Appetite hormone dysregulation and executive dysfunction among adolescents with bipolar disorder and disruptive mood dysregulation disorder.

Appetite hormone dysregulation may play a role in the pathomechanisms of bipolar disorder and chronic irritability. However, its association with executive dysfunction in adolescents with bipolar disorder and those with disruptive mood dysregulation disorder (DMDD) remains unclear. We included 20 adolescents with bipolar disorder, 20 adolescents with DMDD, and 47 healthy controls. Fasting serum levels of appetite hormones, including leptin, ghrelin, insulin, and adiponectin were examined. All participants completed the Wisconsin Card Sorting Test. Generalized linear models with adjustments for age, sex, body mass index, and clinical symptoms revealed that patients with DMDD had elevated fasting log-transformed insulin levels (p = .023) compared to the control group. Adolescents with DMDD performed worse in terms of the number of tries required to complete tasks associated with the first category (p = .035), and adolescents with bipolar disorder performed worse in terms of the number of categories completed (p = .035). A positive correlation was observed between log-transformed insulin levels and the number of tries required for the first category (ß = 1.847, p = .032). Adolescents with DMDD, but not those with bipolar disorder, were more likely to exhibit appetite hormone dysregulation compared to healthy controls. Increased insulin levels were also related to executive dysfunction in these patients. Prospective studies should elucidate the temporal association between appetite hormone dysregulation, executive dysfunction, and emotional dysregulation.

Sexually transmitted infection and teenage pregnancy in adolescents having parents with schizophrenia: a retrospective cohort study of 64,350 participants.

BACKGROUND: The risks of sexually transmitted infections (STIs) and teenage pregnancy in the offspring of parents with schizophrenia remain unknown. METHODS: From the Taiwan National Health Insurance Research Database, 5,850 individuals born between 1980 and 1999 having any parent with schizophrenia and 58,500 age-, sex-, income- and residence-matched controls without parents with severe mental disorders were enrolled in 1996 or on their birthdate and followed up to the end of 2011. Those who contracted any STI or became pregnant in adolescence during the follow-up period were identified. RESULTS: Cox regression analyses demonstrated that offspring of parents with schizophrenia (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.02-1.44), especially daughters (HR: 1.30, 95% CI: 1.06-1.58), were more likely to contract any STI later in life than the control comparisons. In addition, daughters of parents with schizophrenia had an elevated risk of being pregnant in their adolescence (HR: 1.47, 95% CI: 1.29-1.67) compared with those having no parents with severe mental disorders. DISCUSSION: The positive relationship between parental schizophrenia and offspring STIs and teenage pregnancy necessitates clinicians and public health officers to closely monitor the sexual health in the offspring of parents with schizophrenia so that optimal and prompt preventive measures can be taken in the at-risk group.

Appetite hormone dysregulation, body mass index, and emotional dysregulation in nonobese adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder: a cross-sectional association study.

BACKGROUND: Evidence has suggested that emotional dysregulation is a transdiagnostic feature in schizophrenia and major affective disorders. However, the relationship between emotional dysregulation and appetite hormone disturbance remains unknown in nonobese adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder. METHODS: In total, 22 adolescents with schizophrenia; 31 with bipolar disorder; 33 with major depressive disorder; and 41 healthy age-, sex-, and body mass index (BMI)/BMI percentile-matched controls were enrolled for assessing levels of appetite hormones, namely leptin, ghrelin, insulin, and adiponectin. Emotional regulation symptoms were measured using the parent-reported Child Behavior Checklist-Dysregulation Profile. RESULTS: Adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder exhibited greater emotional dysregulation symptoms than the control group (P = .037). Adolescents with bipolar disorder demonstrated higher log-transformed levels of insulin (P = .029) and lower log-transformed levels of leptin (P = .018) compared with the control group. BMI (P < .05) and log-transformed ghrelin levels (P = .028) were positively correlated with emotional dysregulation symptoms. DISCUSSION: Emotional dysregulation and appetite hormone disturbance may occur in the early stage of severe mental disorders. Further studies are required to clarify the unidirectional or bidirectional association of emotional dysregulation with BMI/BMI percentile and appetite hormones among patients with severe mental disorder.

Cardiometabolic comorbidities in autosomal dominant polycystic kidney disease: a 16-year retrospective cohort study.

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease and the fourth leading cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Nevertheless, there is a paucity of epidemiological research examining the risk factors and survival on RRT for ADPKD. Thus, we aimed to investigate the cumulative effects of cardiometabolic comorbidities, including hypertension (HTN), type 2 diabetes mellitus (DM), and dyslipidemia (DLP) to clinical outcomes in ADPKD. METHODS: We identified 6,142 patients with ADPKD aged ≥ 20 years from 2000 to 2015 using a nationwide population-based database. HTN, DM, and DLP diagnoses before or at the time of ADPKD diagnosis and different combinations of the three diagnoses were used as the predictors for the outcomes. Survival analyses were used to estimate the adjusted mortality risk from cardiometabolic comorbidities and the risk for renal survival. RESULTS: Patients with ADPKD who developed ESRD had the higher all-cause mortality (HR, 5.14; [95% CI: 3.88-6.80]). Patients with all three of the diseases had a significantly higher risk of entering ESRD (HR:4.15, [95% CI:3.27-5.27]), followed by those with HTN and DM (HR:3.62, [95% CI:2.82-4.65]), HTN and DLP (HR:3.54, [95% CI:2.91-4.31]), and HTN alone (HR:3.10, [95% CI:2.62-3.66]) compared with those without any three cardiometabolic comorbidities. CONCLUSIONS: Our study discovered the cumulative effect of HTN, DM, and DLP on the risk of developing ESRD, which reinforces the urgency of proactive prevention of cardiometabolic comorbidities to improve renal outcomes and overall survival in ADPKD patients.

The Development of Human Ex Vivo Models of Inflammatory Skin Conditions.

Traditional research in inflammatory dermatoses has relied on animal models and reconstructed human epidermis to study these conditions. However, these models are limited in replicating the complexity of real human skin and reproducing the intricate pathological changes in skin barrier components and lipid profiles. To address this gap, we developed experimental models that mimic various human inflammatory skin phenotypes. Human ex vivo skins were stimulated with various triggers, creating models for inflammation-induced angiogenesis, irritation response, and chronic T-cell activation. We assessed the alterations in skin morphology, cellular infiltrates, cytokine production, and epidermal lipidomic profiles. In the pro-angiogenesis model, we observed increased mast cell degranulation and elevated levels of angiogenic growth factors. Both the irritant and chronic inflammation models exhibited severe epidermal disruption, along with macrophage infiltration, leukocyte exocytosis, and heightened cytokine levels. Lipidomic analysis revealed minor changes in the pro-angiogenesis model, whereas the chronic inflammation and irritant models exhibited significant decreases in barrier essential ceramide subclasses and a shift toward shorter acyl chain lengths (

The influence of sex on major psychiatric comorbidities and parental psychiatric disorders in 22,698 children and adolescents with ICD-9-CM-based autism spectrum disorder.

It remains unclear how major psychiatric comorbidities and parental psychiatric disorders differ in males and females with autism spectrum disorder (ASD). Between 2001 and 2011, 17,627 children and 5071 adolescents with ASD (ICD-9-CM code: 299) were identified from Taiwan's National Health Insurance Research Database and assessed for major psychiatric comorbidities and parental psychiatric disorders. Compared with females with ASD, males with ASD were more likely to be diagnosed as having attention deficit hyperactivity disorder (relative risk [RR], 95% confidence interval [CI] 1.63, 1.51-1.75) and disruptive behavior disorder (1.38, 1.17-1.62) and less likely to be diagnosed as having schizophrenia (0.45, 0.36-0.56), bipolar disorder (0.58, 0.45-0.74), or intellectual disability (0.53, 0.49-0.58). Furthermore, compared with women, having a parental history of schizophrenia (RR, 95% CI 0.66, 0.49-0.89) or intellectual disability (0.34, 0.19-0.61) was less associated with ASD among men. However, the difference in ASD diagnosis between ICD-9-CM and ICD-10/11-CM systems may reflect the different, but surely overlapping, entity of ASD, which may limit the generalization of our results. Additional studies should be performed.

Relationships among green space, ambient fine particulate matter, and cancer incidence in Taiwan: A 16-year retrospective cohort study.

INTRODUCTION: Green space and air pollution have been recognized as vital health determinants. There is a paucity of studies examining the interplay between green space, fine particulate matter (PM2.5), and the incidence of specific cancers. OBJECTIVE: We aimed to explore the contributions of green space and ambient PM2.5 to the risk of specific cancers in terms of the most common cancers based on incidence or mortality rate in Taiwan and to ascertain the interaction between green space and PM2.5 and their role in cancer risk. MATERIALS AND METHODS: This retrospective longitudinal cohort study included 407,415 participants. Data were obtained from the 2000-2015 Mei Jau Health Examination Database linked to the Taiwan Cancer Registry and Causes of Death datasets. All participants were aged ≥20 years and had no history of cancer. The environmental exposure were the normalized difference vegetation index (NDVI) and the 2-year average PM2.5 at baseline. Multivariate adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. We adjusted for covariates including demographics, anthropometrics, comorbidities, health behaviors, biochemical data, and environmental factors. RESULTS: During a median follow-up of 10.37 years, 11,576 cancer cases were reported. PM2.5 exposure increased the risk of all cancers (HR: 1.11, [95% CI: 1.06-1.15]), stomach cancer (HR: 1.27, [1.02-1.58]), endocrine gland cancer (HR: 2.13, [1.39-3.26]), breast cancer (HR: 1.12, [1.03-1.22]), and lung cancer (HR: 1.12, [1.01-1.24]). An increase in NDVI reduced the risk of prostate cancer (HR: 0.93, [0.88-0.99]) and lung cancer (HR: 0.95, [0.91-0.99]). NDVI influenced the incidence of prostate and all cancers by reducing PM2.5 concentrations. CONCLUSION: Long-term PM2.5 exposure is associated with an increased risk of some types of cancers. In contrast, an increase in environmental green space exposure is associated with lowering of the risk of prostate and lung cancer.

Suppressive effect of microRNA319 expression on rice plant height.

KEY MESSAGE: miR319 was identified as a dwarf-inducing gene from Shiokari and its dwarf near isogenic line, and its transgenic rice showed a reduced plant height. This finding reveals the potential application of miR319 in future molecular breeding. It is well known that microRNAs (miRNAs) play important roles in plant physiology, especially in development and stress responses. However, little is known about the role of miRNAs in plant height. In this study, the rice cultivar Shiokari and its dwarf near isogenic line Shiokari-d6 were analysed to identify and characterize plant height-associated miRNAs. This anatomic and morphological investigation revealed that the major cause of the shorter height of Shiokari-d6 is the significantly dis-elongated internodes, particularly the second internode and those underneath it. The results of miRNA microarray profiling and real-time RT-PCR indicated that miR319 is expressed at a significantly higher level in Shiokari-d6 than in Shiokari. Transgenic rice overexpressing miR319 in Oryza sativa L. cv. Tainung 67 generated through Agrobacterium-mediated transformation had a stable dwarf phenotype regardless of whether the plants were from the T1 or T2 generation. We also found that the internodes of miR319-overexpressing rice are shortened, particularly the third internode and those underneath it. Furthermore, we identified three putative miR319 target genes that were previously uncharacterized with expression levels that were negatively correlated with the expression of miR319. In conclusion, miR319 is the first miRNA proposed to be involved in plant height regulation, and its function may influence the elongation of internodes, which leads to decreased plant height.

Symptomatic menopausal transition and subsequent bipolar disorder among midlife women with major depression: a nationwide longitudinal study.

Previous studies suggested that menopausal transition played an important role in the clinical course of major depression and bipolar disorder. However, the role of symptomatic menopausal transition in diagnostic conversion from major depression to bipolar disorder was still unknown. Using the Taiwan National Health Insurance Research Database, 50,273 midlife women aged between 40 and 60 years in 2002∼2008 with major depression were enrolled in our study and divided into two subgroups based on the presence (n = 21,120) or absence (n = 29,153) of symptomatic menopausal transition. Subjects who had subsequent bipolar disorder during the follow-up were identified. Midlife women with major depression and symptomatic menopausal transition had a higher incidence of the diagnostic conversion to bipolar disorder (7.3 vs. 6.6%, p = 0.003) than those with major depression alone. Cox regression analysis after adjusting for demographic data and psychiatric comorbidities further showed that symptomatic menopausal transition was associated with an increased risk of developing bipolar disorder (HR 1.14, 95% CI 1.07∼1.23) among midlife women with major depression. Sensitivity test after excluding the 1-year and 3-year observation exhibited the consistent findings (HR 1.18, 95% CI 1.09∼1.28; HR 1.20, 95% CI 1.08∼1.34). Midlife women with the dual diagnoses of major depression and symptomatic menopausal transition had an increased risk of the diagnostic conversion to bipolar disorder compared to those with major depression alone. Further studies may be required to investigate the underlying mechanisms among menopausal transition and the diagnostic conversion from major depression to bipolar disorder.

Catalog of Erycina pusilla miRNA and categorization of reproductive phase-related miRNAs and their target gene families.

The orchid Erycina pusilla has a short life cycle and relatively low chromosome number, making it a potential model plant for orchid functional genomics. To that end, small RNAs (sRNAs) from different developmental stages of different organs were sequenced. In this miRNA mix, 33 annotated miRNA families and 110 putative miRNA-targeted transcripts were identified in E. pusilla. Fifteen E. pusilla miRNA target genes were found to be similar to those in other species. There were putative novel miRNAs identified by 3 different strategies. The genomic sequences of the four miRNAs that were identified using rice genome as the reference can form the stem loop structure. The t0000354 miRNA, identified using rice genome sequences and a Phalaenopsis study, had a high read count. The target gene of this miRNA is MADS (unigene30603), which belongs to the AP3-PI subfamily. The most abundant miRNA was E. pusilla miR156 (epu-miR156), orthologs of which work to maintain the vegetative phase by repressing the expression of the SQUAMOSA promoter-binding-like (SPL) transcription factors. Fifteen genes in the E. pusilla SPL (EpSPL) family were identified, nine of which contained the putative epu-miR156 target site. Target genes of epu-miR172, also a key regulator of developmental changes in the APETALA2 (EpAP2) family, were identified. Experiments using 5'RLM-RACE demonstrated that the genes EpSPL1, 2, 3, 4, 7, 9, 10, 14 and EpAP2-9, -10, -11 were regulated by epu-miR156 and epu-miR172, respectively.

Risk of type 2 diabetes mellitus between adolescents with antidepressant-resistant and antidepressant-responsive depression: A cohort study of 15,651 adolescents.

BACKGROUND: Whether response to antidepressants is related to the risk of developing type 2 diabetes mellitus (T2DM) in adolescents with depression remains unknown. METHODS: This study used the Taiwan National Health Insurance Research Database to enroll 1739 adolescents with antidepressant-resistant depression, 6956 with antidepressant-responsive depression, and 6956 controls between 2001 and 2010, with an end-of-2011 follow-up. Physician-diagnosed T2DM was identified at follow-up. T2DM-related risk factors, namely hypertension, dyslipidemia, and obesity, were assessed and controlled for as confounding factors. RESULTS: Adolescents with antidepressant-resistant depression (hazard ratio [HR], 95 % confidence interval [CI]: 4.62, 2.75-7.75) and those with antidepressant-responsive depression (HR, 95 % CI: 3.06, 1.98-4.72) had a higher risk of developing T2DM at follow-up than did the control group. Those with antidepressant-resistant depression were more likely to receive a diagnosis of T2DM (HR, 95 % CI: 1.51, 1.04-2.19) later in life than were those with antidepressant-responsive depression. DISCUSSION: Clinicians should closely monitor factors related to T2DM, such as fasting blood sugar, in high-risk populations, especially in adolescents with antidepressant-resistant depression.

Disease progression to bipolar disorder among adolescents and young adults with antidepressant-resistant and antidepressant-responsive depression: Does antidepressant class matter?

Studies have demonstrated a positive relationship between antidepressant resistance and the progression of bipolar disorder. However, the influence of antidepressant classes such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) in this context has yet to be investigated. A total of 5,285 adolescents and young adults with antidepressant-resistant depression and 21,140 with antidepressant-responsive depression were recruited in the present study. The antidepressant-resistant depression group was divided into two subgroups: only resistant to SSRIs (n = 2,242, 42.4%) and additionally resistant to non-SSRIs (n = 3,043, 57.6%) groups. The status of bipolar disorder progression was monitored from the date of depression diagnosis to the end of 2011. Patients with antidepressant-resistant depression were more likely to develop bipolar disorder during the follow-up (hazard ratio [HR]: 2.88, 95% confidence interval [CI]: 2.67-3.09) than those with antidepressant-responsive depression. Furthermore, the group that was additionally resistant to non-SSRIs were at the highest risk of bipolar disorder (HR: 3.02, 95% CI: 2.76-3.29), followed by the group that was only resistant to SSRIs (2.70, 2.44-2.98). Adolescents and young adults with antidepressant-resistant depression, especially those who responded poorly to both SSRIs and SNRIs, were at increased risk of subsequent bipolar disorder compared with those with antidepressant-responsive depression. Further studies are warranted to elucidate the molecular pathomechanisms underlying the resistance to SSRIs and SNRIs and subsequent bipolar disorder.

Effectiveness of controlling COVID-19 epidemic by implementing soft lockdown policy and extensive community screening in Taiwan.

Strict and repeated lockdowns have caused public fatigue regarding policy compliance and had a large impact on several countries' economies. We aimed to evaluate the effectiveness of a soft lockdown policy and the strategy of active community screening for controlling COVID-19 in Taiwan. We used village-based daily confirmed COVID-19 statistics in Taipei City and New Taipei City, between May 2, 2021, and July 17, 2021. The temporal Gi* statistic was used to compute the spatiotemporal hotspots. Simple linear regression was used to evaluate the trend of the epidemic, positivity rate from community screening, and mobility changes in COVID-19 cases and incidence before and after a level three alert in both cities. We used a Bayesian hierarchical zero-inflated Poisson model to estimate the daily infection risk. The cities accounted for 11,403 (81.17%) of 14,048 locally confirmed cases. The mean effective reproduction number (Re) surged before the level three alert and peaked on May 16, 2021, the day after the level three alert in Taipei City (Re = 3.66) and New Taipei City (Re = 3.37). Mobility reduction and a lower positive rate were positively associated with a lower number of cases and incidence. In the spatiotemporal view, seven major districts were identified with a radial spreading pattern from one hard-hit district. Villages with a higher inflow degree centrality among people aged ≥ 60 years, having confirmed cases, specific land-use types, and with a higher aging index had higher infection risks than other villages. Early soft lockdown policy and detection of infected patients showed an effective strategy to control COVID-19 in Taiwan.

Modulation of Inherent Niches in 3D Multicellular MSC Spheroids Reconfigures Metabolism and Enhances Therapeutic Potential.

Multicellular spheroids show three-dimensional (3D) organization with extensive cell-cell and cell-extracellular matrix interactions. Owing to their native tissue-mimicking characteristics, mesenchymal stem cell (MSC) spheroids are considered promising as implantable therapeutics for stem cell therapy. Herein, we aim to further enhance their therapeutic potential by tuning the cultivation parameters and thus the inherent niche of 3D MSC spheroids. Significantly increased expression of multiple pro-regenerative paracrine signaling molecules and immunomodulatory factors by MSCs was observed after optimizing the conditions for spheroid culture. Moreover, these alterations in cellular behaviors may be associated with not only the hypoxic niche developed in the spheroid core but also with the metabolic reconfiguration of MSCs. The present study provides efficient methods for manipulating the therapeutic capacity of 3D MSC spheroids, thus laying solid foundations for future development and clinical application of spheroid-based MSC therapy for regenerative medicine.