Efficacy of medications for the treatment of alcohol use disorder (AUD): A systematic review and meta-analysis considering baseline AUD severity.

Baseline severity of alcohol use disorder (AUD) is an influencing factor in the response to medications recommended for the treatment of AUD. The scarce efficacy of AUD medications partly justifies their limited uses. We were interested in evaluating the efficacy of approved and recommended AUD medications using generic inverse-variance, an analysis facilitating comparison between medications and placebo both at the end of the study and, concomitantly, to baseline values for the same participants. We conducted a systematic review to include randomized controlled trials (RCTs) comparing any medication to placebo providing, both at baseline and end of treatment, percent heavy drinking days (%HDD), percent drinking days (%DD), and/or drinks per drinking day (DDD). We searched PubMed, Embase, PMC, and three CT registers from inception to April 2023. A total of 79 RCTs (11,737 AUD participants; 30 different medications) were included: 47 RCTs (8465 participants) used AUD medications, and 32 RCTs (3272 participants) used other medications. At baseline, participants consumed on average approximately 12 DDD, and experienced 70 % DD, and 61 % HDD. Placebo halved or reduced these values to a third. Compared to placebo, AUD medications further reduced these outcomes (moderate to high certainty evidence). Other medications reduced the DDD without modifying other alcohol outcomes. AUD medications increased the risk of developing adverse events (high-certainty evidence). Despite the large placebo effects, our results support the benefits of providing AUD medications to people with AUD, helping them reduce alcohol consumption.

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.

Availability and threshold of the vasoactive-inotropic score for predicting early extubation in adults after rheumatic heart valve surgery: a single-center retrospective cohort study.

BACKGROUND: Early extubation (EEx) is defined as the removal of the endotracheal tube within 8 h postoperatively. The present study involved determining the availability and threshold of the vasoactive-inotropic score (VIS) for predicting EEx in adults after elective rheumatic heart valve surgery. METHODS: The present study was designed as a single-center retrospective cohort study which was conducted with adults who underwent elective rheumatic heart valve surgery with CPB. The highest VIS in the immediate postoperative period was used in the present study. The primary outcome, the availability of VIS for EEx prediction and the optimal threshold value were determined using ROC curve analysis. The gray zone analysis of the VIS was performed by setting the false negative or positive rate R = 0.05, and the perioperative risk factors for prolonged EEx were identified by multivariate logistic analysis. The postoperative complications and outcomes were compared between different VIS groups. RESULTS: Among the 409 patients initially screened, 379 patients were ultimately included in the study. The incidence of EEx was determined to be 112/379 (29.6%). The VIS had a good predictive value for EEx (AUC = 0.864, 95% CI: [0.828, 0.900], P < 0.001). The optimal VIS threshold for EEx prediction was 16.5, with a sensitivity of 71.54% (65.85-76.61%) and a specificity of 88.39% (81.15-93.09%). The upper and lower limits of the gray zone for the VIS were determined as (12, 17.2). The multivariate logistic analysis identified age (OR, 1.060; 95% CI: 1.017-1.106; P = 0.006), EF% (OR, 0.798; 95% CI: 0.742-0.859; P < 0.001), GFR (OR, 0.933; 95% CI: 0.906-0.961; P < 0.001), multiple valves surgery (OR, 4.587; 95% CI: 1.398-15.056; P = 0.012), and VIS > 16.5 (OR, 12.331; 95% CI: 5.015-30.318; P < 0.001) as the independent risk factors for the prolongation of EEx. The VIS ≤ 16.5 group presented a greater success rate for EEx, a shorter invasive ventilation support duration, and a lower incidence of complications than did the VIS > 16.5 group, while the incidence of reintubation was similar between the two groups. CONCLUSION: In adults, after elective rheumatic heart valve surgery, the highest VIS in the immediate postoperative period was a good predictive value for EEx, with a threshold of 16.5.

Efficacy and Safety of Additional S-1 Chemotherapy to S-1 Plus Oxaliplatin Regimen Chemotherapy for Stage III Gastric Carcinoma after Radical Resection.

OBJECTIVE: To investigate the efficacy and safety of additional S-1 chemotherapy to S-1 plus oxaliplatin (SOX) regimen chemotherapy for Stage III gastric carcinoma (GC) after radical resection. PATIENTS AND METHODS: A total of 161 patients who were pathologically diagnosed as Stage III GC after D2 gastrectomy and received SOX regimen adjuvant chemotherapy between January 2012 and April 2016 were included in this retrospective study. SOX regimen postoperative chemotherapy was composed of Oxaliplatin and S-1, administrated every 3 weeks for 8 scheduled courses. After SOX chemotherapy, 76 patients preferred additional chemotherapy with S-1 (the ACT group), while additional S-1 chemotherapy was not given to the other 85 patients (control group). The ACT with S-1 was administrated every 3 weeks for 8 scheduled courses. Treatment was terminated in case of life-threatening adverse events or tumor progression, or patients' demand for termination. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. RESULTS: ACT group obtained markedly improved 3-year PFS [p = 0.04; hazard ratio (HR) for disease progression, 0.58; 95% confidence interval (CI), 0.34-0.98] and OS than the control group (p = 0.0469; HR for death, 0.56; 95% CI, 0.32-0.99). No chemotherapy-related mortality occurred. Patients of the ACT group suffered more common and severer hand-foot syndrome (HFS) (p = 0.02). CONCLUSIONS: Additional S-1 chemotherapy may be helpful for improving the disease progression and survival for patients with Stage III GC after radical resection with an acceptable safety profile.

Design and Analysis of Small Size Eddy Current Displacement Sensor.

A systematic method is employed for the design and analysis of a small size eddy current (EC) displacement sensor. Simulations are first performed to determine the optimal winding structure and dimensions of the sensor. A linear-fitting approach is then developed for converting the AC displacement signal of the sensor to a DC signal. Finally, a compensation method is proposed for mitigating the temperature drift of the EC sensor under different working temperatures. The experimental results show that the proposed sensor has a sensitivity of approximately 3 µm, a working temperature range of 25-55 °C, and a linearity of ±1.025%.

Single-nucleotide polymorphisms in genes related to oxidative stress and ion channels in chickens are associated with semen quality and hormonal responses to thermal stress.

Heat stress causes economic loss of livestock industry in tropical areas. Exploring genetic markers for selection of thermotolerance will benefit chicken production. Oxidative stress and fluid-salt balance are tightly associated with thermotolerance and productivity in domestic animals. The study aimed to identify single-nucleotide polymorphisms (SNPs) in genes related to oxidative stress and ion-channel regulation and their associations with semen quality and hormonal responses. In total, 28 SNPs within 11 candidate genes were identified to associate with hormonal changes and semen quality in both broiler- and layer-type Taiwan country chickens (TCCs) after exposure to acute heat stress at 38 °C for 4 h. Acute heat stress significantly affected plasma levels of triiodothyronine and corticosterone and reduced sperm motility, viability, and concentrations in both strains at Day 1 after exposure. In the B-strain TCCs, five SNPs within NDUFA8 and DAB2IP had significant effects on plasma adrenaline and corticosterone levels, and six SNPs within TRPC1, SLC9A9, and TRPC7 markedly affected plasma corticosterone and triiodothyronine levels. In the L2 strain, 15 SNPs within PSMA2, TPK1, MTF1, and CUL1 exerted effects on plasma corticosterone and triiodothyronine levels. Five SNPs within CUL3, TRPC1, and SLC9A9 in the B strain and two SNPs within MTF1 in the L2 strain were associated with sperm concentrations at Day 1 after exposure to heat stress. In conclusion, acute heat stress impaired semen quality and altered plasma corticosterone and triiodothyronine levels in TCCs. Some SNPs involved in oxidative stress and ion-channel regulation were identified to associate with the hormonal and semen alterations. These SNPs in conjunction with differential hormonal responses and semen quality serve as genetic markers for thermotolerance selection in sire lines of chickens.

Epidemiology of Cardiomyopathy in Taiwanese Population Aged Younger Than 65 Years.

Background: Few studies have investigated the epidemiology of cardiomyopathy (CMP) in the general population in Taiwan. The aim of this study was to investigate this issue. Methods: We identified patients aged < 65 years and diagnosed with CMP between 2001 and 2014 from the National Health Insurance Database of Taiwan 2000-2014. Those with known or presumed causes of CMP were further identified. Results: We identified 38,868 CMP patients (male/female = 2.13). Half had known or presumed causes of CMP, including coronary artery disease (23.6%), congenital heart disease (1.6%), metabolic disease (8.4%), conduction disturbance/dyssynchrony (2.2%), myocarditis (0.5%), muscular dystrophy (1.42%), Kawasaki disease (0.2%), nutrition problems or alcoholism (2.9%), and unspecified causes (12.4%). The incidence rates of CMP without known causes were 1.13 and 8.70 per 100,000 person-years in pediatric (0-19 years) and adult (20-64 years) populations, respectively. After an initial peak during infancy (9.16 per 100,000 person-years), the incidence declined to a nadir in those aged from 5 to 14 years, and then steadily increased during adulthood (26.51 per 100,000 person-years in those aged 60-64 years). Although mortality was higher in the pediatric (11.4%) than in the adult (1.5%) patients, the proportion of sudden death to all deaths was similar in the pediatric (9.9%) and adult (10.5%) patients. Conclusions: This study provides an epidemiological continuum of CMP in a Taiwanese population aged < 65 years. The results revealed an initial peak during infancy, followed by a decline in adolescence and a subsequent steady rise. The prognosis was poorer in the pediatric patients, and poorest in the infants. However, the risk of sudden death was the same in the adult and pediatric patients.

The Postnatal Risk, Resuscitation Success Rate and Outcomes of Pediatric Sudden Death in Taiwan.

BACKGROUND: The epidemiology of pediatric potentially sudden death (SD) events and the rescue rate remain unclear. METHODS: We established a birth cohort (2000-2014) from a national database 2000-2015. RESULTS: Of 3,097,277 live births, we identified 3126 children (56.1% male) with potentially SD events, including 887 who were rescued. The cumulative risk of potentially SD events for each neonate was 0.30, 0.62, 0.91, 1.05, and 1.13 per 1000 by 2 months, 0, 5, 11 and 14 years of age, respectively. Overall, 28.3% of the children were rescued from SD events, with a higher rate in neonates (69.6%) but lower rate in postneonatal infants. A cardiac diagnosis was noted in 596 (19.1%) patients, including congenital heart disease (CHD) (388), cardiac arrest (151), cardiomyopathy (23), myocarditis (12), Kawasaki disease (7) and arrhythmia (36). Coexisting severe CHD and events in postneonatal infancy were associated with a lower chance of resuscitation, whereas events within 1 week of age had a higher chance of resuscitation. Anoxic brain damage was noted in 174 (19.7%) patients and late death occurred in 348 (39.3%) patients after being rescued from SD. Late death was more common in males, those with anoxic brain damage, those with coexisting severe CHD, and postneonatal infants. CONCLUSIONS: In this birth cohort study, the postnatal cumulative risk of potentially SD events was 1 in 885 newborns by 14 years of age. Postneonatal infants and those with coexisting severe CHD had the highest risk and worst outcomes.

Attenuated vagally-mediated heart rate variability at rest and in response to postural maneuvers in patients with generalized anxiety disorder.

BACKGROUND: Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges. METHODS: In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders. RESULTS: After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36-0.42, respectively. CONCLUSIONS: GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.

Shock and unresponsiveness to repeated courses of intravenous immunoglobulin in Kawasaki disease: a nationwide database study.

BACKGROUND: We aimed to investigate the clinical implications of unresponsiveness to single or repeated courses intravenous immunoglobulin (IVIG) and Kawasaki disease (KD) shock syndrome in patients with KD in an era of a single brand of IVIG. METHODS: Data were collected from National Health Insurance database 2010-2013. Characteristics of the KD patients were analyzed, including age, gender, shock, and associated coronary aneurysms. RESULTS: There were 3043 KD patients (male: 1872) identified. Among them, 46 (1.51%) had KDSS, 261 patients (8.5%) had IVIG unresponsiveness, and 225 patients (7.4%) developed coronary aneurysms. Moreover, 51 patients did not respond to the second course IVIG therapy, i.e., re-IVIG unresponsiveness. KDSS was associated with the occurrence of IVIG unresponsiveness (P < 10-4) and re-IVIG unresponsiveness (P = 0.02). In addition to male gender and KD shock syndrome, IVIG unresponsiveness (OR: 2.18, 95% CI: 1.48-3.22, P = 0.001) and re-IVIG unresponsiveness (OR: 2.87, 95% CI: 1.40-5.89, P = 0.004) were both independent risk factors for coronary aneurysms. CONCLUSIONS: In a nationwide KD cohort, both IVIG unresponsiveness and re-IVIG unresponsiveness increase the risk of coronary aneurysms. Such observation addresses the importance of refining the treatment for IVIG unresponsiveness, at least in those with KD shock syndrome.

Sex-specific pathways among tri-allelic serotonin transporter polymorphism, trait neuroticism and generalized anxiety disorder.

Background: Neuroticism personality trait is recognized as an important endophenotypic predictor of generalized anxiety disorder (GAD). Furthermore, endophenotype-based pathway approaches have recently been shown to have greater advantages for gene-finding strategies than traditional case-control studies. In the present study, in addition to conventional case-control methods, we used pathway analyses to test whether the tri-allelic serotonin transporter promoter polymorphism (combining 5-HTTLPR and rs25531) is associated with risk of GAD through its effects on trait neuroticism. Methods: We included 2236 Han Chinese adults in this study, including 736 patients with GAD and 1500 healthy participants. We genotyped the 5-HTTLPR and rs25531 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism method. We used the Neuroticism scale of the Maudsley Personality Inventory (MPI) short version (MPI-Neuroticism) to measure participants' tendency toward neuroticism. Results: Using endophenotype-based path analyses, we found significant indirect effects of the tri-allelic genotype on risk of GAD, mediated by MPI-Neuroticism in both men and women. Compared to women carrying the S'S' genotype, women carrying the L' allele had higher levels of MPI-Neuroticism, which in turn were associated with higher risk of GAD. Men, however, showed the opposite pattern. Using traditional case-control comparisons, we observed that the effect of tri-allelic genotype on GAD was significant, but only in women. Limitations: Participants were restricted to Han Chinese, and we used only 1 questionnaire to assess neuroticism. Conclusion: These findings are the first to show that the triallelic 5-HTTLPR polymorphism is associated with elevated risk of GAD, and that this effect is mediated via increased trait neuroticism, a sex-dependent risk pathway.

Cumulative postnatal risk of pediatric sudden death and all-cause mortality in nationwide birth cohorts of Taiwan and the United States.

BACKGROUND: To investigate the cumulative postnatal risk of pediatric sudden death (SD) for each neonate and the temporal/regional differences which are still unclear. METHODS: We established a birth cohort (2000-2014) from our national database and obtained reference data about the United States (US) from the national website. RESULTS: Among 3,097,277 live births, we identified 1661 children with SD (56.8% male). The postnatal cumulative risk of SD was 0.35, 0.49, 0.56 and 0.59/1000 by age 0, 5, 11 and 14 years. Coexisting cardiac diagnosis was noted in 347 (20.9%) and non-cardiac diagnosis in 300 (18.1%) patients. Cumulative all-cause mortality was 5.3, 6.78, 7.63 and 8.06/1000 by age 0, 5, 11 and 14 years. Risks of SD and all-cause death decreased over birthyear. SD risk decreased particularly after the 2008 birthyear. Risks of SD and all-cause death were the highest in Eastern Taiwan, but SD/all-cause death ratio was high in Taipei metropolitan and Northern Taiwan. Cumulative risk of SD (0.54/1000 by age 14) and all-cause mortality (9.06/1000 by age 14) in the US decreased over time. African-Americans were at the highest risks of SD and all-cause mortality. However, American-Indians/Alaska-natives exhibited the highest SD/all-cause death ratio. CONCLUSION: This study provides the cumulative risk of SD (1 in 1694 newborns) by age 14 years. The time trend underlines the effect of medical advance and education on SD prevention. Distinct regional/ethnic differences in risks of SD and all-cause death in Taiwan and the US indicate the necessity of different strategies to diminish the disparity.

Genomic regions and pathways associated with thermotolerance in layer-type strain Taiwan indigenous chickens.

This study aimed to investigate genetic markers and candidate genes associated with thermotolerance in a layer-type strain Taiwan indigenous chickens exposed to acute heat stress. One hundred and ninety-two 30-week-old roosters were subjected to acute heat stress. Changes in body temperature (BT, ΔT) were calculated by measuring the difference between the initial BT and the highest BT during heat stress and the results were categorized into dead, susceptible, tolerant, and intermediate groups depending on their survival and ΔT values at the end of the experiment. A genome-wide association study on survival and ΔT values was conducted using the Cochran-Armitage trend test and Fisher's exact test. Association analyses identified 80 significant SNPs being annotated to 23 candidate genes, 440 SNPs to 71 candidate genes, 64 SNPs to 25 candidate genes, and 378 SNPs to 78 candidate genes in the dead versus survivor, tolerant versus susceptible, intermediate versus tolerant, and intermediate versus susceptible groups, respectively. The annotated genes were associated with apoptosis, cellular stress responses, DNA repair, and metabolic oxidative stress. In conclusion, the identified SNPs of candidate genes provide insights into the potential mechanisms underlying physiological responses to acute heat stress in chickens.

Incidence and Postnatal Profile of Fontan Patients by Adolescence from a Nationwide Birth Cohort.

BACKGROUND: Although the Fontan procedure is associated with a variety of long-term complications, it is the mainstay treatment for congenital heart disease with a functioning single ventricle. Data concerning the epidemiological profile are scarce. METHODS: We investigated the current epidemiological profile using a 2000-2008 nationwide birth cohort from a 2000-2014 database (1,967,991 live births), with complete postnatal data for at least 6 years. We identified 363 patients (2792 patient-years of follow-up) who had received the Fontan procedure, giving an incidence of 0.184/1000 live births. RESULTS: The overall Fontan surgical survival rate was 81.8%. In post-Fontan patients, the 10-year survival was 0.822 (±0.026). Causes of death included cardiac (43.8%), infection (20.8%), out-of-hospital death (16.7%), sudden death (8.3%), cerebral vascular accident (8.3%) and malignancy (2.1%). The risk of unexpected death (sudden death and out-of-hospital death) was 4.0%, or 0.55% per post-Fontan patient-year. Arrhythmias were common (12.1%). Supraventricular tachycardia was the most common type of arrhythmia, and occurred prior to the Fontan procedure in 22 patients, with a cumulative risk of 2.2%, 6.3%, and 11.6% by the age of 1, 5 and 10 years, respectively. Arrhythmia intervention was performed in 40.9% of those with arrhythmia, including electrophysiological studies/ablation in 12 and device therapy in 6 patients. CONCLUSIONS: In conclusion, the incidence of Fontan patients was 0.184/1000 live births. Their medical complexity included a high risk of supraventricular tachycardia and unexpected death by adolescence.

Acute Heat Stress Changes Protein Expression in the Testes of a Broiler-Type Strain of Taiwan Country Chickens.

Heat stress leads to decreased fertility in roosters. This study investigated the global protein expression in response to acute heat stress in the testes of a broiler-type strain of Taiwan country chickens (TCCs). Twelve 45-week-old roosters were randomly allocated to the control group maintained at 25°C, and three groups subjected to acute heat stress at 38°C for 4 h, with 0, 2, and 6 h of recovery, respectively. Testis samples were collected for hematoxylin and eosin staining, apoptosis assay, and protein analysis. The results revealed 101 protein spots that differed significantly from the control following exposure to acute heat stress. The proteins that were differentially expressed participated mainly in protein metabolism and other metabolic processes, responses to stimuli, apoptosis, cellular organization, and spermatogenesis. Proteins that negatively regulate apoptosis were downregulated and proteins involved in autophagy and major heat shock proteins (HSP90α, HSPA5, and HSPA8) were upregulated in the testes of heat-stressed chickens. In conclusion, acute heat stress causes a change in protein expression in the testes of broiler-type B strain TCCs and may thus impair cell morphology, spermatogenesis, and apoptosis. The expression of heat shock proteins increased to attenuate the testicular injury induced by acute heat stress.

Effect of Seasonal Change on Testicular Protein Expression in White Roman Geese.

The purpose of this study was to investigate the change in protein expression in the testes of ganders at various breeding stages. A total of nine 3-year-old male White Roman ganders were used. The blood and testis samples were collected at the nonbreeding, sexual reactivation, and breeding stages for sex hormone analysis and proteomic analysis, respectively. The testicular weight and serum testosterone observed for ganders at the breeding stage were higher than those for ganders at nonbreeding and sexual reactivation stages (P < 0.05). There were 124 protein spots differentially expressed in the testes of ganders at various reproductive stages. A total of 107 protein spots of 74 proteins was identified through mass spectrometry. Most of the differentially expressed proteins were responsible for the molecular functions of protein binding (24%) and catalytic activity (16%). A functional pathway analysis suggested that proteins involved in steroidogenesis, metabolism, and spermatogenesis pathways changed in the White Roman geese at various reproductive stages. In conclusion, ganders at various reproductive stages exhibited different levels of testosterone and protein expression in the testes. The varied levels of the proteins might be essential and unique key factors in seasonal reproduction in ganders.

Genome-wide association study on the body temperature changes of a broiler-type strain Taiwan country chickens under acute heat stress.

Body temperature is the simplest parameter for evaluating the physiological conditions of animals under thermal stress. Genome-wide association studies (GWAS) have identified candidate genes related to economic traits in domestic animals. The present study conducted a GWAS on body temperature changes in a broiler-type strain Taiwan country chickens (TCCs) under acute heat stress. A total of two hundred 30-week-old roosters of a broiler-type strain TCCs were used. The roosters were subjected to acute heat stress at 38 °C for 4 h, and their body temperature was recorded before and during heat stress. The change in body temperature (ΔT) of each rooster was calculated according to the difference between the initial temperature and the highest body temperature during heat stress. The roosters were categorized according to survival and ΔT at the end into dead, susceptible, resistant, and intermediate groups. Collected red blood cells were genotyped using a 600 K chicken single-nucleotide polymorphism (SNP) array. A GWAS for ΔT was conducted using the Cochran-Armitage trend test. Significant SNPs were annotated as candidate genes according to the nearest genes. Results indicated that the ΔT of the heat-resistant group was significantly lower than that of the heat-susceptible group. A total of 17 SNPs belonging to 8 candidate genes, 352 SNPs for 78 candidate genes, and 174 significant SNPs for 63 candidate genes were identified in the association analyses in the dead vs. survival, resistant vs. susceptible, and intermediate vs. susceptible groups, respectively. The annotated candidate genes are associated with apoptosis, cellular response to external stimuli, and signal transduction pathways. In conclusion, the significant SNPs located in and proximal to genes in the GWAS analysis were related to apoptosis or responses to external stimuli which serve as potential candidates underlying physiological adaptation to heat stress or thermotolerance in chickens.

Add-On Memantine Treatment for Bipolar II Disorder Comorbid with Alcohol Dependence: A 12-Week Follow-Up Study.

BACKGROUND: Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence. METHODS: In a single-arm 12-week clinical trial, BD-II patients with comorbid alcohol dependence (n = 45) undergoing regular valproic acid treatments were given add-on memantine (5 mg/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-α and C-reactive protein [CRP], transforming growth factor-ß1 [TGF-ß1], interleukin-8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. RESULTS: Mean within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were significantly different from baseline after 12 weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF-ß1 level was significant (B = 0.003, p = 0.019). CONCLUSIONS: BD-II comorbid with alcohol dependence might benefit from add-on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels.

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.