Causes of death in individuals exposed to spousal, parental, and child suicide: a nationwide population-based cohort comparison study.

Exposure to suicide is associated with higher mortality, and the health impact varies depending on the types of kinship. However, the moderating role of kinship remains unclear. Therefore, this study aimed to compare causes of death between individuals exposed to spousal, parental, and child suicide to those exposed to natural or unnatural death. In this study, 1,929,872 individuals were enrolled, of whom 1,726,846 individuals were exposed to natural death, 141,206 individuals were exposed to unnatural death, and 61,820 individuals were exposed to suicide. To compare causes of death between kinship, stratified analysis and moderation analysis were conducted by using the Cox proportional hazard model and the cause-specific hazard model. Although higher mortality from specific causes, such as suicide, homicide, and vascular and unspecified dementia, was observed in individuals exposed to suicide compared to those exposed to natural and unnatural death (adjusted hazard ratio: 1.69 to 23.26), we did not observe higher all-cause mortality when compared to those exposed to unnatural death. Some causes of death were moderated by kinship. When compared to unnatural death, parental or spousal suicide was associated with higher mortality from suicide and homicide than child suicide (adjusted hazard ratio: 1.70 to 15.67), and parental suicide was associated with higher mortality from accidents than spousal suicide (adjusted hazard ratio: 1.81). These findings provide an integral understanding of the role of kinship in the impacts of suicide exposure on causes of death.

Comprehensive Comparisons of Family Health Between Families With One Immigrant Parent and Native Families in Taiwan: Nationwide Population-Based Cohort Study.

BACKGROUND: Mothers and children in families with one immigrant parent have been reported to be healthier than those in native families; however, the health of the fathers in these families has rarely been discussed in literature. OBJECTIVE: We aimed to comprehensively compare the health of all the family members between families with one immigrant parent (native fathers, immigrant mothers, and their children) and native families (native fathers, native mothers, and their children). METHODS: We conducted a cohort study by using the Taiwan Maternal and Child Health Database to recruit live-born children and their parents from 2004 to 2016. Overall, we identified 90,670 fathers, 91,270 mothers, and 132,457 children in families with one immigrant parent and 1,666,775 fathers, 1,734,104 mothers, and 2,637,191 children in native families and followed up with them from 2004 to 2017. The outcomes comprised common physical and mental disorders, catastrophic illnesses, mortality, and child adversities and accidents. The covariates comprised the child's year of birth, parental age, low-income status, and physical or mental disorder status. Logistic regression was performed to compare the risks of the outcomes between families with one immigrant parent and native families. RESULTS: The parents in families with one immigrant parent were more likely to be of low-income status and were older than the parents in native families. After adjusting for the covariates, fathers in families with one immigrant parent were found to have higher risks of physical and mental disorders, catastrophic illness, and mortality than fathers in native families. Conversely, mothers in families with one immigrant parent had lower risks of physical and mental disorders, catastrophic illness, and mortality than mothers in native families. Finally, the children in families with one immigrant parent generally had better physical and mental health but higher risks for leukemia, liver diseases, autism spectrum disorder, and road traffic accidents than children in native families. CONCLUSIONS: The health status of the members of families with one immigrant parent was nonhomogeneous, and the poorer general health of fathers in such families suggests health inequalities in families with one immigrant parent.

Moderating Effects of Friendship and Family Support on the Association Between Bullying Victimization and Perpetration in Adolescents.

School bullying can cause severe mental health problems for both victims and perpetrators. However, the association between bullying victimization and perpetration has rarely been discussed, and no study has investigated the effects of social support, such as friendship and family support, in moderating this association. Therefore, the authors examined the moderating effects of friendship and family support on the association between bullying victimization and perpetration in adolescents. Data were obtained from the 2009 Project for the Health of Adolescents. Through multistage stratified cluster sampling, 13 junior and 10 senior high schools in southern Taiwan were selected, resulting in a representative sample of 6,445 students from grades 7 to 12. School bullying and family support were examined using the Chinese version of the School Bullying Experience Questionnaire and the Family adaptability, partnership, growth, affection, resolve instrument, respectively. Friendship support was measured using the subscale of the Taiwanese Quality of Life Questionnaire for Adolescents and adolescents' number of friends, time spent with friends, and friend distributions. Linear regression modeling and the Johnson-Neyman technique were used to examine the moderating effects of friendship and family support on the association between bullying victimization and perpetration. For active bullying, having fun and talkative friends and friends outside school negatively moderated the intensity of the association between bullying victimization and perpetration (regression coefficients: -0.02 to -0.05), whereas, for passive bullying, only friends outside school negatively moderated the intensity of the association (regression coefficient: -0.05). By contrast, some components of friendship support positively moderated the associations. These findings suggest that higher friendship quality and having more friends outside of school attenuate the association between bullying victimization and perpetration in adolescents, thus increasing the understanding of the moderating role that social support play in such associations.

Circulating cytokines as predictors of depression in patients with breast cancer.

Depression is a common comorbid disorder associated with breast cancer, and it can have considerable physical and psychological impacts. Circulating cytokines have been proposed as a potential tool to predict depression in various diseases; however, limited studies have specifically examined it in breast cancer. In this study, we examined and compared the prediction ability of various circulating cytokines for depression in patients with breast cancer. Eighty-three patients with a new diagnosis of breast cancer not receiving chemotherapy were recruited; among them, 15 patients had depression and 68 did not have depression. Depression was evaluated using the Patient Health Questionnaire 9 (PHQ-9). Cytokine levels in the serum were measured using an immunology multiplex assay. Two types of cytokines were assayed: (1) proinflammatory cytokines (interleukin [IL]-1ß, IL-2, IL-6, IL-12, IL-17A, interferon [IFN]γ, and tumor necrosis factor [TNF]α) and (2) anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). Receiver operating characteristic (ROC) analysis was performed to calculate the area under the curves (AUCs), sensitivities, and specificities of circulating cytokines for predicting depression. As a result, IL-2 (AUC = 0.78) and IL-5 (AUC = 0.76) demonstrated good predictability for depression, even after controlling for the covariates (i.e. age, education, stage of cancer, surgery, radiation therapy, and hormone therapy). The optimal cut-off value of IL-2 for predicting depression was 1.06 pg/mL with a sensitivity of 86.7% and a specificity of 52.9%; this cytokine also had the best prediction ability in this study. Owing to the prediction ability and practical feasibility of circulating cytokines, they may be used as a valid laboratory diagnostic tool for depression in breast cancer.

Increased Alopecia Areata Risk in Children with Attention-Deficit/Hyperactivity Disorder and the Impact of Methylphenidate Use: A Nationwide Population-Based Cohort Study.

Alopecia areata (AA) is an autoimmune disease that causes sudden hair loss. Although few studies have reported the association between AA and attention-deficit/hyperactivity disorder (ADHD), the impact of methylphenidate (MPH) on AA has not been examined. This study examined whether AA risk is higher in children with ADHD than in those without ADHD as well as the impact of MPH use on AA risk in children with ADHD. From the Taiwan Maternal and Child Health Database, we enrolled all 1,750,456 newborns from 2004 to 2017 in Taiwan. Of them, 90,016 children received a diagnosis of ADHD whereas the remaining 1,660,440 did not. To compare AA risk in ADHD and the impact of MPH treatment on it, multiple Cox regression with adjustments for covariates (i.e., age, sex, and psychiatric comorbidities) was performed. The results indicated that 88 (0.098%) children with ADHD and 1191 (0.072%) children without ADHD had AA. Nevertheless, after adjustment for the covariates, AA risk was higher in children with ADHD than in those without ADHD (adjusted hazard ratio [aHR]: 1.30, 95% confidence interval [CI]: 1.04-1.64). Our data indicated a considerable reduction in AA risk (aHR: 0.64) among children with ADHD who received MPH than among those who did not receive MPH; however, this difference was nonsignificant, indicated by a wide 95% CI (0.32-1.25). In conclusion, ADHD and AA may share some underlying mechanisms.

Different impacts of COVID-19-related information sources on public worry: An online survey through social media.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly, as did COVID-19-related information on diverse media platforms. Excessive COVID-19-related information caused substantial mental distress among the public. Although most studies focused on the impact of information on individuals during the pandemic, they usually focused on information from internet sources, and few studies compared the impacts between different information sources. We examine the sociodemographic profiles of participants receiving different information sources and the impact of various COVID-19-related information sources on public worry. METHODS: A cross-sectional online survey with a total of 2007 participants aged 20 years and above recruited anonymously was conducted during the COVID-19 pandemic. The sociodemographic data, frequencies at which participants received COVID-19-related information, the information sources (e.g., traditional media, interpersonal information exchange, and academic courses), and the levels of past, current, and anticipated worry about COVID-19 were assessed. RESULTS: The most common sources of COVID-19-related information were internet media (80.52%), traditional media (52.62%), family members (24.36%), coworkers (23.57%), friends (21.08%), academic courses (20.18%), and medical staff (19.03%). We found that the COVID-19-related information from traditional media, internet media, and friends was associated with higher current worry (the unstandardized regression coefficient, B, ranged from 0.27 to 0.30), and the information from friends was associated with higher past worry (B was 0.18). In contrast, participants who received information from academic courses had lower past worry and anticipated worry (B ranged from -0.15 to -0.17). CONCLUSIONS: Academic courses may play a protective role in public worry during the pandemic. Therefore, academic courses and the information they provide may help facilitate public education and reduce public worry in cases of infectious disease outbreaks.

Differential associations of proinflammatory and anti-inflammatory cytokines with depression severity from noncancer status to breast cancer course and subsequent chemotherapy.

BACKGROUND: In this study, we examined the differential associations of various proinflammatory and anti-inflammatory cytokines with depression severity from the development of breast cancer to subsequent chemotherapy treatment. METHODS: A cross-sectional study was conducted on a sample of 116 women: 29 controls without cancer, 55 patients with breast cancer who were not receiving chemotherapy, and 32 patients with breast cancer who were receiving chemotherapy. Blood samples were assayed to evaluate serum levels of the following cytokines: interferon-γ, interleukin (IL)-12 (p70), IL-1ß, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-10, IL-13, IL-6, and IL-17A. Depression severity was assessed using the Patient Health Questionnaire. RESULTS: After adjustment for sociodemographics, consistent patterns of the association between cytokine and depression were noted in the different groups. No significant associations were observed in the controls. Inverse associations were observed between cytokines levels and depression severity in patients with breast cancer who were not receiving chemotherapy, whereas positive associations were noted in patients with breast cancer who were receiving chemotherapy. Specific differential relationships between IL-5 levels and depression severity were found between patients with breast cancer who were receiving and not receiving chemotherapy. CONCLUSIONS: Our study revealed differential relationships between cytokine levels and depression severity with the development of cancer. Immunostimulation and immunosuppression in breast cancer and cancer treatment may account for the differential responses with the development of breast cancer.

Correlations between Quality of Life, School Bullying, and Suicide in Adolescents with Attention-Deficit Hyperactivity Disorder.

Although adolescents with attention-deficit hyperactivity disorder (ADHD) have a higher risk of suicidality and more problems related to school bullying, and quality of life (QoL) is reportedly associated with school bullying, suicide, and ADHD, no study has examined their correlation. This study examined the complex relationships between QoL, school bullying, suicide, and ADHD symptoms. A total of 203 adolescents with ADHD aged between 12 and 18 years were recruited. School bullying and QoL were examined using the Chinese version of the School Bullying Experience Questionnaire and the Taiwanese Quality of Life Questionnaire for Adolescents. Network model analysis was conducted to graphically present their relationships. We identified triangular correlations between school bullying, QoL, and suicidality, indicating possible pathways from school bullying to suicidality, and the originating or mediating roles of personal competence and psychological well-being. Furthermore, the ADHD symptoms of inattention and hyperactivity/impulsivity may differentially regulate these pathways. Longitudinal studies are warranted to confirm these findings.

Enhanced Risk for Specific Somatic Myeloproliferative Neoplastic Mutations in Patients with Stroke.

BACKGROUND: Somatic mutations of Janus kinase 2 (JAK2V617F), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) are the major clonal molecules that drive the pathogenesis of myeloproliferative neoplasms (MPN). It is well recognized that MPN patients carry an excessive risk of thrombohemorrhagic complications. However, little is known about the prevalence of these clonal markers in patients with cerebral vascular disease. METHODS: To address this issue, 153 consecutive stroke patients in Taiwan were enrolled in the study. Allele-specific PCR (AS-PCR), real-time AS-PCR, and Illumina paired-end sequencing were employed to detect the presence of MPL, JAK2V617F, and CALR exon 9 mutations, respectively. RESULTS: JAK2V617F mutation was detectable in 13 samples (8.5%), but the allele burdens (AB) were greater than 1% in only six (3.9%) of them. Compared to JAK2-unmutated patients, those with JAK2V617F AB > 1% had significantly higher white blood count (p = 0.01), although four of the six did not exhibit MPN phenotypes. Two patients had a heterozygous CALR exon9 mutation locating outside the coding region and did not alter the amino acid sequence of this protein. On the other hand, there were no patients carrying the MPL mutations. Using patient age, baseline hemogram, and stroke-relevant risk factors, we developed a predictive model that could successfully identify stroke patients at risk of carrying clonal JAK2V617F mutation. CONCLUSION: The prevalence of JAK2V617F mutation in stroke patients was higher than that seen in general population. Based on our newly developed probability stratification model, genotyping of JAK2V617F mutation in selected patients with stroke might be warranted.

Aberrant let7a/HMGA2 signaling activity with unique clinical phenotype in JAK2-mutated myeloproliferative neoplasms.

High mobility group AT-hook 2 (HMGA2) is an architectural transcription factor that is negatively regulated by let-7 microRNA through binding to it's 3'-untranslated region. Transgenic mice expressing Hmga2 with a truncation of its 3'-untranslated region has been shown to exhibit a myeloproliferative phenotype. To decipher the let-7-HMGA2 axis in myeloproliferative neoplasms, we employed an in vitro model supplemented with clinical correlation. Ba/F3 cells with inducible JAK2V617F expression (Ton.JAK2.V617F cells) showed upregulation of HMGA2 with concurrent let-7a repression. Ton.JAK2.V617F cells treated with a let-7a inhibitor exhibited further escalation of Hmga2 expression, while a let-7a mimic diminished the Hmga2 transcript level. Hmga2 overexpression conferred JAK2-mutated cells with a survival advantage through inhibited apoptosis. A pan-JAK inhibitor, INC424, increased the expression of let-7a, downregulated the level of Hmga2, and led to increased apoptosis in Ton.JAK2.V617F cells in a dose-dependent manner. In samples from 151 patients with myeloproliferative neoplasms, there was a modest inverse correlation between the expression levels of let-7a and HMGA2 Overexpression of HMGA2 was detected in 29 (19.2%) of the cases, and it was more commonly seen in patients with essential thrombocythemia than in those with polycythemia vera (26.9% vs 12.7%, P=0.044). Patients with upregulated HMGA2 showed an increased propensity for developing major thrombotic events, and they were more likely to harbor one of the 3 driver myeloproliferative neoplasm mutations in JAK2, MPL and CALR Our findings suggest that, in a subset of myeloproliferative neoplasm patients, the let-7-HMGA2 axis plays a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes.

Indirubin-3'-monoxime promotes autophagic and apoptotic death in JM1 human acute lymphoblastic leukemia cells and K562 human chronic myelogenous leukemia cells.

Indirubin is the active component of Dang gui Long hui Wan, a traditional Chinese herbal medicine used as therapy for chronic myelogenous leukemia (CML). In clinical studies, indirubin seldom caused major side-effects. However, the functional effect of indirubin on acute lymphoblastic leukemia (ALL) is unclear. Therefore, we investigated the effects of indirubin-3'-monoxime (I3M) on the ALL cell line JM1 and the CML cell line K562 (control). The anti-leukemia effects and mechanisms of I3M were similar on ALL and CML cells. I3M significantly and dose-dependently decreased cell viability. The G2/M cell cycle phase was arrested and the sub-G1 proportion was relatively increased. In addition, caspase-3 activation led to poly(ADP-ribose) polymerase (PARP)-1 cleavage and the progression of apoptosis. Notably, I3M induced autophagy. However, I3M had no effect on necrosis in either cell line. We specifically found that I3M only marginally affected the survival of primary mature lymphocytes, and was not cytotoxic to granulocytes. Since I3M induced apoptosis and autophagy in human lymphocytic leukemia cells and caused few side-effects in healthy lymphocytes and granulocytes, I3M may be useful for clinical anti-ALL therapy.