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Diagnosing the current health status and disease burden in a population is crucial for public health interventions. The ability to compare the burden of different diseases through a single measure, such as disability-adjusted life years has become feasible and continues to be produced and updated through the Global Burden of Diseases (GBD) study. However, the disease burden values of the GBD study do not accurately reflect the unique situation in a specific country with various circumstances. In response, the Korean National Burden of Disease (KNBD) study was conducted to estimate the disease burden in Koreans by considering Korea’s cultural context and utilizing the available data sources at the national level. Both studies identified non-communicable diseases, such as diabetes mellitus (DM), as the primary cause of disease burden among Koreans. However, the extent of public health interventions currently being conducted by the central and local governments does not align with the severity of the disease burden. This review suggests that despite the high burden of DM in South Korea, the current policies may not fully address its impact, underscoring the need for expanded chronic disease management programs and a shift towards prevention-focused healthcare paradigms.

Abstract Background Progranulin (PGRN) haploinsufficiency due to progranulin gene (GRN) variants can cause frontotemporal dementia (FTD) with aberrant TAR DNA-binding protein 43 (TDP-43) accumulation. Despite microglial burden with TDP-43-related pathophysiology, direct microglial TDP-43 pathology has not been clarified yet, only emphasized in neuronal pathology. Thus, the objective of this study was to investigate TDP-43 pathology in microglia of patients with PGRN haploinsufficiency. Methods To design a human microglial cell model with PGRN haploinsufficiency, monocyte-derived microglia (iMGs) were generated from FTD–GRN patients carrying pathogenic or likely pathogenic variants (p.M1? and p.W147*) and three healthy controls. Results iMGs from FTD–GRN patients with PGRN deficiency exhibited severe neuroinflammation phenotype and failure to maintain their homeostatic molecular signatures, along with impaired phagocytosis. In FTD–GRN patients-derived iMGs, significant cytoplasmic TDP-43 aggregation and accumulation of lipid droplets with profound lysosomal abnormalities were observed. These pathomechanisms were mediated by complement C1q activation and upregulation of pro-inflammatory cytokines. Conclusions Our study provides considerable cellular and molecular evidence that loss-of-function variants of GRN in human microglia can cause microglial dysfunction with abnormal TDP-43 aggregation induced by inflammatory milieu as well as the impaired lysosome. Elucidating the role of microglial TDP-43 pathology in intensifying neuroinflammation in individuals with FTD due to PGRN deficiency and examining consequential effects on microglial dysfunction might yield novel insights into the mechanisms underlying FTD and neurodegenerative disorders.

Background Post-transplant diabetes mellitus (PTDM) is one of the most significant complications after transplantation. Patients with end-stage liver diseases requiring transplantation are prone to sarcopenia, but the association between sarcopenia and PTDM remains to be elucidated. We aimed to investigate the effect of postoperative muscle mass loss on PTDM development. Methods A total of 500 patients who underwent liver transplantation at a tertiary care hospital between 2005 and 2020 were included. Skeletal muscle area at the level of the L3–L5 vertebrae was measured using computed tomography scans performed before and 1 year after the transplantation. The associations between the change in the muscle area after the transplantation and the incidence of PTDM was investigated using a Cox proportional hazard model. Results During the follow-up period (median, 4.9 years), PTDM occurred in 165 patients (33%). The muscle mass loss was greater in patients who developed PTDM than in those without PTDM. Muscle depletion significantly increased risk of developing PTDM after adjustment for other confounding factors (hazard ratio, 1.50; 95% confidence interval, 1.23 to 1.84; P=0.001). Of the 357 subjects who had muscle mass loss, 124 (34.7%) developed PTDM, whereas of the 143 patients in the muscle mass maintenance group, 41 (28.7%) developed PTDM. The cumulative incidence of PTDM was significantly higher in patients with muscle loss than in patients without muscle loss (P=0.034). Conclusion Muscle depletion after liver transplantation is associated with increased risk of PTDM development.

Abstract The TARDBP gene variant is a known major cause of amyotrophic lateral sclerosis (ALS), with limited reports of Korean patients with ALS harboring the variants in TARDBP. This large cohort study introduces four ALS patients who share the p.M337V variant of the TARDBP, allowing for an investigation of clinical characteristics and prognosis by analyzing previously reported cases with the same variant. From November 2014 to August 2022, participants were recruited from two tertiary hospitals in Seoul, Korea. Clinical characteristics of patients diagnosed with ALS carrying the variant in TARDBP were evaluated. Previous articles demonstrating subjects’ characteristics were reviewed. Four patients were identified with the pathogenic missense variant (c.1009A>G; p.M337V) in the TARDBP. The mean age of onset was 55 years old, and none of the patients showed severe cognitive impairment. Sixty-three patients carrying the p.M337V variant in TARDBP from this study and previous reports delineated young age of onset (51.6 years), high frequency of bulbar onset patients (61.9%), and low comorbidity of frontotemporal dementia. This study reveals the presence of pathogenic variant of TARDBP in Korea and emphasizes the importance of genetic screening of the TARDBP gene, in diagnosing ALS and evaluating prognosis among familial and simplex ALS patients in Korea.

Paralytic shellfish toxins (PSTs) are potent neurotoxins produced by certain microalgae, particularly dinoflagellates, and they can accumulate in shellfish in coastal seawater and thus pose significant health risks to humans. To explore the relationship between toxicity and PST profiles in seawater and mussels, the spatiotemporal variations in PST concentrations and profiles were investigated along the southern coast of Korea under peak PST levels during spring. Seawater and mussel samples were collected biweekly from multiple stations, and the toxin concentrations in the samples were measured. Moreover, the dinoflagellate community composition was analyzed using next-generation sequencing to identify potential PST-producing species. The PST concentrations and toxin profiles showed substantial spatiotemporal variability, with GTX1 and GTX4 representing the dominant toxins in both samples, and C1/2 tending to be higher in seawater. Alexandrium species were identified as the primary sources of PSTs. Environmental factors such as water temperature and salinity influenced PST production. This study demonstrates that variability in the amount and composition of PSTs is due to intricate ecological interactions. To mitigate shellfish poisoning, continuous monitoring must be conducted to gain a deeper understanding of these interactions.

Objectives: The risk of severe COVID-19 in children with a solid organ transplant (SOT) is not well established. We compare the relative risk of severe COVID-19 infection between pediatric SOT and non-SOT children. Methods: The newly constructed K-COV-N cohort (Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service) was used. Children with COVID-19 (

Objectives Disability weights require regular updates, as they are influenced by both diseases and societal perceptions. Consequently, it is necessary to develop an up-to-date list of the causes of diseases and establish a survey panel for estimating disability weights. Accordingly, this study was conducted to calculate, assess, modify, and validate disability weights suitable for Korea, accounting for its cultural and social characteristics. Methods The 380 causes of disease used in the survey were derived from the 2019 Global Burden of Disease Collaborative Network and from 2019 and 2020 Korean studies on disability weights for causes of disease. Disability weights were reanalyzed by integrating the findings of an earlier survey on disability weights in Korea with those of the additional survey conducted in this study. The responses were transformed into paired comparisons and analyzed using probit regression analysis. Coefficients for the causes of disease were converted into predicted probabilities, and disability weights in 2 models (model 1 and 2) were rescaled using a normal distribution and the natural logarithm, respectively. Results The mean values for the 380 causes of disease in models 1 and 2 were 0.488 and 0.369, respectively. Both models exhibited the same order of disability weights. The disability weights for the 300 causes of disease present in both the current and 2019 studies demonstrated a Pearson correlation coefficient of 0.994 (p=0.001 for both models). This study presents a detailed add-on approach for calculating disability weights. Conclusions This method can be employed in other countries to obtain timely disability weight estimations.

We established a protocol for the traditional Korean medicine examination (KME) and methodically gathered data following this protocol. Potential indicators for KME were extracted through a literature review; the first KME protocol was developed based on three rounds of expert opinions. The first KME protocol’s feasibility was confirmed, and data were collected over four years from traditional Korean medicine (KM) hospitals, focusing on healthy adults, using the final KME protocol. A literature review identified 175 potential core indicators, condensed into 73 indicators after three rounds of expert consultation. The first KME protocol, which was categorized under questionnaires and medical examinations, was developed after the third round of expert opinions. A pilot study using the first KME protocol was conducted to ensure its validity, leading to modifications resulting in the development of the final KME protocol. Over four years, data were collected from six KM hospitals, focusing on healthy adults; we obtained a dataset comprising 11,036 healthy adults. This is the first protocol incorporating core indicators of KME in a quantitative form and systematically collecting data. Our protocol holds potential merit in evaluating predisposition to diseases or predicting diseases.

Abstract Background Parkin dysfunction associated with the progression of parkinsonism contributes to a progressive systemic skeletal disease characterized by low bone mineral density. However, the role of parkin in bone remodeling has not yet been elucidated in detail. Result We observed that decreased parkin in monocytes is linked to osteoclastic bone-resorbing activity. siRNA-mediated knockdown of parkin significantly enhanced the bone-resorbing activity of osteoclasts (OCs) on dentin without any changes in osteoblast differentiation. Moreover, Parkin-deficient mice exhibited an osteoporotic phenotype with a lower bone volume accompanied by increased OC-mediated bone-resorbing capacity displaying increased acetylation of α-tubulin compared to wild-type (WT) mice. Notably, compared to WT mice, the Parkin-deficient mice displayed increased susceptibility to inflammatory arthritis, reflected by a higher arthritis score and a marked bone loss after arthritis induction using K/BxN serum transfer, but not ovariectomy-induced bone loss. Intriguingly, parkin colocalized with microtubules and parkin-depleted-osteoclast precursor cells (Parkin −/− OCPs) displayed augmented ERK-dependent acetylation of α-tubulin due to failure of interaction with histone deacetylase 6 (HDAC6), which was promoted by IL-1β signaling. The ectopic expression of parkin in Parkin −/− OCPs limited the increase in dentin resorption induced by IL-1β, accompanied by the reduced acetylation of α-tubulin and diminished cathepsin K activity. Conclusion These results indicate that a deficiency in the function of parkin caused by a decrease in parkin expression in OCPs under the inflammatory condition may enhance inflammatory bone erosion by altering microtubule dynamics to maintain OC activity.

BackgroundTo evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN).MethodsUsing proteomics, we screened for potential urine biomarkers that differentiate LN from systemic lupus erythematosus (SLE) patients without nephritis. In addition, urine levels of target biomarkers were measured by ELISA in 13- and 23-week-old MRL-lpr (murine model for LN) and MRL/MpJ mice. Histological analysis was also performed on the kidneys of 23-week-old mice.ResultsUrine SERPINC1 and ORM1 were elevated in SLE patients with newly diagnosed LN compared with SLE patients without LN (SERPINC1, AUC=.892, P

Background: The decoction form of herbal medicine (D-HM) is mainly prescribed to patients with allergic rhinitis (AR) in Korean Medicine (KM) clinics in the Republic of Korea; however, it is difficult to conduct clinical trials of D-HM due to regulatory issues. This study investigated the clinical safety and effectiveness of D-HM combination therapy for the treatment of AR by analyzing the AR outpatient data from 17 KM clinics. Methods: This retrospective cohort study included patients who visited KM clinics for AR treatment from January 1, 2021, to March 31, 2022. Cases were collated using structured case report forms and divided into the D-HM with KM usual care group (D-HM group) and the KM usual care group (UC group). Since D-HM therapy could not be randomly assigned to the study population, we used optimal propensity score (PS) matching to investigate the effectiveness and safety of D-HM combination therapy in the treatment of AR. Results: Data from 228 patients were collected. After PS matching, 144 patients were finally analyzed. The total nasal symptom score (TNSS) and mini-rhinoconjunctivitis quality of life questionnaire (mini-RQLQ) were significantly improved in the D-HM group compared with those in the UC group (TNSS: p=0.02; mini-RQLQ: p=0.04). Four patients in the D-HM group experienced minor adverse events that were mild and resolved within 15 days. Conclusions: D-HM combination therapy may be beneficial in the management of symptoms and rhinitis-associated quality of life and potentially useful in clinical practice. However, randomized placebo-controlled clinical trials are required to confirm their effectiveness. Study registration: This study has been registered at Clinical Research Information Service (KCT0007242).

Efficient induction of astaxanthin (AXT) biosynthesis remains a considerable challenge for the industrialization of the biorefinement of the microalga Haematococcus lacustris. In this study, we evaluated the technical feasibility of photosynthetic electrotreatment to enhance AXT accumulation in H. lacustris. The AXT content of H. lacustris electrotreated at an optimal current intensity (10 mA for 4 h) was 21.8% to 34.9% higher than that of the untreated control group, depending on the physiological state of the initial palmella cells. The contents of other carotenoids (i.e., canthaxanthin, zeaxanthin, and β-carotene) were also increased by this electrotreatment. However, when H. lacustris cells were exposed to more intense electric treatments, particularly at 20 and 30 mA, cell viability significantly decreased to 84.2% and 65.6%, respectively, with a concurrent reduction in the contents of both AXT and the three other carotenoids compared to those of the control group. The cumulative effect of electric stimulation is likely related to two opposing functions of reactive oxygen species, which facilitate AXT biosynthesis as signaling molecules while also causing cellular damage as oxidizing radicals. Collectively, our findings indicate that when adequately controlled, electric stimulation can be an effective and eco-friendly strategy for inducing targeted carotenoid pigments in photosynthetic microalgae.

Pesticides are beneficial in protecting crops from pests and improving agricultural productivity; however, concerns on pesticide pollution in water have increased due to their indiscriminate use and lack of adequate regulations. Many studies have focused on the risks of pesticides considering the limited number and types of pesticide residues in crops and soils, and duration, and very few have focused on surface water throughout the year. Therefore, this study comprehensively identified 308 pesticides in surface water samples collected monthly over one year in the Saemangeum Basin, Korea. Both targeted and non-targeted analyses were used to identify 171 and 24 pesticides, respectively. Results highlight the extensive extent of pesticide contamination. Among the quantified pesticides, bromobutide and pretilachlor consistently exhibited high concentrations and risk levels, as indicated by their elevated risk quotient (RQ) values. Seasonal variations in pesticide concentrations revealed distinct patterns with intensified herbicide use during summer and increased insecticide concentrations during autumn. This study highlights the presence, distribution, and associated ecological risks of pesticides in surface waters, emphasizing the necessity of comprehensive monitoring and regulatory measures to protect aquatic ecosystems. The high RQ values identified for specific pesticides underscore the urgent need to implement effective strategies to mitigate these environmental risks.

Nicotine, an abundant molecule in tobacco, has immunomodulatory effects on inflammatory diseases, primarily due to the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR). We aim to evaluate the expression of the α7 nAChR+ cells in joint tissue and the effect of smoking on immune cells and peripheral arthritis in curdlan-administered SKG mice, a murine model of spondyloarthropathy (SpA). The SKG mice were injected with curdlan two times at 2-week intervals and were divided into two groups; one exposed to cigarette smoke and the other not exposed. We found that the α7 nAChR+ cells increased in the joint tissue of curdlan-administered SKG mice compared to in the wild type. Furthermore, the peripheral arthritis scores and histological scores for synovial inflammation were lower in smoke-exposed curdlan-administered SKG mice than in mice not exposed to smoke. Immunofluorescence staining of the α7 nAChR+ and IL-17A+ cells was lower in the synovia of smoke-exposed mice than the control mice. The proportions of α7 nAChR+IL-17A+ and α7 nAChR+IL-17A+FOXP3+ cells also decreased in the synovia of smoke-exposed mice compared with the controls. We observed an increase in the α7 nAChR+ cells within the joint tissue of curdlan-administered SKG mice and that cigarette smoke had an influence on both peripheral arthritis and immune cell population, especially α7 nAChR+ cells. Thus, exposure to cigarette smoke after arthritogenic stimuli may have an anti-arthritogenic effect in curdlan-administered SKG mice.

BackgroundCerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by a mutation in the CYP27A1 gene. Due to the disruption of bile acid synthesis leading to cholesterol and cholestanol accumulation, CTX manifests as premature cataracts, chronic diarrhea, and intellectual disability in childhood and adolescence. This report presents a case of CTX with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD) in middle age.Case presentationA 60-year-old woman presented with behavioral and personality changes. She showed disinhibition, such as hoarding and becoming aggressive over trifles; compulsive behavior, such as closing doors; apathy; and dietary change. The patient showed a progressive cognitive decline and relatively sparing memory and visuospatial function. She had hyperlipidemia but no family history of neurodegenerative disorders. Initial fluid-attenuated inversion recovery (FLAIR) images showed a high signal in the periventricular area, and brain spectroscopy showed hypoperfusion in the frontal and temporal lobes, mimicking bvFTD. However, on physical examination, xanthomas were found on both the dorsum of the hands and the Achilles tendons. Hyperactive deep tendon reflexes in the bilateral biceps, brachioradialis, and knee and positive Chaddock signs on both sides were observed. Four years later, FLAIR images showed symmetrical high signals in the bilateral dentate nuclei of the cerebellum. Her serum cholestanol (12.4 mg/L; normal value ≤6.0) and 7α,12α-dihydroxycholest-4-en-3-one (0.485 nmol/mL; normal value ≤0.100) levels were elevated. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) and a known pathogenic variant (c.1420C>T, p.Arg474Trp) of the CYP27A1 gene were found in trans-location. The patient was diagnosed with CTX and prescribed chenodeoxycholic acid (750 mg/day).ConclusionsThis report discusses the case of a middle-aged CTX patient with an unusual phenotype of bvFTD. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) was identified in the CYP27A1 gene. Early diagnosis is important because supplying chenodeoxycholic acid can prevent CTX progression.

Abstract Background The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD). Methods A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change. Results Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104). Conclusions Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population. Trial registration The trial was registered at ClinicalTrials.gov (registration number: NCT03434613 ).

Disability-adjusted life-year (DALY) estimates may vary according to factors such as the standard life expectancy, age weighting, time preference and discount rate, calculation of disability weights, and selection of the estimation method. DALY estimation methods are divided into the following 3 approaches: the incidence-based approach, the pure prevalence-based approach, and the hybrid approach. These 3 DALY estimation approaches each reflect different perspectives on the burden of disease using unique characteristics, based on which the selection of a suitable approach may vary by the purpose of the study. The Global Burden of Disease studies, which previously estimated DALYs using the incidence-based approach, switched to using the hybrid approach in 2010, while the National Burden of Disease studies in Korea still mainly apply the incidence-based approach. In order to increase comparability with other international burden of disease studies, more DALY studies using the prevalence-based approach need to be conducted in Korea. However, with the limitations of the hybrid approach in mind, it is necessary to conduct more research using a disease classification system suitable for Korea. Furthermore, more detailed and valid data sources should be established before conducting studies using a broader variety of DALY estimation approaches. This review study will help researchers on burden of disease use an appropriate DALY estimation approach and will contribute to enhancing researchers’ ability to critically interpret burden of disease studies.

An index that evaluates the health level of a population group considering both death and loss of function due to disease is called a summary measure of population health (SMPH). SMPHs are broadly divided into life year indices and life expectancy indices, the latter of which comprise healthy life expectancy (HLE). HLE is included as a policy target in various national and regional level healthcare plans, and the term “HLE” is commonly used in academia and by the public. However, the overall level of understanding of HLE—such as the precise definition of HLE and methods of calculating HLE—still seems to be low. As discussed in this study, the types of HLE are classified into disability-free life expectancy, disease-free life expectancy, quality-adjusted life expectancy, self-rated HLE, and disability-adjusted life expectancy. Their characteristics are examined to facilitate a correct understanding and appropriate utilization of HLE. In addition, the Sullivan method, as a representative method for calculating HLE, is presented in detail, and major issues in the process of calculating HLE, such as selection of the population group and age group, estimation of death probability, calculation of life years, and incorporation of health weights, are reviewed. This study will help researchers to select an appropriate HLE type and evaluate the validity of HLE research results, and it is expected to contribute to the vitalization of HLE research.

The study aims to examine the current status and differences in the burden of disease in Korea during 2008-2018. We calculated the burden of disease for Koreans from 2008 to 2018 using an incidence-based approach. Disability adjusted life years (DALYs) were expressed in units per 100 000 population by adding years of life lost (YLLs) and years lived with disability (YLDs). DALY calculation results were presented by gender, age group, disease, region, and income level. To explore differences in DALYs by region and income level, we used administrative district and insurance premium information from the National Health Insurance Service claims data. The burden of disease among Koreans showed an increasing trend from 2008 to 2018. By 2017, the burden of disease among men was higher than that among women. Diabetes mellitus, low back pain, and chronic lower respiratory disease were ranked high in the burden of disease; the sum of DALY rates for these diseases accounted for 18.4% of the total burden of disease among Koreans in 2018. The top leading causes associated with a high burden of disease differed slightly according to gender, age group, and income level. In this study, we measured the health status of Koreans and differences in the population health level according to gender, age group, region, and income level. This data can be used as an indicator of health equity, and the results derived from this study can be used to guide community-centered (or customized) health promotion policies and projects, and for setting national health policy goals.

Nonalcoholic fatty liver disease (NAFLD) is a global health problem that is closely associated with obesity and metabolic syndrome. Spatholobi caulis (SC) is a herbal medicine with potential hepatoprotective effects; however, its active compounds and underlying mechanisms have not been fully explored. In this study, we combined a multiscale network-level approach with experimental validation to investigate SC’s antioxidant properties and their impact on NAFLD. Data collection and network construction were performed, and active compounds and key mechanisms were identified through multi-scale network analysis. Validation was conducted using in vitro steatotic hepatocyte models and in vivo high-fat diet-induced NAFLD models. Our findings revealed that SC treatment improved NAFLD by modulating multiple proteins and signaling pathways, including AMPK signaling pathways. Subsequent experiments showed that SC treatment reduced lipid accumulation and oxidative stress. We also validated SC’s effects on AMPK and its crosstalk pathways, emphasizing their role in hepatoprotection. We predicted procyanidin B2 to be an active compound of SC and validated it using a lipogenesis in vitro model. Histological and biochemical analyses confirmed that SC ameliorated liver steatosis and inflammation in mice. This study presents SC’s potential use in NAFLD treatment and introduces a novel approach for identifying and validating active compounds in herbal medicine.

Low serum progranulin (PGRN) is known to be associated with granulin (GRN) gene mutation and T alleles of GRN rs5848 polymorphism. However, there have been only a few Asian studies exploring these. We investigated the serum PGRN levels, rs5848 genotypes, and their relations with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in the Korean population. Serum PGRN levels, GRN rs5848 polymorphism, and GRN mutations were evaluated in 239 participants (22 cognitively unimpaired participants and 217 patients with neurodegenerative diseases). CSF AD biomarkers were also evaluated in 214 participants. There was no significant difference in the serum PGRN levels among the diagnostic groups. We could not find any GRN mutation carrier in our sample. The differences in the frequencies of the rs5848 genotypes among the clinical groups or the effects of the rs5848 genotypes on serum PGRN were not observed. There was no correlation between the serum PGRN level or rs5848 genotype and CSF AD biomarkers. Neither the T allele nor the TT genotype had an effect on the development of AD. Our results showed that serum PGRN levels were not associated with rs5848 genotypes, indicating that multiple single nucleotide polymorphisms might affect PGRN concentrations in an ethnicity-specific manner.

We recently reported that transplantation of mesenchymal stem cells (MSCs) significantly reduced bacterial growth and brain injury in neonatal meningitis induced by Escherichia coli (E. coli) infection in newborn rats. As a next step, to verify whether the MSCs protect against brain injury in a paracrine manner, this study was designed to estimate the efficacy of MSC-derived extracellular vesicles (MSC-EVs) in E. coli meningitis in newborn rats. E. coli meningitis was induced without concomitant bacteremia by the intra-cerebroventricular injection of 5 × 102 colony-forming units of K1 (-) E. coli in rats, at postnatal day 11. MSC-EVs were intra-cerebroventricularly transplanted 6 h after the induction of meningitis, and antibiotics were administered for three consecutive days starting at 24 h after the induction of meningitis. The increase in bacterial growth in the cerebrospinal fluid measured at 24 h after the meningitis induction was not significantly reduced following MSC-EV transplantation. However, an increase in brain cell death, reactive gliosis, and inflammation following meningitis were significantly attenuated after MSC-EV transplantation. Taken together, our results indicate that MSCs show anti-apoptotic, anti-gliosis, and anti-inflammatory, but not antibacterial effects, in an EV-mediated paracrine manner in E. coli-induced neonatal meningitis.

Preterm births are often associated with neurodevelopmental impairment. In the critical developmental period of the fetal brain, preterm birth disrupts cortical maturation. Notably, preterm birth leads to alterations in the fronto-striatal and temporal lobes and the limbic region. Recent advances in MRI acquisition and analysis methods have revealed an integrated approach to the genetic influence on brain structure. Based on imaging studies, we hypothesized that the altered cortical structure observed after preterm birth is associated with common genetic variations. We found that the presence of the minor allele at rs1042778 in OXTR was associated with reduced curvature in the right medial orbitofrontal gyrus (p < 0.001). The presence of the minor allele at rs174576 in FADS2 (p < 0.001) or rs740603 in COMT (p < 0.001) was related to reduced curvature in the left posterior cingulate gyrus. This study provides biological insight into altered cortical curvature at term-equivalent age, suggesting that the common genetic variations related to autism spectrum disorder (ASD) and lipid metabolism may mediate vulnerability to early cortical dysmaturation in preterm infants.

No study yet has compared the longitudinal course and prognosis between subcortical vascular cognitive impairment patients with and without genetic component. In this study, we compared the longitudinal changes in cerebral small vessel disease markers and cognitive function between subcortical vascular mild cognitive impairment (svMCI) patients with and without NOTCH3 variant [NOTCH3(+) svMCI vs. NOTCH3(–) svMCI]. We prospectively recruited patients with svMCI and screened for NOTCH3 variants by sequence analysis for mutational hotspots in the NOTCH3 gene. Patients were annually followed-up for 5 years through clinical interviews, neuropsychological tests, and brain magnetic resonance imaging. Among 63 svMCI patients, 9 (14.3%) had either known mutations or possible pathogenic variants. The linear mixed effect models showed that the NOTCH3(+) svMCI group had much greater increases in the lacune and cerebral microbleed counts than the NOTCH3(–) svMCI group. However, there were no significant differences between the two groups regarding dementia conversion rate and neuropsychological score changes over 5 years.

Objectives In 2018, South Korea’s suicide mortality rate was 26.59 deaths per 100 000 people; this figure is 2.2 times higher than that of the year 2000, during which 12.22 deaths per 100 000 people were ascribed to suicide. This study aims to observe the trend of disease burden in years of life lost (YLL) due to suicide from 2000 to 2018 in South Korea and investigate the related sociodemographic risk factors.Design This quantitative research used secondary data—including claim data, cause of death statistics, life tables and census data—from national health insurance corporation and Statistics Korea. Based on the methodology of Korean National Burden of Disease study, this study used an incidence-based approach to measure YLL.Results The total YLL due to suicide during the last two decades was 4 298 886 years; the average YLL per death was 18.65 years. The YLL rate per 100 000 people was 482 (male: 664, female: 300) in 2018, 1.7 times higher than the 387 (male 387, female 183) in 2000. Low education levels and non-marital status were shown to be related to the increase in YLL rate.Conclusion These results show the increasing disease burden of suicide in South Korea and suggest the necessity of more in-depth research to analyse correlation and causation with sociodemographic risk factors.

This study estimated the prevalence and incidence rate of schizophrenia, schizotypal, and delusional disorders (SSDD) in Korea from 2008 to 2017 and analyzed the hospital admission rate, re-admission rate, and hospitalization period. It used the Korean nationwide National Health Insurance Service claims database. SSDD patients who had at least one visit to Korea's primary, secondary, or tertiary referral hospitals with a diagnosis of SSDD, according to the International Classification of Diseases, 10th Revision (ICD-10), were identified as SSDD cases if coded as F20-F29. Data were analyzed using frequency statistics. Results showed that the 12-month prevalence rate of SSDD increased steadily from 0.40% in 2008 to 0.45% in 2017. Analysis of the three-year cumulative prevalence rate of SSDD showed an increase from 0.51% in 2011 to 0.54% in 2017. In 2017, the five-year cumulative prevalence rate was 0.61%, and the 10-year cumulative prevalence rate was 0.75%. The hospital admission rate among SSDD patients decreased from 2008 (30.04%) to 2017 (28.53%). The incidence of SSDD was 0.05% and no yearly change was observed. The proportion of SSDD inpatients whose first hospital visit resulted in immediate hospitalization was 22.4% in 2017. Epidemiological indicators such as prevalence, incidence, and hospitalization rate play an important role in planning social and financial resource allocation. Therefore, efforts to produce more accurate epidemiological indicators are very important and this study's findings could have a significant social impact.

Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients’ characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients’ behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https://nhiss.nhis.or.kr).

In South Korea, people may increase their medical coverage by purchasing private health insurance to augment low coverage provided by the National Health Insurance (NHI). Frequent and excessive use of medical care by those with private health insurance is an issue, especially for musculoskeletal disorders that require excessive care and contribute to moral hazard. In South Korea, since private health insurance is structurally linked to the scope of coverage with public health insurance, this increased use of medical care may adversely affect public health insurance finances. This study aimed to analyze the effects of private health insurance on medical care use for patients with musculoskeletal disorders. We used the Korea Health Panel 2014 to 2015 data that included 5622 participants who used medical care for musculoskeletal disorders in 2015. Two groups were created: those who purchased private health insurance ( n = 3588) and those without private insurance ( n = 2034). We compared their medical utilization using logistic regression, negative binomial regression, and multiple linear regression to determine the associations of private health insurance with medical care use. Medical expenditures by private health insurance purchasers were higher than those of non-purchasers for outpatient care ( P

Atopic dermatitis is a chronic inflammatory skin disease that affects the growth and development of children. The prevalence of atopic dermatitis has been continually increasing, and this has also been accompanied by rising socioeconomic costs. Interest has been growing in alternative medicine as a means of alleviating the burden of atopic dermatitis. This was a single-center, double-blinded, randomized, placebo-controlled investigator-led clinical trial including 60 atopic dermatitis patients. The participants were classified into an experimental group (30 persons) and a control group (30 persons), who were administered, respectively, socheongryong-tang or a placebo for 4 weeks. After 4 weeks of treatment, the participants visited the trial center again and assess their efficacy and safety. The researchers performed statistical comparisons of the changes in the SCORAD Index, amount and frequency of ointment use, and height and weight to assess the efficacy. To assess the safety, diagnostic tests and vital sign checks were performed at each visit, and the presence or absence of adverse events was observed. As a result, the frequency and the amount of steroid ointment application in both groups increased, but the experimental group showed less tendency (p = 0.081). Results of analyzing the children in the experimental group in relation to growth showed a significantly greater height growth than the control group (p < 0.05). In addition, all study participants did not show any remarkable abnormal signs in the safety evaluation. In conclusion, compared to the control group, the experimental group, who took socheongryong-tang showed a tendency to be less dependent on steroid ointment and statistically significant increase in height.

Ionic liquids (ILs) are new green solvents, which are widely used in lignocellulosic and microalgal biorefineries. However, high-temperature operating conditions limit their application in the extraction of heat-labile algal products, such as bioactive astaxanthin. In this study, we report the technical feasibility of room-temperature astaxanthin extraction from Haematococcus lacustris cysts with a thick and complex cell wall structure, by combining ultrathin α-quartz nanoplates (NPLs) with ethyl-3-methylimidazolium ([Emim])-based ILs. When four different [Emim]-based ILs with thiocyanate (SCN), diethylphosphate (DEP), HSO4, and Cl anions were applied to 90-day-old H. lacustris cysts at room temperature (~28 °C), the astaxanthin extraction efficiency was as low as 9.6–14.2%. Under sonication, α-quartz NPLs disrupted the cyst cell wall for a short duration (5 min). The astaxanthin extraction efficacies of a subsequent IL treatment improved significantly to 49.8% for [Emim] SCN, 60.0% for [Emim] DEP, 80.7% for [Emim] HSO4, and 74.3% for [Emim] Cl ions, which were 4.4, 6.1, 8.4, and 5.2 times higher than the extraction efficacy of only ILs, respectively. This finding suggests that α-quartz NPLs can serve as powerful cell-wall-disrupting agents for the room-temperature IL-mediated extraction of astaxanthin from robust algal cyst cells.

This study developed and validated a Korean community health determinants index (K-CHDI), which can be used to assess the health status of the community. To develop composite indicators, we followed the guidelines of the Joint Research Centre of the Organization for Economic Cooperation and Development. We reviewed previous studies and formed a theoretical framework to systematize our domains and indicators, which were decided through a Delphi survey of healthcare experts. Data on indicators were obtained from the Korean Statistics and Community Health Survey. We applied the Min-Max normalization method and measured weights by the analytic hierarchy process. Health outcomes were estimated using mortality, years of life lost, years lived with disability, and disability-adjusted life years by standardizing sex and age. The value of the index is between 0 and 1; higher values indicate more positive health determinants. K-CHDI for 250 subnational regions (cities, counties, and districts, or Si·Gun·Gu) were correlated with health outcomes. The correlation coefficient was stronger in large cities than in medium-sized areas and small areas, and the higher the K-CHDI group, the higher the coefficient. The K-CHDI represents a reference standard for estimating health status using health determinants as composite indicators at the subnational level.

Background: Hypertension is a major cause of cardiovascular disease and associated mortality, and postmenopausal women are at a high risk of hypertension. We aim to investigate the hypotensive effect and safety of acupuncture, focusing on postmenopausal women with prehypertension and stage 1 hypertension. In addition, we aim to investigate whether the effect of acupuncture treatment differed, depending on Sasang Constitution and cold–heat pattern. Methods: This study is designed as an intervention cohort study. Two hundred postmenopausal women aged

Abstract In Drosophila, precise regulation of BMP signaling is essential for normal synaptic growth at the larval neuromuscular junction (NMJ) and neuronal survival in the adult brain. However, the molecular mechanisms underlying fine-tuning of BMP signaling in neurons remain poorly understood. We show that loss of the Drosophila PDZ guanine nucleotide exchange factor Gef26 significantly increases synaptic growth at the NMJ and enhances BMP signaling in motor neurons. We further show that Gef26 functions upstream of Rap1 in motor neurons to restrain synaptic growth. Synaptic overgrowth in gef26 or rap1 mutants requires BMP signaling, indicating that Gef26 and Rap1 regulate synaptic growth via inhibition of BMP signaling. We also show that Gef26 is involved in the endocytic downregulation of surface expression of the BMP receptors thickveins (Tkv) and wishful thinking (Wit). Finally, we demonstrate that loss of Gef26 also induces progressive brain neurodegeneration through Rap1- and BMP signaling-dependent mechanisms. Taken together, these results suggest that the Gef26-Rap1 signaling pathway regulates both synaptic growth and neuronal survival by controlling BMP signaling.

The plant-back intervals (PBIs) of imicyafos were investigated for rotational cultivation of lettuce and spinach in greenhouses. Imicyafos dissipation in soil and its plant uptake were evaluated by liquid chromatography-tandem mass spectrometry. Bioconcentration ratios (BCRs) were calculated by comparing the residues in plants to the initial residue in soil. The BCRs were used to calculate the soil acceptable residues (SARs) transferable to plants at the Positive List System (PLS) level. The number of days, PBIs for reaching SARs were obtained from the dissipation equation for imicyafos in soil. In soil, imicyafos followed first order dissipation kinetics (R2 = 0.975) with a half-life of 40.8 days. The BCRs ranged from 0.041 to 0.469 in the edible leaf parts of lettuce and 0.006 to 0.134 in those of spinach. The SARs ranged from 0.021 to 0.244 for lettuce and 0.075 to 1.667 mg kg−1 for spinach. The PBIs of imicyafos were estimated to be 213.9 to 357.3 days for lettuce and 100.8 to 283.6 days for spinach. This study suggests at least a minimum 1-year interval after the final application of imicyafos as a management method that complies with the PLS for the rotational cultivation of lettuce and spinach.

Objective We aimed to investigate the effect of ropinirole on excessive daytime sleepiness (EDS) and depression in Parkinson’s disease (PD) with a large population. Methods We conducted a cross-sectional observational study at nine hospitals in Korea between April 24, 2013, and April 22, 2015. We analyzed the demographic and clinical features, other medical history, history of antiparkinsonian medication within 6 months, Hoehn and Yahr stage (HY stage), Unified Parkinson’s Disease Rating Scale (UPDRS) part II and III, Epworth Sleepiness Scale (ESS), and 30-item Geriatric Depression Scale (GDS-30). Results Four-hundred-thirteen patients with PD (mean age: 65.2 ± 9.0 years; men: 227 patients) were analyzed. Multivariate logistic regression analysis showed that age at examination, UPDRS II, and GDS-30 were independent risk factors for EDS and that sex, UPDRS II, and ESS were independent risk factors for depression. Conclusion Our large group study did not find any significant associations of ropinirole with EDS and depression in Korean PD patients.

BackgroundPrivate local clinics in Korea have little experience with information technology (IT)-based glucose monitoring (ITGM). Our aim is to examine user satisfaction and the possibility of using ITGM service practically.MethodsPatients sent their blood glucose levels to physicians in local clinics. The physicians reviewed the blood glucose values online and provided personal consultations through text messaging or phone calls. Thereafter, a satisfaction survey on the ITGM service, the modified Morisky scale, and patient assessment of chronic illness care were administered.ResultsOne hundred and seventy patients from seven private local clinics used the ITGM. Overall satisfaction, including that about the ITGM service, the device, and its usefulness, was rated higher than “mostly satisfied” (score 4.2±0.8 out of 5.0) and even higher among the elderly. Satisfaction was positively associated with age, especially in those older than 60 years. The main reason for intent for future use of the service was the time/place flexibility. Highly motivated patients tended to answer positively regarding information satisfaction (P=0.0377).ConclusionOur study is the first to investigate ITGM satisfaction in private local clinics. The feasibility of users utilizing ITGM should be clarified, and future clinical research on the service's clinical effects and cost-benefit analysis is needed.

Purpose This study aims to demonstrate whether the functionalities between the widely used questionnaire in other countries and the Korean-translated version show similarity. Also, it intends to verify their reliability and validity. Methods The original questionnaire was first developed by professor Noe at the University of Minnesota with 29 items named as “mentoring functions” to identify the participants’ psychological and career-development functions. Using the Korean-translated version of the original questionnaire, the study was conducted on total 288 Kyung Hee University medical students, ranging from the first-year students to the third-year students on December 2015. In order to investigate if the survey form could be applied to the Korean participants, exploratory factor analysis and confirmatory factor analysis were conducted, using varimax rotation. Cronbach α statistics and the figures of standardized regression weights were analyzed respectively to indicate construct, convergent, and discriminant validities. Results The result of exploratory factor analysis shows there are a total of three functions, including the additional “friendship function” (Eigen value, 1.152; significant level if higher than 1.0) with its high emphasis. The result of confirmatory factor analysis also demonstrates the similarity (p=0.000). As the whole reliability scale of the three functions is significantly high (Cronbach α , 0.971), each reliability scales of the three functions are shown to be high (0.814–0.955) as well. Conclusion The model, with its three functions, proved the significant statistics regarding the reliability and validity. According to this ground, the conclusion is that the adapted questionnaire used in this study could be applied to Korean medical students.

This study quantitatively analyzes the effects of employment patterns at the time of death of the elderly on the utilization of medical care before death using the cohort data from the National Health Insurance Corporation, controlling mortality to obtain more accurate results. Gender was coded as 0 for males and 1 for females, and average monthly household income was taken as a logarithm to approximate a normal distribution. Care cost at the end of life was defined as the sum of the national health insurance contributions and statutory self-contributions. To measure proximity to death, deceased elderly were divided by the period from last hospital visit to death (except any hospital visit at time of death). We distinguished regular workers, irregular workers, self-employed and employers, unpaid family workers, and unemployed. The data used in this study are sample cohort data from the National Health Insurance Corporation. We examined the relationships between variables through 4 models using negative binomial regression. The effects of employment status on health status were analyzed and adjusted for demographic characteristics, socioeconomic status, and proximity to death. As the dependent variable, medical expenses were taken for 1 year before death. In this study, care costs at end of life were higher when children were economically independent and when the respondent was more educated, had high economic level, and had high average monthly household income. In addition, employment security also had a significant impact on care cost at end of life: Irregular workers spent significantly less than regular workers. The fact that care cost at end of life is differentiated according to employment status suggests that individuals’ health exists within a social context, which may also constrain it: There is a risk that people’s health status will become determined by socioeconomic status.

Nipple-areolar complex (NAC) reconstruction is the final step in the long journey of breast reconstruction for mastectomy patients. Successful NAC reconstruction depends on the use of appropriate surgical techniques that are simple and reliable. To date, numerous techniques have been used for nipple reconstruction, including contralateral nipple sharing and various local flaps. Recently, it has been common to utilize local flaps. However, the most common nipple reconstruction problem encountered with local flaps is the loss of nipple projection; there can be approximately 50% projection loss in reconstructed nipples over long-term follow-up. Several factors might contribute to nipple projection loss, and we tried to overcome these factors by performing nipple reconstructions using a boomerang flap technique, which is a modified C–V flap that utilizes the previous mastectomy scar to maintain long-term nipple projection.

Haematococcus pluvialis accumulates astaxanthin, which is a high-value antioxidant, during the red cyst stage of its lifecycle. The development of a rigid cell wall in the cysts hinders the recovery of astaxanthin. We investigated morphological changes and cell disruption of mature H. pluvialis cyst cells while using high-pressure homogenization for astaxanthin extraction. When treated with French-press-cell (pressure, 10,000−30,000 psi; passage, 1−3), the intact cyst cells were significantly broken or fully ruptured, releasing cytoplasmic components, thereby facilitating the separation of astaxanthin by ethyl acetate. Fluorescence microscopy observations using three different fluorescent dyes revealed that a greater degree of cell breakage caused greater external dispersion of astaxanthin, chlorophyll, lipids, proteins, and carbohydrates. The mechanical treatment resulted in a high cell disruption rate of up to 91% based on microscopic cell typing and Coulter methods. After the ethyl acetate extraction, the astaxanthin concentration significantly increased by 15.2 mg/L in proportion to the increase in cell disruption rate, which indicates that cell disruption is a critical factor for solvent-based astaxanthin recovery. Furthermore, this study recommends a synergistic combination of the fast instrumental particle-volume-distribution analysis and microscope-based morphologic phenotyping for the development of practical H. pluvialis biorefinery processes that co-produce various biological products, including lipids, proteins, carbohydrates, chlorophyll, and astaxanthin.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease, in which the intestinal epithelium loses its barrier function. Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated the role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells, in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways, created by a Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium-binding protein, as the myeloid promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau (Vhl) KO mice, in which HIF-1α and HIF-2α are constitutively activated in myeloid cells, we found that these mice were highly susceptible to DSS-induced colitis, demonstrating greater body weight loss, increased mortality, faster onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1-positive myeloid cells in the colon compared with wild-type (WT) mice. These parameters were restored to, if not better than, the WT levels when we examined hMRP8 Hif-1a KO mice upon 5% DSS feeding. hMRP8 Hif-2a KO mice, on the other hand, exhibited a similar degree of DSS-induced colitis to that of WT mice. Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in the colon, we found that hMRP8 Hif-1a KO mice exhibited comparable levels of colorectal tumors to those of WT mice, indicating that HIF-1α in myeloid cells is dispensable for tumorigenesis. Collectively, our results suggest that HIF-1α activation in myeloid cells critically regulates IBD progression.

Background: In this study, we presented a theoretical model to measure aging rate in OECD countries, quantitatively measuring the effect of aging rate on disease patterns in each country and explaining how these effects were obtained. The purpose of this study was to investigate how disease burden varies according to the level of medical infrastructure and changes in aging index using OECD aging data and WHO disease burden data. Methods: This study used OECD Health data and global burden of disease data from the WHO in 2000 and 2012. We applied a difference-in-differences (DID) model was used to analyze effects of aging. Results: Disease burdens increased over time, especially in the aging population of middle-aged. In the case of loss of life due to premature death, the number of middle- aged and older population was increased significantly. When we examined the econometric model after controlling related factors, there was a significant increase in loss of life due to illness and premature death. On the other hand, the group of piles at the aging level had a significant positive effect on Years of Life Lost (YLL). Although the interaction effect as an important variable showing double difference effect of aging did not affect Disability adjusted Life Year (DALY), it showed a significant positive effect on YLL. Conclusion: Loss of life due to death of the elderly was relatively higher than that of the elderly. Therefore, the impact of population aging on medical resources and medical expenditures in the future should consider population structure changes, disease burden by age group, and interactions of these two incremental factors.

Introduction:Gongjin-dan (GJD) is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans.Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted.Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration (p = 0.25), but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels (p = 0.14). Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07) and the Fatigue Severity Scale (FSS, p = 0.13) questionnaires. BFI and FSS scores in the first stage (before the crossover), however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05) after GJD treatment (relative to placebo). GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire (p = 0.06), with a significant improvement specifically in the condition “Getting To Sleep” (p = 0.02). Five participants experienced minor adverse events, but no adverse events were specific to the GJD administration period.Conclusions: This trial produced the first clinical evidence that GJD might have anti-fatigue properties, especially under sleep deprivation; however, the investigation of cortisol-mediated mechanisms requires further larger-scale studies in the future.Trial registration: World Health Organization International Clinical Trials Registry Platform KCT0001681 (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0001681).

Autosomal dominant neurohypophyseal diabetes insipidus is a rare form of central diabetes insipidus that is caused by mutations in the vasopressin-neurophysin II (AVP-NPII) gene. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP). Here we report a case of familial neurohypophyseal diabetes insipidus in four generations of a Korean family, caused by heterozygous missense mutation in exon 2 of the AVP-NPII gene (c.286G>T). This is the first report of such a case in Korea.

Microalgae have been considered as one of the most promising biomass feedstocks for various industrial applications such as biofuels, animal/aquaculture feeds, food supplements, nutraceuticals, and pharmaceuticals. Several biotechnological challenges associated with algae cultivation, including the small size and negative surface charge of algal cells as well as the dilution of its cultures, need to be circumvented, which increases the cost and labor. Therefore, efficient biomass recovery or harvesting of diverse algal species represents a critical bottleneck for large-scale algal biorefinery process. Among different algae harvesting techniques (e.g., centrifugation, gravity sedimentation, screening, filtration, and air flotation), the flocculation-based processes have acquired much attention due to their promising efficiency and scalability. This review covers the basics and recent research trends of various flocculation techniques, such as auto-flocculation, bio-flocculation, chemical flocculation, particle-based flocculation, and electrochemical flocculation, and also discusses their advantages and disadvantages. The challenges and prospects for the development of eco-friendly and economical algae harvesting processes have also been outlined here.

BACKGROUND:Ferritin is associated with various cardiometabolic risk factors such as dyslipidemia, hypertension, obesity, and insulin resistance in adults. We aimed to study the association between serum ferritin levels and dyslipidemia in adolescents, because dyslipidemia is considered an important modifiable cardiovascular risk factor in the young. METHODS:We analyzed 1,879 subjects (1,026 boys and 853 girls) from the 2009-2010 Korean National Health and Nutrition Examination Survey IV. Subjects were categorized into quartiles according to their lipid parameters, which were classified according to age and gender. Those in the highest quartile groups for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations were diagnosed as having dyslipidemia. Those in the lowest quartile for high-density lipoprotein cholesterol (HDL-C) values were diagnosed with abnormal levels. RESULTS:In boys, total cholesterol, LDL-C, and triglyceride concentrations were significantly correlated with serum ferritin levels. In both boys and girls, serum ferritin levels were negatively associated with HDL-C values, even after adjusting for all covariates. Furthermore, there was no significant correlation between serum ferritin levels and total cholesterol, LDL, and triglyceride concentrations in girls. CONCLUSION:Serum ferritin levels were significantly associated with major dyslipidemia parameters, more prominently in boys than in girls, and this association represents a cardiometabolic risk factor.

The ubiquitin-proteasome system is a major proteolytic systemfor nonlysosomal degradation of cellular proteins. Here, we investigatedthe response of mouse embryonic stem (ES) cells underproteotoxic stress. Proteasome inhibitors induced expressionof heat shock protein 70 (HSP70) in a concentration- andtime-dependent manner, and also induced apoptosis of ES cells.Importantly, more apoptotic cells were observed in ES cellscompared with other somatic cells. To understand this phenomenon,we further investigated the expression of HSP70 and pluripotentcell markers. HSP70 expression was more significantlyincreased in somatic cells than in ES cells, and expression levelsof pluripotent cell markers such as Oct4 and Nanog were decreasedin ES cells. These results suggest that higher sensitivityof ES cells to proteotoxic stress may be related with lower capacityof HSP70 expression and decreased pluripotent cellmarker expression, which is essential for the survival of ES cells.[BMB reports 2012; 45(5): 299-304]

ObjectivesHearing loss is the most common sensory disorder in humans and genetic causes are estimated to cause more than 50% of all incidents of congenital hearing loss. To develop an efficient method for a genetic diagnosis of hearing loss, we have developed and validated a genetic hearing loss DNA chip that allows the simultaneous analysis of 7 different mutations in the GJB2, SLC26A4, and the mtDNA 12S rRNA genes in Koreans.MethodsA genotyping microarray, based on the allele-specific primer extension (ASPE) method, was used and preliminary validation was examined from the five patients and five controls that were already known their genotypes by DNA sequencing analysis.ResultsThe cutoff Genotyping index (GI) of genotyping for each mutation was set up and validated to discriminate among the genotypes. The result of the DNA chip assay was identical to those of previous results.ConclusionWe successfully designed the genetic hearing loss DNA chip for the first time in Korea and it would be useful for a clinical genetic diagnosis of hearing loss. Further consideration will be needed in order to examine the accuracy of this DNA chip with much larger patient sample numbers.