Differential Association of Uncoupling Protein 2 Polymorphisms with Pattern Identification among Korean Stroke Patients: A Diagnostic System in Traditional Korean Medicine

Uncoupling protein 2 (UCP2), a mitochondrial protein present in many organs and cell types, is known to dissipate the proton gradient formed by the electron transport chain. Its function is correlated with predictive parameters, such as obesity, diabetes, and metabolic syndromes. We analyzed the distribution of UCP2 polymorphisms in stroke patients diagnosed with one of the following four stroke subtypes based on the TKM standard pattern identification (PI): Qi-deficiency (QD), Dampness and Phlegm (D&P), Yin-deficiency (YD), and Fire and Heat (F&D). We studied a total of 1,786 stroke patients (397/QD, 645/D&P, 223/YD, and 522/F&D, 586/normal). Genotyping for the G-1957A, G-866A and A55V UCP2 polymorphisms was performed using the TaqMan. G-866A and A55V were significantly associated with the D&P and H&F subtypes. The frequency of subjects with the A allele of G-866A was significantly lower than the frequency of subjects with the GG type. The A55V polymorphism was also shown similar effect with G-866A in the dominant model. In contrast, no SNPs were shown to be associated with the QD or YD subtypes in this study. These results showed that the G-866A and A55V UCP2 polymorphisms may be genetic factors for specific PI types among Korean stroke patients

Insulin Level, RBC Na+ Transport and Blood Pressure in Cushing's Syndrome

To test the hypothesis that hyperinsulinemia and / or abnormalities of RBC Na+ transport are concerned in the pathogenesis of hypertension in Cushing's syndrome, we 'investigated the relationship between insulin level, RBC Na + transport and blood pressure in patients with Cushing's syndrome which is frequently associated with hyperinsulinemia, abnormalities of RBC Na + transport and hypertension. Both systolic and diastolic pressure were significantly higher in Cushing's syndrome than in normal subjects. Fasting serum insulin level was higher and both serum glucose and insulin responses after a 75g glucose load were significantly increased in patients with Cushing's syndrome as compared with normal subjects. Both RBC Na+ concentration and passive Na + permeability were significantly lower but Vmax of Na +, K+-pump was significantly higher in patients with Cushing's syndrome than in normal subjects, while Vmaxs of Na+-K+ cotransport and Na+-Li + countertransport were similar in the two groups. In multiple stepwise regression analysis for patients with Cushing's syndrome, fasting serum insulin level was directly correlated with both systolic and diastolic pressures (r=O. 52, p=O. 01; r=O. 51, p=O. 02, respectively). On the other hand,RBC Na + transport parameters showed little correlation with either systolic or diastolic pressures. These results suggest that hyperinsulinemia may contribute to the hypertension in Cushing's syndrome, but that the abnormalities of RBC Na + transport seen in Cushing's syndrome are not causally related to hypertension

Expression of GA733-Fc Fusion Protein as a Vaccine Candidate for Colorectal Cancer in Transgenic Plants

The tumor-associated antigen GA733 is a cell-surface glycoprotein highly expressed in colorectal carcinomas. In this study, 3 recombinant genes were constructed as follows: GA733 tagged to the ER retention sequence KDEL (GA733K), GA733 fused to the immunoglobulin Fc fragment (GA733-Fc), and GA733-Fc fused to the ER retention sequence (GA733-FcK). Agrobacterium-mediated transformation was used to generate transgenic plants expressing recombinant genes. The presence of transgenes was confirmed by genomic PCR. Western blot, confocal immunofluorescence, and sandwich ELISA showed the expression of recombinant proteins. The stability, flexibility, and bioactivity of recombinant proteins were analyzed and demonstrated through N-glycosylation analysis, animal trials, and sera ELISA. Our results suggest that the KDEL retained proteins in ER with oligomannose glycan structure and enhanced protein accumulation level. The sera of mice immunized with GA733-FcK purified from plants contained immunoglobulins which were at least as efficient as the mammalian-derived GA733-Fc at recognizing human colorectal cancer cell lines. Thus, a plant system can be used to express the KDEL fusion protein with oligomannose glycosylation, and this protein induces an immune response which is comparable to non-KDEL-tagged, mammalian-derived proteins

A Case of Swallow Syncope Associated With Cold Beverage Ingestion

Swallow syncope (also known as deglutition syncope) is a relatively rare type of syncope that is treatable if diagnosed correctly. We report a case of a 39-year-old man with recurrent swallow syncope. The patient did not have structural heart disease. He developed a complete atrioventricular block upon drinking a cold beverage (Chilsung cider) while undergoing a repeated head-up tilt test. The patient was advised to avoid cold beverages and has been symptom free for 5 months

Spectrum of movement disorders in GNAO1 encephalopathy: in-depth phenotyping and case-by-case analysis

Background GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by distinct movement presentations and early onset epileptic encephalopathy. Here, we report the in-depth phenotyping of genetically confirmed patients with GNAO1 encephalopathy, focusing on movement presentations. Results Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing. All medical records and personal video clips were analyzed with a literature review. Three of the 6 patients were male. Median follow-up duration was 41 months (range 7–78 months) and age at last examination was 7.4 years (range 3.3–16.9 years). Initial complaints were hypotonia or developmental delay in 5 and right-hand clumsiness in 1 patient, which were noticed at median age of 3 months (range 0–75 months). All patients showed global developmental delay and 4 had severely retarded development. Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. Whole exome sequencing identified 6 different variants in GNAO1. Three were novel de novo variants and atypical presentation was noted in a patient. One variant turned out to be inherited from patients mother who had mosaic variant. Distinct and characteristics movement phenotypes in patients with variant p.Glu246Lys and p.Arg209His were elucidated by in-depth phenotyping and literature review. Conclusions We reported 6 patients with GNAO1 encephalopathy showing an extremely diverse clinical spectrum on video. Some characteristic movement features identified by careful inspection may also provide important diagnostic insight and practice guidelines.This study was supported by a research program funded by the Korea Centers for Disease Control and Prevention (Grant No. 2018-ER6901-02)

Geographic Distribution of Urologists in Korea, 2007 to 2012

The adequacy of the urologist work force in Korea has never been investigated. This study investigated the geographic distribution of urologists in Korea. County level data from the National Health Insurance Service and National Statistical Office was analyzed in this ecological study. Urologist density was defined by the number of urologists per 100,000 individuals. National patterns of urologist density were mapped graphically at the county level using GIS software. To control the time sequence, regression analysis with fitted line plot was conducted. The difference of distribution of urologist density was analyzed by ANCOVA. Urologists density showed an uneven distribution according to county characteristics (metropolitan cities vs. nonmetropolitan cities vs. rural areas; mean square = 102.329, P < 0.001) and also according to year (mean square = 9.747, P = 0.048). Regression analysis between metropolitan and non-metropolitan cities showed significant difference in the change of urologists per year (P = 0.019). Metropolitan cities vs. rural areas and non-metropolitan cities vs. rural areas showed no differences. Among the factors, the presence of training hospitals was the affecting factor for the uneven distribution of urologist density (P < 0.001). Uneven distribution of urologists in Korea likely originated from the relatively low urologist density in rural areas. However, considering the time sequencing data from 2007 to 2012, there was a difference between the increase of urologist density in metropolitan and non-metropolitan cities.open1122sciescopuskc

Maintained Seroprevalence of Toxoplasmosis among the Residents of Jeju Island, Korea

Seroepidemiological status of toxoplasmosis among the residents of Jeju island was surveyed and evaluated by ELISA with crude extract of Toxoplasma gondii. The sera of 2,348 residents (male 1,157 and female 1,191) were collected and checked for the IgG antibody titers, which showed 13.2% positive rate (309 sera). The positive rates were increasing gradually according to the age from 4.3% in teenage to 20.6% in seventies. The positive rates were significantly different between the sex by 16.2% for male and 10.2% for female (P<0.05). This positive rate of toxoplasmosis in Jeju island residents is regarded relatively higher than any other regions of Korea. And the high positive rate may be maintained continuously among Jeju island residents without any clear reasons until now but due to some parts peculiar socio-cultural tradition of Jeju island. Therefore, it is necessary to study further the epidemiology of toxoplasmosis of Jeju island

Validation of an integrated service model, Health-RESPECT, for older patients in long-term care institution using information and communication technologies: protocol of a cluster randomised controlled trial

Introduction There is an increased healthcare need to manage institutionalised older patients owing to the ageing population. To overcome substantial future challenges, the Health-RESPECT (caRE Systems for Patients/Elderly with Coordinated care using icT), a new information and communication technologies based integrated management service model, was developed to provide effective management, enable consultation with distant professionals and share medical information between acute care hospitals and long-term care institutions. Methods and analysis A cluster randomised controlled trial will be conducted to examine the effectiveness of the Health-RESPECT in older patients with chronic diseases and their medical staff in charge. Intervention involves registration with simple comprehensive geriatric assessment, establishment of an individualised care plan for three chronic diseases (hypertension, diabetes and heart failure), medication and rehabilitation management, periodic video-conference and in-system assessment after intervention period. Primary outcomes are control levels of the three chronic diseases, adequacy of drug management and overall functional status. Patients will be assessed at before and after study period and 3 months after study ended. Analysis will be carried out with an intention-to-treat principle. In addition to evaluate intervention effects, clinical usability and economic evaluation will be assessed. Ethics and dissemination The study protocol was reviewed and approved by the Seoul National University Bundang Hospital Institutional Review Board. Study findings will be published in peer-reviewed journals

Fatal systemic disorder caused by biallelic variants in FARSA

Background : Aminoacyl tRNA transferases play an essential role in protein biosynthesis, and variants of these enzymes result in various human diseases. FARSA, which encodes the α subunit of cytosolic phenylalanyl-tRNA synthetase, was recently reported as a suspected causal gene for multiorgan disorder. This study aimed to validate the pathogenicity of variants in the FARSA gene. Results : Exome sequencing revealed novel compound heterozygous variants in FARSA, P347L and R475Q, from a patient who initially presented neonatal-onset failure to thrive, liver dysfunction, and frequent respiratory infections. His developmental milestones were nearly arrested, and the patient died at 28 months of age as a result of progressive hepatic and respiratory failure. The P347L variant was predicted to disrupt heterodimer interaction and failed to form a functional heterotetramer by structural and biochemical analyses. R475 is located at a highly conserved site and is reported to be involved in phenylalanine activation and transfer to tRNA. The R475Q mutant FARSA were co-purified with FARSB, but the mutant enzyme showed an approximately 36% reduction in activity in our assay relative to the wild-type protein. Additional functional analyses on variants from previous reports (N410K, F256L, R404C, E418D, and F277V) were conducted. The R404C variant from a patient waiting for organ transplantation also failed to form tetramers but the E418D, N410K, F256L, and F277V variants did not affect tetramer formation. In the functional assay, the N410K located at the phenylalanine-binding site exhibited no catalytic activity, whereas other variants (E418D, F256L and F277V) exhibited lower ATPase activity than wild-type FARSA at low phenylalanine concentrations. Conclusions : Our data demonstrated the pathogenicity of biallelic variants in FARSA and suggested the implication of hypomorphic variants in severe phenotypes.This study was supported by a research program funded by the Korea Disease Control and Prevention Agency (Grant Nos. 2021-ER0701-00 and 2020-ER6902-00)