Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits.

BACKGROUND: Dietary and gastrointestinal (GI) problems have been frequently reported in autism spectrum disorder (ASD). However, the relative contributions of autism-linked traits to dietary and GI problems in children with ASD are poorly understood. This study firstly compared the dietary intake and GI symptoms between children with ASD and typically developing children (TDC), and then quantified the relative contributions of autism-linked traits to dietary intake, and relative contributions of autism-linked traits and dietary intake to GI symptoms within the ASD group. METHODS: A sample of 121 children with ASD and 121 age-matched TDC were eligible for this study. The dietary intake indicators included food groups intakes, food variety, and diet quality. The autism-linked traits included ASD symptom severity, restricted repetitive behaviors (RRBs), sensory profiles, mealtime behaviors, and their subtypes. Linear mixed-effects models and mixed-effects logistic regression models were used to estimate the relative contributions. RESULTS: Children with ASD had poorer diets with fewer vegetables/fruits, less variety of food, a higher degree of inadequate/unbalanced dietary intake, and more severe constipation/total GI symptoms than age-matched TDC. Within the ASD group, compulsive behavior (a subtype of RRBs) and taste/smell sensitivity were the only traits associated with lower vegetables and fruit consumption, respectively. Self-injurious behavior (a subtype of RRBs) was the only contributing trait to less variety of food. Limited variety (a subtype of mealtime behavior problems) and ASD symptom severity were the primary and secondary contributors to inadequate dietary intake, respectively. ASD symptom severity and limited variety were the primary and secondary contributors to unbalanced dietary intake, respectively. Notably, unbalanced dietary intake was a significant independent factor associated with constipation/total GI symptoms, and autism-linked traits manifested no contributions. CONCLUSIONS: ASD symptom severity and unbalanced diets were the most important contributors to unbalanced dietary intake and GI symptoms, respectively. Our findings highlight that ASD symptom severity and unbalanced diets could provide the largest benefits for the dietary and GI problems of ASD if they were targeted for early detection and optimal treatment.

Ovarian cancer circulating extracelluar vesicles promote coagulation and have a potential in diagnosis: an iTRAQ based proteomic analysis.

BACKGROUND: Circulating extracelluar vesicles (EVs) in epithelial ovarian cancer (EOC) patients emanate from multiple cells. These EVs are emerging as a new type of biomarker as they can be obtained by non-invasive approaches. The aim of this study was to investigate circulating EVs from EOC patients and healthy women to evaluate their biological function and potential as diagnostic biomarkers. METHODS: A quantitative proteomic analysis (iTRAQ) was applied and performed on 10 EOC patients with advanced stage (stage III-IV) and 10 controls. Twenty EOC patients and 20 controls were applied for validation. The candidate proteins were further validated in another 40-paired cohort to investigate their biomarker potential. Coagulation cascades activation was accessed by determining Factor X activity. RESULTS: Compared with controls, 200 proteins were upregulated and 208 proteins were downregulated in the EOC group. The most significantly involved pathway is complement and coagulation cascades. ApoE multiplexed with EpCAM, plg, serpinC1 and C1q provide optimal diagnostic information for EOC with AUC = 0.913 (95% confidence interval (CI) =0.848-0.957, p < 0.0001). Level of activated Factor X was significantly higher in EOC group than control (5.35 ± 0.14 vs. 3.69 ± 0.29, p < 0.0001). CONCLUSIONS: Our study supports the concept of circulating EVs as a tool for non-invasive diagnosis of ovarian cancer. EVs also play pivotal roles in coagulation process, implying the inherent mechanism of generation of thrombus which often occurred in ovarian cancer patients at late stages.

The associations of secondhand smoke exposure with neurodevelopmental disorders and critical time window identification: A systematic review and meta-analysis.

BACKGROUND: Secondhand smoke (SHS) exposure was harmful for brain development. However, the association between SHS exposure and NDDs diagnosis were unclear. OBJECTIVES: To evaluate associations between SHS exposure and NDDs diagnosis, identify critical time windows, and summarize the strength of evidence. METHODS: To investigate the associations of SHS exposure and the development of NDDs, we searched Ovid, EMBASE, Web of Science, Cochrane Library, and PubMed for all the relevant studies up to 31 March 2023. The risk estimates and standardized mean differences (SMD) for the individuals with any NDDs who were exposed to SHS exposure compared with those unexposed or low-exposed. RESULTS: The results showed that a total of 31,098 citations were identified, of which 54 studies were included. We identified significant associations between SHS exposure and the risks of NDDs including specific types of NDDs like attention deficit hyperactivity disorder (ADHD) and learning disabilities (LD) despite the observed heterogeneity for NDDs and ADHD. We also observed a significant association between cotinine exposure and ADHD. However, inconsistent ratings between the two quality-of-evidence methods for all the meta-analyses indicated the current evidence of the associations and the potential exposure window remained inconclusive. DISCUSSION: Our findings suggested that SHS exposure was associated with a higher risk of developing ADHD and LD, with inconclusive quality-of-evidence. In addition, period-specific associations remained unclear based on current evidence.

Pre-conceptional and prenatal exposure to secondhand smoke and autism spectrum disorder: a national multi-center study in China.

BACKGROUND: Despite extensive research evaluating the association between prenatal exposure to secondhand smoke (SHS) and the development of autism spectrum disorders (ASD), no study has investigated the association by considering the pre-conceptional period. This study aimed to investigate the associations of pre-conceptional and prenatal SHS exposure and the development of ASD among toddlers. METHODS: In this cross-sectional study, parents of 6049 toddlers aged 16-30 months were recruited from 7 tertiary hospitals, 21 communities, and 7 kindergartens located in seven cities in six provinces from five geographical regions of China. We analyzed the associations of SHS exposure and the odds of ASD among toddlers in different exposure windows (pre-conceptional and/or prenatal periods). Data were analyzed from November 2021 to January 2022. RESULTS: Among the 6049 toddlers included in the analysis [22.7 (4.1) months; 44.8% girls], 71 were identified and diagnosed with ASD. Compared with the unexposed toddlers, toddlers with pre-conceptional SHS exposure had higher odds of ASD (OR 2.30, 95% CI 1.36-3.84), while we observed a non-significantly positive association regarding prenatal SHS exposure. When considering both pre-conceptional and prenatal periods, toddlers who were continuously exposed to SHS during these two periods had higher odds than those without SHS exposure (OR 2.32, 95% CI 1.24-4.14). CONCLUSION: We reported positive SHS-ASD associations when exposed during the pre-conceptional period and continuously exposed during pre-conceptional and prenatal periods, emphasizing the critical window of pre-conception for targeted intervention on smoking.

Multi-omics analyses demonstrate the modulating role of gut microbiota on the associations of unbalanced dietary intake with gastrointestinal symptoms in children with autism spectrum disorder.

Our previous work revealed that unbalanced dietary intake was an important independent factor associated with constipation and gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD). Growing evidence has shown the alterations in the gut microbiota and gut microbiota-derived metabolites in ASD. However, how the altered microbiota might affect the associations between unbalanced diets and GI symptoms in ASD remains unknown. We analyzed microbiome and metabolomics data in 90 ASD and 90 typically developing (TD) children based on 16S rRNA and untargeted metabolomics, together with dietary intake and GI symptoms assessment. We found that there existed 11 altered gut microbiota (FDR-corrected P-value <0.05) and 397 altered metabolites (P-value <0.05) in children with ASD compared with TD children. Among the 11 altered microbiota, the Turicibacter, Coprococcus 1, and Lachnospiraceae FCS020 group were positively correlated with constipation (FDR-corrected P-value <0.25). The Eggerthellaceae was positively correlated with total GI symptoms (FDR-corrected P-value <0.25). More importantly, three increased microbiota including Turicibacter, Coprococcus 1, and Eggerthellaceae positively modulated the associations of unbalanced dietary intake with constipation and total GI symptoms, and the decreased Clostridium sp. BR31 negatively modulated their associations in ASD children (P-value <0.05). Together, the altered microbiota strengthens the relationship between unbalanced dietary intake and GI symptoms. Among the altered metabolites, ten metabolites derived from microbiota (Turicibacter, Coprococcus 1, Eggerthellaceae, and Clostridium sp. BR31) were screened out, enriched in eight metabolic pathways, and were identified to correlate with constipation and total GI symptoms in ASD children (FDR-corrected P-value <0.25). These metabolomics findings further support the modulating role of gut microbiota on the associations of unbalanced dietary intake with GI symptoms. Collectively, our research provides insights into the relationship between diet, the gut microbiota, and GI symptoms in children with ASD.

Adherence to 24-hour movement guidelines in children with mental, behavioral, and developmental disorders: Data from the 2016-2020 National Survey of Children's Health.

BACKGROUND: Adopting a healthy lifestyle during childhood could improve physical and mental health outcomes in adulthood and reduce relevant disease burdens. However, the lifestyles of children with mental, behavioral, and developmental disorders (MBDDs) remains under-described within the literature of public health field. This study aimed to examine adherence to 24-hour movement guidelines among children with MBDDs compared to population norms and whether these differences are affected by demographic characteristics. METHODS: Data were from the 2016-2020 National Survey of Children's Health-A national, population-based, cross-sectional study. We used the data of 119,406 children aged 6-17 years, which included 38,571 participants with at least 1 MBDD and 80,835 without. Adherence to the 24-hour movement guidelines was measured using parent-reported physical activity, screen time, and sleep duration. RESULTS: Among children with MBDDs, 20.3%, 37.0%, 60.7%, and 77.3% met the physical activity, screen time, sleep, and at least 1 of the 24-hour movement guidelines. These rates were lower than those in children without MBDDs (22.8%, 46.2%, 66.7%, and 83.4%, respectively; all p < 0.001). Children with MBDDs were less likely to meet these guidelines (odds ratio (OR) = 1.21, 95% confidence interval (95%CI): 1.13-1.30; OR = 1.37, 95%CI: 1.29-1.45; OR = 1.29, 95%CI: 1.21-1.37; OR = 1.45, 95%CI: 1.35-1.56) than children without MBDDs. Children with emotional disorders had the highest odds of not meeting these guidelines (OR = 1.43, 95%CI: 1.29-1.57; OR = 1.48, 95%CI: 1.37-1.60; OR = 1.49, 95%CI: 1.39-1.61; OR = 1.72, 95%CI: 1.57-1.88) in comparison to children with other MBDDs. Among children aged 12-17 years, the difference in proportion of meeting physical activity and screen time guidelines for children with vs. children without MBDD was larger than that among children aged 6-11 years. Furthermore, the above difference of meeting physical activity guidelines in ethnic minority children was smaller than that in white children. CONCLUSION: Children with MBDDs were less likely to meet individual or combined 24-hour movement guidelines than children without MBDDs. In educational and clinical settings, the primary focus should be on increasing physical activity and limiting screen time in children aged 12-17 years who have MBDDs; and specifically for white children who have MBDDs, increasing physical activity may help.

Association of sugar-sweetened beverages with executive function in autistic children.

The association between sugar-sweetened beverages (SSBs) consumption and executive function (EF) among typically developing (TD) children has been investigated in previous studies but with inconsistent results. Furthermore, this relationship has been less investigated among autistic children who perform worse in EF compared with TD children. In this study, we aimed to investigate the association between SSB consumption and EF in autistic children, and whether the association between SSB and EF in autistic children is different from that in TD children. We recruited 106 autistic children and 207 TD children aged 6-12 years in Guangzhou, China. Children's EF was assessed by using the Chinese version of parent-reported Behavior Rating Inventory of Executive Function, Stroop Color-Word Test, and working memory subscales of the Chinese version of Wechsler Intelligence Scale for children, Fourth edition. Meanwhile, we assessed children's dietary intake and SSB consumption with a validated Food Frequency Questionnaire. In this study, 70 (66.0%) autistic children consumed SSB and 20 (18.9%) of them consumed more than two servings SSB a week. Among autistic children, over two servings per week SSB consumption was associated with poorer performance in emotional control [ß = 7.20, 95% confidence interval (CI): 0.94-13.46] and plan/Organize (ß = 6.45, 95% CI: 0.27-12.63). The association between over two servings/week SSB consumption and emotional control among autistic children was significantly different from that among TD children (ß ASD = 7.20; ß TD = -3.09, Z = 2.72, p = 0.006). Results of this study show that SSB consumption was associated with an impairment in some subscales of EF in autistic children. Furthermore, the association between SSB and EF in autistic children might be different from that in TD children.

Association between dietary quality and executive functions in school-aged children with autism spectrum disorder.

Background: It is well known that children with autism spectrum disorder (ASD) had executive functions deficit. However, it is still unclear whether the poor dietary quality is related to the impairment of executive functions. The current study aimed to explore the association between dietary quality and executive functions in children with ASD. Methods: A total of 106 children with ASD (7.7 ± 1.3 years) and 207 typically developing (TD) children (7.8 ± 1.3 years) were enrolled from Guangzhou, China. The Chinese version of Behavior Rating Scale of Executive function (BRIEF), the working memory subscales of the Chinese version of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), and the Stroop Color-Word Test (SCWT) were used to measure the participant's executive functions. The food frequency questionnaire (FFQ) was used to collect the dietary intake information, and the Chinese Diet Balance Index (DBI_16) was used to evaluate the dietary quality. Generalized linear models were used to estimate the association between dietary quality and executive functions. Results: In children with ASD, Low Bound Score (LBS) was positively correlated with the working memory subscale score of BRIEF (ß = 0.23, 95% CI: 0.02-0.44, P < 0.05), while High Bound Score (HBS) and LBS were positively correlated with the organizable subscale score of BRIEF (ß = 0.44, 95% CI: 0.11-0.77, P < 0.01; ß = 0.19, 95% CI: 0.01-0.37, P < 0.05). Compared to TD children, children with ASD had a higher proportion of moderate and high levels of insufficient dietary intake (moderate level, 37.7% vs. 23.2%, high level, 4.7% vs. 1.4%) and moderate level of unbalanced dietary intake (36.8% vs.21.3%), higher scores on all subscales of BRIEF (P < 0.01), and lower score on the working memory (81.3 ± 32.3 vs. 104.6 ± 12.5, P < 0.01), while there was no difference on the SCWT. Conclusion: Poor dietary quality was associated with the impairment of working memory and organizational capacity in children with ASD. This study emphasized the importance of dietary quality in executive functions among children with ASD, and attention should be paid to improving their dietary quality.

Proteomics profiling of plasma exosomes in epithelial ovarian cancer: A potential role in the coagulation cascade, diagnosis and prognosis.

Ovarian cancer remains the most lethal type of cancer among all gynecological malignancies. The majority of patients are diagnosed with ovarian cancer at the late stages of the disease. Therefore, there exists an imperative need for the development of early ovarian cancer diagnostic techniques. Exosomes, secreted by various cell types, play pivotal roles in intercellular communication, which emerge as promising diagnostic and prognostic biomarkers for ovarian cancer. In this study, we present for the first time, at least to the best of our knowledge, the proteomics profiling of exosomes derived from the plasma of patients with ovarian cancer via liquid chromatography tandem mass spectrometry (LC­MS/MS) with tandem mass tagging (TMT). The exosomes enriched from patient plasma samples were characterized by nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), transmission electron microscopy (TEM) and western blot analysis. The size of the plasma exosomes fell into the range of 30 to 100 nm in diameter. The exosomal marker proteins, CD81 and TSG101, were clearly stained in the exosome samples; however, there was no staining for the endoplasmic reticulum protein, calnexin. A total of 294 proteins were identified with all exosome samples. Among these, 225 proteins were detected in both the cancerous and non­cancerous samples. Apart from universal exosomal proteins, exosomes derived from ovarian cancer patient plasma also contained tumor­specific proteins relevant to tumorigenesis and metastasis, particularly in epithelial ovarian carcinoma (EOC). Patients with EOC often suffer from coagulation dysfunction. The function of exosomes in coagulation was also examined. Several genes relevant to the coagulation cascade were screened out as promising diagnostic and prognostic factors that may play important roles in ovarian cancer progression and metastasis. On the whole, in this study, we successfully isolated and purified exosomes from plasma of patients with EOC, and identified a potential role of these exosomes in the coagulation cascade, as well as in the diagnosis and prognosis of patients.

Interferon gamma is involved in apoptosis of trophoblast cells at the maternal-fetal interface following Toxoplasma gondii infection.

OBJECTIVE: To assess whether interferon gamma (IFN-γ) secreted by decidual natural killer (dNK) cells at the maternal-fetal interface is involved in the apoptosis of trophoblast cells (trophoblasts) following Toxoplasma gondii infection. METHODS: Human dNK cells were infected with T. gondii and then co-cultured with trophoblasts. The infected co-cultured cells were treated with or without IFN-γ neutralizing antibodies. Uninfected co-cultured cells were used as controls. The level of IFN-γ in the supernatant of co-culture was measured by ELISA and the apoptosis of trophoblasts was analyzed by flow cytometry. The expression of caspase 3 and caspase 8 of trophoblasts cells was determined by Western blotting and real-time RT-PCR. RESULTS: The levels of IFN-γ were increased at <24h following T. gondii infection and were maintained thereafter. Caspase 3, caspase 8, and the apoptosis of trophoblasts co-cultured with dNK cells were increased compared with the control. Meanwhile, IFN-γ, caspase 3, caspase 8, and trophoblast apoptosis were up-regulated upon increased ratios of dNK cells to trophoblasts. Compared to the infected group, the levels of IFN-γ, caspase 3, caspase 8, and trophoblast apoptosis were significantly decreased upon treatment with the IFN-γ neutralizing antibody. IFN-γ levels were correlated positively with the apoptosis of trophoblasts (r=0.7163, p < 0.01). CONCLUSIONS: The levels of IFN-γ secreted by dNK cells at the maternal-fetal interface were closely correlated with the apoptosis of trophoblasts upon T. gondii infection. The apoptosis of trophoblasts induced by the increase in IFN-γ depended on the caspase pathway, which may contribute to the abnormal pregnancy outcomes that occur with T. gondii infection.