TBBPS caused necroptosis and inflammation in hepatocytes by blocking PINK1-PARKIN-mediated mitochondrial autophagy.

The widespread use of Tetrabromobisphenol S (TBBPS), as an alternative to tetrabromobisphenol A (TBBPA), has been detected at high frequency in environmental media in recent years, TBBPS can enter the body via the digestive tract and other routes, thus long-term TBBPS exposure may cause adverse health effects. Therefore, it is necessary to evaluate the toxicological effects of TBBPS. In the current work, two cell models of the liver were used (a human-derived cell line THLE-2 and a murine-derived AML12). The liver cells were then exposed to different concentrations of TBBPS. The results of cell proliferation assays showed that TBBPS resulted in a significant attenuation of the proliferative capacity of liver cells. Further results from ELISA and Western-blot assays showed that TBBPS induced an inflammatory response in liver cells by detecting the levels of inflammatory factors, such as TNFα, IL-1ß and IL-6. We also found that TBBPS promoted the necroptosis in liver cells by evaluating the levels of RIP3 and pMLKL, and the use of inhibitors of necroptosis confirmed that the type of cell death induced by TBBPS belongs to necroptosis. Molecular mechanistic studies showed that TBBPS suppressed mitochondrial autophagy mediated by the PINK1-PARKIN signaling pathway, which led to accumulation of damaged mitochondria in THLE-2 and AML12 cells. Subsequently, accumulated ROS activated necroptosis of liver cells. Current toxicological studies suggest that we need to better control and regulate the production and use of TBBPS, the current work provide a reference for studying the toxicology of TBBPS.

Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear mechanisms of pathogenesis. Gastrointestinal microbiome alterations were found to correlate with ASD core symptoms, but its specific role in ASD pathogenesis has not been determined. In this study, we used a case-control strategy that simultaneously compared the ASD gastrointestinal microbiome with that from age-sex matched controls and first-degree relative controls, using a statistical framework accounting for confounders such as age. Enterobacteriaceae (including Escherichia/Shigella) and Phyllobacterium were significantly enriched in the ASD group, with their relative abundances all following a pattern of ASD > first degree relative control > healthy control, consistent with our hypothesis of living environment and shared microbial and immunological exposures as key drivers of ASD gastrointestinal microbiome dysbiosis. Using multivariable omnibus testing, we identified clinical factors including ADOS scores, dietary habits, and gastrointestinal symptoms that covary with overall microbiome structure within the ASD cohort. A microbiome-specific multivariate modeling approach (MaAsLin2) demonstrated microbial taxa, such as Lachnoclostridium and Tyzzerella, are significantly associated with ASD core symptoms measured by ADOS. Finally, we identified alterations in predicted biological functions, including tryptophan and tyrosine biosynthesis/metabolism potentially relevant to the pathophysiology of the gut-brain-axis. Overall, our results identified gastrointestinal microbiome signature changes in patients with ASD, highlighted associations between gastrointestinal microbiome and clinical characteristics related to the gut-brain axis and identified contributors to the heterogeneity of gastrointestinal microbiome within the ASD population.

Serum Oxytocin Level Correlates With Gut Microbiome Dysbiosis in Children With Autism Spectrum Disorder.

To investigate the levels of serum oxytocin (OT) in children with autism spectrum disorder (ASD) and explore the association between OT levels and gut microbiota relative abundances, we recruited 39 children with ASD children-mother dyads and 44 healthy controls. Serum OT levels were determined via enzyme-linked immunosorbent assay and gut microbiota abundances were determined by 16S rRNA sequencing. We found that the OT level of ASD was lower than the healthy control group overall (P < 0.05). Furthermore, we present preliminary evidence of gut microbiome dysbiosis observed among children with ASD to lower levels of OT based on correlational analysis between serum OT and specific gut microbiota abundances (P < 0.05). We also found sex-related differences in serum OT levels and GIS index (P < 0.05). However, the generalizability of findings relevant to females with ASD require further validation in future studies involving larger sample sizes and balanced sex distributions due to the small number of females involved in this study. Nonetheless, these new findings further our understanding of the effects of low serum OT levels among individuals with ASD, which provides preliminary evidence in hopes of guiding future study design or mechanistic studies. The findings of the present study may be suggestive of potential ASD subtypes based on ASD severity and gut microbiome composition that may facilitate the prediction of the therapeutic responses of OT among those with ASD.

Transcranial Direct Current Stimulation (tDCS) over the Left Dorsal Lateral Prefrontal Cortex in Children with Autism Spectrum Disorder (ASD).

Recently, transcranial direct current stimulation (tDCS) has been applied to relieve symptoms in individuals with autism spectrum disorder (ASD). In this prospective, parallel, single-blinded, randomized study, we investigate the modulation effect of three-week tDCS treatment at the left dorsal lateral prefrontal cortex (DLPFC) in children with ASD. 47 children with ASD were enrolled, and 40 (20 in each group) completed the study. The primary outcomes are Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and the Repetitive Behavior Scale-Revised (RBS-R). We found that children with ASD can tolerate three-week tDCS treatment with no serious adverse events detected. A within-group comparison showed that real tDCS, but not sham tDCS, can significantly reduce the scores of CARS, Children's Sleep Habits Questionnaire (CSHQ), and general impressions in CARS (15th item). Real tDCS produced significant score reduction in the CSHQ and in CARS general impressions when compared to the effects of sham tDCS. The pilot study suggests that three-week left DLPFC tDCS is well-tolerated and may hold potential in relieving some symptoms in children with ASD.

Dysfunction of the Auditory Brainstem as a Neurophysiology Subtype of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is very heterogeneous, particularly in language. Studies have suggested that language impairment is linked to auditory-brainstem dysfunction in ASD. However, not all ASD children have these deficits, which suggests potential subtypes of ASD. We classified ASD children into two subtypes according to their speech-evoked auditory brainstem response (speech-ABR) and explored the neural substrates for possible subtypes. Twenty-nine children with ASD and 25 typically developing (TD) peers were enrolled to undergo speech-ABR testing and structural magnetic resonance imaging (sMRI). There were significant differences between the ASD group and TD group in surface area, cortical volume and cortical thickness. According to speech-ABR results, ASD participants were divided into the ASD-typical (ASD-T) group and ASD-atypical (ASD-A) group. Compared with the ASD-T group, the ASD-A group had a lower score in language of the Gesell Developmental Diagnosis Scale (GDDS), increased left rostral middle frontal gyrus (lRMFG) area and decreased local gyrification index of the right superior temporal gyrus. GDDS-language and surface area of lRMFG were correlated to the wave-A amplitude in ASD. Surface area of lRMFG had an indirect effect on language performance via alteration of the wave-V amplitude. Thus, cortical deficits may impair language ability in children with ASD by causing subcortical dysfunction at preschool age. These evidences support dysfunction of the auditory brainstem as a potential subtype of ASD. Besides, this subtype-based method may be useful for various clinical applications.

[An experience providing home care to a victim of cerebral vascular accident and purple urine bag syndrome].

This article presents the case of a victim of cerebral vascular accident with long duration of urinary catheterization, who developed a purple urine bag syndrome (PUBS) because of deficiency of knowledge and skills in home care and lack of communication and support among family members. In this case, the main caregivers also experienced psychophysical fatigue and fear, which diminished family coping ability. During the period of nursing care, from March 10 to August 15, 2006, we carried out 10 home care visits and eight telephone consultations. Exiting urinary tract infection, constipation, and compromised coping and ineffective family were identified as the three main nursing care issues. As we successfully instilled trust and developed a positive relationship with the patient, we provided continuous and comprehensive nursing care to resolve the PUBS issue her which was causing her anxiety, and her constipation, as well as stabilizing her family function. Consequently, through this care experience involving a sick elderly patient, we promoted the function of nursing home care. From this case intervention, we found that health education should be closely followed up in order to maintain its effectiveness. Insufficient communication skills, however, were identified through meetings with the patient's family. We suggested related family communication skills and practices should be included in clinical nursing training courses to enhance skills in dealing with family issues and life quality among patients and their families.