A network meta-analysis of non-invasive brain stimulation interventions for autism spectrum disorder: evidence from randomized controlled trials.

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95% confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3+ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = -1.40, 95%CIs = -2.67 to -0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.

Nephrotoxicity of organophosphate flame retardants in patients with chronic kidney disease: A 2-year longitudinal study.

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.

MicroRNAs in Umbilical Cord Blood and Development in Full-Term Newborns: A Prospective Study.

Background: Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays. Objectives: Hence, this research seeks to investigate if the expression of miRNA in the umbilical cord blood of infants can forecast their developmental outcomes as they grow older. Design and method: We enrolled 143 full-term newborns, delivered either via cesarean section (CS) or through natural spontaneous delivery (NSD). We then analyzed the profiles of specific miRNAs (miR-486-5p, miR-126-5p, miR-140-3p, miR-151a-3p, miR-142-5p, and miR-30e-5p) in the umbilical cord blood of these infants. Subsequently, we performed follow-up assessments using Bayley-III scores when the cohort reached 1 year of age. Furthermore, we conducted pathway-enrichment analyses on the target genes associated with these examined miRNAs. Results: When comparing newborns delivered via cesarean section (CS) to those born via natural spontaneous delivery (NSD), we observed notable differences. Specifically, newborns through NSD displayed significantly higher ΔCt values for miR-486-5p, alongside lower ΔCt values for miR-126-5p and miR-151a-3p in their cord blood. At 1 year of age, cognitive development was significantly linked to the ΔCt values of miR-140-3p and miR-142-5p, while language development showed a significant association with the ΔCt values of miR-140-3p. Moreover, our pathway enrichment analyses revealed that the target genes of these miRNAs were consistently involved in the pathways related to neurons, such as axon guidance and the neurotrophin signaling pathway. Conclusion: In summary, this study represents a pioneering effort in elucidating the potential connections between miRNA levels in cord blood and the health indicators and neurodevelopment of newborns at 1 year of age. Our findings underscore the significance of miRNA levels at birth in influencing mechanisms related to neurodevelopment.

The Interrelationship of Benefit Finding, Demoralization, and Stigma among Patients with Parkinson's Disease and Their Caregivers.

Parkinson's disease (PD) is a debilitating neurodegenerative disease with a relentlessly progressive course of illness. This study aimed to assess the dyadic dynamics of benefit finding (BF), demoralization, and stigma on the depression severity of PD patients and their caregivers. This study used a cross-sectional design with purposive sampling. In total, 120 PD patients and 120 caregivers were recruited from the neurological ward or neurological outpatient clinic of a medical center in Taiwan from October 2021 to September 2022. PD patients and their caregivers were enrolled and assessed using the Mini International Neuropsychiatric Interview, the Benefit Finding scale, Demoralization Scale, Stigma Subscale of the Explanatory Model Interview Catalogue, and Taiwanese Depression Questionnaire. Among the 120 patients and 120 caregivers that successfully completed the study, 41.7% (N = 50) and 60% (N = 72) were female, respectively. The most common psychiatric diagnoses of both the PD patients (17.5%) and their caregivers (13.3%) were depressive disorders. Using structural equation modeling, we found that the stigma, BF, and demoralization of PD patients might contribute to their depression severity. Demoralization and stigma of PD patients' caregivers might also contribute to the depression severity of PD patients. Caregivers' BF and demoralization were significantly linked with their depression severity. PD patients' BF degree and their caregivers' BF degree had significant interactive effects. Both patients' and their caregivers' stigma levels had significant interactive effects. Clinicians should be aware of and manage these contributing factors between PD patients and their caregivers in order to prevent them from exacerbating each other's depression.

Neural Network Dynamics and Brain Oscillations Underlying Aberrant Inhibitory Control in Internet Addiction.

Previous studies have reported a role of alterations in the brain's inhibitory control mechanism in addiction. Mounting evidence from neuroimaging studies indicates that its key components can be evaluated with brain oscillations and connectivity during inhibitory control. In this study, we developed an internet-related stop-signal task with electroencephalography (EEG) signal recorded to investigate inhibitory control. Healthy controls and participants with Internet addiction were recruited to participate in the internet-related stop-signal task with 19-channel EEG signal recording, and the corresponding event-related potentials and spectral perturbations were analyzed. Brain effective connections were also evaluated using direct directed transfer function. The results showed that, relative to the healthy controls, participants with Internet addiction had increased Stop-P3 during inhibitory control, suggesting that they have an altered neural mechanism in impulsive control. Furthermore, participants with Internet addiction showed increased low-frequency synchronization and decreased alpha and beta desynchronization in the middle and right frontal regions compared to healthy controls. Aberrant brain effective connectivity was also observed, with increased occipital-parietal and intra-occipital connections, as well as decreased frontal-paracentral connection in participants with Internet addiction. These results suggest that physiological signals are essential in future implementations of cognitive assessment of Internet addiction to further investigate the underlying mechanisms and effective biomarkers.

Human transcriptome array analysis and diffusion tensor imaging in attention-deficit/hyperactivity disorder.

The mRNA markers identified using microarray assay and diffusion tensor magnetic resonance imaging (DTI) were applied to elucidate the pathophysiology of attention-deficit hyperactivity disorder (ADHD). First, we obtained total RNA from leukocytes from three children with ADHD and three healthy controls for analysis with microarray assays. Subsequently, we applied real-time quantitative polymerase chain reaction (qRT‒PCR) assays to validate the differential expression of 7 genes (COX7B, CYCS, TFAM, UTP14A, ZNF280C, IFT57 and NDUFB5) between 130 ADHD patients and 70 controls, and we built an ADHD prediction model based on the ΔCt values of aforementioned seven genes (AUROC = 0.98). Finally, in a validation group (28 patients with ADHD and 27 healthy controls), mRNA expression of the above seven genes also significantly differentiated ADHD patients from controls (AUROC value = 0.91). The DTI analysis showed increased fractional anisotropy (FA) of the forceps minor, superior corona radiata, posterior corona radiata and anterior corona radiata in ADHD patients. Moreover, the FA of the right superior corona radiata tract was positively correlated with ΔCt levels of the COX7B gene and the IFT57 gene. The results shed a new light on a genetic profile of ADHD that may help in deciphering the white matter microstructural features in disease pathogenesis.

Correlation of potential diagnostic biomarkers (circulating miRNA and protein) of bipolar II disorder.

OBJECTIVES: We previously identified certain peripheral biomarkers of bipolar II disorder (BD-II) including circulating miRNAs (miR-7-5p, miR-142-3p, miR-221-5p, and miR-370-3p) and proteins (Matrix metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)). We try to explore the connection between these biomarkers. METHODS: We explored correlations between the peripheral levels of above circulating miRNAs and proteins in our previously collected BD-II (N = 96) patients and control (N = 115) groups. We further searched TargetScan and BioGrid websites to identify direct and indirect interactions between these protein-coding genes and circulating miRNAs. RESULTS: In the BD-II group, we identified significant correlations between the miR-221-5p and CA-1 (rho = -0.323, P = 0.001), FARSB (rho = 0.251, P = 0.014), MMP-9 (rho = 0.313, P = 0.002) and PCSK9 (rho = 0.252, P = 0.014). The miR-370-3p also significantly correlated with FARSB expression (rho = 0.330, P = 0.001) and PCSK9 expression (rho = 0.221, P = 0.031) in the BD-II group. Our findings were in line with the modulating axis identified from TargetScan and BioGrid, miR-221-5p/CA-1/MMP9 and miR-370-3p/FARSB/PCSK9, suggesting their association with BD-II. CONCLUSION: Our result supported that peripheral candidate miRNA and protein biomarkers may interact in BD-II. We concluded that miR-221-5p/CA-1/MMP9 and miR-370-3p/FARSB/PCSK9 axes might act a critical role in the pathomechanism of BD-II.

Mortality and Lithium-Protective Effects after First-Episode Mania Diagnosis in Bipolar Disorder: A Nationwide Retrospective Cohort Study in Taiwan.

INTRODUCTION: This study aimed to estimate all-cause mortality in patients after a first-episode mania (FEM) and examine whether six guideline-recommended medications can reduce mortality. METHODS: The cohort included population-based FEM samples and matched controls from Taiwan, spanning 2007 to 2018. The primary outcomes assessed were all-cause/suicide-related mortality, while the secondary outcome focused on mortality associated with pharmacological treatments. We compared mortality in post-FEM patients and age-/sex-matched controls without any diagnosed bipolar disorders and patients with and without psychopharmacological treatment using Cox regression analysis, respectively. Statistics were presented with time-to-event adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs). RESULTS: The study included 54,092 post-FEM patients and 270,460 controls, totaling 2,467,417 person-years of follow-up. Post-FEM patients had higher risks of all-cause mortality (AHR 2.38, 95% CI: 2.31-2.45) and suicide death (10.80, 5.88-19.84) than controls. Lithium (0.62, 0.55-0.70), divalproex (0.89, 0.83-0.95), and aripiprazole (0.81, 0.66-1.00) were associated with reduced all-cause mortality compared to non-users. There were no significant all-cause mortality differences for quetiapine (0.95, 0.89-1.01), risperidone (0.92, 0.82-1.02), and paliperidone (1.24, 0.88-1.76) users. When accounting for drug action onset times in sensitivity analyses, only lithium significantly reduced all-cause mortality (AHR range 0.65-0.72). There were 35 and 16 suicide deaths in post-FEM patients and controls, respectively. No drug had a significant effect on suicide deaths (lithium: 6; divalproex: 7; aripiprazole: 0; quetiapine: 10; risperidone: 4; paliperidone: 1). CONCLUSION: Post-FEM patients had a higher risk of all-cause/suicide-related mortality, and lithium treatment might reduce all-cause mortality.

Temporal Alpha Dissimilarity of ADHD Brain Network in Comparison With CPT and CATA.

Attention deficit hyperactivity disorder (ADHD) is a chronic neurological and psychiatric disorder that affects children during their development. To find neural patterns for ADHD and provide subjective features as decision references to assist specialists and physicians. Many studies have been devoted to investigating the neural dynamics of the brain through resting-state or continuous performance tests (CPT) with EEG or functional magnetic resonance imaging (fMRI). The present study used coherence, which is one of the functional connectivity (FC) methods, to analyze the neural patterns of children and adolescents (8-16 years old) under CPT and continuous auditory test of attention (CATA) task. In the meantime, electroencephalography (EEG) oscillations were recorded by a wireless brain-computer interface (BCI). 72 children were enrolled, of which 53 participants were diagnosed with ADHD and 19 presented to be typical developing (TD). The experimental results exhibited a higher difference in alpha and theta bands between the TD group and the ADHD group. While the differences between the TD group and the ADHD group in all four frequency domains were greater than under CPT conditions. Statistically significant differences ( [Formula: see text]) were observed between the ADHD and TD groups in the alpha rhythm during the CATA task in the short-range of coherence. For the temporal lobe FC during the CATA task, the TD group exhibited statistically significantly FC ( [Formula: see text]) in the alpha rhythm compared to the ADHD group. These findings offering new possibilities for more techniques and diagnostic methods in finding more ADHD features. The differences in alpha and beta frequencies were more pronounced in the ADHD group during the CPT task compared to the CATA task. Additionally, the disparities in brain activity were more evident across delta, theta, alpha and beta frequency domains when the task given was a CATA as opposed to a CPT. The findings presented the underlying mechanisms of the FC differences between children and adolescents with ADHD. Moreover, these findings should extend to use machine learning approaches to assist the ADHD classification and diagnosis.

Psychological distress and related factors among caregivers of children with attention-deficit/hyperactivity disorder during the COVID-19 pandemic.

The present study examined the relationships of caregiver factors (including caregivers' age, sex and educational year), child-family interactions (caregivers' difficulties in managing children's protective behaviors against COVID-19, learning and daily performance, children's conflict with elders and siblings, and parenting styles), and children's factors (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms) with psychological distress of the caregivers of children with ADHD in the COVID-19 pandemic. This study recruited 252 caregivers of children with ADHD to participate and complete a questionnaire collecting their psychological distress in the COVID-19 pandemic, demographics, difficulties in managing children's protective behaviors against COVID-19, learning and daily performance, and parenting styles as well as children's conflict with elders and siblings, and the ADHD and ODD symptoms. Hierarchical regression models were constructed to examine the factors related to psychological distress among caregivers. Factors across caregiver, child, and child-family interaction dimensions, including children's conflict levels with elders and siblings, inattention symptoms, and caregivers' difficulties in managing children's protective behaviors against COVID-19, learning and daily performance, female sex, and younger age were significantly associated with psychological distress among caregivers in various hierarchical regression models. Health professionals should take the relevant factors identified in this study when developing an intervention to relieve caregivers' psychological distress in the COVID-19 pandemic.

Post COVID-19 condition and behavioral manifestations in Taiwanese children.

BACKGROUND: This study investigated the prevalence of post COVID-19 condition (PCC) in Taiwanese children, explored common symptoms and behavioral manifestations in children with PCC, and examined potential associations with parental stress and family functioning. METHODS: A total of 116 children who had contracted COVID-19 and their parents participated. At 1 month after the confirmed COVID-19 infection (baseline), the parents were asked to complete a questionnaire about the post COVID-19 symptoms, the child behavior checklist (CBCL) based on the child's situation, also the impact event scale of COVID-19 (IES-C) and family APGAR based on the parents' own situation. Three months after the confirmed COVID-19 infection, parents were again asked to complete the same questionnaires as they did at baseline. RESULTS: Results showed that 44.8% of the children met the criteria for PCC, with the most common symptoms being sputum/nasal congestion, tiredness and decreased concentration. Children without PCC exhibited a significant decrease in CBCL scores during the 2-month follow-up, while no such decrease was observed in children with PCC. However, no significant correlations were found between the number of post COVID-19 symptoms, behavioral manifestations, parental stress levels, and family functioning. CONCLUSIONS: Children with PCC have a less favorable trajectory in improving their behavioral manifestations. Additionally, in the post-pandemic era, post COVID-19 symptoms in children are not necessarily correlated with parental stress and family functioning. Further research is needed to better understand the long-term implications of PCC in children and its impact on their mental well-being, as well as their families.

Altered Inhibitory Control Mechanism of Internet Addiction: An Electroencephalogram Study of Brain Oscillations and Connectivity.

The development of the Internet has changed people's lives and has resulted in a new type of addictive behavior. In the past decade, Internet game addiction has been identified as a mental illness. Considering internet game addiction as the only cause of mental illness is limited in its view, as internet games, social platforms and other internet multimedia are also widely used. Thus, other internet-related behaviors, that maybe addictive, should also be included. Previous neuroimaging studies have reported a role of alteration in brain's inhibitory control mechanism in addiction. However, the results are still diverse with inconsistent findings. In this study, we used an Internet-related stop signal task with EEG signals recorded to study the relationship between internet addiction through brain oscillations and functional connectivity. We also compared the differences in the brain connectivity between addicted and non-addicted participants using phase lag index. We found that the brain connectivity in participants addicted to the internet is significantly greater than that of nonaddicted users.Clinical Relevance- In this study, we assessed brain functional networks of participants with Internet Gaming Disorder and internet addiction.

Comparative predictive efficacy of atherogenic indices on metabolic syndrome in patients with schizophrenia.

BACKGROUND: Schizophrenia patients endure high risks of metabolic syndrome and related cardiovascular mortality. Evidence on comparing detective power among atherogenic indices of the metabolic syndrome in schizophrenia patients with antipsychotics treatment is still lacking. METHOD: We recruited 128 schizophrenia patients and collected blood samples to determine plasma levels of fasting glucose, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol. Five components of metabolic syndrome were assessed. Atherogenic indices, such as atherogenic index of plasma (AIP), atherogenic coefficient (AC), Castelli's risk index-I (CRI-I) and Castelli's risk index-II (CRI-II), were calculated. The area under the receiver operating characteristics curve (AUC) and regression analysis were adopted to compare the detective power of each atherogenic index for metabolic syndrome. The optimal cutoff points using maximization of Youden's index and the positive likelihood ratios were calculated. RESULTS: 51 (39.8 %) had metabolic syndrome. AIP (0.2 ± 0.2 vs. 0.6 ± 0.2), AC (2.5 ± 0.9 vs. 3.4 ± 0.9), CRI-I (3.5 ± 0.9 vs. 4.4 ± 0.9,) and CRI-II (2.1 ± 0.7 vs. 2.6 ± 0.7) were higher in the group with metabolic syndrome (all p < 0.001). AIP had the highest AUC (0.845, 95 % CI: 0.770, 0.920). The optimal cut-off point of AIP to predict metabolic syndrome was 0.4 with the corresponding sensitivity 83.7 %, specificity 80.3 %, and positive likelihood ratio 4.2. Regression analysis revealed that only AIP significantly correlated with the metabolic syndrome (p < 0.001). CONCLUSION: Among atherogenic indices, only AIP has superior discrimination for detecting metabolic syndrome in schizophrenia with antipsychotics treatment.

Perception and Mental Health Status Regarding COVID-19 Vaccination Among Taiwanese Adolescents and Their Caregivers.

Background: Vaccinating adolescents is a vital strategy to enhance population protection without imposing overly restrictive measures on our daily lives during the COVID-19 pandemic. As teenagers gain more independence, their willingness to get vaccinated may depend on their own understanding of the pandemic, vaccines, and mental well-being, as well as that of their caregivers. Our study aimed to examine how Taiwanese adolescents and their caregivers perceive COVID-19 vaccination and assess their mental health status. Methods: We invited a total of 138 vaccinated adolescents and their caregivers to complete several questionnaires, including the Drivers of COVID-19 Vaccination Acceptance Scale (DrVac-COVID19S), Impact of Event Scale (IES), and Chinese Health Questionnaire (CHQ). Results: Among the adolescents, 76.8% considered the BNT162b2 vaccine (Pfizer-BioNTech) as the ideal option for COVID-19 vaccination, while 27.5% of caregivers expressed acceptance of any available vaccine. Adolescents scored higher than caregivers in terms of vaccine value (p<0.001) and autonomy (p<0.001), but lower in knowledge (p<0.001), as assessed by the DrVac-COVID19S subscales. The adolescents' intention to get vaccinated against COVID-19 (DrVac-COVID19S total score) showed a positive correlation with their perception of the pandemic's impact (IES scores, r=0.214, p=0.012) and their caregivers' vaccination intention (r=0.371, p<0.001). Furthermore, adolescents' mental health demonstrated a positive association with the mental health of their caregiver (CHQ total scores, r=0.481, p<0.001). Conclusion: During the COVID-19 outbreak, caregivers have encountered heightened levels of mental stress, and this stress has been found to be positively correlated with the mental stress experienced by adolescents and their intentions regarding vaccination. These findings can serve as crucial references for healthcare providers and governments when formulating vaccination policies for adolescents in the future.

Levels of organophosphate flame retardants and their metabolites among 391 volunteers in Taiwan: difference between adults and children.

Background: Organophosphate flame retardants (OPFRs) are ubiquitous in the environment. The compositions and concentrations of different OPFRs metabolites vary in different environments depending on different human activities. The objective of the present study was to evaluate the exposure of different age groups to OPFRs in Taiwan. Methods: Volunteers provided urine samples and responded to questionnaires including demographic factors, underlying disease, lifestyle information, and occupation from October 2021 to January 2022. OPFR measurements were performed using a Waters Acquity Ultra-Performance Liquid Chromatography system coupled with a Waters Xevo TQ-XS mass spectrometer. Results: A total of 391 volunteers (74 children and 317 adults) were enrolled in this study. The concentrations (presented as µg/g creatinine) of bis(1,3-dichloro-2-propyl) phosphate (BDCPP, p = 0.029) and tri-n-butyl phosphate (TNBP, p = 0.008) were higher in the adult group, while the concentrations of bis-2-chloroethyl phosphate (BCEP, p = 0.024), diphenyl phosphate (DPHP, p < 0.001), tris(1,3-dichloro-2-propyl) phosphate (TDCPP, p = 0.009), and Tris(2-butoxyethyl) phosphate (TBEP, p = 0.007) were higher in the child group. Compared with school age children (>6 years), the concentration of di(2-n-butoxyethyl) phthalate (DBEP, 1.14 vs. 0.20 µg/g creatinine, p = 0.001), DPHP (1.23 vs. 0.54 µg/g creatinine, p = 0.036), TBEP (1.63 vs. 0.29 µg/g creatinine, p < 0.001), and the sum of OPFR metabolites (ΣOPFRs, 6.58 vs. 2.04 µg/g creatinine, p < 0.001) were statistically higher in preschool-aged children. After adjusting for confounding factors, pre-school age [odds ratio (OR): 4.579, 95% confidence interval (CI): 1.389-13.115] and current smoker (OR: 5.328, 95%CI: 1.858-14.955) were independently associated with the risk of ΣOPFRs higher than 90 percentile. Conclusion: This study revealed the distribution of different OPFRs metabolites in children and adults. DBEP, DPHP, TBEP, and ΣOPFR were higher in preschool-aged children. Pre-school age and current smoking status were independent risk factors for ΣOPFRs higher than 90 percentile.

Sex differences in vitamin D and behavioral profiles among children with allergic diseases.

Previous studies have suggested that vitamin D has a protective effect on allergic diseases, while an individual's sex may have a moderating effect on the relationship between vitamin D and allergic-related immunity. This study aimed to determine the role of vitamin D in children with coexisting allergic diseases in the context of sex differences and to explore the behavioral profiles of these patients. We recruited a total of 103 children with atopic diseases and divided them into four groups: males with one allergic disease (MA1, n = 20), males with two or more allergic diseases (MA2, n = 26), females with one allergic disease (FA1, n = 30), and females with two or more allergic diseases (FA2, n = 27). We measured serum calcium levels using the colorimetric method and serum 25-OH vitamin D total levels using electrochemiluminescence immunoassay. We found that MA2 had significantly lower vitamin D levels than MA1 and FA2. The levels of IgE were negatively correlated with vitamin D in females, whereas the levels of IgE were not significantly correlated with vitamin D in males. Furthermore, serum IgE was significantly correlated with children's adaptive skills, and different sexes were associated with different aspects of adaptive skills. Our findings suggest a protective role of vitamin D in the development of one allergic disease against the coexistence of allergic diseases in males, as well as extend the evidence for sex differences in immunity by demonstrating a sex-different correlation between IgE and vitamin D and the relationship between IgE and children's adaptive skills.

The Morbidity and Associated Factors of Depression in Caregivers of Patients with Depressive Disorder.

Objective: Depressive disorder significantly impacts patients' daily living activities and quality of life. Caregivers of patients with depression may also suffer from psychological distress related to the chronic burden of caring for the patient's mood changes. The purpose of this study was to evaluate the morbidity and associated factors of depression in caregivers of patients with depressive disorder. Methods: In this study, we used a cross-sectional design with consecutive sampling. Study subjects were recruited from the psychiatric outpatient clinic of a medical center from August 2021 to June 2022. Caregivers of depressive disorder patients were enrolled and assessed using the Mini International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale (HADS), Suicide Assessment Scale (SAS), Stigma Scale of the Explanatory Model Interview Catalogue (EMIC), and Family APGAR Index. Results: Of the 120 caregivers that completed the study, 59.2% (n=71) were females. The most common psychiatric diagnosis was depressive disorders (25.8%), followed by anxiety disorders (17.5%) and insomnia disorder (15.8%); 54.2% of the caregivers had a psychiatric diagnosis. Using logistic regression analysis, we found that anxiolytics/hypnotics use (OR=5.58; 95% CI, 1.84-16.96; p<0.01), higher suicide risk (SAS) (OR=1.10; 95% CI, 1.05-1.16; p<0.001), and lower family support (APGAR scores) (OR=0.82; 95% CI, 0.71-0.94; p<0.01) were three significant associated factors. Conclusion: Depression was the most prevalent psychiatric diagnosis in caregivers of patients with depressive disorder. Early psychiatric diagnosis for caregivers of patients with depression is crucial to offering suitable support and treatment and may improve caregivers' quality of life.

The Outcome of Antipsychotics-induced Tardive Syndromes: A Ten-year Follow-up Study.

Objective: Tardive syndrome (TS) is an umbrella term used to describe a group of abnormal movement disorders caused by chronic exposure to dopamine receptor blocking agents. Few follow-up studies have been performed on the outcome of TS in patients using antipsychotics. The purpose of our study was to investigate the prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics. Methods: This retrospective cohort study consisted of 123 patients who received continuous treatment of antipsychotics in a medical center in Taiwan, from April 1, 2011 to May 31, 2021. We assessed the demographic and clinical characteristics, prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics. TS remission was defined as a Visual Analogue Scale score ≤ 3. Results: Of the 92 patients who completed the 10-year follow-up, 39 (42.4%) were found to have at least one episode of TS, with tardive dyskinesia (TD) being the most prevalent subtype (51.3%). With regard to concurrent physical illness, a history of extrapyramidal symptoms were significant risk factors for TS. During the 10-year follow-up period, the remission rate of TS was 74.3%. The use of antioxidants including vitamin B6 and piracetam was related to the remission of TS. Patients with tardive dystonia had a higher remission rate (87.5%) compared to TD (70%). Conclusion: Our study suggests that TS may be a treatable condition, and the key to a better outcome is early detection and prompt intervention, including closely monitoring antipsychotics-related TS symptoms and using antioxidants.

Predicting new-onset post-stroke depression from real-world data using machine learning algorithm.

Introduction: Post-stroke depression (PSD) is a serious mental disorder after ischemic stroke. Early detection is important for clinical practice. This research aims to develop machine learning models to predict new-onset PSD using real-world data. Methods: We collected data for ischemic stroke patients from multiple medical institutions in Taiwan between 2001 and 2019. We developed models from 61,460 patients and used 15,366 independent patients to test the models' performance by evaluating their specificities and sensitivities. The predicted targets were whether PSD occurred at 30, 90, 180, and 365 days post-stroke. We ranked the important clinical features in these models. Results: In the study's database sample, 1.3% of patients were diagnosed with PSD. The average specificity and sensitivity of these four models were 0.83-0.91 and 0.30-0.48, respectively. Ten features were listed as important features related to PSD at different time points, namely old age, high height, low weight post-stroke, higher diastolic blood pressure after stroke, no pre-stroke hypertension but post-stroke hypertension (new-onset hypertension), post-stroke sleep-wake disorders, post-stroke anxiety disorders, post-stroke hemiplegia, and lower blood urea nitrogen during stroke. Discussion: Machine learning models can provide as potential predictive tools for PSD and important factors are identified to alert clinicians for early detection of depression in high-risk stroke patients.

Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects.

Background: Organophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years. Objectives: Investigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population. Methods: Different age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined. Results: The mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 µg/L (standard deviation (SD) of 1.91 µg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 µg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p<0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns. Conclusion: To our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships.