Gender Differences among Children with Autism Spectrum Disorder: Differential Symptom Patterns

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever that was first described in China in 2011. We report a patient who died of Severe fever with thrombocytopenia syndrome virus (SFTSV) infection, with a rapidly progressive central nervous system (CNS) disturbance, in Dongyang, Zhejiang Province, China, in 2017.Case presentationA 64-year-old man was admitted to hospital after 4 days of fever. SFTSV was detected 1 day after the patient was admitted to hospital. The patient presented with CNS disturbance and died 4 days after admission. Detailed clinical and epidemiological investigations and laboratory tests were conducted. Reduced platelet, white blood cell, lymphocyte, and neutrophil counts, elevated lactate dehydrogenase, creatine kinase, aspartate aminotransferaseand alanine aminotransferase concentrations, and an increased activated partial thromboplastin time were observed. In a phylogenetic analysis, the isolate clustered close to a strain derived from South Korea.Conclusions: This is the first case of SFTSV infection with CNS disturbance in Dongyang, Zhejiang Province, China. The surveillance of suspected cases of SFTS is important in SFTSV endemic regions.

Some neurotropic enteroviruses hijack Trojan horse/raft commensal gut bacteria to render devastating biomimicking cryptic attacks on human/animal hosts. Such virus-microbe interactions manipulate hosts' gut-brain axes with accompanying infection-cycle-optimizing central nervous system (CNS) disturbances, including severe neurodevelopmental, neuromotor, and neuropsychiatric conditions. Co-opted bacteria thus indirectly influence host health, development, behavior, and mind as possible "fair-weather-friend" symbionts, switching from commensal to context-dependent pathogen-like strategies benefiting gut-bacteria fitness.

Clinical toxicity of reserpine in hospitalized patients: a report from the Boston Collaborative Drug Surveillance Program.

Research involving autism spectrum disorder (ASD) most frequently focuses on its key diagnostic criteria: restricted interests and repetitive behaviors, altered sensory perception, and communication impairments. These core criteria, however, are often accompanied by numerous comorbidities, many of which result in severe negative impacts on quality of life, including seizures, epilepsy, sleep disturbance, hypotonia, and GI distress. While ASD is a clinically heterogeneous disorder, gastrointestinal (GI) distress is among the most prevalent co-occurring symptom complex, manifesting in upward of 70% of all individuals with ASD. Consistent with this high prevalence, over a dozen family foundations that represent genetically distinct, molecularly defined forms of ASD have identified GI symptoms as an understudied area with significant negative impacts on quality of life for both individuals and their caregivers. Moreover, GI symptoms are also correlated with more pronounced irritability, social withdrawal, stereotypy, hyperactivity, and sleep disturbances, suggesting that they may exacerbate the defining behavioral symptoms of ASD. Despite these facts (and to the detriment of the community), GI distress remains largely unaddressed by ASD research and is frequently regarded as a symptomatic outcome rather than a potential contributory factor to the behavioral symptoms. Allowing for examination of both ASD’s impact on the central nervous system (CNS) as well as its impact on the GI tract and the associated microbiome, the zebrafish has recently emerged as a powerful tool to study ASD. This is in no small part due to the advantages zebrafish present as a model system: their precocious development, their small transparent larval form, and their parallels with humans in genetics and physiology. While ASD research centered on the CNS has leveraged these advantages, there has been a critical lack of GI-centric ASD research in zebrafish models, making a holistic view of the gut-brain-microbiome axis incomplete. Similarly, high-throughput ASD drug screens have recently been developed but primarily focus on CNS and behavioral impacts while potential GI impacts have not been investigated. In this review, we aim to explore the great promise of the zebrafish model for elucidating the roles of the gut-brain-microbiome axis in ASD.

The purpose of this work is investigating possibilities of non-pharmacological correction methods of the central nervous system (CNS) disturbances. The advantages of the organism natural reserves mobilization have been determined. A new software concept combining bioacoustic correction and music therapy has been developed. This method joins three audio tracks into a single record and creates music using encephalogram signals. While listening to this music of the brain we can correct a person's emotional state and treat some CNS disorders.

Retrospective analysis of 40 infants born to heroin addicted mothers revealed that 85% developed withdrawal symptoms consisting of central nervous system, gastrointestinal and respiratory disturbances, some within hours of their birth. Respiratory depression at time of delivery was not a prominent feature of these children, suggesting that even in utero, tolerance to chronic narcotic usage develops. A high incidence of low birth weight infants noted by previous authors is substantiated by our study. More than half of these infants were small for gestational age infants rather than true premature infants. Although the morbidity was high, the mortality was limited to two infants both below 1,000 gm birth weight. Serious congenital malformations were not noted in our study. Withdrawal symptoms were also observed in infants born to methadone-maintained mothers. These infants exhibited a withdrawal pattern consisting of central nervous system, gastrointestinal and respiratory disturbances. Pediatricians should be aware that infants born to methadone maintained mothers may be seriously compromised in the newborn period.

Autism spectrum disorder (ASD) is a severe, complex neurodevelopmental disorder, characterized by impairments in social interaction and communication with restricted and stereotyped behavior patterns. ASD symptoms result from a complex interaction between genetic and environment factors. Food intolerances, allergies, altered intestinal permeability (leaky gut), immune dysregulation, neuroinflammation and oxidative stress may trigger ASD symptoms. ASD patients have shown increased urinary levels of β-casomorphin and gliadorphin peptides produced by incomplete digestion of gluten proteins and milk casein. “Leaky gut” may facilitate the transport of these peptides into the central nervous system (CNS) inducing direct “opioid activity” and thus affecting neurotransmission. ASD patients on gluten and/or casein-free diet have shown improvement in most behavior and cognitive scores. Immune dysregulation leads to a neuroinflammatory response that correlates between immune dysfunction with behavioral and cognitive impairments in ASD patients. Genetic variants of the MET gene (7q31.2) are risk factors for ASD. The MET receptor participates in brain cortex and cerebellum development and in gastrointestinal and immunological functions. A high percentage of ASD children have shown non-celiac gluten sensitivity, an immune reaction against gluten in subjects not affected with celiac disease with prominent mucosal eosinophil infiltration and increased blood eosinophilia. ASD patients have shown alterations in brain anatomy involved in language and social interaction skills, correlating with specific aspects of ASD symptoms. ASD behavior results from abnormal interactions between the opioid system and various pathways together with anatomical alterations in the CNS. Individualized diagnosis and prognostic predictions should provide effective personalized therapies in ASD patients.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, and it has a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free and casein-free, and probiotic-rich diets, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact among children. This review aims to highlight the food preferences of the ASD population, analyze the effect of the physicochemical and nutritional properties of foods on the selectivity in its consumption, GI problems, and antioxidant deficiencies in individuals with ASD, and evaluate the effectiveness of therapeutic diets, including diets rich in antioxidants, gluten-free and casein-free, ketogenic and essential fatty acids, and probiotic-rich diets in managing these challenges.

Background: Autistic traits exist along a continuum that extends into social functioning in the general population, and they aggregate in the family members of children with autism spectrum disorder (ASD). Quantitative measures are therefore essential when investigating the patterns of familiality of these traits. Prior studies have suggested differential inheritance patterns of autistic traits that depend on the cognitive level of the child with ASD as well as the family type. Objective: Our goal was to examine the family patterns of quantitative autism traits (QAT) in a group of simplex autism families of high-functioning children with ASD. Method: We used the Social Responsiveness Scale (SRS) to evaluate QAT in 47 ASD families and 46 control families. SRS assessments (parental/spousal evaluations) were collected for the children with ASD, their siblings, and their parents as well as for the control children and their parents. Results: The SRS was able to distinguish individuals with ASD from the control children and from their unaffected siblings. Significant group differences were also found when comparing the fathers of ASD families to control fathers and when comparing the brothers of individuals with ASD to control boys, with male members of ASD families having higher SRS scores. Gender differences were observed in the group of siblings of children with ASD and the group of parents of children with ASD, with males having higher scores than females. In ASD families, a positive trend between child and father QAT was found, whereas mothers’ scores were not associated with child outcomes. By contrast, in control families, mothers’ QAT correlated more strongly with child QAT. Conclusions: Autistic traits aggregate in the fathers and brothers of children with ASD in simplex autism families. The QAT levels of the family members should be taken into consideration when planning the rehabilitation of the child or adolescent with ASD and when designing family interventions.

Autism spectrum disorders are potentially associated with gastrointestinal dysfunction, although the underlying mechanisms remain unclear. Recently, the oral cavity has gained attention as the starting point of the digestive tract. We aim to explore the potential association between altered oral microbiota and oxidative stress in individuals with autism spectrum disorders. We conducted a case-control study involving 54 subjects with autism spectrum disorders and 46 typically developing participants. Oral epithelial cells and saliva samples were collected to analyze oxidative stress markers and oral microbiota composition using 16S rDNA sequencing. Compared with typically developing participants, individuals with autism spectrum disorders exhibited suppressed mRNA levels of superoxide dismutase 2 and RAR-related orphan receptor α, increased H3K9me2 modifications at superoxide dismutase 2 promoter, elevated levels of 8-oxo-dG in oral epithelial cells, and a reduced ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in saliva. In addition, alpha and beta diversity analyses showed significant differences in microbial richness, evenness, and intersample variation between the autism spectrum disorder and typically developing groups. Statistical analyses confirmed marked distinctions in microbial diversity and community structure between the two groups. Individuals with autism spectrum disorders show increased oxidative stress and altered oral microbiota compared with typically developing participants. While the underlying mechanisms remain unclear, these findings suggest that altered oral microbiota may be linked to oxidative stress, providing insights into autism spectrum disorder pathology and potential avenues for clinical intervention.Lay Autism spectrum disorders are linked to gut-related issues, but the exact causes are still unclear. Recent research focuses on the mouth, the first part of the digestive system, to understand how it may play a role. This study looked at how the oral microbiome (the community of microorganisms in the mouth) and oxidative stress (an imbalance between harmful free radicals and antioxidants in the body) differ in people with autism spectrum disorders compared with typically developing individuals. Researchers studied 54 people with autism spectrum disorders and 46 typically developing individuals by analyzing their saliva and oral cells. Results showed that people with autism spectrum disorders had higher levels of oxidative stress markers and noticeable differences in their oral microbiota diversity and structure. These findings suggest a potential connection between changes in oral bacteria and oxidative stress in autism spectrum disorders, opening the door for new ways to study and treat autism spectrum disorders–related health issues.

The objective of this study is to investigate whether parentally-reported gastro-intestinal (GI) symptoms are increased in a population-derived sample of children with autism spectrum disorders (ASD) compared to controls. Participants included 132 children with ASD and 81 with special educational needs (SEN) but no ASD, aged 10-14years plus 82 typically developing (TD) children. Data were collected on GI symptoms, diet, cognitive abilities, and developmental histories. Nearly half (weighted rate 46.5%) of children with ASD had at least one individual lifetime GI symptom compared with 21.8% of TD children and 29.2% of those with SEN. Children with ASD had more past and current GI symptoms than TD or SEN groups although fewer current symptoms were reported in all groups compared with the past. The ASD group had significantly increased past vomiting and diarrhoea compared with the TD group and more abdominal pain than the SEN group. The ASD group had more current constipation (when defined as bowel movement less than three times per week) and soiling than either the TD or SEN groups. No association was found between GI symptoms and intellectual ability, ASD severity, ASD regression or limited or faddy diet. Parents report more GI symptoms in children with ASD than children with either SEN or TD children but the frequency of reported symptoms is greater in the past than currently in all groups.

BackgroundRetinoic acid-related orphan receptor alpha (RORA) has been reported to be suppressed in autistic patients and is associated with autism spectrum disorders (ASD), although the potential role and mechanism of RORA on gastrointestinal (GI) symptoms in ASD patients is still not reported. In this study, we aim to investigate the contribution of RORA to GI symptoms through a maternal diabetes-mediated autism-like mouse model.ResultsMale offspring of diabetic dams were treated with either superoxide dismutase (SOD) mimetic MnTBAP or RORA agonist SR1078, or were crossbred with intestine epithelial cells (IEC)-specific RORA knockout (RORA−/−) mouse. Gene expression, oxidative stress and inflammation were measured in brain tissues, peripheral blood mononuclear cells (PBMC) and IEC, and GI symptoms were evaluated. Our results showed that SOD mimetic MnTBAP completely, while RORA agonist SR1078 partly, reversed maternal diabetes-mediated oxidative stress and inflammation in the brain, PBMC and IEC, as well as GI symptoms, including intestine permeability and altered gut microbiota compositions. IEC-specific RORA deficiency either mimicked or worsened maternal diabetes-mediated GI symptoms as well as oxidative stress and inflammation in IEC, while there was little effect on maternal diabetes-mediated autism-like behaviors.ConclusionsWe conclude that RORA suppression contributes to maternal diabetes-mediated GI symptoms in autism-like mouse offspring, this study provides a potential therapeutical target for maternal diabetes-mediated GI symptoms in offspring through RORA activation.

Thirteen leukemic patients with disease refractory to conventional chemotherapy were treated with 1.0 to 7.5 g/m2 of Cytosine Arabinoside (Ara-C) over 29 drug cycles. Drug infusions were spaced at 12-hour intervals; a maximum of four doses was administered over 36 hours. After single dose tolerance had been established, three or four dose cycles were given at 2- to 30-day intervals. There were three partial remissions (PR) and one complete remission (CR) in a treatment group of four patients with AML, five with ALL, two with lymphoma converted to leukemic phase, one CML in blast crisis, and one promyelocytic leukemia. Five of the patients were septic and considered terminally ill at the time of treatment. All other patients had evidence of drug responsiveness. The nadir of the white count occurred from 3 to 12 days after treatment, with subsequent recovery of the peripheral granulocyte count between days 12 and 28. Toxicity included nausea and vomiting (GI symptoms) in twelve patients, central nervous system (CNS) disturbances in eight patients, one episode of inappropriate antidiuretic hormone syndromes (SIADH), one of hyperuricemia, and fever in eleven patients. There was no evidence of hepatic or renal dysfunction. These high doses of Ara-C appear useful for treatment of patients with refractory leukemia. Hospitalization is brief and toxicity acceptable.

Human microbiota are colonies of microorganisms located in different parts of the human body with diverse functions. Healthy gut microbiota comprises differing ratios of microoganisms wholly contributing to metabolic and other molecular reactions in a healthy, functioning body. After the demonstration of the bidirectional interaction between the central nervous system and gut microbiota through neuroendocrine, neuroimmune, and autonomic nervous mechanisms, investigations have been started on the microbiota-gut-brain axis in psychiatric disorders. Autism spectrum disorder (ASD), which is a neurodevelopmental disorder of early childhood, is one of these disorders. Most of such studies were cross-sectional and mainly investigated the bacterial species. Changes in gut microbiota composition and the leaky gut syndrome are some of the hypotheses proposed to explain the core symptoms and gastrointestinal (GI) symptoms of ASD. Probiotics, prebiotics, fecal microbiota transplantation, diet have been proposed as treatment options. However, the role of microbiota in diagnosis, followup, and treatment is not yet clear. The bidirectional interaction between central nervous system and intestinal microbiota makes it difficult to establish the cause-effect relationship. The current data on microbiota may be useful to plan patient-specific treatment in autistic children with GI symptoms. This article aims to review the results of the studies on microbiota in animal models and children and discuss the emerging clinical relationship of ASD and gut microbiota.

The first aim of this study was to evaluate the association between different subgroups of autism spectrum disorders (ASDs) (childhood autism, Asperger syndrome, and pervasive developmental disorder/pervasive developmental disorder - not otherwise specified [PDD/PDD-NOS]) and congenital anomalies. Second, we assessed the association among intellectually disabled children with ASDs in the subgroups of childhood autism and PDD/PDD-NOS. Nationwide population-based register data for children with a diagnosis of ASD (n=4449; 3548 males, 901 females) were collected during years 1987-2000 from the Finnish Hospital Discharge Register. Data on congenital anomalies were derived from the National Register of Congenital Malformations. Conditional logistic regression models were used as a statistical method. The association between ASD subgroups and congenital anomalies was stratified by the presence or absence of intellectual disability. Congenital anomalies occurred more frequently in all subgroups of ASD than in comparison participants (adjusted odds ratio [OR] for major congenital anomalies 1.8, 95% confidence interval [CI] 1.5-2.2, p<0.001). The association between congenital anomalies and childhood autism (OR 2.4, 95% CI 1.6-3.6, p<0.001) and between congenital anomalies and PDD/PDD-NOS (OR 3.7, 95% CI 2.4-5.7, p<0.001) among children with an intellectual disability was strong but remained significant also without intellectual disability (childhood autism: OR 1.7, 95% CI 1.3-2.3, p<0.001; PDD/PDD-NOS: OR 2.3, 95% CI 1.9-2.8, p<0.001). The results suggest a significant association between ASDs and congenital anomalies regardless of the ASD subgroup. The association between childhood autism and PDD/PDD-NOS and congenital anomalies is stronger among children with intellectual disability is stronger than among those without intellectual disability. These results may have relevance in examining early risk factors in autism during fetal neurodevelopment.