Role of autoimmunity in Neuronal damage in children with Autism spectrum disorder.

"Autism spectrum disorder (ASD) is complex neurodevelopmental disorder characterized by impairments in three core behavioral: social deficits, impaired communication, and repetitive behaviors." There is developing indication and emerging data that irregular autoimmune responses to the central nervous system may play a pathogenic role in patients with autism spectrum disorder." The aim of this review was to discuss the updated research carried out at Autism research and treatment center, King Saud University, Riyadh, Kingdom of Saudi Arabia particularly on the role of autoimmunity in Autism spectrum disorder. This review also present state of information available about the role of autoimmunity biomarkers involved in the neuronal damage of central nervous system in autistic children. The systematic literature search was carried out using Google Scholar, Science direct and PubMed databases on the role of autoimmunity in autism and reviewed all relevant articles published in peer reviewed journals by Autism research and treatment center, King Saud University, Riyadh, Kingdom of Saudi Arabia till April, 2022. We searched relevant articles using key words Autism spectrum disorder, Autoimmunity, Neuroinflamation and Central nervous system. This review revealed that plasma levels of autoimmunity related factors/ markers were altered in patients with autism. Significant change in blood markers in subjects with ASD may resulted in several years of decreased neutrotrophic support along with increasing impairment in relationship with down-regulated inflammation that may play a role in the ASD. Overall, the role of autoimmunity in ASD subjects with excess of anti-brain antibodies suggest that in some patients, autoantibodies that target the CNS may be pathological factor in neuronal growth in autistic children. Large cohort studies with well-defined and specially pheno typed autistic groups and matched healthy controls are required to examine the role of autoantibodies in the pathology of subjects with ASD.

Seasonal variations impact on SARS-CoV-2 incidence and mortality in southern and northern hemispheres: Two years pandemic period based study.

Objectives: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection is a highly challenging problem in the world. The impact of weather conditions on the spread of SARS-CoV-2 has been hypothesized, but the level of understanding remains lacking. This study investigates the impact of seasonal variations on SARS-CoV-2 incidence and mortality in the Southern and Northern hemispheres. Methods: We enlisted all the countries from both hemispheres and then randomly selected 20 countries, 10 countries from each hemisphere. After that, we recorded the SARS-CoV-2 daily cases and deaths in these selected countries from the Worldometer for the period of two years from December 31, 2019, to December 31, 2021. Results: During the study period, in 10 selected countries of the Northern hemisphere, the number of SARS-CoV-2 cases was 18381.6 ± 419.7 and deaths 300.4 ± 6.4. However, the number of cases in the southern hemisphere is 6282.9 ± 205.8, and mortality was 210.0 ± 7.7. In the Northern hemisphere, the number of SARS-CoV-2 cases (p = 0.001) and deaths (p = 0.001) significantly increased compared to the southern hemisphere. The maximum number of cases and deaths occurred during the winter (18806.4 ± 785.3) and autumn (17034.1 ± 538.4) periods in both the hemisphere compared to spring and summer. Similarly, the number of deaths increased in winter (391.0 ± 13.4, p = 0.001) and autumn (308.6 ± 11.6) compared to spring and summer in both hemispheres. Conclusions: The highest occurrence of SARS-CoV-2 cases and deaths was found during the winter and autumn seasons, while the lowest was found in the spring and summer during the study period of two years. The health officials inform the public about the seasonal occurrence of the SARS-CoV-2 outbreak and take priority preventive measures to minimize the disease burden.

An insightful estimation of undergraduate medical students' experience about the Flipped Classroom.

BACKGROUND AND OBJECTIVE: The Flipped Classroom (FC) approach has become increasingly predominant and popular in medical education. This study aimed to explore the usefulness and the scope of FC based on medical students' experience, with their adaptation challenges. METHODS: The present study was a mixed-method accomplished during the academic years 2019-20, involving fourth-year students at the College of Medicine in Riyadh, Saudi Arabia. A self-administered questionnaire was used to seek their first experience and opinion of the FC. RESULTS: A total of 234 questionnaires were distributed to the students, and 214 students completed the survey (response rate of 91.45%). Out of this total, 68.2 % were males and 31.8% were females. Most of the students agreed 156 (72.9%) that the flipped classroom was more engaging than the traditional lecture, among them 100 (68.5%) males and 56 (82.3) females agreed. Almost ~79% of students liked FC as it enabled them knowing the material in advance, and the class time was spent clarifying the facts and principles with active interaction, as commented during focus group discussion "More chance for discussing with the doctors, and I got the chance to answer" (St. 6). CONCLUSION: The results showed that the students like the FC more than the conventional classroom. Suggestions were given by students to improve the active learning sessions within the FC modality.

The possible link between Fetuin-A Protein and Neuro-inflammation in Children with Autism Spectrum Disorder.

OBJECTIVES: To investigate the blood plasma levels of Fetuin-A protein in children with Autism Spectrum Disorder (ASD) and healthy controls that could offer novel diagnostic biomarkers of disease development in ASD. Another objective was to investigate the severity of autistic children by Childhood Autism Rating Scale (CARS) and Short Sensory Profile (SSP). METHODS: This case control study was carried out at Autism Research and Treatment (ART) Center, King Saud University, Riyadh, Saudi Arabia, from October 2019 to February 2020. Plasma concentration of Fetuin-A was analyzed by enzyme-linked immunosorbent assay (ELISA) in ASD subjects (n=46) and normal controls (n=44). Correlation among Fetuin-A levels, CARS and SSP was established by Spearman's correlation coefficient (r). RESULTS: Overall, autistic children had significantly (p= 0.0.02) lower Fetuin-A concentration [50.76 (22.2-68.5) ng/ml] than those of healthy controls [53.7 (35.6-99.7) ng/ml] [median (interquartile range)]. Children with mild to moderate autism (n=24, 52%) also showed significantly lower Fetuin-A levels [50.0 (30.0-68.2) ng/ml], (p =0.02} than healthy controls [53.7 (35.6-99.7) ng/ml] [median (IQR)]. However, there was no significant change (p = 0.71) observed between the Fetuin-A levels of children with severe autism [51.8 (22.2-68.5)] ng/ml, mild to moderate autism [50 (30-68.2)] ng/ml [median (IQR)] and healthy controls (p=0.12). Also no significant correlations between Fetuin-A, CARS and SSP were observed (CARS, r= 0.024, p=0.88; SSP, r= -0.003, p=0.98). CONCLUSION: Overall the low Fetuin-A plasma values in ASD subjects, most likely show that Fetuin-A could be associated in the physiology of autism. Further studies with larger patient and control cohorts will be necessary to determine whether Fetuin-A can be used as a biomarker for ASD.

Impact of environmental pollution, dietary factors and diabetes mellitus on Autism Spectrum Disorder (ASD).

Autism spectrum disorder (ASD) is complex neurodevelopmental condition described by impairments in three main behavioral areas: social deficits, impaired communication, and repetitive behaviors. Despite many years of vast study, the causes of ASD are still unknown. Various risk factors including genetic, infectious, metabolic and immunological have been investigated however, environmental, nutritional and diabetes related risk factors have not received sufficient attention. This study has provided an insight into the comprehensive interaction between environmental pollution, dietary factors and diabetes mellitus that could lead to the advancement of this debilitating neurodevelopment disorder. The literature search was done using PubMed and Google Scholar databases up to October 2018. Key words "Environmental Pollution", "Nutritional Factors", "Diabetes Mellitus", "Autism Spectrum Disorder" were selected.

Impact of Auditory Integrative Training on Transforming Growth Factor-ß1 and Its Effect on Behavioral and Social Emotions in Children with Autism Spectrum Disorder.

OBJECTIVE: To explore the impact of auditory integrative training (AIT) on the inflammatory biomarker transforming growth factor (TGF)-ß1 and to assess its effect on social behavior in children with autism spectrum disorder (ASD). SUBJECTS AND METHODS: In this cross-sectional study, 15 patients (14 males and 1 female) with ASD aged 3-12 years were recruited. All were screened for autism using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Plasma levels of TGF-ß1 were measured in all patients using a sandwich enzyme-linked immunoassay (ELISA) immediately and 1 and 3 months after the AIT sessions. Pre- and post-AIT behavioral scores were also calculated for each child using the Childhood Autism Rating Scale (CARS), the Social Responsiveness Scale (SRS), and the Short Sensory Profile (SSP). Data were analyzed using the Statistical Package for the Social Sciences (SPSS 21.0 for Windows). RESULTS: Plasma levels of TGF-ß1 significantly increased to 85% immediately after AIT (20.13 ± 12 ng/mL, p < 0.05), to 95% 1 month after AIT (21.2 ± 11 ng/mL, p < 0.01), and to 105% 3 months after AIT (22.25 ± 16 ng/mL, p < 0.01) compared to before AIT (10.85 ± 8 ng/mL). Results also revealed that behavioral rating scales (CARS, SRS, and SSP) improved in terms of disease severity after AIT. CONCLUSION: Increased plasma levels of TGF-ß1 support the therapeutic effect of AIT on TGF-ß1 followed by improvement in social awareness, social cognition, and social communication in children with ASD. Furthermore, TGF-ß1 was associated with severity in all scores tested (CARS, SRS, and SSP); if confirmed in studies with larger sample sizes, TGF-ß1 may be considered as a marker of ASD severity and to assess the efficacy of therapeutic interventions.

Secretagogin (SCGN) Plasma Levels and their Association with Cognitive and Social Behavior in Children with Autism Spectrum Disorder ASD).

OBJECTIVE: To investigate the secretagogin (SCGN) plasma levels in children with autism spectrum disorder (ASD) compared to age and gender-matched healthy control, and its association with cognitive and social behaviors by using childhood autism rating scale (CARS) and social responsiveness scale (SRS). STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2015 to May 2016. METHODOLOGY: SCGN levels were determined in the plasma of thirty-seven (37) autistic children using enzyme-linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as indicated by their CARS scores and compared with thirty (30) age and gender-matched control samples. Correlation between SCGN levels and different cognitive and social behavior scales (CARS and SRS) was determined by Spearman's correlation coefficient (r). RESULTS: The results indicated that autistic children (n=37) had significantly (p= 0.005) lower plasma level of SCGN {45.7 (26.2) ng/ml [median (IQR)]} than those of healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. Children with severe (n=28, 76%) as well as mild to moderate autism (n=09, 24%) also exhibited significantly lower SCGN levels {47.5 (27) ng/ml [median (IQR)], p =0.014} and {45.7 (16.6) ng/ml [median (IQR)], p = 0.02)}, respectively than healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. However, there was no significant difference between the SCGN levels of children with mild to moderate and severe autism (p = 0.66). Spearman's correlation coefficient (r) was used to determine the relationships between SCGN levels and different variables (CARS, SRS). However, the results showed no significant correlation between SCGN and these scales. (CARS, r=-0.03, p=0.86; SRS, r=0.21, p=0.20). CONCLUSION: The low SCGN plasma levels in children with ASD probably indicate that SCGN might be implicated in the pathogenesis of autism. However, these data should be treated with caution until further investigations are performed using larger sample sizes to determine whether the decrease in plasma SCGN levels is a mere consequence of autism or it plays a pathogenic role in the disease.

Cluster of Differentiation 5 (CD5) Levels in the Plasma of Children with Autism Spectrum Disorder (ASD).

OBJECTIVE: To investigate the cluster of differentiation 5 (CD5) plasma levels and their association with childhood autism rating scale (CARS) in subjects with autism spectrum disorder (ASD) compared to age and gender matched healthy controls, and to explore the link between CD5, severity, and autoimmunity in autism. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2014 to May 2015. METHODOLOGY: CD5 levels were determined in the plasma of thirty-one (31) patients using enzyme-linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS) score and compared to thirty-three (33) age and gender-matched control samples. RESULTS: The preliminary data indicated that children with severe autism (n=12), exhibited significantly (p=0.02) higher plasma level of CD5 [0.55 (0.14-12) pg/ml {median (interquartile range=IQR)}] than those of normal controls [n=33, 0.29 (0.08-0.79) pg/ml {median (IQR)}] and children with mild to moderate autism [n=19, 0.26 (0.13-1.42) pg/ml, {median (IQR)}, p=0.08]. However, there was no significant difference between the CD5 levels of children with mild to moderate autism and normal controls (p = 0.62). Diagnoses of autistic children based on the CARS score >30. Disease severity and the CARS score, which represent stereotyped patterns of behavior in children with autism, were positively correlated (r = 0.43, p = 0.02). CONCLUSION: The high CD5 plasma levels in patients with severe ASD, probably indicated that CD5 might be implicated in the physiology of autism. However, this finding should be treated with caution until further investigations are performed with larger populations to determine whether the increase in plasma CD5 levels is a mere consequence of autism or it plays a pathogenic role in the disease.

Correlation Between Hedgehog (Hh) Protein Family and Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder (ASD).

OBJECTIVE: To determine the correlation of Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Brain-Derived Neurotrophic Factor (BDNF) in children with Autism Spectrum Disorder (ASD). STUDY DESIGN: An observational, comparative study. PLACE AND DURATION OF STUDY: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2011 to May 2012. METHODOLOGY: Serum levels of SHH, IHH and BDNF were determined in recently diagnosed autistic patients and age-matched healthy children (n=25), using the Enzyme-Linked Immunosorbent Assay (ELISA). Childhood Autism Rating Scale (CARS) was used for the assessment of autistic severity. Spearman correlation co-efficient 'r' was determined. RESULTS: The serum levels of IHH and SHH were significantly higher in autistic subjects than those of control subjects. There was significant correlation between age and IHH (r = 0.176, p = 0.03), BDNF and severe IHH (r = 0.1763, p = 0.003), and severe BDNF and severe SHH (r = 0.143, p < 0.001). However, there were no significant relationships among the serum levels of SHH, IHH and BDNF and the CARS score, age or gender. CONCLUSION: The findings support a correlation between SHH, IHH and BDNF in autistic children, suggesting their pathological role in autism.

Behavioral Benefits of Camel Milk in Subjects with Autism Spectrum Disorder.

OBJECTIVE: To investigate the possible therapeutic effects of camel milk on behavioral characteristics as an interventional strategy in autistic children. STUDY DESIGN: Double-blind, Randomized Clinical Trial (RCT). PLACE AND DURATION OF STUDY: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2012 to May 2013. METHODOLOGY: Changes in behavioral characteristics in 65 (boys=60, girls=5) children with autism (aged from 2 to 12 years) were assessed. The behavioral symptoms were evaluated by Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Treatment Evaluation Checklist (ATEC) before and after the 2 weeks of camel milk therapy. RESULTS: Significant differences were detected on Autism Spectrum Disorder (ASD) by CARS, SRS and ATEC scales, following 2 weeks of camel milk consumption, but not in the placebo group. CONCLUSION: The present study demonstrates that camel milk could be very promising therapeutic intervention in ASD. Further wide scale studies are strongly recommended.

Therapeutic use of hyperbaric oxygen therapy for children with autism spectrum disorder.

Autism spectrum disorder (ASD) is neurodevelopment disorder, characterized by impairment in social interaction, verbal and non-verbal communication and the presence of restricted and repetitive stereotyped behaviors. The condition manifests within the first 3 years of life and persists till adulthood. At present, the etiology of ASD is largely unknown, but genetic, environmental, immunological, and neurological factors are thought to play a role in the development of ASD. The prevalence of ASD has increased dramatically in the past few decades. According to current estimates from the United States Centers for Disease Control and Prevention (CDC) as many as 1 in 91 children have ASD in USA. Studies from the Middle East on this topic are limited. Autism in Saudi Arabia is slightly higher than reported in the developed countries. Hyperbaric oxygen therapy (HBOT) has been growing in popularity for the treatment of ASD over recent years. However, few studies of its effectiveness have been reported. This article reviews important publications regarding the physiologic and clinical influence of HBO on ASD. Several case series and randomized trials have all proposed that low pressure/ low oxygen concentration hyperbaric treatment can improve the clinical manifestations of autism.

Possible role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder: current status.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays a vital role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecule's actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals.

Serum level of desert hedgehog protein in autism spectrum disorder: preliminary results.

OBJECTIVE: To investigate the role of desert hedgehog (Dhh) in a neurodevelopmental disorder known as autism. SUBJECTS AND METHODS: This study was conducted at the Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from October 2011 to May 2012. The serum levels of the Dhh protein in 57 patients recently diagnosed with autism and 37 age-matched healthy children were measured using ELISA. The Childhood Autism Rating Scale (CARS) was used for the assessment of autistic severity. RESULTS: The mean serum level of Dhh in patients with autism (1.38 ± 0.50 ng/ml) was significantly lower (p = 0.0003) than that of normal controls (1.73 ± 0.37 ng/ml). There was no significant relationship between the serum level of Dhh and the CARS score (p = 0.28), age (p = 0.51) or gender (p = 0.76). CONCLUSIONS: The Dhh serum level of patients with autism was lower than that of controls, probably indicating that the serum level of Dhh might be implicated in the physiology of autism. However, this finding should be treated with caution until further investigations are performed with larger populations.

Impact of GDP, spending on R&D, the number of universities and scientific journals on research publications in environmental sciences in the Middle East.

OBJECTIVES: This study aimed to assess the impact of the Gross Domestic Product (GDP), spending on Research and Development (R&D), the number of universities and scientific journals on the published research documents, citable documents, citations per document and H-index in environmental sciences in the Middle East countries. MATERIALS AND METHODS: All the 16 Middle East countries were included in the study. Information regarding the GDP, spending on R&D, the total number of universities and indexed journals was collected. Total number of research documents (papers), citable documents, citations per document and H-index in environmental sciences during the period 1996-2011 was recorded. The study used the World Bank, SCI-mago/Scopus, Web of Science, Journal Citation Reports (Thomson Reuters) as the main sources of information. RESULTS: The mean GDP per capita of all the Middle East countries amounted to 18 125.49±5386.28 US$, spending on R&D was 0.63±0.28 US$, the number of universities equaled 36.56±11.33 and mean ISI indexed journals amounted to 8.25±3.93. The mean number of research documents published in environmental sciences in the Middle East countries during the period 1996-2011 was 2202.12±883.98; citable documents: 2156.87±865.09; citations per document: 8.74±0.73; and the H-index: 35.37±6.17. There was a positive correlation between the money spent on R&D and citations per documents (r = 0.6, p = 0.01), H-Index (r = 0.6, p = 0.01); the number of universities and a total of research documents (r = 0.65, p = 0.006), citable documents (r = 0.65, p = 0.006), H-Index (r = 0.50, p = 0.04), as well as ISI indexed journals and total research documents (r = 0.94, p = 0.0001), citable documents (r = 0.94, p = 0.0001), H-Index (r = 0.73, p = 0.001). CONCLUSIONS: The Middle East countries which spend more on R&D and which have a large number of universities and ISI indexed journals are likely to produce more significant volume of research papers in the field of environmental science.

Role of proteomics in the discovery of autism biomarkers.

The epidemiology of autism is continuously increasing all over the world with social, behavioural and economical burdens. Autism is considered as a multi-factorial disorder, influenced by genetic, neurological, environmental and immunological aspects. Autism is still believed to be incurable disorder with little information about the role of proteins patterns in the diagnosis of the disease. Knowing the applications of proteomic tools, it is possible to identify quantitative and qualitative protein patterns in a wide variety of tissues and body fluids such as blood, urine, saliva and cerebrospinal fluid in order to establish specific diagnostic and prognostic biomarkers. The aim of this review is to provide an overview of the various protocols available for proteomics by using mass spectrometry analysis, discuss reports in which these techniques have been previously applied in biomarker discovery for the diagnosis of autism, and consider the future development of this area of research.