p-Nrf2/HO-1 Pathway Involved in Methamphetamine-induced Executive Dysfunction through Endoplasmic Reticulum Stress and Apoptosis in the Dorsal Striatum.

Methamphetamine (METH) abuse is known to cause executive dysfunction. However, the molecular mechanism underlying METH induced executive dysfunction remains unclear. Go/NoGo experiment was performed in mice to evaluate METH-induced executive dysfunction. Immunoblot analysis of Nuclear factor-E2-related factor 2 (Nrf2), phosphorylated Nrf2 (p-Nrf2), heme-oxygenase-1 (HO-1), Glucose Regulated Protein 78(GRP78), C/EBP homologous protein (CHOP), Bcl-2, Bax and Caspase3 was performed to evaluate the levels of oxidative stress, endoplasmic reticulum (ER) stress and apoptosis in the dorsal striatum (Dstr). Malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activity was conducted to evaluate the level of oxidative stress. TUNEL staining was conducted to detect apoptotic neurons. The animal Go/NoGo testing confirmed that METH abuse impaired the inhibitory control ability of executive function. Meanwhile, METH down-regulated the expression of p-Nrf2, HO-1 and GSH-Px and activated ER stress and apoptosis in the Dstr. Microinjection of Tert-butylhydroxyquinone (TBHQ), an Nrf2 agonist, into the Dstr increased the expression of p-Nrf2, HO-1, and GSH-Px, ameliorated ER stress, apoptosis and executive dysfunction caused by METH. Our results indicated that the p-Nrf2/HO-1 pathway was potentially involved in mediating methamphetamine-induced executive dysfunction by inducing endoplasmic reticulum stress and apoptosis in the dorsal striatum.

The chain-mediation pathway of gender regarding academic delay of gratification in college students is regulated by anxiety/depressive mood and prospective memory.

Objective: This study investigated the relationship between gender and academic delay of gratification (ADOG) in college students and explored the mediating roles of anxiety/depressive mood and prospective memory to provide a theoretical intervention approach based on internal mechanisms. Methods: Random cluster sampling was conducted on 609 students from three universities situated in the Province of Anhui, China with the use of data from several questionnaires: the general information questionnaire, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, Prospective and Retrospective Memory (PRM) Questionnaire, and ADOG Scale. Results: The females' anxiety and depression levels were lower than that of the males, while the female PRM and ADOG performance improved when compared to that of the males. Anxiety and depression were negatively correlated with PRM and ADOG, respectively, whereas the PRM and ADOG data demonstrated a positive correlation. Depression/anxiety and prospective memory also played a chain intermediary role between gender and ADOG. Conclusion: Gender not only directly affects college students' ADOG, but it also has indirect effects through depression/anxiety and prospective memory. Therefore, it is very important to treat students' mental health differently according to gender to improve prospective memory and delayed academic satisfaction.

Associations of executive function and age of first use of methamphetamine with methamphetamine relapse.

Background and aims: Methamphetamine (MA) is a psychostimulant associated with a high relapse rate among patients with MA use disorder (MUD). Long-term use of MA is associated with mental disorders, executive dysfunction, aggressive behaviors, and impulsivity among patients with MUD. However, identifying which factors may be more closely associated with relapse has not been investigated. Thus, we aimed to investigate the psychological factors and the history of MA use that may influence MA relapse. Methods: This cross-sectional study included 168 male MUD patients (MUD group) and 65 healthy male residents (control group). Each patient was evaluated with self-report measures of executive dysfunction, psychopathological symptoms, impulsiveness, aggressiveness, and history of MA use. Data were analyzed with t-tests, analyses of variance, and correlation and regression analyses. Results: The MUD group reported greater executive dysfunction, psychopathological symptoms, impulsivity, and aggression than the control group. Lower age of first MA use was associated both with having relapsed one or more times and with having relapsed two or more times; greater executive dysfunction was associated only with having relapsed two or more times. Conclusion: Patients with MUD reported worse executive function and mental health. Current results also suggest that lower age of first MA use may influence relapse rate in general, while executive dysfunction may influence repeated relapse in particular. The present results add to the literature concerning factors that may increase the risk of relapse in individuals with MUD.

Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan.

In 1998, an epidemic of hand-foot-and-mouth disease and herpangina caused by enterovirus 71 occurred in Taiwan, leaving many fatalities and severely handicapped survivors in its wake. The reasons this rather common pathogen would cause such a large-scale epidemic remain unknown. A seroepidemiological survey to elucidate the epidemiological characteristics of this outbreak, including its incidence and case-fatality rates was undertaken. Microneutralization tests for antibodies against enterovirus 71 were used to screen four collections of serum samples: 1) 202 specimens taken from individuals > or = 4 years old in 1994; 2) 245 specimens collected from individuals of all ages in 1997; 3) 1,258 specimens collected from individuals of all ages in 1999; and 4) sera samples from a birth cohort of 81 children who had yearly blood samples taken from 1988-98. After the maternal antibody had declined, the seropositive rates began to increase with age. Approximately half of all children aged 6 years or older were enterovirus 71 seropositive. Significantly higher seropositive rates were noted in 1999 than in 1997, in children aged 0.5-3 years. The incidence of enterovirus 71 infection during the epidemic was estimated to be 13-22%, with the higher rates in younger children. The case-fatality rate was highest (96.96 per 100,000) in infants aged 6-11 months, and declined in older children. The results showed that enterovirus 71 is endemic in Taiwan. The apparent lack of large-scale enterovirus 71 activity in the 3 years before 1998 might have been the prelude to the epidemic's appearance in 1998, and might suggest that enterovirus 71 infection will reappear every few years. The lack of a protective antibody in younger children may account for the high incidence and case-fatality rate in this age group.