Search

OBJECTIVE The serum kynurenine pathway metabolites kynurenic acid (KYNA), kynurenine (KYN), and tryptophan (TRP) were examined in chronic ketamine users and in schizophrenic patients. The correlations of the metabolites with sociodemographic data, clinical characteristics, and drug use status were analyzed. METHODS Seventy-nine healthy controls, 78 ketamine users, and 80 schizophrenic patients were recruited. Serum TRP, KYN, and KYNA levels were measured by high-performance liquid chromatography following tandem mass spectrometry (MS/MS). Psychotic symptoms were evaluated using the positive and negative syndrome scale (PANSS), the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI). RESULTS Serum levels of TRP, KYNA, and KYN (in ketamine users only) were lower in ketamine users and schizophrenic patients than in controls (p

Purpose This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady-state dose-corrected serum concentrations (C/D) of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV). Methods A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected. Results We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33-59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2-fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration. Conclusion Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy.

BackgroundActigraphs are wrist-worn devices that record tri-axial accelerometry data used clinically and in research studies. The expense of research-grade actigraphs, however, limit their widespread adoption, especially in clinical settings. Tri-axial accelerometer-based consumer wearable devices have gained worldwide popularity and hold potential for a cost-effective alternative. The lack of independent validation of minute-to-minute accelerometer data with polysomnographic data or even research-grade actigraphs, as well as access to raw data has hindered the utility and acceptance of consumer-grade actigraphs.MethodsSleep clinic patients wore a consumer-grade wearable (Huami Arc) on their non-dominant wrist while undergoing an overnight polysomnography (PSG) study. The sample was split into two, 20 in a training group and 21 in a testing group. In addition to the Arc, the testing group also wore a research-grade actigraph (Philips Actiwatch Spectrum). Sleep was scored for each 60-s epoch on both devices using the Cole-Kripke algorithm.ResultsBased on analysis of our training group, Arc and PSG data were aligned best when a threshold of 10 units was used to examine the Arc data. Using this threshold value in our testing group, the Arc has an accuracy of 90.3%±4.3%, sleep sensitivity (or wake specificity) of 95.5%±3.5%, and sleep specificity (wake sensitivity) of 55.6%±22.7%. Compared to PSG, Actiwatch has an accuracy of 88.7%±4.5%, sleep sensitivity of 92.6%±5.2%, and sleep specificity of 60.5%±20.2%, comparable to that observed in the Arc.ConclusionsAn optimized sleep/wake threshold value was identified for a consumer-grade wearable Arc trained by PSG data. By applying this sleep/wake threshold value for Arc generated accelerometer data, when compared to PSG, sleep and wake estimates were adequate and comparable to those generated by a clinical-grade actigraph. As with other actigraphs, sleep specificity plateaus due to limitations in distinguishing wake without movement from sleep. Further studies are needed to evaluate the Arc's ability to differentiate between sleep and wake using other sources of data available from the Arc, such as high resolution accelerometry and photoplethysmography.

The present study explored the early development of social attention of toddlers at high familial risk (HR) for autism spectrum disorder (ASD). Eighteen HR toddlers and twenty-two toddlers at low familial risk for ASD (LR) between 11 and 24 months were asked to watch paired social and non-social videos. We found that: (1) the initial social preference in HR group decreased with age, but not in LR group; (2) both groups showed significant social habituation across trials, but HR group habituated slightly slower as age increased. These findings suggest that atypical social attention could be an early characteristic of toddlers at high familial risk for ASD.

P-arsanilic acid (p-ASA), as a widely used feed additive, is potentially toxic to aquatic organisms and seriously affects the water environment. Therefore, the development of an intelligent multi-functional material for selective simultaneous detection and removal of p-ASA in water has become a top priority. Here, we report one case of novel nitrogen-rich two-dimensional metal–organic framework, Cu(I)-tpp (Htpp = 1-(4-(tetrazol-5-yl))3-(pyrzin-2-yl) pyrazol), which has outstanding fluorescence emission at 655 nm; and nitrogen-rich sites exposed on the surface make it an excellent self-assembly template to induce the formation of heterostructures. According to the target requirements, ZIF-8 is selected to construct the Cu(I)-tpp@ZIF-8 heterostructure by liquid-phase epitaxy ignoring the lattice mismatch problem. And the electronic structure of the Cu(I)-tpp framework is analyzed by electrostatic potential (ESP) to determine the nucleation site of ZIF-8. The prepared Cu(I)-tpp@ZIF-8 heterostructure assembles adsorption and fluorescence sensing properties, exhibiting significant adsorption (qmax = 303.0 mg g−1) and fluorescence quenching response (LOD = 0.4 µg·L−1) for p-ASA. Notably, Cu(I)-tpp@ZIF-8 achieves a special response to p-ASA that is different from other organic arsenic acids, especially compared with its isomer (o-ASA) and roxarsone (ROX). As a smart multifunctional material, Cu(I)-tpp@ZIF-8 realizes the specificity in the simultaneous detection and removal of p-ASA, presenting excellent application prospects in water quality monitoring.

Background Actigraphs are widely used portable wrist-worn devices that record tri-axial accelerometry data. These data can be used to approximate amount and timing of sleep and wake. Their clinical utility is limited, however, by their expense. Tri-axial accelerometer-based consumer wearable devices (so-called fitness monitors) have gained popularity and could represent cost-effective research alternatives to more expensive devices. Lack of independent validation of minute-to-minute accelerometer data for consumer devices has hindered their utility and acceptance. Methods We studied a consumer-grade wearable device, Arc (Huami Inc., Mountain View CA), for which minute-to-minute accelerometer data (vector magnitude) could be obtained. Twelve healthy participants and 19 sleep clinic patients wore on their non-dominant wrist, both an Arc and a research-grade actigraph (Actiwatch Spectrum, Philips, Bend OR) continuously over a period of 48 h in free-living conditions. Time-stamped data from each participant were aligned and the Cole-Kripke algorithm was used to assign a state of “sleep” or “wake” for each minute-long epoch recorded by the Arc. The auto and low scoring settings on the Actiwatch software (Actiware) were used to determine sleep and wake from the Actiwatch data and were used as the comparators. Receiver operating characteristic curves were used to optimize the relationship between the devices. Results Minute-by-minute Arc and Actiwatch data were highly correlated (r = 0.94, Spearman correlation) over the 48-h study period. Treating the Actiwatch auto scoring as the gold standard for determination of sleep and wake, Arc has an overall accuracy of 99.0% ± 0.17% (SEM), a sensitivity of 99.4% ± 0.19%, and a specificity of 84.5% ± 1.9% for the determination of sleep. As compared to the Actiwatch low scoring, Arc has an overall accuracy of 95.2% ± 0.36%, a sensitivity of 95.7% ± 0.47%, and a specificity of 91.7% ± 0.60% for the determination of sleep. Conclusions The Arc, a consumer wearable device in which minute-by-minute activity data could be collected and compared, yielded fundamentally similar sleep scoring metrics as compared to a commonly used clinical-grade actigraph (Actiwatch). We found high degrees of agreement in minute-to-minute data scoring for sleep and wake periods between the two devices.

Many IoT applications have stringent requirements on wireless transmission delay, but have to compete for channel access with other wireless traffic. Traditional techniques enable multiple access to wireless channels, but yield severe delay when the channel is congested. In this paper, we present EasyPass, a wireless PHY technique that allows multiple IoT devices to simultaneously transmit data over a congested wireless link without being delayed. The key idea of EasyPass is to exploit the excessive SNR margin in a wireless channel as a dedicated side channel for IoT traffic, and allow multiple access to the side channel by separating signals from different transmitters on the air. We implemented EasyPass on software-defined radio platforms. Experiment results demonstrate that EasyPass reduces the data transmission delay in congested IoT networks by 90%, but provides a throughput up to 2.5 Mbps over a narrowband 20MHz wireless link that can be accessed by more than 100 IoT devices.

There must be a non-negligible communication time-delay in the transmission process of wide area information through the power system. Communication time-delay will reduce the system stability or e...

The objective of this study was to evaluate the prevalence and relative risk of off-label prescription of antidepressants in Chinese pediatric outpatients according to China Food and Drug Administration (C-FDA) and USFDA regulations. Medical records of 18 459 pediatric outpatients were identified between 2013 and 2015. Patient characteristics, prevalence of off-label antidepressant prescriptions, and relative risk factors associated with off-label prescribing were analyzed. The results indicate that patients aged from 12 to 17 years account for 88.1% of antidepressant prescriptions, with the most commonly prescribed being sertraline (41.4%). In total, 90.0 and 84.1% of antidepressant prescriptions were off-labeled according to C-FDA and USFDA, respectively, and off-label indications was the most frequent type in this study. Depression was the most common indication for antidepressant treatment, followed by bipolar disorder and schizophrenia. Patients aged 12-17 years diagnosed with bipolar affective disorder have a high risk of off-label antidepressant prescription according to C-FDA regulations. Patients diagnosed with obsessive-compulsive disorder have a low risk of off-label antidepressant prescription according to both regulations. Therefore, future studies are recommended to collect evidence to safeguard appropriate prescribing of off-label antidepressants among pediatric patients.

Restricted and repetitive behaviors (RRBs) are one of the core features of autism spectrum disorders (ASD). RRBs encompass a broad range of heterogeneous behaviors, such as repetitive and stereotyped motor behavior or speech, atypical sensory behavior, inflexible interest and rituals, and insistence on the sameness of environment. While a large amount of previous research has focused on social deficits in ASD, little attention has been paid to their RRBs. The definition, classification, and underlying mechanism of RRBs have remained to be clarified. Recently, Diagnostic and Statistical Manual of Mental Disorders (5th ed, DSM-V) has classified RRBs into several subcategories and renewed the diagnostic criteria of RRBs. New theories and evidence from neurobiological, cognitive psychological, and developmental psychological research are also emerging about the etiology of RRBs. The first aim of this review is to introduce the newest definition and subcategories of RRBs based on DSM-V. We also discuss and compare different structural models of RRBs derived from several factor analysis studies. The second aim is to summarize the current assessment tools of RRBs in autism. Besides the “golden standard” -- the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R), and several common used questionnaires such as Repetitive Behavior Scale-Revised (RBS-R) and Repetitive Behavior Questionnaire-2 (RBQ-2), new techniques including eye-tracking, accelerometry, and electrodermal activity (EDA) have been applied into the studies of RRBs. The third aim of this review is to discuss the potential causal origins underlying the RRBs. The neurobiological and cognitive mechanism of RRBs, as well as other factors that directly related to the onset of RRBs have been summarized. The neurobiological evidence indicates that the atypical activity of neurotransmitters, the imbalanced activity among the corticostriatal circuits, and the neuroanatomical alterations play important roles on the RRBs. From the perspective of cognitive psychology, classical theories such as executive functions, weak central coherence, extreme male brain theory, and operational conditioning all offer their own explanations for the onset of RRBs. Besides, the hyper- or hypo-arousal theory indicates that RRBs may function as coping strategies for the individuals with ASD to regulate levels of arousal or anxiety, with the intolerance of uncertainty as the mediator. The evidence from developmental psychology focus on the developmental trajectory of RRBs across age. Results from longitudinal studies identify the significant influence of age and intelligence on the developmental trajectory of RRBs. Severe impacts of environmental deprivation and social isolation on the RRBs have also been shown in animal and human studies and provide implication for early intervention. Finally, several future directions for the research on RRBs in ASD have also been proposed based on the current literature. We recommend future research that focuses on the united standard for classification and the direct connection between neurobiology and behavior. Also, a clear understanding of the developmental trajectories of RRBs in typical developing children and children with ASD is of importance for effective early interventions. Last but not least, the characteristics of parents and the prenatal maternal stress are worthy of future investigations.

PURPOSE/BACKGROUND Blonanserin is a novel antipsychotic drug approved for the treatment of schizophrenia in East Asia. The main objective of the present study was to investigate the effect of alcohol on the pharmacokinetic properties of blonanserin and its metabolite N-deethyl blonanserin in healthy Chinese male subjects under fasting conditions. METHODS/PROCEDURES The study was designed as a randomized, open-label, crossover clinical investigation in 10 male volunteers, each of whom received 2 treatments under fasted conditions: treatment A, blonanserin (8 mg) with water, and treatment B, blonanserin (8 mg) with alcohol (1 mL/kg). FINDINGS/RESULTS The average values of areas under the curve (AUCs) and mean peak plasma concentrations (Cmax) were noticeably increased by alcohol consumption. In treatment A, average values of AUC0-24h, AUC0-∞, and Cmax were 3178 ng/h/L, 3879 ng/h/L, and 492 ng/L for blonanserin, and 1932 ng/h/L, 4208 ng/h/L, and 137 ng/L for N-deethylated blonanserin, respectively. In treatment B, AUC0-∞ and Cmax were both increased 2.4-fold for blonanserin and 1.4-fold and 1.7-fold, respectively, for N-deethylated blonanserin (P < 0.05). Compared with treatment A, clearance (Clz/F) of blonanserin and N-deethylated blonanserin decreased significantly (2.4-fold and 1.7-fold, respectively) in treatment B (P < 0.05). Alcohol delayed the absorption and reduced the clearance of blonanserin, leading to a 1.8-fold increase in the time to reach Cmax (Tmax) and half life time (t1/2) (P < 0.05). IMPLICATIONS/CONCLUSIONS Alcohol increased the bioavailability of blonanserin and N-deethyl blonanserin in healthy subjects and the marked effect of alcohol on blonanserin bioavailability should be taken into consideration in deciding dosing schedules in clinical therapy.

This paper focuses on synchronized wireless measurement of high-voltage (HV) power system frequency using mobile embedded systems (MESs) integrated with a wireless electric field sensor (WEFS). Unlike traditional synchronized frequency measurement devices, which rely on potential transformers and current transformers physically connected to system elements, a WEFS is used to realize wireless signal acquisition in the vicinity of any HV apparatus. The MES performs real-time frequency estimation using a recursive discrete Fourier transform based algorithm. Network time protocol (NTP) is used for time synchronization, increasing the system flexibility by eliminating global positioning system reliance. An NTP-based synchronized sampling control method is proposed and implemented in MES to compensate the sampling time error caused by local time drift and division residue. The proposed system has the advantages of portability and lower cost, making it highly accessible and useful for a wide array of synchronized frequency measurement applications. Experiment results verify the accuracy and effectiveness of the proposed system.

The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUCt) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice.

Exposure to Bisphenol A (BPA) has been associated with the development of nonalcoholic fatty liver disease (NAFLD) but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study was designed to explore whether exposure to BPA-triggered abnormal steatosis and lipid accumulation in the liver could be modulated by miR-192. We showed that male post-weaning C57BL/6 mice exposed to 50μg/kg/day of BPA by oral gavage for 90days displayed a NAFLD-like phenotype. In addition, we found in mouse liver and human HepG2 cells that BPA-induced hepatic steatosis and lipid accumulation were associated with decreased expression of miR-192, upregulation of SREBF1 and a series of genes involved in de novo lipogenesis. Downregulation of miR-192 in BPA-exposed hepatocytes could be due to defective pre-miR-192 processing by DROSHA. Using HepG2 cells, we further confirmed that miR-192 directly acted on the 3'UTR of SREBF1, contributing to dysregulation of lipid homeostasis in hepatocytes. MiR-192 mimic and lentivirus-mediated overexpression of miR-192 improved BPA-induced hepatic steatosis by suppressing SREBF1. Lastly, we noted that lipid accumulation was not a strict requirement for developing insulin resistance in mice after BPA treatment. In conclusion, this study demonstrated a novel mechanism in which NAFLD associated with BPA exposure arose from alterations in the miR-192-SREBF1 axis.

Previous research has demonstrated abnormal trust and deception behaviors in children with Autism Spectrum Disorders (ASD), and we aimed to examine whether these abnormalities were primarily due to their specific deficits in social learning. We tested 42 high-functioning children with ASD and 38 age- and ability-matched typically developing (TD) children in trust and deception tasks and a novel condition with reduced social components. Results indicated that while TD children improved their performance with more social components, children with ASD lacked this additional performance gain, though they performed similarly as TD children in the condition with reduced social components. Our findings highlight that deficits of ASD in trust and deception are primarily associated with failure of use of social cues.

L-Asparagine (ASN) is the catalyze substrate of L-asparaginase (ASNase), which is an important drug for acute lymphoblastic leukemia (ALL) patients. The ASN level is found to be closely associated with the effectiveness of ASNase treatment. In this study, a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method was developed for the determination of ASN in the human serum using a stable isotope-labeled internal standard (ASN-D3). Serum samples were prepared by a one-step precipitation procedure using methanol and separated by an Agilent HILIC Plus column with the mobile phase of methanol-water (95 : 5, v/v, containing 5 mM ammonium formate and 0.1% formic acid), at a constant flow rate of 0.3 mL/min. Mass spectrometric analysis was conducted using multiple-reaction monitoring in the positive electrospray ionization mode. Serum ASN concentrations were determined over a linear calibration curve range of 2–200 μM, with acceptable accuracies and precisions. The validated HILIC-MS/MS method was successfully applied to the quantification of ASN levels in the serum from patients with ALL. Collectively, the research may shed new light on an alternative rapid, simple, and convenient quantitative method for determination of serum ASN in ALL patients treated with ASNase.

Targeted metabolomics analysis based on triple quadrupole (QQQ) MS coupled with multiple reaction monitoring mode (MRM) is the gold standard for metabolite quantification and it is widely applied in metabolomics. However, standard compounds for each metabolite and the corresponding analogs are necessary for quantitative measurements. To identify the differentially present metabolites in various groups, determining the relative concentration of metabolites would be more efficient than accurate quantification. In this study, a relatively quantitative targeted method was established for metabonomics research, on the basis of hydrophilic interaction liquid chromatography (HILIC)/QQQ MS operated in MRM mode. The quality control-base random forest signal correction algorithm (QC-RFSC algorithm) was applied for quality control instead of the internal standard method. High quality relative quantification was achieved without internal standards, and integrated peak areas were successfully used for statistical and pathway analyses. Amino acids and neurotransmitters (dopamine, kynurenic acid, urocanic acid, tryptophan, kynurenine, tyrosine, valine, threonine, serine, alanine, glycine, glutamine, citrulline, GABA, glutamate, aspartate, arginine, ornithine and histidine) in serum samples were simultaneously determined with the newly developed method. To demonstrate the applicability of this method in large-scale analyses, we analyzed the above metabolites in serum from patients with major depression. The serum levels of glutamate, aspartate, threonine, glycine and alanine were significantly higher, and those of citrulline, kynurenic acid and urocanic acid were significantly lower, in patients with major depression than in controls. This is the first report of the difference in urocanic acid, a compound reported to improve glutamate biosynthesis and release in the central nervous system, between healthy controls and patients with major depression.

1. A new oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone is effective in improving the symptoms of common cold. The pharmacokinetic properties of the individual components were evaluated in a randomized, open-label, four-period study in 12 healthy Chinese volunteers following single and multiple doses. The data were compared with data for the individual ingredients in Antuss®. 2. In the single-dose period, exposure levels (AUC and Cmax) for guaifenesin, pseudoephedrine and hydrocodone increased directly as the dose of the oral liquid formulation increased from 5 to 15 mL. Only minor amounts of guaifenesin and hydrocodone were excreted in urine (∼0.10% and 4.66%, respectively). Pseudoephedrine was mainly excreted unchanged, with 44.95% of the dose excreted in urine within 24 h. After multiple dosing, there was no obvious accumulation of any drug, as assessed by AUC. When considering Cmax, there was a trend toward accumulation of hydrocodone and pseudoephedrine. The pharmacokinetic profiles of guaifenesin and pseudoephedrine in the oral liquid formulation were similar to those in the branded preparation, Antuss®. 3. The newly developed oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone was safe and well tolerated and might provide a reliable alternative to the branded formulation for patients with common colds.

Wide-area monitoring systems (WAMS) are beincreasingly vital for enhancing power grid operators' situational awareness capabilities. As a pilot WAMS that was initially deployed in 2003, the frequency monitoring network FNET/GridEye uses GPS-time-synchronized monitors called fredisturbance recorders (FDRs) to capture dynamic grid behaviors. Over the past ten years, a large number of publications to FNET/GridEye have been reported. In this paper, most recent developments of FNET/GridEye sensors, data centers, and data analytics applications are reviewed. These demonstrate that FNET/GridEye will become a costeffective situational awareness tool for the future smart grid.

The kynurenine pathway, in which tryptophan is metabolized to kynurenine and kynurenic acid, has been linked to depression. A rapid and highly reproducible liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method were established for determining tryptophan, kynurenine and kynurenic acid in human serum. Biological samples were precipitated with methanol before separation on an Agilent Eclipse XDB-C18. The stable-isotope-labeled internal standards (kynurenine-13C415N and kynurenic acid-d5) were used for quantification. Detection was performed using multiple reaction monitoring in electrospray ionization mode at m/z 205.1→188.1 for tryptophan, m/z 209.1→146.1 for kynurenine, m/z 190.1→144.1 for kynurenic acid. Good linearity of analyte to internal standard peak area ratios was seen in the concentration range 1,000-50,000 ng/mL for tryptophan, 100-5,000 ng/mL for kynurenine and 1-60 ng/mL for kynurenic acid. Pooled drug-free human serum was purified using activated charcoal and the method was shown to be linear, with validation parameters within acceptable limits. The newly developed method was successfully used to determine concentrations of tryptophan, kynurenine and kynurenic acid in serum from 26 healthy volunteers and 54 patients with depression. Concentrations of tryptophan and kynurenine were lower in serum from depressed individuals than from healthy individuals.

Real-time awareness of the phasor state, including the volatile frequency and phase angle, is critical to maintain reliable and stable operations of the power grid. However, the high cost and low accessibility of current synchrophasors restrict their large-scale deployment over highly distributed microgrids. In this paper, we present a practical system design for monitoring the microgrid frequency and phase angle over mobile platforms and significantly reduce the cost of such monitoring. Being different from current synchrophasors, our system does not rely on continuous GPS reception and hence it is highly accessible and applicable to heterogeneous microgrid scenarios. We develop various techniques to provide the timing signal that is necessary for precise microgrid monitoring. For frequency monitoring, the network time protocol is exploited for time synchronization. For phase angle monitoring which requires a higher timing accuracy, 200 Hz primary synchronization signal being embedded in the 4G LTE cellular signal is harvested for time synchronization. We implemented our system over off-the-shelf smartphones with a few peripheral hardware components and realized an accuracy of 1.7 MHz and 0.01 rad for frequency and phase angle monitoring, respectively. Although the accuracy of the prototype is lower than that of the GPS-based systems, the system could still satisfy the requirements of microgrid monitoring. The total cost of the system can be controlled within $100 and no installation cost is required. Experiment results compared with the traditional frequency disturbance recorders verify the effectiveness of our proposed system.

Internet of Things has stringent requirements on the wireless network throughput for timely transmission of the big data being produced. In order to maximize the throughput over dynamic fluctuations of wireless channel quality, current wireless systems adapt the link rate to the instantaneous channel condition, but fail to fully utilize the channel capacity due to the discrete choices of available link rates and the gap between these rates. Instead, in this paper we present vMod, a lightweight and practical solution towards maximum wireless network throughput by redesigning the wireless link rates from discrete to continuous. The key idea of vMod is to modulate a fractional number of data bits into each symbol by employing the Variable-Length Code (VLC), which is able to statistically yield any link rate. We implemented vMod on software-defined radio platforms. Experiment results demonstrate that under highly dynamic wireless network conditions, vMod greatly improves the WiFi throughput by 30% over a single narrowband link, but incurs only negligible overhead.

Adjunctive therapy with olanzapine and fluoxetine has been shown to be beneficial in treatment-resistant depression and the depressive phase of bipolar disorder. Consensus guidelines issued by the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie strongly recommend that patients taking olanzapine undergo therapeutic drug monitoring (TDM), and suggest that TDM is useful for patients taking fluoxetine. The aim of the current study was to develop and validate a sensitive, practical, and robust liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for simultaneous determination of olanzapine, fluoxetine, and norfluoxetine in human plasma for routine TDM. Simple liquid-liquid extraction using ethyl acetate was used to extract olanzapine, fluoxetine, and norfluoxetine from 200 μL of pre-basified human plasma. Analytes were separated on an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 5 μm) eluted with a mobile phase consisting of methanol:20 mM ammonium formate buffer (82.5:17.5, v/v), and then quantified using an electrospray ionization source operated in positive ion multiple reaction monitoring mode. The linear range for the analytes was 0.2–25 ng/mL, covering the vast majority of levels encountered in real-life samples. A weighting factor of 1/x2 best fit the calibration curves. The mean internal standard-normalized matrix effects for all analytes were 99.5%–110%. The extraction recoveries were 75%–85% for olanzapine and olanzapine‑d3, and 58%–69% for fluoxetine, norfluoxetine, and their deuterated internal standards. Accuracy and precision values also met the acceptance criteria. The stability assessments showed that QC samples containing the three analytes were stable for at least 1 d at room temperature, 21 d at −70 °C, and through three freeze-thaw cycles. Post-preparation storage for 2 d in the autosampler did not cause obvious degradation of the investigated compounds. This validated high performance LC-MS/MS method was successfully applied to a pharmacokinetic study in healthy male volunteers.

The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate (TMPP) in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes: intranasal (i.n.), intragastric (i.g.) and intravenous (i.v.) administration. After i.n., i.g. and i.v. administration of a single-dose at 10 mg/kg, cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals. The concentration of TMPP in the samples was analyzed by HPLC. The area under the concentration–time curve (AUC) and the ratio of the AUCbrain to the AUCplasma (drug targeting efficiency, DTE) was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration. After i.n. administration, TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex (tmax=15 min). The ratio of the AUCbrain dialysates value between i.n. route and i.v. injection was 0.68, which was greater than that obtained after i.g. administration (0.43). The systemic bioavailability obtained with i.n. administration was greater than that obtained by the i.g. route (86.33% vs. 50.39%), whereas the DTE of the nasal route was 78.89%, close to that of oral administration (85.69%). These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation, and then crosses the blood–brain barrier (BBB) to reach the cerebral cortex. Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches., Graphical abstract Pharmacokinetic analysis of tetramethylpyrazine phosphate (TMPP) in plasma and extracellular fluid in cerebral cortex of rats after intranasal, intragastric and intravenous administration was carried out with microdialysis sampling and HPLC-UV analysis. The results indicated that TMPP was rapidly absorbed from the nasal mucosa into the systemic circulation and then across the blood–brain barrier to reach the cerebral cortex. Intranasal administration of TMPP may be a promising alternative to intravenous and oral approaches.

White mustard (Sinapis alba L.), a traditional Chinese medicine, is widely used in China for clinical prevention and treatment of the common winter diseases of asthma and bronchitis by percutaneous administration in the summer. The present study is to investigate the skin penetration behavior of white mustard extract to elucidate the possible mechanism underlying its immune regulation activity. The principle active compound of the extract, sinapine thiocyanate (ST), was used as a marker. The skin penetration of ST in white mustard extract was examined in vitro and in vivo. In vitro study on excised guinea pig hairless skin using Franz diffusion cell revealed ST can permeate through the skin and also accumulate in the skin. In vivo study was carried out on the guinea pig hairless skin for 24 h, and then skin was excised for frozen section, ST from the sections were extracted to quantify the amount of drug in different skin layers. The detailed distribution of ST showed that it accumulated in the epidermis, especially in the stratum corneum. After treatment with white mustard extract for 24h, the skin was stained with ATPase, and the morphometric parameters of epidermal LCs were compared to the untreated control through image-analysis system. A statistically significant reduction in LC density and increase in shape factor were observed. Cytokines related to LCs migration including interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were also measured after white mustard extract treated at different time points. Compared to the untreated group, white mustard extract significantly enhanced the release of IL-1β and TNFα. The morphometric changes of LCs and the local cytokine release after topical white mustard treatment may explain the activity of the white mustard extract against asthma and bronchitis.

Performance of modern cognitive and interactive mobile applications highly depends on the data transmission delay in the wireless link that is vital to supporting real-time wireless traffic. To eliminate wireless network congestion caused by large amounts of concurrent network traffic and support such real-time traffic, traditional schemes adopt various flow control and QoS-aware traffic scheduling techniques, but fail when the amount of network traffic further increases. In this paper, we present a novel design of high-throughput wireless side channel, which operates concurrently with the existing wireless network channel over the same spectrum but dedicates to real-time traffic. Our key idea of realizing such a side channel is to exploit the excessive SNR margin in the wireless network to encode data as patterned interference. We design such patterned interference in form of energy erasure over specific subcarriers in an OFDM-based wireless network, and achieve a data rate of 1.25 Mbps in the side channel without affecting the existing wireless network links. Experimental results over software-defined radio platforms demonstrate the effectiveness of our side channel design in reducing the latency of real-time wireless traffic, while providing sufficient data throughput for such traffic.

Peramivir, an antiviral agent for intravenous administration, is used to treat progressive influenza in patients with serious complications. The present study was designed to determine the pharmacokinetics of single and multiple intravenous infusions of peramivir in healthy Chinese subjects.Single (150, 300 and 600 mg) and multiple (600 mg) doses of peramivir were intravenously administered to 12 healthy Chinese subjects. There was a 7-day washout period between dosing periods. Blood samples were collected in heparinized tubes at various times. Plasma peramivir and urine peramivir concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry method.Following single doses of peramivir (150, 300 and 600 mg), the maximum concentration (C max) values were 12,416 ± 3078, 23,147 ± 3668 and 44,113 ± 3787 µg/L, respectively, and the area under the plasma concentration-time curve (AUC) from 0 h to infinity post-dose (AUC∞) values were 24.68 ± 6.48, 47.33 ± 9.22 and 92.43 ± 12.72 mg·h/L, respectively. C max, AUC from 0 to 36 h (AUC0-36) and AUC∞ of peramivir increased proportionally with the dose, and no trend towards accumulation after multiple doses was observed. About 65 % of the peramivir was excreted unchanged in the urine within the first 24 h.Peramivir pharmacokinetics were dose proportional with increasing doses, with no accumulation after multiple dosing. Peramivir was generally well tolerated, and no serious adverse events occurred.

1. Ingestion of grapefruit juice and food could be factors affecting the pharmacokinetics of pirfenidone, a promising drug for treatment of idiopathic pulmonary fibrosis. 2. A randomized, open-label, three-period crossover study was carried out in 12 healthy Chinese male volunteers who were randomized to one of the three treatments: pirfenidone tablets (0.4 g) were orally administered to fasted or fed subjects, or with grapefruit juice. The washout period was 7 d. 3. Significantly reduced maximum plasma concentration (Cmax, 5.0 5 ± 1.39 versus 10.9 0 ± 2.94 mg·L(- 1)), modestly affected area-under-the-plasma concentration-time curve (AUC) from time zero to 12 h post dosing (AUC0-12 h, 21.8 9 ± 6.47 versus 26.1 6 ± 7.32 mg·h·L(- 1)) and delayed time to reach Cmax (Tmax) were observed in fed group compared with fasted group. Similar effects on Cmax (5.8 2 ± 1.23 versus 10.9 0 ± 2.94 mg·L(- 1)) and AUC0-12 h (modest but not statistically significant, 24.4 4 ± 7.40 versus 26.1 6 ± 7.32 mg·h·L(- 1)) were observed for grapefruit juice compared to fasted subjects. 4. Co-administration of pirfenidone with grapefruit juice resulted in modestly reduced overall oral absorption and significantly reduced peak concentrations compared to fasting, which was similar to effect of food ingestion. No adverse events were observed in the study, but relatively dramatic reduction of peak concentrations should raise concerns for clinical efficacy and safety.

1. Pitavastatin is an effective treatment for primary hyperlipidemia and mixed dyslipidemia. The aim of the present study was to investigate the effect of food on the pharmacokinetic properties and bioequivalence of the original, branded, formulation of pitavastatin calcium and a new generic formulation in healthy Chinese male subjects under fasting and fed conditions. 2. Under fasting and fed conditions, 90% CIs of the geometric mean of generic/branded AUC0-48 h ratios were 92.2-102.4%, 93.1-104.5%, the ratios of ln(AUC0-∞) were 92.6-103.7%, 93.2-103.5%, and ln(Cmax) ratios were 90.7-110.3%, 84.7-100.8%, respectively. The generic and branded formulations were bioequivalent in terms of rate and extent of absorption under both the conditions. The average values of AUC0-48 h, AUC0-∞ and Cmax decreased noticeably following a high-fat breakfast. Values for AUC0-48 h were 87.69% and 83.7%, values for AUC0-∞ were 87.5% and 84.6%, and values for Cmax were 45.0% and 50.4% in subjects given the generic and branded preparations, respectively. The absorption of pitavastatin calcium tablets was delayed following a high-fat meal, with Tmax increasing by up to 2.43-fold. 3. Both formulations were generally well tolerated, with no serious adverse reactions reported. The newly developed generic formulation may provide a reliable alternative to the branded tablets for patients with primary hyperlipidemia or mixed dyslipidemia.

In smart grids, the deviation of frequency and phase angle serves as an important indicator of abnormal events, the detection of which is critical to maintain reliable and stable operations of the power grid. However, the high cost and low accessibility of current power grid monitoring systems restrict their large-scale deployment over highly distributed microgrids. In this paper, we present a practical frequency and phase angle monitoring system design over mobile platforms, which significantly reduces the cost of power grid monitoring by utilizing the functionalities of modern mobile devices. We harvest the 200 Hz Primary Synchronization Signal (PSS) embedded in the 4G Long Term Evolution (LTE) cellular signal for time synchronization in power grid monitoring, replacing the Pulse-Per-Second (PPS) signal that is retrieved from GPS receivers and being used by current monitoring systems. We implement our system over realistic smartphones with a few peripheral hardware, and realize a frequency monitoring accuracy of 0.2 mHz and a phase angle monitoring accuracy of 0.01 rad. Experiment results compared with the traditional Frequency Disturbance Recorders (FDRs) verify the effectiveness of our proposed system.

Reviewed the summary and classification of PV mounting system for solar power station. Analyzed the advantages and disadvantages of the optimum tilt angle of fixed, the horizontal single-axis tracking type, the diagonal single axis tracking type and the dual axis tracking type mounting system for solar power station, compared the performance of the different installation methods and materials of the PV mounting system from the bearing capacity, corrosion resistance, beautiful degree ,stability, construction speed, connection strength and other aspects. Introduced in detail of PV mounting system for solar power station design principles and load cases, compared and analyzed comprehensive performance of the four forms of PV mounting systems from the covering area, solar radiation gain, the capacity gain and other aspects. Summarized the problems and proposed solutions of existing PV mounting system, and proposed the development direction of PV mounting system for solar power station. Keywords-Solar; PV systems; Mounting; Tracking system; solar power station

With the sustainable development of economy, sol ar energy has been widely used as a clean energy, photovolta ic industry has been rapid development. This article summar izes the summary and classification of solar photovoltaic mo dules frame; Comparative analysis is mainly focused on the aluminum frame, stainless steel frame and composite frame etc. The advantages and disadvantages of solar energy photo voltaic component frame; Aluminum frame, with its good pe rformance, the advantage, low cost and large-scale applicatio n. Also expounds on the role and structure and fixed way an d way of surface treatment of aluminum frame, and the stru cture of different, contrasted the fixed way and surface treat ment method, analyzes its advantages and disadvantages. Fi nally this paper summarizes the present status of solar photo voltaic modules border, summarizes the problems that exist i n the solar photovoltaic modules border, and explains the ca uses of the problem; Put forward the photovoltaic componen t frame will towards lightweight, refinement, high strength, t he direction of integration. Keywords-Solar;PV modules;Border;Encapsulation; alumi num

Energy shortage and environment pollutes aggravate ceaselessly all over the world. As a green clean pollution-free renewable energy, tidal current energy has characteristics such as large reserves, wide distribution, predictability, little environmental pollution, etc. Development and utilization of tidal energy has important practical significance to ease the energy shortage and reduce the pollution of the environment. The western developed countries take the leading position in tidal current energy utilization, having entered early stage of commercialize. In this paper, the state of exploiting tidal current energy, the development of tidal current power generation and the related technical problems in tidal current energy development were introduced. The technical characteristics of different turbines were compared. Based on the technology and application comparative study, some suggests are given to the tidal current energy development and utilization in China.

Mobile Cloud Computing (MCC) bridges the gap between limited capabilities of mobile devices and the increasing users' demand of mobile multimedia applications, by offloading the computational workloads from local devices to the remote cloud. Current MCC research focuses on making offloading decisions over different methods of a MCC application, but may inappropriately increase the energy consumption if having transmitted a large amount of program states over expensive wireless channels. Limited research has been done on avoiding such energy waste by exploiting the dynamic patterns of applications' run-time execution for workload offloading. In this paper, we adaptively offload the local computational workload with respect to the run-time application dynamics. Our basic idea is to formulate the dynamic executions of user applications using a semi-Markov model, and to further make offloading decisions based on probabilistic estimations of the offloading operation's energy saving. Such estimation is motivated by experimental investigations over practical smart phone applications, and then builds on analytical modeling of methods' execution times and offloading expenses. Systematic evaluations show that our scheme significantly improves the efficiency of workload offloading compared to existing schemes over various smart phone applications.

Mobile phone sensing is a critical underpinning of pervasive mobile computing, and is one of the key factors for improving people’s quality of life in modern society via collective utilization of the on-board sensing capabilities of people’s smartphones. The increasing demands for sensing services and ambient awareness in mobile environments highlight the necessity of active participation of individual mobile users in sensing tasks. User incentives for such participation have been continuously offered from an application-centric perspective, i.e., as payments from the sensing server, to compensate users’ sensing costs. These payments, however, are manipulated to maximize the benefits of the sensing server, ignoring the runtime flexibility and benefits of participating users. This paper presents a novel framework of user-centric incentive design, and develops a universal sensing platform which translates heterogenous sensing tasks to a generic sensing plan specifying the task-independent requirements of sensing performance. We use this sensing plan as input to reduce three categories of sensing costs, which together cover the possible sources hindering users’ participation in sensing.

The objective of this study was to develop proniosome-derived niosomes for topical ophthalmic delivery of Tacrolimus (FK506). The FK506 loaded proniosomes containing poloxamer 188 and lecithin as surfactants, cholesterol as a stabilizer, and minimal amount of ethanol and trace water reconstituted to niosomes prior to use. The stability of FK506 loaded proniosomes was assessed, and the morphology, size, zeta potential, surface tension, and entrapment efficiency of the derived niosomes were characterized, indicating they were feasible for instillation in the eyes. The in vitro permeation of FK506 through the freshly excised rabbit cornea, the cumulative permeation amount of FK506 from niosomes, and the drug retention in the cornea all exhibited significant increase as compared to 0.1% FK506 commercial ointments. The in vivo ocular irritation test of 0.1% FK506 loaded niosomes instilled 4 times per day in rat eyes for 21 consecutive days showed no irritation and good biocompatibility with cornea. The in vivo anti-allograft rejection assessment was performed in a Sprague-Dawley (SD) rat corneal xenotransplantation model. The results showed treatment with 0.1% FK506 loaded niosomes delayed the occurrence of corneal allograft rejection and significantly prolonged the median survival time of corneal allografts to13.86±0.80days as compared with those treated with 1% Cyclosporine (CsA) eye drops, drug-free niosomes, or untreated. In conclusion, the proniosome-derived niosomes may be a promising vehicle for effective ocular drug delivery of FK506.

Ethnopharmacological relevance Acupoint application of cold asthma recipe (CAR) was a traditional Chinese medicine (TCM) method, widely used as an alternative medicine for clinical prevention of the common winter diseases of asthma and bronchitis. Tetrahydropalmatine (THP) was a main active ingredient of CAR extract. The aim of this study is to compare plasma pharmacokinetics and lung distribution of THP between Feishu (FS) acupoint (BL 13) and Non- Feishu (NFS) acupoint application of CAR extract by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Materials and methods The extract of CAR was topically administrated in FS and NFS acupoint of rats for plasma pharmacokinetics, and topically administrated in FS and NFS acupoint of mice for lung distribution. The plasma and lung homogenates were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column with a mobile phase consisted of 0.1% formic acid in acetonitrile and 0.1% formic acid in water. The detection was accomplished by multiple-reaction monitoring (MRM) scanning in the positive electrospray ionization (ESI + ) mode. All pharmacokinetic parameters were estimated by non-compartmental analysis. Results A sensitive, accurate and precise UPLC-MS/MS method was successfully established for determination of THP in 100 μL plasma and lung homogenate. The lower limit of quantification (LLOQ) of THP was 0.05 ng/mL and 0.072 ng/mL, respectively. The pharmacokinetic results manifested that THP was absorbed and eliminated slowly in plasma. Additionally, it was found that there was significantly higher amount of THP absorbed into blood and lung after FS acupoint application compared to NFS acupoint application. Conclusions Both of the rat plasma pharmacokinetics and mice lung distribution of THP could support that FS acupoint application of CAR extract has greater advantages of absorption into the blood circulation and distribution in target tissue over NFS acupoint application. The results might be helpful in providing a rational explanation for why the TCM chose the acupoint application and elucidating the underlying mechanism of this treatment.

Epigenetic alterations represent a sort of functional modifications related to the genome that are not responsible for changes in the nucleotide sequence. DNA methylation is one of such epigenetic modifications that have been studied intensively for the past several decades. The transfer of a methyl group to the 5 position of a cytosine is the key feature of DNA methylation. A simple change as such can be caused by a variety of factors, which can be the cause of many serious diseases including several neurodegenerative diseases. In this review, we have reviewed and summarized recent progress regarding DNA methylation in four major neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The studies of these four major neurodegenerative diseases conclude the strong suggestion of the important role DNA methylation plays in these diseases. However, each of these diseases has not yet been understood completely as details in some areas remain unclear, and will be investigated in future studies. We hope this review can provide new insights into the understanding of neurodegenerative diseases from the epigenetic perspective.

This project was carried out to exploit the feasibility of using microemulsion (ME) as an alternative carrier for percutaneous delivery econazole nitrate (ECN) and elucidate the underlying mechanism of permeation enhancement. The ME was developed based on Labrafil M 1944 Cs as oil phase, Solutol HS15 and Span 80 as surfactants, Transcutol P as cosurfactant and water as aqueous phase. The solubility of ECN was firstly determined for screening the ingredients of the system. Pseudo-ternary phase diagrams were constructed to formulate ME and select surfactant and cosurfactant. Central composite design-response surface methodology (CCD-RSM) was utilized to optimize the formulation of ME. The ECN loaded ME was characterized in terms of morphology, particle size and size distribution, pH value, refractive index, viscosity and conductivity, and storage stability of the ECN loaded ME was assayed. Percutaneous permeation of ECN from ME in vitro through rat skin was investigated in comparison with PBS aqueous suspension (1%, w/w), and results showed that ME enhanced drug retention in the skin and permeation through the skin, the enhancement of ME on skin deposition was further visualized through fluorescent-labeled ME by confocal laser scanning microscope (CLSM). The action mechanism of ME on improving percutaneous delivery was studied by performing a pretreatment test. It can speculate that ME does not simply behave as enhancer but it also acts as drug carrier. Furthermore, ME-skin interaction was elucidated through transmission electron microscope (TEM), and attenuated total reflectance fourier-transform infrared (ATR-FTIR). TEM was performed to visualize the micro morphological change of skin. ATR-FTIR was carried out to investigate the molecular vibrations of the components of stratum corneum (SC). The results indicate that the ME system may be a promising vehicle for percutaneous delivery of ECN.