ABSTRACT
BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.
Subject(s)
Autistic Disorder , Brain , Cognition , Problem Behavior , Humans , Female , Male , Child , Brain/growth & development , Adolescent , Cognition/physiology , Family Conflict , Mothers , Adult , Pregnancy , Young Adult , Pregnancy in Adolescence , Sex FactorsABSTRACT
BACKGROUND AND AIMS: Genetics plays a role in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP); however, empirical evidence on familial clustering of ICP is scarce. We aimed to assess the extent of familial recurrence of ICP. APPROACH AND RESULTS: This population-based cohort study included all 668,461 primiparous women who gave birth between 1995 and 2018 in Denmark. Women diagnosed with ICP were included to the index cohort. Kinship with index women was determined with the Danish Civil Registration System. Log-binomial regression was used to calculate the relative recurrence risk (RRR) of ICP in relatives of index women. A total of 6722 (1.0%) primiparous women were diagnosed with ICP. In co-twins (n=57), first-degree (n=2279), second-degree (n=1373), and third-degree (n=1758) relatives of the index women, the incidence of ICP reached 5.3%, 2.6%, 0.7%, and 1.4%, respectively, corresponding to adjusted RRRs of 4.82 (95% CI, 1.60-14.48), 2.54 (1.98-3.26), 0.81 (0.44-1.51), and 1.15 (0.77-1.71), respectively. The first-degree relatives of women who had recurrent ICP or first-trimester ICP seemed to be at higher risks [RRR, 4.30 (2.85-6.48), 3.04 (1.93-4.77), respectively]. A minor increased risk was observed in nonbiological relatives [RRR, 1.35 (1.05-1.73); n=4274, including women's full-brothers' partner and women's husbands' full sisters]. CONCLUSIONS: Co-twins and first-degree relatives of ICP patients were at ~5- and ~2.5-fold increased risk of ICP, respectively. No increased risk was observed in second-degree and third-degree relatives. Recurrent ICP and first-trimester ICP might indicate a higher degree of family clustering. Further investigation is needed to investigate the increased risk of ICP in nonbiological relatives.
Subject(s)
Cholestasis, Intrahepatic , Pregnancy Complications , Male , Pregnancy , Humans , Female , Cohort Studies , Risk Factors , Pregnancy Complications/epidemiology , Pregnancy Complications/genetics , Cholestasis, Intrahepatic/epidemiology , Cholestasis, Intrahepatic/genetics , Cluster Analysis , Denmark/epidemiologyABSTRACT
BACKGROUND: COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns. METHODS: Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects. RESULTS: Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement (ß = 0.49, 95% confidence interval (CI) [0.19-0.79], p = 0.001) and this difference was greatest for social cognition (2.62 [0.94-4.30], p = 0.002). We found that this association was modulated by parental agreeableness in a protective way (-0.11 [-0.17 to -0.05], p = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus. CONCLUSIONS: This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , COVID-19 , Child , Humans , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/psychology , Cohort Studies , Protective Factors , COVID-19/prevention & control , Communicable Disease Control , China/epidemiologyABSTRACT
INTRODUCTION: Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor α (anti-TNFα) agents and adverse birth outcomes. METHODS: This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n = 1,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis. RESULTS: Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFα agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFα and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection. DISCUSSION: Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFα had a minor role. The association between anti-TNFα agents and pediatric infection could be partially explained by maternal CD.
Subject(s)
Colitis, Ulcerative , Communicable Diseases , Crohn Disease , Inflammatory Bowel Diseases , Pregnancy Complications , Premature Birth , Pregnancy , Female , Infant, Newborn , Humans , Child , Cohort Studies , Premature Birth/epidemiology , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/chemically induced , Crohn Disease/drug therapy , Crohn Disease/epidemiology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/epidemiology , Pregnancy Complications/epidemiology , Pregnancy Complications/pathology , Anti-Bacterial Agents/adverse effects , Tumor Necrosis Factor-alpha , Communicable Diseases/chemically induced , Communicable Diseases/complicationsABSTRACT
BACKGROUND: The use of labor neuraxial analgesia (NA) in China has increased significantly in the past decade, and the current rate of use is unknown. This study aimed to describe the epidemiology of NA based on a large multicenter cross-sectional survey, the China Labor and Delivery Survey (CLDS) (2015-2016), and to evaluate the association between NA and intrapartum caesarean delivery (CD) and maternal and neonatal outcomes. METHODS: The CLDS was a facility-based cross-sectional investigation with a cluster random sampling scheme conducted from 2015 to 2016. A specific weight was assigned to each individual based on the sampling frame. Logistic regression was adopted to analyze the factors associated with the use of NA. A propensity score matching scheme was used to analyze the associations between NA and intrapartum CD and perinatal outcomes. RESULTS: A total of 51,488 vaginal deliveries or intrapartum CD were included in our study, excluding prelabor CDs. The weighted NA rate was 17.3% (95% confidence interval [CI], 16.6-18.0) in this survey population. Nulliparous, previous CD, hypertensive disorders, and labor augmentation were associated with higher use of NA. In the propensity score-matched analysis, NA was associated with reduced risks of intrapartum CD, especially intrapartum CD by maternal request (adjusted odds ratio [aOR], 0.68; 95% CI, 0.60-0.78 and aOR, 0.48; 95% CI, 0.30-0.76, respectively), 3rd or 4th degree perineal laceration (aOR, 0.36; 95% CI, 0.15-0.89), and 5-minute Apgar score ≤3 (aOR, 0.15; 95% CI, 0.03-0.66). CONCLUSIONS: The use of NA may be associated with improved obstetric outcomes, including fewer intrapartum CD, less birth canal trauma, and better neonatal outcomes in China.
Subject(s)
Analgesia, Epidural , Labor, Obstetric , Pregnancy , Female , Humans , Propensity Score , Cross-Sectional Studies , Parturition , Delivery, Obstetric , Analgesia, Epidural/adverse effectsABSTRACT
BACKGROUND: Whether labour epidural analgesia impacts risk of neurodevelopmental disorders in offspring is unsettled, raising public and scientific concerns. We explored the association between maternal labour epidural analgesia and autism spectrum disorder, and specific developmental disorder, attention-deficit hyperactivity disorder, intellectual disability, and epilepsy in offspring. METHODS: This nationwide population-based cohort study included 624 952 live-born singletons delivered by women who intended to deliver vaginally (i.e. vaginal and intrapartum Caesarean deliveries) in Denmark from 2005 to 2016. A total of 80 862 siblings discordant for exposure to labour epidural analgesia were analysed in a sibling-matched analysis. Both full-cohort and sibling-matched analyses were performed to estimate hazard ratios (HRs) of offspring risk of autism spectrum disorder, specific developmental disorder, attention-deficit hyperactivity disorder, intellectual disability, and epilepsy, according to exposure to labour epidural analgesia, adjusted for maternal socio-economic, pregnancy, and perinatal covariates. RESULTS: In the full cohort, maternal labour epidural analgesia was associated with autism spectrum disorder in offspring (HR 1.11; 95% confidence interval [CI]: 1.04-1.18); however, in the sibling-matched analysis, no association with autism spectrum disorder was found (HR 1.03; 95% CI: 0.84-1.27). The association between labour epidural analgesia and specific developmental disorder (HR 1.12; 95% CI: 1.03-1.22) in the full cohort also disappeared in the sibling-matched analysis (HR 1.01; 95% CI: 0.78-1.31). No association between maternal labour epidural analgesia and the remaining neurodevelopmental disorders was found overall (attention-deficit hyperactivity disorder, HR 0.98; 95% CI: 0.92-1.03; intellectual disability, HR 0.98; 95% CI: 0.85-1.14; epilepsy, HR 0.89; 95% CI: 0.79-1.00) or in the sibling-matched analyses. CONCLUSIONS: Our findings did not support an association between maternal attention-deficit hyperactivity disorder and autism spectrum disorder, specific developmental disorder, attention-deficit hyperactivity disorder, intellectual disability, or epilepsy.
Subject(s)
Analgesia, Epidural/adverse effects , Developmental Disabilities/etiology , Labor, Obstetric/drug effects , Neurodevelopmental Disorders/genetics , Prenatal Exposure Delayed Effects/etiology , Adult , Cesarean Section/methods , Cohort Studies , Denmark , Family , Female , Humans , Male , Pregnancy , Proportional Hazards Models , Risk Factors , Young AdultABSTRACT
BACKGROUND: Gemcitabine plus platinum as the first-line chemotherapy for cholangiocarcinoma (CCA) has limited efficacy. The aim of this study was to evaluate the effectiveness of modified FOLFIRINOX (mFOLFIRINOX) compared to that of gemcitabine plus oxaliplatin (Gemox) for patients with locally advanced or metastatic CCA. METHODS: From January 2016 to December 2019, consecutive patients who were diagnosed with locally advanced or metastatic CCA were treated with either mFOLFIRINOX or Gemox as a first-line chemotherapy. The main endpoint was Progression free survival (PFS). The second endpoints were Overall survival (OS), Disease control rate (DCR) and incidence of severe toxicity (grade 3-4). Tumors were evaluated at baseline and thence every 4-6 weeks. The study was designed and carried out in accordance with the principles of the declaration of Helsinki, approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHEC-D-2020-154) and registered with ClinicalTrials.gov , number NCT04305288 (registration date: 12/03/2020). RESULTS: Of 49 patients in this study, 27 were in the FOLFIRINOX regimen group and 22 in the Gemox regimen group. There were no significant differences between groups in baseline characteristics. The DCR was 77.8% in the mFOLFIRINOX group and 63.5% in the Gemox group. The corresponding median PFS was 9.9 months (95% confidence interval [CI], 7.3-12.4) in the mFOLFIRINOX group versus 6.4 months (95% CI,3.6-9.2, p = 0.040) in the Gemox group. The corresponding median OS was 15.7 months (95% CI, 12.5-19.0) versus 12.0 months (95% CI, 9.3-14.8, p = 0.099). Significantly more grade 3-4 vomiting occurred in the mFOLFIRINOX than the Gemox groups (7 (25.9%) vs 1 (4.5%), p = 0.044). CONCLUSIONS: First-line mFOLFIRINOX offered more promising results in patients with advanced or metastatic CCA.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cholangiocarcinoma/drug therapy , Deoxycytidine/analogs & derivatives , Oxaliplatin/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cholangiocarcinoma/pathology , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Female , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Humans , Irinotecan/pharmacology , Irinotecan/therapeutic use , Leucovorin/pharmacology , Leucovorin/therapeutic use , Male , Middle Aged , Oxaliplatin/pharmacology , Retrospective Studies , GemcitabineABSTRACT
OBJECTIVE: To investigate the surgical indication and tactics for liver hemangioma in the caudate lobe METHODS: From January 1994 to July 2019, 137 patients, including 51 males and 86 females with the average age of 49.2 years old were diagnosed with liver hemangioma in caudate lobe and received treatment at five tertiary referral hospitals. Clinical features, correlations between tumor size and clinical manifestations, treatments, and prognosis were analyzed. RESULTS: Of the 137 patients identified, 40 (29.20%) patients were asymptomatic, whereas other 94 patients had clinical symptoms mainly presented as upper abdominal discomfort, epigastric distention, upper abdominal dull pain, nausea, and vomiting. Fifteen (93.75%), 18 (39.13%), and 7 (10.45%) patients presented no clinical symptoms among those tumor size was less than 3 cm (D ≤ 3 cm, n = 16), 3 cm < D ≤ 6 cm (n = 46), and 6 cm < D ≤ 9 cm (n = 67), respectively, while all 8 patients with tumor larger than 9 cm were symptomatic. Tumor diameter was obviously associated with the presence of clinical symptoms. In follow-up period, 7 patients in the conservative group (n = 39) received surgery because of tumor growth or symptom appearance. Totally 105 patients received operation including partial resection or isolated complete resection of caudate lobe and caudate lobe resection combined with liver segment resection, right liver resection, or left liver resection. All operations went smoothly, and no severe complications appeared. CONCLUSION: Tumor diameter was obviously associated with the presence of clinical symptoms in patients with hemangioma in caudate lobe. Surgical therapy is not recommended for asymptomatic patients and available for patient who has symptoms. Effective surgical strategies should be put into use to reduce operative bleeding.
Subject(s)
Blood Loss, Surgical/prevention & control , Hemangioma/surgery , Liver Neoplasms/surgery , Adult , Aged , Female , Hemangioma/pathology , Hepatectomy/adverse effects , Hepatectomy/methods , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Postoperative Complications/prevention & control , Prognosis , Retrospective Studies , Tumor BurdenABSTRACT
BACKGROUND: Emerging evidence has shown that miR-1275 plays a critical role in tumour metastasis and the progression of various types of cancer. In this study, we analysed the role and mechanism of miR-1275 in the progression and prognosis of gastric cancer (GC). METHODS: Target genes of miR-1275 were identified and verified by luciferase assay and Western blotting. The function of miR-1275 in invasion and metastasis was analysed in vitro and in vivo in nude mice. The signal pathway regulated by miR-1275 was examined by qRT-PCR, Western blotting and chromatin immunoprecipitation analyses. The expression of miR-1275and JAZF1 were measured in specimens of GC and adjacent non cancerous tissues. RESULTS: We identified JAZF1 as a direct miR-1275 target. miR-1275 supresses migration and invasion of GC cells in vitro and in vivo, which was restored by JAZF1 overexpression. Moreover, JAZF1 was recognized as a direct regulator of Vimentin. Knocking-down miR-1275 or overexpressing JAZF1 resulted in upregulation of Vimentin but downregulation of E-cadherin. Meanwhile, we validated in 120 GC patients specimens that low miR-1275expression and high JAZF1 mRNA expression levels were closely associated with lymph node metastasis and poor prognosis. The expression of JAZF1 in protein level displayed the correlations with Vimentin but inversely with E-cadherin. CONCLUSIONS: Increased miR-1275 expression inhibited GC metastasis by regulating vimentin/E-cadherin via direct suppression of JAZF1expression, suggesting that miR-1275 is a tumour-suppressor miRNA with the potential as a prognostic biomarker or therapeutic target in GC.
Subject(s)
Antigens, CD/metabolism , Cadherins/metabolism , Cell Movement , Co-Repressor Proteins/metabolism , DNA-Binding Proteins/metabolism , MicroRNAs/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Vimentin/metabolism , Adult , Aged , Aged, 80 and over , Animals , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Co-Repressor Proteins/genetics , DNA-Binding Proteins/genetics , Disease Models, Animal , Female , Humans , Kaplan-Meier Estimate , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Mice , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Prognosis , Stomach Neoplasms/surgery , TransfectionABSTRACT
Osthole is an antitumor compound, which effect on Gallbladder cancer (GBC) has been not elucidated. This study focused on its anti-GBC effect and mechanism both in vitro and in vivo. The antiproliferation effect on cell lines NOZ and SGC-996 were measured by cell counting kit-8 (CCK-8) and colony formation assay. The effects on cell apoptosis and cell cycle were investigated by flow cytometry assay. The migration effect was checked by transwell assay and the expressions of proteins were examined by Western Blots. Also, we did an in-vivo experiment by intraperitoneal injection of osthole in nude mice. The results showed that cell proliferation and viability were inhibited in a dose- and time-dependent manner. The similar phenomenon was also found in vivo. Flow cytometric assay confirmed that osthole inhibited cells proliferation via inducing apoptosis and G2/M arrest. Transwell assay indicated that osthole inhibited the migration in a dose-dependent manner. Expression of key proteins related with apoptosis and cell cycle were testified after osthole treatment. Also, we found the key proteins involved in the JAK/STAT3 signal way decreased after osthole treatment. This study suggested that osthole can inhibit the progression of human GBC cell lines, thus maybe a potential drug for GBC treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Coumarins/pharmacology , Gallbladder Neoplasms/drug therapy , STAT3 Transcription Factor/metabolism , Animals , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Gallbladder Neoplasms/metabolism , Gallbladder Neoplasms/pathology , Humans , Janus Kinases/metabolism , Male , Mice, Inbred BALB C , Mice, Nude , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND AND OBJECTIVES: To investigate whether children born to mothers who used carbamazepine during pregnancy had worse academic performance in adolescence. METHODS: This population-based cohort study included all live-born singletons in Denmark between 1996 and 2002 who participated in the national ninth-grade exit examination (n = 370,859). Those born to mothers with prescription of antiseizure medications other than carbamazepine during pregnancy were excluded. We examined the association of in utero exposure to maternal carbamazepine redeemed during pregnancy (n = 290) with academic performance of offspring, defined by the scores in Danish and mathematics in ninth-grade exit examination. We estimated mean z-score difference with linear regression adjusted for socioeconomic factors and potential indications, including epilepsy and medication for other psychiatric disorders. Additional analyses addressing confounding by indication included comparison between in utero exposed vs past exposed and between past exposed and never exposed. In utero exposure to valproate monotherapy was used as a positive control and in utero exposure to lamotrigine as a negative control. RESULTS: At the age of 16.1 (SD 0.4) years, adolescents in utero exposed to maternal carbamazepine monotherapy had lower scores both in Danish and mathematics in ninth-grade exit examination (adjusted z-score difference, -0.14 [95% CI -0.24 to -0.05] and -0.17 [95% CI -0.28 to -0.07], respectively). In utero exposure to carbamazepine monotherapy was associated with lower scores than past exposure only (adjusted z-score difference, -0.24 [95% CI -0.41 to -0.06] for Danish and -0.25 [95% CI -0.44 to -0.06] for mathematics), while past exposure to carbamazepine was associated with minor decrease in offspring's academic performance (adjusted z-score difference, -0.02 [95% CI -0.09 to 0.06] for Danish and -0.07 [95% CI -0.16 to 0.01] for mathematics). The association was also observed for in utero exposure to valproate monotherapy, but not for in utero exposure to lamotrigine. DISCUSSION: In utero exposure to carbamazepine was associated with poorer academic performance in adolescence, as represented by lower scores in ninth-grade exit examination in Danish and mathematics. Additional studies are needed to confirm these findings because of limitations in this study and variable findings in prior studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that academic performance, as reflected in ninth-grade exit examinations in Danish and mathematics, was worse among those exposed to carbamazepine monotherapy in utero, compared with those without in utero exposure to antiseizure medications.
Subject(s)
Academic Performance , Prenatal Exposure Delayed Effects , Pregnancy , Child , Female , Adolescent , Humans , Valproic Acid , Lamotrigine , Cohort Studies , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/epidemiology , Carbamazepine/adverse effects , Anticonvulsants/adverse effects , Benzodiazepines , MothersABSTRACT
BACKGROUND: Exposure to poly-and perfluoroalkyl substances (PFASs) has been linked to psychiatric disorders in the general population. Because women in the postpartum period are susceptible to mental disorders, we aimed to investigate the association between exposure to PFASs during pregnancy and postpartum depression (PPD). METHODS: Our study consisted of 2741 pregnant women who were enrolled in the Shanghai Birth Cohort during the early pregnancy and gave birth to a singleton live birth between 2013 and 2016. A total of 10 PFASs were measured in maternal plasma collected in early gestation by high-performance liquid chromatography/tandem mass spectrometry. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 42 days after the child birth. We used multivariable logistic regression to estimate the association between exposure to PFASs and PPD, adjusted for potential confounders. Negative binomial regression was used to assess the association between PFASs exposure during pregnancy and EPDS subscales including anhedonia, anxiety, and depression. A quantile-based g-computation approach was used to evaluate the joint and independent effects of PFASs on PPD. RESULTS: Around 11.7% of the mothers had probable PPD (EPDS cut-off ≥10). Overall, exposure to PFASs in early pregnancy was not associated with PPD or EPDS subscales. Quantile g-computation method also showed that increasing PFASs mixture by one quartile was not associated with PPD (odds ratio, 1.08; 95% confidence interval: 0.91, 1.29). CONCLUSION: Our findings indicate that exposure to PFASs during pregnancy was not associated with PPD at 6 weeks postpartum.
Subject(s)
Depression, Postpartum , Fluorocarbons , Pregnancy , Child , Humans , Female , Depression, Postpartum/epidemiology , Depression, Postpartum/psychology , Birth Cohort , China/epidemiology , Mothers/psychology , Fluorocarbons/toxicity , Risk FactorsABSTRACT
BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic. METHODS: We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators. RESULTS: Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%). CONCLUSION: Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening.
ABSTRACT
A terbium-based metal-organic framework, namely {[Tb2(ADIP)(H2ADIP)(HCOOH)(H2O)2]·2DMF·2H2O}n (Tb-MOF, H4ADIP = 5,5'-(anthracene-9,10-diyl) diisophthalic acid), was synthesized and characterized. The single-crystal structure analysis shows that the Tb-MOF crystallizes in the C2/C space group in the monoclinic system and its asymmetric unit contains two TbIII ions, one ADIP4-, one H2ADIP2-, one coordinating formic acid and two coordination water molecules. Tb-MOF has a three-dimensional porous structure with a porosity of 41.5%. Tb-MOF is a highly selective and sensitive fluorescence turn-on and blue-shift sensor for L-aspartate (Asp), L-glutamine (Glu), Al3+ and Ga3+with detection limits of 0.25, 0.23, 0.069 and 0.079 µM, respectively. Experimental studies and theoretical calculations show that the sensing process is mainly attributed to the energy transfer and the absorbance caused enhancement (ACE) mechanism. Therefore, Tb-MOF is a good multi-response fluorescence sensor for acidic amino acids and Al3+, Ga3+cations.
Subject(s)
Metal-Organic Frameworks , Terbium , Amino Acids, Acidic , Anthracenes , Aspartic Acid , Cations , Formates , Glutamine , Metal-Organic Frameworks/chemistry , Terbium/chemistry , WaterABSTRACT
ABSTRACT: A quasi-dynamic food chain model (Chi-FDMT) was developed to predict the consequences of nuclear accidents on the food chain through the ingestion pathway in Chinese agricultural conditions. The Chi-FDMT structure is based on ECOSYS-87, with some revised calculation processes and the adoption of new parameters; herein, it was applied to two regions in China. The model was used to estimate the spatial and temporal patterns of crop plant activity and ingestion dose in the Chinese agricultural environment at the scale of the Fukushima nuclear disaster. A comparative study between Chi-FDMT and an equilibrium model demonstrated good agreement for depositions occurring during the growth season. The parameter sensitivity analysis of Chi-FDMT indicated that the parameters of food intake and processing factor are sensitive, and the sensitivity of the transfer factors within plant and soil-plant systems are dependent on the deposition scenario.
Subject(s)
Food Chain , Fukushima Nuclear Accident , Agriculture , China , Soil/chemistryABSTRACT
Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors. The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer (GBC), therefore, it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC. This case-control study (n = 85 pairs) found that the high level of plasma soy isoflavone-genistein (GEN) was associated with a lower risk of gallbladder cancer (≥326.00 ng/mL compared to ≤19.30 ng/mL, crude odds ratio 0.15, 95% CI 0.04-0.59; P for trend = 0.016), and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue (n = 85). Consistent with these results, the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo. The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3ß axis, leading to downregulation of the MCM complex in GBC cells. In summary, long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells.
Subject(s)
Carcinoma in Situ , Gallbladder Neoplasms , Humans , Genistein/pharmacology , Gallbladder Neoplasms/metabolism , Case-Control Studies , Cell ProliferationABSTRACT
BACKGROUND: Coagulation and fibrinolysis activation are frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis and worse long-term outcome. The specific aim of this study was to develop an effective prognostic nomogram to help make individualized estimates for patients with resected gallbladder cancer (GBC). METHODS: Patients with resected GBC who were diagnosed between 2006 and 2014 at Xinhua Hospital were selected. Model performance was measured by c-index and calibration curve. The results were further validated using bootstrap and a cohort of 38 patients from a branch hospital who underwent surgery from 2006 to 2014. RESULTS: Backward stepwise selection and Lasso were applied respectively to select predictors. T stage, N stage, and preoperative serum fibrinogen were included in the final model. Predictions correlated well with observed 1- and 3-year survival. The c-index for predicting survival was 0.74 (95% confidence interval, 0.70-0.78), which was statistically higher than that of the AJCC 7th system and Nevin system (P=0.04, 0.04, respectively). In the validation cohort, the nomogram performed better than the other two staging systems (c-index: 0.71 vs. 0.67 and 0.67). CONCLUSIONS: The validated nomogram is a practical tool for predicting the overall survival (OS) of postoperative GBC patients. Preoperative serum fibrinogen levels were associated with tumor progression and may be an independent predictor for GBC patients.
ABSTRACT
BACKGROUND: Atopic diseases are characterized by dysregulated inflammatory response, which may incur the onset of peripartum mental disorders, but the impact remains unknown. This study examined whether and to what extent the history of atopic diseases is associated with newly onset peripartum mental disorders. METHODS: Using population-based registries, we identified all primiparous women who gave birth to live singletons in Denmark during 1978-2016 (n = 937,422). The exposure was hospital contact due to the three major types of atopic diseases-asthma, atopic dermatitis, and allergic rhinitis-before conception. The primary outcome was any hospital contact for mental disorder during pregnancy and 1-year postpartum, which was further classified into affective disorders, neurotic, stress-related and somatoform disorders, and substance abuse. The follow-up started from the date of conception and ended at the date of the first diagnosis of mental disorders, 1-year postpartum, death, emigration, or December 31, 2016, whichever came first. Cox regression was used, adjusted for calendar year, age at childbirth, education, residence, and Charlson comorbidity index. RESULTS: A total of 24,016 (2.6%) women received diagnosis of at least one of the three atopic diseases before conception (asthma, 1.7%; atopic dermatitis, 0.6%; and allergic rhinitis, 0.8%). Exposure to asthma, atopic dermatitis, or allergic rhinitis was associated with a 37% increased overall risk of peripartum mental disorders (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.27-1.49). Higher risks were observed among women with more frequent hospital contacts for atopic disease (HR, 1.80; 95% CI, 1.37-2.35; ≥5 times), and with recent hospital contacts for atopic disease (HR, 1.74; 95% CI, 1.48-2.06; within 2 years before conception). Specific associations were observed between asthma and neurotic, stress-related and somatoform disorders (HR, 1.40; 95% CI, 1.21-1.62), and between atopic dermatitis and substance abuse (HR, 1.62; 95% CI, 1.12-2.34). CONCLUSIONS: History of asthma, atopic dermatitis, and allergic rhinitis before conception was associated with increased risks of peripartum mental disorders. Women who have atopic diseases before pregnancy may benefit from systematic mental health monitoring.
ABSTRACT
Aberrant expression of lysyl oxidase-like 1 (LOXL1) reportedly leads to fibrous diseases. Recent studies have revealed its role in cancers. In this study, we observed an elevated level of LOXL1 in the tissues and sera of patients with intrahepatic cholangiocarcinoma (ICC) compared with levels in nontumor tissues and sera of unaffected individuals. Overexpression of LOXL1 in RBE and 9810 cell lines promoted cell proliferation, colony formation, and metastasis in vivo and in vitro and induced angiogenesis. In contrast, depletion of LOXL1 showed the opposite effects. We further showed that LOXL1 interacted with fibulin 5 (FBLN5), which regulates angiogenesis, through binding to the αvß3 integrin in an arginine-glycine-aspartic (Arg-Gly-Asp) domain-dependent mechanism and enhanced the focal adhesion kinase (FAK)-mitogen-activated protein kinase (MAPK) signaling pathway inside vascular endothelial cells. Our findings shed light on the molecular mechanism underlying LOXL1 regulation of angiogenesis in ICC development and indicate that the LOXL1-FBLN5/αvß3 integrin/FAK-MAPK axis might be the critical pathological link leading to angiogenesis in ICC.