Cerebrospinal Fluid Neutrophil Gelatinase-Associated Lipocalin as a Novel Biomarker for Postneurosurgical Bacterial Meningitis: A Prospective Observational Cohort Study.

BACKGROUND AND OBJECTIVES: Postneurosurgical bacterial meningitis (PNBM) was a significant clinical challenge, as early identification remains difficult. This study aimed to explore the potential of neutrophil gelatinase-associated lipocalin (NGAL) as a novel biomarker for the early diagnosis of PNBM in patients who have undergone neurosurgery. METHODS: A total of 436 postneurosurgical adult patients were enrolled in this study. Clinical information, cerebrospinal fluid (CSF), and blood samples were collected. After the screening, the remaining 267 patients were divided into the PNBM and non-PNBM groups, and measured CSF and serum NGAL levels to determine the diagnostic utility of PNBM. Subsequently, patients with PNBM were categorized into gram-positive and gram-negative bacterial infection groups to assess the effectiveness of CSF NGAL in differentiating between these types of infections. We analyzed the changes in CSF NGAL expression before and after anti-infection treatment in PNBM. Finally, an additional 60 patients were included as an independent validation cohort to further validate the diagnostic performance of CSF NGAL. RESULTS: Compared with the non-PNBM group, CSF NGAL was significantly higher in the PNBM group (305.1 [151.6-596.5] vs 58.5 [30.7-105.8] ng/mL; P < .0001). The area under the curve of CSF NGAL for diagnosing PNBM was 0.928 (95% CI: 0.897-0.960), at a threshold of 119.7 ng/mL. However, there was no significant difference in serum NGAL between the 2 groups (142.5 [105.0-248.6] vs 161.9 [126.6-246.6] ng/mL, P = .201). Furthermore, CSF NGAL levels were significantly higher in patients with gram-negative bacterial infections than those with gram-positive bacteria (P = .023). In addition, CSF NGAL levels decrease after treatment compared with the initial stage of infection (P < .0001). Finally, in this validation cohort, the threshold of 119.7 ng/mL CSF NGAL shows good diagnostic performance with a sensitivity and specificity of 90% and 80%, respectively. CONCLUSION: CSF NGAL holds promise as a potential biomarker for the diagnosis, early drug selection, and efficacy monitoring of PNBM.

SIRT1 and miR-34a-5p Expression in PBMCs as Potential Biomarkers for Patients With Type 2 Diabetes With Cognitive Impairments.

CONTEXT: Patients with type 2 diabetes mellitus (T2DM) are at significantly increased risk of Alzheimer disease (AD). However, no biomarkers are available for early identification of patients with T2DM with cognitive impairment (T2DM-CI). Mitochondrial dysfunction is linked to AD. Silent Information Regulator 1 (SIRT1), which is responsible for regulating mitochondrial biogenesis, and its related miRNAs were also altered in AD. OBJECTIVE: This study aimed to determine whether mitochondrial function in peripheral blood mononuclear cells (PBMCs) of patients with T2DM-CI was altered and if these alterations could be used as biomarkers. METHODS: A total of 374 subjects were enrolled, including AD, T2DM-CI, T2DM-nCI (T2DM without cognitive impairment), and healthy controls. The mitochondrial function was determined using a commercial assay kit. The mitochondrial DNA (mtDNA) content, the expression of SIRT1, and selected miRNAs in PBMCs were measured by quantitative polymerase chain reaction. The correlations and diagnostic accuracy were assessed using the Spearman correlation coefficient or receiver operating characteristics analysis, respectively. RESULTS: We found significant changes in mitochondrial function in PBMCs of patients with AD compared with controls (all P < .05), which were not found in T2DM-CI. However, mtDNA content and SIRT1 mRNA expression were lower in PBMCs of patients with T2DM-CI, while miR-34a-5p expression was higher than in patients with T2DM-nCI (all P < .05). A combination of SIRT1 and miR-34a-5p demonstrated excellent discrimination between T2DM-CI and T2DM-nCI (area under the curve = 0.793; sensitivity: 80.01%; specificity: 78.46%). Furthermore, correlation analysis revealed a link between miR-34a-5p expression and hyperglycemia in T2DM-CI. CONCLUSION: Our findings revealed that there was an alteration of mitochondria at the peripheral level in patients with T2DM-CI. SIRT1 combined with miR-34a-5p in PBMCs performed well in identifying patients with T2DM-CI and may be a promising biomarker.

Diagnostic value of cerebrospinal fluid Neutrophil Gelatinase-Associated Lipocalin for differentiation of bacterial meningitis from tuberculous meningitis or cryptococcal meningitis: a prospective cohort study.

BACKGROUND: The early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM) remains a significant clinical challenge. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been reported as a novel inflammatory biomarker in the early stages of infection. This study aimed to investigate whether cerebrospinal fluid (CSF) NGAL can serve as a potential biomarker for distinguishing between BM and TBM or CM. METHODS: We prospectively enrolled the patients with suspected CNS infections at admission and divided them into three case groups: BM (n = 67), TBM (n = 55), CM (n = 51), and an age- and sex-matched hospitalized control (HC, n = 58). Detected the CSF NGAL and assessed its diagnostic accuracy in distinguishing between BM and TBM or CM. Additionally, longitudinally measured the CSF NGAL levels in patients with BM to evaluate its potential as a monitoring tool for antibacterial treatment. RESULTS: The concentration of CSF NGAL in BM was significantly higher than in TBM, CM, and HC (all P < 0.05), while the serum NGAL did not show significant differences among the three case groups. The ROC analysis demonstrated that CSF NGAL presented a good diagnostic performance with an AUC of 0.834 (0.770-0.886) and at the optimal cutoff value of 74.27 ng/mL with 70.15% sensitivity and 77.36% specificity for discriminating BM with TBM and CM. Additionally, the CSF NGAL in the convalescent period of BM was significantly lower than in the acute period (P < 0.05). CONCLUSIONS: CSF NGAL may serve as a potential biomarker for distinguishing between acute BM and TBM or CM. Additionally, it holds clinical significance in monitoring the effectiveness of antibiotic therapy for BM.

Effect of the Current on the Fire Characteristics of Overloaded Polyvinyl Chloride Copper Wires.

In this study, the fire behavior variation of unenergized polyvinyl chloride (PVC) copper wires subjected to overload with different currents was investigated by a cone calorimeter. Overload currents were selected from 1 times safe-rated current (Ie) to 3.5 times Ie to obtain tested sample wires. The mass fraction, time to ignition (TTI), heat release rate (HRR), gas emission, and residue were measured. If the current flowing through the wire increased up to 3.5 times Ie, the TTI of this unenergized wire increased drastically and the peak HRR (pHRR) decreased notably so that the flame growing index (FGI) reduced considerably. When the wire carried less than three times Ie, the FGI remained stable. For all overloaded PVC copper wires, the increase in the heat flux resulted in a higher pHRR and a lower burning duration. However, regardless of the external heat flux exposure, the FGI of copper wires overloaded at 3.5 times Ie was lower than that of copper wires carrying less than other times Ie. Moreover, the consumption of O2 and generation of CO2 as the heat flux varied were consistent with that of the HRR. Opposed to expectation, the flame propagation of unenergized PVC copper wires would decline in a fire, if the wire has been damaged by overload with some currents.

Serum-Derived Exosomal miR-140-5p as a Promising Biomarker for Differential Diagnosis of Anti-NMDAR Encephalitis With Viral Encephalitis.

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. Early recognition and treatment, especially distinguishing from viral encephalitis (VE) in the early stages, are crucial for the outcomes of patients with anti-NMDAR encephalitis. Compared with plasma microRNAs (miRNAs), exosomal miRNAs are more abundant and not easy to degrade. Moreover, exosomes can pass through the blood-brain barrier. This study aimed to explore the clinical value of serum exosomal miRNAs in the differential diagnosis of anti-NMDAR encephalitis with VE. Method: Serum samples from a total of 30 patients with anti-NMDAR encephalitis, 30 patients with VE, and 30 cases of control patients hospitalized in the same period were collected. Firstly, the serum exosomes were isolated and identified by transmission electron microscope (TEM), nanoparticle-tracking analyzer (NTA), and Western blot (WB). The expression levels of let-7b and miR-140-5p from serum exosomes were detected by real-time quantitative PCR (qPCR). At the same time, we also detected complement 3 (C3), complement 4 (C4), and high sensitivity CRP (hs-CRP) expression levels in three groups. Finally, we analyzed the difference and diagnostic value of the test results. Results: Isolated particles showed identical characteristics to the exosomes through TEM, NTA, and WB analyses. Compared with the VE group and control group, the expression of miR-140-5p was significantly upregulated in serum exosomes of the NMDAR group. In contrast, the serum C3 in the NMDAR group was significantly lower than the other two groups. ROC curve analysis showed the area under the curve (AUC) of serum exosomal miR-140-5p and serum C3 was 0.748 (76.67% sensitivity and 73.33% specificity) and 0.724 (76.67% sensitivity and 60% specificity) to distinguish anti-NMDAR encephalitis from VE, respectively. The AUC of serum exosomal miR-140-5p combined with serum C3 was 0.811, the sensitivity was 70.00%, and the specificity was 86.67%. Conclusion: Serum exosomal miR-140-5p combined with serum C3 would be a promising marker in the differential diagnosis of anti-NMDAR encephalitis with VE.

The effects of genetic polymorphisms of APOE on circulating lipid levels in middle-aged and elderly chinese Fujian Han population: toward age- and sex-personalized management.

BACKGROUND: Increased evidence has reported the association of genetic polymorphisms of Apolipoprotein E (APOE) with serum lipids. However, few studies have explored the combined effects of APOE, gender, and age. METHODS: A total of 1,419 middle-aged and elderly subjects were randomly selected and studied. The APOE genotypes and the serum lipids were detected. The effects of APOE, gender, and age on serum lipids were preliminarily observed in general. The subjects were then divided into the middle-aged group (40-64 years old) and the elderly group (≥ 65 years old), for both males and females, to explore the combined effects of the APOE, gender, and age on serum lipids. Finally, a multivariate logistic regression model was used to evaluate the associations between the APOE allele carriers and the at-risk levels of dyslipidemia. RESULTS: The serum TC, LDL-C, and ApoB in the ε2 carriers were lower than the ε3 carriers (all P < 0.05), and there was no significant difference in the ε4 carriers compared to the ε3 carriers in general (all P > 0.05). The serum LDL-C and ApoB of the ε2 carriers were lower than the noncarriers in the middle-aged and elderly males (all P < 0.05). The serum TC in the ε2 carriers was lower than the noncarriers only in middle-aged males (P < 0.05). As to the levels of serum HDL-C and ApoA1, the ε2 carriers were higher than the noncarriers in middle-aged females (all P < 0.05), and the ε4 carriers were lower than noncarriers in middle-aged males (P < 0.05). Especially, the serum TG in the ε4 carriers was significantly higher than the noncarriers in elderly females. The logistic regression analysis indicated that the ε2 carriers were less likely to have at-risk levels of high LDL-C in middle-aged and elderly males (all P < 0.05) versus low HDL-C in middle-aged females (P < 0.05). In contrast, the ε4 carriers were more likely to have at-risk levels of high TG in elderly females (P < 0.05). CONCLUSIONS: The effects of the genetic polymorphisms of APOE on the serum lipids were both gender- and age-dependent in the middle-aged and elderly Chinese Fujian Han population.

Analysing wideband absorbance immittance in normal and ears with otitis media with effusion using machine learning.

Wideband Absorbance Immittance (WAI) has been available for more than a decade, however its clinical use still faces the challenges of limited understanding and poor interpretation of WAI results. This study aimed to develop Machine Learning (ML) tools to identify the WAI absorbance characteristics across different frequency-pressure regions in the normal middle ear and ears with otitis media with effusion (OME) to enable diagnosis of middle ear conditions automatically. Data analysis included pre-processing of the WAI data, statistical analysis and classification model development, and key regions extraction from the 2D frequency-pressure WAI images. The experimental results show that ML tools appear to hold great potential for the automated diagnosis of middle ear diseases from WAI data. The identified key regions in the WAI provide guidance to practitioners to better understand and interpret WAI data and offer the prospect of quick and accurate diagnostic decisions.

TAK-875 Mitigates ß-Cell Lipotoxicity-Induced Metaflammation Damage through Inhibiting the TLR4-NF-κB Pathway.

Metabolic inflammatory damage, characterized by Toll-like receptor 4 (TLR4) signaling activation, is a major mechanism underlying lipotoxicity-induced ß-cell damage. The present study is aimed at determining whether G protein-coupled receptor 4 (GPR40) agonist can improve ß-cell lipotoxicity-induced damage by inhibiting the TLR4-NF-κB pathway. Lipotoxicity, inflammation-damaged ß-cells, obese SD, and TLR4KO rat models were used in the study. In vitro, TAK-875 inhibited the lipotoxicity- and LPS-induced ß-cell apoptosis in a concentration-dependent manner, improved the insulin secretion, and inhibited the expression of TLR4 and NF-κB subunit P65. Besides, silencing of TLR4 expression enhanced the protective effects of TAK-875, while TLR4 overexpression attenuated this protective effect. Activation of TLR4 or NF-κB attenuated the antagonism of TAK-875 on PA-induced damage. Moreover, the above process of TAK-875 was partially independent of GPR40 expression. TAK-875 reduced the body weight and inflammatory factors, rebalanced the number and distribution of α or ß-cells, inhibited the apoptosis of islet cells, and inhibited the expression of TLR4 and NF-κB subunit P65 in obese rats. Further knockout of the rat TLR4 gene delayed the damage induced by the high-fat diet and synergy with the action of TAK-875. These data suggest that GPR40 agonists antagonized the lipotoxicity ß-cell damage by inhibiting the TLR4-NF-κB pathway.

Adsorption studies of Orange II onto polyaniline/bentonite nanocomposite.

Modification of bentonite is essential for the adsorption of anionic dyes, as its negative surface charge. In this study, polyaniline/bentonite (PAni-Bent) nanocomposite was synthesized by in-situ intercalative polymerization technique and used to remove anionic dye Orange II (ORII) from synthetic wastewater. Its structure was confirmed by X-ray diffraction (XRD), scanning electron microscopy, Fourier-transform infrared spectra and Brunauer-Emmett-Teller specific surface area measurements. The adsorption behaviours of PAni-Bent towards ORII in the single anionic dye wastewater, the cationic/anionic mixture dye wastewater, with or without salt or surfactant, were investigated principally. The results show that cetyl trimethyl ammonium bromide have an obviously suppressing effect on dye removal in the MB/ORII mixture system. The Langmuir and Temkin isotherm models described the adsorption process better than Freundlich or Dubinin-Radushkevich (D-R) model, and the pseudo-second-order and Boyd kinetic models fit better with the experimental data. Considering all these unique characteristics, PAni-Bent can be considered as effective adsorbent material for potential removal of dye from aqueous solution in industry.

Synthesis of magnetic epichlorohydrin cross-linked carboxymethyl cellulose microspheres and their adsorption behavior for methylene blue.

Epichlorohydrin cross-linked carboxymethyl cellulose microspheres (ECH/CMC) obtained by inverse suspension method and magnetic Fe3O4 nanoparticles encasing the ECH/CMC microspheres (M-ECH/CMC) obtained by two different methods were successfully prepared and compared. Their structures and morphologies were analyzed using polarizing microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The adsorption behaviors of M1-ECH/CMC for methylene blue (MB) in the single cationic dye wastewater, the cationic/anionic dye mixture in the absence or presence of co-existed additives (salt and surfactant) wastewater, were also investigated with UV-vis spectrometer. The results showed that the magnetic Fe3O4 nanoparticles were loaded readily in situ into ECH/CMC by specific, chemical interactions between COO- groups of ECH/CMC and magnetic responsive Fe3O4. The Langmuir isotherm and pseudo-second-order kinetic model provide best correlation with the experimental data for the adsorption of MB onto ECH/CMC and M1-ECH/CMC microspheres, while the Langmuir isotherm and pseudo-first-order kinetic model for M2-ECH/CMC. These microspheres are easily recyclable and exhibit high desorption and adsorption, which suggests that they can be applied as potential environmental adsorbents.

Adsorption properties of crosslinking carboxymethyl cellulose grafting dimethyldiallylammonium chloride for cationic and anionic dyes.

Novel and efficient microspheres adsorbent (MCA-E0.7/CMC-g- PDMDAAC), based on monochloroacetic acid (MCA) modified epichlorohydrin (ECH) cross-linked carboxymethyl cellulose (CMC), then grafting by dimethyldiallylammonium chloride (DMDAAC), was synthesized and its adsorption properties on cationic and anionic dyes were investigated. The results demonstrated that such MCA-E0.7/CMC-g-PDMDAAC microspheres showed pH-sensitive and could effectively adsorb cationic dye methylene blue (MB) or anionic dye orange II (OR II), at near neutral (pH>4) or acidic (pH<3) condition, respectively. Moreover, it could selectively adsorb the cationic dye MB from the cationic/anionic dye mixture at neutral pH condition. The desorption experiments were mainly performed under acidic (pH 3) or basic (pH 11) condition, over 98.54% of MB and 83.07% of OR II can be desorbed within 20min, respectively. The pseudo-second-order kinetic model and Langmuir isotherm provide better correlation with the experimental data for the adsorption of dyes onto MCA-E0.7/CMC-g-PDMDAAC microspheres.