Association between socioeconomic and motherhood characteristics with receiving community-based treatment services among justice-involved young female drug users: a retrospective cohort study in Taiwan.

BACKGROUND: Drug-involved individuals who contact treatment services in Taiwan are mostly driven by criminal justice systems either as an alternative or adjunct to criminal sanctions for a drug offence. With a focus on justice-involved young female drug users, the present study examines the extent to which socioeconomic and motherhood characteristics are associated with receiving deferred prosecution, a scheme diverting drug offenders to community-based addiction treatment. METHODS: We identified a cohort of 5869 women under the age of 30 arrested for using Schedule II drugs (primarily amphetamine-like stimulants) from the 2011-2017 National Police Criminal Records in Taiwan. Information concerning socioeconomic characteristics, pregnancy and live birth history, and deferred prosecution was obtained through linkage with the 2006-2019 National Health Insurance, birth registration, and deferred prosecution datasets. Multinomial logistic regression was used to evaluate the association with stratification by recidivism status. RESULTS: Within six months of arrest, 21% of first-time offenders (n = 2645) received deferred prosecution and 23% received correction-based rehabilitation; the corresponding estimates for recidivists (n = 3224) were 6% and 15%, respectively. Among first-time offenders, low/unstable income was associated with lower odds of deferred prosecution (adjusted odds ratio [aOR] = 0.71; 95% CI: 0.58, 0.88). For recidivists, those with low/unstable income (aOR = 1.58) or unemployment (aOR = 1.58) had higher odds of correction-based rehabilitation; being pregnant at arrest was linked with reduced odds of deferred prosecution (aOR = 0.31, 95% CI: 0.13, 0.71) and correction-based rehabilitation (aOR = 0.50, 95% CI: 0.32, 0.77). CONCLUSIONS: For the young women arrested for drug offences, disadvantaged socioeconomic conditions were generally unfavored by the diversion to treatment in the community. Childbearing upon arrest may lower not only the odds of receiving medical treatment but also correctional intervention. The criminal prosecution policy and process should be informed by female drug offenders' need for treatment and recovery.

Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment.

Methadone is a synthetic opioid used for the maintenance treatment (MMT) of heroin dependence. It primarily binds to the µ-opioid receptor (MOR; with its gene, namely OPRM1). Methadone is also an N-methyl-D-aspartate (NMDA) receptor antagonist. The role of NMDA receptor in the regulatory mechanisms of methadone dosage in heroin dependent patients is so far not clear. D-amino acid oxidase (DAO) is an important enzyme that indirectly activates the NMDA receptor through its effect on the D-serine level. To test the hypothesis that genetic polymorphisms in the DAO gene are associated with methadone treatment dose and responses, we selected four single nucleotide polymorphisms (SNPs) in DAO from the literature reports of the Taiwanese population. SNPs were genotyped in 344 MMT patients. In this study, we identified a functional SNP rs55944529 in the DAO gene that reveals a modest but significant association with the methadone dosage in the recessive model of analysis (P = 0.003) and plasma concentrations (P = 0.003) in MMT patients. However, it did not show association with plasma methadone concentration in multiple linear regression analysis. It is also associated with the methadone adverse reactions of dry mouth (P = 0.002), difficulty with urination (P = 0.0003) in the dominant model, and the withdrawal symptoms of yawning (P = 0.005) and gooseflesh skin (P = 0.004) in the recessive model. Our results suggest a role of the indirect regulatory mechanisms of the NMDA reporter, possibly via the DAO genetic variants, in the methadone dose and some adverse reactions in MMT patients.

Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment.

Chronic opioid use disorder patients often also use other substances such as amphetamines. The gene-based analysis method was applied in the genomic database obtained from our previous study with 343 methadone maintenance treatment (MMT) patients. We found that the gene encoding gamma-aminobutyric acid type A receptors (GABA-A receptor) delta subunit isoforms (GABRD) was associated with amphetamine use in heroin dependent patients under MMT in Taiwan. A total of 15% of the 343 MMT patients tested positive for amphetamine in the urine toxicology test. Two genetic variants in the GABRD, rs2889475 and rs2376805, were found to be associated with the positive urine amphetamine test. They are located in the exon 1 of the splice variant and altered amino acid compositions (T126I, C/T, for rs2889475, and R252Q, G/A, for rs2376805). The CC genotype carriers of rs2889475 showed a four times higher risk of amphetamine use than those with TT genotype. The GG genotype carriers of rs2376805 showed a three times higher risk of amphetamine use than the AA genotype carriers. To our knowledge, this is the first report that demonstrated an association of the delta splice variant isoform in the GABA-A receptor with an increased risk of amphetamine use in MMT patients. Our results suggest that rs2889475 and rs2376805 may be indicators for the functional role and risk of amphetamine use in MMT patients.

Genetic polymorphisms in the opioid receptor delta 1 (OPRD1) gene are associated with methadone dose in methadone maintenance treatment for heroin dependence.

Delta opioid receptor (DOR) is well known to be involved in heroin dependence. This study tested the hypothesis that single nucleotide polymorphisms (SNPs) in the opioid receptor delta 1 (OPRD1) gene coding region are associated with treatment responses in a methadone maintenance therapy (MMT) cohort in Taiwan. Three hundred forty-four MMT patients were recruited. Diastolic/systolic blood pressure, heart rate, methadone dosage, and plasma concentrations of methadone were recorded. Twenty-five SNPs located within the OPRD1 genetic region were selected and genotyped from the genomic DNA of all 344 participants. After pairwise tagger analyses, tagger SNP rs204047 showed a significant association with methadone dosage (P = 0.0019), and tagger SNPs rs204047 and rs797397 were significantly associated with plasma R, S-methadone concentrations (P < 0.0006) in patients tested negative in the urine morphine test, which indicated patients with a better response to MMT. The major genotype carriers showed a higher methadone dosage and higher plasma concentrations of R, S-methadone than the minor genotype carriers. The results indicated that OPRD1 genetic variants were associated with methadone dosage and methadone plasma concentration in MMT patients with a negative morphine test result.

Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients.

Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.

GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.

Background: There is no countable biomarker for opioid dependence treatment responses thus far. In this study, we recruited Taiwanese methadone maintenance treatment patients to search for genes involving the regulatory mechanisms of methadone dose by genome-wide association analyses. Methods: A total of 344 Taiwanese methadone maintenance treatment patients were included in a genome-wide association study. The involvement of GRK5 in opioid dependence was then further confirmed by gene expression study on lymphoblastoid cell lines derived from 3 independent age- and gender-matched groups: methadone maintenance treatment patients, medication-free former heroin abusers, and normal controls. Results: The results indicated that GRK5, the gene encoding an enzyme related to µ-opioid receptor desensitization, is associated with methadone dose by additive model of gene-based association analysis (P=6.76×10-5). We found that 6 of the 55 single nucleotide polymorphisms from the genome-wide genotype platform and 2 single nucleotide polymorphisms from the 29 additionally selected single nucleotide polymorphisms were significantly associated with methadone maintenance dose in both genotype and allele type (P ≤ .006), especially in patients who tested negative in the urine morphine test. The levels of GRK5 gene expression were similar between methadone maintenance treatment patients and medication-free former heroin abusers. However, the normal controls showed a significantly lower level of GRK5 gene expression than the other groups (P=.019). Conclusions: The results suggested an important role for GRK5 in the regulatory mechanisms of methadone dose and course of heroin dependence.

Clozapine use reduced psychiatric hospitalization and emergency room visits in patients with bipolar disorder independent of improved treatment regularity in a three-year follow-up period.

OBJECTIVES: The efficacy of clozapine in bipolar disorder remains to be systemically examined. In the current study, we sought to disentangle the effect of clozapine from that of improved treatment regularity and to compare the effect of clozapine with the effect of regular treatment for bipolar disorder by exploring the complete 10-year clozapine prescription data from a Taiwanese total population health claims database. METHODS: In the period between 2000 and 2009, 3,874 (3.3%) out of the 117,785 patients identified as having bipolar disorder in a Taiwanese total population health claims database were ever prescribed clozapine. Among them, 920 patients with bipolar disorder who had good pre-clozapine medication compliance and received at least two clozapine prescriptions were further categorized according to their clozapine medication possession ratio (MPR) as regular users (MPR ≥ 0.8; n = 476) and irregular users (MPR < 0.8; n = 444). Using a mirror-image design, we compared the numbers of emergency room (ER) visits, hospitalizations and hospital days, and the average durations of a single hospitalization during the pre- and post-clozapine mirror periods with a follow-up time of up to three years, controlling for time-variant course confounders. RESULTS: The patterns of change in outcome indices from the pre-clozapine period to the post-clozapine period differed significantly between the two clozapine-user groups. Clinical outcome indices improved only in regular users, while they deteriorated in irregular users. Over the three-year follow-up period, the irregular users consistently had a higher adjusted risk for increased numbers of ER visits [odds ratio (OR): 2.06-2.43], hospitalizations (OR: 2.52-3.22), and total hospital days (OR: 2.42-2.91) when compared to the regular users. Thus, effects of clozapine were consistently demonstrated in one- to three-year mirror comparison periods. CONCLUSIONS: Clozapine, when used with high treatment regularity (MPR > 0.8), was effective in reducing the numbers of ER visits, hospitalizations, and total hospital days in patients with bipolar disorder with previous frequent hospitalizations and ER visits despite regular pre-clozapine treatment for bipolar disorder. However, high early attrition and suboptimal treatment compliance need to be rectified in order to optimize the outcome of clozapine treatment in bipolar disorders.

A Room Temperature H2 Sensor Fabricated Using High Performance Pt-Loaded SnO2 Nanoparticles.

Highly sensitive H2 gas sensors were prepared using pure and Pt-loaded SnO2 nanoparticles. Thick film sensors (~35 µm) were fabricated that showed a highly porous interconnected structure made of high density small grained nanoparticles. Using Pt as catalyst improved sensor response and reduced the operating temperature for achieving high sensitivity because of the negative temperature coefficient observed in Pt-loaded SnO2. The highest sensor response to 1000 ppm H2 was 10,500 at room temperature with a response time of 20 s. The morphology of the SnO2 nanoparticles, the surface loading concentration and dispersion of the Pt catalyst and the microstructure of the sensing layer all play a key role in the development of an effective gas sensing device.

The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance.

Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients. Six SNPs from rs7843965 to rs1051660 (intron 2 to exon 2) were significantly associated with body weight (P < 0.007). A haplotype of 4 SNPs rs7832417-rs16918853-rs702764-rs7817710 (exon 4 to intron 3) was associated with bone or joint aches (P ≤ 0.004) and with the amount of alcohol use (standard drinks per day; global P < 0.0001). The haplotype rs10958350-rs7016778-rs12675595 was associated with gooseflesh skin (global P < 0.0001), yawning (global P = 0.0001), and restlessness (global P < 0.0001) withdrawal symptoms. The findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.

Prediction of lncRNA and disease associations based on residual graph convolutional networks with attention mechanism.

LncRNAs are non-coding RNAs with a length of more than 200 nucleotides. More and more evidence shows that lncRNAs are inextricably linked with diseases. To make up for the shortcomings of traditional methods, researchers began to collect relevant biological data in the database and used bioinformatics prediction tools to predict the associations between lncRNAs and diseases, which greatly improved the efficiency of the study. To improve the prediction accuracy of current methods, we propose a new lncRNA-disease associations prediction method with attention mechanism, called ResGCN-A. Firstly, we integrated lncRNA functional similarity, lncRNA Gaussian interaction profile kernel similarity, disease semantic similarity, and disease Gaussian interaction profile kernel similarity to obtain lncRNA comprehensive similarity and disease comprehensive similarity. Secondly, the residual graph convolutional network was used to extract the local features of lncRNAs and diseases. Thirdly, the new attention mechanism was used to assign the weight of the above features to further obtain the potential features of lncRNAs and diseases. Finally, the training set required by the Extra-Trees classifier was obtained by concatenating potential features, and the potential associations between lncRNAs and diseases were obtained by the trained Extra-Trees classifier. ResGCN-A combines the residual graph convolutional network with the attention mechanism to realize the local and global features fusion of lncRNA and diseases, which is beneficial to obtain more accurate features and improve the prediction accuracy. In the experiment, ResGCN-A was compared with five other methods through 5-fold cross-validation. The results show that the AUC value and AUPR value obtained by ResGCN-A are 0.9916 and 0.9951, which are superior to the other five methods. In addition, case studies and robustness evaluation have shown that ResGCN-A is an effective method for predicting lncRNA-disease associations. The source code for ResGCN-A will be available at https://github.com/Wangxiuxiun/ResGCN-A .

Assessing the impact of public funding in alleviating participant reduction and improving the retention rate in methadone maintenance treatment clinics in Taiwan: an interrupted time series analysis.

BACKGROUND: Given the steady decline in patient numbers at methadone maintenance treatment (MMT) clinics in Taiwan since 2013, the government initiated Patients' Medical Expenditure Supplements (PMES) in January 2019 and the MMT Clinics Accessibility Maintenance Program (MCAM) in September 2019. This study aims to evaluate the impact of the PMES and MCAM on the enrollment and retention of patients attending MMT clinics and whether there are differential impacts on MMT clinics with different capacities. METHODS: The monthly average number of daily participants and 3-month retention rate from 2013 to 2019 were extracted from MMT databases and subjected to single interrupted time series analysis. Pre-PMES (from February 2013 to December 2018) was contrasted with post-PMES, either from January 2019 to December 2019 for clinics funded solely by the PMES or from January 2019 to August 2019 for clinics with additional MCAM. Pre-MCAM (from January 2019 to August 2019) was contrasted with post-MCAM (from September 2019 to December 2019). Based on the monthly average number of daily patients in 2018, each MMT clinic was categorized as tiny (1-50), small (51-100), medium (101-150), or large (151-700) for subsequent stratification analysis. RESULTS: In terms of participant numbers after the PMES intervention, a level elevation and slope increase were detected in the clinics at every scale except medium in MMT clinics funded solely by PMES. In MMT clinics with subsequent MCAM, a level elevation was only detected in small-scale clinics, and a slope increase in the participant numbers was detected in tiny- and small-scale clinics. The slope decrease was also detected in medium-scale clinics. In terms of the 3-month retention rate, a post-PMES level elevation was detected at almost every scale of the clinics, and a slope decrease was detected in the overall and tiny-scale clinics for both types of clinics. CONCLUSIONS: Supplementing the cost of a broad treatment repertoire enhances the enrollment of people with heroin use in MMTs. Further funding of human resources is vital for MMT clinics to keep up with the increasing numbers of participants and their retention.

OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study.

Majority of the heroin-dependent patients smoke cigarettes. Although it has been reported that the OPRM1 genetic polymorphism is associated with the brain mu-opioid receptor binding potential in cigarette smokers, there is no direct evidence showing the impact of plasma cotinine, a nicotine metabolite, on treatment responses to methadone maintenance treatment (MMT). In this study, we aimed to test the hypothesis that the genetic polymorphisms in the OPRM1 are associated with the methadone treatment responses and the severity of cigarette smoking directly measured by the plasma concentration of cotinine in a Taiwanese MMT cohort. Fifteen OPRM1 single-nucleotide polymorphisms (SNPs) were selected and genotyped on DNA samples of 366 MMT patients. Plasma concentrations of cotinine were measured by cotinine enzyme-linked immunosorbent assay. The plasma cotinine concentration had positive correlation with concentrations of methadone (P = 0.042) and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (P = 0.037). Methadone treatment non-responders, defined by a positive urine morphine test, had a higher plasma concentration of cotinine (P = 0.005), but a lower plasma concentration-to-dose ratio of both R- and S-methadone (P = 0.001 and 0.012, respectively) than the responders. OPRM1 genetic variants, rs1074287, rs6912029, rs1799971, rs12209447, rs510769, rs3798676, rs553202, rs7748401, rs495491, rs10457090, rs589046, rs3778152 and rs563649, were significantly associated with the plasma concentration of cotinine when using recessive model for genotypes (general linear model (GLM), P<0.038; false discovery rate (FDR)<0.035) and additive model for allele types (GLM, P<0.03; FDR<0.049) in association analyses. The G allele carriers of SNP rs1799971 (A118G) on exon 1 of OPRM1 gene had a lower plasma cotinine concentration than the A allele carriers (GLM, P = 0.029). OPRM1 genetic polymorphisms are associated with the plasma concentration of cotinine in a Taiwanese MMT cohort. Carriers with the major allele of SNP rs1799971 had a higher plasma cotinine concentration.

Spinodal decomposition of mono- to few-layer graphene on Ni substrates at low temperature.

Mono to few-layer graphene were prepared on pre-annealed polycrystalline nickel substrates by chemical vapor deposition at a relatively low temperature of 800 degrees C using fast cooling rate. It was observed that the reduced solubility of Carbon in Ni at low temperature and an optimum gas mixing ratio (CH4:H2 = 60/80 (sccm)) can be used to synthesize mano-layer graphene that covers about 100 microm2 area. The number of graphene layers strongly depends upon the hydrogen and methane flow rates. An increase in the methane flow is found to increase the growth density of the single-layer graphene. The number of graphene layers was identified from micro-Raman spectra. The thinnest areas containing mono-layer graphene formed at small Ni grains surrounded by large Ni Grains can be explained in terms of Spinodal decomposition. Scanning tunneling microscopy observations of the graphene samples indicate that the graphene structure exhibits no defects, and extremely symmetry hexagon carbon at flat graphene surface is observed.

Comparative Transcriptome Analysis Provides Insight into Spatio-Temporal Expression Characteristics and Genetic Regulatory Network in Postnatal Developing Subcutaneous and Visceral Fat of Bama Pig.

The depot differences between Subcutaneous Fat (SAF) and Visceral Fat (VAF) are critical for human well-being and disease processes in regard to energy metabolism and endocrine function. Miniature pigs (Sus scrofa) are ideal biomedical models for human energy metabolism and obesity due to the similarity of their lipid metabolism with that of humans. However, the regulation of differences in fat deposition and development remains unclear. In this study, the development of SAF and VAF was characterized and compared in Bama pig during postnatal development (infancy, puberty and adulthood), using RNA sequencing techniques (RNA-Seq). The transcriptome of SAF and VAF was profiled and isolated from 1-, 3- and 6 months-old pigs and identified 23,636 expressed genes, of which 1,165 genes were differentially expressed between the depots and/or developmental stages. Upregulated genes in SAF showed significant function and pathway enrichment in the central nervous system development, lipid metabolism, oxidation-reduction process and cell adhesion, whereas genes involved in the immune system, actin cytoskeleton organization, male gonad development and the hippo signaling pathway were preferentially expressed in VAF. Miner analysis of short time-series expression demonstrated that differentiation in gene expression patterns between the two depots corresponded to their distinct responses in sexual development, hormone signaling pathways, lipid metabolism and the hippo signaling pathway. Transcriptome analysis of SAF and VAF suggested that the depot differences in adipose tissue are not only related to lipid metabolism and endocrine function, but are closely associated with sexual development and organ size regulation.

CYP2B6 polymorphisms influence the plasma concentration and clearance of the methadone S-enantiomer.

Methadone is a racemic compound composed of the R-form and S-form enantiomers. The drug is usually used in maintenance therapy for the heroin-addicted patients. In our previous study, we found that the cytochrome P-450 (CYP) isozyme 2B6 preferentially metabolizes the S-methadone enantiomer. We thus tested whether CYP2B6 gene polymorphisms had any influence on the concentration or clearance of methadone. Ten single nucleotide polymorphisms within this gene region were evaluated in 366 patients undergoing methadone maintenance for at least 3 months. The plasma steady-state levels of racemic methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine were then measured in these individuals. The rs10403955 (T allele in intron 1), rs3745274 (G allele in exon 4), rs2279345 (T allele in intron 5), and rs707265 (A allele in exon 9) CYP2B6 allele types were found to be significantly associated with a higher clearance, a lower plasma concentration, and a lower concentration-to-dosage (C/D) ratio of (S)-methadone (P < 0.0017). Two haplotype blocks of a trinucleotide haplotype (rs8100458-rs10500282-rs10403955 in intron 1) and a hexanucleotide haplotype (rs2279342-rs3745274-rs2279343-rs2279345-rs1038376-rs707265 from intron 2 to exon 9) were constructed within CYP2B6. The major combinations of T-T-T and A-G-A-T-A-A of these particular haplotypes showed significant associations with the plasma concentrations of S-methadone and its C/D ratio (P < 0.0001, respectively). We conclude that genetic polymorphisms in the CYP2B6 gene may therefore be indicators of the clearance, plasma concentration and C/D ratio of S-methadone.

Effect of benzodiazepine discontinuation on dementia risk.

OBJECTIVES: This study aimed to examine whether benzodiazepine (BZD) discontinuation would decrease the risk of dementia. DESIGN: A population-based nested case-control study of dementia was used. SETTING: All subjects aged 45 years or older and enrolled in the National Health Insurance Research Database in Taiwan between 1997 and 2007 were randomly selected. PARTICIPANTS: A total of 8,434 cases had been identified with dementia at least three times in ambulatory claims or with one record in inpatient claims. They were individually matched with two comparison subjects (N = 16,706) by age, gender, and index date. MEASUREMENTS: The lengths of discontinuation, cumulative BZD dose, and potential confounding factors, including medical and psychiatric disorders, were measured and used for further analysis. RESULTS: Compared with nonusers, current users had an increased risk of dementia (adjusted odds ratio [aOR] = 2.71; 95% confidence interval [CI], 2.46-2.99). The dementia risk for former users was reduced as the duration of discontinuation lengthened (<1 month aOR = 2.40, 95% CI, 1.98-2.92; 1-3 months aOR = 1.93, 95% CI, 1.67-2.23; 3-6 months aOR = 1.49, 95% CI, 1.28-1.74; 6-12 months aOR = 1.43, 95% CI, 1.25-1.64; 1-2 years aOR = 1.23, 95% CI, 1.09-1.40; 2-3 years aOR = 1.22, 95% CI, 1.06-1.40; and >3 years aOR = 1.08, 95% CI, 0.98-1.20). The decreasing trend was significant (p < 0.001). CONCLUSION: The risk of dementia was high for current users and decreased as the duration of BZD discontinuation lengthened. Further investigations are needed to replicate this association and explore the underlying mechanism that links long-term BZD use, BZD discontinuation, and the pathogenesis of neurocognitive dysfunction.

Finding social phobia patients from the Internet.

Patients with social phobia commonly resist face-to-face assessments, and a number of alternative assessment methods based on the Internet are being developed. The aim of this study was to identify patients with social phobia on the Internet and characterize their condition, using the Social Phobia Inventory (SPIN). In Stage I, this study recruited 1307 participants from the Internet, most of whom were well-educated young females, who had remained unmarried and unemployed. The Internet-based SPIN demonstrated excellent internal consistency (Cronbach's α=0.937) and good test-retest reliability (intraclass correlation coefficient=0.942). In Stage II, we examined the discriminant validity of the SPIN via structured telephone interviews. The area under the receiver operating characteristic curve used to discriminate social phobia was 0.871 with an optimal cut-off point of 24 on the total score for the SPIN. According to the SPIN scores, 919 of Stage I participants (70.3%) reached the threshold of social phobia, 531 of which (57.8%) had never sought professional help. These results suggest that the Internet is a potential avenue through which to find untreated patients with social phobia.

The Production of Carbon Nanofiber on Rubber Fruit Shell-Derived Activated Carbon by Chemical Activation and Hydrothermal Process with Low Temperature.

Recently, the conversion of biomass into carbon nanofibers has been extensively studied. In this study, carbon nanofibers (CNFs) were prepared from rubber fruit shell (RFS) by chemical activation with H3PO4, followed by a simple hydrothermal process at low temperature and without a vacuum and gas catalyst. XRD and Raman studies show that the structure formed is an amorphous graphite formation. From the thermal analysis, it is shown that CNFs have a high thermal stability. Furthermore, an SEM/TEM analysis showed that CNFs' morphology varied in size and thickness. The obtained results reveal that by converting RFS into an amorphous carbon through chemical activation and hydrothermal processes, RFS is considered a potential biomass source material to produce carbon nanofibers.

AZO-Based ZnO Nanosheet MEMS Sensor with Different Al Concentrations for Enhanced H2S Gas Sensing.

The properties of H2S gas sensing were investigated using a ZnO nanostructure prepared with AZO (zinc oxide with aluminium) and Al surfaces which were developed on a MEMS (Micro Electromechanical System) device. Hydrothermal synthesis was implemented for the deposition of the ZnO nanostructure. To find the optimal conditions for H2S gas sensing, different ZnO growth times and different temperatures were considered and tested, and the results were analysed. At 250 °C and 90 min growth time, a ZnO sensor prepared with AZO and 40 nm Al recorded an 8.5% H2S gas-sensing response at a 200 ppb gas concentration and a 14% sensing response at a gas concentration of 1000 ppb. The dominant sensing response provided the optimal conditions for the ZnO sensor, which were 250 °C temperature and 90 min growth time. Gas sensor selectivity was tested with five different gases (CO, SO2, NO2, NH3 and H2S) and the sensor showed great selectivity towards H2S gas.

Genome-wide association study revealed genetic variations of ABA sensitivity controlled by multiple stress-related genes in rice.

Abscisic acid (ABA) is a critical phytohormone that regulates multiple physiological processes including plant growth and stress tolerance. The core ABA signaling pathway has been well established, but genetic variations mediating ABA responses remain largely unknown. In this study, we performed genome-wide association study (GWAS) to identify loci and genes associated with ABA sensitivity (reflected by seed germination inhibition by ABA) in a panel of 425 rice accessions. The seed germination assay revealed that Aus and indica rice had stronger ABA sensitivity than japonica rice. A total of 48 non-redundant association loci were detected in the indica subpopulation and whole population, and 386 genes in these loci were responsive to ABA or abiotic stresses. Eight association loci were overlapped with previously reported loci for yield under drought stress or for drought-indicative image traits. Haplotype analyses of important candidate genes such as OsSAPK6, a key component in the ABA signaling core, were performed to identify key SNPs/InDels that may affect gene functions through promoter activity regulation, amino acid variation, or gene splicing. These results provide insights into the genetic basis of ABA sensitivity related to stress responses.