Preoperative Anxiolytic and Sedative Effects of Intranasal Remimazolam and Dexmedetomidine: A Randomized Controlled Clinical Study in Children Undergoing General Surgeries.

Purpose: Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries. Patients and Methods: Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg-1), Group D (intranasal dexmedetomidine 2 mcg kg-1), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS). Results: Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010). Conclusion: Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation. Trial Registration: NCT04720963, January 22, 2021, ClinicalTrials.Gov.

The ARPKD Protein DZIP1L Regulates Ciliary Protein Entry by Modulating the Architecture and Function of Ciliary Transition Fibers.

Serving as the cell's sensory antennae, primary cilia are linked to numerous human genetic diseases when they malfunction. DZIP1L, identified as one of the genetic causes of human autosomal recessive polycystic kidney disease (ARPKD), is an evolutionarily conserved ciliary basal body protein. Although it has been reported that DZIP1L is involved in the ciliary entry of PKD proteins, the underlying mechanism remains elusive. Here, an uncharacterized role of DZIP1L is reported in modulating the architecture and function of transition fibers (TFs), striking ciliary base structures essential for selective cilia gating. Using C. elegans as a model, C01G5.7 (hereafter termed DZIP-1) is identified as the sole homolog of DZIP1L, which specifically localizes to TFs. While DZIP-1 or ANKR-26 (the ortholog of ANKRD26) deficiency shows subtle impact on TFs, co-depletion of DZIP-1 and ANKR-26 disrupts TF assembly and cilia gating for soluble and membrane proteins, including the ortholog of ADPKD protein polycystin-2. Notably, the synergistic role for DZIP1L and ANKRD26 in the formation and function of TFs is highly conserved in mammalian cilia. Hence, the findings illuminate an evolutionarily conserved role of DZIP1L in TFs architecture and function, highlighting TFs as a vital part of the ciliary gate implicated in ciliopathies ARPKD.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

A Dielectric MXene-Induced Self-Built Electric Field in Polymer Electrolyte Triggering Fast Lithium-Ion Transport and High-Voltage Cycling Stability.

Quasi-solid polymer electrolyte (QPE) lithium (Li)-metal battery holds significant promise in the application of high-energy-density batteries, yet it suffers from low ionic conductivity and poor oxidation stability. Herein, a novel self-built electric field (SBEF) strategy is proposed to enhance Li+ transportation and accelerate the degradation dynamics of carbon-fluorine bond cleavage in LiTFSI by optimizing the termination of MXene. Among them, the SBEF induced by dielectric Nb4C3F2 MXene effectively constructs highly conductive LiF-enriched SEI and CEI stable interfaces, moreover, enhances the electrochemical performance of the QPE. The related Li-ion transfer mechanism and dual-reinforced stable interface are thoroughly investigated using ab initio molecular dynamics, COMSOL, XPS depth profiling, and ToF-SIMS. This comprehensive approach results in a high conductivity of 1.34 mS cm-1, leading to a small polarization of approximately 25 mV for Li//Li symmetric cell after 6000 h. Furthermore, it enables a prolonged cycle life at a high voltage of up to 4.6 V. Overall, this work not only broadens the application of MXene for QPE but also inspires the great potential of the self-built electric field in QPE-based high-voltage batteries.

Correlative relationship between body mass index and heart rate variability in psychiatric disorders.

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.

Transcriptomics Provide Insights into the Photoperiodic Regulation of Reproductive Diapause in the Green Lacewing, Chrysoperla nipponensis (Okamoto) (Neuroptera: Chrysopidae).

Chrysoperla nipponensis (Okamoto) displays typical adult reproductive diapause under short photoperiods; however, our understanding of the molecular mechanism underlying photoperiod-sensitive reproduction remains limited. In this study, we performed transcriptome profiling of four treatments (the diapause-sensitive stage and pre-diapause phase under long and short photoperiods) of C. nipponensis using RNA sequencing (RNA-seq). A total of 71,654 unigenes were obtained from the samples. Enrichment analysis showed that fatty acid metabolism-related pathways were altered under a short photoperiod. Moreover, ß-oxidation-related gene expression was active during the diapause-sensitive period under a short photoperiod. The knockdown of juvenile hormone acid methyltransferase 1 (Jhamt1) prolonged the pre-oviposition period but did not affect the reproductive ability of female individuals in C. nipponensis. These findings provided us with a more comprehensive understanding of the molecular mechanisms of photoperiod-sensitive diapause and show that groundwork is crucial for bolstering the long-term storage and biocontrol potential of C. nipponensis.

Parameter optimization method for light field 3D display.

A parameter optimization method for light field three-dimensional (3D) display is proposed to improve the performance of integral imaging (InI) and super multi-view (SMV) display. The parameters of light field display are divided into system parameters and display parameters. The multi-objective genetic algorithm is used to optimize the system parameters so that the display parameters can reach the target values. The influence of all display parameters on the imaging quality of light field 3D display are comprehensively considered. When the weight of the depth of field (DOF) and field of view (FOV) are set to the maximum, the DOF and FOV are respectively improved compared with the original display parameters. By setting the weight of resolution to the maximum, the image quality of InI and SMV is improved by 32% and 21%, respectively.

Cardiovascular variations in patients with major depressive disorder versus bipolar disorder.

BACKGROUND: Differentiating depression in major depressive disorder and bipolar disorder is challenging in clinical practice. Therefore, reliable biomarkers are urgently needed to differentiate between these diseases. This study's main objective was to assess whether cardiac autonomic function can distinguish patients with unipolar depression (UD), bipolar depression (BD), and bipolar mania (BM). METHODS: We recruited 791 patients with mood disorders, including 191 with UD, 286 with BD, and 314 with BM, who had been drug free for at least 2 weeks. Cardiovascular status was measured using heart rate variability (HRV) and pulse wave velocity (PWV) indicators via finger photoplethysmography during a 5-min rest period. RESULTS: Patients with BD showed lower HRV but higher heart rates than those with UD and BM. The PWV indicators were lower in the UD group than in the bipolar disorder group. The covariates of age, sex, and body mass index affected the cardiovascular characteristics. After adjusting for covariates, the HRV and PWV variations among the three groups remained significant. Comparisons between the UD and BD groups showed that the variable with the largest effect size was the frequency-domain indices of HRV, very low and high frequency, followed by heart rate. The area under the receiver operating characteristic curve (AUC) for each cardiovascular variable ranged from 0.661 to 0.714. The High-frequency index reached the highest AUC. LIMITATIONS: Cross-sectional design and the magnitude of heterogeneity across participants with mood disorders limited our findings. CONCLUSION: Patients with BD, but not BM, had a greater extent of cardiac imbalance than those with UD. Thus, HRV may serve as a psychophysiological biomarker for the differential diagnosis of UD and BD.

Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children.

BACKGROUND: The pharmacokinetic properties of the new benzodiazepine remimazolam have been studied only in adults. We investigated the pharmacokinetics of remimazolam after i.v. infusion in anaesthetised paediatric patients. METHODS: Twenty-four children (2-6 yr, ASA physical status 1-2, BMI 15-18 kg m-2) undergoing general anaesthesia with sevoflurane were enrolled. During surgery, remimazolam was administered as an i.v. infusion over 1 h at 5 mg kg-1 h-1 for 5 min, followed by 1.5 mg kg-1 h-1 for 55 min. Plasma concentrations of remimazolam and its metabolite CNS7054 were determined from arterial blood samples using ultra-high performance liquid chromatography-mass spectrometry. Pharmacokinetic modelling was performed by population analysis. RESULTS: Pharmacokinetics were best described by a three-compartment model for remimazolam and a two-compartment model for CNS7054 linked by a transit compartment. Remimazolam showed a high clearance of 15.9 (12.9, 18.2) ml kg-1 min-1 (median, Q25, Q75), a small central volume of distribution of 0.11 (0.08, 0.14) L kg-1 and a short terminal half-life of 67 (49, 85) min. The context-sensitive half-time after an infusion of 4 h was 17 (12, 21) min. The metabolite CNS7054 showed a low clearance of 0.89 (0.33, 1.40) ml kg-1 min-1, a small central volume of distribution of 0.011 (0.005, 0.016) L kg-1, and a long terminal half-life of 321 (230, 770) min. CONCLUSIONS: Remimazolam in children was characterised by a high clearance and short context-sensitive half-time. When normalised to weight, pharmacokinetic properties were similar to those reported for adults. CLINICAL TRIAL REGISTRATION: ChiCTR2200057629.

Heart rate variability in patients with psychiatric disorders from adolescence to adulthood.

OBJECTIVE: Age is associated with changes in autonomic nervous system activity. These changes are assessed using heart rate variability(HRV) indicators; however, the effect of age on HRV in patients with psychiatric disorders remains unclear. Our study aimed to explore this effect and determine its variance across different lifespans. METHOD: Consecutive patients(N = 3315), comprising 1833 patients with psychotic disorders, 1040 with mood disorders, and 442 with anxiety disorders, were recruited. The patients were divided into four age groups: adolescence(10-24 years), early adulthood(25-39 years), middle adulthood(40-59 years), and late adulthood(60+ years). HRV indicators were measured during a 5-min rest period. RESULTS: The heart rate and HRV indices were higher in the adolescent and early adulthood groups than they were in the middle and late adulthood groups(increased HRV is beneficial for health, while reduced HRV is detrimental). Age and all the HRV indices were negatively correlated(r-values 0.153-0.350, p < 0.001), with these correlation patterns being more evident in the adolescent and early adulthood groups than in the middle and late adulthood groups. Stratified by sex, the low-frequency/high-frequency ratio was higher in men than in women across most age groups(p < 0.05), except the late adulthood group(p = 0.085). Stratified by diagnosis, most HRV variables(except very low-frequency) were lower in the psychotic disorder group than they were in the mood and anxiety disorder groups, especially in middle and late adulthood patients. After adjusting for confounders, the HRV variables were significantly associated with age, while older age was associated with lower HRV. CONCLUSIONS: These results indicate that the substantial reduction in HRV with age in patients with psychiatric disorders. The association remains significant after correction for sex, heart rate, and diagnoses; this may prove useful to clinical practice and further research.

Serum Levels of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in the Subtypes of Clinical High Risk Individuals: A Prospective Cohort Study.

Introduction: Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment. Methods: A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score. Results: Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = -0.212, p = 0.010) and in the subgroup with higher positive scores (r = -0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines. Discussion: TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.

Enabling Scalable Polymer Electrolyte with Dual-Reinforced Stable Interface for 4.5 V Lithium-Metal Batteries.

Hitherto, it remains a great challenge to stabilize electrolyte-electrode interfaces and impede lithium dendrite proliferation in lithium-metal batteries with high-capacity nickel-rich LiNx Coy Mn1- x-y O2 (NCM) layer cathodes. Herein, a special molecular-level-designed polymer electrolyte is prepared by the copolymerization of hexafluorobutyl acrylate and methylene bisacrylamide to construct dual-reinforced stable interfaces. Verified by X-ray photoelectron spectroscopy depth profiling, there are favorable solid electrolyte interphase (SEI) layers on Li metal anodes and robust cathode electrolyte interphase (CEI) on Ni-rich cathodes. The SEI enriched in lithiophilic N-(C)3 guides the homogenous distribution of Li+ and facilitates the transport of Li+ through LiF and Li3 N, promoting uniform Li+ plating and stripping. Moreover, the CEI with antioxidative amide groups can suppress the parasitic reactions between cathode and electrolyte and the structural degradation of cathode. Meanwhile, a unique two-stage rheology-tuning UV polymerization strategy is utilized, which is quite suited for continuous electrolyte fabrication with environmental friendliness. The fabricated polymer electrolyte exhibits a high ionic conductivity of 1.01 mS cm-1 at room temperature. 4.5 V NCM622//Li batteries achieve prolonged operation with a retention rate of 85.0% after 500 cycles at 0.5 C. This work provides new insights into molecular design and processibility design for polymer-based high-voltage batteries.

Association of Attenuated Niacin Response With Inflammatory Imbalance and Prediction of Conversion to Psychosis From Clinical High-risk Stage.

Objective: Attenuated niacin responses and changes in cytokine levels have been reported in schizophrenia. However, prior studies have typically focused on schizophrenia, and little is known about the association between niacin response and inflammatory imbalance in clinically high-risk psychosis (CHR). This study aimed to assess the niacin response to inflammatory imbalance for association with conversion to psychosis within 2 years.Methods: A prospective case-control study was performed to assess the niacin response and interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels in 60 CHR individuals and 60 age- and sex-matched healthy controls (HC) from May 2019 to December 2021. Participants with CHR were identified using the Structured Interview for Prodromal Syndromes. The niacin-induced responses were measured using laser Doppler flowmetry. From the dose-response curves, the log-transferred concentration of methylnicotinate required to elicit a half-maximal blood flow response (LogEC50) and maximal minus minimal blood flow response (Span) values were calculated for each subject. Serum cytokine levels were measured using enzyme-linked immunosorbent assay. Individuals with CHR were then divided into converters (CHR-C, n = 15) and non-converters (CHR-NC, n = 45) to psychosis based on their 2-year follow-up clinical status.Results: The CHR group exhibited significantly higher LogEC50 (t = 3.650, P < .001) and Span (t = 2.657, P = .009) values than the HC group. The CHR-C group exhibited a significantly shorter Span (t = 4.027, P < .001) than the CHR-NC group. The LogEC50 showed a trend toward significance (t = 1.875, P = .066). None of the cytokine levels were significant. The conversion outcome can therefore be predicted by applying LogEC50 (P = .049) and Span (P < .001). The regression model with variables of LogEC50, Span, family history, and scores of positive symptoms showed good discrimination of subsequent conversion to psychosis and achieved a classification accuracy of 91.7%. The decreased LogEC50 in the CHR-C group was significantly correlated with the increased IL-1ß/IL-10 ratio (Spearman ρ = -0.600, P = .018), but this correlation was nonsignificant in the CHR-NC group.Conclusions: Our findings indicate a significant association between niacin response and psychosis conversion outcomes in individuals with CHR. Compared with peripheral inflammatory cytokines, the niacin response can better predict conversion, although there may be an intersection between the two in biological mechanisms.

Chimeric antigen receptor T cells targeting FcRH5 provide robust tumour-specific responses in murine xenograft models of multiple myeloma.

BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.

Impacts of COVID-19 on Appropriate Use of Screening Colonoscopy in a Large Integrated Healthcare Delivery System.

BACKGROUND: Decreasing low-value colonoscopy is critical to optimizing access for high-need patients, particularly in resource-constrained environments such as those created by the COVID-19 pandemic. We hypothesized that rates of screening colonoscopy overuse would decline during COVID compared to pre-COVID due to enhanced procedural scrutiny and prioritization in the setting of constrained access. OBJECTIVE: To characterize impacts of COVID-19 on screening colonoscopy overuse DESIGN: Retrospective national cohort study using Veterans Health Administration administrative data PARTICIPANTS: Veterans undergoing screening colonoscopy in Q4 2019 (pre-COVID) and Q4 2020 (COVID) at 109 endoscopy facilities MAIN MEASURES: Rates of screening colonoscopy overuse KEY RESULTS: 18,376 screening colonoscopies were performed pre-COVID, 19% (3,641) of which met overuse criteria. While only 9,360 screening colonoscopies were performed in Q4 2020, 25% met overuse criteria. Overall change in median facility-level overuse during COVID compared to pre-COVID was 6% (95%CI 5%-7%), with significant variability across facilities (IQR: 2%-11%). Of colonoscopies meeting overuse criteria, the top reason for overuse in both periods was screening colonoscopy performed <9 years after previous screening procedure (55% pre-COVID, 49% during COVID). The largest shifts in overuse category were in screening procedures performed <9 years after prior screening colonoscopy (-6% decline COVID vs. pre-COVID) and screening procedures performed in patients below average-risk screening age (i.e., age <40 (5% increase COVID compared to pre-COVID), age 40-44 (4% increase COVID vs. pre-COVID)). Within facility performance was stable over time; 83/109 facilities changed their performance by <=1 quartile during COVID compared to pre-COVID. CONCLUSIONS: Despite pandemic-related resource constraints and enhanced procedural scrutiny and prioritization in the setting of COVID-related backlogs, screening colonoscopy overuse rates remained roughly stable during COVID compared to pre-COVID, with continued variability across facilities. These data highlight the need for systematic and concerted efforts to address overuse, even in the face of strong external motivating factors.

The safety and efficacy of remimazolam tosylate for induction and maintenance of general anesthesia in pediatric patients undergoing elective surgery: Study protocol for a multicenter, randomized, single-blind, positive-controlled clinical trial.

Introduction: Remimazolam is an ultra-short-acting benzodiazepine sedative agent commonly used in general anesthesia, procedural sedation, and intensive care unit (ICU) sedation. This study aimed to explore the efficacy and safety of remimazolam versus propofol for the induction and maintenance of general anesthesia in preschool-age children undergoing elective surgery. Methods and analysis: In this multicenter, randomized, single-blind, positive-controlled non-inferior clinical trial, one hundred ninety-two children aged 3-6 years will be randomly allocated as a 3:1 ratio into two groups: Group R with an intravenous dose of remimazolam 0.3 mg/kg for the induction of anesthesia followed by a constant infusion rate of remimazolam 1-3 mg/kg/h to maintain anesthesia, and Group P with an intravenous dose of propofol 2.5 mg/kg for the induction of anesthesia followed by a constant infusion rate of propofol 4-12 mg/kg/h to maintain anesthesia. The primary outcome will be the rate of the successful induction and maintenance of anesthesia. The secondary outcomes will include the time to LoC, the Bispectral Index (BIS) value, awakening time, extubation time, post-anesthesia care unit (PACU) discharge time, usage of additional sedative drugs during the induction period, usage of remedial drugs in PACU, emergence delirium, pain in PACU, behavior scores at day 3 after surgery, parental and anesthesiologists' satisfaction, and adverse events. Ethics and dissemination: This study has been approved by the ethics review boards at all participating hospitals. The Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Reference No. LCKY 2020-380, November 13, 2020) is the central ethics committee.

Quantitative transcriptomic and proteomic analyses reveal the potential maintenance mechanism of female adult reproductive diapause in Chrysoperla nipponensis.

BACKGROUND: The green lacewing Chrysoperla nipponensis is an important natural enemy of many insect pests and exhibits reproductive diapause to overwinter. Our previous studies showed that adult C. nipponensis enters reproductive diapause under a short-day photoperiod. However, the molecular mechanism underlying diapause maintenance in C. nipponensis is still unknown. RESULTS: The total lipid and triglyceride content showed the reservation and degradation of energy during diapause in C. nipponensis. Thus, we performed combined transcriptomic and proteomic analyses of female reproductive diapause in C. nipponensis at three ecophysiological phases (initiation, maintenance and termination). A total of 64 388 unigenes and 5532 proteins were identified from the transcriptome and proteome. In-depth dissection of the gene-expression dynamics revealed that differentially expressed genes and proteins were predominately involved in the lipid and carbohydrate metabolic pathways, in particular fatty acid metabolism, metabolic pathways and the citrate cycle. Among of these genes, TIM, CLK, JHAMT2, PMK, HMGS, HMGR, FKBP39, Kr-h1, Phm, ECR, IR1, ILP3, ILP4, mTOR, ACC, LSD1 and LSD2 were differentially expressed in diapause and non-diapause female adults of C. nipponensis. The expression patterns of these genes were consistent with the occurrence of vitellogenesis and expression of either Vg or VgR. CONCLUSION: Our findings indicated that diapause adult C. nipponensis accumulate energy resources to overwinter. Transcriptomic and proteomic analyses suggested candidate key genes involved in the maintenance of C. nipponensis during adult reproductive diapause. Taken together, these results provide in-depth knowledge to understand the maintenance mechanism of C. nipponensis during adult reproductive diapause. © 2023 Society of Chemical Industry.

Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at clinical high risk.

Immunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1ß, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.

A defect localization method based on self-sensing and orthogonal matching pursuit.

In conventional structural health monitoring (SHM), a sensor array enables to localize a potential defect by using at least three lead zirconate titanate (PZT) patches. To reduce the vast number of patches needed for large-scaled structure, this paper presents an extremely sparse sensor array with only one single PZT patch, which could actuate and sense simultaneously. Firstly, a half-bridge circuit, referred as a self-sensing circuit is developed with a capacitor connected with the PZT patch, and the capacitance parameter and self-sensing performance are studied subsequently. Then, an orthogonal matching pursuit (OMP)-based sparse decomposition and dispersion removal algorithm is proposed to separate and reconstruct wave packets which are acutely overlapped. Subsequently, a matching strategy is proposed to determine the matching relationship between wave packets and wave paths. Finally, the ellipse-type imaging approach is employed to image the defect location. Two cases: one and two defects respectively are implemented to verify its efficacy. Experimental results illustrate that the proposed self-sensing unit and signal process method could erase the adverse effect of sensor-actuator interval and dispersion characteristic to the localization resolution and accuracy.

Development and validation of a new ICD-10-based screening colonoscopy overuse measure in a large integrated healthcare system: a retrospective observational study.

BACKGROUND: Low-value use of screening colonoscopy is wasteful and potentially harmful to patients. Decreasing low-value colonoscopy prevents procedural complications, saves patient time and reduces patient discomfort, and can improve access by reducing procedural demand. The objective of this study was to develop and validate an electronic measure of screening colonoscopy overuse using International Classification of Diseases, Tenth Edition codes and then apply this measure to estimate facility-level overuse to target quality improvement initiatives to reduce overuse in a large integrated healthcare system. METHODS: Retrospective national observational study of US Veterans undergoing screening colonoscopy at 119 Veterans Health Administration (VHA) endoscopy facilities in 2017. A measure of screening colonoscopy overuse was specified by an expert workgroup, and electronic approximation of the measure numerator and denominator was performed ('electronic measure'). The electronic measure was then validated via manual record review (n=511). Reliability statistics (n=100) were calculated along with diagnostic test characteristics of the electronic measure. The measure was then applied to estimate overall rates of overuse and facility-level variation in overuse among all eligible patients. RESULTS: The electronic measure had high specificity (99%) and moderate sensitivity (46%). Adjusted positive predictive value and negative predictive value were 33% and 95%, respectively. Inter-rater reliability testing revealed near perfect agreement between raters (k=0.81). 269 572 colonoscopies were performed in VHA in 2017 (88 143 classified as screening procedures). Applying the measure to these 88 143 screening colonoscopies, 24.5% were identified as potential overuse. Median facility-level overuse was 22.5%, with substantial variability across facilities (IQR 19.1%-27.0%). CONCLUSIONS: An International Classification of Diseases, Tenth Edition based electronic measure of screening colonoscopy overuse has high specificity and improved sensitivity compared with a previous International Classification of Diseases, Ninth Edition based measure. Despite increased focus on reducing low-value care and improving access, a quarter of VHA screening colonoscopies in 2017 were identified as potential low-value procedures, with substantial facility-level variability.