Population pharmacokinetics and dosage optimization of linezolid in Chinese older patients.

PURPOSE: To assess the pharmacokinetics and pharmacodynamics of linezolid in a retrospective cohort of hospitalized Chinese older patients. METHODS: Patients > 60 years of age, who received intravenous linezolid (600 mg), were included. A population pharmacokinetics (PPK) model was established using nonlinear mixed-effects modeling. The predictive performance of the final model was assessed using goodness-of-fit plots, bootstrap analyses, and visual predictive checks. Monte Carlo simulations were used to evaluate the achievement of a pharmacodynamics target for the area under the serum concentration-time curve/minimum inhibitory concentration (AUC0-24/MIC). RESULTS: A total of 210 samples were collected from 120 patients. A one-compartment PPK model with linear elimination best predicted the linezolid plasma concentrations. Linezolid clearance (CL) was 4.22 L h-1 and volume of distribution (Vd) was 45.80 L; serum uric acid (SUA) was a significant covariate of CL. CONCLUSION: The results of this study indicated that the standard dose was associated with a risk of overexposure in older patients, particularly those with high SUA values; these patients would benefit from a lower dose (300 mg every 12 h).

Population pharmacokinetics, dosing optimization and clinical outcomes of biapenem in patients with sepsis.

Introduction: Biapenem is a carbapenem antibiotic widely used in Asia, can be used for the treatment of adults and children with infections due to susceptible bacteria. Although biapenem is utilized in the treatment of a diverse range of bacterial infections, current pharmacokinetic data in the context of septic populations remain limited. Consequently, our research aims to evaluate the pharmacokinetics and efficacy of biapenem within a septic population to optimize biapenem therapy. Methods: In this study, we characterized the pharmacokinetics of biapenem in septic patients using a population pharmacokinetic (PPK) approach. The clinical PK data to develop the PPK model were obtained from 317 septic patients admitted to Nanjing Drum Tower Hospital between 2018 and 2022. All patients were randomized to the modeling and validation cohorts at a 3:1 ratio, with PPK modeling and validation performed utilizing the NONMEM software. Results: The model found to best describe the available data was a two-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V2), and intercompartmental clearance (Q). A covariate analysis identified that creatinine clearance (CLCR) was a significant covariate influencing biapenem CL, while blood urea nitrogen (BUN) was a significant covariate influencing biapenem Q. Accoding to the clinical outcome analyses, 70% of the time that the free antimicrobial drug concentration exceeds the MIC (fT >MIC) is associated with favourable clinical outcomes. The PPK model was then used to perform Monte Carlo simulations to evaluate the probability of attaining 70% fT >MIC. Conclusions: A final PPK model of biapenem was established for patients with sepsis. The current daily dosage regimen of 1.2 g may insufficient to achieve 70% fT >MIC in septic patients. The dosage regimen of 600 mg every 6 h appears to be the optimal choice.

FlexDTI: flexible diffusion gradient encoding scheme-based highly efficient diffusion tensor imaging using deep learning.

Objective. Most deep neural network-based diffusion tensor imaging methods require the diffusion gradients' number and directions in the data to be reconstructed to match those in the training data. This work aims to develop and evaluate a novel dynamic-convolution-based method called FlexDTI for highly efficient diffusion tensor reconstruction with flexible diffusion encoding gradient scheme.Approach. FlexDTI was developed to achieve high-quality DTI parametric mapping with flexible number and directions of diffusion encoding gradients. The method used dynamic convolution kernels to embed diffusion gradient direction information into feature maps of the corresponding diffusion signal. Furthermore, it realized the generalization of a flexible number of diffusion gradient directions by setting the maximum number of input channels of the network. The network was trained and tested using datasets from the Human Connectome Project and local hospitals. Results from FlexDTI and other advanced tensor parameter estimation methods were compared.Main results. Compared to other methods, FlexDTI successfully achieves high-quality diffusion tensor-derived parameters even if the number and directions of diffusion encoding gradients change. It reduces normalized root mean squared error by about 50% on fractional anisotropy and 15% on mean diffusivity, compared with the state-of-the-art deep learning method with flexible diffusion encoding gradient scheme.Significance. FlexDTI can well learn diffusion gradient direction information to achieve generalized DTI reconstruction with flexible diffusion gradient scheme. Both flexibility and reconstruction quality can be taken into account in this network.

Population Pharmacokinetics of Voriconazole and Dose Optimization in Elderly Chinese Patients.

Voriconazole is commonly recommended as a first-line therapy for invasive aspergillosis infections. Elderly patients are susceptible to infectious diseases owing to their decreased physical function and immune system. Our study aims to establish a population pharmacokinetics model for elderly patients receiving intravenous voriconazole, and to optimize dosing protocols through a simulated approach. An accurate fit to the concentration-time profile of voriconazole was achieved by employing a 1-compartment model featuring first-order elimination. The typical clearance rate of voriconazole was found to be 3.22 L/h, with a typical volume of distribution of 194 L. The covariate analysis revealed that albumin (ALB), gamma-glutamyl transpeptidase, and direct bilirubin had significant impacts on voriconazole clearance. Additionally, body weight was found to be associated with the volume of distribution. Individualized dosing regimens were recommended for different ALB levels based on population pharmacokinetics model prediction. The proposed dosing regimens could provide a rationale for dosage individualization, improve the clinical outcomes, and minimize drug-related toxicities.

Preoperative Fibrinogen Levels and Function as Predictive Factors for Acute Bleeding in the Hematoma Cavity After Burr Hole Drainage in Patients with CSDH.

OBJECTIVE: Burr hole drainage (BHD) is the primary surgical intervention for managing chronic subdural hematoma (CSDH). However, it can lead to postoperative complications such as acute bleeding within the hematoma cavity and hematoma recurrence. The objective of this study is to identify the risk factors for these complications and develop a predictive model for acute hematoma cavity bleeding after BHD in patients with CSDH. METHODS: This study presents a retrospective cohort investigation conducted at a single center. The clinical dataset of 308 CSDH patients who underwent BHD at a hospital from 2016 to 2022 was analyzed to develop and assess a prognostic model. RESULTS: The nonbleeding group exhibited a significant correlation between fibrinogen (FIB) and thrombin time (TT), whereas no correlation was observed in the bleeding group. Notably, both FIB and TT were identified as risk factors for postoperative acute bleeding within the hematoma cavity. We developed a prognostic model to predict the occurrence of postoperative acute bleeding within the hematoma cavity after BHD in patients with CSDH. The model incorporated FIB, TT, coronary artery disease, and Glasgow Coma Scale scores. The model exhibited good discrimination (area under the curve: 0.725) and calibration (Hosmer-Leeshawn goodness of fit test: P > 0.1). Furthermore, decision curve analysis demonstrated the potential clinical benefit of implementing this prediction model. CONCLUSIONS: The predictive model developed in this study can forecast the risk of postoperative acute bleeding within the hematoma cavity, thus aiding clinicians in selecting the optimal treatment approach for patients with CSDH.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report.

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

Effects of selenite on the responses of lettuce (Lactuca sativa L.) to polystyrene nano-plastic stress.

Nowadays, nano-plastics are widespread in agricultural soils and could be uptaken by crops to cause an increased risk for food safety. As a beneficial element for plants, selenium (Se) can alleviate oxidative damages under various environmental stresses (eg. heavy metals, heat, cold). This study investigated the single and co-applications of nano-size polystyrene (PS) (80 nm and 200 nm) and selenite (0.8 ppm and 5 ppm) in lettuce (Lactuca sativa L.). Results showed nano-PS significantly decreased the root-shoot fresh biomass ratios, inhibited physiological functions in roots and leaves (e.g. root length, chlorophyll content and net photosynthetic rate), as well as stimulated the activities of the antioxidant enzymes in roots and shoots with greater toxicity at the smaller particle size (80 nm). However, both exogenous selenite applications significantly alleviated the above toxic effects of nano-PS in lettuces, especially at a high Se level of 5 ppm. Regression Path Analysis (RPA) revealed that regulation of chlorophyll levels by Se might be a key mechanism for counteracting PS stress in lettuces, which led to the increase in indigenous defense capacity. The present findings provide a novel but safer and cleaner agricultural strategy to alleviate or minimize nano-plastics toxicity in agricultural soils for staple crops and vegetables via application of Se.

Modelling method of inter-building movement for campus-scale occupancy simulation: A case study.

As an important factor in the investigation of building energy consumption, occupant behavior (OB) has been widely studied on the building level. However so far, studies of OB modelling on the district scale remain limited. Indeed, district-scale OB modelling has been facing the challenges from the scarcity of district-scale data, modelling methods, as well as simulation application. This study initiates the extrapolation of occupancy modelling methodology from building level to district scale through proposing modelling methods of inter-building movements. The proposed modelling methods utilize multiple distribution fittings and Bayesian network to upscale the event description methods from inter-zone movement events at the building level to inter-building movement events at the district level. This study provides a framework on the application of the proposed modelling methods for a university campus in the suburbs of Shanghai, taking advantages of data sensing, monitoring and survey techniques. With the collected campus-scale occupancy data, this paper defines five patterns of inter-building movement. One pattern represents the dominated inter-building movement events for one kind of students in their daily campus life. Based on the quantitative descriptions for various inter-building movement events, this study performs the stochastic simulation for the campus district, using Markov chain models. The simulation results are then validated with the campus-scale occupancy measurement data. Furthermore, the impact of inter-building movement modelling methods on building energy demand is evaluated for the library building, taking the deterministic occupancy schedules suggested by current building design standard as a baseline.

Simultaneous Quantification of Six Bioactive Components in Decoction of Ziziphi spinosae Semen Using Ultrahigh Performance Liquid Chromatography Coupled with Triple-Quadrupole Mass Spectrometry.

This paper was conducted to develop a method containing ultrahigh performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry for simultaneous quantification of six bioactive components in the decoction of Ziziphi spinosae Semen. Analysis was performed on an Agilent ZORBAX Extend-C18 column (2.1 × 100 mm, 1.8 µm) and eluted with a mobile phase system consisting of acetonitrile and water under a gradient program with a flow rate of 0.3 ml/min. The injection volume was 2 µl. Multiple-reaction monitoring scanning detection was employed for quantification with an electrospray ion source in the negative ion mode. All the six compounds showed good linearities (r ≥ 0.9996). The LODs of the six bioactive compounds were 0.039 ng/ml, 0.092 ng/ml, 3.112 ng/ml, 2.131 ng/ml, 0.099 ng/ml, and 0.071 ng/ml for spinosin, 6‴-feruloylspinosin, jujuboside A, jujuboside B, camelliaside B, and betulinic acid, respectively. The LOQs were 0.118 ng/ml, 0.276 ng/ml, 9.336 ng/ml, 6.393 ng/ml, 0.299 ng/ml, and 0.213 ng/ml for spinosin, 6‴-feruloylspinosin, jujuboside A, jujuboside B, camelliaside B, and betulinic acid, respectively. According to our knowledge, it was the first time to establish a method with high efficiency and accuracy for the quantification of six bioactive components in the decoction of Ziziphi spinosae Semen, which would provide references for quality control and evaluation of Ziziphi spinosae Semen.

Development of an analytical strategy to identify and classify the global chemical constituents of Ziziphi Spinosae Semen by using UHPLC with quadrupole time-of-flight mass spectrometry combined with multiple data-processing approaches.

According to traditional Chinese medical theory, Ziziphi Spinosae Semen needs to be stir-fried before clinical application for its sedative-hypnotic effect enhancement. A rapid and comprehensive analysis strategy of ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and multiple data analysis platforms was developed for the efficient and sensitive identification of components in crude and parched Ziziphi Spinosae Semen to explore the composition changes that happen during the stir-frying process. Both positive and negative ion modes were applied for mass spectrometry detection, and 40 components were identified from crude and parched Ziziphi Spinosae Semen, respectively. Principal component analysis and t-test were applied to find differences between crude and parched Ziziphi Spinosae Semen. As a result, Ziziphi Spinosae Semen samples could be clearly divided into two groups according to their processing methods, and 19 key markers that contributed to the classification significantly (P < 0.05) were found. This kind of change in contents of components might be responsible for the recommended clinical application of parched Ziziphi Spinosae Semen.

Flexible 3D reconstruction method based on phase-matching in multi-sensor system.

Considering the measuring range limitation of a single sensor system, multi-sensor system has become essential in obtaining complete image information of the object in the field of 3D image reconstruction. However, for the traditional multi-sensors worked independently in its system, there was some point in calibrating each sensor system separately. And the calibration between all single sensor systems was complicated and required a long time. In this paper, we present a flexible 3D reconstruction method based on phase-matching in multi-sensor system. While calibrating each sensor, it realizes the data registration of multi-sensor system in a unified coordinate system simultaneously. After all sensors are calibrated, the whole 3D image data directly exist in the unified coordinate system, and there is no need to calibrate the positions between sensors any more. Experimental results prove that the method is simple in operation, accurate in measurement, and fast in 3D image reconstruction.

Magnetic/polymer/nanogold complex using as a novel enzyme support.

A novel enzyme support based on magnetic/polymer/nanogold complex was prepared in this study. At first, carboxymethyl chitosan (CMC) were connected onto the surface of Fe3O4 nanoparticles, and then gold nanoparticles were in situ synthesized and bound to CMC chains, resulting in Fe3O4/CMC/nanogold complex. The complex was determined by UV-vis spectroscopy, transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). Horseradish peroxidase (HRP) was immobilized on the Fe3O4/CMC/nanogold complex. Compared with free HRP, the immobilized HRP exhibits higher catalytic activity and better storage stability. This Fe3O4/CMC/nanogold complex can serve as an excellent support for enzymes.