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Metastasis is the leading cause of cancer-related deaths, and greater knowledge of the metastatic microenvironment is necessary to effectively target this process. Microenvironmental changes occur at distant sites prior to clinically detectable metastatic disease; however, the key niche regulatory signals during metastatic progression remain poorly characterized. Here, we identify a core immune suppression gene signature in pre-metastatic niche formation that is expressed predominantly by myeloid cells. We target this immune suppression program by utilizing genetically engineered myeloid cells (GEMys) to deliver IL-12 to modulate the metastatic microenvironment. Our data demonstrate that IL12-GEMy treatment reverses immune suppression in the pre-metastatic niche by activating antigen presentation and T cell activation, resulting in reduced metastatic and primary tumor burden and improved survival of tumor-bearing mice. We demonstrate that IL12-GEMys can functionally modulate the core program of immune suppression in the pre-metastatic niche to successfully rebalance the dysregulated metastatic microenvironment in cancer.
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Terapia de Imunossupressão , Células Mieloides/metabolismo , Imunidade Adaptativa , Animais , Linhagem Celular Tumoral , Engenharia Genética , Humanos , Interleucina-12/genética , Interleucina-12/metabolismo , Pulmão/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células Mieloides/citologia , Células Mieloides/imunologia , Metástase Neoplásica , Rabdomiossarcoma/metabolismo , Rabdomiossarcoma/patologia , Taxa de Sobrevida , Linfócitos T/imunologia , Linfócitos T/metabolismo , Microambiente TumoralRESUMO
Plant metaxylem vessels provide physical support to promote upright growth and the transport of water and nutrients. A detailed characterization of the molecular network controlling metaxylem development is lacking. However, knowledge of the events that regulate metaxylem development could contribute to the development of germplasm with improved yield. In this paper, we screened an EMS-induced B73 mutant library, which covers 92% of maize (Zea mays) genes, to identify drought-sensitive phenotypes. Three mutants were identified, named iqd27-1, iqd27-2, and iqd27-3, and genetic crosses showed that they were allelic to each other. The causal gene in these 3 mutants encodes the IQ domain-containing protein ZmIQD27. Our study showed that defective metaxylem vessel development likely causes the drought sensitivity and abnormal water transport phenotypes in the iqd27 mutants. ZmIQD27 was expressed in the root meristematic zone where secondary cell wall deposition is initiated, and loss-of-function iqd27 mutants exhibited a microtubular arrangement disorder. We propose that association of functional ZmIQD27 with microtubules is essential for correct targeted deposition of the building blocks for secondary cell wall development in maize.
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Meristema , Zea mays , Zea mays/metabolismo , Plântula/genética , Secas , Água/metabolismoRESUMO
Interleukin-2 (IL-2) regulates lymphocyte function by signaling through heterodimerization of the IL-2Rß and γc receptor subunits. IL-2 is of considerable therapeutic interest, but harnessing its actions in a controllable manner remains a challenge. Previously, we have engineered an IL-2 "superkine" with enhanced affinity for IL-2Rß. Here, we describe next-generation IL-2 variants that function as "receptor signaling clamps." They retained high affinity for IL-2Rß, inhibiting binding of endogenous IL-2, but their interaction with γc was weakened, attenuating IL-2Rß-γc heterodimerization. These IL-2 analogs acted as partial agonists and differentially affected lymphocytes poised at distinct activation thresholds. Moreover, one variant, H9-RETR, antagonized IL-2 and IL-15 better than blocking antibodies against IL-2Rα or IL-2Rß. Furthermore, this mutein prolonged survival in a model of graft-versus-host disease and blocked spontaneous proliferation of smoldering adult T cell leukemia (ATL) T cells. This receptor-clamping approach might be a general mechanism-based strategy for engineering cytokine partial agonists for therapeutic immunomodulation.
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Interleucina-2/antagonistas & inibidores , Engenharia de Proteínas , Receptores de Interleucina-2/metabolismo , Transdução de Sinais/imunologia , Animais , Linhagem Celular , Proliferação de Células , Feminino , Regulação da Expressão Gênica , Doença Enxerto-Hospedeiro , Humanos , Interleucina-2/química , Interleucina-2/genética , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Mutação , Ligação Proteica , Estrutura Terciária de Proteína , Receptores de Interleucina-2/química , Fator de Transcrição STAT5/metabolismo , Análise de SobrevidaRESUMO
BACKGROUND: As the relationship between attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) is gaining increasing attention, the TBI risk in patients with ADHD, unaffected siblings of ADHD probands, and non-ADHD controls remains unclear. METHODS: Overall, 18,645 patients with ADHD, 18,880 unaffected siblings of ADHD probands, and 188,800 age-/sex-matched controls were followed up from enrollment to the end of 2011. The cases of TBI and TBI requiring hospitalization were identified during follow-up. RESULTS: Patients with ADHD (hazard ratio [HR]: 1.57) and unaffected siblings (HR: 1.20) had an increased risk of any TBI compared with non-ADHD controls. Surprisingly, the likelihood of developing TBI requiring hospitalization during follow-up was higher in the unaffected siblings group (HR: 1.21) than in the control group, whereas it was lower in the ADHD probands group (HR: 0.86). CONCLUSIONS: Patients with ADHD and unaffected siblings of ADHD probands were more likely to develop any TBI during follow-up than controls. Unaffected siblings of patients with ADHD exhibited the highest risk of subsequent TBI requiring hospitalization compared with patients with ADHD and healthy controls. Therefore, TBI risk in patients with ADHD and their unaffected siblings would require further investigation. IMPACT: ADHD diagnosis and ADHD trait are associated with risk of traumatic brain injury (TBI). Both patients with ADHD and their unaffected siblings were more likely to develop TBI during the follow-up compared with the control group. TBI requiring hospitalization occurred more in the sibling group than in the proband group. TBI risk should be closely monitored among unaffected siblings of patients with ADHD.
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Whether proinflammatory cytokine dysregulation and cognitive dysfunction are associated with suicidal symptoms in adolescents and young adults with major depressive disorder (MDD) remains uncertain. We assessed the cognitive function and proinflammatory cytokine levels of 43 and 51 patients aged 15-29 years with MDD and severe and mild suicidal symptoms, respectively, as well as those of 85 age- and sex-matched healthy controls. Specifically, we measured serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-2, and interleukin-6 and assessed cognitive function by using working memory and go/no-go tasks. The severity of the patients' suicidal symptoms was based on Item 10 of the Montgomery-Åsberg Depression Rating Scale; scores of ≤ 2 and ≥ 4 indicated mild and severe symptoms, respectively. The patients with MDD and severe suicidal symptoms had higher levels of C-reactive protein (p = .019) and TNF-α (p = .002) than did the patients with mild symptoms or the healthy controls. The number of errors committed on the go/no-go by patients with MDD and severe suicidal symptoms (p = .001) was significantly higher than those by patients with MDD and mild symptoms or by controls. After adjusting for nonsuicidal depressive symptoms, we observed suicidal symptoms to be positively associated with TNF-α levels (p = .050) and errors on the go/no-go task (p = .021). Compared with mild suicidal symptoms, severe symptoms are associated with greater serum levels of proinflammatory cytokines and inferior cognitive function in adolescents and young adults with MDD.
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For metal-based phosphate adsorbents, the dispersity and utilization of surface metal active sites are crucial factors in their adsorption performance and synthesis cost. In this study, a biochar material modified with amorphous Zr-Ce (carbonate) oxides (BZCCO-13) was synthesized for the phosphate uptake, and the adsorption process was enhanced by magnetic field. The beside-magnetic field was shown to have a better influence than under-magnetic field on adsorption, with maximum adsorption capacities (123.67 mg P/g) 1.14-fold greater than that without magnetic field. The beside-magnetic field could also accelerate the adsorption rate, and the time to reach 90% maximum adsorption capacity decreased by 83%. BZCCO-13 has a wide range of application pHs from 5.0 to 10.0, with great selectivity and reusability. The results of XPS and ELNES showed that the "magnetophoresis" of Ce3+ under the magnetic field was the main reason for the enhanced adsorption performance. In addition, increased surface roughness, pore size and oxygen vacancies, enhanced mass transfer by Lorentz force under a magnetic field, all beneficially influenced the adsorption process. The mechanism of phosphate adsorption by BZCCO-13 could be attributed to electrostatic attraction and CO32-dominated ligand exchange. This study not only provided an effective strategy for designing highly effective phosphate adsorbents, but also provides a new light on the application of rare earth metal-based adsorbent in magnetic field.
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Carvão Vegetal , Fosfatos , Zircônio , Adsorção , Carvão Vegetal/química , Zircônio/química , Fosfatos/química , Campos Magnéticos , Óxidos/química , Carbonatos/químicaRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy affecting the head and neck region. The prognosis for OSCC patients remains unfavorable due to the absence of precise and efficient early diagnostic techniques. Metabolomics offers a promising approach for identifying distinct metabolites, thereby facilitating early detection and treatment of OSCC. OBJECTIVE: This review aims to provide a comprehensive overview of recent advancements in metabolic marker identification for early OSCC diagnosis. Additionally, the clinical significance and potential applications of metabolic markers for the management of OSCC are discussed. RESULTS: This review summarizes metabolic changes during the occurrence and development of oral squamous cell carcinoma and reviews prospects for the clinical application of characteristic, differential metabolites in saliva, serum, and OSCC tissue. In this review, the application of metabolomic technology in OSCC research was summarized, and future research directions were proposed. CONCLUSION: Metabolomics, detection technology that is the closest to phenotype, can efficiently identify differential metabolites. Combined with statistical data analyses and artificial intelligence technology, it can rapidly screen characteristic biomarkers for early diagnosis, treatment, and prognosis evaluations.
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Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level.
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Bactérias , Fermentação , RNA Ribossômico 16S , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , China , Microbiota , Filogenia , DNA Bacteriano/genética , Biodiversidade , Bebidas Alcoólicas/microbiologia , Bebidas Alcoólicas/análise , Microbiologia de Alimentos , Metagenoma , Alimentos Fermentados/microbiologiaRESUMO
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.
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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.
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OBJECTIVES: Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD. METHODS: We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive, and apoptotic levels were measured using in vitro assays. RESULTS: The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups. CONCLUSION: The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.
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Transtorno Depressivo Maior , Células Progenitoras Endoteliais , Humanos , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/psicologia , Feminino , Masculino , Células Progenitoras Endoteliais/metabolismo , Adulto , Pessoa de Meia-Idade , Apoptose/fisiologia , Função Executiva/fisiologia , Adesão Celular , Estudos de Casos e Controles , Escalas de Graduação Psiquiátrica , Testes NeuropsicológicosRESUMO
Membrane fouling is a bottleneck issue that hindered the further application of ultrafiltration technology. To alleviate membrane fouling, coagulation-ultrafiltration (C-UF) process using polyaluminum chloride (PACl) and PACl-Al13 with high proportion of Al13O4(OH)247+ as coagulants, respectively, were investigated at various pH conditions. Results indicated that an increase in solution pH contributed to larger floc size and looser floc structure for both PACl and PACl-Al13. It was conducive to the formation of more porous cake, as evidenced by mean pore area and pore area distribution of cake, leading to lower reversible fouling. Furthermore, humic acid (HA) removal presented a trend of first increasing and then decreasing with the increase of pH. The optimal HA removal was achieved at pH 6 regardless of coagulant type, suggesting that the slightest irreversible fouling should be occurred at this point. Interestingly, the irreversible fouling with PACl coagulant achieved a minimum value at pH 9, while the minimal irreversible fouling with PACl-Al13 was observed at pH 6. We speculated that the cake formed by PACl could further intercept HA prior to UF process at alkaline pH. Furthermore, compared with PACl, PACl-Al13 had a stronger charge neutralization ability, thus contributing to more compact floc structure and higher HA removal at various pH conditions. By UF fractionation measurement, higher HA removal for PACl-Al13 was due to higher removal of HA with molecular weight less than 50 kDa.
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Substâncias Húmicas , Membranas Artificiais , Ultrafiltração , Ultrafiltração/métodos , Substâncias Húmicas/análise , Floculação , Hidróxido de Alumínio/química , Purificação da Água/métodos , Concentração de Íons de Hidrogênio , Eliminação de Resíduos Líquidos/métodosRESUMO
Catalytic ozonation is an effective wastewater purification process. However, the low ozone mass transfer in packed bubble columns leads to low ozone utilization efficiency (OUE), poor organic degradation performance, and high energy consumption. Therefore, there is an urgent need to develop efficient supported catalysts that can enhance mass transfer and performance. However, the reaction mechanism of the support on ozone mass transfer remains unclear, which hinders the development of catalytic ozonation applications. In this study, lava rocks (LR)-supported catalysts, specifically CuMn2O4@LR and MnO2Co3O4@LR, were proposed for catalytic ozonation of IBP degradation due to their superior catalytic activity, stability, and high OUE. Addition of CuMn2O4@LR or MnO2Co3O4@LR increased IBP removal efficiency from 85% to 91% or 88%, and reduced energy consumption from 2.86 to 2.14 kWh/m3 or 2.60 kWh/m3, respectively. This improvement was attributed to LR-supported catalysts enhancing mass transfer and promoting O3 decomposition to generate â¢OH and â¢O2-, leading to IBP degradation. Furthermore, this study investigated the effects of ozone dose, supporter sizes, and catalyst components on ozone-liquid mass transfer. The results revealed that the size of the supporter influenced stacked porosity and consequently affected ozone mass transfer. Larger-sized LR (kLa= 0.172 min-1) exhibited better mass transfer compared to smaller-sized supports. Based on these findings, it was concluded that both CuMn2O4@LR and MnO2Co3O4@LR are potential catalysts for catalytic ozonation in residual IBP degradation of pharmaceutical wastewater, and LR showed good credibility as a catalyst supporter. Understanding the effects of supporters and active components on ozone mass transfer provides a fundamental principle for designing supported catalysts in catalytic ozonation applications.
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Ibuprofeno , Ozônio , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água , Ozônio/química , Catálise , Poluentes Químicos da Água/química , Ibuprofeno/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Purificação da Água/métodosRESUMO
Direct counting and mapping the chain lengths of fatty acids on a microscopic scale are of particular importance but remain an unsolvable challenge. Although the current hyperspectral stimulated Raman scattering (SRS) microscopy has gained exceptional capability in chemical imaging of the degree of desaturation, the complete lipid characterization, including the carbon chain length quantification, is awaiting a major breakthrough. Here, we pushed the spectral resolution limit of hyperspectral SRS microscopy to 5.4 cm-1 by employing a highly efficient spectral compressor, which achieved spectral narrowing of the fs laser without much energy loss. The SRS imaging with such high spectral resolution enabled us to differ eight types of saturated lipids with carbon chain lengths from C8:0 to C22:0 by interrogating their subtly red-shifting Raman bands of alkyl C-C gauche stretches between 1070 and 1110 cm-1. The SRS microscopy with superior spectral resolution will pave the way for comprehensive lipid characterization and contribute to uncovering the abnormal pathways of lipid metabolism in cancer.
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Microscopia , Microscopia Óptica não Linear , Microscopia Óptica não Linear/métodos , Microscopia/métodos , Metabolismo dos Lipídeos , Lipídeos , Carbono , Análise Espectral Raman/métodosRESUMO
BACKGROUND: Evidence suggests an association of insulin and leptin with attention and executive function. The roles of dysregulated appetite hormones, including insulin and leptin, in the pathomechanisms of attention deficit hyperactivity disorder (ADHD) and associated cognitive function impairment remain unknown. METHODS: In total, 50 adolescents with ADHD were enrolled and age and sex matched with 50 typically developing controls. The parent-reported Swanson, Nolan, and Pelham IV scale and self-reported Barratt Impulsiveness Scale were employed for symptom assessment. The fasting serum concentrations of appetite hormones-leptin, ghrelin, insulin, and adiponectin-were measured. The Wisconsin Card Sorting Test was used to examine executive function. RESULTS: Generalized linear models with adjustment for age, sex, body mass index, and medications indicated that the adolescents with ADHD had higher levels of insulin (P = .039) and leptin (P = .006) than did those in the control group. Self-reported attention and self-control symptoms were negatively associated with insulin level (P = .025 and .018, respectively) and positively associated with leptin level (both P < .001). In addition, insulin level was positively associated with executive function (P = .031). CONCLUSION: Appetite hormone dysregulation was associated with the symptomology and executive function among adolescents with ADHD. Our results may inspire researchers to further examine the role of appetite hormone dysregulation in ADHD pathogenesis.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Função Executiva , Leptina/uso terapêutico , Apetite , InsulinaRESUMO
BACKGROUND: Evidence suggests a familial coaggregation of major psychiatric disorders, including schizophrenia, bipolar disorder, major depression (MDD), autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Those disorders are further related to suicide and accidental death. However, whether death by suicide may coaggregate with accidental death and major psychiatric disorders within families remains unclear. AIMS: To clarify the familial coaggregation of deaths by suicide with accidental death and five major psychiatric disorders. METHOD: Using a database linked to the entire Taiwanese population, 68 214 first-degree relatives of individuals who died by suicide between 2003 and 2017 and 272 856 age- and gender-matched controls were assessed for the risks of death by suicide, accidental death and major psychiatric disorders. RESULTS: A Poisson regression model showed that the first-degree relatives of individuals who died by suicide were more likely to die by suicide (relative risk RR = 4.61, 95% CI 4.02-5.29) or accident (RR = 1.62, 95% CI 1.43-1.84) or to be diagnosed with schizophrenia (RR = 1.53, 95% CI 1.40-1.66), bipolar disorder (RR = 1.99, 95% CI 1.83-2.16), MDD (RR = 1.98, 95% CI 1.89-2.08) or ADHD (RR = 1.34, 95% CI 1.24-1.44). CONCLUSIONS: Our findings identified a familial coaggregation of death by suicide with accidental death, schizophrenia, major affective disorders and ADHD. Further studies would be required to elucidate the pathological mechanisms underlying this coaggregation.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtorno Bipolar , Transtorno Depressivo Maior , Suicídio , Humanos , Transtorno Bipolar/genética , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genéticaRESUMO
BACKGROUND: Because of a relative dearth of longitudinal studies, the directionality of the relationship between mood and inflammation among patients with bipolar disorder (BD) is still unclear. We aimed to investigate the longitudinal associations of pro-inflammatory markers with mood symptom severity in BD. METHODS: Hundred and thirty-two adult patients with BD were enrolled. At the baseline and 1-year follow-up visit, all participants received mood assessment with Montgomery Åsberg depression rating scale (MADRS) and Young mania rating scale, and underwent blood draws to quantify metabolic profile and serum levels of the pro-inflammatory markers, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein. A four-factor model of MADRS, consisting of sadness, negative thoughts, detachment, and neurovegetative symptoms, were applied. RESULTS: At baseline, 65 patients with BD were in depressed state, and 67 patients with BD were in euthymic state. Among patients in depressed state, baseline MADRS total score positively correlated with sTNF-αR1 level at follow-up. While baseline sTNF-αR1 level positively predicted sadness symptom in euthymic patients with BD who later developed depression (n = 22), sadness in patients with bipolar depression predicted later increase in serum sTNF-αR1 level even after remission (n = 17). Moreover, lithium had a stronger effect of lowering peripheral sTNF-αR1 level as compared with other mood stabilizers. CONCLUSION: Our results indicate the bidirectional inflammation-depression relationship in BD.
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Transtorno Bipolar , Adulto , Humanos , Transtorno Bipolar/diagnóstico , Citocinas , Escalas de Graduação Psiquiátrica , Estudos Longitudinais , InflamaçãoRESUMO
BACKGROUND: To investigate the association between exposure to antidepressants (ADs) and the risk of epilepsy among patients exposed to ADs. METHOD: We conducted a case-control study using Taiwan's National Health Insurance Research Database between 1998 and 2013. A total of 863 patients with epilepsy and 3,452 controls were included. The dose of ADs was categorized according to the cumulative defined daily dose (cDDD). The risk of epilepsy was assessed using conditional logistic regression analysis. RESULTS: Compared with cDDD < 90, ADs exposure with cDDD > 365 (odds ratio [OR]: 1.37, 95% confidence interval [CI]:1.12-1.68) was associated with an increased risk of epilepsy, but not for those with cDDD 90-365 (OR: 1.07,95% CI: 0.87-1.30) after adjustment for several comorbidities and indications of ADs use. Other identified risk factors include cerebrovascular disease, traumatic brain injury, and central nervous system infection. Subgroup analysis of individual ADs showed that escitalopram (OR: 1.93, 95% CI: 1.12-3.31), venlafaxine (OR: 1.62, 95% CI: 1.13-2.31), mirtazapine (OR: 1.56, 95% CI: 1.00-2.43), paroxetine (OR: 1.44, 95% CI: 1.08-1.94), and fluoxetine (OR: 1.25, 95% CI: 1.01-1.56) had a significantly higher risk of epilepsy. Sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion did not show any proconvulsant effects. CONCLUSIONS: The study found an increased risk of epilepsy among patients who were exposed to any ADs, particularly longer-term users. Given the nature of observational studies with residual bias, interpretation should be cautious.
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Epilepsia , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Estudos de Casos e Controles , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Antidepressivos/efeitos adversos , Citalopram/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/induzido quimicamenteRESUMO
BACKGROUND: The genetic load for major depressive disorder (MDD) may be higher in people who develop MDD earlier in life. This study aimed to investigate whether the parents of adolescents with MDD were more likely to have MDD, bipolar disorder (BD), schizophrenic disorder (SZ), alcohol use disorder, or substance use disorder than the parents of adolescents without MDD. We also examined whether the response to antidepressant treatment predicted the likelihood of parental psychiatric disorders. METHODS: In all, 1,758 adolescents aged 12-19 years with antidepressant-resistant depression, 7,032 (1:4) age-/sex-matched adolescents with antidepressant-responsive depression and 7,032 (1:4) age-/sex-matched controls were included. Parental psychiatric disorders of individuals enrolled were assessed. RESULTS: The parents of the adolescents with MDD were more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than the parents of the control group. The parents of adolescents who were antidepressant resistant and the mothers of adolescents who were either treatment resistant or treatment responsive were more likely to be diagnosed with a psychiatric disorder. DISCUSSION: Our study demonstrated that parents of adolescents with MDD may be more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than parents of adolescents without MDD, suggesting the within-disorder transmission and cross-disorder transmission of these psychiatric disorders. Furthermore, the parent's sex and the response to antidepressant treatment may affect the within-disorder transmission of MDD.
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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.