Plasma enhanced atomic layer deposition of silicon nitride using magnetized very high frequency plasma.

To obtain high-quality SiNxfilms applicable to an extensive range of processes, such as gate spacers in fin field-effect transistors (FinFETs), the self-aligned quadruple patterning process, etc, a study of plasma with higher plasma density and lower plasma damage is crucial in addition to study on novel precursors for SiNxplasma-enhanced atomic layer deposition (PEALD) processes. In this study, a novel magnetized PEALD process was developed for depositing high-quality SiNxfilms using di(isopropylamino)silane (DIPAS) and magnetized N2plasma at a low substrate temperature of 200 °C. The properties of the deposited SiNxfilms were analyzed and compared with those obtained by the PEALD process using a non-magnetized N2plasma source under the same conditions. The PEALD SiNxfilm, produced using an external magnetic field (ranging from 0 to 100 G) during the plasma exposure step, exhibited a higher growth rate (∼1 Å/cycle) due to the increased plasma density. Additionally, it showed lower surface roughness, higher film density, and enhanced wet etch resistance compared to films deposited using the PEALD process with non-magnetized plasmas. This improvement can be attributed to the higher ion flux and lower ion energy of the magnetized plasma. The electrical characteristics, such as interface trap density and breakdown voltage, were also enhanced when the magnetized plasma was used for the PEALD process. Furthermore, when SiNxfilms were deposited on high-aspect-ratio (30:1) trench patterns using the magnetized PEALD process, an improved step coverage of over 98% was achieved, in contrast to the conformality of SiNxdeposited using non-magnetized plasma. This enhancement is possibly a result of deeper radical penetration enabled by the magnetized plasma.

Sol-Gel-Processed Y2O3 Multilevel Resistive Random-Access Memory Cells for Neural Networks.

Yttrium oxide (Y2O3) resistive random-access memory (RRAM) devices were fabricated using the sol-gel process on indium tin oxide/glass substrates. These devices exhibited conventional bipolar RRAM characteristics without requiring a high-voltage forming process. The effect of current compliance on the Y2O3 RRAM devices was investigated, and the results revealed that the resistance values gradually decreased with increasing set current compliance values. By regulating these values, the formation of pure Ag conductive filament could be restricted. The dominant oxygen ion diffusion and migration within Y2O3 leads to the formation of oxygen vacancies and Ag metal-mixed conductive filaments between the two electrodes. The filament composition changes from pure Ag metal to Ag metal mixed with oxygen vacancies, which is crucial for realizing multilevel cell (MLC) switching. Consequently, intermediate resistance values were obtained, which were suitable for MLC switching. The fabricated Y2O3 RRAM devices could function as a MLC with a capacity of two bits in one cell, utilizing three low-resistance states and one common high-resistance state. The potential of the Y2O3 RRAM devices for neural networks was further explored through numerical simulations. Hardware neural networks based on the Y2O3 RRAM devices demonstrated effective digit image classification with a high accuracy rate of approximately 88%, comparable to the ideal software-based classification (~92%). This indicates that the proposed RRAM can be utilized as a memory component in practical neuromorphic systems.

Sol-Gel-Processed Y2O3-Al2O3 Mixed Oxide-Based Resistive Random-Access-Memory Devices.

Herein, sol-gel-processed Y2O3-Al2O3 mixed oxide-based resistive random-access-memory (RRAM) devices with different proportions of the involved Y2O3 and Al2O3 precursors were fabricated on indium tin oxide/glass substrates. The corresponding structural, chemical, and electrical properties were investigated. The fabricated devices exhibited conventional bipolar RRAM characteristics without requiring a high-voltage forming process. With an increase in the percentage of Al2O3 precursor above 50 mol%, the crystallinity reduced, with the amorphous phase increasing owing to internal stress. Moreover, with increasing Al2O3 percentage, the lattice oxygen percentage increased and the oxygen vacancy percentage decreased. A 50% Y2O3-50% Al2O3 mixed oxide-based RRAM device exhibited the maximum high-resistance-state/low-resistance-state (HRS/LRS) ratio, as required for a large readout margin and array size. Additionally, this device demonstrated good endurance characteristics, maintaining stability for approximately 100 cycles with a high HRS/LRS ratio (>104). The HRS and LRS resistances were also retained up to 104 s without considerable degradation.

Physical Therapy Assessment Tool Threshold Values to Identify Sarcopenia and Locomotive Syndrome in the Elderly.

This study aimed to evaluate sarcopenia and locomotive syndrome in Korean elderly patients, analyze the closely related factors, and determine the threshold for distinguishing participants with sarcopenia, locomotive syndrome, and non-disease. To this end, we enrolled 210 subjects aged 65 years or more and classified them into the sarcopenia (n = 36) and locomotive syndrome (n = 164) groups; a control group was also included (n = 10). We evaluated the characteristics of these patients using the Timed Up and Go (TUG) test and Berg Balance Scale (BBS) and performed statistical analysis. Our findings showed statistically significant differences between the groups, leading to the derivation of a significant threshold value. The threshold value of the TUG test between the control and locomotive syndrome groups was 9.47 s; the threshold value of the BBS was 54 points, respectively. The threshold value of the TUG test between the locomotive syndrome and sarcopenia groups was 10.27 s, and the threshold value of the BBS was 50 points, respectively. These findings suggest that sarcopenia is closely related to locomotive syndrome, and that sarcopenia and locomotive syndrome can be identified using a physical therapy diagnostic evaluation tool.

Plasma Enhanced Atomic Layer Deposition of Silicon Nitride for Two Different Aminosilane Precursors Using Very High Frequency (162 MHz) Plasma Source.

Plasma enhanced atomic layer deposition (PEALD) of silicon nitride (SiNx) using very high frequency (VHF, 162 MHz) plasma source was investigated at the process temperatures of 100, 200, and 300 °C. Two aminosilane precursors having different numbers of amino ligands, bis(tert-butylamino)silane (BTBAS) and di(sec-butylamino)silane (DSBAS), were used as Si precursors. A comparative study was also conducted to verify the effect of the number of amino ligands on the properties of SiNx film. At all process temperatures, DSBAS, having one amino ligand, performed better than BTBAS in various aspects. SiNx films deposited using DSBAS had lower surface roughness, higher film density, lower wet etch rate, improved electrical characteristics, and higher growth rate than those deposited using BTBAS. With the combination of a VHF plasma source and DSBAS with one amino ligand, the SiNx films grown at 300 °C exhibited low wet etch rates (≤2 nm/min) in a dilute HF solution (100:1 of deionized water:HF) as well as low C content below the XPS detection limit. Also, excellent step coverage close to 100% on high aspect ratio (30:1) trench structures was obtained by using VHF plasma, which could provide sufficient flux of plasma species inside the trenches in conjunction with DSBAS having fewer amino ligands than BTBAS.

Relationships of Antidepressant Medication With Its Various Factors Including Nitrogen Dioxides Seasonality: Machine Learning Analysis Using National Health Insurance Data.

OBJECTIVE: This study employs machine learning and population-based data to examine major factors of antidepressant medication including nitrogen dioxides (NO2) seasonality. METHODS: Retrospective cohort data came from Korea National Health Insurance Service claims data for 43,251 participants with the age of 15-79 years, residence in the same districts of Seoul and no history of antidepressant medication during 2002-2012. The dependent variable was antidepressant-free months during 2013-2015 and the 103 independent variables for 2012 or 2015 were considered, e.g., particulate matter less than 2.5 micrometer in diameter (PM2.5), PM10, NO2, ozone (O3), sulphur dioxide (SO2) and carbon monoxide (CO) in each of 12 months in 2015. RESULTS: It was found that the Cox hazard ratios of NO2 were statistically significant and registered values larger than 10 for every three months: March, June-July, October, and December. Based on random forest variable importance and Cox hazard ratios in brackets, indeed, the top 20 factors of antidepressant medication included age (0.0041 [1.69-2.25]), migraine and sleep disorder (0.0029 [1.82]), liver disease (0.0017 [1.33-1.34]), exercise (0.0014), thyroid disease (0.0013), cardiovascular disease (0.0013 [1.20]), asthma (0.0008 [1.19-1.20]), September NO2 (0.0008 [0.01]), alcohol consumption (0.0008 [1.31-1.32]), gender - woman (0.0007 [1.80-1.81]), July NO2 (0.0007 [14.93]), July PM10 (0.0007), the proportion of the married (0.0005), January PM2.5 (0.0004), September PM2.5 (0.0004), chronic obstructive pulmonary disease (0.0004), economic satisfaction (0.0004), January PM10 (0.0003), residents in welfare facilities per 1,000 (0.0003 [0.97]), and October NO2 (0.0003). CONCLUSION: Antidepressant medication has strong associations with neighborhood conditions including NO2 seasonality and welfare support.

Blood Transfusion, All-Cause Mortality and Hospitalization Period in COVID-19 Patients: Machine Learning Analysis of National Health Insurance Claims Data.

This study presents the most comprehensive machine-learning analysis for the predictors of blood transfusion, all-cause mortality, and hospitalization period in COVID-19 patients. Data came from Korea National Health Insurance claims data with 7943 COVID-19 patients diagnosed during November 2019−May 2020. The dependent variables were all-cause mortality and the hospitalization period, and their 28 independent variables were considered. Random forest variable importance (GINI) was introduced for identifying the main factors of the dependent variables and evaluating their associations with these predictors, including blood transfusion. Based on the results of this study, blood transfusion had a positive association with all-cause mortality. The proportions of red blood cell, platelet, fresh frozen plasma, and cryoprecipitate transfusions were significantly higher in those with death than in those without death (p-values < 0.01). Likewise, the top ten factors of all-cause mortality based on random forest variable importance were the Charlson Comorbidity Index (53.54), age (45.68), socioeconomic status (45.65), red blood cell transfusion (27.08), dementia (19.27), antiplatelet (16.81), gender (14.60), diabetes mellitus (13.00), liver disease (11.19) and platelet transfusion (10.11). The top ten predictors of the hospitalization period were the Charlson Comorbidity Index, socioeconomic status, dementia, age, gender, hemiplegia, antiplatelet, diabetes mellitus, liver disease, and cardiovascular disease. In conclusion, comorbidity, red blood cell transfusion, and platelet transfusion were the major factors of all-cause mortality based on machine learning analysis. The effective management of these predictors is needed in COVID-19 patients.

Investigation of the effect of SRSF9 overexpression on HIV-1 production.

Serine-arginine-rich splicing factors (SRSFs) are members of RNA processing proteins in the serine-arginine-rich (SR) family that could regulate the alternative splicing of the human immunodeficiency virus-1 (HIV-1). Whether SRSF9 has any effect on HIV-1 regulation requires elucidation. Here, we report for the first time the effects and mechanisms of SRSF9 on HIV-1 regulation. The overexpression of SRSF9 inhibits viral production and infectivity in both HEK293T and MT-4 cells. Deletion analysis of SRSF9 determined that the RNA regulation motif domain of SRSF9 is important for anti-HIV-1 effects. Furthermore, overexpression of SRSF9 increases multiple spliced forms of viral mRNA, such as Vpr mRNA. These data suggest that SRSF9 overexpression inhibits HIV-1 production by inducing the imbalanced HIV-1 mRNA splicing that could be exploited further for a novel HIV-1 therapeutic molecule. [BMB Reports 2022; 55(12): 639-644].

Improved Environment Stability of Y2O3 RRAM Devices with Au Passivated Ag Top Electrodes.

In this study, we fabricated sol-gel-processed Y2O3-based resistive random-access memory (RRAM) devices. The fabricated Y2O3 RRAM devices exhibited conventional bipolar RRAM device characteristics and did not require the forming process. The long-term stability of the RRAM devices was investigated. The Y2O3 RRAM devices with a 20 nm thick Ag top electrode showed an increase in the low resistance state (LRS) and high resistance state (HRS) and a decrease in the HRS/LRS ratio after 30 days owing to oxidation and corrosion of the Ag electrodes. However, Y2O3 RRAM devices with inert Au-passivated Ag electrodes showed a constant RRAM device performance after 30 days. The 150 nm-thick Au passivation layer successfully suppressed the oxidation and corrosion of the Ag electrode by minimizing the chance of contact between water or oxygen molecules and Ag electrodes. The Au/Ag/Y2O3/ITO RRAM devices exhibited more than 300 switching cycles with a decent resistive window (>103). They maintained constant LRS and HRS resistances for up to 104 s, without significant degradation of nonvolatile memory properties for 30 days while stored in air.

Identification of Novel Nucleocapsid Chimeric Proteins Inhibiting HIV-1 Replication.

The positive transcription elongation factor b (P-TEFb) is an essential factor that induces transcription elongation and is also negatively regulated by the cellular factor HEXIM1. Previously, the chimeric protein HEXIM1-Tat (HT) was demonstrated to inhibit human immunodeficiency virus-1 (HIV)-1 transcription. In this study, we attempted to develop an improved antiviral protein that specifically binds viral RNA (vRNA) by fusing HT to HIV-1 nucleocapsid (NC). Thus, we synthesized NC-HEXIM1-Tat (NHT) and HEXIM1-Tat-NC (HTN). NHT and HTN inhibited virus proliferation more effectively than HT, and they did not attenuate the function of HT. Notably, NHT and HTN inhibited the infectivity of the progeny virus, whereas HT had no such effect. NHT and HTN selectively and effectively interacted with vRNA and inhibited the proper packaging of the HIV-1 genome. Taken together, our results illustrated that the novel NC-fused chimeric proteins NHT and HTN display novel mechanisms of anti-HIV effects by inhibiting both HIV-1 transcription and packaging.

An analysis study of sarcopenia and locomotive syndrome in the old people using evaluation tool.

This study was conducted to analyze the relationship between locomotive syndrome and sarcopenia in the old people using a functional evaluation tool. In this study, 237 Korean old people selected from the Miraeseum Seongnam Senior Complex and the Misa Riverside Welfare Center were diagnosed with the two diseases and the Berg balance scale was performed to confirm the deterioration of dynamic balance sensory. Through the diagnostic evaluation of the two diseases, the locomotive group (n=180) and the sarcopenia group (n=34) were classified and statistically analyzed. As a result of the study, a significant difference in dynamic balance sensory between the two diseases was confirmed, and a significant negative correlation was confirmed with 25-question geriatric locomotive function scale and grip strength among the diagnostic evaluation items of the two diseases. These results suggest that gradual deterioration of locomotive syndrome and sarcopenia occurs in the deterioration of physical performance in the old people, suggesting that the evaluation of locomotive syndrome can be used as a screening test for sarcopenia.

COVID-19 and vaccination during pregnancy: a systematic analysis using Korea National Health Insurance claims data.

OBJECTIVE: This study systematically analyzed coronavirus disease 2019 (COVID-19) and vaccination details during pregnancy by using the national health insurance claims data. METHODS: Population-based retrospective cohort data of 12,399,065 women aged 15-49 years were obtained from the Korea National Health Insurance Service claims database between 2019 and 2021. Univariate analysis was performed to compare the obstetric outcomes of pregnant women (ICD-10 O00-O94) and their newborns (ICD-10 P00-P96) with and without COVID-19. Univariate analysis was also performed to compare the age and obstetric outcomes of pregnant women receiving different types of vaccines. RESULTS: The percentage of pregnant women with COVID-19 during pregnancy was 0.11%. Some obstetric outcomes of pregnant women with COVID-19, including the rates of preterm birth or cesarean delivery, were significantly better than those of pregnant women without COVID-19. The rate of miscarriage was higher in pregnant women with COVID-19 than without COVID-19. However, the outcomes of newborns of women with and without COVID-19 were not significantly different. Regarding vaccination type, obstetric outcomes of pregnant women appeared to be worse with the viral vector vaccine than with the mRNA vaccine. CONCLUSION: To the best of our knowledge, this is the first study to systematically analyze COVID-19 and vaccination details during pregnancy using the national health insurance claims data in Korea. The obstetric outcomes in pregnant women with and without COVID-19 and their newborns were similar.

Association of Preterm Birth with Inflammatory Bowel Disease and Salivary Gland Disease: Machine Learning Analysis Using National Health Insurance Data.

This study employs machine learning and population data for testing the associations of preterm birth with inflammatory bowel disease (IBD), salivary gland disease, socioeconomic status and medication history, including proton pump inhibitors. The source of population-based retrospective cohort data was the Korea National Health Insurance Service claims data for all women aged 25-40 years and who experience their first childbirths as singleton pregnancy during 2015 to 2017 (402,092 women). These participants were divided into the Ulcerative Colitis (UC) Group (1782 women), the Crohn Group (1954 women) and the Non-IBD Group (398,219 women). For each group, the dependent variable was preterm birth during 2015-2017, and 51 independent variables were included. Random forest variable importance was employed for investigating the main factors of preterm birth and testing its associations with salivary gland disease, socioeconomic status and medication history for each group. The proportion of preterm birth was higher for the UC Group and the Non-IBD Group than for the Crohn Group: 7.86%, 7.17% vs. 6.76%. Based on random forest variable importance, salivary gland disease was a top 10 determinant for the prediction of preterm birth for the UC Group, but this was not the case for the Crohn Group or the Non-IBD Group. The top 5 variables of preterm birth for the UC Group during 2015-2017 were socioeconomic status (8.58), age (8.00), proton pump inhibitors (2.35), progesterone (2.13) and salivary gland disease in 2014 (1.72). In conclusion, preterm birth has strong associations with ulcerative colitis, salivary gland disease, socioeconomic status and medication history including proton pump inhibitors.

Association of preterm birth with medications: machine learning analysis using national health insurance data.

PURPOSE: To use machine learning and population data for testing the associations of preterm birth with socioeconomic status, gastroesophageal reflux disease (GERD) and medication history including proton pump inhibitors, sleeping pills and antidepressants. METHODS: Population-based retrospective cohort data came from Korea National Health Insurance Service claims data for all women who aged 25-40 years and gave births for the first time as singleton pregnancy during 2015-2017 (405,586 women). The dependent variable was preterm birth during 2015-2017 and 65 independent variables were included (demographic/socioeconomic determinants, disease information, medication history, obstetric information). Random forest variable importance (outcome measure) was used for identifying major determinants of preterm birth and testing its associations with socioeconomic status, GERD and medication history including proton pump inhibitors, sleeping pills and antidepressants. RESULTS: Based on random forest variable importance, major determinants of preterm birth during 2015-2017 were socioeconomic status (645.34), age (556.86), proton pump inhibitors (107.61), GERD for the years 2014, 2012 and 2013 (106.78, 105.87 and 104.96), sleeping pills (97.23), GERD for the years 2010, 2011 and 2009 (95.56, 94.84 and 93.81), and antidepressants (90.13). CONCLUSION: Preterm birth has strong associations with low socioeconomic status, GERD and medication history such as proton pump inhibitors, sleeping pills and antidepressants. For preventing preterm birth, appropriate medication would be needed alongside preventive measures for GERD and the promotion of socioeconomic status for pregnant women.

Metamaterial-Integrated High-Gain Rectenna for RF Sensing and Energy Harvesting Applications.

This paper presents a metamaterial (MTM)-integrated high-gain rectenna for RF sensing and energy harvesting applications that operates at 2.45 GHz, an industry, science, medicine (ISM) band. The novel MTM superstrate approach with a three-layered integration method is firstly introduced for rectenna applications. The integrated rectenna consists of three layers, where the first layer is an MTM superstrate consisting of four-by-four MTM unit cell arrays, the second layer a patch antenna, and the third layer a rectifier circuit. By integrating the MTM superstrate on top of the patch antenna, the gain of the antenna is enhanced, owing to its beam focusing capability of the MTM superstrate. This induces the increase of the captured RF power at the rectifier input, resulting in high-output DC power and high entire end-to-end efficiency. A parametric analysis is performed in order to optimize the near-zero property of the MTM unit cell. In addition, the effects of the number of MTM unit cells on the performance of the integrated rectenna are studied. A prototype MTM-integrated rectenna, which is designed on an RO5880 substrate, is fabricated and characterized. The measured gain of the MTM-integrated rectenna is 11.87 dB. It shows a gain improvement of 6.12 dB compared to a counterpart patch antenna without an MTM superstrate and a maximum RF-DC conversion efficiency of 78.9% at an input RF power of 9 dBm. This results in the improvement of the RF-DC efficiency from 39.2% to 78.9% and the increase of the output DC power from 0.7 mW to 6.27 mW (a factor of 8.96 improvements). The demonstrated MTM-integrated rectenna has shown outstanding performance compared to other previously reported work. We emphasize that the demonstrated MTM-integrated rectenna has a low design complexity compared with other work, as the MTM superstrate layer is integrated on top of the simple patch antenna and rectifier circuit. In addition, the number of MTM units can be determined depending on applications. It is highly envisioned that the demonstrated MTM-integrated rectenna will provide new possibilities for practical energy harvesting applications with improved antenna gain and efficiency in various IoT environments.

Investigation of the effect of Staufen1 overexpression on the HIV-1 virus production.

In this study, we investigated how Staufen1 influences the HIV-1 production. The overexpression of Staufen1 increased virus production without any negative affect on the viral infectivity. This increase was not caused by transcriptional activation; but by influencing post-transcriptional steps. Using multiple Gag protein derivatives, we confirmed that the zinc-finger domains of the HIV-1 nucleocapsid (NC) are important for its interaction with Staufen1. We also found that Staufen1 colocalized in stress granules with the mature form of the HIV-1 NC protein. [BMB Reports 2021; 54(11): 551-556].

Association of Preterm Birth with Depression and Particulate Matter: Machine Learning Analysis Using National Health Insurance Data.

This study uses machine learning and population data to analyze major determinants of preterm birth including depression and particulate matter. Retrospective cohort data came from Korea National Health Insurance Service claims data for 405,586 women who were aged 25-40 years and gave births for the first time after a singleton pregnancy during 2015-2017. The dependent variable was preterm birth during 2015-2017 and 90 independent variables were included (demographic/socioeconomic information, particulate matter, disease information, medication history, obstetric information). Random forest variable importance was used to identify major determinants of preterm birth including depression and particulate matter. Based on random forest variable importance, the top 40 determinants of preterm birth during 2015-2017 included socioeconomic status, age, proton pump inhibitor, benzodiazepine, tricyclic antidepressant, sleeping pills, progesterone, gastroesophageal reflux disease (GERD) for the years 2002-2014, particulate matter for the months January-December 2014, region, myoma uteri, diabetes for the years 2013-2014 and depression for the years 2011-2014. In conclusion, preterm birth has strong associations with depression and particulate matter. What is really needed for effective prenatal care is strong intervention for particulate matters together with active counseling and medication for common depressive symptoms (neglected by pregnant women).

Rapid discriminative detection of dengue viruses via loop mediated isothermal amplification.

Dengue virus (DENV) is one of the life-threatening viruses to the human. In this study, we have designed specific novel primers for rapid discriminative detection of DENV-1, DENV-2, and DENV-4 by real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction. The effect of parameters such as reaction temperature and magnesium sulfate was investigated on the RT-LAMP reaction for detection of DENV RNA. Under the optimal conditions, this method is able to differentiate and to detect DENV within 25 min, exhibiting detection limit of 3.5 copies/µL. Importantly, the novel specific primers-based RT-LAMP assay did not react with other viruses, suggesting the selectivity of the method towards DENV RNA. The RT-LAMP reaction products are easily visualized with naked-eye when irradiated them under UV light at 365 nm. Amplification products could be visualized directly for color changes. This method provides a facile, and accurate molecular amplication technique for the rapid discriminative detection of dengue viruses. The RT-LAMP platform can be used as a promissing diagnostic tool for discriminative detection of DENV without aid of complicated protocols or sophisticated equipment.

Sex Differences in Cancer: Epidemiology, Genetics and Therapy.

The incidence and mortality of various cancers are associated with sex-specific disparities. Sex differences in cancer epidemiology are one of the most significant findings. Men are more prone to die from cancer, particularly hematological malignancies. Sex difference in cancer incidence is attributed to regulation at the genetic/molecular level and sex hormones such as estrogen. At the genetic/molecular level, gene polymorphism and altered enzymes involving drug metabolism generate differences in cancer incidence between men and women. Sex hormones modulate gene expression in various cancers. Genetic or hormonal differences between men and women determine the effect of chemotherapy. Until today, animal studies and clinical trials investigating chemotherapy showed sex imbalance. Chemotherapy has been used without consideration of sex differences, resulting in disparity of efficacy and toxicity between sexes. Based on accumulating evidence supporting sex differences in chemotherapy, all clinical trials in cancer must incorporate sex differences for a better understanding of biological differences between men and women. In the present review, we summarized the sex differences in (1) incidence and mortality of cancer, (2) genetic and molecular basis of cancer, (3) sex hormones in cancer incidence, and (4) efficacy and toxicity of chemotherapy. This review provides useful information for sex-based chemotherapy and development of personalized therapeutic strategies against cancer.

Age- and gender-specific reference intervals of TSH and free T4 in an iodine-replete area: Data from Korean National Health and Nutrition Examination Survey IV (2013-2015).

BACKGROUND: Establishment of the reference interval of thyroid-stimulating hormone (TSH) is critical in the diagnosis of thyroid dysfunction and is affected by age, gender, iodine nutrition, and ethnicity. The aim of this study was to determine the reference intervals of TSH and free thyroxin (FT4) from a large, nationwide data of Korea where iodine intake is more than adequate. METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey VI that measured serum TSH, FT4, and thyroid peroxidase antibody from 7,061 individuals (urinary iodine measurement in 6,565). Age- and gender-specific reference intervals were established from 95% confidence limits from the 2.5 to 97.5 percentile of TSH (log-transformed) and FT4 in reference populations. RESULTS: The geometric mean of TSH was 2.16 ± 0.01 mIU/L, with the lowest value found in the middle aged group (2.04 ± 0.02 mIU/L) and higher values noted in age groups of 10-19 and over 70 years (2.38 ± 0.02 and 2.32 ± 0.07 mIU/L, respectively). The association of TSH and age was U-shaped. The overall reference interval of TSH was 0.59-7.03 mIU/L. Mean FT4 was 1.25 ± 0.003 ng/dL (16.09 ± 0.039 pmol/L), and it showed a small but continuous decrease after 20 years of age (P < 0.001). There was a significant positive correlation between TSH and urine iodine concentration (r = 0.154, P < 0.001). CONCLUSIONS: The reference interval of TSH in Korea, where iodine intake is above the requirement, was 0.59-7.03 mIU/L and showed U-shaped change with age, which was a similar pattern to iodine intake. The reference interval of FT4 was 0.92-1.60 ng/dL. The geometric mean and upper limit of TSH were higher than those of Western populations, reflecting the paramount importance of iodine intake on thyroid function.