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.

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.

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.

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.

Diagnostic Reliability and Validity of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) Chinese Version.

The Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) is a polydiagnostic instrument for substance use and psychiatric disorders. We translated the SSADDA English version into Chinese (SSADDA-Chinese) and report here our examination of the diagnostic reliability and validity of DSM-IV substance dependence (SD) diagnoses in a Mandarin-speaking sample in Taiwan. We recruited 125 subjects who underwent an assessment of lifetime SD diagnoses using both the SSADDA-Chinese and the Structured Clinical Interview for DSM-IV, Clinician Version (SCID-Chinese). Thirty-one subjects were retested with the SSADDA-Chinese. Cohen's κ statistic, which measures chance-corrected agreement, was used to measure the test-retest reliability and concurrent validity of the individual SD diagnoses. There was a high degree of concordance between SD diagnoses made using the SSADDA-Chinese and the SCID-Chinese, including those for dependence on alcohol (κ = 0.83), ketamine (κ = 0.97), methamphetamine (κ = 0.93), and opioids (κ = 0.95). The test-retest reliability of dependence diagnoses for ketamine (κ = 0.95), methamphetamine (κ = 0.80), and opioids (κ = 1.00) obtained using the SSADDA-Chinese was excellent, while that for alcohol dependence (κ = 0.63) and nicotine dependence (κ = 0.65) was good. We conclude that the SSADDA-Chinese is a reliable and valid instrument for the diagnosis of major SD traits in Mandarin-speaking populations.

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.

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.

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.

Suicide attempts and death among heroin-involved women seeking methadone treatment in Taiwan.

BACKGROUND: The present study aims to profile the hazard fluctuation of suicide attempts and deaths among heroin-involved women seeking methadone maintenance treatment (MMT) and to investigate sociodemographic and clinical factors predicting the time to have suicidal behaviors. METHODS: We identified a retrospective cohort comprising 2780 women receiving methadone treatment in the period of 2012-2016. Healthcare records were obtained from Taiwan's National Health Insurance Research Database, and suicide deaths were ascertained from the national death register. Competing risk survival analyses were used to estimate the risk of suicide attempts and deaths within one year and three years of MMT enrollment. RESULTS: A total of 1.2 % of MMT-treated women ever visited hospital for suicide attempt, and 0.5 % died by confirmed suicide. The risk of treated suicide attempt reached its peak at the end of the 8th month after methadone initiation, whereas the risk of confirmed suicide death was relatively stable during the first one and a half years. A history of treated depressive disorders appears to be the strongest risk predictor for treated suicide attempts (Adjusted Hazard Ratio [aHR] = 3.45; 95 % CI = 1.66-7.19) and confirmed suicide death (aHR = 3.47; 95 % CI = 1.20-10.0). Retaining in methadone treatment may significantly lower the hazard of probable suicide death by 52 %. CONCLUSIONS: Women with heroin use disorders should receive careful attention for suicide risk at intake assessment and over the course of treatment and recovery. Preventive strategies should target unmet clinical and social needs and evaluate gender-specific barriers for treatment engagement.

MoS2-Carbon Inter-overlapped Structures as Effective Electrocatalysts for the Hydrogen Evolution Reaction.

The ability to generate hydrogen in an economic and sustainable manner is critical to the realization of a future hydrogen economy. Electrocatalytic water splitting into molecular hydrogen using the hydrogen evolution reaction (HER) provides a viable option for hydrogen generation. Consequently, advanced non-precious metal based electrocatalysts that promote HER and reduce the overpotential are being widely researched. Here, we report on the development of MoS2-carbon inter-overlapped structures and their applicability for enhancing electrocatalytic HER. These structures were synthesized by a facile hot-injection method using ammonium tetrathiomolybdate ((NH4)2MoS4) as the precursor and oleylamine (OLA) as the solvent, followed by a carbonization step. During the synthesis protocol, OLA not only plays the role of a reacting solvent but also acts as an intercalating agent which enlarges the interlayer spacing of MoS2 to form OLA-protected monolayer MoS2. After the carbonization step, the crystallinity improves substantially, and OLA can be completely converted into carbon, thus forming an inter-overlapped superstructure, as characterized in detail using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). A Tafel slope of 118 mV/dec is obtained for the monolayer MoS2-carbon superstructure, which shows a significant improvement, as compared to the 202 mV/dec observed for OLA-protected monolayer MoS2. The enhanced HER performance is attributed to the improved conductivity along the c-axis due to the presence of carbon and the abundance of active sites due to the interlayer expansion of the monolayer MoS2 by OLA.

Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use.

Methadone is a synthetic opioid used as maintenance treatment for patients addicted to heroin. Skin irritation is one of the adverse events caused by opioid use. 344 methadone maintenance treatment (MMT) patients were recruited with records and measurements on methadone dose, plasma methadone concentrations, and treatment emergent symptom scales (TESS). 15 patients reported with skin irritation. Five SNPs located within the NECTIN4 genetic region were genotyped. The NECTIN4 gene within the adherens junction interaction pathway was associated with methadone dose in pathway-based genome wide association analyses (P = 0.0008). Three highly-linked SNPs, rs11265549, rs3820097, and rs4656978, were significantly associated with methadone dose (P = 0.0003), plasma concentrations of R,S-methadone (P = 0.0004) and TNF-α (P = 0.010) in all 344 MMT patients, and with self-report skin irritation symptom scores (P = 0.010) in the 15 MMT patients who reported with skin irritation. To identify the possible roles of plasma level of Nectin-4 in the responses to MMT and opioid use, additional age- and gender-matched 51 controls and 83 methadone-free abstinent former heroin users were recruited. Plasma level of Nectin-4 was the highest in MMT patients among the three groups. The results suggest involvement of genetic variants on NECTIN4 in methadone dose. Plasma Nectin-4 level is likely an indicator for continued use of opioids.

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.

Optical Properties and Growth Mechanism of La3Ga5.5Nb0.5O14 Macroporous Ceramic.

Optical properties and growth mechanism of La3Ga5.5Nb0.5O14 oxides by a Pechini process were investigated. The structure and morphology were obtained after sintering at 600-800 °C. This crystallized orthorhombic La3Ga5.5Nb0.5O14 can be obtained by the heat treatment process at 800 °C from XRD. A proposed schematic growth mechanism of La3Ga5.5Nb0.5O14 macroporous based on the details provided is shown. The photo-luminescence spectra shown that under 327 nm excitation spectra, a broad and blue emission peak is observed at 475 nm at 77 K and this spectrum is originated from the [NbO6]7- octahedra group. The optical absorption spectra of the 800 °C sample exhibited a well-crystalline and very low oxygen vacancy, which corresponded to the band gap energies of 3.95 eV.

Functional Correlates of Resting-State Connectivity in the Default Mode Network of Heroin Users on Methadone Treatment and Medication-Free Therapeutic Community Program.

The treatment of heroin addiction is a complex process involving changes in addictive behavior and brain functioning. The goal of this study was to explore the brain default mode network (DMN) functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) and decision-making performance based on the Cambridge gambling task in heroin-dependent individuals undergoing methadone treatment (MT, n = 11) and medication-free faith-based therapeutic community program (TC, n = 11). The DMN involved the medial prefrontal cortex (mPFC), left inferior parietal lobe (IPLL), right inferior parietal lobe (IPLR), and posterior cingulate cortex (PCC) subregions for all participants in both the MT and TC groups. Compared with MT, TC had an increased functional connectivity in IPLL-IPLR and IPLR-PCC and decreased functional connectivity in mPFC-IPLL and IPLL-PCC. Both groups exhibited no significant difference in the regional rs-fMRI metric [i.e., amplitude of low-frequency fluctuation (ALFF)]. In the analysis of the neural correlates for decision-making performance, risk adjustment was positively associated with ALFF in IPLL for all participants considering the group effects. The involvement of IPL in decision-making performance and treatment response among heroin-dependent patients warrants further investigation.

Resolution of transmission electron backscatter diffraction in aluminum and silver: Effect of the atomic number.

This work aims to investigate the influence of intrinsic and extrinsic factors on the physical resolution of the transmission electron backscattered diffraction technique (t-EBSD) in aluminum and silver. Here, we focus on the intrinsic factors, namely, atomic number and thickness of the specimen, and extrinsic set-up factors, which include the electron beam voltage, working distance, and specimen tilt. The working distance and tilt angle, which are selected as 12 mm and 60° for Al and 12 mm and 50° for Ag, respectively, reveal a sharp pattern with high contrast. The physical resolutions at the lateral and longitudinal directions depend on the depth resolution. The depth and lateral and longitudinal resolutions increase in Al but decrease in Ag with increased accelerating voltage. The decrease in specimen thickness for Al and Ag from 400 nm to 100 nm reduces the lateral and longitudinal resolutions. The most ideal depth and lateral and longitudinal resolutions obtained under a thickness of 100 nm are 22.7, 18.9, and 33.7 nm at 30 kV for Ag and 34.7, 22.8, and 36.6 nm at 15 kV for Al, respectively.

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.

APBB2 is associated with amphetamine use and plasma beta-amyloids in patients receiving methadone maintenance treatment.

APBB2, amyloid beta (A4) precursor protein-binding family B member 2, has been reported to be associated with opioid dependence. In this study, we reported the first time that the genetic variants in the APBB2 gene were associated with use of amphetamine in opioid dependent patients undergoing methadone maintenance treatment (MMT). 344 heroin-dependent patients undergoing MMT were recruited and assessed for use of amphetamine and opioids by urine toxicology, withdrawal severity, and side effects. DNAs were genome-widely genotyped for all patients. Single nucleotide polymorphisms (SNPs) in APBB2 were selected for association analyses for methadone treatment responses. Gene expression levels of APBB2 were measured by real-time polymerase chain reaction (PCR) in the EBV-transformed lymphoblastoids from patients. MMT patients who used amphetamine showed a significantly higher percentage of positive results in the urine morphine test (P=0.005), and insomnia (P=0.018). In single locus association analyses, SNPs rs3935357 and rs4861075 located at intron 6 were significantly associated with amphetamine use in both genotype and allele type (general linear model (GLM), P=0.0003, and 0.0002 for genotype, and 0.0003, and 0.002 for allele type, respectively). The major allele type carriers had twice risk of amphetamine use compared to the minor allele type carriers. Subjects with the TT genotype of rs4861075 showed significantly higher levels of APBB2 gene expression in both total (P=0.02) and long-form (P=0.037) than those with CC genotype. Detailed mechanisms underlying the association of APBB2 with amphetamine use and level of plasma amyloid beta in MMT patients require further investigation.