Attenuation of in vitro and in vivo melanin synthesis using a Chinese herbal medicine through the inhibition of tyrosinase activity.

BACKGROUND: In traditional Chinese medicine, the skin reflects the health of body organs. A skin whitening agent, named seven whitening creams (also called Chi-Bai-San), has been used since ancient times in China. Chi-Bai-San reduces melanin and helps to reduce wrinkles. PURPOSE: We aimed to determine the skin-whitening ability and safe dose of the seven compounds in Chi-Bai-San. STUDY DESIGN: A common use for Chinese medicine is decocted in water. To mimic the function of Chi-Bai-San apply in clinical, we boiled all seven compound in water, respectively. These single recipe extractions and a mixture of these seven items were used in zebrafish embryo and B16F10 melanoma cell to identify the anti-melanogenesis function. METHODS: Chi-Bai-San comprises Bai-Lian (Ampelopsis japonica), Bai-Ji (Bletilla striata), Bai-Zhi (Angelica dahurica), Bai-Zhu (Atractylodes macrocephala), Bai-Shau (Paeonia lactiflora), Fu-Ling (Wolfiporia cocos), and Jen-Ju-Fen (Pearl powder). All components were extracted by heating in distilled water. The supernatant was collected after centrifugation. The extracted components were introduced into zebrafish embryos at different doses to determine the safe dose. B16F10 melanoma cells were treated with the final dose of each component and the component mixture. Melanin content and tyrosinase activity were assessed in zebrafish and B16F10 cells. Chi-Bai-San and its components were exposed to α MSH-induced B16F10 cells, and detected for mechanism of anti-melanogenesis pathway. RESULTS: Most compounds were not toxic at a low dose (0.1 mg/ml), except A. macrocephala, which resulted in a survival rate of only 30% at 72 hpf. The final dose of A. dahurica, P. lactiflora, W. cocos, and pearl was 1 mg/ml; that of A. japonica was 0.5 mg/ml; and that of A. macrocephala and B. striata was 0.1 mg/ml. Chi-Bai-San markedly decreased melanin content 37.47% in zebrafish embryos. Further, Chi-Bai-San abolished tyrosinase activity and MITF-mediated tyrosinase expression by down regulating the upstream transcription factors ZEB2, ß-catenin, and CREB2 in α MSH-induced B16F10 cells. Additionally, Chi-Bai-San might reduce melanosome secretion from melanocytes. CONCLUSION: Our findings indicate that safety and efficacy of heat-extracted Chi-Bai-San, which can reduce αMSH-induced melanin production by inhibiting the key role of melogenic-related transcription factor and promote the synergic effect of seven types of traditional Chinese herbal medicines.

The relationships between body mass index and television viewing, internet use and cellular phone use: the moderating effects of socio-demographic characteristics and exercise.

OBJECTIVE: This study aimed to examine the relationships between body mass index (BMI) and television viewing, Internet use and cellular phone use and the moderators for these relationships in adolescents. METHOD: The relationship between BMI and the time spent on three kinds of sedentary activities and the moderators for these relationships were analyzed among 9,278 Taiwanese adolescents. The different relationships between BMI and various Internet and cellular phone-related activities were analyzed. RESULTS: High television viewing and high Internet use were associated with increased BMI in adolescents. Exercising had a moderating effect on the relationship between BMI and television viewing. Several Internet and cellular phone-related activities were associated with increased BMI. DISCUSSION: The results support the relationships between adolescent BMI and television viewing and Internet use. The moderating effect of exercise and various Internet and cellular phone-related activities should be considered when developing intervention strategies for overweight adolescents.

Concern over weight and dieting in Taiwanese adolescents: correlations of gender, age, weight, and multidimensional characteristics.

The aims of this study were to compare the levels of concern over weight and dieting (COWD) among adolescents with different body weight status, gender, and age, and to examine the associations of COWD with multidimensional characteristics. Nine thousand eighty-seven adolescents completed the questionnaires. The levels of COWD were compared among the groups with different body weight status, gender, and age. The correlates of COWD in gender- and age-specified groups were examined. The results indicated that the levels of COWD varied across the groups of adolescents with different body weight status, gender, and age. Being overweight or obese, depression, and low self-esteem were associated with high COWD in all gender- and age-specified groups. A variety of socio-demographic, personal, family, peer, and school characteristics were also associated with high COWD in adolescents with specified gender and age. Gender- and age-specified intervention programs targeting adolescents with the correlates of high COWD should be considered.

Suicide and its association with individual, family, peer, and school factors in an adolescent population in southern Taiwan.

A representative sample of 10,233 adolescent students was recruited to examine the rate of suicidal attempt and its correlates in the adolescents living in southern Taiwan. Five questions from the Kiddie Schedule for Affective Disorders and Schizophrenia (Kiddie-SADS-E) were used to inquire about the participants' suicidality. The associations between suicidal attempt and multidimensional factors were examined by using logistic regression analysis: 9.1% of the participants reported a suicidal attempt in the preceding year. Female gender, low self-esteem, weekly alcohol use, illicit drugs use, depression, high family conflict, low maternal education level, poor family function, low connectedness to school, low rank, poor feeling in peer group, and drop out from school were associated with adolescent suicidal attempt. The rate of suicidal attempt was found to be high in Taiwanese adolescents, and multidimensional factors were correlated to adolescent suicidal attempt.

Symptoms of problematic cellular phone use, functional impairment and its association with depression among adolescents in Southern Taiwan.

The aims of this study were: (1) to examine the prevalence of symptoms of problematic cellular phone use (CPU); (2) to examine the associations between the symptoms of problematic CPU, functional impairment caused by CPU and the characteristics of CPU; (3) to establish the optimal cut-off point of the number of symptoms for functional impairment caused by CPU; and (4) to examine the association between problematic CPU and depression in adolescents. A total of 10,191 adolescent students in Southern Taiwan were recruited into this study. Participants' self-reported symptoms of problematic CPU and functional impairments caused by CPU were collected. The associations of symptoms of problematic CPU with functional impairments and with the characteristics of CPU were examined. The cut-off point of the number of symptoms for functional impairment was also determined. The association between problematic CPU and depression was examined by logistic regression analysis. The results indicated that the symptoms of problematic CPU were prevalent in adolescents. The adolescents who had any one of the symptoms of problematic CPU were more likely to report at least one dimension of functional impairment caused by CPU, called more on cellular phones, sent more text messages, or spent more time and higher fees on CPU. Having four or more symptoms of problematic CPU had the highest potential to differentiate between the adolescents with and without functional impairment caused by CPU. Adolescents who had significant depression were more likely to have four or more symptoms of problematic CPU. The results of this study may provide a basis for detecting symptoms of problematic CPU in adolescents.

Acupuncture for smoking cessation: A systematic review and meta-analysis of 24 randomized controlled trials.

INTRODUCTION: We evaluate the effectiveness and safety of transdermal acupuncture by needles for smoking cessation. METHODS: A literature search for randomized controlled trials (RCTs) was performed in seven electronic databases from inception to February 2017. Meta-analysis was conducted using Revman 5.3.0 software. We used either a random effects model (REM) or a fixed effects model (FEM) for pooling data according to the result of a heterogeneity test (defined as significant if I2>75%). Trial sequential analysis (TSA) was applied by TSA 0.9.5.10 Beta software. RESULTS: Twenty-four trials involving 3984 participants were included. The methodological quality was generally low. With regard to smoking abstinence, meta-analysis showed acupuncture was more effective compared to no intervention/waiting list for short-term (4 weeks) cessation (1 trial, RR=2.37, 95% 1.41, 3.97) and long-term (longer than 6 months) (2 trials, RR=2.66, 95% CI: 1.50, 4.70). Compared to acupuncture/auricular acupressure alone, acupuncture plus auricular acupressure showed more benefit for short-term cessation (3 trials, RR=1.52, 95% CI: 1.03, 2.25). Acupuncture plus auricular acupressure was more effective compared to sham acupuncture plus sham auricular acupressure for short-term cessation (3 trials, RR=2.50, 95% CI: 1.44, 4.33) and long-term (2 trials, RR=3.61, 95% CI: 1.37, 9.48). Acupuncture in combination with counseling, educational smoking cessation program or moxibustion had more benefit compared to acupuncture for short-term cessation (3 trials, RR=0.75, 95% 0.63, 0.91) and long-term (2 trials, RR=0.77, 95% CI: 0.56, 1.05), and TSA illustrated the cumulative Z-curve of this comparison for long-term across the traditional boundary of 5% significance and monitoring boundaries. No serious adverse events occurred. CONCLUSIONS: Acupuncture combined with counseling, educational smoking cessation program or moxibustion was more effective than acupuncture as monotherapy with regard to long-term smoking cessation. Further, high quality trials are needed to confirm the result.

Depression and its association with self-esteem, family, peer and school factors in a population of 9586 adolescents in southern Taiwan.

AIMS: The aim of the present study was to gain insight into the prevalence of depression and its association with self-esteem, family, peer and school factors in a large-scale representative Taiwanese adolescent population. METHODS: A total of 12,210 adolescent students were recruited into the present study. Subjects with a score >28 on the Center for Epidemiological Studies' Depression Scale were defined as having significant depression; the Rosenberg Self-Esteem Scale, Adolescent Family and Social Life Questionnaire and Family C-APGAR Index were applied to assess subjects' self-esteem, family, peer and school factors. The association between depression and correlates were examined on t-test and chi(2) test. The significant factors were further included in logistic regression analysis. RESULTS: Among 9586 participants (response rate: 86.3%), the prevalence of depression was 12.3%. The risk factors associated with depression in univariate analysis included female gender, older age, residency in urban areas, lower self-esteem, disruptive parental marriage, low family income, family conflict, poorer family function, less satisfaction with peer relationships, less connectedness to school, and poor academic performance. After adjusting the effects of sex, age and location, only subjects with lower self-esteem, higher family conflict, poorer family function, lower rank and decreased satisfaction in their peer group, and less connectedness to school were prone to depression on logistic regression. CONCLUSION: The prevalence of depression is high in Taiwanese adolescents, and the multiple factors of family, peer, school and individuals are associated with adolescent depression. The factors identified in the present study may be helpful when designing and implementing preventive intervention programs.

Insight into alcohol-related problems and its associations with severity of alcohol consumption, mental health status, race, and level of acculturation in southern Taiwanese indigenous people with alcoholism.

OBJECTIVE: While not well known in the West, Taiwan has a substantial indigenous population, and this population has rapidly developed alcohol problems. This study examined the level of insight into alcohol-related problems and its associations with the severity of alcohol consumption, mental health status, race, and the level of acculturation among indigenous populations with alcohol problems in southern Taiwan. METHODS: A total of 332 indigenes, whose total Alcohol Use Disorders Identification Test (AUDIT) score was equal to 8 or higher, were interviewed. The associations between the level of insight into alcohol-related problems and the severity of alcohol drinking on the AUDIT, mental health status on the Chinese Health Questionnaire-12 (>or= 4 vs. < 4), race (Bunun vs. non-Bunun), and the level of acculturation on the Taiwan Aboriginal Acculturation Scale were examined using logistic regression models. RESULTS: The results of this study found that 72.6% of the participants had poor insight into alcohol-related problems and no participant had good insight. Participants who had more severe alcohol drinking or poor mental health were more likely to have a higher level of insight into alcohol-related problems. Participants who were non-Bunun were also more likely to have a higher level of insight into alcohol-related problems, but the level of acculturation was not associated with the level of insight into alcohol-related problems. CONCLUSIONS: These findings suggest that most alcoholic indigenes in southern Taiwan have poor insight into their own alcohol-related problems. Cultural specific interventions targeting and improving the indigenes' insight into alcohol-related problems are needed.

Factors related to abstinence from drug use and seeking help from medical services in Taiwanese heroin and methamphetamine users.

The aim of this study was to examine the factors related to abstinence from heroin and methamphetamine (MAMP) use and to seeking help from medical services in Taiwanese drug users. A total of 196 heroin users and 226 MAMP users were recruited in this study. Their experience of previous abstinence from drug use and the routes taken to seek help for abstinence were determined at interview. Demographic data, characteristics of drug use and reasons to abstain from drug use were compared between subjects who had and those who had never tried to abstain from drug use before, as well as between the subjects who had previously sought help from medical services and those who had tried to abstain from drug use by themselves. Those who had previously tried to abstain from heroin use had longer durations of heroin use, spent more money on getting heroin, were more likely to have a criminal record of illicit drug use and had longer durations of being detained due to illicit drug use compared with those who had never tried to abstain from heroin use. Those who had sought help from medical services for abstinence were more likely to be heroin users and to spend more money on getting illicit drugs, and tried to abstain due to concerns about relationships with family. Demographic data, characteristics of drug use and reasons to abstain from drug use were different between drug users who had different experiences of abstinence.

A bibliometric analysis of clinical study literature of traditional Chinese medicine therapies for smoking cessation.

INTRODUCTION: Traditional Chinese medicine (TCM) is commonly used for smoking cessation in China. The aim of this study is to perform a comprehensive literature search to identify clinical studies on TCM therapies for smoking cessation. METHODS: Publications of randomized controlled trials, controlled clinical studies, cohort studies, case-control studies, case series and case reports, reviews and cross-sectional studies on smoking cessation using TCM therapies were retrieved from seven databases from their inception to February 2017. The following data were extracted and analyzed: study type, year of publication, language, country or region, journals, participants, intervention and comparison, and outcome. RESULTS: In total, 260 publications on TCM therapies for smoking cessation were identified from 1980 to 2016, including 52 randomized clinical trials, 7 controlled clinical studies, 1 cohort study, 110 case series, 18 case reports, 50 narrative reviews, 17 systematic reviews, and 5 cross-sectional studies. Of these, 68.5% (178) were published in Chinese and the remaining published in English. Mainland China (n=129, 49.6%) was the leading country in this field, followed by USA (n=27, 10.4%) and UK (n=25, 9.6%). A total of 36 645 participants from 40 countries with age ranging from 12 to 86 years were involved in 188 clinical studies (excluding reviews and cross-sectional studies). The most commonly reported therapies were auricular acupressure (25, 13.3%), body acupuncture (14, 7.4%), and body acupuncture plus auricular acupressure (14, 7.4%). Composite outcomes were most frequently reported (110, 58.5%). CONCLUSIONS: A substantial number of clinical studies have been conducted and published on TCM therapy for smoking cessation, mainly focusing on acupuncture stimulation techniques. The findings suggest that future research should pay more attention to acupuncture for smoking cessation.

Comparisons of substance use disorders and correlates between aboriginal and non-aboriginal adolescents living in a mountain region in southern Taiwan.

The purposes of this study were to examine the differences in prevalence of lifetime substance use disorders (SUDs), age at initial substance use, and knowledge and attitudes toward substance use between aboriginal and non-aboriginal adolescents living in a mountain region of southern Taiwan, and to separately examine the correlates of SUDs among the two groups. A total of 251 aboriginal and 79 non-aboriginal adolescents were recruited into this study. The results revealed that although the prevalence of SUDs was high in both aboriginal and non-aboriginal adolescents, no difference in the prevalence of SUDs between the two groups was found. Attitudes toward substance use and several dimensions of peer influence were associated with SUDs in both aboriginal and non-aboriginal adolescents. However, there were different socio-demographic and family correlates with SUDs in aboriginal and non-aboriginal adolescents, and an association between characteristics of personality and SUDs was found only in aboriginal adolescents. Those who devise strategies to prevent adolescent substance use may consider the differences in the correlates of SUDs between aboriginal and non-aboriginal adolescents.

Psychopathology of aboriginal and non-aboriginal adolescents living in the mountainous region of southern Taiwan.

The aim of this study was to examine the hypothesis that Taiwanese aboriginal adolescents feature more severe psychopathology than non-aboriginal adolescents who live in the same mountainous region of southern Taiwan, and to test the hypothesis by controlling other individual and environ-mental factors. In this study, a total of 251 aboriginal and 79 non-aboriginal Taiwanese adolescents were enrolled. Their psychopathology was measured by the Symptom Checklist-90-Revised Scale; demographic and family characteristics, and their affinity with their peer group and with their school were also assessed. The results of the multiple regression analysis revealed that aboriginal adolescents feature more severe psychopathology than non-aboriginal adolescents, and indicated that females and adolescents perceiving higher levels of family conflict and lower family support were more likely to experience more severe psychopathology than those perceiving the contrary. Those who devise strategies to improve the mental health of adolescents living in impoverished regions must take into consideration their ethnicity, gender, and family context when devising such treatment strategies.

[Changes of cycle and apoptosis of spermatogenic cells and antioxidant capacity in male rats with diabetes mellitus].

OBJECTIVE: To explore the changes of cycle and apoptosis of spermatogenic cells and antioxidant capacity of the serum and testis in male rats with diabetes mellitus. METHODS: Thirty male rats were divided into two groups, 10 for normal control and 20 for the diabetes group. The rats were injected intraperitoneally with streptozocin (TZ) to develop diabetes, and 12 weeks later, their survival rate and testis weight were recorded. The percentage of G0/G, S and G2/M phases and apoptosis in spermatogenic cells were measured with flow cytometry (FCM). Malondialdehyde (MDA) and nitric oxide (NO) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and NO synthase (NOS) activities in the serum and testis were measured with thiobarbituric acid reactive substances (TBARs), nitric acid reoxidized enzyme, xanthine oxidative enzyme, 5,5 Dithiobis (2,2 nitrobenzoate) (TNB) and visible light photometer methods, respectively. RESULTS: Twelve weeks after the male rats got diabetes, their survival rate, body weight and testis weight were significantly lower (p < 0.05), and the percentages of G0/G1 phases and apoptotic spermatogenic cells were obviously higher (P < 0.05) than the normal control. At the same time, the percentage of S and G2/M phases spermatogenic cells decreased. So the spermatogenic cells were arrested in G0/G1 phase. In the diabetic rat serum and testis, especially in the testis, MDA levels were distinctly higher and SOD activities were significantly lower than those in the control. Serum GSH-Px activities of the diabetic rats were significantly lower (p < 0.05), while testis GSH-Px activities were significantly higher than those in control group (P < 0.01). NO contents in the serum and testis of the diabetic rats (P < 0.01) increased significantly, particularly the former, while NOS activities in the serum decreased significantly as compared with the control (P < 0.5). CONCLUSION: The increase in testis and serum MDA levels and NO contents and the decrease in the antioxidant enzyme activity of the diabetic rats may be relevant to spermatogenic disorder caused by the increase of G0/G1 phases arrest and spermatogenic cells apoptosis.

Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis.

OBJECTIVE: To examine the diagnostic value of serum B-type natriuretic peptide (BNP) in acute Kawasaki disease (KD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE and the Cochrane Library from inception to December 2013. We also performed manual screening of the bibliographies of primary studies and review articles, and contacted authors for additional data. STUDY ELIGIBILITY CRITERIA: We included all BNP and NT-pro (N-terminal prohormone) BNP assay studies that compared paediatric patients with KD to patients with febrile illness unrelated to KD. We excluded case reports, case series, review articles, editorials, congress abstracts, clinical guidelines and all studies that compared healthy controls. PRIMARY AND SECONDARY OUTCOME MEASURES: The performance characteristics of BNP were summarised using forest plots, hierarchical summary receiver operating characteristic (ROC) curves and bivariate random effects models. RESULTS: We found six eligible studies including 279 cases of patients with KD and 203 febrile controls. Six studies examined NT-proBNP and one examined BNP. In general, NT-proBNP is a specific and moderately sensitive test for identifying KD. The pooled sensitivity was 0.89 (95% CI 0.78 to 0.95) and the pooled specificity was 0.72 (95% CI 0.58 to 0.82). The area under the summary ROC curve was 0.87 (95% CI 0.83 to 0.89). The positive likelihood ratio (LR+ 3.20, 95% CI 2.10 to 4.80) was sufficiently high to be qualified as a rule-in diagnostic tool in the context of high pre-test probability and compatible clinical symptoms. A high degree of heterogeneity was found using the Cochran Q statistic. CONCLUSIONS: Current evidence suggests that NT-proBNP may be used as a diagnostic tool for KD. NT-proBNP has high diagnostic value for identifying KD in patients with protracted undifferentiated febrile illness. Prospective large cohort studies are needed to help determine best cut-off values and further clarify the role of NT-proBNP in the diagnosis process of KD.

Unfavorable attitudes toward receiving methadone maintenance therapy and associated factors among the inmates using intravenous heroin.

The aims of this study were to examine unfavorable attitudes toward receiving methadone maintenance therapy (MMT) and associated factors among inmates using intravenous heroin in Taiwan. A total of 315 inmates using intravenous heroin were recruited. Their unfavorable attitudes toward receiving MMT after discharge from prison were evaluated using the Client Attitudes Toward Methadone Programs Scale. The associations of unfavorable attitudes toward receiving MMT with sociodemographic and drug-using characteristics, human immunodeficiency virus serostatus, perceived family support, and depression were examined using multiple regression analysis. The results of this study showed that the mean score of unfavorable attitudes toward receiving MMT, determined on the Client Attitudes Toward Methadone Programs Scale, was 9.918 (standard deviation=2.277, range=5-20). Heroin-using inmates who were young, started using heroin earlier, perceived many advantages and few disadvantages of heroin use, had never received MMT, and had severe depression, had unfavorable attitudes toward receiving MMT. Based on the results of this study, we suggest that inmates who have the factors associated with unfavorable attitudes toward receiving MMT should receive intervention and motivational interviewing to improve their attitudes toward MMT and to increase their opportunity to receive MMT after discharge from prison.

Body weight statuses and their sociodemographic correlates among adolescents in southern Taiwan: results using two sets of cutoff references.

PURPOSE: To examine the differences in the prevalence of overweight and obesity based on the cutoff references established by the International Obesity Task Force (IOTF) and the Working Group on Obesity in China (WGOC), the prevalence of underweight on the IOTF reference, and the sociodemographic correlates of body weight statuses in Taiwanese adolescents. METHODS: Overweight and obesity in 10,371 Taiwanese adolescents were determined by the IOTF and WGOC cutoff references for body mass index (BMI). Underweight was determined by the IOTF. The prevalence of overweight and obesity using the IOTF standard were compared to those using the WGOC standard. Associations of body weight statuses with gender, age, residential status, and parental education level were also examined. RESULTS: Using the IOTF standard, 3.4% were underweight, 15.2% were overweight, and 6.1% obese, whereas 14.1% were considered overweight and 8.7% were obese by the WGOC standard. For both genders, more adolescents were classified as overweight by the IOTF standard and as obese by the WGOC standard. Although females were more likely to be underweight than males, males were more likely to be overweight or obese than females. For both genders, although older age increased the risk of being underweight, younger age increased the risk of being overweight or obese. For males, living in urban areas was associated with being overweight, and low paternal education level was associated with being obese. CONCLUSIONS: The prevalence of overweight and obesity may differ depending on the reference standard consulted. Paternal education level and urbanicity were associated with gender differences in the proportion of adolescents who were overweight or obese.

The associations between aggressive behaviors and internet addiction and online activities in adolescents.

PURPOSE: To evaluate (a) the association between Internet addiction and aggressive behaviors, as well as the moderating effects of gender, school, and depression on this association; and (b) to evaluate the association between Internet activities and aggressive behaviors. METHODS: A total of 9405 adolescents were recruited into this study and completed the questionnaires. Their aggressive behaviors, with or without Internet addiction, Internet activities, demographic data, with or without depression, self-esteem, family function, and the watching of violent TV were assessed. RESULTS: The results demonstrated that after controlling for the effects of shared associated factors and watching violent TV programs, adolescents with Internet addiction were more likely to have aggressive behaviors during the previous year. The association was more significant among adolescents in junior high schools than in senior high/vocational schools. Online chatting, adult sex Web viewing, online gaming, online gambling, and Bulletin Board System were all associated with aggressive behaviors. CONCLUSIONS: The results suggest that preventive programs for aggressive behaviors should pay attention to Internet addiction among adolescents. Also, intervention to prevent the effects of Internet addiction on aggressive behaviors should be conducted as early as possible.

Relationships among mental health status, social context, and demographic characteristics in Taiwanese aboriginal adolescents: a structural equation model.

The purposes of this study were to examine the relationships among mental health status, demographic characteristics, and social contexts, including family conflict and support, connectedness to school, and affiliation with peers who exhibit delinquent behavior and who use substances, among Taiwanese aboriginal adolescents. A total of 251 aboriginal junior high school students in an isolated mountainous area of southern Taiwan were recruited, and the relationships among mental health status, demographic characteristics, and social contexts among them were examined using a structural equation model (SEM). The SEM revealed that family conflict and support had direct influences on mental health status and connectedness to school. Family conflict had a direct relationship with affiliation with peers who use substances, and family conflict and support were both indirectly linked with affiliation with peers who exhibit delinquent behavior and who used substances; these were mediated by a poor mental health status. Female and older age were directly linked with a poor mental health status and were indirectly linked with a greater number of peers who exhibit delinquent behavior and who use substances via the poor mental health status. Disruptive parenting was directly linked with affiliation with peers who use substances. The authors suggest that those who devise strategies to improve aboriginal adolescents' mental health and discourage substance use should take these relationships among mental health, demographic characteristics, and social contexts into account.