Use of pressure muscle index to predict the contribution of patient's inspiratory effort during pressure support ventilation: a prospective physiological study.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Data-Physics Fusion-Driven Defect Predictions for Titanium Alloy Casing Using Neural Network.

The quality of Ti alloy casing is crucial for the safe and stable operation of aero engines. However, the fluctuation of key process parameters during the investment casting process of titanium alloy casings has a significant influence on the volume and number of porosity defects, and this influence cannot be effectively suppressed at present. Therefore, this paper proposes a strategy to control the influence of process parameters on shrinkage volume and number. This study constructed multiple regression prediction models and neural network prediction models of porosity volume and number for a ZTC4 casing by simulating the gravity investment casting process. The results show that the multiple regression prediction model and neural network prediction model of shrinkage cavity total volume have an accuracy of over 99%. The accuracy of the neural network prediction model is higher than that of the multiple regression model, and the neural network model realizes the accurate prediction of shrinkage defect volume and defect number through pouring temperature, pouring time, and mold shell temperature. The sensitivity degree of casing defects to key process parameters, from high to low, is as follows: pouring temperature, pouring time, and mold temperature. Further optimizing the key process parameter window reduces the influence of process parameter fluctuation on the volume and number of porosity defects in casing castings. This study provides a reference for actual production control process parameters to reduce shrinkage cavity and loose defects.

Improvements in Wear and Corrosion Resistance of Ti-W-Alloyed Gray Cast Iron by Tailoring Its Microstructural Properties.

The improved wear and corrosion resistance of gray cast iron (GCI) with enhanced mechanical properties is a proven stepping stone towards the longevity of its versatile industrial applications. In this article, we have tailored the microstructural properties of GCI by alloying it with titanium (Ti) and tungsten (W) additives, which resulted in improved mechanical, wear, and corrosion resistance. The results also show the nucleation of the B-, D-, and E-type graphite flakes with the A-type graphite flake in the alloyed GCI microstructure. Additionally, the alloyed microstructure demonstrated that the ratio of the pearlite volume percentage to the ferrite volume percentage was improved from 67/33 to 87/13, whereas a reduction in the maximum graphite length and average grain size from 356 ± 31 µm to 297 ± 16 µm and 378 ± 18 µm to 349 ± 19 µm was detected. Consequently, it improved the mechanical properties and wear and corrosion resistance of alloyed GCI. A significant improvement in Brinell hardness, yield strength, and tensile strength of the modified microstructure from 213 ± 7 BHN to 272 ± 8 BHN, 260 ± 3 MPa to 310 ± 2 MPa, and 346 ± 12 MPa to 375 ± 7 MPa was achieved, respectively. The substantial reduction in the wear rate of alloyed GCI from 8.49 × 10-3 mm3/N.m to 1.59 × 10-3 mm3/N.m resulted in the upgradation of the surface roughness quality from 297.625 nm to 192.553 nm. Due to the increase in the corrosion potential from -0.5832 V to -0.4813 V, the impedance of the alloyed GCI was increased from 1545 Ohm·cm2 to 2290 Ohm·cm2. On the basis of the achieved experimental results, it is suggested that the reliability of alloyed GCI based on experimentally validated microstructural compositions can be ensured during the operation of plants and components in a severe wear and corrosive environment. It can be predicted that the proposed alloyed GCI components are capable of preventing the premature failure of high-tech components susceptible to a wear and corrosion environment.

Risk Factors and Clinical Significance of Ultra-Long-Term Microischemia After Intracranial Aneurysm Embolization.

INTRODUCTION: This study aimed to explore influencing factors and clinical significance of ultra-long-term microischemia following intracranial aneurysm (IA) embolization and establish a theoretical foundation for reducing both the incidence of ultra-long-term microischemia and cognitive dysfunction in patients post embolization. METHODS: A retrospective analysis was conducted on data from 147 patients who received endovascular treatment for IAs. Patients were categorized into microischemic and control (non-microischemic) groups on the based on the findings of high-resolution magnetic resonance vessel wall imaging (HR-VWI) examinations performed 3 days postoperatively and 6 months postoperatively. Risk factors for the occurrence of ultra-long-term microischemia were determined by univariate analysis and multivariate logistic regression analysis. RESULTS: Out of 147 patients included in the study, 51 (34.69%) developed microischemia while the remaining 96 (65.31%) did not experience this condition. Analysis revealed that factors such as sex, age, history of underlying diseases (hypertension, diabetes mellitus), aneurysmal site characteristics, the presence or absence of stenosis in the aneurysm-bearing artery, modified Fisher score at admission, Barthel's index at discharge, immunoinflammatory index at 3 days postoperatively and at the 6-month follow-up, the presence or absence of aneurysmal wall enhancement, and the presence or absence of aneurysmal lumen showed no statistically significant differences between the two groups (all P > 0.05). By contrast, variables like in operative time, rupture status of the aneurysm before surgery according to World Federation of Neurologic Surgeons (WFNS) grade, aneurysm size, number of stents used, number of guidewires and catheters used, and Evans index between the two groups were found to have statistically significant disparities between those who developed microischemia and those who did not (P < 0.05). A subsequent multivariate analysis revealed that aneurysm size, Evans index, and the number of stents used were independent risk factors for the occurrence of ultra-long-term microischemia after surgical intervention of aneurysms (P < 0.05). The receiver operating characteristic (ROC) curves of the patients were constructed on the basis of risk factors determined through multivariate logistic regression analysis. Results indicated that aneurysm size (area under ROC curve (AUC) 0.619, sensitivity 94.7%, specificity 17.1%, P = 0.049), Evans index (AUC 0.670, sensitivity 96.4%, specificity 26.8%, P = 0.004), and number of stents (AUC 0.639, sensitivity 44.6%, specificity 90.2%, P < 0.001) effectively predicted the occurrence of microischemia. The incidence of cognitive dysfunction was higher in the microischemic group than in the control group (P < 0.05), and a greater number of microischemic foci was associated with a higher incidence of cognitive dysfunction. The proportion of microschemia foci in the thalamus and basal ganglia in patients with cognitive dysfunction (60.87%) was significantly higher than that in patients without cognitive dysfunction (34.55%) (P < 0.05). CONCLUSION: Aneurysm size, Evans index > 0.3, and the quantity of stents were independent risk factors for the occurrence of ultra-long-term microischemia after aneurysm embolization and provided good predictive performance. Cognitive dysfunction was closely associated with microischemia, with its severity increasing with an increase in the number of ischemic foci.

DIAGNOSTIC PERFORMANCE OF CENTRAL NERVOUS SYSTEM INFECTIONS IN PATIENTS WITH NEUROSURGICAL INTENSIVE CARE USING METAGENOMIC NEXT-GENERATION SEQUENCING: A PROSPECTIVE OBSERVATIONAL STUDY.

ABSTRACT: Background. Identifying the causative pathogens of central nervous system infections (CNSIs) is crucial, but the low detection rate of traditional culture methods in cerebrospinal fluid (CSF) has made the pathogenic diagnosis of CNSIs a longstanding challenge. Patients with CNSIs after neurosurgery often overlap with inflammatory and bleeding. Metagenomic next-generation sequencing (mNGS) has shown some benefits in pathogen detection. This study aimed to investigate the diagnostic performance of mNGS in the etiological diagnosis of CNSIs in patients after neurosurgery. Methods. In this prospective observational study, we enrolled patients with suspected CNSIs after neurosurgical operations who were admitted to the intensive care unit of Beijing Tiantan Hospital. All enrolled patients' CSF was tested using mNGS and pathogen culture. According to comprehensive clinical diagnosis, the enrolled patients were divided into CNSIs group and non-CNSIs group to compare the diagnostic efficiency of mNGS and pathogen culture. Results. From December 2021 to March 2023, 139 patients were enrolled while 66 in CNSIs group and 73 in non-CNSIs. The mNGS exceeded culture in the variety and quantity of pathogens detected. The mNGS outperformed traditional pathogen culture in terms of positive percent agreement (63.63%), accuracy (82.01%), and negative predictive value (75.00%), with statistically significant differences ( P < 0.05) for traditional pathogen culture. The mNGS also detected bacterial spectrum and antimicrobial resistance genes. Conclusions. Metagenomics has the potential to assist in the diagnosis of patients with CNSIs who have a negative culture.

Incidence of injury and illness at the Beijing 2022 Paralympic Winter Games held in a closed-loop environment: a prospective cohort study of 7332 athlete days.

OBJECTIVE: To describe the epidemiology of injuries and illnesses sustained during the Beijing 2022 Paralympic Winter Games, organised in a closed-loop environment to adhere with COVID-19 restrictions. METHODS: Injuries and illnesses from all teams were recorded on a daily basis by team medical staff on a web-based form and by local organising committee medical (polyclinic) facilities and venue medical support. Duplicates recorded on both systems were removed. Incidence of injuries and illnesses are reported per 1000 athlete days (95% CI). RESULTS: 564 athletes (426 male and 138 female) representing 46 countries were monitored for the 13-day period of the Beijing 2022 Paralympic Winter Games (7332 athlete days). The overall incidences were 13.0 injuries (10.6-15.8) and 6.1 illnesses (4.5-8.4) per 1000 athlete days. The incidence of injury in alpine skiing (19.9; 15.2-26.1) was significantly higher compared with Nordic skiing, ice hockey and wheelchair curling (p<0.05), while the incidence of respiratory illness was significantly higher in Nordic skiing (1.6; 0.9-2.9) compared with alpine skiing, ice hockey and snowboarding (p<0.05). CONCLUSION: The incidence of both injury and illness at the Beijing 2022 Games were the lowest yet reported in the Paralympic Winter Games. The incidence of injury was highest in alpine skiing. These findings underscore the importance of ongoing vigilance and continued injury risk mitigation strategies to safeguard the well-being of athletes in these high-risk competitions. Respiratory illnesses were most commonly reported in Nordic skiing, which included the three cases of COVID-19 recorded at the games.

A quinoa peptide protects impaired mucus barriers in colitis mice by inhibiting NF-κB-TRPV1 signaling and regulating the gut microbiota.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions that lead to the disruption of the colonic mucus barrier. Quinoa has a well-balanced profile of essential amino acids and exhibits excellent anti-inflammatory effects. We recently explored the beneficial effects and relevant mechanisms of a novel quinoa peptide TPGAFF on impaired mucus barriers in mice with chemically induced colitis. Our findings demonstrated that TPGAFF, administered in low and high doses for 28 days, effectively attenuated the pathological phenotype and reduced intestinal permeability in colitis mice. TPGAFF demonstrated its protective abilities by restoring the impaired mucus barrier, inhibiting the activation of inflammatory signaling and reducing inflammatory cytokine levels. Moreover, TPGAFF positively influenced the composition of the gut microbiota by reducing inflammation-related microbes. Additionally, TPGAFF inhibited the activation of TRPV1 nociceptor and decreased the levels of neuropeptides. Conclusively, our results indicated that oral administration of TPGAFF may be an optional approach for the treatment of mucus barrier damage.

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study.

BACKGROUND: Assessment of the patient's respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation. METHODS: In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus-time product per minute (PTPmus/min) were used as the reference standard for the patient's effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min-1, respectively. RESULTS: A total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83-0.96), specificity (0.74-0.88), and positive (0.80-0.91) and negative predictive values (0.78-0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93-0.95). A high sensitivity (0.80-1.00) and negative predictive value (0.97-1.00) were found with a low positive predictive value (0.23-0.64). CONCLUSIONS: By performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

Sparking potential over 1200 V by a falling water droplet.

Hydrovoltaic technology has achieved notable breakthroughs in electric output via using the moving boundary of electric double layer, but the output voltage induced by droplets is saturated around 350 volts, and the underlying mechanism remains to be further clarified. Here, we show that falling water droplets can stably spark an unprecedented voltage up to 1200 volts within microseconds that they contact an electrode placed on top of an electret surface, approaching the theoretical upper limit. This sparking potential can be explained and described by a comprehensive model considering the water-electrode contact dynamics from both the macroscale droplet spreading and the microscale electric double layer formation, as well as the presence of a circuit capacitance. It is demonstrated that a droplet-induced electric spark is sufficient to directly ionize gas at atmospheric pressure and split water into hydrogen and oxygen, showing wide application potential in fields of green energy and intelligence.

Economic impact of metagenomic next-generation sequencing versus traditional bacterial culture for postoperative central nervous system infections using a decision analysis mode: study protocol for a randomized controlled trial.

IMPORTANCE: Diagnosing and treating postoperative central nervous system infections (PCNSIs) remains challenging due to the low detection rate and time-consuming nature of traditional methods for identifying microorganisms in cerebrospinal fluid. Metagenomic next-generation sequencing (mNGS) technology provides a rapid and comprehensive understanding of microbial composition in PCNSIs by swiftly sequencing and analyzing the microbial genome. The current study aimed to assess the economic impact of using mNGS versus traditional bacterial culture-directed PCNSIs diagnosis and therapy in post-neurosurgical patients from Beijing Tiantan Hospital. mNGS is a relatively expensive test item, and whether it has the corresponding health-economic significance in the clinical application of diagnosing intracranial infection has not been studied clearly. Therefore, the investigators hope to explore the clinical application value of mNGS detection in PCNSIs after neurosurgery.

Effect of modified high-flow oxygen therapy on positive end-expiratory pressure and end-expiratory lung volume based on simulated lung platform.

Objective: The aim of this study was to assess the effect of modified high-flow oxygen therapy on end-expiratory lung volume (EELV) and positive end-expiratory pressure (PEEP) in tracheotomized patients with normal pulmonary, acute hypoxic respiratory failure (AHRF) or chronic obstructive pulmonary disease (COPD). Methods: A ventilator and an artificial lung model were used to simulate the normal or strong inspiratory effort state of normal lung, AHRF and COPD patients. The traditional high-flow respiratory humidification therapy device connected with a standard interface (group A), and the modified therapy device added two types of resistance valves (group B, inner diameter 7.7 mm, length 24.0 mm; group C, inner diameter 7.7 mm, length 34.0 mm) to the exhalation end of the standard interface. The changes of end-expiratory lung volume (ΔEELV) and PEEP with the increase of flow rate (10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min) in the three groups was recorded. Results: Under simulated conditions of normal lung, AHRF and COPD, as the flow rate increased by using the modified therapy device, the PEEP values in all groups showed an exponential increasing trend, and the ΔEELV also increased accordingly. In addition, under the same flow rate level, the PEEP values of the two modified high-flow oxygen therapies (Group B and Group C) were significantly higher than those of the standard high-flow oxygen therapy (Group A) (p < 0.05). In the normal lung model with normal or strong inspiratory effort, and in the AHRF or COPD model with strong inspiratory effort, when the flow rate was higher than 30 L/min, the PEEP levels of Group B were significantly lower than those of Group C (p < 0.05). In the AHRF model with normal inspiratory effort, when the flow rate was between 10 L/min and 60 L/min, the PEEP levels of Group B were significantly lower than those of Group C (p < 0.05). Moreover, in the COPD model with normal inspiratory effort, the PEEP levels of Group B were significantly lower than that of Group C only when the flow rate was 60 L/min (p < 0.05). Conclusion: The addition of different types of resistance valves to the high-flow exhalation end may be a feasible solution to improve the clinical efficacy of tracheotomized high-flow oxygen therapy.

Recommendation of SLM Process Parameters Based on Analytic Hierarchy Process and Weighted Particle Swarm Optimization for High-Temperature Alloys.

Selective laser melting (SLM) of high-temperature alloys involves intricate interdependencies among key process parameters, such as laser power and scanning speed, affecting properties such as density and tensile strength. However, relying solely on experiential knowledge for process parameter design often hampers the precise attainment of target requirements. To address this challenge, we propose an innovative approach that integrates the analytic hierarchy process (AHP) and weighted particle swarm optimization (WPSO) to recommend SLM process parameters for high-temperature alloy fabrication. Our proposed AHP-WPSO model consists of three main steps. First, a comprehensive historical database is established, capturing the process parameters and performance metrics of high-temperature alloy SLM parts. Utilizing an AHP framework, we compute the performance similarity between target and historical cases, applying rational thresholds to identify analogous cases. When suitable analogs are elusive, the model seamlessly transitions to the second step. Here, the WPSO model optimizes and recommends process parameters according to target specifications. Lastly, our experimental validation of the GH4169 high-temperature alloy through SLM experiments corroborates the effectiveness of our AHP-WPSO model in making process parameter recommendations. The outcomes underscore the model's high accuracy, attaining a recommendation precision of 99.81% and 96.32% when historical analogs are present and absent, respectively. This innovative approach offers a robust and reliable solution to the challenges posed in SLM process parameter optimization for high-temperature alloy applications.

[Protocol for the development of the Expert consensus on sedation and analgesia for neurocritical care patients (2023)].

To further standardize the sedation and analgesia treatment for neurocritical care patients, the National Center for Healthcare Quality Management in Neurological Diseases and Chinese Society of Critical Care Medicine organized national experts in this fields to form Working group of the Expert consensus on sedation and analgesia for neurocritical care patients in order to update the Expert consensus on sedation and analgesia for patients with severe brain injury (2013) based on evidence-based medicine. This update aims to provide scientific guidance for the clinical diagnosis and treatment of neurocritical care patients. The working group followed the definition of clinical practice guidelines by the Institution of Medicine (IOM) and the World Health Organization guidelines development handbook and Guidelines for the formulation/revision of clinical guidelines in China (2022) to register and draft the Expert consensus on sedation and analgesia for neurocritical care patients. The working group will strictly adhere to the consensus development process to formulate and publish the Expert consensus on sedation and analgesia for neurocritical care patients (2023). This protocol primarily introduces the development methodology and process of the Expert consensus on sedation and analgesia for neurocritical care patients (2023), including the purpose of the update, the target population, the composition of the consensus development working group, the presentation and collection of clinical questions, evidence evaluation and summarization, and the generation of recommended opinions. This will make the consensus development process more standardized and transparent.

Development of a Prediction Score for Evaluation of Extubation Readiness in Neurosurgical Patients with Mechanical Ventilation.

BACKGROUND: There is no widely accepted consensus on the weaning and extubating protocols for neurosurgical patients, leading to heterogeneity in clinical practices and high rates of delayed extubation and extubation failure-related health complications. METHODS: In this single-center prospective observational diagnostic study, mechanically ventilated neurosurgical patients with extubation attempts were consecutively enrolled for 1 yr. Responsive physicians were surveyed for the reasons for delayed extubation and developed the Swallowing, Tongue protrusion, Airway protection reflected by spontaneous and suctioning cough, and Glasgow Coma Scale Evaluation (STAGE) score to predict the extubation success for neurosurgical patients already meeting other general extubation criteria. RESULTS: A total of 3,171 patients were screened consecutively, and 226 patients were enrolled in this study. The rates of delayed extubation and extubation failure were 25% (57 of 226) and 19% (43 of 226), respectively. The most common reasons for the extubation delay were weak airway-protecting function and poor consciousness. The area under the receiver operating characteristics curve of the total STAGE score associated with extubation success was 0.72 (95% CI, 0.64 to 0.79). Guided by the highest Youden index, the cutoff point for the STAGE score was set at 6 with 59% (95% CI, 51 to 66%) sensitivity, 74% (95% CI, 59 to 86%) specificity, 90% (95% CI, 84 to 95%) positive predictive value, and 30% (95% CI, 21 to 39%) negative predictive value. At STAGE scores of 9 or higher, the model exhibited a 100% (95% CI, 90 to 100%) specificity and 100% (95% CI, 72 to 100%) positive predictive value for predicting extubation success. CONCLUSIONS: After a survey of the reasons for delayed extubation, the STAGE scoring system was developed to better predict the extubation success rate. This scoring system has promising potential in predicting extubation readiness and may help clinicians avoid delayed extubation and failed extubation-related health complications in neurosurgical patients.

Comprehensive transcript-level analysis reveals transcriptional reprogramming during the progression of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder that has a multi-step disease progression. Differences between moderate and advanced stages of AD have not yet been fully characterized. Materials and methods: Herein, we performed a transcript-resolution analysis in 454 AD-related samples, including 145 non-demented control, 140 asymptomatic AD (AsymAD), and 169 AD samples. We comparatively characterized the transcriptome dysregulation in AsymAD and AD samples at transcript level. Results: We identified 4,056 and 1,200 differentially spliced alternative splicing events (ASEs) that might play roles in the disease progression of AsymAD and AD, respectively. Our further analysis revealed 287 and 222 isoform switching events in AsymAD and AD, respectively. In particular, a total of 163 and 119 transcripts showed increased usage, while 124 and 103 transcripts exhibited decreased usage in AsymAD and AD, respectively. For example, gene APOA2 showed no expression changes between AD and non-demented control samples, but expressed higher proportion of transcript ENST00000367990.3 and lower proportion of transcript ENST00000463812.1 in AD compared to non-demented control samples. Furthermore, we constructed RNA binding protein (RBP)-ASE regulatory networks to reveal potential RBP-mediated isoform switch in AsymAD and AD. Conclusion: In summary, our study provided transcript-resolution insights into the transcriptome disturbance of AsymAD and AD, which will promote the discovery of early diagnosis biomarkers and the development of new therapeutic strategies for patients with AD.

Emulsifying properties of wheat germ protein: Effect of different ultrasonic treatment.

The effect of ultrasonic treatment on emulsifying properties of wheat germ protein (WGP) was studied in this paper. WGP was subjected to low frequency (20 kHz), high intensity ultrasonic treatment at different power (200, 400, 600, 800 W) for 10 min, or different time (2, 4, 6, 8, 10, 15, 20 min) at 400 W. The emulsifying activity index and emulsion stability index of WGP were significantly improved, and the emulsion droplet was smaller and more uniform after ultrasound treatment. Ultrasound increased the adsorbed WGP concentration at the oil-water interface and reduced the interfacial tension, which explained the improved emulsifying properties of WGP. The investigation on molecular properties and protein conformation showed that ultrasound processing increased solubility, but decreased particle size and surface charge of WGP. Ultrasound processing resulted in the unfolding of the protein molecular structure indicated by the increase of surface hydrophobicity and surface free sulfhydryl group levels, and the decrease of intrinsic fluorescence intensity. Correlation analysis showed that the changes in WGP solubility, particle size, and surface hydrophobicity were the main driven factors for the improved emulsifying properties of WGP.

Clinical Features, Brain-Structure Changes, and Cognitive Impairment in Basal Ganglia Infarcts: A Pilot Study.

Introduction: Stroke has been considered to raise the risk of dementia in several studies, but the relationship between brain structural changes and poststroke cognitive impairment (PSCI) is unclear. Methods: In this study, 23 PSCI patients with basal ganglia infarcts after 2 weeks and 29 age-matched controls underwent magnetic resonance imaging measuring cortical thickness and volume changes, as well as neuropsychological tests. CI was derived from a performance score <1.5 standard deviations for normally distributed scores. We compared Z scores in different cognitive domains and cortical thickness and volumes in two groups. Multiple linear regressions were used to investigate the relationship between cortical thickness and volumes and neuropsychological tests. Results: A majority of PSCI patients were in their 50s (55.19±8.52 years). PSCI patients exhibited significantly decreased Z scores in multiple domains, such as memory, language, visuomotor speed, and attention/executive function. The volumes of the middle posterior corpus callosum, middle anterior corpus callosum, and hippocampus in PSCI patients were markedly lower than controls. The thickness of the right inferior temporal cortex and insula were significantly smaller than controls. It found that the reduced right hippocampus was related to executive dysfunction. Hippocampus dysfunction may be involved in language impairment (p<0.05) in PSCI patients with basal ganglia infarcts. Conclusion: These findings demonstrated that brain structure changed after ischemic stroke, and different gray-matter structural changes could lead to specific cognitive decline in PSCI patients with basal ganglia infarcts. Atrophy of the right hippocampus potentially serves as an imaging marker of early executive function of PSCI.

Safety, tolerability, pharmacokinetics, and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial.

PURPOSE: To evaluate the safety, tolerability, pharmacokinetics, and efficacy of kukoamine B (KB), an alkaloid compound with high affinity for both lipopolysaccharide (LPS) and oligodeoxynucle-otides containing CpG motifs (CpG DNA), in patients with sepsis-induced organ failure. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Patients with sepsis-induced organ failure were randomized to receive either KB (0.06, 0.12, or 0.24 mg/kg) or placebo, every 8 h for 7 days. Primary endpoint was safety, and secondary endpoints included pharmacokinetic (PK) parameters, changes in inflammatory mediators' level, and prognostic parameters. RESULTS: Of 44 patients enrolled, adverse events occurred in 28 patients [n = 20, 66.7% (KB pooled); n = 8, 57.1% (placebo)], while treatment emergent adverse events were reported in 14 patients [n = 10, 33.3% (KB pooled); n = 4, 28.6% (placebo)]. Seven patients died at 28-day follow-up [n = 4, 13.3% (KB pooled); n = 3, 21.4% (placebo)], none was related to study drug. PK parameters suggested dose-dependent drug exposure and no drug accumulation. KB did not affect clinical outcomes such as ΔSOFA score, vasopressor-free days or ventilator-free days. CONCLUSIONS: In patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted. TRIAL REGISTRATION: http://ClinicalTrials.gov, NCT03237728.