Ring finger 213 ( RNF213) is a susceptibility gene for moyamoya disease (MMD), a progressive cerebrovascular disease. Recent studies suggest that RNF213 plays an important role not only in MMD, but also in extracranial vascular diseases, such as pulmonary hypertension (PH). In this study, we undertook genetic screening of RNF213 in patients with PH and performed functional analysis of an RNF213 variant using mouse models. Direct sequencing of the exons in the C-terminal region of RNF213, where MMD-associated mutations are highly clustered, and of the entire coding exons of BMPR2 and CAV1, the causative genes for PH, was performed in 27 Japanese patients with PH. Two MMD-associated rare variants (p.R4810K and p.A4399T) in RNF213 were identified in two patients, three BMPR2 mutations (p.Q92H, p.L198Rfs*4, and p.S930X) were found in three patients, whereas no CAV1 mutations were identified. To test the effect of the RNF213 variants on PH, vascular endothelial cell (EC)-specific Rnf213 mutant transgenic mice were exposed to hypoxia. Overexpression of the EC-specific Rnf213 mutant, but neither Rnf213 ablation nor EC-specific wild-type Rnf213 overexpression, aggravated the hypoxia-induced PH phenotype (high right ventricular pressure, right ventricular hypertrophy, and muscularization of pulmonary vessels). Under hypoxia, electron microscopy showed unique EC detachment in pulmonary vessels, and western blots demonstrated a significant reduction in caveolin-1 (encoded by CAV1), a key molecule involved in EC functions, in lungs of EC-specific Rnf213 mutant transgenic mice, suggestive of EC dysfunction. RNF213 appears to be a genetic risk factor for PH and could play a role in systemic vasculopathy.
ABSTRACTObjectives: The purpose of this study is to provide the basic data for se arching for the method to induce morepositive knowledges and attitudes about the old from the university students majoring in dental hygienics, healthand social welfare university students majoring in the old, who will face the change of aging society directly. Methods: The study selected 1 school in Busan and Daegu respectively w ith convenience sampling from Septem-ber 2010 to October 2010, performed questionnaire(self administered questionnaire) to 401 students majoring indental hygienics, health and social welfare and achieved following conclusions. Results: 1. When the students without the education experience about t he old have negative experiences, thedegree of interest in the old was high and when they have posit ive experiences, the attitude score about the oldwas high(p＜0.001). 2. For education experience about the old, the students majoring in dental hygienics have thelowest experiences(p＜0.001). 3. For knowledge, attitude and behavior about the old depending on major, the stu-dents majoring in social welfare have the highest interest and for the knowledge about the old in physical area,the students majoring in health have the highest knowledge(p＜0.01).4. The area related with the knowledgeabout the old showed significant correlation in all of physical, psychological and social area(p＜0.001). 5. The fac-tors giving effects to the attitude about the old were gender(p=.006), experience(p=.003) and education experiencerelated with the old(p=.022) and the factors giving effects to the behavior about the old were experience(p=.036)and attitude about the old(p=.000). Conclusions: It is necessary to develop actual education program that can provide preliminary dental hygienistswith positive attitude about the old and reflect a lot of matte rs related with psychological area and social areaabout the old. In addition, it is necessary to establish the op portunity to understand the old through voluntaryservice activity related with the old in connection with local community. It is necessary to recognize the old posi-tively by showing the positive figure. Keywords: attitude, behavior, dental hygiene students’, knowledge, the old색인: 노인, 지식, 치위생과학생, 태도, 행동
Detecting cognitive impairment in its early stage is important for timely care for dementia. Clinically useful markers for the purpose of screening of dementia should be easy to use, low cost and simple to implement to clinical setting. Numerous studies showed that electroencephalography (EEG) was one of such candidates to be used to detect early signs of brain dysfunction. The objective of this study is to investigate whether cognitive impairment can be explained by resting-state electroencephalography (EEG) markers reflecting the slowing of the intrinsic EEG oscillations in the eyes-closed resting-state. As a part of Brain Aging Map Project in Uiryeong County, Korea, we conducted the Korean version of Mini-Mental State Examination (MMSE) and measured resting-state EEG among other investigations in aged community dwellers over 50 years old or older from September 2017 to January 2018. As a result, a total of 500 were recruited. Excluding 4 participants under age 50 years old, a total of 496 (males=163, females=331) were included in the analysis. According to the MMSE score, we categorized the participants in one of the four cognitive stages, namely, M4 (MMSE 26-30), M3 (MMSE 21-25), M2 (MMSE 16-20), and M1 (MMSE 0-15). The resting-state EEG markers of median frequency, peak frequency, and alpha-to-theta ratio decreased monotonically as the MMSE scores decreased from M4 to M1 (p<0.001), and the decreases were more significant between M4 and M3 for males and between M3 and M2 stages for females. Finally, we developed a prediction model for the MMSE scores using the resting-state EEG markers with demographic covariates of sex, age and education level. As a result, we obtained the intra-class correlation coefficient between the MMSE scores and model-predicted values up to 0.748.
Methyl bromide (MB) is a fumigant that has been widely used for killing pests on plants in trade, soils, and structures worldwide due to its excellent permeability and insecticidal effect; however, MB should be replaced because it is an ozone-depleting substance. It is well-known that MB is highly toxic and hazardous to workers, but the effects of exposure in asymptomatic workers have not been explored. The purpose of this study is to investigate the impact of MB fumigation on the health of fumigators at a sensitive level. The electroencephalogram (EEG) and urinary bromide ion levels of 44 fumigators (the study group) and 20 inspectors (the control) were measured before and after fumigation work from February to August 2019 in Busan, Korea. The mean post-work concentration of bromide ion (18.311 μg/mg CRE) in the fumigators was significantly increased from the pre-work level (7.390 μg/mg CRE) (P<0.001). The fumigator post-work median frequencies (MDF) and alpha-to-theta ratios (ATR) of EEG index were significantly decreased compared to the pre-work values (P<0.05 for all indices). In contrast, there were no significant differences in inspector EEG indices and urinary bromide ion. The urinary bromide ion levels in all the subjects were negatively correlated with MDF (P = 0.032). In conclusion, fumigators' EEG indices and urinary bromide ion suggested that occupational exposure to MB negatively affected the health of workers, although the workers were asymptomatic.
G o , a member of the G o / i family, is the most abundant heterotrimeric G protein in brain. Most functions of G o are mediated by the G βγ dimer; effector(s) for its α-subunit have not been clearly defined. Here we report that G oα interacts directly with cAMP-dependent protein kinase (PKA) through its GTPase domain. This interaction did not inhibit the kinase function of PKA but interfered with nuclear translocation of PKA while sparing its cytosolic function. This regulatory mechanism by which G o bifurcates PKA signaling may provide insights into how G o regulates complex processes such as neuritogenesis, synaptic plasticity, and cell transformation.
In the Great East Japan Earthquake of 11 March 2011, an earthquake and accompanying tsunami struck the Tohoku region of northeastern Japan. Buildings collapsed and the tsunami spread waste, including hazardous materials. This study aimed to determine the concentrations of persistent organic pollutants (POPs) in the breast milk of mothers living in the disaster-affected area of Sendai 1 year after the earthquake. Temporal trends in the POPs concentrations were evaluated by comparison with previous studies.One hundred breast milk samples were obtained from lactating mothers at a hospital in Sendai in 2012. The results were compared with those from other years to examine whether there were changes in the POPs concentrations after the earthquake. We measured polychlorinated biphenyls (PCBs) and organochlorine pesticides, such as chlordanes, using gas chromatography-mass spectrometer (GC-MS) with negative chemical ionization, and dichlorodiphenyl trichloroethane (DDT) and its metabolites using GC-MS with electron impact ionization.The mean total PCBs (11 congeners), total chlordane, and total DDT concentrations were 76.2 ng/g lipid, 39.8 ng/g lipid, and 73.5 ng/g lipid, respectively. For the samples collected in 2012, the concentrations of POPs in breast milk showed minimal changes compared with results from previous years for samples collected at the same hospital in Sendai.Our study demonstrates that 1 year after the earthquake and tsunami, the concentrations of chlorinated POPs in breast milk had not changed substantially.
Postoperative delirium (POD) is associated with adverse outcomes in elderly patients after surgery. Electroencephalography (EEG) can be used to develop a potential biomarker for degenerative cerebral dysfunctions, including mild cognitive impairment and dementia. This study aimed to explore the relationship between preoperative EEG and POD. We included 257 patients aged >70 years who underwent spinal surgery. We measured the median dominant frequency (MDF), which is a resting-state EEG biomarker involving intrinsic alpha oscillations that reflect an idle cortical state, from the prefrontal regions. Additionally, the mini-mental state examination and Montreal cognitive assessment (MoCA) were performed before surgery as well as 5 days after surgery. For long-term cognitive function follow up, the telephone interview for cognitive status™ (TICS) was performed 1 month and 1 year after surgery. Fifty-two (20.2%) patients were diagnosed with POD. A multivariable logistic regression analysis that included age, MoCA score, Charlson comorbidity index score, Mini Nutritional Assessment, and the MDF as variables revealed that the MDF had a significant odds ratio of 0.48 (95% confidence interval 0.27-0.85). Among the patients with POD, the postoperative neurocognitive disorders could last up to 1 year. Low MDF on preoperative EEG was associated with POD in elderly patients undergoing surgery. EEG could be a novel potential tool for identifying patients at a high risk of POD.
Abstract We investigated whether cognitive decline could be explained by resting-state electroencephalography (EEG) biomarkers measured in prefrontal regions that reflect the slowing of intrinsic EEG oscillations. In an aged population dwelling in a rural community (total = 496, males = 165, females = 331), we estimated the global cognitive decline using the Mini-Mental State Examination (MMSE) and measured resting-state EEG parameters at the prefrontal regions of Fp1 and Fp2 in an eyes-closed state. Using a tertile split method, the subjects were classified as T3 (MMSE 28–30, N = 162), T2 (MMSE 25–27, N = 179), or T1 (MMSE ≤ 24, N = 155). The EEG slowing biomarkers of the median frequency, peak frequency and alpha-to-theta ratio decreased as the MMSE scores decreased from T2 to T1 for both sexes (−5.19 ≤ t-value ≤ −3.41 for males and −7.24 ≤ t-value ≤ −4.43 for females) after adjusting for age and education level. Using a double cross-validation procedure, we developed a prediction model for the MMSE scores using the EEG slowing biomarkers and demographic covariates of sex, age and education level. The maximum intraclass correlation coefficient between the MMSE scores and model-predicted values was 0.757 with RMSE = 2.685. The resting-state EEG biomarkers showed significant changes in people with early cognitive decline and correlated well with the MMSE scores. Resting-state EEG slowing measured in the prefrontal regions may be useful for the screening and follow-up of global cognitive decline in elderly individuals.
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