Effect of prolonged sedation with dexmedetomidine, midazolam, propofol, and sevoflurane on sleep homeostasis in rats.

BACKGROUND: Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative-hypnotics on sleep homeostasis is not clear. METHODS: We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague-Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index. RESULTS: Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01). CONCLUSIONS: In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis.

Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats.

BACKGROUND: Neurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics. However, the neurochemical substrates underlying changes in neurophysiologic complexity are poorly characterized. Cortical acetylcholine appears to relate to cortical activation and changes in states of consciousness, but the relationship between cortical acetylcholine and complexity has not been formally studied. We addressed this gap by analyzing simultaneous changes in cortical acetylcholine (prefrontal and parietal) and neurophysiologic complexity before, during, and after subanesthetic ketamine (10 mg/kg/h) or 50% nitrous oxide. METHODS: Under isoflurane anesthesia, adult Sprague Dawley rats (n = 24, 12 male and 12 female) were implanted with stainless-steel electrodes across the cortex to record monopolar electroencephalogram (0.5-175 Hz; 30 channels) and guide canulae in prefrontal and parietal cortices for local microdialysis quantification of acetylcholine levels. One subgroup of these rats was instrumented with a chronic catheter in jugular vein for ketamine infusion (n = 12, 6 male and 6 female). The electroencephalographic data were analyzed to determine subanesthetic ketamine or nitrous oxide-induced changes in Lempel-Ziv complexity and directed frontoparietal connectivity. Changes in complexity and connectivity were analyzed for correlation with concurrent changes in prefrontal and parietal acetylcholine. RESULTS: Subanesthetic ketamine produced sustained increases in normalized Lempel-Ziv complexity (0.5-175 Hz; P < .001) and high gamma frontoparietal connectivity (125-175 Hz; P < .001). This was accompanied by progressive increases in prefrontal (104%; P < .001) and parietal (159%; P < .001) acetylcholine levels that peaked after 50 minutes of infusion. Nitrous oxide induction produced a transient increase in complexity (P < .05) and high gamma connectivity (P < .001), which was accompanied by increases (P < .001) in prefrontal (56%) and parietal (43%) acetylcholine levels. In contrast, the final 50 minutes of nitrous oxide administration were characterized by a decrease in prefrontal (38%; P < .001) and parietal (45%; P < .001) acetylcholine levels, reduced complexity (P < .001), and comparatively weaker frontoparietal high gamma connectivity (P < .001). Cortical acetylcholine and complexity were correlated with both subanesthetic ketamine (prefrontal: cluster-weighted marginal correlation [CW r] [144] = 0.42, P < .001; parietal: CW r[144] = 0.42, P < .001) and nitrous oxide (prefrontal: CW r[156] = 0.46, P < .001; parietal: CW r[156] = 0.56, P < .001) cohorts. CONCLUSIONS: These data bridge changes in cortical acetylcholine with concurrent changes in neurophysiologic complexity, frontoparietal connectivity, and the level of consciousness.

Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia.

BACKGROUND: Cholinergic stimulation of prefrontal cortex (PFC) can reverse anesthesia. Conversely, inactivation of PFC can delay emergence from anesthesia. PFC receives cholinergic projections from basal forebrain, which contains wake-promoting neurons. However, the role of basal forebrain cholinergic neurons in arousal from the anesthetized state requires refinement, and it is currently unknown whether the arousal-promoting effect of basal forebrain is mediated through PFC. To address these gaps in knowledge, we implemented a novel approach to the use of chemogenetic stimulation and tested the role of basal forebrain cholinergic neurons in behavioral arousal during sevoflurane anesthesia. Next, we investigated the effect of tetrodotoxin-mediated inactivation of PFC on behavioral arousal produced by electrical stimulation of basal forebrain during sevoflurane anesthesia. METHODS: Adult male and female transgenic rats (Long-Evans-Tg [ChAT-Cre]5.1 Deis; n = 22) were surgically prepared for expression of excitatory hM3D(Gq) receptors or mCherry in basal forebrain cholinergic neurons, and activation of these neurons by local delivery of compound 21, an agonist for hM3D(Gq) receptors. The transgenic rats were fitted with microdialysis probes for agonist delivery into basal forebrain and simultaneous prefrontal acetylcholine measurement. Adult male and female Sprague Dawley rats were surgically prepared for bilateral electrical stimulation of basal forebrain and tetrodotoxin infusion (156 µM and 500 nL) into PFC (n = 9) or bilateral electrical stimulation of piriform cortex (n = 9) as an anatomical control. All rats were implanted with electrodes to monitor the electroencephalogram. Heart and respiration rates were monitored using noninvasive sensors. A 6-point scale was used to score behavioral arousal (0 = no arousal and 5 = return of righting reflex). RESULTS: Compound 21 delivery into basal forebrain of rats with hM3D(Gq) receptors during sevoflurane anesthesia produced increases in arousal score (P < .001; confidence interval [CI], 1.80-4.35), heart rate (P < .001; CI, 36.19-85.32), respiration rate (P < .001; CI, 22.81-58.78), theta/delta ratio (P = .008; CI, 0.028-0.16), and prefrontal acetylcholine (P < .001; CI, 1.73-7.46). Electrical stimulation of basal forebrain also produced increases in arousal score (P < .001; CI, 1.85-4.08), heart rate (P = .018; CI, 9.38-98.04), respiration rate (P < .001; CI, 24.15-53.82), and theta/delta ratio (P = .020; CI, 0.019-0.22), which were attenuated by tetrodotoxin-mediated inactivation of PFC. CONCLUSIONS: This study validates the role of basal forebrain cholinergic neurons in behavioral arousal and demonstrates that the arousal-promoting effects of basal forebrain are mediated in part through PFC.

Level of Consciousness Is Dissociable from Electroencephalographic Measures of Cortical Connectivity, Slow Oscillations, and Complexity.

Leading neuroscientific theories posit a central role for the functional integration of cortical areas in conscious states. Considerable evidence supporting this hypothesis is based on network changes during anesthesia, but it is unclear whether these changes represent state-related (conscious vs unconscious) or drug-related (anesthetic vs no anesthetic) effects. We recently demonstrated that carbachol delivery to prefrontal cortex (PFC) restored wakefulness despite continuous administration of the general anesthetic sevoflurane. By contrast, carbachol delivery to parietal cortex, or noradrenaline delivery to either prefrontal or parietal cortices, failed to restore wakefulness. Thus, carbachol-induced reversal of sevoflurane anesthesia represents a unique state that combines wakefulness with clinically relevant anesthetic concentrations in the brain. To differentiate the state-related and drug-related associations of cortical connectivity and dynamics, we analyzed the electroencephalographic data gathered from adult male Sprague Dawley rats during the aforementioned experiments for changes in functional cortical gamma connectivity (25-155 Hz), slow oscillations (0.5-1 Hz), and complexity (<175 Hz). We show that higher gamma (85-155 Hz) connectivity is decreased (p ≤ 0.02) during sevoflurane anesthesia, an expected finding, but was not restored during wakefulness induced by carbachol delivery to PFC. Conversely, for rats in which wakefulness was not restored, the functional gamma connectivity remained reduced, but there was a significant decrease (p < 0.001) in the power of slow oscillations and increase (p < 0.001) in cortical complexity, which was similar to that observed during wakefulness induced after carbachol delivery to PFC. We conclude that the level of consciousness can be dissociated from cortical connectivity, oscillations, and dynamics.SIGNIFICANCE STATEMENT Numerous theories of consciousness suggest that functional connectivity across the cortex is characteristic of the conscious state and is reduced during anesthesia. However, it is unknown whether the observed changes are state-related (conscious vs unconscious) or drug-related (drug vs no drug). We used a novel rat model in which cholinergic stimulation of PFC produced wakefulness despite continuous exposure to a general anesthetic. We demonstrate that, as expected, general anesthesia reduces connectivity. Surprisingly, the connectivity remains suppressed despite pharmacologically induced wakefulness in the presence of anesthetic, with restoration occurring only after the anesthetic is discontinued. Thus, whether an animal exhibits wakefulness or not can be dissociated from cortical connectivity, prompting a reevaluation of the role of connectivity in level of consciousness.

Strict mathematical model of mechanical stress birefringence for optical plates.

The mechanical stress birefringence (SBR) has received attention due to its effect on polarization in immersion lithography. In this paper, we present a strict mathematical model to obtain the correct SBR and slow-axis distributions of optical plates. First, the linear conditions of the model are solved to ensure the reasonable assembly of optical plates. Then we strictly define the plane principal stresses and slow-axis angle, and we give the correct expressions. Utilizing this model, we simulate a transmissivity variable plate, which is divided into 11 layers to obtain the effective SBR experienced by incident light crossing the plate. In this case, the simulation results achieve convergence. The validity of the model is verified by comparing the SBR and slow-axis distributions obtained by different expressions of the plate. This model is of great significance for polarization analysis in lithography systems and the reasonable assembly of optical elements.

Mechanical stress birefringence of optical plates.

Modeling the mechanical stress birefringence and slow-axis distributions of optical plates is critical for optical lithography systems. In this paper, the distributions of mechanical stress birefringence and the slow axes of optical plates were modeled by the finite element (FE) model, stress optic relations, and the ray-traced Jones matrices method. To validate this model, the load incremental approach was utilized to reduce the disturbance of residual birefringence in mechanical stress birefringence measurement. The measured distributions of birefringence and the slow axis of the optical plate show a good agreement with our numerical simulation results. This model provides a better understanding of simulation of mechanical stress birefringence and provides a reference for optical design and polarization analysis of other optical elements.

Surge of corticocardiac coupling in SHRSP rats exposed to forebrain cerebral ischemia.

Sudden death is an important but underrecognized consequence of stroke. Acute stroke can disturb central control of autonomic function and result in cardiac dysfunction and sudden death. Previous study showed that bilateral common carotid artery ligation (BCCAL) in the spontaneously hypertensive stroke-prone rat strain (SHRSP) is a well-established model for forebrain ischemic sudden death. This study aims to investigate the temporal dynamic changes in electrical activities of the brain and heart and functional interactions between the two vital organs following forebrain ischemia. EEG and ECG signals were simultaneously collected from nine SHRSP and eight Wistar-Kyoto (WKY) rats. RR interval was analyzed to investigate the cardiac response to brain ischemia. EEG power and coherence (CCoh) analysis were conducted to study the cortical response. Corticocardiac coherence (CCCoh) and directional connectivity (CCCon) were analyzed to determine brain-heart connection. Heart rate variability (HRV) was analyzed to evaluate autonomic functionality. BCCAL resulted in 100% mortality in SHRSP within 14 h, whereas no mortality was observed in WKY rats. The functionality of both the brain and the heart were significantly altered in SHRSP compared with WKY rats after BCCAL. SHRSP, but not WKY rats, exhibited intermittent surge of CCCoh, which paralleled the elevated CCCon and reduced HRV, following the onset of ischemia until sudden death. Elevated brain-heart coupling invariably associated with the disruption of the autonomic nervous system and the risk of sudden death. This study may improve our understanding of the mechanism of forebrain ischemia-induced sudden death. NEW & NOTEWORTHY This study demonstrates a marked surge of corticocardiac coupling in rats dying from focal cerebral ischemia, consistent with our earlier data in rats exposed to fatal asphyxia. Since the bidirectional electrical signal coupling (corticocardiac coherence) and communication (corticocardiac connectivity) between the brain and the heart are only identified in dying animals, they could be used as potential biomarkers to predict the risk of sudden death.

Identification of Hub Genes and Pathways in a Rat Model of Renal Ischemia-Reperfusion Injury Using Bioinformatics Analysis of the Gene Expression Omnibus (GEO) Dataset and Integration of Gene Expression Profiles.

BACKGROUND This study aimed to identify hub genes and pathways in a rat model of renal ischemia-reperfusion injury (IRI) using bioinformatics analysis of the Gene Expression Omnibus (GEO) microarray dataset and integration of gene expression profiles. MATERIAL AND METHODS GEO software and the GEO2R calculation method were used to analyze two mRNA profiles, including GSE 39548 and GSE 108195. The co-expression of differentially expressed genes (DEGs) were identified and searched in the DAVID and STRING databases for pathway and protein-protein interaction (PPI) analysis. Cytoscape was used to draw the PPI network. DEGs were also analyzed using the Molecular Complex Detection (MCODE) algorithm. Cytoscape and cytoHubba were used to analyze the hub genes and visualize the molecular interaction networks. Rats (n=20) included the IRI model group (n=10) and a control group (n=10). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure and compare the expression of the identified genes in rat renal tissue in the IRI model and the control group. RESULTS Ten hub genes were identified, STAT3, CD44, ITGAM, CCL2, TIMP1, MYC, THBS1, IGF1, SOCS3, and CD14. Apart from IGF1, qRT-PCR showed that expression of these genes was significantly increased in renal tissue in the rat model of IRI. The HIF-1alpha signaling pathway was involved in IRI in the rat model, which was supported by MCODE analysis. CONCLUSIONS In a rat model of renal IRI, bioinformatics analysis of the GEO dataset and integration of gene expression profiles identified involvement of HIF-1alpha signaling and the STAT3 hub gene.

Polarization simulation and analysis of residual birefringence in optical materials for a hyper-NA lithography illumination system.

A polarization simulation and analysis method was carried out for a hyper numerical apertures (NA) lithography illumination system which is affected by residual birefringence in optical materials. The lens is divided into multiple small annuli according to the finite element method, and the retardation distribution is obtained by setting the residual birefringence of each annulus. Finally, the polarized ray tracing is cleverly changed to geometric ray tracing. A hyper-NA lithography illumination system is modeled, and the residual birefringence is set between 0.1 nm/cm and 1 nm/cm. The simulation result shows that the degree of polarization performance degradation is proportional to the magnitude of residual birefringence, and the tolerance of residual birefringence in lens materials is below 1 nm/cm for the system. The polarization simulation and analysis method provides a powerful tool to calculate the polarized parameters of the system, which is helpful for selecting lens material of the hyper-NA illumination system.

Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest.

The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain-heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain's autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain.

Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells.

This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10-regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor-regulated gene pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer-related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif 10 regulates many gene pathways involving in the tumor development or progression.

Sevoflurane prevents stroke-induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I-dependent interaction between ß-arrestin 2 and extracellular signal-regulated kinases 1/2 in the rat hippocampus.

One of the most frequent psychological consequences of stroke is depression. Previous animal studies have demonstrated that post-conditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury. Thus, we hypothesized that repeated exposure to sevoflurane after transient ischemia can prevent the development of depressive-like behavior. To test this hypothesis, we induced transient cerebral ischemia via transient occlusion of bilateral common carotid arteries and examined the effects of subsequent repeated exposure to sevoflurane on sucrose preference, locomotor activity, and rearing activity in rats. To explore the putative neurobiological mechanisms, we further investigated the roles of hippocampal CB1 receptor in the behavioral effects of sevoflurane. We found that repeated sevoflurane exposures reversed ischemia-induced depressive-like behaviors. Furthermore, CB1 receptor inhibition in the dorsal hippocampus (DH) abolished the effects of sevoflurane exposures on ischemia-induced depressive-like behaviors. In addition, repeated sevoflurane exposures increased CB1 receptor expression and endocannabinoids levels in the DH of ischemic rats. Moreover, repeated sevoflurane exposures enhanced the expression of ß-arrestin 2, increased the activation of extracellular signal-regulated kinases (ERK)1/2, and promoted the interaction of ß-arrestin 2 and ERK1/2 in the DH, and such effects were reversed by CB1 receptor antagonism in the DH. Finally, ß-arrestin 2 expression and ERK1/2 activation in the DH were critical for the preventative effects of sevoflurane exposures on ischemia-induced depressive-like behaviors. Taken together, our results suggested that sevoflurane exposure after brain ischemia may prevent the development of depression, and such preventative effects of sevoflurane are likely ascribed to the activation of CB1 receptor-mediated ß-arrestin 2-ERK1/2 signaling pathways. We propose that the following mechanisms are critical for the preventative effects of sevoflurane against post-stroke depressive and anxiety behaviors: repeated sevoflurane exposure after transient brain ischemia enhances N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) levels and normalize cannabinoid receptor type 1 (CB1) receptor expression in the dorsal hippocampus, which results in enhanced interaction of ß-arrestin 2 and extracellular signal-regulated kinases (ERK1/2) and increased ERK1/2 activation, leading to decreased depressive and anxiety behaviors. We think these findings should provide a new strategy for treatment of post-stroke depression.

Surge of neurophysiological coherence and connectivity in the dying brain.

The brain is assumed to be hypoactive during cardiac arrest. However, the neurophysiological state of the brain immediately following cardiac arrest has not been systematically investigated. In this study, we performed continuous electroencephalography in rats undergoing experimental cardiac arrest and analyzed changes in power density, coherence, directed connectivity, and cross-frequency coupling. We identified a transient surge of synchronous gamma oscillations that occurred within the first 30 s after cardiac arrest and preceded isoelectric electroencephalogram. Gamma oscillations during cardiac arrest were global and highly coherent; moreover, this frequency band exhibited a striking increase in anterior-posterior-directed connectivity and tight phase-coupling to both theta and alpha waves. High-frequency neurophysiological activity in the near-death state exceeded levels found during the conscious waking state. These data demonstrate that the mammalian brain can, albeit paradoxically, generate neural correlates of heightened conscious processing at near-death.

Evaluation of the safety of sclerotomy incision in patients with choroidal colobomas with/without associated microcornea.

PURPOSE: Whether the position of the ora serrata is normal in patients with choroidal colobomas remains unknown. The aim of this study was to measure the distance between the ora serrata and limbus in these patients and define safe sclerotomy sites for standard three-port pars plana vitrectomy. METHODS: Twelve patients with choroidal colobomas with normal corneas (Group 1) and 11 patients with choroidal colobomas with microcornea (Group 2) were included in the study. Twelve patients with simple retinal detachment served as control subjects. All participants underwent vitrectomy. The distance between the limbus and ora serrata, corneal diameter, and ocular axial length were measured. RESULTS: The average corneal diameter was 10.9 mm in Group 1, 7.9 mm in Group 2, and 11.4 mm in the control group. The average distance between the limbus and ora serrata was 6.3 mm in Group 1, 7.6 mm in Group 2, and 6.2 mm in the control group. There were significant differences in the distance between the limbus and ora serrata among the 3 groups (analysis of variance test, P < 0.05). CONCLUSION: Our study confirmed that it is safe to perform a sclerotic puncture 4 mm posterior to the limbus for vitrectomy in patients with choroidal colobomas with or without microcornea.

[Resonance raman spectra of linear polymer molecule].

The present paper summarizes the characteristics of resonance Raman spectra of the linear polymer molecule, and its relations with the molecular structure, including: electronic spectra(ultraviolet-visible absorption spectrum), Raman spectra characteristics and its relations with external field; Modulation relation between the electron energy gap and CC atom vibration; Several experimental results were obtained: The UV-visible absorption spectra are red-shifted with decreasing temperature, increasing solvent density and reducing solution concentration, and because the linear polymer molecule has high structured order, decreasing pi electron energy gap; extended pi electronic delocalization, large effective conjugation length, large intensity of the Raman activity, Ramrnan spectrum are red-shifted, with large scattering cross section. "Am plitude modes" are the ideal theory models to study the linear polymer molecule.

Model construction and application for predicting pre-eclampsia by Sonoclot coagulation analyzer.

Maternal age has significantly increased among Chinese women, thereby posing risk of pregnancy-related complications. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, and coagulation analysis in conjunction with clinical signs and symptoms are generally used for its diagnosis with limited efficacy. Sonoclot coagulation analyzer is effective in assessing coagulation function used during cerebral surgery and cardiovascular surgery. However, its use has not been explored in preeclampsia. Here, we investigated the potential use of Sonoclot in diagnosing preeclampsia in obstetrics cases. Subjects meeting the screening criteria were divided either into a test group or a control group, according to whether they were preeclamptic or not. We recorded the Sonoclot-derived coagulation and the routine coagulation parameters including platelet function (PF), activated clotting time (ACT) and clot rate (CR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and platelet count. Regression analysis was done on the relevant parameters to assess the feasibility of Sonoclot analyzer in preeclampsia diagnosis. In parallel, changes in preeclampsia lncRNAs was also evaluated. Significant differences were recorded in PT and ACT between the two groups. In the monovariant logistic regression, PT and ACT appeared to be reliable predictor variables. In the multinomial logistic regression, a total of five regression steps were performed with decreasing AIC values. The K-fold cross validation resulted in an accuracy rate (ACC) of 77.5%, a false positive rate of 16.4%, and a false negative rate of 33.2%. lncRNAs ANRIL and HOXD-AS1 were found deregulated. Our findings indicate that Sonoclot may be useful for diagnosis of preeclampsia in obstetrics.

Psilocybin induces dose-dependent changes in functional network organization in rat cortex.

Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex (n=6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p<0.05], 2) increased frontal high gamma connectivity [p<0.05] and posterior theta connectivity [p≤0.049], and 3) increased frontal high gamma [p<0.05] and posterior theta [p≤0.046] network density. The medium gamma frontoparietal connectivity showed a nonlinear relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.

Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism.

The mammalian clock regulates major aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism. The biochemical basis for coordinated control of the circadian clock and diverse metabolic pathways is not well understood. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Mice lacking PGC-1alpha show abnormal diurnal rhythms of activity, body temperature and metabolic rate. The disruption of physiological rhythms in these animals is correlated with aberrant expression of clock genes and those involved in energy metabolism. Analyses of PGC-1alpha-deficient fibroblasts and mice with liver-specific knockdown of PGC-1alpha indicate that it is required for cell-autonomous clock function. We have thus identified PGC-1alpha as a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism.

A novel heterozygous c.733 T > G MYOC mutation associated with juvenile-onset open-angle glaucoma in a Chinese family.

AIMS: To detect mutations in juvenile-onset open-angle glaucoma in a Chinese family and to describe the characteristic ophthalmic phenotypes of this pedigree. METHODS: There were 14 individuals in this four-generation pedigree. All living members of the family underwent comprehensive ophthalmic examinations. Five patients presented with elevated intraocular pressures. All of them shared early-onset disease, with a mean onset age of 14.4 years and continuing aggressive damage to their optic nerves. Hyperpigmentation in the trabecular meshwork and sometimes-broad iris processes were noted in this family using gonioscopy. All exons of candidate genes (MYOC, OPTN, CYP1B1) were amplified using the polymerase chain reaction, and analysed with an ABI 3700XL Genetic Analyser. RESULTS: A heterozygous missense mutation in exon 3 (c.733 T > G) of the MYOC gene was found in the five JOAG patients and one 7-year-old boy with no ophthalmic manifestation of glaucoma, but it was absent in other members of the family and in the controls. This mutation resulted in a transversion of cysteine to glycine (Cys245Gly). CONCLUSIONS: We concluded the novel MYOC c.733 T > G mutation found in a Chinese family with JOAG caused a severe type of JOAG exhibiting early onset, high IOP, and severe optic nerve damage. Interestingly, unlike other reported MYOC mutation families, our patients exhibited marked angle pigmentation and iris processes.