblique astigmatism, compound myopic astigmatism, and simple hyperopic astigmatism decreased, whereas the proportions of with-the-rule astigmatism, mixed astigmatism, and compound hyperopic astigmatism increased. Conclusions: The prevalence of astigmatism among school-age children aged 5 to 13 years in northeast Sichuan is notably high, with compound myopic astigmatism and with-the-rule astigmatism being the most common types. Regular refractive examinations are crucial for the early detection and management of astigmatism.

A novel real-time model for predicting acute kidney injury in critically ill patients within 12 hours.

BACKGROUND: A major challenge in prevention and early treatment of acute kidney injury (AKI) is the lack of high-performance predictors in critically ill patients. Therefore, we innovatively constructed U-AKIpredTM for predicting AKI in critically ill patients within 12 h of panel measurement. METHODS: The prospective cohort study included 680 patients in the training set and 249 patients in the validation set. After performing inclusion and exclusion criteria, 417 patients were enrolled in the training set and 164 patients were enrolled in the validation set finally. AKI was diagnosed by Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Twelve urinary kidney injury biomarkers (mALB, IgG, TRF, α1MG, NAG, NGAL, KIM-1, L-FABP, TIMP2, IGFBP7, CAF22 and IL-18) exhibited good predictive performance for AKI within 12 h in critically ill patients. U-AKIpredTM, combined with three crucial biomarkers (α1MG, L-FABP and IGFBP7) by multivariate logistic regression analysis, exhibited better predictive performance for AKI in critically ill patients within 12 h than the other twelve kidney injury biomarkers. The area under the curve (AUC) of the U-AKIpredTM, as a predictor of AKI within 12 h, was 0.802 (95% CI: 0.771-0.833, P < 0.001) in the training set and 0.844 (95% CI: 0.792-0.896, P < 0.001) in validation cohort. A nomogram based on the results of the training and validation sets of U-AKIpredTM was developed which showed optimal predictive performance for AKI. The fitting effect and prediction accuracy of U-AKIpredTM was evaluated by multiple statistical indicators. To provide a more flexible predictive tool, the dynamic nomogram (https://www.xsmartanalysis.com/model/U-AKIpredTM) was constructed using a web-calculator. Decision curve analysis (DCA) and a clinical impact curve were used to reveal that U-AKIpredTM with the three crucial biomarkers had a higher net benefit than these twelve kidney injury biomarkers respectively. The net reclassification index (NRI) and integrated discrimination index (IDI) were used to improve the significant risk reclassification of AKI compared with the 12 kidney injury biomarkers. The predictive efficiency of U-AKIpredTM was better than the NephroCheck® when testing for AKI and severe AKI. CONCLUSION: U-AKIpredTM is an excellent predictive model of AKI in critically ill patients within 12 h and would assist clinicians in identifying those at high risk of AKI.

Quality characteristics and volatile compounds of plant-based patties supplemented with biji powder.

Biji (okara or soybean curd residue), a by-product of soybean processing, contains proteins. In this study, control plant-based patties were compared with patties supplemented with biji powder (5, 10, 15, and 20 g). Increasing the amount of biji added to patties was found to be favorably associated with increased water-holding capacity, decreased cooking loss, and reduced diameter and thickness. Texture profile analysis revealed trends of increased hardness, springiness, cohesiveness, and chewiness which were proportional to the inclusion of biji powder. The volatile compounds in plant-based patties supplemented with biji were analyzed using HS-SPME-Arrow-GC/MS. Notably, benzaldehyde, nonanal, and 2-heptanone, which are undesirable flavors, were detected at significantly lower levels in patties supplemented with biji. Therefore, biji can serve as a supplementary ingredient to enhance the texture and flavor of plant-based patties.

The Spectrum of Isolated Retinal Artery Occlusion Secondary to Giant Cell Arteritis.

We systematically reviewed the literature to investigate the clinical features of isolated arteritic retinal artery occlusion (A-RAO) associated with giant cell arteritis (GCA). The four primary types of A-RAO were central retinal artery occlusion (CRAO), hemi-central retinal artery occlusion (hCRAO), branch retinal artery occlusion (BRAO), and cilioretinal artery occlusion (CLRAO). The most reported presentation was unilateral CRAO, followed by bilateral CRAO, unilateral CLRAO, and bilateral BRAO. Most RAOs were accompanied by typical GCA signs and symptoms, which can help distinguish them from non-arteritic RAOs. When reported, temporal artery biopsy confirmed GCA in most cases. Patients with GCA may present with a broad spectrum of isolated unilateral and bilateral A-RAOs. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Contemporary Perspectives on the Role of Vitamin D in Enhancing Gut Health and Its Implications for Preventing and Managing Intestinal Diseases.

Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases.

Temporal Changes in 18 F-FDG PET/CT in Familial Neuronal Intranuclear Inclusion Disease, Based on the Clinical Course.

ABSTRACT: We report temporal changes in 18 F-FDG PET/CT in neuronal intranuclear inclusion disease (NIID). In a patient with encephalitis-like episodes, PET showed hypermetabolism correlating with EEG alterations. Affected sites later became hypometabolic and showed diffusion changes on MRI. In another patient, hypermetabolic regions correlated well with the EEG, whereas MRI showed changes after only 1 month. One chronic patient had diffuse hypometabolism, which correlated with atrophy on MRI and cerebral dysfunction on EEG. This is the first report of temporal changes in PET in NIID and suggests that it reflects the disease activity of NIID while correlating well with EEG.

CE9A215 (inotodiol), a lanostane-type oxysterol, mitigates LPS-induced sepsis through multifaceted mechanisms.

Dysregulated host response against infection triggers sepsis that leads to multiple organ dysfunction due to uncontrolled inflammatory responses. Despite marked progress in understanding of sepsis, numerous clinical trials for treatment of sepsis have proven daunting and a new therapeutic approach is highly needed. CE9A215 (inotodiol), a fungal secondary metabolite, has been researched for its pharmacological activities and has shown potent anti-allergic effects. In this study, we evaluated the anti-inflammatory activities of CE9A215 upon lipopolysaccharide (LPS) stimulation in vivo and in vitro for the first time. CE9A215 decreased the production of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-1ß in a concentration-dependent manner in LPS-stimulated RAW264.7 cells. Intriguingly, in human mast cell line LUVA, CE9A215 significantly lowered IL-4 and IL-10, and this effect could be beneficial for the clearance of bacterial infection. In addition, administration of CE9A215 improved the survival rate of LPS-stimulated mice and inhibited the pro-inflammatory cytokines, IL-6, TNF-α, and IL-1ß in blood. Moreover, CE9A215 enhanced the expression levels of plasma phospholipid transfer protein (PLTP), apolipoprotein E (ApoE), and ATP-binding cassette transporter (ABCA1) in LPS-stimulated RAW246.7 cells. Liver PLTP level increased significantly in the CE9A215-administered group compared with the control group, which implies that CE9A215 promotes LPS clearance and neutralization by reverse transport of LPS by increasing the expressions of PLTP, ApoE, and ABCA1. Our results highlight CE9A215's potential as a novel therapeutic option for the treatment of sepsis.

Prospective Audit and Feedback for Antimicrobial Treatment of Patients Receiving Renal Replacement Therapy in Community-Based University Hospitals: A before-and-after Study.

In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at two community-based university hospitals. During three years of PAF, 27,906 antimicrobial prescriptions were reviewed, with 622 (2.2%) interventions. The mean incidence density per 1000 patient days of multidrug-resistant organisms, except for carbapenem-resistant Acinetobacter baumannii, decreased in the study population, whereas it increased among inpatients. Multivariable Poisson regression analysis revealed that after PAF, the incidences of vancomycin-resistant Enterococcus and mortality decreased (incidence risk ratio, 95% confidence interval: 0.53, 0.31-0.93 and 0.70, 0.55-0.90, respectively). Notably, after PAF, incorrect antimicrobial dosing rates significantly decreased (tau -0.244; p = 0.02). However, the incidences of other multidrug-resistant organisms, Clostridioides difficile, length of stay, and readmission did not significantly change. This study shows that in patients undergoing intermittent hemodialysis or continuous renal replacement, targeted PAF can significantly reduce multidrug-resistant organism rates and all-cause hospital mortality, despite limited resources. Furthermore, it can improve antimicrobial dosage accuracy.

Platycodon grandiflorum root extract inhibits Aß deposition by breaking the vicious circle linking oxidative stress and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by irreversible cognitive impairment. A deleterious feedback loop between oxidative stress and neuroinflammation in early AD exacerbates AD-related pathology. Platycodon grandiflorum root extract (PGE) has antioxidant and anti-inflammatory effects in several organs. However, the mechanisms underlying the effects of PGE in the brain remain unclear, particularly regarding its impact on oxidative/inflammatory damage and Aß deposition. Thus, we aim to identify the mechanism through which PGE inhibits Aß deposition and oxidative stress in the brain by conducting biochemical and histological analyses. First, to explore the antioxidant mechanism of PGE in the brain, we induced oxidative stress in mice injected with scopolamine and investigated the effect of PGE on cognitive decline and oxidative damage. We also assessed the effect of PGE on reactive oxygen species (ROS) generation and the expressions of antioxidant enzymes and neurotrophic factor in H2O2- and Aß-treated HT22 hippocampal cells. Next, we investigated whether PGE, which showed antioxidant effects, could reduce Aß deposition by mitigating neuroinflammation, especially microglial phagocytosis. We directly verified the effect of PGE on microglial phagocytosis, microglial activation markers, and pro-inflammatory cytokines in Aß-treated BV2 microglial cells. Moreover, we examined the effect of PGE on neuroinflammation, inducing microglial responses in Aß-overexpressing 5XFAD transgenic mice. PGE exerts antioxidant effects in the brain, enhances microglial phagocytosis of Aß, and inhibits neuroinflammation and Aß deposition, ultimately preventing neuronal cell death in AD. Taken together, our findings indicate that the therapeutic potential of PGE in AD is mediated by its targeting of multiple pathological processes.

Inhibition of Toll-like Receptors Alters Macrophage Cholesterol Efflux and Foam Cell Formation.

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.