Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability

Intellectual disability (ID) is a neurodevelopmental disorder defined by below-average intelligence (intelligence quotient of <70) accompanied by adaptive behavior deficits. Defects in the functions of neural stem cells during brain development are closely linked to the pathogenesis of ID. To understand the molecular etiology of ID, we examined neural stem cells from individuals with Duchenne muscular dystrophy (DMD), a genetic disorder in which approximately one-third of the patients exhibit ID. In this study, we generated induced pluripotent stem cells from peripheral blood mononuclear cells from a normal individual and DMD patients with and without ID to identify ID-specific functional and molecular abnormalities. We found defects in neural ectoderm formation in the group of DMD patients with ID. Our transcriptome analysis of patient-derived neural stem cells revealed altered expression of genes related to the hippo signaling pathway and neuroactive ligand-receptor interaction, implicating these in the pathogenesis of ID in patients with DMD.

Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability

Intellectual disability (ID) is a neurodevelopmental disorder defined by below-average intelligence (intelligence quotient of <70) accompanied by adaptive behavior deficits. Defects in the functions of neural stem cells during brain development are closely linked to the pathogenesis of ID. To understand the molecular etiology of ID, we examined neural stem cells from individuals with Duchenne muscular dystrophy (DMD), a genetic disorder in which approximately one-third of the patients exhibit ID. In this study, we generated induced pluripotent stem cells from peripheral blood mononuclear cells from a normal individual and DMD patients with and without ID to identify ID-specific functional and molecular abnormalities. We found defects in neural ectoderm formation in the group of DMD patients with ID. Our transcriptome analysis of patient-derived neural stem cells revealed altered expression of genes related to the hippo signaling pathway and neuroactive ligand-receptor interaction, implicating these in the pathogenesis of ID in patients with DMD.

STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance

Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEP(C230X−/−) mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEP(C230X−/−) mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine.

Analysis of Parricide and Filicide in Korea / 대한법의학회지

Parricide, the crime of murdering a parent, accounts for about 5% of all homicides. Filicide is the crime of murdering one's own child. This study aimed to review demographic features and criminal characteristics of individuals who committed parricide and filicide in Republic of Korea (ROK). This study is based on data from the Korea Police Crime Analysis System, from 2006~2013. We assessed the diverse characteristics of both victims and perpetrators. Over the selected period, 381 parents were killed by their children and 230 children were killed by parents in the ROK. Parricides caused by schizophrenic murders accounted for 39.6% of all cases. Moreover, approximately 44.4% of the perpetrators attempted suicide following the maternal filicide. In our findings, psychiatric illness was a very important predictor in parricide, and these further suggest that young mothers with severe mental illness require careful monitoring by mental health support service.

A Survey of Patients Who Were Admitted for Life-Sustaining Therapy in Nationwide Medical Institutions / 대한구급학회지

BACKGROUND: The study focused on figuring out the present status and distribution of the underlying diseases of Korean terminally ill patients (TIP) who were on life-support care (LSC) by conducting a nationwide health care survey. METHODS: The authors of this study requested that the 308 nationwide hospitals that operate intensive care units answer a questionnaire that asked about the number of admitted TIPs and their underlying diseases at 12 Am, 22 July, 2009. The proportion of TIPs among all the admitted patients and the percentages of the TIP's underlying diseases were calculated. RESULTS: In a total of 83.1% of the eligible hospitals responded, the proportion of TIP was 1.6 of 100 admitted patients. Terminal cancer was the leading underlying disease in the TIPs (42.4%). Five % of the patients on LSC were brain dead. More TIPs were admitted in the national/public or university hospitals than in the private or non-university hospitals. CONCLUSIONS: Futile treatment seems to be administered to the TIPs in Korean hospitals. The quality of terminal care in Korean hospitals should be improved by the application of socially acceptable LSC guidelines. Timely government health plans, including hospice care, to improve the quality of palliative care should be launched and maintained.