Application of AI in Multilevel Pain Assessment Using Facial Images: Systematic Review and Meta-Analysis.

BACKGROUND: The continuous monitoring and recording of patients' pain status is a major problem in current research on postoperative pain management. In the large number of original or review articles focusing on different approaches for pain assessment, many researchers have investigated how computer vision (CV) can help by capturing facial expressions. However, there is a lack of proper comparison of results between studies to identify current research gaps. OBJECTIVE: The purpose of this systematic review and meta-analysis was to investigate the diagnostic performance of artificial intelligence models for multilevel pain assessment from facial images. METHODS: The PubMed, Embase, IEEE, Web of Science, and Cochrane Library databases were searched for related publications before September 30, 2023. Studies that used facial images alone to estimate multiple pain values were included in the systematic review. A study quality assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies, 2nd edition tool. The performance of these studies was assessed by metrics including sensitivity, specificity, log diagnostic odds ratio (LDOR), and area under the curve (AUC). The intermodal variability was assessed and presented by forest plots. RESULTS: A total of 45 reports were included in the systematic review. The reported test accuracies ranged from 0.27-0.99, and the other metrics, including the mean standard error (MSE), mean absolute error (MAE), intraclass correlation coefficient (ICC), and Pearson correlation coefficient (PCC), ranged from 0.31-4.61, 0.24-2.8, 0.19-0.83, and 0.48-0.92, respectively. In total, 6 studies were included in the meta-analysis. Their combined sensitivity was 98% (95% CI 96%-99%), specificity was 98% (95% CI 97%-99%), LDOR was 7.99 (95% CI 6.73-9.31), and AUC was 0.99 (95% CI 0.99-1). The subgroup analysis showed that the diagnostic performance was acceptable, although imbalanced data were still emphasized as a major problem. All studies had at least one domain with a high risk of bias, and for 20% (9/45) of studies, there were no applicability concerns. CONCLUSIONS: This review summarizes recent evidence in automatic multilevel pain estimation from facial expressions and compared the test accuracy of results in a meta-analysis. Promising performance for pain estimation from facial images was established by current CV algorithms. Weaknesses in current studies were also identified, suggesting that larger databases and metrics evaluating multiclass classification performance could improve future studies. TRIAL REGISTRATION: PROSPERO CRD42023418181; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=418181.

Correction: Application of AI in Multilevel Pain Assessment Using Facial Images: Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.2196/51250.].

Opioids increase the risk of delirium in critically ill patients: A propensity score analysis.

BACKGROUND: Medications are biologically plausible and potentially modifiable risk factors for delirium. Therapies for delirium might involve more specific strategies such as avoiding the use of delirium-inducing drugs to reduce the incidence of delirium. The association between opioid exposure within 24 hours prior to delirium assessment and the risk of delirium was studied. MATERIALS AND METHODS: Using three large databases, the MIMIC III v1.4, MIMIC-IV v0.4 and eICU Collaborative Research, we performed a multicenter, observational cohort study with two cohorts to estimate the relative risks of outcomes among patients administered opioids within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1 : 1 matched cohort and to identify potential prognostic factors. The outcomes included mortality, length of intensive care unit (ICU) stay, length of hospitalization, and odds of being discharged home. RESULTS: Propensity matching successfully balanced the covariates for the 9,529 patients in each group. Opioid use was associated with a significantly higher risk for delirium than not using opioids (p < 0.001). Additionally, treatment with opioids was associated with higher mortality and a longer ICU stay (p < 0.001) than treatment without opioids. However, patients treated with opioids were more likely to be discharged home (p < 0.001). CONCLUSION: Opioids may be an independent risk factor for delirium in critically ill patients.

Electrochemically reduced graphene oxide (ERGO)-Cu bilayer structure fabricated at room temperature for future interconnects.

Copper is an important interconnect material in integrated circuits (IC) due to its outstanding electrical and thermal properties. However, the development of the IC industry requires novel interconnect materials with higher conductivity. Here, uniform graphene oxide (GO) is deposited on copper by electrophoretic deposition (EPD) to obtain a GO-Cu bilayer structure at room temperature. (3-Mercaptopropyl) trimethoxysilane (MPTS) is self-assembled on the Cu anode surface, which protects the anode from oxidation during the EPD process. We find that the in situ hydrolysis of methoxy under the promotion of EPD voltage can facilitate the uniform deposition of GO and enhance the interface bonding force. In order to achieve better electrical performance, different reduction methods are conducted to reduce the structural disorder of GO. ERGO-Cu reduced by the electrochemical reduction method at -0.75 V for 1 min shows the lowest square resistance with a 16% resistance decrease compared with the GO-Cu structure and a 4.5% decrease compared with Cu substrate, due to the proper adjustment of the GO crystal structure. The room temperature fabricated ERGO-Cu bilayer structure provides a possibility for future interconnects with improved conductivity.

Effect of midazolam on delirium in critically ill patients: a propensity score analysis.

OBJECTIVE: To observe the association between exposure to midazolam within 24 hours prior to delirium assessment and the risk of delirium. METHODS: We performed a systematic cohort study with two sets of cohorts to estimate the relative risks of outcomes among patients administered midazolam within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1:1 matched cohort and identify potential prognostic factors. The outcomes included the odds of delirium, mortality, length of intensive care unit stay, length of hospitalization, and odds of being discharged home. RESULTS: A total of 78,364 patients were included in this study, of whom 22,159 (28.28%) had positive records. Propensity matching successfully balanced covariates for 9348 patients (4674 per group). Compared with no administration of midazolam, midazolam administration was associated with a significantly higher risk of delirium, higher mortality, and a longer intensive care unit stay. Patients treated with midazolam were relatively less likely to be discharged home. There was no significant difference in hospitalization duration. CONCLUSIONS: Midazolam may be an independent risk factor for delirium in critically ill patients.

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study.

Background: Sedatives are commonly used in patients with or at risk for acute respiratory distress syndrome (ARDS) during mechanical ventilation. To systematically compare the outcomes of sedation with midazolam, propofol, and dexmedetomidine in patients with or at risk for ARDS. Methods: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of sedatives and the associated outcomes from the MIMIC-III database and the eICU Collaborative Research database. We performed a systematic study with six cohorts to estimate the relative risks of outcomes among patients administered different sedatives. Propensity score matching was performed to generate a balanced 1:1 matched cohort and to identify potential prognostic factors. The outcomes included hospital mortality, duration of mechanical ventilation, length of intensive care unit stay, length of hospitalization, and likelihood of being discharged home. Results: We performed 60 calibrated analyses among all groups and outcomes with 17,410 eligible patients. Sedation with dexmedetomidine was associated with a lower in-hospital mortality rate than sedation with midazolam and propofol or sedation without dexmedetomidine (p < 0.001). When compared with no sedation, the use of midazolam, propofol or dexmedetomidine was associated with a longer ICU stay and longer hospitalization duration (p < 0.01). Patients treated with midazolam were relatively less likely to be discharged home (p < 0.05). Conclusion: Patients treated with dexmedetomidine had a reduced risk of mortality. These data suggest that dexmedetomidine may be the preferred sedative in patients with or at risk for ARDS.

Comparative Efficacy of Fentanyl and Morphine in Patients with or At Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Opioids are potent painkillers but can have severe adverse effects in the intensive care unit (ICU). The aim of this study was to compare the outcomes of fentanyl and morphine use among patients at risk for and with acute respiratory distress syndrome (ARDS). METHODS: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of opioids and the associated outcomes from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC)-III database and the eICU Collaborative Research Database. Patients who were admitted to the ICU with a diagnosis of or at risk for ARDS and received mechanical ventilation for at least 12 h were included. Patients were enrolled sequentially into one of six groups in three cohorts: treated with fentanyl or not; treated with morphine or not; and treated with fentanyl or morphine. Propensity score matching and multivariable analyses were performed. RESULTS: Fentanyl was associated with higher in-hospital mortality in the propensity score-matched model but not in the linear regression model. The use of morphine was associated with a higher in-hospital mortality in both models. Both fentanyl and morphine were associated with longer duration of mechanical ventilation, ICU stay, and hospitalization and a decreased likelihood of being discharged home in both models. Notably, compared with morphine, fentanyl was associated with a lower mortality and an increased likelihood of being discharged home. CONCLUSIONS: Both fentanyl and morphine were independent risk factors for worse outcomes in patients with or at risk for ARDS. Compared with morphine, fentanyl may be preferred in these patients.

Associations Between Elevated Systolic Blood Pressure and Outcomes in Critically Ill Patients: A Retrospective Cohort Study and Propensity Analysis.

INTRODUCTION: Studies have shown nonlinear relationships between systolic blood pressure (SBP) and outcomes, with increased risk observed at both low and high blood pressure levels. However, the relationships between cumulative times at different SBP levels and outcomes in critically ill patients remain unclear. We hypothesized that an appropriate SBP level is associated with a decrease in adverse outcomes after intensive care unit (ICU) admission. METHODS: This study was a retrospective analysis of data from the Medical Information Mart for Intensive Care (MIMIC) III database, which includes more than 1,000,000 SBP records from 12,820 patients. Associations of cumulative times at four SBP ranges (<100 mm Hg, 100-120 mm Hg, 120-140 mm Hg, and ≥140 mm Hg) with mortality (12-, 3-, 1-month mortality and in-hospital mortality) were evaluated. Restricted cubic splines and multivariable Cox regression models were employed to assess associations between mortality and cumulative times at SBP levels (4 levels: <2, 2-12, 12-36, and ≥36 h) over 72 h of ICU admission. Additionally, 120 mm Hg to 140 mm Hg was subdivided into <12 h (Group L) and ≥12 h (Group M) subsets and subjected to propensity-score matching and subgroup analyses. RESULTS: At 120 mm Hg to 140 mm Hg, level-4 SBP was associated with lower adjusted risks of mortality at 12 months (OR, 0.71; CI, 0.61-0.81), 3 months (OR, 0.72; CI, 0.61-0.85), and 1 month (OR, 0.61; CI, 0.48-0.79) and in the hospital (OR, 0.71; CI, 0.58-0.88) than level-1 SBP. The cumulative times at the other 3 SBP ranges (<100 mm Hg, 100-120 mm Hg, and ≥140 mm Hg) were not independent risk predictors of prognosis. Furthermore, Group M had lower 12-month mortality than Group L, which remained in the propensity-score matched and subgroup analyses. CONCLUSIONS: SBP at 120 mm Hg to 140 mm Hg was associated with decreased adverse outcomes. Randomized trials are required to determine whether the outcomes in critically ill patients improve with early maintenance of a SBP level at 120 mm Hg to 140 mm Hg.

Higher versus lower mean arterial pressure target management in older patients having non-cardiothoracic surgery: A prospective randomized controlled trial.

STUDY OBJECTIVE: This study aimed to evaluate the effects of low versus high mean arterial pressure (MAP) levels on the incidence of postoperative delirium during non-cardiothoracic surgery in older patients. DESIGN: Multicenter, randomized, parallel-controlled, open-label, and assessor-blinded clinical trial. SETTING: University hospital. PATIENTS: Three hundred twenty-two patients aged ≥65 with an American Society of Anesthesiologists physical status of I-II who underwent non-cardiothoracic surgery with general anaesthesia. INTERVENTIONS: Participants were randomly assigned into a low-level MAP (60-70 mmHg) or high-level MAP (90-100 mmHg) group during general anaesthesia. The study was conducted from November 2016 to February 2020. Participants were older patients having non-cardiothoracic surgery. The follow-up period ranged from 1 to 7 days after surgery. The primary outcome was the incidence of postoperative delirium. MAIN RESULTS: In total, 322 patients were included and randomized; 298 completed in-hospital delirium assessments [median (interquartile range) age, 73 (68-77) years; 173 (58.1%) women]. Fifty-four (18.1%) patients total, including 36 (24.5%) and 18 (11.9%) in the low-level and high-level MAP groups [relative risk (RR) 0.48, 95% confidence interval (CI) 0.25 to 0.87, P = 0.02], respectively, experienced postoperative delirium. The adjusted RR was 0.34 (95% CI 0.16 to 0.70, P < 0.01) in the multiple regression analysis. High-level MAP was associated with a shorter delirium span and a higher intraoperative urine volume than low-level MAP. CONCLUSIONS: In older patients during non-cardiothoracic surgery, high-level blood pressure management might help reduce the incidence of postoperative delirium.

Dexmedetomidine alleviated sepsis­induced myocardial ferroptosis and septic heart injury.

Cardiac dysfunction resulting from sepsis may cause significant morbidity and mortality, and ferroptosis plays a role in this pathology. Dexmedetomidine (Dex), a α2­adrenergic receptor (α2­AR) agonist exerts cardioprotective effects against septic heart dysfunction, but the exact mechanism is unknown. In the present study, sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Dex and yohimbine hydrochloride (YOH), an α2­AR inhibitor, were administered before inducing CLP. Then, 24 h after CLP, serum and heart tissue were collected to detect changes of troponin­I (TN­I), interleukin 6 (IL­6), superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels, and iron release. Ferroptosis­targeting proteins, apoptosis and inflammatory factors were assessed by western blotting or ELISA. It was found that, 24 h after CLP, TN­I, a biomarker of myocardial injury, was significantly increased compared with the control group. Furthermore, the levels of MDA, 8­hydroxy­2'­deoxyguanosine and the inflammatory factors IL­6 and monocyte chemoattractant protein­1 were also significantly increased. It was demonstrated that treatment with Dex reverted or attenuated these changes (CLP + Dex vs. CLP; P<0.05), but these protective effects of Dex were reversed by YOH. Moreover, CLP significantly decreased the protein expression levels of glutathione peroxidase 4 (GPX4), SOD and GSH. However, CLP increased expression levels of heme oxygenase­1 (HO­1), transferrin receptor, cleaved caspase 3, inducible nitric oxide synthase and gasdermin D, and iron concentrations. It was found that Dex reversed these changes, but YOH abrogated the protective effects of Dex (CLP + Dex + YOH vs. CLP + Dex; P<0.05). Therefore, the present results suggested that the attenuation of sepsis­induced HO­1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dex alleviates sepsis­induced myocardial cellular injury.

Applicable Superamphiphobic Ni/Cu Surface with High Liquid Repellency Enabled by the Electrochemical-Deposited Dual-Scale Structure.

Until now, scalable fabrication and utilization of superamphiphobic surfaces based on sophisticated structures has remained challenging. Herein, we develop an applicable superamphiphobic surface with nano-Ni pyramid/micro-Cu cone structures prepared by cost-effective electrochemical deposition. More importantly, excellent dynamic wettability is achieved, exhibiting as ultralow sliding angle (∼0°), multiple droplets rebounding (13 times), and a total rejection. The supportive cushions trapped within the dual-scale micro/nanostructures is proved to be the key factor contributing to such high liquid repellency, whose existence is intuitively ascertained at both solid-air-liquid and water-solid-oil systems in this work. In addition, the enduring reliability of the wetting performance under various harsh conditions further endows the surface with broader application prospects.

Low-Temperature Copper Bonding Strategy with Graphene Interlayer.

The reliability of lead-free Cu bonding technology is often limited by high bonding temperature and perpetual growth of intermetallic compounds between Sn solder and Cu substrate. Here, we report a low-bonding-temperature and highly reliable Cu bonding strategy with the use of graphene as an interlayer. By integrating a nanoscale graphene/Cu composite on the Cu substrate prior to thermocompression bonding, we observe a macroscale phenomenon where reliable Sn-Cu joints can be fabricated at a bonding temperature as low as 150 °C. During the bonding process, nanoscale features are replicated in the Sn solder by the Cu nanocone array morphology. Compared to microscale Sn, nanoscale Sn is mechanically weaker and thus can distribute on the Cu substrate at a much lower temperature. Furthermore, insertion of a graphene interlayer, which is one atom thick, can successfully retard the intermetallic compounds' growth and preserve a high bonding yield, following 96 h of aging, as confirmed through SEM and shear strength analyses. Our graphene-based Cu bonding strategy demonstrated in this work is highly reliable, cost-effective, and environmentally friendly, representing a much closer step toward industrial applications.

Comparison of the effect of high versus low mean arterial pressure levels on clinical outcomes and complications in elderly patients during non-cardiothoracic surgery under general anesthesia: study protocol for a randomized controlled trial.

BACKGROUND: Intraoperative blood pressure (BP) is a concern in daily clinic anesthesia and contributes to the differences in clinical outcome. We conducted a randomized controlled trial (RCT) to compare the effect of high vs. low mean arterial pressure (MAP) levels on clinical outcomes and complications in elderly patients under general anesthesia (GA). METHODS: In this multicenter, randomized, parallel-controlled, open-label, assessor-blinded clinical trial, 322 patients aged more than 65 years will be randomized for a low-level MAP (60-70 mmHg) or high-level MAP (90-100 mmHg) during non-cardiothoracic surgery under GA. The primary outcome will be the incidence of postoperative delirium. The secondary outcomes will include the delirium duration days, intraoperative urine volume, intraoperative blood loss, specific postoperative complications, and all-cause 28-day mortality. DISCUSSION: Results of this trial will help clarify whether BP management is beneficial for elderly patients under GA and will make clear whether the effect of high-level MAP can reduce the postoperative complication compared to low-level MAP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02857153 . Registered on 15 July 2016.

Ethanol alters the expression of ion channel genes in Daphnia pulex.

BACKGROUND: Heavy drinking can increase heart rate and blood glucose, induce hypoxic tolerance, impair brain cognitive functions, and alter gene expressions. These phenomena may occur even in response to small dose of ethanol exposure or during its withdrawal. OBJECTIVES: To evaluate whether persistent low concentrations of ethanol exposure affect organism function and the gene expressions of ion channels. METHODS: Daphnids were randomized to receive placebo 300 min, 2 mM ethanol 300 min, or 2 mM ethanol 240 min and then placebo 60 min. Heart rate, glucose levels, phototactic behavior, and hypoxic tolerance were recorded during experiment. At the end of the study, changes in the mRNA levels of ion channel genes were assessed in response to exposure to ethanol using quantitative polymerase chain reaction (PCR) techniques. RESULTS: Heart rate was reversibly increased by ethanol withdrawal and returned to basal levels upon re-exposure to ethanol. Fifteen of 120 ion channel transcripts were affected by persistent ethanol exposure. Neither ethanol withdrawal nor persistent exposures showed an effect on blood glucose, phototactic behavior, or hypoxic tolerance. CONCLUSIONS: Small doses of ethanol can increase heart rate and alter gene expression of multiple ion channels in Daphnia pulex. Affected ion channel genes may assist in understanding the mechanism of ethanol adaptation and tolerance.

Dorsal penile nerve block for rigid cystoscopy in men: study protocol for a randomized controlled trial.

BACKGROUND: Pain is common in men undergoing rigid cystoscopy. Even with the application of a lubricant containing 2 % lidocaine, about 76 % of men suffer from mild to severe pain when undergoing rigid cystoscopy. The most painful part of the procedure for men is when the cystoscope passes through the membranous urethra. Song et al. (Neurourol Urodyn 29:592-5, 2010) did autopsies on males and found that the dorsal nerve of the penis (DNP), the terminal branch of the pudendal nerve, innervates the membranous urethra in 53.3 % of specimens. In addition, the urethral mucosa has branches of innervated DNP. Dorsal penile nerve block (DPNB) is usually used for circumcision in children, and it has been shown to provide effective analgesia for penile surgeries. In this study, we hypothesized that DPNB could reduce the overall pain level in men during rigid cystoscopy. METHODS/DESIGN: The trial is a prospective, randomized, double-blind, placebo-controlled, single-center trial to evaluate the effectiveness and safety of DPNB in analgesia for men undergoing rigid cystoscopy. Participants will be enrolled and randomly allocated into one of three groups according to the different analgesia regimens: 1) tetracaine gel group (DPNB with saline), 2) DPNB group (DPNB with ropivacaine plus plain lubricant), 3) combination group (DPNB with ropivacaine plus tetracaine gel). The primary outcome of this study is the visual analog scale (VAS, 0-10) for pain at cystoscopic inspection of the external sphincter. VAS scores evaluated at other time points serve as secondary outcomes. Vital signs are secondary outcomes that address the discomfort and pain during the procedure. Furthermore, the incidence of adverse events as secondary outcomes will also be recorded for evaluation of the safety of DPNB in rigid cystoscopy. Clinical assessments will be evaluated prior to DPNB, at administration of the lubricant gel, at cystoscopic inspection of the penile and bulbar urethra, external sphincter, prostate, and bladder, as well as at withdrawal of the cystoscope. DISCUSSION: This research will determine the effectiveness and safety of DPNB in men undergoing rigid cystoscopy. The results of this trial may have important implications for exploring the role of DPNB in analgesia for cystoscopy in men. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02502487 (6 Jul 2015).

Establishment of An Alloxan-induced Diabetes Model in Daphnia Pulex.

Objective To establish a Daphnia model of alloxan-induced diabetes. Methods Daphnia were exposed to three different concentrations of alloxan (3, 5, and 10 mmol/L) for 30 minutes. Blood glucose and survival rate were recorded for 72 hours after alloxan insult. Sequence analysis and phylogenetic inference for glucose transporters (GLUT) were clustered with the maximum-likelihood method. Using reverse transcription and quantitative polymerase chain reaction techniques, we investigated the transcriptional changes of GLUT at 12 hours after alloxan (5 mmol/L) exposure. Results Compared with control, 3 mmol/L, and 5 mmol/L as well as 10 mmol/L alloxan initially induced transient blood glucose decline by 15% for 2 hours and 12 hours respectively. In Daphnia with 5 and 10 mmol/L alloxan, their blood glucose was persistently raised by about 150% since after 24-hour insult. Survival rate of Daphnia exposure to alloxan with concentrations of 3, 5, and 10 mmol/L were 90%, 75%, and 25% respectively. We predicted seven GLUT genes in the Daphnia genome and successfully amplified them using real-time polymerase chain reaction. Two of seven GLUT transcripts were down-regulated in Daphnia with 5 mmol/L alloxan-induced diabetes. Conclusion Alloxan-induced diabetes model was successfully established in the Daphnia pulex, suggesting diabetes-relevant experiments can be conducted using Daphnia.

[Effects of Etomidate on mRNA Expression of Ion Channels in Daphnia Pulex].

Ion channels are involved in the mechanism of anesthetic action and side effect.The transcription and expression of ion channel genes can be modulated by general anesthetics.The adverse effect of continuous infusion of etomidate has been concerned.However,the effects of etomidate on mRNA expressions of ion channel genes remain unclear.In this study,we exposed Daphnia pulexin 250µmol/L of etomidate for 240 min and observed the change of heart rate,phototactic behavior and blood glucose during the period of exposure,as well as the mRNA expressions of 120 ion channel genes at the end of the experiment.Compared to the controls,heart rate,phototactic behavior and blood glucose were not influenced by 250µmol/L of etomidate.According to the quantitative PCR results,18 of 120Daphnia pulexion channel genes transcripts were affected by persistent 240 min exposure to 250µmol/L of etomidate:2genes were upregulated and 16 genes were down-regulated,suggesting that etomidate showed effects on many different ion channels in transcription level.Systematical exploration of transcriptional changes of ion channels could contribute to understanding of the pharmacological mechanism of etomidate.

[Effects of propofol, etomidate and ethanol on GPCR mRNA expression in Daphnia pulex ].

The mechanisms of general anesthesia, which was introduced about 170 years ago, remain poorly under- stood. Even less well understood are the effects of general anesthesia on the human body. Recently we identified 18 G-protein coupled receptor (GPCR) genes of Daphnia pulex, an invertebrate model organism. Phylogenetic analysis identified these genes to be the homologs of the human γ-aminobutyric acid, type B (GABAB) receptor, metabotropic glutamate receptors (mGluR), adrenergic receptor, serotonin (5-HT) receptor, dopamine receptor and muscarinic acetylcholine receptor (mAChR). Using reverse transcription and quantitative PCR techniques, we systematically measured the effects of propofol, etomidate and ethanol on these 18 GPCR mRNA expressions in Daphnia pulex.

Effects of midazolam, pentobarbital and ketamine on the mRNA expression of ion channels in a model organism Daphnia pulex.

BACKGROUND: Over the last few decades intensive studies have been carried out on the molecular targets mediating general anesthesia as well as the effects of general anesthetics. The γ-aminobutyric acid type A receptor (GABAAR) has been indicated as the primary target of general anaesthetics such as propofol, etomidate and isoflurane, and sedating drugs including benzodiazepines and barbiturates. The GABAAR is also involved in drug tolerance and dependence. However, the involvement of other ion channels is possible. METHODS: Using reverse transcription and quantitative PCR techniques, we systematically investigated changes in the mRNA levels of ion channel genes in response to exposure to midazolam, pentobarbital and ketamine in a freshwater model animal, Daphnia pulex. To retrieve the sequences of Daphnia ion channel genes, Blast searches were performed based on known human or Drosophila ion channel genes. Retrieved sequences were clustered with the maximum-likelihood method. To quantify changes in gene expression after the drug treatments for 4 hours, total RNA was extracted and reverse transcribed into cDNA and then amplified using quantitative PCR. RESULTS: A total of 108 ion channel transcripts were examined, and 19, 11 and 11 of them are affected by midazolam (100 µM), pentobarbital (200 µM) and ketamine (100 µM), respectively, covering a wide variety of ion channel types. There is some degree of overlap with midazolam- and pentobarbital-induced changes in the mRNA expression profiles, but ketamine causes distinct changes in gene expression pattern.In addition, flumazenil (10 µM) eliminates the effect of midazolam on the mRNA expression of the GABAA receptor subunit Rdl, suggesting a direct interaction between midazolam and GABAA receptors. CONCLUSIONS: Recent research using high throughput technology suggests that changes in mRNA expression correlate with delayed protein expression. Therefore, the mRNA profile changes in our study may reflect the molecular targets not only in drug actions, but also in chronic drug addiction. Our data also suggest the possibility that hypnotic/anesthetic drugs are capable of altering the functions of the nervous system, as well as those non-nerve tissues with abundant ion channel expressions.

Nano-crystal glass-ceramics obtained by crystallization of vitrified red mud.

Glass has been obtained by melting red mud from Shandong Province in China with different additives. Suitable thermal treatments were employed to convert the obtained glass into nano-crystal glass-ceramics. X-ray diffraction (XRD) patterns showed that the main crystalline phase in both the glass-ceramics is wollastonite (CaSiO3). These crystals are homogeneously dispersed within the parent glass, with an average crystal size of less than 100 nm. The size of nano-crystals varies when different thermal processes were used. Physical and mechanical properties, such as density, thermal expansion coefficient, hardness, and bending strength, of the two glasses have been examined and the corresponding microstructures are discussed. These results demonstrate that both glass-ceramics have potential for a wide range of construction application.