Factors linked to prognosis in children with provisional tic disorder: a prospective cohort study.

The purpose of the present study was to estimate the factors linked to the prognosis of children with provisional tic disorder (PTD). We conducted a prospective cohort study enrolled children with PTD who were subsequently followed-up at three-month intervals for 1 year post-enrolment. A total of 259 PTD patients were included in the final analysis. At the end of the follow-up period, 77 (30%) of the patients had achieved clinical remission. Result of the LASSO logistic regression analysis revealed that a disease duration >3 months (OR=4.20, 95% CI 1.20-14.73), moderate/severe tic severity (OR=5.57, 95% CI 2.26-13.76), and comorbid behavioral problems (OR=2.78, 95% CI 1.15-6.69) were significant factors linked to remission in the PTD patients. The path analysis model showed that comorbid behavioral problems and recurrence partially mediated the association between tic severity and remission, with a mediating effect of 37%. Conclusions: We have identified several significant factors linked to prognosis in children with PTD, including comorbid behavioral problems and recurrence, which were found to be important mediators. These findings provide new insights for the clinical management of patients with PTD.

Sociodemographic and clinical characteristics of children with tic disorders and behavioral problems: A real-world study and development of a prediction model.

BACKGROUND: Tic disorders (TD) are complex neuropsychiatric disorders frequently associated with a variety of comorbid problems, whose negative effects may exceed those of the tics themselves. In this study, we aimed to explore the sociodemographic and clinical characteristics of children with TD and behavioral problems, and develop a prediction model of behavioral problems based on the predictors under real-world conditions. METHODS: A hospital-based cross-sectional study was conducted on children with TD. Behavioral problems were surveyed using the Achenbach Child Behavior Checklist (CBCL). Sociodemographic information was collected from face-to-face interviews using an electronic questionnaire administered during the initial ambulatory visit. Clinical data were collected from medical records, and quality control was performed. The sociodemographic and clinical characteristics of patients with and without behavioral problems were statistically compared, and a nomogram prediction model was developed based on multivariate logistic regression analysis. The discriminatory ability and clinical utility of the nomogram were assessed by concordance index (C-index), receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: A total of 343 TD cases were included in the final analysis, of which 30.32% had behavioral problems. The prediction model showed age 12-16 years, abnormal birth history, parenting pattern of indulgence, parent/close relatives with psychiatric disorders, chronic motor or vocal tic disorder (CTD)/Tourette syndrome (TS) and moderate/severe tic severity were associated with behavioral problems in children with TD. The C-index of the prediction model (nomogram) was 0.763 (95% confidence interval, 0.710 ~ 0.816). The nomogram was feasible for making beneficial clinical decisions, according to the satisfactory results of the DCA and CIC. CONCLUSIONS: A nomogram prediction model for comorbid behavioral problems in children with TD was established. The prediction model demonstrated a good discriminative ability and predictive performance for beneficial clinical decisions. This model further provides a comprehensive understanding of associated sociodemographic and clinical characteristics by visual graphs and allows clinicians to rapidly identify patients with a higher risk of behavioral problems and tailor necessary interventions to improve clinical outcomes.

Research on Heterogeneous Traveler Travel Mode Choices with Differences under a Mixed Traffic Environment.

Autonomous vehicles (AVs) have been made possible by advances in sensing and computing technologies. However, the high cost of AVs makes privatization take longer. Therefore, companies with autonomous vehicles can develop shared autonomous vehicle (SAV) projects. AVs with a high level of automation require high upgrade and use costs. In order to meet the needs of more customers and reduce the investment cost of the company, SAVs with different levels of automation may coexist for a long time. Faced with multiple travel modes (autonomous cars with different levels of automation, private cars, and buses), travelers' travel mode choices are worth studying. To further differentiate the types of travelers, this paper defines high-income travelers and low-income travelers. The difference between these two types of travelers is whether they have a private car. The differences in time value and willingness to pay of the two types of travelers are considered. Based on the above considerations, this paper establishes a multi-modal selection model with the goal of maximizing the total utility of all travelers and uses the imperial competition algorithm to solve it. The results show that low-income travelers are more likely to choose buses and autonomous vehicles with lower levels of automation, while high-income travelers tend to choose higher levels of automation due to their high value of travel time.

NLRP3 Inflammasome Activation Enhances ADK Expression to Accelerate Epilepsy in Mice.

Epilepsy (SE) is a common and serious neurological disease. NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome participates in the pathogenesis of SE, while its underlying mechanism is still unclear. Here, we attempted to explore the mechanism of action of NLRP3 inflammasome in SE. SE mouse model was constructed by administration of kainic acid (KA). Astrocytes were treated with KA to mimic SE cell model. MCC950 (NLRP3 inhibitor) and Z-YVAD-FMK (Caspase-1 inhibitor) were used to treat astrocytes to inhibit the activity of NLRP3 and Caspase-1. Nissl staining was performed to examine the morphology of neuron. Western blot, enzyme-linked immunosorbent assay and immunofluorescence staining were performed to assess protein expression. SE mouse model exhibited an increase of neuronal loss, and an up-regulation of Cleaved-Caspase-1, IL-1ß and IL-18 in hippocampus. The levels of GFAP+ADK+ cells were significantly increased in SE mice. MCC950 or Z-YVAD-FMK abolished these impacts conferred by KA in SE mice. Moreover, KA treatment enhanced the expression of NLRP3, Cleaved-Caspase-1, IL-1ß and IL-18 in astrocytes, which was rescued by knockdown of NLRP3 or Caspase-1. Additionally, CREB, p-CREB, REST were up-regulated, and SP1 was down-regulated in the KA-treated SE mice and KA-treated astrocytes. Inhibition of NLRP3 or Caspase-1 rescued these proteins expression in KA-treated astrocytes. CREB or REST silencing reduced adenosine kinase (ADK) expression, while SP1 knockdown enhanced ADK expression in KA-treated astrocytes. In conclusion, NLRP3 inflammasome activation enhances ADK expression to accelerate SE in mice through regulating CREB/REST/SP1 signaling pathway. Thus, inhibition of NLRP3 inflammasome may be a treatment for SE.

Arc and Homer1 are involved in comorbid epilepsy and depression: A microarray data analysis.

BACKGROUND: Depression is one of the most common comorbid psychiatric condition associated with epilepsy. It has a negative impact on the patient's quality of life. However, the underlying molecular mechanisms leading to depression are currently unclear. The aim of this study was to determine the hub genes associated with epilepsy and depression. METHODS: Gene expression profiles (GSE47752 and GSE20388) were downloaded from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) for epilepsy and depression groups were separately searched. Subsequently, network analyses methods were employed to establish protein-protein interaction (PPI) networks, and to perform Gene Ontology (GO) terms and pathway enrichment analyses for co-expressed DEGs. RESULTS: A total of 772 genes were upregulated in patients with epilepsy whereas 91 genes were up-regulated in patients with depression. In addition, 1304 genes were down-regulated in epilepsy whereas 141 genes were down-regulated in patients with depression. Among co-expressed DEGs, 5 DEGs were up-regulated and 19 were down-regulated. Further analysis revealed that the co-expressed DEGs were involved in regulation of vasculature development, regulation of angiogenesis, glutamate receptor signaling pathway, cellular response to interleukin-1 and positive regulation of protein kinase B signaling. The Arc and Homer1 genes were identified as the common candidate genes involved in the pathogenesis of epilepsy and depression. CONCLUSIONS: Arc and Homer1 may contribute to the comorbidity of epilepsy and depression.

Investigating the effectiveness of COVID-19 pandemic countermeasures on the use of public transport: A case study of The Netherlands.

During the COVID-19 pandemic, public transport in many cities faces dramatic reduction of passenger demand. Various countermeasures such as social distancing and in-vehicle disinfection have been implemented to reduce the potential risks concerning infection, the effectiveness in promoting the use of public transport however remains unclear. Unlike the usual situation where time and cost are the main factors affecting travel decisions, the uncertainty hiding behind the behavior change of public transport users in a pandemic might be greatly affected by the control measures and the perception of people. This paper therefore aims to examine the effects of COVID-19 related countermeasures implemented in public transport on individuals' travel decisions. We explore the extent to which do policy countermeasures influence different groups of people on the use of public transport. An error component latent class choice model was estimated using the data collected in the Netherlands. Results show that the restrictions policy lifted by the Dutch central government have significant effect on individuals' transportation mode choice decision during the pandemic. The related measures adopted by the public transport sector, by contrast, present different effects on different people. The older and highly educated people are more susceptible to enforcement measures, whereas young and single Dutch citizens are more accessible to non-compulsory measures. Moreover, compared with other private modes, public transport is generally identified as a riskier option, and the average willingness to travel descends. Findings of this study are helpful for the authorities in designing and promoting effective policies in the context of pandemics.

Cardiac Biomarker Abnormalities Are Closely Related to Prognosis in Patients with COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is erupting and spreading globally. Cardiovascular complications secondary to the infection have caught notice. This study aims to delineate the relationship of cardiac biomarkers and outcomes in severe cases of corona virus disease 2019 (COVID-19). One hundred forty-eight critically ill adult patients with COVID-19 were enrolled. From these patients, the demographic data, symptoms, cardiac biomarkers, treatments, and clinical outcomes were collected. Data were compared between survivors and non-survivors. Four patients in the non-survivor group were selected, and their cardiac biomarkers were collected and analyzed. Among the 148 patients, the incidence of cardiovascular complications was 19 (12.8%). Five of them were survivors (5.2%), and 14 of them were non-survivors (26.9%). Compared with the survivors, the non-survivors had higher levels of high-sensitivity cardiac troponin I, creatine kinase isoenzyme-MB, myoglobin, and N-terminal pro-brain natriuretic peptide (P < 0.05). The occurrence of cardiovascular events began at 11-15 days after the onset of the disease and reached a peak at 14-20 days. COVID-19 not only is a respiratory disease but also causes damage to the cardiovascular system. Cardiac biomarkers have the potential for early warning and prognostic evaluation in patients with COVID-19. It is recommended that cardiac biomarker monitoring in patients with COVID-19 should be initiated at least from the 11th day of the disease course.

Association between breastfeeding and Kawasaki disease: a case-control study.

The association between breastfeeding and Kawasaki disease is not fully understood. We performed a case-control study to examine the association between breastfeeding and Kawasaki disease. In this study, 389 children diagnosed with Kawasaki disease and 426 gender- and age-matched controls were identified at Renmin Hospital of Wuhan University between November 2013 and March 2019. Demographic and clinical data were collected from a structured telephone interview and medical record database. Odds ratio and 95% confidence interval for risk of Kawasaki disease were estimated. Children who were breastfed exclusively had a decrease in developing Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.53 (0.38-0.74). Although the risk reduction was not statistically different, partial breastfeeding also provided a protective effect (adjusted odds ratios and 95% confidence intervals 0.70 (0.48-1.01). In the stratified analysis, we still observed that exclusive breastfeeding was inversely associated with the development of complete Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.52 (0.31-0.88) and incomplete Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.54 (0.38-0.77). However, there was no significant association between exclusive breastfeeding and the intravenous immunoglobulin treatment response (adjusted odds ratios and 95% confidence intervals 0.69 (0.27-1.69) and the risk of coronary artery lesions (adjusted odds ratios and 95% confidence intervals 0.79 (0.49-1.31) in Kawasaki disease.Conclusion: Our analysis suggests that exclusive breastfeeding was inversely associated with the development of Kawasaki disease and that breastfeeding might be a potential protective factor against Kawasaki diseaseWhat is known• Previous studies have demonstrated that breastfeeding has been shown to potentially confer protection against several autoimmune disorders of childhood.• The association between breastfeeding and Kawasaki disease is not fully understood.What is newThe first study to evaluate the association between breastfeeding and the development of Kawasaki disease in China with a large sample size.• Exclusive breastfeeding was inversely associated with the development of Kawasaki disease and breastfeeding might be a potential protective factor against Kawasaki disease.

Construction of prognostic risk prediction model based on high-throughput sequencing expression profile data in childhood acute myeloid leukemia.

This study aimed to identify critical prognostic molecular markers in Childhood acute myeloid leukemia (AML) and construct nomogram-based model for prognostic prediction. The RNA-sequencing profiles and corresponding clinical information were downloaded from TCGA database. Differential expressed genes (DEG) were screened using limma package, subsequently following by GO and KEGG pathway analysis. Univariate and multivariate cox regression analysis were performed to screen critical DEGs. Nomogram-based prediction model were constructed to identify clinical factors with independent prognostic values, and the accuracy of this model was validated. A total of 214 DEGs were identified from relapse AML samples compared with non-relapse samples. These DEGs were mainly involved in twenty GO terms and three signaling pathways, such as chromatin assembly or disassembly, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathway. Among these genes, Univariate and multivariate cox regression analysis results showed that relapse and risk score were significantly correlated with survival outcomes. Finally, the accuracy ability of nomogram-based prediction model was validated. These six DEGs (ABCA5, CYP7A1, HERC5, etc.) play major roles in AMLs progression. Our nomogram-based prognostic predictive model might be an effective method to estimate survival probability of AML patients with different risk status.

Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a treatment option for depression and anxiety. However, its role in epilepsy comorbid with depression and anxiety is unclear. Therefore, we evaluated whether low-frequency rTMS can alleviate depression- and anxiety-like behavior in epileptic rats. Forty-eight adult rats were allocated at random to four groups: Control, Pentylenetetrazol (PTZ), PTZ-rTMS and PTZ-Sham. The control group received intraperitoneal injections of normal saline, while the other groups received intraperitoneal injections of pentylenetetrazol (35 mg/kg/d) once a day for 15 days. Low-frequency rTMS or sham stimulation were administered to the PTZ-rTMS and PTZ-Sham group, respectively, over the two-week period. The open-field test (OFT), elevated plus-maze test (EPM) and forced swimming test (FST) were carried out before the experiment, on the 8th and 15th day to assess depression- and anxiety-like behavior in the rats. Two weeks of low-frequency rTMS treatment could not impair the increases of seizure severity in epileptic rats. However, relative to the PTZ and PTZ-Sham group, the two-week low-frequency rTMS treatment significantly reduced the immobility time in the forced swimming test and attenuated the progressive decrease in total distance traveled, frequency of rearing, velocity in the open-field test, number of entries in the open arms (%) and the time spent in the open arms (%) in the elevated plus-maze test of the PTZ-rTMS group. We proposed that low-frequency rTMS can benefit epileptic rats via amelioration of comorbid depression and anxiety, but it can not alleviate the seizure severity.

Inhibition of MicroRNA-23b Attenuates Immunosuppression During Late Sepsis Through NIK, TRAF1, and XIAP.

Background: microRNA-23b (miR-23b) is a multiple functional miRNA. We hypothesize that miR-23b plays a role in the pathogenesis of sepsis. Our study investigated the effect of miR-23b on sepsis-induced immunosuppression. Methods: Mice were treated with miR-23b inhibitors by tail vein injection 2 days after cecal ligation puncture (CLP)-induced sepsis. Apoptosis in spleens and apoptotic signals were investigated, and survival was monitored. T-cell immunoreactivities were examined during late sepsis. Nuclear factor κB (NF-κB)-inducing kinase (NIK), tumor necrosis factor (TNF)-receptor associated factor 1 (TRAF1), and X-linked inhibitor of apoptosis protein (XIAP), the putative targets of miR-23b, were identified by a dual-luciferase reporter assay. Results: miR-23b expression is upregulated and sustained during sepsis. The activation of the TLR4/TLR9/p38 MAPK/STAT3 signal pathway contributes to the production of miR-23b in CLP-induced sepsis. miR-23b inhibitor decreased the number of spleen cells positive by terminal deoxynucleotidyl transferase dUTP nick-end labeling and improved survival. miR-23b inhibitor restored the immunoreactivity by alleviating the development of T-cell exhaustion and producing smaller amounts of immunosuppressive interleukin 10 and interleukin 4 during late sepsis. We demonstrated that miR-23b mediated immunosuppression during late sepsis by inhibiting the noncanonical NF-κB signal and promoting the proapoptotic signal pathway by targeting NIK, TRAF1, and XIAP. Conclusions: Inhibition of miR-23b reduces late-sepsis-induced immunosuppression and improves survival. miR-23b might be a target for immunosuppression.

[Clinical manifestations and genetic diagnosis of paroxysmal kinesigenic dyskinesia].

The clinical manifestations of five children with paroxysmal kinesigenic dyskinesia (PKD) were retrospectively analyzed and their gene mutations were analyzed by high-throughput sequencing and chromosome microarray. The 5 patients consisted of 4 males and 1 female and the age of onset was 6-9 years. Dyskinesia was induced by sudden turn movement, scare, mental stress, or other factors. These patients were conscious and had abnormal posture of unilateral or bilateral extremities, athetosis, facial muscle twitching, and abnormal body posture. The frequency of onset ranged from 3-5 times a month to 2-7 times a day, with a duration of <30 seconds every time. Electroencephalography showed no abnormality in these patients. Three patients had a family history of similar disease. The high-throughput sequencing results showed that a heterozygous mutation in the PRRT2 gene, c.649_650insC (p.R217PfsX8), was found in two patients; the mutation c.436C>T (p.P146S) was found in one patient; a splice site mutation, IVS2-1G>A, was found in one patient. The two mutations c.436C>T and IVS2-1G>A had not been reported previously. The chromosome microarray analysis was performed in one patient with negative results of gene detection, and the chromosome 16p11.2 deletion (0.55 Mb) was observed. Low-dose carbamazepine was effective for treatment of the 5 patients. PKD is a rare neurological disease. The detection of the PRRT2 gene by multiple genetic analysis can help the early diagnosis of PKD.

How is the P2X7 receptor signaling pathway involved in epileptogenesis?

Epilepsy, a condition characterized by spontaneous recurrent epileptic seizures, is among the most prevalent neurological disorders. This disorder is estimated to affect approximately 70 million people worldwide. Although antiseizure medications are considered the first-line treatments for epilepsy, most of the available antiepileptic drugs are not effective in nearly one-third of patients. This calls for the development of more effective drugs. Evidence from animal models and epilepsy patients suggests that strategies that interfere with the P2X7 receptor by binding to adenosine triphosphate (ATP) are potential treatments for this patient population. This review describes the role of the P2X7 receptor signaling pathways in epileptogenesis. We highlight the genes, purinergic signaling, Pannexin1, glutamatergic signaling, adenosine kinase, calcium signaling, and inflammatory response factors involved in the process, and conclude with a synopsis of these key connections. By unraveling the intricate interplay between P2X7 receptors and epileptogenesis, this review provides ideas for designing potent clinical therapies that will revolutionize both prevention and treatment for epileptic patients.

MCC950 alleviates seizure severity and angiogenesis by inhibiting NLRP3/ IL-1ß signaling pathway-mediated pyroptosis in mouse model of epilepsy.

Epilepsy is one of the most common serious chronic brain disorders, affecting up to 70 million people worldwide. Vascular disruption, including blood-brain barrier impairment and pathological angiogenesis, exacerbates its occurrence. However, its underlying mechanisms remain elusive. MCC950 is a specific small-molecule inhibitor that selectively blocks NLRP3 inflammatory vesicle activation across the blood-brain barrier, limits downstream IL-1ß maturation and release, and exerts therapeutic effects across multiple diseases. In the present study, an epilepsy model was established by intraperitoneal administration of Kainic acid to adult male C57BL/6J wild-type mice. The results revealed that the epilepsy susceptibility of MCC950-treated mice was decreased, and neural damage following seizure episodes was reduced. In addition, immunofluorescence staining, RT-qPCR, and Western blot demonstrated that MCC950 inhibited the expression of the NLRP3 inflammasome and its related proteins in microglia, whereas microangiogenesis was found to be increased in the cerebral cortex and hippocampus of epileptic mice, and these effects could be reversed by MCC950. Furthermore, neurobehavioral impairment was observed in the epileptic mouse model, and MCC950 similarly alleviated the aforementioned pathological process. To the best of our knowledge, this is the first study to establish that pathological microangiogenesis is associated with NLRP3/IL-1ß signaling pathway activation in a Kainic acid-induced epilepsy mouse model and that MCC950 administration attenuates the above-mentioned pathological changes and exerts neuroprotective effects. Therefore, MCC950 is a promising therapeutic agent for the treatment of epilepsy.

Novel compound heterozygous variants in the CSPP1 gene causes Joubert syndrome: case report and literature review of the CSPP1 gene's pathogenic mechanism.

Joubert syndrome (JS) is a rare autosomal recessive neurodevelopmental condition characterized by congenital mid-hindbrain abnormalities and a variety of clinical manifestations. This article describes a case of Joubert syndrome type 21 with microcephaly, seizures, developmental delay and language regression, caused by a CSPP1 gene variant and examines the contributing variables. This paper advances the understanding of JS by summarizing the literature and offering detection patterns for practitioners with clinical suspicions of JS.

Cross-sectional investigation of quality of life determinants among children with tic disorders: The roles of family environmental and clinical factors.

Objective: To examine the association between family environmental and clinical factors with the whole range of quality of life (QOL) in children with tic disorders (TD). Methods: A hospital-based cross-sectional study was conducted among children with TD. All participants were given a family environmental survey and scale evaluations with Yale Global Tic Severity Scale (YGTSS), Achenbach Child Behavior Checklist (CBCL) and PedsQL-Generic Core Scale of the Chinese Version (PedsQL). Variable selection and data analysis was done by the least absolute shrinkage and selection operator (LASSO) method and multivariate logistic regression analysis. Results: A total of 363 TD cases were included in the analysis. YGTSS scores, total CBCL score had significant negative correlations with PedsQL scores (P < 0.05). Of the total 15 factors, 8, 6, 11, 7, 5, 10 potential predictors with nonzero coefficients were identified by LASSO regression models of physical functioning, emotional functioning, social functioning, school functioning, social-psychological domain and PedsQL total scale respectively. Results of multivariate logistic regression analysis showed older age (physical functioning, ORs: 1.77, 3.67; total scale: ORs: 1.73, 2.28), no presence of chronic conditions (school functioning, OR: 1.61), moderate/severe tic severity (physical functioning, OR: 0.57; social functioning, OR: 0.44; social-psychological domain, OR: 0.57), co-morbid behavioral problems (physical functioning, OR: 0.52; emotional functioning, OR: 0.31; social functioning, OR: 0.30; school functioning, OR: 0.35; social-psychological domain, OR: 0.34; total scale, OR: 0.30), no fully parental involvement in care (physical functioning, OR: 0.62), higher paternal (physical functioning, ORs: 2.89, 2.07) and maternal education level (social functioning, ORs: 1.74, 2.03), democratic parenting pattern (emotional functioning, OR: 1.89; social functioning, OR: 2.17; social-psychological domain, OR: 2.33; total scale, OR: 2.11) and inharmony family relationship (emotional functioning, OR: 0.47; total scale, OR: 0.50) were the most important determinants to QOL of TD. Conclusions: This study identifies several QOL determinants among children with TD. Clinicians should be encouraged to screen for family environmental and clinical factors in TD patients, and take tailored interventions to help TD children improve their QOL.

Comorbidity of epilepsy and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis.

Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are common neurological and neuropsychiatric disorders, respectively, that can exist as comorbidities. However, the degree of comorbidity between both disorders has never been quantified based on a systematic review with meta-analysis. We performed a systematic search of the literature in Embase, PubMed, PsychINFO and the Cochrane Library on June 20, 2022. In a meta-analysis of 63 studies with a total sample size of 1,073,188 individuals (172,206 with epilepsy and 900,982 with ADHD) from 17 countries, the pooled prevalence of ADHD in epilepsy was 22.3% (95% CI 20.3-24.4%). The highest pooled prevalence was 12.7% (95% CI 9-17.1%) for ADHD-I subtype, whereas the pooled prevalence of epilepsy in ADHD was 3.4% (95% CI 2.53-4.21%). However, substantial heterogeneity in comorbidity rates was observed and partially attributed to the following factors: sample size, sample specification, geographical variations and diagnostic methods. Our study highlights the need for increased awareness of this diagnostic co-occurrence, and research is warranted to elucidate the underlying pathophysiological mechanisms.

Impact of Prenatal Acetaminophen Exposure for Hippocampal Development Disorder on Mice.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesic agents. They have been detected in various environmental matrices. The degradation of environmental contaminants and the long-term adverse effects have become a major public concern. Prenatal exposure to acetaminophen can cause damage to the developing hippocampus. However, the molecular mechanisms behind hippocampal damage following prenatal acetaminophen exposure (PAcE) remain unclear. The present study shows an increased risk of adverse neurodevelopmental outcomes in offspring following exposure to acetaminophen during pregnancy on mice. The results revealed that different doses, timings, and duration of exposure to acetaminophen during pregnancy were associated with dose-dependent changes in the hippocampus of the offspring. Furthermore, exposure to high doses, multiple-treatment courses, and late pregnancy induced pathological changes, such as wrinkling and vacuolation, inhibited hippocampal proliferation and increased apoptosis. In addition, PAcE significantly decreased the expression of genes related to synaptic development in fetal hippocampal neurons and hippocampal astrocyte and microglia were also damaged to varying degrees. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the SOX2/Notch pathway may suggest that the role of SOX2/Notch pathway in impaired hippocampal development in the offspring due to PAcE. In general, PAcE at high doses, multiple-treatment courses, and mid- and late gestation were associated with neurodevelopmental toxicity to the offspring.

Impact of prenatal amoxicillin exposure on hippocampal development deficiency.

BACKGROUND: Amoxicillin has been widely used to treat infectious diseases during pregnancy. Current studies suggest that amoxicillin exposure during pregnancy could lead to developmental disorders in the offspring and increase the incidence of long-term complications such as asthma and kidney damage in adulthood. However, the adverse effects of prenatal amoxicillin exposure (PAmE) including administration stage, doses and courses on fetal hippocampal neurodevelopment and its function in the offspring have not been elucidated. In this study, we intend to investigate the effects of PAmE on fetal hippocampal development and its possible mechanisms. METHOD: Pregnant Kunming mice were given intragastric administration with amoxicillin at different administration stage, doses and courses, and GD (gestational day) 18 offspring hippocampus was collected for morphological and development-related functional assays, and the molecular mechanisms were explored. RESULTS: PAmE induced hippocampal hypoplasia in the offspring with suppressed hippocampal neuronal cell proliferation and impaired neuronal synaptic plasticity comparatively; hippocampal astrocyte and microglia were damaged to varying degrees. The developmental toxicity of PAmE in fetal mices varies by time, dose, and course of treatment. The most severe damage was observed in the late gestation, high dose, and multi-course dosing groups. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the Wnt/ß-catenin pathway may suggest that the key role of SOX2/Wnt/ß-catenin pathway in impaired hippocampal development in the offspring due to PAmE. CONCLUSION: In this study, PAmE was found to be developmentally toxic to the hippocampus thus to induce developmental damage to various hippocampal cells; Even with current clinically safe doses, potential hippocampal damage to offspring may still present; This study provides a theoretical and experimental basis for guiding the rational usage of drugs during pregnancy and giving effectively assessment of the risk on fetal hippocampal developmental toxicity.