Early predictors for maltreatment-related injuries in infancy and long-term mortality: a population-based study.

INTRODUCTION: Incidence, health consequences, and social burden associated with child maltreatment appeared to be borne disproportionately by very young children. We conducted a population-based data linkage study to explore child- and family-level factors that affect receiving different diagnoses of maltreatment injuries and investigate excessive mortality throughout toddlerhood. METHODS: We conducted a retrospective cohort study comprising 2.2 million infants born in 2004-2014 in Taiwan. Incident cases of child maltreatment were defined by hospitalization or emergency department visits for three heterogeneous diagnostic groups of maltreatment-related injuries (i.e., maltreatment syndrome, assaults, and undetermined causes) within 12 months after birth. The generalized linear model and landmark survival analyses were used to evaluate risk factors. RESULTS: An estimated 2.9‰ of infants experienced at least one maltreatment-related injury, with a three-year mortality rate of 1.3%. Low birthweight was associated with increased risk of receiving the diagnosis of three maltreatment injuries, particularly maltreatment syndrome (adjusted Incidence Rate Ratio [aIRR] = 4.08, 95% confidence interval [CI]: 2.93-5.68). Socially advantaged family condition was inversely linked with receiving the diagnosis of maltreatment syndrome and assaults (e.g., high income: aIRR = 0.55 and 0.47), yet positively linked with undetermined cause (aIRR = 2.05, 95% CI: 1.89-2.23). For infants exposed to maltreatment, low birth weight and non-attendance of postnatal care were highly predictive of fatality; low birthweight served as a vital predictor for premature death during toddlerhood (aIRR = 6.17, 95% CI: 2.36-15.4). CONCLUSIONS: Raising awareness of maltreatment-related injuries in infancy and predictors should be a priority for appropriate follow-up assessment and timely intervention.

Urban-Rural Differences in Depression Literacy Among High School Teachers in the Kingdom of Eswatini.

BACKGROUND: Concerns have been raised over teachers' mental health literacy in low-income countries and lower- and middle-income countries wherein pediatric mental health resources are limited. This study aims to investigate adolescent depression literacy among teachers in Eswatini and to explore the role of urbanicity. METHODS: We conducted a cross-sectional survey in 59 public high schools in Eswatini in 2019-2020. Data were collected by a paper-and-pencil questionnaire; depression literacy was assessed by the 17-item Adolescent Depression Knowledge Questionnaire. RESULTS: Teachers' adolescent depression literacy item-level correct rates fell between 27 and 80%. Although the multivariate response models indicated that teaching in urban areas was slightly associated with having higher depression literacy in general (adjusted odds ratio [aOR] = 1.46; 95% confidence interval = 1.00-2.12), such urban-rural differences did not manifest homogeneously across all items: urban teaching was significantly linked with reduced correct responses toward certain items concerning depression etiology and treatment, including "depression runs in some families," "major stress as a necessary cause," and "a curable illness" (aOR = 0.57 ∼ 0.68). CONCLUSION: Urban-rural differences in teachers' depression literacy were manifested at both scale- and item-levels. A critical need exists for urban/rural areas-tailored intervention on teachers' literacy toward mental disorders in the resource-limited regions to better improve health and developmental outcomes of students.

Gender differences in the risk of depressive disorders following the loss of a young child: a nationwide population-based longitudinal study.

BACKGROUND: Losing a child to death is one of the most stressful life events experienced in adulthood. The aim of the current study is to investigate parental risk of seeking treatment for major depression disorders (MDD) after a child's death and to explore whether such connection may operate differentially by parents' prior medical condition. METHODS: We studied a retrospective cohort of 7245 parents (2987 mothers and 4258 fathers) identified in the National Health Insurance Research Database of Taiwan (NHIRD) who had lost a child with age between 1 and 12 years. For comparison, the parents of 1:4 birth year- and gender-matched non-deceased children were retrieved (16,512 mothers and 17,753 fathers). Gender-specific Cox regression analyses were performed to estimate risk. RESULTS: Nearly 5.0% and 2.4% of bereaved mothers and fathers sought treatment for MDD within three years after a child's death, significantly higher than 0.8% and 0.5% in the non-bereaved parents. With covariate adjustment, the hazard ratio (HR) for maternal and paternal seeking treatment for MDD was estimated 4.71 (95% confidence interval [CI]: 3.35-6.64) and 1.93 (95% CI: 1.27-2.95), respectively. The increased risk of MDD varied by prior disease history; specifically, the increased risk of seeking treatment for MDD was especially prominent for those without chronic physical condition (CPC) (e.g., mothers with CPC: aHR = 2.38, 95% CI: 1.56-3.65 vs. no CPC: aHR = 9.55, 95% CI: 6.17-14.79). CONCLUSIONS: After the death of a child, parental elevated risk of MDD was especially prominent for the women and those without prior medical condition. Effective strategies addressing bereavement may require family-based, integrated physical and mental healthcare and even extended counseling service.

Association between childhood negative life events with alcohol expectancies in early adolescence: Cumulative risk and latent class approaches.

BACKGROUND: The present study aims to investigate the effects of childhood negative life events (NLEs) on alcohol expectancies (AEs) in early adolescence through cumulative risk and latent class approaches. METHODS: Data were obtained from a prospective cohort of 945 sixth graders (age 11-12) ascertained from 17 elementary schools in northern Taiwan (response rate = 61.0 %wt); subsequent assessments were conducted during eighth grade (n = 775, follow-up rate [FR] = 82.6 %wt). Information concerning socio-demographics, 14 NLEs, alcohol-related experience, and four-domain AEs was collected by self-administered questionnaires at childhood and follow-up. Latent class and multivariate analyses were used to evaluate the association estimates. RESULTS: Nearly one half of children had experienced at least one NLE in sixth grade, with one-tenth experiencing four or more NLEs. Three latent classes of NLEs were identified: "lesser experience (68.1 %wt)," "stressed relationship (27.6 %wt)," and "family instability (4.3 %wt)." The observed NLE-associated increase in AEs was relatively stronger in the cumulative approach: children experiencing four or more NLEs (ßwt = 1.27, 95 % CI = 0.27-2.27) and in the "stressed relationship" NLE class appeared to develop greater AEs (ßwt = 0.86, 95 % CI = 0.30-1.42). Moreover, such NLE-associated increase was especially salient in the AE domains regarding "global positive transformation" and "promoting relaxation or tension reduction". CONCLUSIONS: Our results provide insight into which experiences of multiple and "stressed relationship" negative life events arising from the family context in childhood may shape endorsed alcohol expectancies in adolescence, and implied that such effects may not uniformly operate across AE domain.

Differential Nonenrollment of Taiwanese Children in School-Based Substance Use Prevention Studies: A Multilevel Analysis.

OBJECTIVE: The present study investigated the extent to which individual and school characteristics may differentially affect parental consent and child assent in the enrollment of a school-based substance use prevention study in Taiwan. METHOD: This study linked field notes on response and consent status during enrollment of the school-based prevention study with administrative survey data reported by the targeted students when they were in fourth grade (age 10-11) (N = 2,560; 53% male, 97.8% matched). The outcome variables, defined by the combined status of parental consent/child assent, were nonresponse and negative, discordant, and positive consent. Individual characteristics included family (parental education, employment) and child (psychological/behavioral, substance use) factors. Aggregate school-level substance use and percentage of aboriginal students and nonnative parents served as school-level factors. Multilevel multinomial regression analyses were performed. RESULTS: Successful consent was obtained from only 820 students (32%). Male gender and feeling neglected by families were associated with failing to respond (adjusted odds ratio = 1.78 and 1.71, respectively). Higher parental educational attainment reduced the odds of negative consent by 30%, whereas having unemployed parents increased the odds of discordant consent by 326%. Children attending schools with a higher percentage of indigenous students were two times more likely to have nonresponse, negative consent, and discordant consent. CONCLUSIONS: Nonresponse to the consent request or negative consent appeared to be associated with disadvantaged background and unfavorable parent-child interaction. This suggests complex pathways underlying ascertainment and a need to modify the consent practices in school-based prevention studies involving minors, especially in schools with higher ethnic minority composition.

Adverse effects on birth weight of parental illegal drug use during pregnancy and within two years before pregnancy.

This study investigates possible links between maternal illegal drug use during pregnancy and up to two years before pregnancy with birth weight (BW), and explores the potential role of paternal illegal drug use on low birth weight. A population-based retrospective cohort study was conducted that linked four national databases in Taiwan. A total of 1,698 subjects with a criminal record of schedule I or II illegal drug use within two years before pregnancy were enrolled as the drug-exposed group, and 16,980 matched subjects were enrolled as the unexposed group. Multivariate analysis of BW found a decrease of 108.63 g (95% CI: -172.29, -44.96), 79.67 g (95% CI: -116.91, -42.43), and 69.78 g (95% CI: -106.71, -32.84) in newborns whose mothers used illegal drugs only during pregnancy (period I), only within one year before pregnancy (period II), and only within the second year before pregnancy (period III), respectively. Paternal use of illegal drugs before maternal pregnancy was significantly associated with low birth weight. The paternal effect on low birth weight was opposite the maternal effect. The adverse effect of illegal drug use on birth weight existed even if the mother did not use drugs during pregnancy but had ever used drugs during the two years before pregnancy. Paternal factors' contribution to low birth weight persisted, and the decrement of BW was even greater than the maternal effect within one or two years before pregnancy. Maternal and paternal illegal drug use may have a lasting effect on their offspring's birth weight.

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

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

Statin inhibits large hepatitis delta antigen-Smad3 -twist-mediated epithelial-to-mesenchymal transition and hepatitis D virus secretion.

BACKGROUND: Hepatitis D virus (HDV) infection may induce fulminant hepatitis in chronic hepatitis B patients (CHB) or rapid progression of CHB to cirrhosis or hepatocellular carcinoma. There is no effective treatment for HDV infection. HDV encodes small delta antigens (S-HDAg) and large delta antigens (L-HDAg). S-HDAg is essential for HDV replication. Prenylated L-HDAg plays a key role in HDV assembly. Previous studies indicate that L-HDAg transactivates transforming growth factor beta (TGF-ß) and induces epithelial-mesenchymal transition (EMT), possibly leading to liver fibrosis. However, the mechanism is unclear. METHODS: The mechanisms of the activation of Twist promoter by L-HDAg were investigated by luciferase reporter assay, chromatin immunoprecipitation, and co-immunoprecipitation analysis. ELISA and Western blotting were used to analyze L-HDAg prenylation, TGF-ß secretion, expression of EMT markers, and to evaluate efficacy of statins for HDV treatment. RESULTS: We found that L-HDAg activated Twist expression, TGF-ß expression and consequently induced EMT, based on its interaction with Smad3 on Twist promoter. The treatment of statin, a prenylation inhibitor, resulted in reduction of Twist promoter activity, TGF-ß expression, and EMT, and reduces the release of HDV virions into the culture medium. CONCLUSIONS: We demonstrate that L-HDAg activates EMT via Twist and TGF-ß activation. Treatment with statins suppressed Twist expression, and TGF-ß secretion, leading to downregulation of EMT. Our findings clarify the mechanism of HDV-induced EMT, and provide a basis for possible novel therapeutic strategies against HDV infection.

Family and school social capitals in late childhood predict youthful drinking behaviors and problems.

BACKGROUND: The present study aims to investigate the connection linking late childhood's family- and school- social capitals with subsequent alcohol drinking and problems. METHODS: Data were obtained from the Alcohol-Related Experiences among Children survey in Taiwan. A total of 928 6th graders (age 11-12) were recruited from 17 elementary schools in an urban region in 2006 (response rate = 61.0%wt); follow-ups were conducted at 8th grade (n = 783, follow-up rate = 82.6%wt) and young adulthood (age 18-19; n = 645, follow-up rate = 68.0%wt). Information concerning family social capital, alcohol drinking, and teacher-student relationship was collected by self-administered questionnaires; school social capitals were assessed via questionnaires and official statistics. Multilevel logistic regression analyses were used to evaluate relationship estimates. RESULTS: At 8th grade, nearly one in ten reported having drunk alcohol on four or more occasions (i.e., occasional drinking) in the past year; and 14% reported past-month binge drinking in young adulthood. Effects of family social capital differed by developmental stage; parental involvement appeared prominent in reducing occasional drinking only in adolescence (adjusted Odds Ratio [aOR] = 0.54). School social capital (e.g., teacher-student ratio) was salient in shaping alcohol involvement in adolescence (occasional drinking: aOR = 0.80, 95% CI = 0.63-0.98) and young adulthood (binge drinking: aOR = 0.71, 95% CI = 0.67-0.86). CONCLUSIONS: Our findings warrant future research on social capitals at family- and school- levels in late childhood, and inform preventive strategies targeting alcohol drinking and problems in young people.

Inadequate prenatal care utilization among women with and without methadone-treated opioid use disorders in Taiwan.

AIMS: The present study aims to investigate the utilization pattern of prenatal care and correlates for women with opioid use disorders (OUD) in Taiwan. METHOD: Using the data linkage between the Methadone Maintenance Treatment (MMT) register with national health insurance, national birth notification system, and birth registration system, we identified 1712 pregnancies with 20 or more gestational weeks from women enrolled in the MMT (heroin-exposed: receiving no methadone treatment during pregnancy, n = 1053 by 882 women; methadone-treated: receiving methadone for at least one day during pregnancy, n = 659 by 574 women) and their 1:10 matched pregnancies from 17,060 women without substance use disorder in the period of 2004-2013. The generalized linear mixed models with negative binomial and logit distributions were performed to evaluate the relationship between individual sociodemographic, health, and addiction treatment characteristics with the number of prenatal visits and receiving prenatal care in the first trimester (i.e., early entry). FINDINGS: Eighteen percent of pregnancies by women with OUD received no prenatal services and 21% had started prenatal care in the first trimester as compared with 1% and 46% in pregnancies by women without substance use disorders. For pregnancies by women with OUD, methadone treatment was not linked associated with prenatal care visits (adjusted relative risk [aRR] = 1.02; 95% = 0.92, 1.12). For methadone-treated pregnancies, treatment enrollment before pregnancy and spousal methadone treatment elevated prenatal visits by 8% and 18% (0.48 and 1.08 visits, respectively). Additionally, HIV infection (adjusted odds ratio [aOR] = 0.30, 95% CI = 0.10, 0.83) and prior delivery (aOR = 0.05, 95% CI = 0.01, 0.19) significantly reduced the odds of early entry into prenatal care. CONCLUSION: Integrating addiction treatment programs with prenatal care is urgently needed to increase adequate prenatal care for pregnant women with OUD, especially the multiparous ones.

Leisure activity participation in relation to alcohol purchasing and consumption in adolescence.

BACKGROUND: Building upon the socioecological perspective, this study examines prospective associations linking leisure activity participation with alcohol purchasing and consumption in early adolescence. METHODS: A total of 1763 seventh graders (age 12-13 years) were recruited from middle schools in urban Taiwan via multi-stage sampling and followed-up 1.5 years later during ninth grade. Information about leisure activities, covariates (i.e., gender, puberty development, family structure, parental educational attainment, monthly allowance, peer drinking, and childhood alcohol experience), and two outcome variables (i.e., alcohol purchasing and drinking behaviors) was gathered via web-based self-administered questionnaires. Data concerning alcohol outlets and recreational resource for each community district were retrieved from official statistics and commercial sources. Two-level hierarchical generalized linear models were used to evaluate association estimates. FINDINGS: Five percent of ninth graders ever purchased alcohol and nearly one in seven drank alcohol on three or more occasions (i.e., occasional drinking) in the past year. Sports, unstructured, and organized leisure activities were not linked with illegal alcohol purchasing when community contexts were statistically adjusted; a higher community on-premised alcohol outlet density increased alcohol purchasing by 94% (95% CI = 1.24-3.06). In contrast, unstructured leisure activity participation at 7th grade predicted occasional drinking (adjusted Odds Ratio [aOR] = 5.52; 95% CI = 3.13-9.74). Sports participation was associated with reduced risk of occasional drinking in the communities with high unregulated alcohol outlets (aOR for interaction = 0.58; P < .001). CONCLUSION: Our research provides insights to differential roles of leisure activity participation in shaping adolescents' commercial alcohol access and occasional drinking. Macro-social contexts should be considered in the efforts to reduce underage drinking problems through leisure activities.

Interaction of glycosphingolipids GD3 and GD2 with growth factor receptors maintains breast cancer stem cell phenotype.

Many studies have suggested that disialogangliosides, GD2 and GD3, are involved in the development of various tumor types. However, the functional relationships between ganglioside expression and cancer development or aggressiveness are not fully described. GD3 is upregulated in approximately half of all invasive ductal breast carcinoma cases, and enhanced expression of GD3 synthase (GD3S, alpha-N-acetylneuraminide alpha-2,8-sialyltransferase) in estrogen receptor-negative breast tumors, was shown to correlate with reduced overall patient survival. We previously found that GD2 and GD3, together with their common upstream glycosyltransferases, GD3S and GD2/GM2 synthase, maintain a stem cell phenotype in breast cancer stem cells (CSCs). In the current study, we demonstrate that GD3S alone can sustain CSC properties and also promote malignant cancer properties. Using MALDI-MS and flow cytometry, we found that breast cancer cell lines, of various subtypes with or without ectopic GD3S-expression, exhibited distinct GD2/GD3 expression profiles. Furthermore, we found that GD3 was associated with EGFR and activated EGFR signaling in both breast CSCs and breast cancer cell lines. In addition, GD3S knockdown enhanced cytotoxicity of the EGFR-inhibitor gefitinib in resistant MDA-MB468 cells, both in vitro and in vivo. Based on this evidence, we propose that GD3S contributes to gefitinib-resistance in EGFR-positive breast cancer cells and may be an effective therapeutic target in drug-resistant breast cancers.