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Pseudomonas aeruginosa is a major pulmonary pathogen causing chronic pulmonary infections in people with cystic fibrosis (CF). The P. aeruginosa filamentous and lysogenic bacteriophage, Pf phage, is abundant in the airways of many people with CF and has been associated with poor outcomes in a cross-sectional cohort study. Previous studies have identified roles for Pf phage in biofilm formation, specifically forming higher-order birefringent, liquid crystals when in contact with other biopolymers in biofilms. Liquid crystalline biofilms are more adherent and viscous than those without liquid crystals. A key feature of biofilms is to enhance bacterial adherence and resist physical clearance. The effect of Pf phage on mucociliary transport is unknown. We found that primary CF and non-CF nasal epithelial cells cultured at air-liquid interface treated with Pf phage exhibit liquid crystalline structures in the overlying mucus. On these cell cultures, Pf phage entangles cilia but does not affect ciliary beat frequency. In both these in vitro cell cultures and in an ex vivo porcine trachea model, introduction of Pf phage decreases mucociliary transport velocity. Pf phage also blocks the rescue of mucociliary transport by CF transmembrane conductance regulator modulators in CF cultures. Thus, Pf phage may contribute to the pathogenesis of P. aeruginosa -associated CF lung disease via induction of liquid crystalline characteristics to airway secretions, leading to impaired mucociliary transport. Targeting Pf phage may be useful in treatment CF as well as other settings of chronic P. aeruginosa infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Calcium and vitamin D deficiencies have been ongoing problems in Koreans due to a lack of food sources of calcium and vitamin D. Postmenopausal women aged 50 to 64 years ( n = 25) were randomly assigned to consume three home meal replacements (HMRs)/week with (treatment) and without (control) eggshell powder and vitamin D for 6 months. Additionally, subjects who agreed to continue the study consumed the same three HMRs/week for an additional 6 months in this randomized double-blind study. We confirmed the high compliance of the study participants by analyzing carotenoids, the bioactive substances of HMRs, in the blood. The treatment group consumed an additional 261 mg/d of calcium and 10.3 μg/d of vitamin D from the HMRs, thus meeting the recommended intakes of calcium and vitamin D for Koreans. As a result of consuming fortified HMRs for 6 months, the decline in femoral neck bone density was significantly reduced in the treatment group ( p = 0.035). This study indicates that inexpensive eggshell powder may be a good source of calcium for populations with low consumption of milk and dairy products. Additionally, functional HMRs fortified with eggshell powder and vitamin D can be a good dietary strategy for bone health.

Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans 1,2 , but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-Cre ERT2 ::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-Cre ERT2 ::CFTR L/L ). By comparing these models with cystic fibrosis ferrets 3,4 , we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-Cre ERT2 ::CFTR L/L ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl - and HCO 3 - . Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets., (© 2023. The Author(s).)

Multiciliated cell loss is a hallmark of airway epithelial remodeling in chronic inflammatory airway diseases including cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease. It disrupts mucociliary clearance, which fuels disease progression. Effective clearance requires an optimal proportion of multiciliated and secretory cells. This is controlled by Notch signaling such that between two adjacent cells the one that activates Notch becomes a secretory cell and the one that avoids Notch activation becomes a multiciliated cell. Consequently, blocking Notch by a small molecule inhibitor of the γ-secretase enzyme that cleaves the Notch receptor for signal activation directs differentiation toward the multiciliated lineage. Thus, γ-secretase inhibitor (GSI) treatment may alleviate multiciliated cell loss in lung disease. Here, we demonstrate the therapeutic restoration of multiciliated cells by the GSI LY450139 (semagacestat). LY450139 increased multiciliated cell numbers in a dose-dependent manner in healthy primary human nasal epithelial cells (HNECs) during differentiation and in mature cultures, but not when applied during early epithelialization of progenitors. LY450139 did not impact stem cell proliferation. Basal and apical administration were equally effective. In healthy adult mice, LY450139 increased multiciliated cell numbers without detectible toxicity. LY450139 also increased multiciliated cells and decreased excess mucus secretory cells in CF HNECs and IL-13 remodeled healthy HNECs. LY450139 normalized multiciliated cell numbers in CF HNECs without interfering with the activity of CFTR modulator compounds. In summary, we demonstrate that GSI administration is a promising therapeutic to restore multiciliated cells and potentially improve epithelial function in a wide range of chronic lung diseases. NEW & NOTEWORTHY Our findings show that low-dose, short-term topical or systemic γ-secretase inhibitor treatment may lead to restoration of multiciliated cells without toxicity and potentially improve epithelial function in a wide range of chronic lung diseases.

Background: Serum thyroid-stimulating hormone (TSH) levels change during body weight reduction. However, the changes that occur during short-term body weight control interventions remain controversial. Thus, this study aimed to evaluate the changes in TSH levels according to body fat reduction., Methods: We performed a 3-month intervention study involving partial meal replacement. Forty-nine participants completed the study. Correlations between changes in TSH levels and other body composition parameters were determined. The subjects were divided into two groups according to their body fat reduction (>1 kg, n=20; <1 kg, n=29). The changes in metabolic parameters, including TSH levels, were compared. For significant values, a multivariate analysis was performed after adjustment to evaluate the relationship between TSH changes and body fat reduction., Results: The 3-month intervention caused favorable changes in body proportions and metabolic parameters. TSH levels changed significantly only after changes in total body fat, showing a partial correlation. Changes in TSH levels were significantly different between groups (P=0.014). Moreover, the change in TSH levels was significantly different after adjustment (P=0.012)., Conclusion: A body fat reduction, especially >1 kg, can reduce serum TSH concentrations in subjects with metabolic syndrome after short-term body weight intervention.

Background/objectives: The incidence of cardiovascular diseases (CVDs) has increased worldwide. Although a low serum vitamin D level is known to be associated with the risk of CVD, the mechanism is not well understood yet. The aim of this study was to determine the relationship of serum 25-hydroxyvitamin D 3 (25[OH]D) with homocysteine and apolipoprotein B (ApoB)., Subjects/methods: Of 777 subjects recruited from one health promotion center for routine heath exam from January 2010 to December 2016, 518 subjects were included in this study. Serum 25(OH)D, serum homocysteine, and other metabolic parameters including ApoB were analyzed. Simple and partial correlations were carried out after adjustments. Simple linear regression analysis was used for precise correlation of parameters. Multivariate regression analysis was done to know which factor (serum homocysteine or ApoB) was more related to serum 25(OH)D after adjustments. Finally, logarithms of homocysteine concentrations according to tertiles of serum 25(OH)D were compared., Results: After sex and age adjustments, serum 25(OH)D showed negative correlations with serum homocysteine ( r ' = -0.114) and ApoB ( r ' = -0.098). In simple linear regression analysis, serum 25(OH)D showed a significant negative correlation with ApoB ( P = 0.035). However, in multivariate regression analysis, serum 25(OH)D was significantly associated with serum homocysteine after adjustments ( P = 0.022). In addition, serum homocysteine concentration was significantly high in the lowest 25(OH)D group ( P = 0.046)., Conclusion: Serum 25(OH)D concentration showed a stronger negative association with serum homocysteine than with ApoB., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2022 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Identifying and preventing modifiable risk factors for cardiovascular disease is very important. Vascular calcification has been studied clinically as an asymptomatic preclinical marker of atherosclerosis and a risk factor for cardio-cerebrovascular disease. It is known that higher homocysteine levels are associated with calcified plaques and the higher the homocysteine level, the higher the prevalence and progression of vascular calcification. Homocysteine is a byproduct of methionine metabolism and is generally maintained at a physiological level. Moreover, it may increase if the patient has a genetic deficiency of metabolic enzymes, nutritional deficiencies of related cofactors (vitamins), chronic diseases, or a poor lifestyle. Homocysteine is an oxidative stress factor that can lead to calcified plaques and trigger vascular inflammation. Hyperhomocysteinemia causes endothelial dysfunction, transdifferentiation of vascular smooth muscle cells, and the induction of apoptosis. As a result of transdifferentiation and cell apoptosis, hydroxyapatite accumulates in the walls of blood vessels. Several studies have reported on the mechanisms of multiple cellular signaling pathways that cause inflammation and calcification in blood vessels. Therefore, in this review, we take a closer look at understanding the clinical consequences of hyperhomocysteinemia and apply clinical approaches to reduce its prevalence.

It is known that ultraviolet B exposure increases serum 25-hydroxyvitamin D(25(OH)D) concentrations. However, little is known about the influence of narrowband ultraviolet B exposure from a light-emitting diode (NBUVB-LED) on serum 25(OH)D levels. Thus, the purpose of this study was to investigate the effect of NBUVB-LED exposure on serum 25(OH)D concentrations. Two healthy adults were enrolled in this pilot study. Their skin was exposed to ultraviolet B light (60 mJ/cm2) 3 times a week for 4 weeks in the first intervention and every day for 4 weeks in the second intervention. Serum levels of 25(OH)D were measured every 2 weeks. Serum 25(OH)D levels were decreased in both subjects at the end of the first intervention (32.1 → 21.4 ng/mL, 33.9 → 21.4 ng/mL, respectively), whereas serum 25(OH)D levels were increased in the 2 weeks of the second intervention (29.5 and 28.0 ng/mL, respectively). At the end of the second intervention, the 25(OH)D concentrations were 19.0 and 20.4 ng/mL, respectively. NBUVB-LED exposure might increase serum 25(OH)D concentrations. Future studies should expand the number of participants and adjust for confounding factors., Competing Interests: Conflict of interests: Seoul Viosys Co., Ltd. (Ansan, Korea) provided narrowband ultraviolet B light-emitting diodes. The authors have no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The genetic disease cystic fibrosis (CF) results when mutations in the gene for the anion channel CFTR reduce CFTR's activity below a critical level. CFTR activity = N·PO·γ (number of channels x open probability x channel conductance). Small molecules are now available that partially restore CFTR function with dramatic improvements in health of CF subjects. Continued evaluation of these and other compounds in development will be aided by accurate assessments of CFTR function. However, measuring CFTR activity in vivo is challenging and estimates vary widely. The most accurate known measure of CFTR activity in vivo is the 'β/M' ratio of sweat rates, which is produced by stimulation with a β-adrenergic agonist cocktail referenced to the same individual's methacholine-stimulated sweat rate. The most meaningful metric of CFTR activity is to express it as a percent of normal function, so it is critical to establish β/M carefully in a population of healthy control subjects. Here, we analyze β/M from a sample of 50 healthy adults in which sweat rates to cholinergic and β-adrenergic agonists were measured repeatedly (3 times) in multiple, (~50) identified sweat glands from each individual (giving ~20,000 measurements). The results show an approximately 7-fold range, 26-187% of the WT average set to 100%. These provide a benchmark against which other measures of CFTR activity can be compared. Factors contributing to β/M variation in healthy controls are discussed., Competing Interests: The authors have declared that no competing interests exist.

Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na + absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases., (© 2021. The Author(s).)

A recent study reported that coronary artery calcification (CAC) and serum homocysteine were well associated; however, no report is available for the cut-off value of serum homocysteine according to increase of coronary-artery calcification volume score (CVS). The data of 469 out of 777 subjects in 1 health promotion center located in Seoul were selected after exclusion of the missing data of serum homocysteine and CVS. CVS was categorized into 2 groups: CVS=0 and CVS>0. Serum homocysteine according to the CVS groups was compared, and the cut-off value of serum homocysteine according to the increase of CVS (>0) was calculated using the receiver operating characteristic curve. Mean age was 54.5 years and the proportion of females was 22.2%. Mean serum homocysteine concentration and CVS were 11.2 μmol/L and 50.4, respectively. After adjustments for age and sex, serum homocysteine was associated with CVS (r=0.167, p=0.001), and Log(Homocysteine) also showed a significant difference according to the CVS groups. The cut-off value of serum homocysteine according to the increase of CVS (>0) was 9.45 μmol/L (area under the curve=0.569 (95% CI 0.512 to 0.625), p=0.015). The cut-off value of serum homocysteine was 9.45 μmol/L according to the increase of coronary-artery CVS., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Metabolic syndrome is well known to increase the risk of cardiovascular diseases. We have reported that phytochemicals rich black rice with giant embryo reduced fat mass and metabolic disorders in an animal model. However, such effects have not been evaluated in humans. Subjects with metabolic syndrome ( n  = 49, 38 male, 44.3 ± 6.1 years) were randomly assigned into two groups and ingested roasted black-rice with giant embryo (BR, n  = 26, 20 male) or white-rice (WR, n  = 23, 18 male) powders mixed with water for breakfast for three months. Subjects were evaluated for various metabolic parameters before and after intervention. All parameters were not significantly different between groups before starting the intervention. After three months of consumption of either BR or WR, changes of body weight in BR vs WR groups (-1.54 kg vs -1.29 kg, p  = 0.649) as well as waist circumference (-1.63 cm vs -1.02 cm, p  = 0.365) were not significantly different between groups. However, changes in highly-sensitive C reactive proteins in BR vs WR groups (-0.110 mg/dl vs 0.017 mg/dl, p  = 0.003) had significant differences. Three months of meal replacement with BR had a significant reduction of highly-sensitive C reactive protein compared to those with WR in adults with metabolic syndrome., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2020 JCBN.)

Background: Recently, new concepts about obesity and normal weight subtypes with metabolic conditions are rising and ketone bodies are emerging as a significant indicator of metabolic health. This study aimed to find a relationship between ketonuria and those subtypes., Methods: The data of 19,036 subjects were analyzed in this cross-sectional study (2013-2017 Korea National Health and Nutrition Examination Survey, KNHANES). Based on body mass index and adult treatment panel III with modification of waist circumference, individuals were categorized into 4 groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). Individuals were divided into 2 groups, positive and negative ketonuria groups, and the metabolic parameters were compared., Results: The metabolic indicators of the positive ketonuria group showed better results than those of the negative ketonuria group and the MHNW group showed the highest proportion of positive ketonuria. The MHNW group showed higher urinary ketones than the MUO group (odds ratio [OR], 0.391; 95% confidence interval [CI], 0.254-0.601) in men. In women, OR of having ketonuria was 0.698 (95% CI, 0.486-1.002) in the MHO group and 0.467 (95% CI, 0.226-0.966) in the MUNW group compared to the MHNW group, respectively., Conclusion: Compared to the MHNW group, the MUO group showed lower presence of ketonuria in men, and tendency to have less ketonuria in women., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: Ketone bodies are a well-known metabolite from the utilization of fatty acids in the fasting state. Some studies have demonstrated the metabolic benefits of urinary ketones in a specific population in whom ketone bodies were detected. However, other studies described the influence of associated factors on the presence of urinary ketone bodies. In the present study, we analyzed lifestyle factors that are hypothesized to be related to the presence of ketone bodies in urine., Methods: Data from the Korea National Health and Nutrition Examination Survey (KNHANES, 2014-2015) were analyzed. The urinary ketone-positive group was defined as the population in whom urinary ketones were detected. We compared differences in metabolic characteristics as well as lifestyle characteristics such as smoking, alcohol intake, education levels, and exercise between the urine ketone-positive and -negative groups., Results: Of the 9,379 identified eligible subjects, the urine-ketone group showed metabolic benefits with respect to several factors such as body mass index, waist circumference, triglyceride, and high density lipoprotein cholesterol after adjustment for sex and age. A higher proportion of urinary ketones was associated with current smoking ( P =0.050), high education level ( P =0.008), and aerobic exercise ( P =0.021)., Conclusion: Aerobic exercise was identified as a factor associated with the presence of urinary ketones. It is also an important lifestyle intervention factor for the recovery of urinary ketones in patients with obesity.

Hydrogen formed by small intestinal bacterial overgrowth in patients with non-constipated irritable bowel syndrome has an inverse relationship with obesity. However, the effect of eradicating small intestinal hydrogen-producing bacterial overgrowth on the body weight of these patients has not yet been reported. The aim of this study was to investigate body weight changes after eradicating small intestinal bacterial overgrowth with rifaximin treatment in patients with non-constipated irritable bowel syndrome.We reviewed the charts of patients with non-constipated irritable bowel syndrome who showed abdominal symptoms with documented lactulose hydrogen breath test results in order to diagnose small intestinal bacterial overgrowth. A total of 153 patients were enrolled in the study and divided into quartiles according to body mass index (BMI) and body weight.In the lowest body weight quartile, the BMI and body weight were significantly increased (0.4 kg/m, P = .038; 0.6 kg, P = .010, respectively) in patients with negative lactulose hydrogen breath tests after rifaximin treatment. However, there was no significant change in body weight in the other quartiles. Despite treatment with rifaximin for 12 weeks, there was no change in BMI or body weight in any group of patients with consistently positive lactulose hydrogen breath tests.Eradication of hydrogen formed by small intestinal bacterial overgrowth does not cause clinically significant changes in body weight.

Backgrounds: Recent studies suggest that diarrhea-predominant irritable bowel syndrome (IBS) is associated with intestinal bacterial microflora, colonic inflammation, and small intestinal bacterial overgrowth (SIBO). The purpose of this study was to evaluate the effect of a multistrain probiotic intake on these associated factors in patients with diarrhea-predominant IBS., Methods: The recruited volunteers were adults who were diagnosed with diarrhea-predominant IBS according to the Rome III criteria. After 8 weeks of probiotic ingestion, changes in gastrointestinal symptoms, fecal microbiome, SIBO, and fecal calprotectin were determined., Results: There was an increase in beneficial bacteria (41.2 ± 16.8% vs. 53.7 ± 15.3%, P = 0.018) and a decrease in harmful bacteria (13.0 ± 13.9% vs. 4.7 ± 4.0%, P = 0.010) in the microbial stool analysis. The SIBO prevalence also decreased at the end of treatment. However, the average levels of fecal calprotectin showed a decreasing tendency, without reaching statistical significance (364.4 ± 729.1 mg/kg vs. 200.9 ± 347.6 mg/kg, P = 0.375)., Conclusion: Treatment with a multistrain probiotic for 8 weeks led to significant increases in beneficial bacteria in the gut as well as the improvement of gastrointestinal symptoms. This study is registered at the Clinical Research Information Service (KCT0002906).

Background: Metabolic syndrome (MS) is a well-known risk factor of cardiovascular diseases that is focused on central obesity. Recent studies have reported the association between pericardial adipose tissue (PAT) volume and MS. However, no studies have demonstrated the cutoff PAT volume that represents the best association with MS., Methods: The data of 374 subjects were analyzed cross-sectionally to compare PAT, measured on coronary multidetector computed tomography, and various metabolic parameters according to MS. After PAT volumes were divided into tertiles, various metabolic parameters were compared among tertiles; furthermore, the odds ratio for developing MS was calculated. Finally, we demonstrated the cutoff PAT volume that represented the best association with MS by using the receiver-operating characteristic curve., Results: We found that 27.5% of the subjects had MS, and the mean PAT volume was 123.9 cm3 . PAT showed a significant positive correlation with body mass index, waist circumference, and levels of glucose, triglyceride, high-sensitivity C-reactive protein, uric acid, and homocysteine, but a negative correlation with high-density lipoprotein cholesterol. Furthermore, after dividing into tertiles, PAT volume was also significantly associated with various metabolic parameters. The odds ratio for having MS was 4.19 (95% confidence interval, 2.27-7.74) in the top tertile of PAT volumes after adjusting for age, sex, and smoking. The cutoff PAT volume that represented the best association with MS was 142.2 cm3 ., Conclusion: PAT was significantly associated with MS and various metabolic parameters. The cutoff PAT volume of 142.2 cm3 showed the best association with MS.

There are no large community-based studies examining the association of body size vs. body fat with vitamin D status. Association of serum 25-hydroxyvitamin D (25OHD) with body weight and subcategories of body weight defined by fat mass were evaluated in a large, free living population. Out of a total of 29,235 subjects from the 2008⁻2010 Korean National Health and Nutrition Examination Survey, the relevant data included 6458 subjects over 50 years of age who were analyzed cross-sectionally. Serum 25OHD concentrations were compared in men ( n = 3164) and in women ( n = 3294) by tertiles of body weight and body fat mass, as measured by Dual-energy X-ray Absorptiometry (DXA) within sex-specific tertiles of body weight. Serum 25OHD was weakly inversely correlated with body weight in the men and the women after adjustment for age ( r = &minus;0.075 and &minus;0.073, respectively, p < 0.001 for both). Within each tertile of body weight, serum 25OHD decreased progressively as fat mass increased in men. This pattern was similar in the women but not consistently significant. Whereas body weight predicted a small decrease in serum 25OHD in the men and the women, greater adiposity, for any given weight, predicted larger decreases in the men, but not consistently in women., Competing Interests: The authors declare no conflict of interest.

Introduction: A nonspecific symptom, fatigue accompanies a variety of diseases, including cancer, and can have a grave impact on patients' quality of life. As for multidimensional instruments, one of the most widely used is the Multidimensional Fatigue Inventory (MFI). This study aims to verify the reliability and validity of the MFI Korean (MFI-K) version., Materials and Method: This study was performed at four university hospitals in the Republic of Korea. Among outpatients visiting the Department of Family Medicine, those complaining of fatigue or visiting a chronic care clinic were enrolled in this study. A total of 595 participants were included, and the mean age was 42.2 years., Results: The Cronbach's alpha coefficient of the MFI-K was 0.88. The MFI-K had good convergent validity. Most subscales of the MFI-K were significantly correlated with the Visual Analogue Scale (VAS) and Fatigue Severity Scale (FSS). In particular, general and physical fatigue had the greatest correlation with the VAS and FSS. Although the English version of MFI had five subscales, the factor analysis led to four subscales in the Korean version., Conclusion: This study demonstrated the clinical usefulness of MFI-K instrument, particularly in assessing the degree of fatigue and performing a multidimensional assessment of fatigue.

Normal airways below the carina maintain an essentially sterile environment via a multi-pronged innate defence system that includes mucus clearance via mucociliary clearance and cough, multiple antimicrobials and cellular components including macrophages and neutrophils. In cystic fibrosis (CF), loss of CFTR function compromises these defences, and with present standard of care virtually all people with CF eventually develop mucus accumulation, plugging and chronic infections. This review focuses on how mucus is affected by CFTR loss., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background/aims: Although associations between serum alanine aminotransferase and metabolic syndrome are well-recognized in Western countries, only a limited number of prospective studies have been performed in Asian populations. The aim of the study was to cross-sectionally and longitudinally examine whether serum alanine aminotransferase levels are associated with metabolic syndrome and its associated components in a Korean population., Materials and Methods: A total of 31,832 subjects who received health screenings were included in cross-sectional analyses; a subgroup of 4.070 subjects without metabolic syndrome at baseline was included in the longitudinal analyses. The metabolic syndrome definition was based on the National Cholesterol Education Program Third Adult Treatment Panel criteria with modification on waist circumference cut-off to be more appropriate for an Asian population., Results: In the cross-sectional analyses, serum alanine aminotransferase is positively associated with metabolic syndrome and its components. In the longitudinal analyses, the prevalence of metabolic syndrome increased across serum alanine aminotransferase quartiles in a dose-dependent manner after extensive adjustments (hazard ratios were 1.000, 1.609, 2.601, and 3.015 for quartiles, 1 through quartile 4; P for trend<0.001)., Conclusion: Our study confirmed a positive association between components of metabolic syndrome and elevated serum alanine aminotransferase in a Korean population.

Background: Vitamin D and calcium are important factors involved in the regulation of blood glucose and insulin secretion. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score is a useful variable for evaluating insulin resistance, and therefore we cross-sectionally compared HOMA-IR scores according to serum vitamin D levels and dietary calcium intake., Methods: We selected data from healthy males (n=5,163) and females (n=7,506) analyzed over 5 years (2008-2012) via the Korea National Health and Nutrition Examination Survey (KNHANES). We calculated HOMA-IR scores and compared them according to serum 25-hydroxyvitamin D (25(OH)D) concentration classification (<20, 20-30, >30 ng/mL) and dietary calcium quintile after adjustment for relevant variables using complex sample analysis. Comparisons were done after data weighting., Results: The mean dietary calcium intake in males and females was 558.1 mg/day and 445.9 mg/day, respectively. The mean serum 25(OH)D concentration in males and females was 19.4 ng/mL and 16.8 ng/mL, respectively. After adjustment for relevant variables, HOMA-IR score was significantly correlated with serum 25(OH)D concentration and dietary calcium intake in females, whereas it was only correlated with serum 25(OH)D concentration in males. HOMA-IR was significantly lower in the top quintile of dietary calcium intake (mean, 866 mg/day) within females with vitamin D deficiency ( P =0.047)., Conclusion: Adequate dietary calcium intake may be important for normal HOMA-IR in females with vitamin D deficiency., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflict of interest.

Background: Airway mucociliary clearance (MCC) is an important defense mechanism against pulmonary infections and is compromised in cystic fibrosis (CF). Cl- and HCO3- epithelial transport are integral to MCC. During pulmonary infections prostaglandin E2 (PGE2) production is abundant., Aim: To determine the effect of PGE2 on airway Cl- and HCO3- secretion and MCC in normal and CF airways., Methods: We examined PGE2 stimulated MCC, Cl- and HCO3- secretion using ferret trachea, human bronchial epithelial cell cultures (CFBE41o- with wildtype CFTR (CFBE41 WT) or homozygous F508del CFTR (CFBE41 CF) and human normal bronchial submucosal gland cell line (Calu-3) in Ussing chambers with or without pH-stat., Results: PGE2 stimulated MCC in a dose-dependent manner and was partially impaired by CFTRinh-172. PGE2-stimulated Cl- current in ferret trachea was partially inhibited by CFTRinh-172, with niflumic acid eliminating the residual current. CFBE41 WT cell monolayers produced a robust Cl- and HCO3- secretory response to PGE2, both of which were completely inhibited by CFTRinh-172. CFBE41 CF cells exhibited no response to PGE2. In Calu-3 cells, PGE2 stimulated Cl- and HCO3- secretion. Cl- secretion was partially inhibited by CFTRinh-172, with additional inhibition by niflumic acid. HCO3- secretion was completely inhibited by CFTRinh-172., Conclusions: PGE2 stimulates bronchotracheal MCC and this response is decreased in CF. In CF airway, PGE2-stimulated Cl- and HCO3- conductance is impaired and may contribute to decreased MCC. There remains a CFTR-independent Cl- current in submucosal glands, which if exploited, could represent a means of improving airway Cl- secretion and MCC in CF.

Results regarding the association between adipokine levels and bone mineral density (BMD) have been inconsistent; the effects of sex, menopause, and central obesity remain unknown. We evaluated the association between serum leptin, adiponectin, and high-molecular-weight (HMW) adiponectin levels and BMD according to menopause and central obesity status in Korean women. This cross-sectional study comprised 255 women undergoing examinations at the CHA Bundang Medical Center. Participants were divided according to menopause, and central obesity status. We measured serum adipokine levels and BMD using an enzyme-linked immunosorbent assay and dual-energy X-ray absorptiometry, respectively. After adjusting for age, body mass index, alkaline phosphatase levels and the Homeostasis Model Assessment index, leptin levels were negatively associated with non-vertebral BMD (total hip, β = -0.576, P = 0.006; femoral neck, β = -0.608, P = 0.007) in postmenopausal women without central obesity. Among women without central obesity, HMW adiponectin levels were positively associated with total hip BMD (β = 0.240, P = 0.010) in premenopausal women but negatively associated with BMD (lumbar, β = -0.436, P = 0.012; femoral neck, β = -0.468, P = 0.007) in postmenopausal women. Thus, the association between adipokine levels and BMD varies according to the menopause and central obesity status.

Testosterone and insulin-like growth factor-1 (IGF-1) are essential factors for the maintenance of bone health in men. However, the results for the association of testosterone and IGF-1 with bone parameters were not consistent in prior studies. We evaluated the relationship of testosterone, sex hormone-binding globulin (SHBG), and IGF-1 with bone mineral density (BMD) and bone turnover markers (BTMs) in Korean men. We enrolled 1227 men aged ≥50 years in this cross-sectional study. Serum levels of total testosterone (TT), SHBG, IGF-1, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen (CTX) were measured. Free testosterone (FT) was calculated using Vermeulen's method. BMD was measured by dual-energy X-ray absorptiometry. TT level was not related to BMD or BTMs in the unadjusted model; however, after adjusting for SHBG and IGF-1, the association between TT and BTMs was significant (β = -0.139 for osteocalcin and β = -0.204 for CTX). SHBG levels were negatively associated with lumbar BMD, and positively associated with BTMs in all models. As SHBG level increased, the prevalence of osteopenia or osteoporosis defined by BMD significantly increased (OR of 1SD change, 1.24). IGF-1 levels were significantly related with BMD, but not with BTMs. Meanwhile, FT levels were positively associated with BMD and negatively associated with BTMs. In conclusion, SHBG levels were independently related with bone parameters and osteopenia in men aged ≥50 years. IGF-1 levels were positively associated with BMD, but not with BTMs. SHBG may play a role in regulating age-related bone loss in men after middle-age.

Background: Increased blood mercury concentration is associated with inflammation, and chronic inflammation can cause insulin resistance. We examined the cut-off value of blood mercury in relation to an increased score on the homeostasis model assessment for insulin resistance (HOMA-IR)., Methods: We used data from the Korean National Health and Nutrition Examination Survey (2008-2010). Relevant data from 5,184 subjects (2,523 men and 2,661 women) were analyzed cross-sectionally. General linear analysis was performed to evaluate the relationship between HOMA-IR score and blood mercury concentration. In addition, we determined the cut-off value of blood mercury concentration in relation to increased HOMA-IR score (> 2.34) using an ROC curve., Results: The mean value of blood mercury concentration in men and women was 5.88 μg/L and 4.11 μg/L, respectively. In men, comparing to the first quartile, HOMA-IR score increased significantly in the third and fourth blood mercury quartiles. In women, however, the increase in HOMA-IR score was not significant. The cut-off value that best represented the association between increased HOMA-IR score and blood mercury concentration in men was found to be 4.71 μg/L., Conclusion: Blood mercury concentration was associated with increased HOMA-IR score in men, and the cut-off value of blood mercury concentration that was correlated with increased HOMA-IR score was around 4.71 μg/L., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflict of interest.

The purpose of the study is to analyse how the standard of resting metabolic rate (RMR) affects estimation of the metabolic equivalent of task (MET) using an accelerometer. In order to investigate the effect on estimation according to intensity of activity, comparisons were conducted between the 3.5 ml O 2  · kg -1  · min -1 and individually measured resting VO 2 as the standard of 1 MET. MET was estimated by linear regression equations that were derived through five-fold cross-validation using 2 types of MET values and accelerations; the accuracy of estimation was analysed through cross-validation, Bland and Altman plot, and one-way ANOVA test. There were no significant differences in the RMS error after cross-validation. However, the individual RMR-based estimations had as many as 0.5 METs of mean difference in modified Bland and Altman plots than RMR of 3.5 ml O 2  · kg -1  · min -1 . Finally, the results of an ANOVA test indicated that the individual RMR-based estimations had less significant differences between the reference and estimated values at each intensity of activity. In conclusion, the RMR standard is a factor that affects accurate estimation of METs by acceleration; therefore, RMR requires individual specification when it is used for estimation of METs using an accelerometer.

There have been inconsistent findings on the association of obesity and non-constipation irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) with hydrogen (H₂) gas forming-microflora causes non-constipation IBS. But, the effect of H₂ producing SIBO on obesity in non-constipation IBS patients has not been studied yet. The aim of this study was to investigate the association between obesity and SIBO in non-constipation IBS patients. We reviewed the charts of patients who showed IBS symptoms along with the documented results of their lactulose hydrogen breath test (LHBT) for SIBO. Multivariate models were used to assess the association between obesity and SIBO. Four-hundred fifty-eight patients were retrospectively included in the study. Of the 485 IBS patients, 158 (30.7%) subjects had positive results for LHBT. Subjects without SIBO showed significantly higher levels of body mass index (24.8 vs. 23.3; P < 0.001) and waist circumference (86.5 vs. 82.7; P < 0.001) as compared to subjects with SIBO. In multivariate analysis, the odds ratios of SIBO were 0.396 (P = 0.018) for obesity and 0.482 (P = 0.021) for abdominal obesity. This is the first human study to demonstrate that obesity is inversely related to SIBO with H₂ gas production in non-constipation IBS patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

The association between sex hormone-binding globulin (SHBG) and arterial stiffness in women is not conclusive. In addition, obesity might also be involved in the relationship between SHBG and atherosclerosis. The aim of this study was to determine the relationship between SHBG and arterial stiffness in association with central obesity in women. This cross-sectional study included 381 women who participated in the health checkup programs in one hospital. The brachial-ankle pulse wave velocity (baPWV) was measured as a marker for arterial stiffness. A negative correlation was observed between SHBG levels and baPWV (rho = -0.281). The relationship was significant even after adjusting for potential confounders (beta = -0.087 in fully adjusted model). After considering the interaction between central obesity and SHBG levels, the significant association was evident only in obese women ( P for interaction = 0.025). Adjustment for a 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores, instead of each cardiovascular risk factor individually, did not affect the significance of the relationship between SHBG levels and baPWV. Serum levels of SHBG were negatively associated with arterial stiffness independent of cardiovascular risk factors or 10-year ASCVD risk scores in Korean women. The relationship may be potentiated by central obesity.

Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca 2+ -activated chloride channels mediate anion/fluid secretion. MCCV was increased by the cAMP-elevating agonists, forskolin or isoproterenol (10 μM) and by the Ca 2+ -elevating agonist, carbachol (0.3 μM). The CFTR-selective inhibitor, CFTR inh -172, modestly reduced MCCV-increases induced by forskolin or isoproterenol but not increases induced by carbachol. The ENaC inhibitor benzamil increased basal MCCV as well as MCCV increases produced by forskolin or carbachol. MCC velocity was most dramatically accelerated by the synergistic combination of forskolin and carbachol, which produced near-maximal clearance rates regardless of prior treatment with CFTR or ENaC inhibitors. In CF airways, where CFTR-mediated secretion (and possibly synergistic MCC) is lost, ENaC inhibition via exogenous agents may provide therapeutic benefit, as has long been proposed.

Purpose: High-density lipoprotein cholesterol (HDLC) is anti-inflammatory in the basal state and pro-inflammatory during the acute-phase response. Blood mercury also has an inflammatory property. Therefore, the aim of this study was to investigate the relationship between serum HDLC and blood mercury concentration in relation with metabolic syndrome (MS)., Methods: The data of 7616 subjects (3713 men and 3903 women), over 20 years of age, from 2008 to 2013, Korea National Health and Nutrition Examination Survey were selected for cross-sectional analyses. Correlation and regression of serum HDLC and blood mercury were initially done. We compared serum HDLC concentration according to blood mercury quartile after adjustment for relevant variables in subjects with MS., Results: Mean blood mercury concentrations is 5.6 and 3.9 μg/dL in men and women, respectively. Blood mercury concentration in MS subjects was positively correlated with serum HDLC concentration, especially in men. In addition, HDLC concentration was significantly higher according to the higher blood mercury quartile., Conclusion: Serum HDLC was positively associated with blood mercury concentration in MS Korean men. Therefore, elevated blood mercury may be a factor to increase serum HDLC concentration in MS men.

Blood mercury (methyl-mercury) from environmental exposure may be related to inflammation in our body. We investigated the cut-off values of blood mercury concentration in relation to increased body mass index (BMI) and waist circumference. On the basis of data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012), 11,159 subjects (5543 males and 5616 females) were analyzed cross-sectionally. Partial correlation, linear regression, and analysis of covariance (according to the mercury quartile) tests were performed to evaluate the relationship between blood mercury and BMI or waist circumference. In addition, we determined the cut-off values of blood mercury concentration in relation to increased BMI and waist circumference in both genders. Mean values of blood mercury concentration were 5.07 ± 0.07 μg/L in males and 3.59 ± 0.04 μg/L in females. After log transformation of blood mercury, significant (p < 0.001) correlation was found between blood mercury concentration and BMI or waist circumference. BMI and waist circumference showed a significant and gradual increase as mercury quartile increased in both genders. Blood mercury concentration was weakly but significantly (p < 0.001) associated with BMI and waist circumference. Cut-off values of blood mercury concentration correlated with increased BMI and waist circumference were around 3.95 μg/L in males and 3.40 μg/L in females., (Copyright © 2016 American Federation for Medical Research.)

Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel lead to viscous secretions from submucosal glands that cannot be properly hydrated and cleared by beating cilia in cystic fibrosis (CF) airways. The mechanisms by which CFTR, and the predominant epithelial sodium channel (ENaC), control the hydration and clearance of glandular secretions remain unclear. We used a proteomics approach to characterize the proteins contained in CF and non-CF submucosal gland fluid droplets and found that differentially regulated proteases (cathepsin S and H) and their antiprotease (cystatin C) influenced the equilibration of fluid on the airway surface and tracheal mucociliary clearance (MCC). Contrary to prevailing models of airway hydration and clearance, cystatin C, or raising the airway surface liquid (ASL) pH, inhibited cathepsin-dependent ENaC-mediated fluid absorption and raised the height of ASL, and yet decreased MCC velocity. Importantly, coupling of both CFTR and ENaC activities were required for effective MCC and for effective ASL height equilibration after volume challenge. Cystatin C-inhibitable cathepsins controlled initial phases of ENaC-mediated fluid absorption, whereas CFTR activity was required to prevent ASL dehydration. Interestingly, CF airway epithelia absorbed fluid more slowly owing to reduced cysteine protease activity in the ASL but became abnormally dehydrated with time. Our findings demonstrate that, after volume challenge, pH-dependent protease-mediated coupling of CFTR and ENaC activities are required for rapid fluid equilibration at the airway surface and for effective MCC. These findings provide new insights into how glandular fluid secretions may be equilibrated at the airway surface and how this process may be impaired in CF.

In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20-70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways.

A significant decline of serum 25-hydroxyvitamin D concentration [25(OH)D] with increasing latitude has been reported only for Caucasians. To determine the association between serum 25(OH)D and geographic location and its impact on bone mineral density (BMD) in an Asian population, a total of 17,508 subjects (8910 men and 8598 women) from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES) were stratified into four age groups and analyzed for 25(OH)D and BMD according to geographic location (South, 33° N-35° N; Middle, 36° N; North, 37° N-38° N). Mean 25(OH)D were 47.7 and 41.2 nmol/L; calcium intake, 564.9 & 442.3 mg/d; femoral neck BMD, 0.829 & 0.721 g/cm²; and lumbar spine BMD, 0.960 & 0.918 g/cm² for men and women, respectively. Both men and women living in the South had significantly higher 25(OH)D and femoral neck BMD for those ≥50 years old. Lumbar spine BMD was significantly higher in men ≥50 years old, and for women 10-29 & 50-69 years old living in the South. A 1 or 2 degree difference in latitude has a significant effect on serum 25(OH)D and BMD in this low vitamin D status population. Thus, consideration of geographic location for a recommendation of vitamin D intake may be necessary.

Purpose: The benefit of milk intake remains controversial. The association between milk consumption and Framingham Risk Score (FRS) in a population consuming relatively low amounts of dairy products is undetermined., Materials and Methods: A total of 13736 adults (5718 male and 8018 female) aged 20-80 years from the Korea National Health and Nutrition Examination Survey (2008-2011) were divided into groups according to milk consumption (rarely, monthly, weekly, and daily) and compared according to FRS after relevant variable adjustments., Results: The mean FRS in males and females were 6.53 and 5.74, respectively. Males who consumed milk daily (15.9%) had a significantly lower FRS than males having milk rarely (31.6%) or monthly (17.4%; p=0.007). Females who consumed milk daily (22.3%) also had significantly lower FRS than rarely (29.8%), monthly (13.8%), or weekly (34%; p=0.001) consumers. In particular, males ≥60 years old who consumed milk daily had a significantly lower FRS than males who consumed less milk (p<0.001). The odds ratio in this age group showed a significant and gradual increase in the weekly [OR=2.15; 95% confidence interval (CI) 1.14-4.03], monthly (OR=2.29; 95% CI 1.15-4.54), and rarely (OR=3.79; 95% CI 2.01-7.14) milk consumption groups when compared with the daily milk consumption group., Conclusion: Milk consumption was associated with a lower FRS in a low milk-consuming population. In particular, daily milk consumption in males over 60 years old may be beneficial for those at risk for cardiovascular disease.

Purpose: Recent studies have revealed close relationships between hepatic injury, metabolic pathways, and gut microbiota. The microorganisms in the intestine also cause irritable bowel syndrome (IBS). The aim of this study was to examine whether IBS was associated with elevated hepatic enzyme [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], gamma-glutamyl transferase (γ-GT) levels, and metabolic syndrome (MS)., Materials and Methods: This was a retrospective, cross-sectional, case-control study. The case and control groups comprised subjects who visited our health promotion center for general check-ups from June 2010 to December 2010. Of the 1127 initially screened subjects, 83 had IBS according to the Rome III criteria. The control group consisted of 260 age- and sex-matched subjects without IBS who visited our health promotion center during the same period., Results: Compared to control subjects, patients with IBS showed significantly higher values of anthropometric parameters (body mass index, waist circumference), liver enzymes, γ-GT, and lipid levels. The prevalences of elevated ALT (16.9% vs. 7.7%; p=0.015) and γ-GT (24.1% vs. 11.5%; p=0.037) levels were significantly higher in patients with IBS than in control subjects. A statistically significant difference was observed in the prevalence of MS between controls and IBS patients (12.7% vs. 32.5%; p<0.001). The relationships between elevated ALT levels, MS, and IBS remained statistically significant after controlling for potential confounding factors., Conclusion: On the basis of our study results, IBS may be an important condition in certain patients with elevated ALT levels and MS.

Context: Osteocalcin is associated with energy metabolism and atherosclerosis, besides bone metabolism. However, the association between osteocalcin or its undercarboxylated form (ucOC) and coronary artery calcification is controversial., Objective: To evaluate the relationship between coronary artery calcium score (CACS) and the concentration of serum osteocalcin and ucOC., Design: Cross-sectional., Patients: A total of 162 subjects (114 men and 48 women) with no angina symptom., Measurements: Serum analyses included glucose, insulin and lipid profiles as well as osteocalcin and ucOC. Bone mineral density (BMD) was measured by dual X-ray absorptiometry. CACS was measured using multidetector computed tomography and categorized into CACS = 0 and CACS > 0., Results: The mean osteocalcin concentration in men was 15·6 ± 4·2 for CACS = 0 group and 14·1 ± 4·0 for CACS > 0 group, respectively (P = 0·050). In women, the osteocalcin concentration, ucOC concentration and ucOC to osteocalcin ratio (OCR) were not different between the CACS groups. However, the concentrations of osteocalcin and ucOC were significantly lower in women with hypertension or diabetes than those without, respectively. In the multivariate logistic regression models adjusted for medical history, body mass index, lipid profiles, insulin resistance and BMD in men, the higher concentration of ucOC and higher OCR showed significant association with coronary calcification (CACS > 0)., Conclusion: Higher ucOC concentration was associated with coronary artery calcification independent of conventional cardiovascular risk factors and BMD in men., (© 2015 John Wiley & Sons Ltd.)

Background: A majority of patients with cystic fibrosis (CF) have chronic rhinosinusitis (CRS) and/or nasal polyps, both of which may be secondary to reduced fluid secretion from nasal submucosal glands., Objective: To determine whether decreased fluid secretion from nasal submucosal glands also occurs in patients without CF and with CRS., Methods: Inferior turbinates of the nasal cavity were harvested from controls, subjects with CRS, and subjects with CF (n = 5-7 per group). The secretion rates of the nasal submucosal glands of the three groups in response to carbachol and forskolin were measured by using time lapse digital imaging of mucus bubbles from single glands as they formed on the mucosal surface under oil., Results: Carbachol-stimulated secretion rates were the following: controls, 1670 ± 381 pl·min(-1)·gland(-1); CRS, 965 ± 440 pl·min(-1)·gland(-1); and CF, 933 ± 588 pl·min(-1)·gland(-1) (p = 0.23, Kruskal-Wallis test). Forskolin-stimulated secretion rates were the following: controls, 229 ± 14 pl·min(-1)·gland(-1); CRS, 154 ± 48 pl·min(-1)·gland(-1); and CF, 22 ± 15 pl·min(-1)·gland(-1) (p = 0.008, Kruskal-Wallis test). The ratio of the average secretion rate induced by forskolin to that induced by carbachol was 13.7% in the controls, and 15.9% in CRS and 2.3% in CF groups., Conclusion: The only significant difference in this small study was decreased forskolin-stimulated secretion in subjects with CF relative to the other subjects. However, there was a trend toward reduced carbachol-stimulated secretion rates in subjects with CRS and with and without CF relative to controls. Additional studies are needed to determine if nasal submucosal gland hyposecretion occurs in CRS either as a contributor to or as a consequence of CRS pathogenesis.

Purpose: Blood mercury levels are associated with inflammation, and chronic low-grade inflammation is a cause of insulin resistance. This study aimed to investigate the association between serum mercury and insulin resistance., Materials and Methods: Subjects from the 2008-2010 Korean National Health and Nutrition Examination Survey were selected (n=29235) and the relevant data of 5388 subjects (2643 males and 2745 females) were analyzed cross-sectionally. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was compared according to blood mercury quartiles, and the odds ratio (OR) of having the highest quartile of HOMA-IR according to blood mercury quartiles was calculated., Results: Blood mercury levels in men and women were 29.4 nmol/L and 20.5 nmol/L, respectively, and fasting blood sugar (FBS), insulin, and HOMA-IR were significantly correlated with blood mercury levels. The correlation was stronger in men than in women. In men, FBS and HOMA-IR showed step-wise increases as the quartiles of blood mercury increased; only HOMA-IR differed significantly in the third and fourth blood mercury quartiles, compared to the first quartile. In women, however, both FBS and HOMA-IR differed significantly in the third and fourth blood mercury quartiles, compared to the first quartile. Among men, the OR of being in the highest HOMA-IR quartile was greatest for the highest blood mercury quartile (OR=1.720, 95% CI; 1.172-2.526), compared with the lowest quartile., Conclusion: In this large population-based study, blood mercury levels were weakly correlated with HOMA-IR and may be a risk factor for insulin resistance in nondiabetic Koreans.

Purpose: The association between excess calcium intake and cardiovascular mortality has already been reported. In the present study, we investigated the relation between dietary calcium intake and Framingham Risk Score (FRS) according to serum 25-hydroxyvitamin D [25(OH)D] status., Materials and Methods: A total of 7809 subjects (3452 males and 4357 female) aged over 40 years were selected for this cross-sectional study from data obtained from the Korea National Health and Nutrition Examination Survey (2008-2011). Daily dietary calcium intake was categorized into <300, 300-600, 600-900, 900-1200, and >1200 mg/day and serum 25(OH)D concentration classified into <50, 50-75, >75 mmol/L. The FRS was compared by the daily dietary calcium intake categories according to 25(OH)D concentration after adjustment with relevant variables in both genders., Results: Higher FRS was observed in males with both <300 mg and >1200 mg of dietary calcium intake and females with <300 mg of dietary calcium intake without adjustment. The significantly higher FRS remained in the <300 mg and >1200 mg of dietary calcium intake groups in both genders after adjustments for relevant variables. FRS was significantly higher in the group with >1200 mg of dietary calcium intake and serum 25(OH)D <50 nmol/L, which was the male only vitamin D deficient group., Conclusion: Very low (<300 mg/day) and excess (>1200 mg/day) dietary calcium intake were related with higher FRS in both genders. In particular, higher FRS was observed in the excess (>1200 mg/day) dietary calcium intake male group under vitamin D deficiency (<50 nmol/L).

The association of high vitamin A intake and low bone mineral density (BMD) is still controversial. To determine the association of dietary vitamin A intake and serum 25-hydroxyvitamin D (25(OH)D) concentration with BMD, a total of 6481 subjects (2907 men and 3574 women) aged ≥50 years from the Korean National Health and Nutrition Examination Survey (2008-2011) were divided into groups according to dietary vitamin A intake (tertiles) and serum 25(OH)D (<50, 50-75, >75 nmol/L), and evaluated for BMD after adjusting for relevant variables. Mean dietary vitamin A intakes were 737 and 600 μg RE (Retinol Equivalents) in men and women, respectively. Total hip and femoral neck BMD in men and lumbar spine BMD in women were both positively correlated with dietary vitamin A intake in subjects with serum 25(OH)D >75 nmol/L. Among men with serum 25(OH)D <50 nmol/L, both the top (mean 1353 μg RE) and bottom (mean 218 μg RE) tertiles of dietary vitamin A intake had lower BMD than the middle group (mean 577 μg RE). In this population, BMD was the highest among men and women with serum 25(OH)D = 50-75 nmol/L and that there were no differences in BMD by vitamin A intake in these vitamin D adequate groups. This cross-sectional study indicates that vitamin A intake does not affect bone mineral density as long as the serum 25(OH)D concentration is maintained in the moderate level of 50-75 nmol/L.

Serum ferritin as well as blood mercury are reported to be associated with chronic inflammation. However, the relation between serum ferritin and blood mercury has not yet been established. We utilized the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012) 10,977 subjects (5433 males and 5544 females). To evaluate the association of serum ferritin and blood mercury cross-sectionally, complex sample analysis was conducted after adjustment for the relevant variables. Serum concentrations of ferritin and blood mercury were higher in males than in females (115.7 ± 1.7 vs. 40.9 ± 0.7 ng/mL and 5.0 ± 0.1 vs. 3.6 ± 0.1 μg/L, respectively). Serum ferritin and blood mercury concentrations had significant correlations in both genders after adjustment (r = 0.062, P < 0.001 in males; r = 0.055, P < 0.001 in females). The analysis of covariance (ANCOVA) test showed significantly higher serum ferritin according to the tertile of blood mercury (P = 0.007) in males. The adjusted odds ratio of having the highest tertile of serum ferritin in the top tertile of blood mercury in males was 1.52 (95 % confidence interval (CI), 1.05-2.21). Thus, the current study indicates that blood mercury concentration can be a factor for the elevated serum ferritin concentration.

Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269-319 proteins per subject). We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38%) had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican). A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment.

The impact of simultaneously elevated serum ferritin and mercury concentrations on hypertension in the general population is not known. To determine the association of serum ferritin and mercury concentrations with hypertension, 6213 subjects (3060 men and 3153 women) over 20 years of age from 2008 to 2010 Korea National Health and Nutrition Examination Survey were divided into tertiles according to serum ferritin and mercury concentrations in each gender. Serum ferritin (258.2 vs. 94.8 pmol/L) and mercury concentrations (28.4 vs. 19.9 nmol/L) were higher in men than in women. Serum ferritin (men; P = 0.029, women; P < 0.001) and mercury (men; P < 0.001, women; P = 0.003) concentrations were significantly associated with the prevalence of hypertension. In addition, significant correlation between serum ferritin and mercury concentrations in both men (r = 0.193, P < 0.001) and women (r = 0.145, P < 0.001) were found. Also, the increase of serum ferritin concentrations were more prominent in men (P < 0.001) than in women (P = 0.017) as the serum mercury tertiles increased after proper adjustments. Furthermore, significantly higher odds ratios of hypertension were found in the second (OR = 1.86, 95% CI; 1.05-3.30), and third (OR = 1.84, 95% CI; 1.01-3.36) tertiles of serum ferritin with the top tertile of serum mercury in men. The current study indicate that serum ferritin and mercury concentrations are associated with the prevalence of hypertension and that simultaneously elevated serum ferritin and mercury concentrations are related to the risk for hypertension in men., (© 2013 The Authors. The Environmental Toxicology published by Wiley Periodicals, Inc.)

X-box binding protein 1 (XBP1), a transcription factor of the unfolded protein response, plays various roles in many biological processes. We examined its pro-adipogenic activity and target genes during adipogenic differentiation in wild-type and genetically modified 3T3-L1 cells. Signalling pathways that contribute to Xbp1 mRNA splicing, and the correlation of the transcriptionally active XBP1 isoform (XBP1s) level with body mass index and the level of peroxisome proliferator-activated receptor γ2 (PPARγ2) in human adipose tissues were also examined. The mRNA and nuclear protein expression levels of XBP1s increased immediately following hormonal induction of adipogenesis, reaching a peak at 6 h. Results from cDNA microarray and gene expression analyses using genetically modified cells indicated that PPARγ2 was a principal target of XBP1s. The XBP1s-specific binding motif, which is distinct from the CCAAT/enhancer-binding protein α binding site, was identified in the PPARγ2 promoter by site-directed mutagenesis. Fetal bovine serum, insulin, 3-isobutyl-1-methylxanthine and dexamethasone contributed independently to Xbp1 mRNA splicing. In human subcutaneous adipose tissues, the levels of both Xbp1s and Pparγ2 mRNA increased proportionally with body mass index, and there was a significant positive correlation between the two genes. These data suggest for the first time that positive regulation of PPARγ2 is a principal mechanism of XBP1s-mediated adipogenesis in 3T3-L1 cells., (© 2014 FEBS.)

Although zinc was known to be associated with insulin metabolism and diabetes, the relationship of serum zinc concentration with insulin resistance (IR) and metabolic syndrome (MetS) was not well investigated in general population. The aim of this study is to evaluate the relationships of serum zinc concentration with IR and MetS in a nondiabetic adult population. This cross-sectional study included 656 men and 825 women who were nondiabetic adults from the fifth Korea National Health and Nutrition Examination Survey conducted in 2010. Serum zinc concentration and metabolic parameters were measured. IR was estimated by homeostatic model assessment (HOMA2). MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Serum zinc concentration was negatively correlated with homeostasis model assessment for insulin resistance (HOMA2-IR) in men (r = -0.104, P = 0.008), but not in women. After adjusting for conventional cardiovascular risk factors, the inverse correlation was significant in both men and women (B = -0.262, SE = 0.060 for men, and B = -0.129, SE = 0.052 for women). However, serum zinc concentration was not different between the groups with and without MetS (P = 0.752 for men and P = 0.371 for women). In conclusion, serum zinc concentration was inversely associated with IR but not related to MetS in nondiabetic adult population.

Purpose: We performed a study to determine the best appropriate wearing site of a triaxial accelerometer at different exercise speeds., Materials and Methods: We conducted an observational study with 66 healthy Korean adults (26 men and 40 women). Resting metabolic rate (RMR) before exercise, physical activity-related energy expenditure (PAEE) by cardiorespiratory gas analyzer and Signal Vector Magnitude (SVM) were measured while wearing four triaxial accelerometers on four different sites (wrist, waist, upper arm, and ankle) at exercise speeds from 2-10 km/h., Results: The mean RMR was 4.03 mL/kg/min and Actual METs (oxygen consumption at different exercise speeds divided by individual RMR) compared with the calculated METs (oxygen consumption divided by 3.5 mL/kg/min) showed relatively low value. The overall correlation between PAEE and SVM was highest when the accelerometer was worn on the wrist at low exercise speed (r=0.751, p<0.001), waist at a moderate speed (r=0.821, p<0.001), and ankle at a high speed (r=0.559, p<0.001). Using regression analysis, it was shown that the ankle at a low speed (R²=0.564, p<0.001), high speed (R²=0.559, p<0.001), and the waist at a moderate speed (R²=0.821, p<0.001) were the best appropriate sites., Conclusion: When measuring the PAEE and SVM at different exercise speeds, the ankle in low and high exercise speed, and waist in moderate speed are the most appropriate sites for an accelerometer.