Phase 1/2 trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate to severe atopic dermatitis.

BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 106 and 5 × 105 cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 105 cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.

Risk of Head and Neck Cancer in Patients with Psoriasis: A Nationwide Population-based Study.

An association between psoriasis and cancer risk has been suggested in prior studies, but few have focused on head and neck cancers. Using the Korean National Health Insurance Service database, the relevance between psoriasis and head and neck cancer risks was investigated in a cross-sectional study of 3,869,264 individuals over 20 years of age, who received general health examination in 2009 and were followed until 2020. Head and neck cancer incidence rates were compared between individuals with and without psoriasis, and contributing factors were analysed. The head and neck cancer risk was significantly increased in the psoriasis group compared with the non-psoriasis group (hazard ratio [HR] 1.36; 95% confidence interval [CI] 1.07-1.74; p = 0.01) after adjusting for age, sex, body mass index, income, smoking, alcohol, exercise, diabetes mellitus, hypertension and dyslipidaemia. The risk was especially elevated for nasopharyngeal (HR 2.04; 95% CI 1.12-3.70; p = 0.02) and salivary gland cancer (HR 1.96; 95% CI 1.08-3.56; p = 0.03). Alcohol consumption significantly influenced the risk, particularly for oropharyngeal and oral cavity cancer. Our study provides insights into the potential risks of head and neck cancer in patients with psoriasis, which could aid in refining patient management strategies.

Aurantiacibacter sediminis sp. nov., a marine bacterium isolated from a tidal flat.

A yellow-coloured bacterium, designated as strain JGD-13T, was isolated from a tidal flat in the Republic of Korea. Cells were Gram-stain-negative, aerobic, non-flagellated and rod-shaped. Growth was observed at 4-42 °C (optimum, 30 °C), at pH 6.0-12.0 (pH 7.0-8.0) and at 1-7 % (w/v) NaCl concentration (3 %). The 16S rRNA gene sequence analysis indicated that strain JGD-13T was closely related to Aurantiacibacter gangjinensis K7-2T with a sequence similarity of 98.2 %, followed by Aurantiacibacter aquimixticola JSSK-14T (98.1 %), Aurantiacibacter atlanticus s21-N3T (97.6 %), Aurantiacibacter zhengii V18T (97.6 %) and Aurantiacibacter luteus KA37T (97.5 %). The average nucleotide identity and digital DNA-DNA hybridization values with related strains were 70.3-76.2 % and 18.5-20.3 %. The genomic DNA G+C content was 60.2 mol%. Phylogenetic analysis using the maximum-likelihood method showed that strain JGD-13T formed a clade with A. aquimixticola JSSK-14T and A. gangjinensis K7-2T. The major fatty acids were summed feature 8 (39.7 %) and C17 : 1 ω6c (14.4 %). The predominant respiratory quinone was ubiquinone-10. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one sphingoglycolipid and three unidentified lipids. On the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, strain JGD-13T represents a novel species within the genus Aurantiacibacter, for which the name Aurantiacibacter sediminis JGD-13Tsp. nov. is proposed. The type strain is JGD-13T (=KCTC 72892T=KACC 21676T=JCM 33995T).

Concise syntheses and anti-inflammatory effects of isocorniculatolide B and corniculatolide B and C.

The first total syntheses of isocorniculatolide B, corniculatolide B, and corniculatolide C, consisting of isomeric corniculatolide skeletons, have been accomplished in a divergent manner. The key features of the synthesis involve the construction of diaryl ether linkages by nucleophilic aromatic substitution, installation of a C14-substituted alkyl side chain via a sequence of Baeyer-Villiger reaction and Claisen rearrangement, and efficient construction of corniculatolide and isocorniculatolide frameworks, including 17-membered (exterior) macrolactone skeletons from a versatile diaryl ether intermediate by Mitsunobu macrolactonization. Moreover, we prepared the structural congeners of isomeric corniculatolides via diverted total synthesis approach including desmethyl analogues and related dimeric macrolides. The anti-inflammatory activities of the synthesized natural products, analogues and synthetic intermediates were also investigated. In particular, corniculatolide B significantly inhibited the protein expression of COX-2 and the mRNA expressions of TNF-α, IL-1ß and IL-6 by inhibiting of NF-κB signaling in intestinal epithelial cells induced by lipopolysaccharide treatment. It also significantly inhibited the promoter activity and the phosphorylation of subunits p50 and p65 of NF-κB to the same extent as Bay 11-7082, a potent IκB kinase inhibitor. These results suggest that corniculatolide B might have therapeutic potential in inflammatory bowel disease via NF-κB signaling pathway.

Novosphingobium aureum sp. nov., a marine bacterium isolated from salt flat sediment.

A Gram-stain-negative, aerobic, pale yellow-coloured, rod-shaped marine bacterium designated strain YJ-S2-02T was isolated from salt flat sediment sampled in Yongyu-do, Republic of Korea. Strain YJ-S2-02T grew at pH 6.0-9.0 (optimum, pH 7.0), 10-40 °C (optimum, 30 °C) and with optimum 1 % (w/v) NaCl. The 16S rRNA gene sequence analysis indicated that strain YJ-S2-02T was closely related to Novosphingobium naphthalenivorans NBRC 102051T (97.8 %) followed by Novosphingobium mathurense SM117T (97.5 %), Novosphingobium indicum H25T (97.3 %), Novosphingobium pentaromativorans US6-1T (96.8 %), Novosphingobium fontis STM-14T (96.6 %), Novosphingobium endophyticum EGI60015T (96.5 %), Novosphingobium naphthae D39T (96.5 %) and Novosphingobium malaysiense MUSC 273T (95.9 %). The average nucleotide identity and estimated DNA-DNA hybridization values between YJ-S2-02T and related type strains were 77.0-77.9 % and 19.1-24.0 %. Strain YJ-S2-02T was characterized as having Q-10 as the predominant respiratory quinone and the principal fatty acids (>10 %) were summed feature 8 (C18 : 1 ω6c/ω7c, 20.7 %), C18 : 3 ω6c (16.3 %) and C17 : 1 ω6c (11.8 %). The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids and two unidentified lipids. The DNA G+C content of strain YJ-S2-02T was 65.6 mol%. On the basis of the polyphasic taxonomic evidence presented in this study, YJ-S2-02T should be classified as representing a novel species within the genus Novosphingobium, for which name Novosphingobium aureum is proposed, with the type strain YJ-S2-02T (=KACC 21677T =KCTC 72891T=JCM 33996T).

Jazf1 acts as a regulator of insulin-producing ß-cell differentiation in induced pluripotent stem cells and glucose homeostasis in mice.

Genetic susceptibility of type 2 diabetes and Juxtaposed with another zinc finger protein 1 (Jazf1) has been reported; however, the precise role of Jazf1 in metabolic processes remains elusive. In this study, using Jazf1-knockout (KO)-induced pluripotent stem cells (iPSC), pancreatic beta cell line MIN6 cells, and Jazf-1 heterozygous KO (Jazf1+/- ) mice, the effect of Jazf1 on gradual differentiation was investigated. We checked the alterations of the genes related with ß-cell specification, maturation, and insulin release against glucose treatment by the gain and loss of the Jazf1 gene in the MIN6 cells. Because undifferentiated Jazf1-KO iPSC were not significantly different from wild-type (WT) iPSC, the size and endoderm marker expression after embryoid body (EB) and teratoma formation were investigated. Compared to EB and teratomas formed with WT iPSC, the EB and teratomas from with Jazf1-KO iPSC were smaller, and in teratomas, the expression of proliferation markers was reduced. Moreover, the expression of the gene sets for ß-cell differentiation and the levels of insulin and C-peptide secreted by insulin precursor cells were notably reduced in ß-cells differentiated from Jazf1-KO iPSC compared with those differentiated from WT iPSC. A comparison of Jazf1+/- and WT mice showed that Jazf1+/- mice had lower levels of serum insulin, pancreatic insulin expression, and decreased pancreatic ß-cell size, which resulted in defects in the glucose homeostasis. These findings suggest that Jazf1 plays a pivotal role in the differentiation of ß-cells and glucose homeostasis.

The prevalence of and factors associated with depressive symptoms in the Korean adults: the 2014 and 2016 Korea National Health and Nutrition Examination Survey.

PURPOSE: This study was performed to investigate the prevalence of and factors associated with depressive symptoms in the Korean adult population. METHODS: 10,710 participants in the 2014 and 2016 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed in this study. Assessment of depressive symptoms was performed using the self-administered nine-item Patient Health Questionnaire (PHQ-9). RESULTS: The weighted prevalence of clinically relevant depression (PHQ-9 score ≥ 10) in the Korean adult population was 6.1% [5.5-6.8%]. Female sex, adults aged 19-29 years, elementary school graduation, living alone were significantly associated with clinically relevant depression. Having a household income ≤ 24th percentile was associated with a 2.26 (CI 1.49-3.45, p < 0.001)-fold higher prevalence of clinically relevant depression compared to having a household income ≥ 75th percentile. Regarding occupation, treating managers and professionals as controls, we found that unemployed individuals (OR 2.36, 95% CI 1.52-3.65, p < 0.001) had an increased risk of clinically relevant depression. Alcohol consumption < 30 g/day was reversely associated with clinically relevant depression (OR 0.75, 95% CI 0.62-0.93, p = 0.007), when abstain from alcohol was treated as control. Current smokers (OR 3.42, 95% CI 2.54-4.60, p < 0.001) and ex-smokers (OR 1.73, 95% CI 1.24-2.42, p = 0.001) had a higher risk of clinically relevant depression than never-smokers. CONCLUSIONS: The estimated prevalence of depressive symptoms in a representative sample of the Korean adult population was 6.1%. This study suggests that younger age, female sex, elementary school graduation, living alone, low household income, current smoking, and being unemployed are associated with depressive symptoms.

Association between serum uric acid and spirometric pulmonary function in Korean adults: The 2016 Korea National Health and Nutrition Examination Survey.

BACKGROUND: A limited number of epidemiological studies have investigated the association between serum uric acid and pulmonary function in the general population. However, the results have been inconclusive. OBJECTIVES: This study was performed to investigate the association between serum uric acid and spirometric pulmonary function in general population. METHODS: Among the 8,150 participants who participated in the 2016 Korea National Health and Nutrition Examination Survey, 2,901 participants were analyzed in this study. Subjects were divided into four groups according to forced vital capacity (FVC)% predicted or forced expiratory volume in 1 second (FEV1) % predicted quartiles. Participants in the lowest quartile of FVC % predicted and FEV1% predicted were compared to those in the remaining quartiles according to age, education level, household income, smoking status, alcohol consumption, aerobic exercise, obesity, hypertension, diabetes, renal impairment, serum uric acid, and hyperuricemia. Multivariable logistic regression analyses were used to calculate the odds ratio (OR) of hyperuricemia for participants in the lowest quartile of FVC% and FEV1 predicted, with above covariates. RESULTS: In women, hyperuricemia was associated with lowest quartile of FVC% predicted (OR 1.71, 95% CI 1.06-2.75, p = 0.027) and FEV1 predicted (OR 1.70, 95% CI 1.06-2.74, p = 0.028) respectively, serving as above confounding variables. In men, hyperuricemia (OR 1.54, 95% CI 1.07-2.22, p = 0.021) was associated with the lowest quartile of FEV1% predicted, not FVC% predicted. According to median age, in women, age ≥ 56 years old with hyperuricemia was associated with lowest quartile of FVC% predicted (OR 1.85, 95% CI 1.04-3.28, p = 0.037) and FEV1% predicted (OR 1.99, 95% CI 1.11-3.75, p = 0.021), respectively. In men, age ≥ 56 years old with hyperuricemia was associated with lowest quartile of FEV1% predicted (OR 1.75, 95% CI 1.05-2.94, p = 0.033), not FCV% predicted. CONCLUSIONS: Hyperuricemia was associated with lowest quartile of FEV1% or FVC% predicted in Korean general population. This correlation between hyperuricemia and low pulmonary function was more pronounced in women and older age.

Muricauda ochracea sp. nov., isolated from a tidal flat in the Republic of Korea.

A yellowish-brown-coloured bacterium, designated strain JGD-17T, was isolated from a tidal flat of Janggu-do, Garorim bay, Taean-gun, Chungcheongbuk-do, Republic of Korea. Cells were Gram-stain-negative, aerobic, non-flagellated and long-rod-shaped. Growth was observed at 20-45 °C (optimum, 25-30 °C), at pH 6.0-10.0 (9.0) and with 1-5 % (w/v) NaCl (1-3 %). Results of 16S rRNA gene sequence analysis indicated that strain JGD-17T was closely related to Muricauda nanhaiensis SM1704T (96.1 %), Muricauda olearia CL-SS4T (95.0 %), Muricauda beolgyonensis BB-My12T (94.9 %), Muricauda marina H19-56T (94.7 %) and Muricauda indica 3PC125-7T (94.5 %). The ranges of values for the average nucleotide identity and digital DNA-DNA hybridization analyses with related strains were 71.3-74.1 % and 16.9-18.2 %. The genomic DNA G+C content was 41.1 mol%. Phylogenetic analysis using the neighbour-joining method showed that strain JGD-17T formed a clade with Muricauda nanhaiensis SM1704T, Muricauda lutaonensis CC-HSB-11T, Muricauda lutea CSW06T and Muricauda pacifica SM027T. The major fatty acids were iso-C15 : 0 (26.9 %), iso-C15 : 1 G (19.5 %) and iso-C17 : 0 3-OH (12.7 %). The predominant respiratory quinone was menaquinone-6. The polar lipids were phosphatidylethanolamine, an unidentified aminolipid, an unidentified phospholipid and two unidentified lipids. On the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, strain JGD-17T represents a novel species within the genus Muricauda, for which the name Muricauda ochracea sp. nov. is proposed. The type strain is JGD-17T (=KCTC 72732T=KACC 21486T=JCM 33817T).

Clinical Factors and Cellular Responses of In Situ Human Alveolar Bone-Derived Mesenchymal Stromal Cells Associated With Early Periimplant Marginal Bone Loss: A Prospective Cohort Pilot Study.

PURPOSE: To investigate clinical factors and cellular responses of in situ human alveolar bone-derived mesenchymal stromal cells involved in early periimplant marginal bone loss. MATERIALS AND METHODS: Thirty-seven completely or partially edentulous patients were enrolled in this study. Periapical radiographs were taken at the time of implant surgery, at 3-month follow-up, and at 1-year follow-up. Univariate analysis and multiple logistic regression were performed to investigate the associations between marginal bone loss and study variables. The mRNA expression levels of 21 bone-remodeling- and tissue-healing-associated genes were analyzed by subgroup. RESULTS: Thirty-one patients with 98 implants were followed. The incidence and mean amount of bone loss were higher for overdentures than for other prosthesis and higher for the maxilla than for the mandible. The bone loss group showed lower mRNA expression levels of runt-related transcription factor-2, bone morphogenetic protein-2, and peroxisome proliferator-activated receptor gamma-2 and higher receptor activator of NKκB ligand/osteoprotegerin (RANKL/OPG) ratio. CONCLUSION: Within the limitations of the study, certain genes involved in bone remodeling (runt-related transcription factor-2 [Runx-2], bone morphogenetic protein-2 [BMP-2], and peroxisome proliferator-activated receptor gamma-2 [PPARγ-2]) and RANKL/OPG are correlated with early periimplant bone loss, with the type of suprastructure and the involved jaw being significant clinical factors.

Association between subclinical thyroid dysfunction and depressive symptoms in the Korean adult population: The 2014 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Clinical hyper and hypothyroidism are associated with a risk for depression. OBJECTIVES: This study was performed to investigate the association between depressive symptoms and subclinical thyroid dysfunction. METHODS: Among the 7,550 subjects who participated in the 2014 Korea National Health and Nutrition Examination Survey, 1,763 participants without overt thyroid disease were included in this study. Serum thyroid stimulating hormone (TSH), serum free thyroxine (fT4), and depressive symptoms were analyzed based on the Patient Health Questionnaire (PHQ9). RESULTS: The percentages of subjects with subclinical hypothyroidism and subclinical hyperthyroidism were 3.3% and 2.6%, respectively. The percentages of subjects with moderate (10-14 points), moderately severe (15-19 points), and severe (≥20 points) depression according to the distribution of PHQ-9 scores were 4.7%, 1.1%, and 0.3%, respectively. TSH, fT4, and the percentage of patients with subclinical hypothyroidism were not significantly associated with PHQ-9 score. However, the percentage of patients with subclinical hyperthyroidism increased significantly with PHQ9 score (P = 0.002). Subjects with subclinical hyperthyroidism had higher PHQ-9 scores than those with normal thyroid function (mean ± standard error [SE], 4.2 ± 0.5 vs. 2.7 ± 0.1 points, P = 0.010). More subjects with subclinical hyperthyroidism had a PHQ9 score ≥ 10 than did those with normal thyroid function (mean ± SE, 17.1 ± 3.5 vs. 5.8 ± 0.6%, P = 0.005). We performed logistic regression analyses for the presence of depressive symptoms, using age, sex, education, household income, alcohol drinking, smoking, diabetes, cerebrovascular disease history, subclinical hypothyroidism, and subclinical hyperthyroidism as variables. Subclinical hyperthyroidism was associated with the presence of clinically relevant depression (PHQ9 score ≥ 10), (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.75-9.31; P = 0.001), and clinically significant depression (PHQ9 score ≥ 15), (OR, 7.05; 95% CI, 1.67-29.67; P = 0.008), respectively. However, subclinical hypothyroidism was not associated with the presence of clinically relevant depression (OR, 1.15; 95% CI, 0.39-3.38; P = 0.800), or clinically significant depression (OR, 3.35; 95% CI, 0.71-15.79; P = 0.127). CONCLUSIONS: We demonstrated that subclinical hyperthyroidism was independently associated with depressive symptoms in the Korean general population using national cross-sectional data.

The prevalence of and factors associated with urinary cotinine-verified smoking in Korean adults: The 2008-2011 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Smoking rate based on self-reporting questionnaire might be underestimated. Cotinine is the principal metabolite of nicotine and is considered an accurate biomarker of exposure to cigarette smoke. OBJECTIVES: This study evaluated the prevalence of and factors associated with urinary cotinine-verified smoking in Korean adults. METHODS: We analyzed data from 12,110 adults in the 2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES), using three threshold levels of urinary cotinine ≥100ng/ml, ≥50ng/ml, and ≥30ng/ml. RESULTS: The weighted prevalence of urinary cotinine levels of ≥100, ≥50, and ≥30 ng/mL in the whole study population was 34.7%, 37.1%, and 41.1%, respectively. Male sex, younger age, elementary school graduation, household income in the ≤24th percentile, service and sales workers and assembly workers, and high-risk alcohol drinking were associated with a higher prevalence of urinary cotinine level of ≥ 50 or 30 ng/mL, after we adjusted for age, sex, education level, number of family members, household income, occupation, and alcohol drinking. Logistic regression analyses were performed using the aforementioned variables as covariates to identify factors independently associated with cotinine-verified smoking. Men had a higher risk than women of having a urinary cotinine level of ≥50 ng/mL (OR 4.67, 95% CI 4.09-5.32, p < 0.001). When subjects ages 19-29 years were used as controls, adults ages 30-39 years had a 1.19-fold (CI 1.02-1.39, p = 0.026) higher risk of having a urinary cotinine level of ≥50 ng/mL. College graduates had a 32% lower risk of having a urinary cotinine level of ≥50 ng/mL than elementary school graduates (p < 0.001). A household income in the 25-49th percentile (OR 0.82, 95% CI 0.69-0.98, p = 0.026), 50-74th percentile (OR 0.64, 95% CI 0.53-0.76, p < 0.001), or ≥75th percentile (OR 0.64, 95% CI 0.53-0.77, p < 0.001) was associated with a lower risk of having a urinary cotinine level of ≥50 ng/mL compared to a household income in the ≤24th percentile. High-risk (OR 2.75, 95% CI 2.37-3.18, p < 0.001) and intermediate-risk (OR 2.04, 95% CI 1.82-2.30, p < 0.001) alcohol drinking were associated with having a urinary cotinine level of ≥50 ng/mL compared to low-risk alcohol drinking. Similar to the results of the logistic regression analyses of urinary cotinine ≥50 ng/mL, male sex, younger age, elementary school education, household income in the ≤24th percentile, and high-risk alcohol drinking were significantly associated with having a urinary cotinine level of ≥30 ng/mL. Service and sales workers (OR 1.22, 95% CI 1.01-1.48, p = 0.041) had a significantly higher risk of having a urinary cotinine level of ≥30 ng/mL. CONCLUSIONS: Based on a threshold urinary cotinine level of 50 ng/mL, the prevalence of cotinine-verified smoking in a representative sample of Korean adults was 37.1% (men 52.7%, women 15.4%). Younger age, male sex, low education level, service and sales workers, low household income, and high-risk alcohol drinking were associated with the risk of smoking.

Influence of growth hormone treatment on radiographic indices of the spine: propensity-matched analysis.

BACKGROUND: We performed this study to investigate the influence of recombinant human growth hormone (rhGH) therapy on radiographic indices of the spine using propensity-matched analysis. METHODS: Patients with idiopathic short stature who had undergone both growth hormone therapy and whole-spine radiographs more than twice prior to 15 years of age were included in the patient group. Other patients who had undergone whole-spine radiographs more than twice prior to the same age during regular checkups for idiopathic scoliosis formed the control group. Propensity-matched analysis was performed to reduce the selection bias. The scoliosis Cobb angle, coronal balance, apical vertebral translation, apical rotation, and pelvic obliquity were measured from the radiographs taken at the periodic follow-ups. The rate of progression of the measurements was adjusted by multiple factors using a linear mixed model with sex as the fixed effect and age and each subject as the random effects. RESULTS: Using a propensity-matched analysis, 48 patients were finally included in both groups. The scoliosis Cobb angle increased by 1.0° (p < 0.001) per year in the patient group, whereas there was no significant annual change in the control group (p = 0.496). Female patients showed a greater scoliosis Cobb angle (1.8°, p = 0.039) compared with male patients. There was no significant difference between the patient and control groups in coronal balance (p = 0.264). Apical vertebral translation per year was increased by 1.2 mm (p < 0.001) in the patient group and 0.5 mm in the control group (p = 0.003). CONCLUSION: Radiographic examination revealed that growth hormone therapy for idiopathic short stature affected the progression of the scoliosis Cobb angle and apical vertebral translation on the coronal plane. Physicians should be aware that annual follow-up is required to evaluate the change in the curvature of the spine in patients undergoing rhGH treatment.

A magnetic resonance image-guided breast needle intervention robot system: overview and design considerations.

PURPOSE: We developed an image-guided intervention robot system that can be operated in a magnetic resonance (MR) imaging gantry. The system incorporates a bendable needle intervention robot for breast cancer patients that overcomes the space limitations of the MR gantry. METHODS: Most breast coil designs for breast MR imaging have side openings to allow manual localization. However, for many intervention procedures, the patient must be removed from the gantry. A robotic manipulation system with integrated image guidance software was developed. Our robotic manipulator was designed to be slim, so as to fit between the patient's side and the MR gantry wall. Only non-magnetic materials were used, and an electromagnetic shield was employed for cables and circuits. The image guidance software was built using open source libraries. In situ feasibility tests were performed in a 3-T MR system. One target point in the breast phantom was chosen by the clinician for each experiment, and our robot moved the needle close to the target point. RESULTS: Without image-guided feedback control, the needle end could not hit the target point (distance = 5 mm) in the first experiment. Using our robotic system, the needle hits the target lesion of the breast phantom at a distance of 2.3 mm from the same target point using image-guided feedback. The second experiment was performed using other target points, and the distance between the final needle end point and the target point was 0.8 mm. CONCLUSIONS: We successfully developed an MR-guided needle intervention robot for breast cancer patients. Further research will allow the expansion of these interventions.

The Association of Resting Heart Rate with the Presence of Diabetes in Korean Adults: The 2010-2013 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Previous epidemiologic studies have shown that elevated resting heart rate (HR) is associated with higher cardiovascular disease (CVD) morbidity and mortality. Although the relationship between elevated HR and CVD is well established, the association between resting HR and diabetes has been relatively understudied, particularly in non-Western populations. OBJECTIVES: We confirmed the association between the presence of type 2 diabetes and resting HR in the Korean adult population using data from the 2010-2013 Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: Among 25,712 adults (≥ 19 years of age) who participated in the 2010-2013 KNHANES, a total of 22,512 subjects completed laboratory examinations and were included in this analysis. The fasting plasma glucose (FPG) level was categorized into the following five groups: normal fasting glucose (NFG) 1 (<90 mg/dL), NFG 2 (90-99 mg/dL), impaired fasting glucose (IFG) 1 (100-110 mg/dL), IFG 2 (111-125 mg/dL), and diabetes (≥ 126 mg/dL). RESULTS: The unadjusted weighted resting HRs were 69.6, 69.4, 69.8, 70.1, and 72.0 beats per minute (bpm) in the NFG 1, NFG 2, IFG 1, IFG 2, and diabetes groups, respectively (P<0.001). We assessed the adjusted weighted resting HR according to the FPG level after adjusting for age, sex, smoking history, high risk alcohol drinking, daily energy intake, waist circumference, serum total cholesterol level, serum triglyceride (TG) level, serum white blood cell (WBC) count, serum hemoglobin (Hb), and the presence of hypertension. The adjusted weighted resting HR significantly increased across the FPG groups (P<0.001). The weighted prevalence rates of diabetes were 6.8% (6.2-7.5%), 7.6% (6.7-8.5%), 8.0% (7.0-9.1%), and 11.8% (10.8-12.7%) in subjects with HR ≤ 64, 65-69, 70-75, and ≥ 76 bpm, respectively (P<0.001), after adjusting for the confounding factors mentioned above. Using resting HR ≤ 64 bpm as the control, resting HR ≥ 76 bpm was correlated with the presence of diabetes (adjusted OR 1.83, 95% CI 1.55-2.16, P<0.001). Each 10 bpm increment of HR increased the risk of the presence of diabetes by 35% (P<0.001). This association of high resting HR with the presence of diabetes was not influenced by the status of blood pressure (BP) medication. CONCLUSION: We demonstrated that higher HR was associated with diabetes in a representative sample of Korean adults. These positive associations were independent of age, sex, current smoking, high risk alcohol drinking, daily energy intake, waist circumference, and the presence of hypertension and other potential confounders. This study suggests that individuals with higher resting HR are at risk of diabetes and that HR might provide an easy and simple surrogate marker for the risk of diabetes.

Association between Alcohol Intake and Hemoglobin A1c in the Korean Adults: The 2011-2013 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Although alcohol consumption is commonly encountered in clinical practice, few studies have investigated the clinical significance of alcohol intake on the use of the hemoglobin A1c (HbA1c) level. OBJECTIVES: This study was performed to investigate the association between alcohol intake and HbA1c level in the general population. METHODS: Among the 24,594 participants who participated in the 2011-2013 Korea National Health and Nutrition Examination Survey (KNHANES), 12,923 participants were analyzed in this study. We excluded diabetic patients currently taking antidiabetes medication. We compared the HbA1c level and proportions of patients with an HbA1c level of ≥5.7%, ≥6.1%, and ≥6.5% according to the fasting plasma glucose (FPG) concentration range and the amount of alcohol intake. The average amounts of daily alcohol intake were categorized into three groups: 0 g/day, <30 g/day, ≥30 g/day. RESULTS: The mean HbA1c level was 5.65%, and the mean FPG concentration was 95.3 mg/dl. The percentages of patients with an HbA1c level of ≥5.7%, ≥6.1%, and ≥6.5% were 42.6%, 13.4%, and 4.5%, respectively. The average amount of alcohol intake was 12.3 g/day. The percentages of subjects with alcohol intake 0, <30, and ≥ 30 g/day were 16.5%, 69.7%, and 13.8%, respectively. There was a significant positive relationship between alcohol intake and FPG concentration (P < 0.001), the prevalence of impaired fasting glucose (P < 0.001), and the prevalence of diabetes (P < 0.001). However, there was no significant relationship between the alcohol intake and HbA1c level. Overall, the adjusted HbA1c levels decreased across alcohol intake (5.70% ± 0.01%, 5.66% ± 0.01%, and 5.55% ± 0.01%) after adjustment for confounding factors such as age, sex, FPG concentration, college graduation, smoking history, presence of hypertension, waist circumference, serum total cholesterol concentration, serum high-density lipoprotein cholesterol concentration, serum triglyceride concentration, presence of anemia, serum white blood cell count, and serum alanine aminotransferase concentration (P < 0.001). The adjusted proportions (%) of patients with an HbA1c level of ≥5.7% (P < 0.001), ≥6.1% (P < 0.001), and ≥6.5% (P < 0.001) showed significant negative trends across alcohol intake after adjustment for confounders. Logistic regression analyses showed that, when using the group that abstained as the control, the group that consumed ≥ 30g/day was negatively associated with the risk of an HbA1c level of ≥5.7% (P < 0.001), ≥6.1% (P < 0.001), and ≥6.5% (P < 0.001), using the above-mentioned variables as covariates. CONCLUSIONS: Higher alcohol intake was associated with lower HbA1c levels, even after adjusting for confounding factors, including the FPG concentration, in this nationally representative sample of Korean adults. These results suggest that excessive drinking shifts the HbA1c level downward, which might complicate use of the HbA1c level for the diagnosis of diabetes or prediabetes.

Association Between Age at Menarche and Risk Factors for Cardiovascular Diseases in Korean Women: The 2010 to 2013 Korea National Health and Nutrition Examination Survey.

Early menarche is strongly associated with adulthood obesity; however, the relationship between age at menarche and cardiovascular disease (CVD) in Korean women remains poorly understood. Here, we investigated the association between early menarche and risk factors for developing CVD during adulthood using a nationwide population database.In total, 12,336 women (weighted n = 17,483,406; weighted age, 45.7 years) who participated in the Korean National Health and Nutrition Examination Survey 2010 to 2013 were included in this study. Participants were scored using the National Cholesterol Education Program Adult Treatment Panel III criteria for metabolic syndrome. Risk of CVD was estimated using the 10-year Framingham Coronary Heart Disease Risk Point Scale (10-year FRS).Early menarche (≤11 years) was reported in 5.2% (weighted n = 917,493) of subjects. The weighted prevalences of metabolic syndrome and ≥20% 10-year FRS were 23.6% [95% confidence interval (95% CI), 22.7-24.6] and 7.7% (7.1-8.3), respectively. Women with early menarche reported a significantly higher body mass index and waist circumference, along with a higher prevalence of hypertension, diabetes, and metabolic syndrome than those with later menarche (≥13 years). Furthermore, the prevalence of women with a ≥10% or ≥20% 10-year FRS was higher in those with early menarche than in other groups after adjusting for age, smoking, education level, and menstruation. Logistic regression analyses controlling for these and other confounding factors revealed odds ratios of 2.29 (95% CI = 1.25-4.19) and 1.78 (0.96-3.30) for ≥10% and ≥20% 10-year FRS in women with early menarche, respectively, compared with those in the latest menarche group (≥17 years).Taken together, this nationwide study revealed that women with early menarche are at increased risks of metabolic syndrome and CVD. Early menarche may therefore represent an important marker for early preventive interventions.

The Prevalence and Associated Factors of Periodontitis According to Fasting Plasma Glucose in the Korean Adults: The 2012-2013 Korea National Health and Nutrition Examination Survey.

Although the relationship between diabetes and periodontitis is well established, the association between periodontitis and prediabetes has been investigated less extensively. Furthermore, there has been little research on the prevalence of periodontitis among individuals with prediabetes and diabetes as well as in the overall population using nationally representative data.Among 12,406 adults (≥19 years' old) who participated in the 2012-2013 Korea National Health and Nutrition Examination Survey, a total of 9977 subjects completed oral and laboratory examinations and were included in this analysis. Periodontitis was defined as a community periodontal index score of ≥ 3 according to the World Health Organization criteria. The fasting plasma glucose level was categorized into the following 5 groups: normal fasting glucose (NFG) 1 (<90  mg/dL), NFG 2 (90-99  mg/dL), impaired fasting glucose (IFG) 1 (100-110  mg/dL), IFG 2 (111-125  mg/dL), and diabetes (≥126  mg/dL).Overall, the weighted prevalence of periodontitis among the Korean adult population was 24.8% (23.3-26.4%) (weight n = 8,455,952/34,086,014). The unadjusted weighted prevalences of periodontitis were 16.7%, 22.8%, 29.6%, 40.7%, and 46.7% in the NFG 1, NFG 2, IFG 1, IFG 2, and diabetes groups, respectively (P < 0.001). After adjusting for age, sex, smoking history, heavy alcohol drinking, college graduation, household income, waist circumference, serum triglyceride level, serum high-density lipoprotein cholesterol level, and the presence of hypertension, the adjusted weighted prevalence of periodontitis increased to 29.7% in the IFG 2 group (P = 0.045) and 32.5% in the diabetes group (P < 0.001), compared with the NFG 1 group (24%). The odds ratios for periodontitis with the above-mentioned variables as covariates were 1.42 (95% confidence interval [CI] 1.14-1.77, P = 0.002) in the diabetes group and 1.33 (95% CI 1.01-1.75, P = 0.044) in the IFG 2 group, respectively, compared with the NFG1 group.In conclusion, a higher range of IFG levels as well as diabetes, were positively associated with chronic periodontitis in a representative sample of Korean adults. This study suggests that individuals with a higher range of IFG levels before diabetes are at risk of periodontitis, and may benefit from dental screening.

Association of Estimated Glomerular Filtration Rate with Hemoglobin Level in Korean Adults: The 2010-2012 Korea National Health and Nutrition Examination Survey.

PURPOSE: Little is known about anemia in patients with early renal dysfunction. We aimed to investigate the association of hemoglobin level and anemia prevalence with estimated glomerular filtration rate (eGFR) decline using a nation-wide representative sample of the adult Korean population. METHODS: In total, 17,373 participants (7,296 men; weighted n = 18,330,187; mean age, 44.2±0.3 years; 9,886 women, weighted n = 18,317,454; mean age, 46.9±0.3 years) were included. eGFR was divided into 5 groups: Group 1, ≥105; Group 2, 90-104; 75-89; Group 4, 60-74; and Group 5, <60 mL/min/1.73m2. RESULTS: The weighted anemia prevalence rates were 2.6% in men and 12.8% in women. In men, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked at an eGFR of 60-89 mL/min/1.73m2 and decreased thereafter at an eGFR of <60 mL/min/1.73m2 (15.19±0.03, 15.35±0.03, 15.53±0.03, 15.52±0.06, and 14.90±0.12 g/dL from Groups 1 to 5) after adjustment for age, college graduation, cancer history, current smoking, waist circumference, serum cholesterol level, serum triglyceride level, and diastolic blood pressure. In women, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked with an eGFR of 75-89 mL/min/1.73m2 and decreased thereafter (12.90±0.03, 13.08±0.02, 13.20±0.04, 13.14±0.05, and 12.47±0.11 g/dL from Groups 1 to 5) after adjustment for menstruation, pregnancy, estrogen replacement, and the above-mentioned variables. In both sexes, the weighted prevalence of anemia with an eGFR of 60-104 mL/min/1.73m2 was significantly lower than that with an eGFR of ≥105 mL/min/1.73m2 (men, 3.2±0.4%, 1.9±0.3%, 1.8±0.3%, 2.0±0.9%, and 18.1±3.1%; women, 14.0±0.8%, 11.2±0.7%, 10.5±1.0%, 13.2±1.6%, and 32.3±3.2% from Groups 1 to 5). CONCLUSIONS: We noted a compensatory increase in the hemoglobin level with a minor decline in kidney function (in the range of eGFR ≥60 mL/min/1.73m2) prior to a marked decrease in hemoglobin level with severe renal dysfunction.