Nerve growth factor gene polymorphisms may be associated with heroin dependence in women but do not mediate specific personality traits.

Heroin dependence (HD) is a complex disease with a substantial genetic contribution and is associated with traits of impulsivity and specific personality traits. The neurotrophic factor nerve growth factor (NGF) may mediate the reward processes in HD. This study aims to investigate whether NGF gene polymorphisms are associated with the co-occurrence of HD and impulsivity/specific personality traits in HD patients. To minimize the potential confounding effects of population stratification, we selected a homogeneous Han Chinese population and recruited 1364 participants (831 HD patients and 533 healthy controls). In addition, 163 female HD patients completed the Chinese version of the Barratt Impulsiveness Scale Version 11 (BIS-11), and 440 HD patients completed the Chinese version of the Tridimensional Personality Questionnaire (TPQ) for subsequent analysis. We identified three polymorphisms with altered allele and genotype frequency in HD patients versus controls (p = 0.035 for rs2254527; p = 0.005 for rs6678788; p = 0.006 for rs7523654), especially in the female subgroup. Four associations identified via haplotype analysis were significant in the female subgroup (p = 0.003 for T-T-A haplotype and p = 0.002 for C-C-A haplotype in block 1; p = 0.011 for T-T haplotype and p = 0.009 for C-T haplotypes in block 2), but not in the male subgroup. Male HD patients had higher novelty-seeking (NS) scores, and female HD patients had higher harm avoidance (HA) scores. However, there was no significant association between the selected NGF polymorphisms and BIS or TPQ scores in HD patients. NGF variants may contribute to the risk of HD development in females but do not mediate the relationship between impulsivity and specific personality traits in the female population.

Serum Albumin was Associated with a Long Term Cardiovascular Mortality among Elderly Patients with Stable Coronary Artery Disease.

Background: Serum albumin (SA), a multifunction protein, contributes to maintaining a variety of physiological functions. Studies have linked SA to atherosclerosis with possible mechanisms including a response to inflammation. The contribution of albumin to cardiovascular (CV) mortality in elderly patients with stable coronary artery disease (CAD) remains unclear. Methods: We investigated 321 elderly patients with stable CAD undergoing coronary angiography between 2003 and 2006. CV mortality data were obtained from the National Registry of Deaths in Taiwan. CV mortality included deaths attributable to ischemic heart disease, congestive heart disease, and stroke. The association between baseline SA and CV mortality was assessed using a Cox model and Fine-Gray model when non-CV mortality was considered a competing event. Results: During a median follow-up of 97 months, 39 (12.1%) participants died from CV disease and 76 (23.7%) died from non-CV diseases. After adjusting for covariates, patients in the SA ≥ 3.75 g/dL group had a lower frequency of CV mortality compared with those in the SA < 3.75 g/dL group [hazard ratio (HR): 0.20; 95% confidence interval (CI): 0.08-0.49; p < 0.001]. Similarly, compared to the participants with non-CV mortality, the SA ≥ 3.75 g/dL group had a lower frequency of CV mortality compared with the SA < 3.75 g/dL group (subdistribution HR: 0.27; 95% CI: 0.11-0.65; p < 0.001) in adjusted competing risk models. Conclusions: A SA level ≥ 3.75 g/dL at admission was associated with decreased long-term CV mortality and may be useful for risk prediction in elderly patients with stable CAD.

Automated ECG classification based on 1D deep learning network.

The standard 12-lead electrocardiogram (ECG) records the heart's electrical activity from electrodes on the skin, and is widely used in screening and diagnosis of the cardiac conditions due to its low price and non-invasive characteristics. Manual examination of ECGs requires professional medical skills, and is strenuous and time consuming. Recently, deep learning methodologies have been successfully applied in the analysis of medical images. In this paper, we present an automated system for the identification of normal and abnormal ECG signals. A multi-channel multi-scale deep neural network (DNN) model is proposed, which is an end-to-end structure to classify the ECG signals without any feature extraction. Convolutional layers are used to extract primary features, and long short-term memory (LSTM) and attention are incorporated to improve the performance of the DNN model. The system was developed with a 12-lead ECG dataset provided by the Kaohsiung Medical University Hospital (KMUH). Experimental results show that the proposed system can yield high recognition rates in classifying normal and abnormal ECG signals.

High-level production and extraction of C-phycocyanin from cyanobacteria Synechococcus sp. PCC7002 for antioxidation, antibacterial and lead adsorption.

Global warming and climate change because carbon dioxide (CO2) release to atmosphere is the forecasting challenges to human being. We are facing how to overcome the dilemma on the balance between economic and environment, thus taking more efforts on green processes to meet agreement of sustainable society are urgent and crucial. The absorption of CO2 by microalgae reduces the impact of CO2 on the environment. In this study, the CO2 removal efficiency was the highest in the culture of Cyanobacterium Synechococcus sp. PCC7002 (also called blue-green algae), at 2% CO2 to reach a value of 0.86 g-CO2/g-DCW. The main product of PCC7002 is C-phycocyanin (C-PC) which regarding to phycobilisome complex in all cyanobacterial species. A 160% increasing C-PC was achieved in the cultivation under 100 µmol/m2/s light intensity, 12:12 light-period with 2% CO2 at 30 °C. The mix-culture of nitric and ammonia ions had positive effect on the cell growth and C-PC accumulation, thus realized the highest yield of 0.439 g-CPC/g-DCW. Additionally, the partial purified C-PC displayed 89% antioxidant activity of 2,2-diphenyl-1-picryhydrazyl (DPPH) and 11% of superoxide free radical scavenging activity, respectively. The production of C-PC from PCC7002 reduced the CO2 emission and exhibited antibacterial activity against Escherichia coli and lead ion adsorption at room temperature, which has the great potential for eco-friendly application.

Structural insights into Arabidopsis ethylene response factor 96 with an extended N-terminal binding to GCC box.

The phytohormone ethylene is widely involved in many developmental processes and is a crucial regulator of defense responses against biotic and abiotic stresses in plants. Ethylene-responsive element binding protein, a member of the APETALA2/ethylene response factor (AP2/ERF) superfamily, is a transcription factor that regulates stress-responsive genes by recognizing a specific cis-acting element of target DNA. A previous study showed only the NMR structure of the AP2/ERF domain of AtERF100 in complex with a GCC box DNA motif. In this report, we determined the crystal structure of AtERF96 in complex with a GCC box at atomic resolution. We analyzed the binding residues of the conserved AP2/ERF domain in the DNA recognition sequence. In addition to the AP2/ERF domain, an N-terminal α-helix of AtERF96 participates in DNA interaction in the flanking region. We also demonstrated the structure of AtERF96 EDLL motif, a unique conserved motif in the group IX of AP2/ERF family, might involve in the transactivation of defense-related genes. Our study establishes the structural basis of the AtERF96 transcription factor in complex with the GCC box, as well as the DNA binding mechanisms of the N-terminal α-helix and AP2/ERF domain.

Structural basis of jasmonate-amido synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation.

Far-red (FR) light-coupled jasmonate (JA) signaling is necessary for plant defense and development. FR insensitive 219 (FIN219) is a member of the Gretchen Hagen 3 (GH3) family of proteins in Arabidopsis and belongs to the adenylate-forming family of enzymes. It directly controls biosynthesis of jasmonoyl-isoleucine in JA-mediated defense responses and interacts with FIN219-interacting protein 1 (FIP1) under FR light conditions. FIN219 and FIP1 are involved in FR light signaling and are regulators of the interplay between light and JA signaling. However, how their interactions affect plant physiological functions remains unclear. Here, we demonstrate the crystal structures of FIN219-FIP1 while binding with substrates at atomic resolution. Our results show an unexpected FIN219 conformation and demonstrate various differences between this protein and other members of the GH3 family. We show that the rotated C-terminal domain of FIN219 alters ATP binding and the core structure of the active site. We further demonstrate that this unique FIN219-FIP1 structure is crucial for increasing FIN219 activity and determines the priority of substrate binding. We suggest that the increased FIN219 activity resulting from the complex form, a conformation for domain switching, allows FIN219 to switch to its high-affinity mode and thereby enhances JA signaling under continuous FR light conditions.

Application and Comparison of Different Prognostic Scoring Systems in Patients Who Underwent Cardiologist-Managed Percutaneous Cardiopulmonary Support.

BACKGROUND: Temporary mechanical support, including percutaneous cardiopulmonary support (PCPS), is crucial for reversing patients' compromised hemodynamic function. Knowledge about whether cardiologists can directly manage patients receiving PCPS and about the predictive values of different prognostic scores is insufficient. METHODS: We examined the data and in-hospital mortality of 45 eligible patients receiving cardiologist-managed PCPS from July 2012 to January 2019 in our institute. We compared different prognostic scores [namely Survival After Veno-arterial ECMO (SAVE), modified SAVE, prEdictioN of Cardiogenic shock OUtcome foR acute myocardial infarction patients salvaGed by VA-ECMO (ENCOURAGE), and Sequential Organ Failure Assessment (SOFA) scores] through area under the receiver operating characteristic curve (AUC) analysis. RESULTS: The patients' mean age was 64.3 ± 11.3 years, and 71.1% were men. The overall in-hospital survival rate was 35.6%. Compared to survivors, nonsurvivors were more likely to have an ischemic etiology, cardiopulmonary resuscitation, and higher lactate levels. Survivors had higher SAVE (-5.9 vs. -11.4) and modified SAVE (4.2 vs. -7.1) scores than nonsurvivors (both p = 0.001), but SOFA (9.7 vs. 10.3) and ENCOURAGE (24.8 vs. 26.8) scores were similar (both p > 0.1). In multivariate models, only modified SAVE score remained statistically significant (hazard ratio: 0.96, 95% confidence interval: 0.93-1.00; p = 0.047). Modified SAVE score showed the best risk discrimination (AUC = 0.78). CONCLUSIONS: Establishing regular and continual training protocols can enable cardiologists to perform emergency PCPS (without on-site surgery) and daily care for patients with refractory cardiogenic shock. The modified SAVE score facilitates risk stratification and future decision-making processes.

Relations between baseline burden, maximum duration, and relative reduction of atrial fibrillation: Insights from continuous monitoring in rhythm control.

INTRODUCTION: Cardiac implantable electronic devices (CIEDs) can measure atrial fibrillation (AF) early; however, the timing for administering antiarrhythmic drugs (AADs) to suppress AF remains unclear. This study aimed to investigate the association between baseline values and changes after AAD in terms of relative reduction of AF burden (RRAB) and maximum AF duration (RRMD). METHODS: This multicenter retrospective study screened all patients with nonpermanent AF who had dual-chamber pacemakers and only enrolled those receiving a naive AAD between September 2009 and December 2014. AF burden and maximum duration were calculated using CIED at 0 and 3 to 6 months after starting rhythm control. All the enrolled patients were divided into four groups according to baseline AF burden. RRAB and RRMD were monitored using CIEDs. RESULTS: Overall, 145 eligible subjects received a naive AAD for nonpermanent AF. The mean RRAB in the four groups (AF burden <1%, 1%-4%, 4%-18%, and ≥18%) were -65.3%, -46.4%, -34.7%, and -27.9% (P = 0.005), respectively. Mean RRMD were -26.8%, -12.4%, 4.2%, and 6.0%, respectively ( P = 0.006). Multivariate analysis revealed that the lowest baseline AF burden (<1%) was significantly associated with greater RRAB, which was not observed in the RRMD model. CONCLUSIONS: Lower baseline AF burden was associated with greater RRAB by AADs. Our finding suggests that rhythm control should be started in the early stage to achieve better responses to AADs.

Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Bare Metal Stent Implantation: A Nationwide Cohort Study.

BACKGROUND: To investigate whether there is an increased risk of cardiovascular (CV) events in patients with diabetes associated with adding proton pump inhibitors (PPIs) to clopidogrel (CLO) therapy after bare-metal stent (BMS) deployment. METHODS: We used the National Health Insurance Research Database to conduct this retrospective cohort study. We enrolled 6,757 patients with diabetes who underwent BMS deployment and received CLO with/without PPIs for 90 days (6,243 in the CLO subgroup and 514 in the CLO plus PPI subgroup). The endpoints were acute coronary syndrome and re-admission for revascularization (PCI or coronary artery bypass graft surgery) after 3, 6, and 12 months. RESULTS: The patients who received CLO with PPIs had no significant increase in adverse CV events compared to those without PPIs within 1 year after BMS deployment [3-month hazard ratio (HR) = 0.87, 95% confidence interval (CI), 0.65-1.15; 6 months, HR = 0.95, 95% CI, 0.78-1.15; 1 year, HR = 0.60, 95% CI, 0.81-1.12]. CONCLUSIONS: In patients with diabetes undergoing BMS deployment, there was no evidence of an increased risk of CV events among concomitant users of CLO and PPIs. Our results indicate that the use of PPIs may not modify the protective effect of CLO after BMS implantation.

Novelty seeking mediates the effect of DRD3 variation on onset age of amphetamine dependence in Han Chinese population.

The dopamine receptor D3 (DRD3) gene, one of the candidate genes for amphetamine dependence (AD), is involved in the mesolimbic dopaminergic system, implicated as the underlying mechanism of addiction. Our case-control study aimed to investigate whether the DRD3 gene is associated with the susceptibility to AD and specific personality traits in AD patients. A total of 1060 unrelated Han Chinese subjects (559 AD patients and 501 controls) were screened using the same assessment tool and genotyped for eight DRD3 polymorphisms. All patients met the DSM-IV-TR criteria for AD, and personality traits of 539 were assessed using a Tridimensional Personality Questionnaire. Furthermore, AD individuals were divided into four clinical subgroups based on gender and psychosis status, to reduce the clinical heterogeneity. We found that the ATA haplotype combination for SNPs rs324029, rs6280, and rs9825563, respectively, was significantly associated with total AD patients (p = 0.0003 after 10,000 permutations). Similar results were observed in the both male and non-psychosis subgroup but not in other subgroups. In addition, DRD3 rs9825563 may influence onset age of drug use, partially mediated by novelty seeking in the non-psychosis AD group. In conclusion, DRD3 is a potential genetic factor in the susceptibility to AD and is associated with onset age of drug use through interaction with novelty seeking in a specific patient group in the Han Chinese population.

NGF gene polymorphisms are not associated with heroin dependence in a Taiwanese male population.

BACKGROUND AND OBJECTIVES: Heroin dependence (HD) is a chronic relapsing brain illness with substantial heritability. Nerve growth factor (NGF) is a crucial modulator in the neurodevelopment, and may be a key mediator of reward processes in HD. The purpose of this genetic study was to investigate whether NGF gene polymorphisms associate with the occurrence of HD and the specific personality traits of patients with HD. METHODS: We selected a homogeneous Han Chinese male population to overcome possible confounding effects of population and gender. For the study, 272 HD patients and 141 controls completed the Tridimensional Personality Questionnaire to evaluate their personality traits. In addition, a further sample 303 HD patients and 204 controls was added (with totally 920 participants) for the gene association and genotype-phenotype interaction studies. RESULTS: Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. Nonetheless, NGF gene polymorphisms did not associate with specific personality traits in HD patients and controls. There is no significant difference in NGF gene polymorphisms between patients with HD and controls. DISCUSSION AND CONCLUSIONS: The NGF gene may neither contribute to the risk of development of HD, nor mediate the relationship between specific personality traits and HD in Han Chinese male population. SCIENTIFIC SIGNIFICANCE: Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. However, none of the polymorphisms in the NGF gene affected the NS and HA scores in both patients and healthy subjects. (Am J Addict 2018;27:516-523).

Changes of Atrial Natriuretic Peptides after Defibrillation Threshold Testing Predicted Future Ventricular Arrhythmia Event.

BACKGROUND: We investigated the change of natriuretic peptides during defibrillation threshold (DFT) testing and its relationship with future ventricular arrhythmia (VA) events in patients implanted with an implantable cardioverter defibrillator (ICD). METHODS: Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were measured in 21 patients (mean age 61 ± 13 years; 67% male) undergoing ICD implantation. Blood samples of the patients were drawn at pre-implantation, 30 minutes, 60 minutes, and 24 hours after DFT testing. The patients were followed and divided into two groups according to the occurrence of VA in 18 months. The biomarker levels and their changes were compared in patients with and without further VA. RESULTS: The pre-implantation ANP levels were higher at pre-implantation and increased significantly at 30 minutes after DFT testing (Δ30minANP) among patients with VA events. The BNP and CNP levels did not change significantly after DFT testing in both groups. The area under curve was 0.82 for the change in Δ30minANP determining further ventricular events. The optimal Δ30minANP cutoff value was 0.51 pg/ml, with sensitivity of 0.83 and specificity of 0.68. Multivariable analysis confirmed that patients with Δ30minANP more than 0.51 pg/ml have a higher risk of further ventricular events (hazard ratio 39.8, 95% confidence interval: 2.87-553.01, p = 0.006). The pre-implantation ANP level could not predict future VA events (hazard ratio 1.06, 95% CI: 1.00-1.14, p = 0.06). CONCLUSIONS: The increase of ANP concentration after DFT testing predicted future VA events after ICD implantation while the BNP and CNP levels did not predict future VA events.

Responses of cardiac natriuretic peptides after paroxysmal supraventricular tachycardia: ANP surges faster than BNP and CNP.

Atrial natriuretic peptide (ANP) secretion increases after 30 min of paroxysmal supraventricular tachycardia (PSVT). Whether this phenomenon also applies to brain or C-type natriuretic peptides (BNP or CNP) remains unknown. Blood samples of 18 patients (41 ± 11 yr old; 4 men) with symptomatic PSVT and normal left ventricular systolic function (ejection fraction 65 ± 6%) were collected from the coronary sinus (CS) and the femoral artery (FA) before and 30 min after the induction, and 30 min after the termination of PSVT. The results showed that the ANP levels rose steeply after the PSVT and then reduced at 30 min after the termination (baseline vs. post-PSVT vs. posttermination: CS: 34.0 ± 29.6 vs. 74.1 ± 42.3 vs. 46.1 ± 32.9; FA: 5.9 ± 3.24 vs. 28.2 ± 20.7 vs. 10.0 ± 4.6 pg/ml; all P < 0.05). In contrast, compared with ANP, the increases of BNP and CNP in CS after the PSVT were less sharp, but continued to rise after the termination of tachycardia (BNP, 10.2 ± 6.4 vs. 11.3 ± 7.1 vs. 11.8 ± 7.9; CNP, 4.5 ± 1.2 vs. 4.9 ± 1.4 vs. 5.0 ± 1.4 pg/ml; all P < 0.05). The rise of BNP and CNP in FA was similarly less sharp after the PSVT and remained stationary after the termination. PSVT exerted differential effects on cardiac natriuretic peptide levels. ANP increased greater after a 30-min induced PSVT, but dropped faster after termination of PSVT, compared with BNP and CNP.

Reduced striatal dopamine transporter density associated with working memory deficits in opioid-dependent male subjects: a SPECT study.

Research on the effects of repeated opioid use on striatal dopamine transporters has yielded inconsistent results, possibly confounded by a history of methamphetamine or methadone exposure in opioid-dependent individuals. Previous studies have shown that striatal dopamine transporter density is positively correlated with the cognitive performance of healthy volunteers. This study aimed to investigate changes in striatal dopamine transporter density and their functional significance in opioid-dependent individuals. Single-photon emission computed tomography with [(99m) Tc]TRODAT-1 as a ligand was used to measure striatal dopamine transporter levels in 20 opioid-dependent individuals and 20 age- and sex-matched healthy controls. Opioid-dependent individuals had no history of methamphetamine or methadone use. The Wisconsin Card Sorting Test (WCST) was performed to assess neurocognitive function. We found that compared with healthy controls, opioid-dependent individuals showed a significant reduction in striatal dopamine transporter density. They also showed poorer performance on the WCST in terms of the trials administered, total errors, perseverative responses, perseverative errors, and non-perseverative errors. Striatal dopamine transporter levels negatively correlated with non-perseverative errors not only in opioid-dependent individuals but also in healthy controls. These findings suggest that in human, repeated opioid exposure reduces striatal dopamine transporter density, which can be associated with non-perseverative errors. Non-perseverative errors may be one of the more sensitive parameters in WCST to identify working memory deficits associated with striatal dopamine transporter reduction. Moreover, we suggest that whether opioid-associated neurotoxicity is reversible depends on the brain region.

Pre-germinated brown rice prevented high fat diet induced hyperlipidemia through ameliorating lipid synthesis and metabolism in C57BL/6J mice.

Pre-germinated brown rice (PGBR) can ameliorate hyperlipidemia, but the action mechanism is not clear. We focus the mechanisms of PGBR prevented hyperlipidemia. Six-week-old mice were divided into: standard-regular diet (SRD), high-fat diet (HFD) and HFD with PGBR (HFD + PGBR) groups for 16 weeks. The HFD group has higher concentrations of TG, TC, HDL and Non-HDL in the blood, and a higher atherosclerosis index (AI). The TG levels in the liver, and TG, bile acid levels in the feces were enhanced; and the total adipocytokines level in adipose tissue was reduced. The HFD group had higher protein expressions of SREBP-1, SCD-1, FAS, LDLR, and CYP7α1 in the liver. Moreover, the greater expressions of SREBP-1, SCD-1, FAS and the less expressions of PPAR-α and adiponectin were in adipose tissue. In the HFD + PGBR group, the PGBR regulated the levels of TG, TC, HDL, Non-HDL, AI and adipocytokines. PGBR increased more cholesterol and bile acid exhaust in feces. The SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α proteins in the liver; and the SREBP-1, SCD-1, FAS, PPAR-α and adiponectin proteins in adipose tissue were reversed by PGBR. Taken together, PGBR can improve lipid synthesis and metabolism, and we suggest PGBR is a recommendable food for controlling hyperlipidemia.