So far, most research studying the causality of autism has focused on neurobiological or psychological aspects. However, most studies have dealt with only proximal causality of autism, and there is little research on its ultimate causality. 'Evolutionary perspective', which has received attention recently in various academic fields, suggests several theories regarding the ultimate causality of autism. We reviewed different theories on the evolution of autism, and discussed both the merits and the limitations of the theories.
Autistic Disorder*

Growth factor-stimulated phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC), generating phosphatidic acid (PA) which may act as a second messenger during cell proliferation and survival. Therefore, PLD is believed to play an important role in tumorigenesis. In this study, a potential mechanism for PLD-mediated tumorigenesis was explored. Ectopic expression of PLD1 or PLD2 in human glioma U87 cells increased the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) protein. PLD-induced HIF-1 activation led to the secretion of vascular endothelial growth factor (VEGF), a HIF-1 target gene involved in tumorigenesis. PLD induction of HIF-1alpha was significantly attenuated by 1-butanol which blocks PA production by PLD, and PA per se was able to elevate HIF-1alpha protein level. Inhibition of mTOR, a PA-responsive kinase, reduced the levels of HIF-1alpha and VEGF in PLD-overexpressed cells. Epidermal growth factor activated PLD and increased the levels of HIF-1alpha and VEGF in U87 cells. A specific PLD inhibitor abolished expression of HIF-1alpha and secretion of VEGF. PLD may utilize HIF-1-VEGF pathway for PLD-mediated tumor cell proliferation and survival.
Cell Line, Tumor ; Epidermal Growth Factor/metabolism ; Gene Expression Regulation, Neoplastic ; Glioma/genetics/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Phosphatidic Acids/*metabolism ; Phospholipase D/genetics/*metabolism ; *Signal Transduction ; Transfection ; Vascular Endothelial Growth Factor A/*metabolism

Individuals with autism spectrum disorder (ASD) have altered gut microbiota, which appears to regulate ASD symptoms via gut microbiota-brain interactions. Rapid assessment of gut microbiota profiles in ASD individuals in varying physiological contexts is important to understanding the role of the microbiota in regulating ASD symptoms. Microbiomes secrete extracellular membrane vesicles (EVs) to communicate with host cells and secreted EVs are widely distributed throughout the body including the blood and urine. In the present study, we investigated whether bacteria-derived EVs in urine are useful for the metagenome analysis of microbiota in ASD individuals. To address this, bacterial DNA was isolated from bacteria-derived EVs in the urine of ASD individuals. Subsequent metagenome analysis indicated markedly altered microbiota profiles at the levels of the phylum, class, order, family, and genus in ASD individuals relative to control subjects. Microbiota identified from urine EVs included gut microbiota reported in previous studies and their up- and down-regulation in ASD individuals were partially consistent with microbiota profiles previously assessed from ASD fecal samples. However, overall microbiota profiles identified in the present study represented a distinctive microbiota landscape for ASD. Particularly, the occupancy of g_Pseudomonas, g_Sphingomonas, g_Agrobacterium, g_Achromobacter, and g_Roseateles decreased in ASD, whereas g_Streptococcus, g_Akkermansia, g_Rhodococcus, and g_Halomonas increased. These results demonstrate distinctively altered gut microbiota profiles in ASD, and validate the utilization of urine EVs for the rapid assessment of microbiota in ASD.
Autism Spectrum Disorder* ; Autistic Disorder* ; DNA, Bacterial ; Down-Regulation ; Gastrointestinal Microbiome ; Humans ; Membranes* ; Metagenome ; Microbiota*

Emerging evidence has suggested that the gut microbiota contribute to brain dysfunction, including pathological symptoms of Alzheimer disease (AD). Microbiota secrete membrane vesicles, also called extracellular vesicles (EVs), which contain bacterial genomic DNA fragments and other molecules and are distributed throughout the host body, including blood. In the present study, we investigated whether bacteria-derived EVs in blood are useful for metagenome analysis in an AD mouse model. Sequence readings of variable regions of 16S rRNA genes prepared from blood EVs in Tg-APP/PS1 mice allowed us to identify over 3,200 operational taxonomic units corresponding to gut microbiota reported in previous studies. Further analysis revealed a distinctive microbiota landscape in Tg-APP/PS1 mice, with a dramatic alteration in specific microbiota at all taxonomy levels examined. Specifically, at the phylum level, the occupancy of p_Firmicutes increased, while the occupancy of p_Proteobacteria and p_Bacteroidetes moderately decreased in Tg-APP/PS1 mice. At the genus level, the occupancy of g_Aerococcus, g_Jeotgalicoccus, g_Blautia, g_Pseudomonas and unclassified members of f_Clostridiale and f_Ruminococcaceae increased, while the occupancy of g_Lactobacillus, unclassified members of f_S24-7, and g_Corynebacterium decreased in Tg-APP/PS1 mice. A number of genus members were detected in Tg-APP/PS1 mice, but not in wild-type mice, while other genus members were detected in wild-type mice, but lost in Tg-APP/PS1 mice. The results of the present study suggest that the bodily microbiota profile is altered in Tg-APP/PS1 mice, and that blood EVs are useful for the metagenome analysis of bodily microbiota in AD.
Alzheimer Disease* ; Animals ; Brain ; Classification ; DNA ; Extracellular Vesicles ; Gastrointestinal Microbiome ; Genes, rRNA ; Membranes* ; Metagenome* ; Metagenomics ; Mice* ; Microbiota* ; Reading

BACKGROUND/AIMS: Immune thrombocytopenic purpura (ITP) is an autoimmune disease that is mediated by anti-platelet antibodies. Based on the pathogenesis of ITP we evaluated the efficacy of intravenous anti-D immunoglobulin for adult chronic ITP. METHODS: Fourteen patients (4 without splenectomy and 10 with splenectomy) with refractory chronic ITP were treated with 50-70 microgram/kg of intravenous anti-D immunoglobulin only once. Treatment effects were evaluated by measuring the platelet counts and hemoglobin levels. RESULTS: Five patients (36%) showed a response; improvement in the platelet count lasted for on average 7 days (range: 2~24 days). There were no serious adverse effects. CONCLUSION: Anti-D immunoglobulin, which is associated with an Fc receptor blockade, appeared to be safe and effective for the treatment of adults with chronic ITP. Further studies are needed to confirm these findings and define further potentially effective treatment protocols with intravenous anti-D immunoglobulin.
Adult ; Antibodies ; Autoimmune Diseases ; Clinical Protocols ; Hemoglobins ; Humans ; Immunoglobulins ; Isoantibodies ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Receptors, Fc ; Rho(D) Immune Globulin ; Splenectomy

Background: There are several differences in the clinical course of hypertension due to the biological and social differences between men and women. Resistant hypertension is an advanced disease state, and significant gender difference could be expected, but much has not been revealed yet. The purpose of this study was to compare gender differences on the current status of blood pressure (BP) control and clinical prognosis in patients with resistant hypertension. Methods: This is a multicenter, retrospective cohort study using common data model databases of 3 tertiary hospitals in Korea. Total 4,926 patients with resistant hypertension were selected from January 2017 to December 2018. Occurrence of dialysis, heart failure (HF) hospitalization, myocardial infarction, stroke, dementia or all-cause mortality was followed up for 3 years. Results: Male patients with resistant hypertension were younger but had a higher cardiovascular risk than female patients. Prevalence of left ventricular hypertrophy and proteinuria was higher in men than in women. On-treatment diastolic BP was lower in women than in men and target BP achievement rate was higher in women than in men.During 3 years, the incidence of dialysis and myocardial infarction was higher in men, and the incidence of stroke and dementia was higher in women. After adjustment, male sex was an independent risk factor for HF hospitalization, myocardial infarction, and all-cause death. Conclusion In resistant hypertension, men were younger than women, but end-organ damage was more common and the risk of cardiovascular event was higher. More intensive cardiovascular prevention strategies may be required in male patients with resistant hypertension.

Objectives: Electrocardiography (ECG)-based diagnosis by experts cannot maintain uniform quality because individual differences may occur. Previous public databases can be used for clinical studies, but there is no common standard that would allow databases to be combined. For this reason, it is difficult to conduct research that derives results by combining databases. Recent commercial ECG machines offer diagnoses similar to those of a physician. Therefore, the purpose of this study was to construct a standardized ECG database using computerized diagnoses. Methods: The constructed database was standardized using Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) and Observational Medical Outcomes Partnership–common data model (OMOP-CDM), and data were then categorized into 10 groups based on the Minnesota classification. In addition, to extract high-quality waveforms, poor-quality ECGs were removed, and database bias was minimized by extracting at least 2,000 cases for each group. To check database quality, the difference in baseline displacement according to whether poor ECGs were removed was analyzed, and the usefulness of the database was verified with seven classification models using waveforms. Results: The standardized KURIAS-ECG database consists of high-quality ECGs from 13,862 patients, with about 20,000 data points, making it possible to obtain more than 2,000 for each Minnesota classification. An artificial intelligence classification model using the data extracted through SNOMED-CT showed an average accuracy of 88.03%. Conclusions The KURIAS-ECG database contains standardized ECG data extracted from various machines. The proposed protocol should promote cardiovascular disease research using big data and artificial intelligence.