Changes in gut microbiome can be associated with abrupt seizure exacerbation in epilepsy patients.

OBJECTIVE: Seizures can be triggered by a variety of endogenous or exogenous factors. We hypothesized that alterations in the gut microbiome may be a seizure precipitant and analyzed the composition and characteristics of the gut microbiome in epilepsy patients who experienced an abrupt seizure exacerbation without a clear seizure precipitant. METHODS: We prospectively enrolled 25 adult patients with epilepsy and collected fecal samples on the admission and after seizure recovery for next-generation sequencing analysis. We performed nonparametric paired t-test analysis to evaluate changes in the gut microbiota as seizures worsened and when it recovered and also estimated alpha and beta diversities in each category. RESULTS: A total of 19 patients (13 males) aged between 19 and 78 years (mean 45.2 years) were included in the study. The composition of the gut microbiota underwent a significant change following an abrupt seizure exacerbation. At the phylum level, the relative abundance of Fusobacteria and Synergistetes was decreased in the seizure recovery state compared to the acute seizure exacerbation. A similar trend was observed at the lower hierarchical levels, with a decrease in the relative abundance of Fusobacteria, Tissierellia, and Synergistia at the class level, and that of Synergistales, Tissierellales, and Fusobacteriales at the order level. At the family level, the relative abundance of Fusobacteriaceae and Staphylococcaceae was decreased, whereas that of Leuconostocaceae was increased. No statistical differences were observed in alpha and beta diversity between the pre- and post-acute seizure exacerbation periods. SIGNIFICANCE: Our study suggests that the changes in Fusobacteriaceae and Lecuonostocaceae may be associated with acute seizure exacerbation in epilepsy patients. Given that Fusobacteriaceae are associated with various systemic diseases due to their invasive properties and that Leuconostocaceae are known to produce GABA, our results may suggest a gut microbiome-based treatment option for epilepsy patients.

Vaginal microbiota of pregnant women with Ureaplasma urealyticum and Mycoplasma hominis infections.

Background: The association between preterm birth and Mycoplasma species such as Mycoplasma hominis and Ureaplasma urealyticum has been extensively investigated. In a clinical setting, conventional diagnostic methods for them involve culture methods for Mycoplasma spp. and Ureaplasma spp., along with PCR tests. However, the clinical utility of these tests remains controversial, highlighting the necessity for more robust and reliable methods for identifying and understanding Mycoplasma infections. Objective: This study aimed to assess the distribution of microbiota in pregnant women with Mycoplasma hominis and Ureaplasma urealyticum infection by the comparison of conventional diagnostic methods with vaginal microbial community analysis. Study Design: This prospective case-control study involved 228 Korean pregnant women and utilized vaginal microbial community analysis, Ureaplasma/Mycoplasma culture, and 12-multiplex PCR for sexually transmitted diseases. Cross-correlation analysis in SPSS 27 compared the results of two conventional methods with vaginal microbial community analysis. R software generated box plots depicting the relative abundance of microorganisms. Network analysis was conducted using Cytoscape. Results: Positive Ureaplasma urealyticum culture findings were observed in 60.2% of patients, with 76.4% positive for Ureaplasma parvum PCR and 13.2% positive for Ureaplasma urealyticum PCR. Mycoplasma hominis culture was positive only in two patients, while Mycoplasma hominis PCR was positive in eight women. Vaginal microbial community analysis identified significant differences in relative abundances of Gardnerella species type I and Fannyhessea vaginae between the Ureaplasma urealyticum PCR positive and negative groups. Mycoplasma hominis PCR positive patients exhibited significant differences in 11 bacterial species, including Gardnerella species I and Fannyhessea vaginae. Conclusion: This study suggests that STD-PCR may be more accurate than Ureaplasma/Mycoplasma culture for the diagnosis of Mycoplasma hominis and Ureaplasma urealyticum infection. Also, the presence of Gardnerella species I and Fannyhessea vaginae implies their potential influences on Ureaplasma urealyticum and Mycoplasma hominis infections based on results of vaginal microbial community analysis. Therefore, vaginal microbial community analysis may give the more information of their pathophysiology.

Multidisciplinary nutritional support team and survival outcomes in patients with sepsis: a nationwide population-based cohort study in South Korea.

BACKGROUND: The South Korean government implemented a multidisciplinary nutritional support team (NST) system to focus on the proper evaluation and supply of nutritional status in hospitalized patients who are at a higher risk of malnutrition. METHODS: This nationwide population-based cohort study included patients diagnosed with sepsis who were admitted to hospitals from 2016 to 2020. The NST should consist of four professional personnel (physicians, full-time nurses, full-time pharmacists, and full-time clinical dietitians). The NST group included patients with sepsis admitted to a hospital with an NST system, whereas the non-NST group included patients with sepsis admitted to a hospital without an NST system. RESULTS: A total of 323,841 patients with sepsis were included in the final analysis, and 120,274 (37.1%) admitted to a hospital with an NST system were included in the NST group. In the multivariable Cox regression analysis, the NST group showed a 15% lower 90-day mortality than the non-NST group (hazard ratio [HR]:0.85, 95% confidence interval [CI]:0.83, 0.86; P < 0.001). The NST group shows 11% lower 1-year all-cause mortality than the non-NST group (HR:0.89, 95% CI:0.87, 0.90; P < 0.001). In subgroup analyses, a more evident association of the NST group with lower 90-day mortality was shown in the intensive care unit admission group and age ≥65 years old group. CONCLUSIONS: Multidisciplinary NST intervention is associated with improved survival outcomes in patients with sepsis. Moreover, this association was more evident in patients with sepsis aged ≥65 years old who were admitted to the ICU.

Concentration-Dependent Effects of Curcumin on Membrane Permeability and Structure.

Growing evidence suggests that many bioactive molecules can nonspecifically modulate the physicochemical properties of membranes and influence the action of embedded membrane proteins. This study investigates the interactions of curcumin with protein-free model membranes consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and DOPC with cholesterol (4/1 mol ratio). The focus is on the capability of curcumin to modify membrane barrier properties such as water permeability assayed through the droplet interface bilayer (DIB) model membrane. For pure DOPC, our findings show a concentration-dependent biphasic effect: a reduction in water permeability is observed at low concentrations (up to 2 mol %), whereas at high concentrations of curcumin, water permeability increases. In the presence of cholesterol, we observed an overall reduction in water permeability. A combination of complementary experimental methods, including phase transition parameters studied by differential scanning calorimetry (DSC) and structural properties measured by attenuated total reflectance (ATR)-FTIR, provides a deeper understanding of concentration-dependent interactions of curcumin with DOPC bilayers in the absence and presence of cholesterol. Our experimental findings align with a molecular mechanism of curcumin's interaction with model membranes, wherein its effect is contingent on its concentration. At low concentrations, curcumin binds to the lipid-water interface through hydrogen bonding with the phosphate headgroup, thereby obstructing the transport of water molecules. Conversely, at high concentrations, curcumin permeates the acyl chain region, inducing packing disorders and demonstrating evidence of phase separation. Enhanced knowledge of the impact of curcumin on membranes, which, in turn, can affect protein function, is likely to be beneficial for the successful translation of curcumin into effective medicine.

Effects of noise exposure on stress hormone changes during task performance in young Korean men: quasi-experimental study.

Numerous studies have suggested that noise exposure might be associated with changes in stress hormone levels. However, quantitative evidence for these effects in humans is rare and remains controversial. This study aimed to investigate the acute effects of exposure to noise and its different levels on stress hormone changes in task performance. Quasi-experimental noise exposure environment was established for 90 male university student volunteers in their twenties, and each was exposed to different noise levels during task performance. The stress hormones tested included cortisol, adrenocorticotropic hormone (ACTH), adrenaline, and noradrenaline. A one-way ANOVA was performed to investigate differences in hormone levels measured in the three groups according to the noise exposure levels (35, 45, or 75 dB). Analysis of covariance (ANCOVA) was used to adjust for confounding factors that might affect hormone levels. After adjusting for confounders, significant exposure-dependent differences were found in hormone levels in salivary cortisol, serum cortisol, serum ACTH, and serum adrenaline. The amount of hormonal increase in 75 dB exposure group compared to 35 or 45 dB groups was detected. Similar results were also seen in the rate of change analysis. Our findings indicate that short-term noise exposure during task performance elevates stress hormone levels. Further, the extent of stress hormone alterations varies with noise exposure levels. Changes in hormone levels are an objective measure that may be used to identify health effects and stress responses in various noise environments.

Distribution of volatile organic compounds by distance from industrial complexes and potential health impact on the residents.

Volatile organic compounds (VOCs) are the air pollutants emitted from the petrochemical industry known to pose adverse health effects on workers. The database based on the third phase of The Environmental Health Study in the Korean National Industrial Complexes (EHSNIC) in Ulsan conducted from 2018 to 2021 was used. Subjects were divided into the exposed and control group according to the estimated pollution level and distances from the industrial complexes. Ambient benzene, ethylbenzene, and xylene were significantly higher in the exposed group compared to the controls, as well as their metabolites. Risk of chronic disease and atopic dermatitis was higher in the exposed group which was supported by higher serum inflammatory markers and high hazard index of the exposed region. These results can draw attention to people engaged with environmental plans and used as primary data when making policies to reduce pollutant levels around industrial complexes.

Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.

The Role of Lipid Intrinsic Curvature in the Droplet Interface Bilayer.

Model bilayers are constructed from lipids having different intrinsic curvatures using the droplet interface bilayer (DIB) method, and their static physicochemical properties are determined. Geometrical and tensiometric measurements are used to derive the free energy of formation (ΔF) of a two-droplet DIB relative to a pair of isolated aqueous droplets, each decorated with a phospholipid monolayer. The lipid molecules employed have different headgroup sizes but identical hydrophobic tail structure, and each is characterized by an intrinsic curvature value (c0) that increases in absolute value with decreasing size of headgroup. Mixtures of lipids at different ratios were also investigated. The role of curvature stress on the values of ΔF of the respective lipid bilayers in these model membranes is discussed and is illuminated by the observation of a decrement in ΔF that scales as a near linear function of c02. Overall, the results reveal an association that should prove useful in studies of ion channels and other membrane proteins embedded in model droplet bilayer systems that will impact the understanding of protein function in cellular membranes composed of lipids of high and low curvature.

Radiation dose estimation with multiple artificial neural networks in dicentric chromosome assay.

PURPOSE: The dicentric chromosome assay (DCA), often referred to as the 'gold standard' in radiation dose estimation, exhibits significant challenges as a consequence of its labor-intensive nature and dependency on expert knowledge. Existing automated technologies face limitations in accurately identifying dicentric chromosomes (DCs), resulting in decreased precision for radiation dose estimation. Furthermore, in the process of identifying DCs through automatic or semi-automatic methods, the resulting distribution could demonstrate under-dispersion or over-dispersion, which results in significant deviations from the Poisson distribution. In response to these issues, we developed an algorithm that employs deep learning to automatically identify chromosomes and perform fully automatic and accurate estimation of diverse radiation doses, adhering to a Poisson distribution. MATERIALS AND METHODS: The dataset utilized for the dose estimation algorithm was generated from 30 healthy donors, with samples created across seven doses, ranging from 0 to 4 Gy. The procedure encompasses several steps: extracting images for dose estimation, counting chromosomes, and detecting DC and fragments. To accomplish these tasks, we utilize a diverse array of artificial neural networks (ANNs). The identification of DCs was accomplished using a detection mechanism that integrates both deep learning-based object detection and classification methods. Based on these detection results, dose-response curves were constructed. A dose estimation was carried out by combining a regression-based ANN with the Monte-Carlo method. RESULTS: In the process of extracting images for dose analysis and identifying DCs, an under-dispersion tendency was observed. To rectify the discrepancy, classification ANN was employed to identify the results of DC detection. This approach led to satisfaction of Poisson distribution criteria by 32 out of the initial pool of 35 data points. In the subsequent stage, dose-response curves were constructed using data from 25 donors. Data provided by the remaining five donors served in performing dose estimations, which were subsequently calibrated by incorporating a regression-based ANN. Of the 23 points, 22 fell within their respective confidence intervals at p < .05 (95%), except for those associated with doses at levels below 0.5 Gy, where accurate calculation was obstructed by numerical issues. The accuracy of dose estimation has been improved for all radiation levels, with the exception of 1 Gy. CONCLUSIONS: This study successfully demonstrates a high-precision dose estimation method across a general range up to 4 Gy through fully automated detection of DCs, adhering strictly to Poisson distribution. Incorporating multiple ANNs confirms the ability to perform fully automated radiation dose estimation. This approach is particularly advantageous in scenarios such as large-scale radiological incidents, improving operational efficiency and speeding up procedures while maintaining consistency in assessments. Moreover, it reduces potential human error and enhances the reliability of results.

Drug-loaded adhesive microparticles for biofilm prevention on oral surfaces.

The oral cavity, a warm and moist environment, is prone to the proliferation of microorganisms like Candida albicans (C. albicans), which forms robust biofilms on biotic and abiotic surfaces, leading to challenging infections. These biofilms are resistant to conventional treatments due to their resilience against antimicrobials and immune responses. The dynamic nature of the oral cavity, including the salivary flow and varying surface properties, complicates the delivery of therapeutic agents. To address these challenges, we introduce dendritic microparticles engineered for enhanced adhesion to dental surfaces and effective delivery of antifungal agents and antibiofilm enzymes. These microparticles are fabricated using a water-in-oil-in-water emulsion process involving a blend of poly(lactic-co-glycolic acid) (PLGA) random copolymer (RCP) and PLGA-b-poly(ethylene glycol) (PLGA-b-PEG) block copolymer (BCP), resulting in particles with surface dendrites that exhibit strong adhesion to oral surfaces. Our study demonstrates the potential of these adhesive microparticles for oral applications. The adhesion tests on various oral surfaces, including dental resin, hydroxyapatite, tooth enamel, and mucosal tissues, reveal superior adhesion of these microparticles compared to conventional spherical ones. Furthermore, the release kinetics of nystatin from these microparticles show a sustained release pattern that can kill C. albicans. The biodegradation of these microparticles on tooth surfaces and their efficacy in preventing fungal biofilms have also been demonstrated. Our findings highlight the effectiveness of adhesive microparticles in delivering therapeutic agents within the oral cavity, offering a promising approach to combat biofilm-associated infections.