PAF remodels the DREAM complex to bypass cell quiescence and promote lung tumorigenesis.

The DREAM complex orchestrates cell quiescence and the cell cycle. However, how the DREAM complex is deregulated in cancer remains elusive. Here, we report that PAF (PCLAF/KIAA0101) drives cell quiescence exit to promote lung tumorigenesis by remodeling the DREAM complex. PAF is highly expressed in lung adenocarcinoma (LUAD) and is associated with poor prognosis. Importantly, Paf knockout markedly suppressed LUAD development in mouse models. PAF depletion induced LUAD cell quiescence and growth arrest. PAF is required for the global expression of cell-cycle genes controlled by the repressive DREAM complex. Mechanistically, PAF inhibits DREAM complex formation by binding to RBBP4, a core DREAM subunit, leading to transactivation of DREAM target genes. Furthermore, pharmacological mimicking of PAF-depleted transcriptomes inhibited LUAD tumor growth. Our results unveil how the PAF-remodeled DREAM complex bypasses cell quiescence to promote lung tumorigenesis and suggest that the PAF-DREAM axis may be a therapeutic vulnerability in lung cancer.

A Surge of DNA Damage Links Transcriptional Reprogramming and Hematopoietic Deficit in Fanconi Anemia.

Impaired DNA crosslink repair leads to Fanconi anemia (FA), characterized by a unique manifestation of bone marrow failure and pancytopenia among diseases caused by DNA damage response defects. As a germline disorder, why the hematopoietic hierarchy is specifically affected is not fully understood. We find that reprogramming transcription during hematopoietic differentiation results in an overload of genotoxic stress, which causes aborted differentiation and depletion of FA mutant progenitor cells. DNA damage onset most likely arises from formaldehyde, an obligate by-product of oxidative protein demethylation during transcription regulation. Our results demonstrate that rapid and extensive transcription reprogramming associated with hematopoietic differentiation poses a major threat to genome stability and cell viability in the absence of the FA pathway. The connection between differentiation and DNA damage accumulation reveals a novel mechanism of genome scarring and is critical to exploring therapies to counteract the aplastic anemia for the treatment of FA patients.

Clinical characteristics and salivary biomarkers of burning mouth syndrome.

OBJECTIVES: To investigate the clinical characteristics and salivary biomarkers in each type of burning mouth syndrome (BMS) patients. MATERIALS AND METHODS: Ninety-eight postmenopausal female patients with BMS were included. Fifty and 21 patients were assigned to the primary and secondary groups, respectively. Twenty-seven patients with both primary and secondary characteristics were assigned to the intermediate group. Comprehensive clinical characteristics and salivary biomarkers were analyzed. RESULTS: Significant differences in age, proportion of hyposalivator patients based on unstimulated whole saliva (UWS), symptom distribution, severties of burning sensation and effect of oral complaints in daily life (Eff-life), and positive symptom distress index (PSDI) were observed among the three groups. The primary group had significant higher UWS flow rate, fewer UWS hyposalivator proportions, and lesser severity of Eff-life than the secondary group. The intermediate group had significantly greater intensities of burning sensation and Eff-life and higher PSDI score than did the primary group. The primary group had significantly higher cortisol and dehydroepiandrosterone (DHEA) levels in stimulated whole saliva than did the secondary group. CONCLUSIONS: This study's findings show that clinical characteristics differentiate each BMS type. Cortisol and DHEA levels are potential salivary biomarkers for discriminating between the primary and secondary types of BMS.

Changes in the lesion surface suggesting transformation of oral potentially malignant disorders to malignancy - a report of eight cases.

BACKGROUND: In the case of oral potentially malignant disorders (OPMD), the possibility of malignant transformation of the lesion necessitates a decision on the need for an additional biopsy at each visit. Among many clinical characteristics, change on the lesion surface is one of the important factors that determine the need for additional biopsy at each visit. The purpose of the study was to provide information on the characteristics of lesions related to malignant transformation during the follow-up period of OPMD. METHODS: Eight patients (four men and four women) with OPMD that transformed into malignancy during long-term follow-up were included and their mean age was 65.8 ± 12.4 years. Clinical information and histopathological diagnosis were investigated at the initial visit and during the long-term follow-up period. The focus was on information on changes on the lesion surface at the time the lesion was confirmed to be malignant. The period from initial diagnosis to dysplasia and from dysplasia to malignancy was also investigated. RESULTS: The OPMD diagnoses were oral lichen planus or oral lichenoid lesions (n = 2), oral leukoplakia (n = 5), and hyperplastic candidiasis (n = 1). During the follow-up period of the lesions, when dysplasia was obtained by additional biopsy, changes in the lesions consisted of an increase in the size of the white or red area. The lesion surface of the OPMD showed verrucous, papillary, exophytic, corrugated, and ulcerative changes at the time of malignancy diagnosis. The period for the initial lesion to become dysplasia, from dysplasia to malignancy, and from the initial lesion to malignancy was very variable. CONCLUSIONS: Attention should be paid to verrucous, papillary, exophytic, corrugated, and ulcerative changes on the lesion surface of OPMD. Considering that the period for OPMD to become malignant is highly variable, a longer follow-up of the lesion is necessary.

TMEM9-v-ATPase Activates Wnt/ß-Catenin Signaling Via APC Lysosomal Degradation for Liver Regeneration and Tumorigenesis.

BACKGROUND AND AIMS: How Wnt signaling is orchestrated in liver regeneration and tumorigenesis remains elusive. Recently, we identified transmembrane protein 9 (TMEM9) as a Wnt signaling amplifier. APPROACH AND RESULTS: TMEM9 facilitates v-ATPase assembly for vesicular acidification and lysosomal protein degradation. TMEM9 is highly expressed in regenerating liver and hepatocellular carcinoma (HCC) cells. TMEM9 expression is enriched in the hepatocytes around the central vein and acutely induced by injury. In mice, Tmem9 knockout impairs hepatic regeneration with aberrantly increased adenomatosis polyposis coli (Apc) and reduced Wnt signaling. Mechanistically, TMEM9 down-regulates APC through lysosomal protein degradation through v-ATPase. In HCC, TMEM9 is overexpressed and necessary to maintain ß-catenin hyperactivation. TMEM9-up-regulated APC binds to and inhibits nuclear translocation of ß-catenin, independent of HCC-associated ß-catenin mutations. Pharmacological blockade of TMEM9-v-ATPase or lysosomal degradation suppresses Wnt/ß-catenin through APC stabilization and ß-catenin cytosolic retention. CONCLUSIONS: Our results reveal that TMEM9 hyperactivates Wnt signaling for liver regeneration and tumorigenesis through lysosomal degradation of APC.

Treatment outcomes and related clinical characteristics in patients with burning mouth syndrome.

OBJECTIVES: To evaluate the treatment outcomes of medication therapies in patients with burning mouth syndrome (BMS) and to identify the clinical characteristics that may affect the efficacy of prescribed medications. METHODS: This is a retrospective study of 769 patients with oral burning sensations. Of these patients, 420 patients diagnosed as the primary BMS received an "Initial Approach" that involved a detailed explanation about its etiopathophysiology, self-care instruction, and use of an oral lubricant. Neuropathic medications were prescribed for 277 patients who did not respond to the initial approach. Clinical characteristics, prescribed medications, and changes in intensity of oral symptoms were reviewed. RESULTS: Clonazepam was administered as the first-line medication. Alpha-lipoic acid (ALA), gabapentin, and nortriptyline were commonly administered in combination with clonazepam. More than two-thirds of the patients reported a marked improvement in oral symptoms after treatments with combination of neuropathic medications and ALA. The efficacies of the initial approach and clonazepam had significant positive associations with the initial intensity of oral symptoms and significant negative associations with depression. CONCLUSIONS: Clonazepam therapy in combination with appropriate medications was effective for managing patients with BMS. The initial intensity of oral symptoms and psychological status were significantly associated with treatment outcomes.

Oral health-related quality of life and associated factors in patients with burning mouth syndrome.

OBJECTIVE: The purpose of this study was to assess oral health-related quality of life (OHRQoL) in patients with burning mouth syndrome (BMS) and to identify clinical factors associated with OHRQoL. METHODS: Fifty-seven patients with BMS (56.4 ± 10.7 years) participated in the study. Patients underwent oral examination, laboratory tests, psychological evaluation, measurement of salivary flow rates and evaluation of clinical characteristics using a BMS questionnaire. The OHRQoL of patients was assessed using the Oral Health Impact Profile-14 (OHIP-14). RESULTS: The OHIP-14 score for patients with BMS was 38.6 ± 12.8. Patients had higher scores for the psychological discomfort and physical pain dimensions of the OHIP-14. The intensity of taste disturbance or xerostomia symptoms (ß = 0.464, P < .001), worry about symptoms (ß = 0.307, P = .020), and results of psychological evaluation (ß = 0.311, P = .026) were significantly associated with OHIP-14 score. Multiple linear regression showed that the intensity of taste disturbance or xerostomia symptoms was significantly associated with decreased OHRQoL (ß = 0.637, P = .026). CONCLUSIONS: This study suggests that severity of taste disturbance or xerostomia is an important factor that influences OHRQoL in patients with BMS.

Oral health-related quality of life and associated factors in patients with xerostomia.

OBJECTIVE: This study aimed to investigate clinical and demographic factors associated with oral health-related quality of life (OHRQoL) in patients with xerostomia. METHODS: Forty-one patients (55.2 ± 13.8 years) with xerostomia as a chief complaint participated in the study. Comprehensive information about clinical and demographic characteristics of the patients with xerostomia, xerostomia-related symptoms and behaviours, and xerostomia-associated complaints was investigated using a xerostomia questionnaire. Flow rates of unstimulated and stimulated whole saliva were measured. The Oral Health Impact Profile-14 (OHIP-14) score was used to assess the OHRQoL of patients. The relationships between various factors and the OHIP-14 score were assessed by simple and multiple linear regression analyses. RESULTS: The OHIP-14 score of patients with xerostomia was high (44.3 ± 13.2). Characteristics of the patients with xerostomia associated with high OHIP-14 score were the intensity of xerostomia-related symptoms, frequency of xerostomia-related behaviours and the presence of speaking difficulty. Results from multiple linear regressions found that self-reported amount of saliva in usual, everyday life (ß = 0.622, p = 0.012) and the presence of a speaking difficulty (ß = 0.348, p = 0.014) had significant adversely affected the OHRQoL in patients with xerostomia. CONCLUSIONS: Subjective perceptions of the amount of saliva in the mouth and the experience of speaking difficulty affected the OHRQoL in patients with xerostomia.

Necrotic cell death induces melanotic mass formation in Drosophila.

The immune system protects its host from not only invading parasites and parasitoids, but also altered self tissue, including dying cells. Necrotic cells are strongly immunogenic, but in Drosophila this has not been directly addressed, due partially to the fact that knowledge about necrosis in Drosophila currently lags behind that for other models. Upon the loss of cell matrix attachment, endocycling polyploid tissues of the Drosophila larva undergo autophagy instead of apoptosis; we employed this system as a model to examine cell death modalities and immunity. Here, we report that larval fat body cells depleted of integrin undergo not only autophagy, but also necrotic cell death, and that a blockade of reaper, grim, hid, or the downstream caspases enhances necrosis. These cells elicit melanotic mass formation, an autoimmune-like response. We also show that necrosis is the main cause of melanotic mass formation in these anchorage-depleted polyploid cells.

Characteristics of metabolic factors related to arterial stiffness in young and old adults.

It has not been adequately studied which biomarkers for cardiovascular risk indicate changes of atherosclerosis by aging process. The current study aimed to investigate the characteristics of metabolic factors related to arterial stiffness in young and old adults. Our cross-sectional study enrolled 851 healthy young adults and 719 old adults. Metabolic biomarkers included glucose, lipid profiles, and liver enzymes. In young adults, additional biomarkers such as C-reactive protein, apolipoproteins, lipoprotein(a), ferritin, and 25-hydroxycholecalciferol were measured. Arterial stiffness was evaluated by measuring brachial-ankle pulse wave velocity (baPWV). The mean age was 37.8 and 65.1 years old in the young and old groups, respectively. Without adjustment, most parameters were significantly correlated with baPWV in both young and old groups. Mean baPWV was significantly different according to metabolic syndrome (MetS) in both groups (13.1 and 12.1 m/s in the young subjects with and without MetS, respectively; 17.4 and 15.8 m/s, respectively, in the old group). After adjusting for age, sex, and hemodynamic factors, the difference in baPWV according to MetS was significant only in the old group. The relationship between most biomarkers and baPWV was influenced by metabolic disorders such as hypertension and diabetes in old adults. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and apolipoprotein B were significant in young group. In conclusion, the metabolic biomarkers related to arterial stiffness were different between young and old adults. Contrary to old adults, TC, LDLC, and apolipoprotein B were independent biomarkers for arterial stiffness in healthy young adults.

A cross-sectional study of the association between adipokine levels and bone mineral density according to obesity and menopausal status in Korean women.

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, ß = -0.576, P = 0.006; femoral neck, ß = -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 (ß = 0.240, P = 0.010) in premenopausal women but negatively associated with BMD (lumbar, ß = -0.436, P = 0.012; femoral neck, ß = -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.

The association of testosterone, sex hormone-binding globulin, and insulin-like growth factor-1 with bone parameters in Korean men aged 50 years or older.

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 (ß = -0.139 for osteocalcin and ß = -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.

Association of serum 25-hydroxyvitamin D and serum total cholesterol with depressive symptoms in Korean adults: the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012).

OBJECTIVE: To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population. DESIGN: This was a population-based cross-sectional study. SETTING: The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). SUBJECTS: We included 7198 adults aged 20-88 years. RESULTS: The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1·54-fold (95 % CI 1·20, 1·98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D ≥20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1·60; 95 % CI 1·23, 2·08) and non-significant in individuals with high serum total cholesterol (OR=0·97; 95 % CI 0·52, 1·81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles). CONCLUSIONS: The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression.

Basement membrane and cell integrity of self-tissues in maintaining Drosophila immunological tolerance.

The mechanism underlying immune system recognition of different types of pathogens has been extensively studied over the past few decades; however, the mechanism by which healthy self-tissue evades an attack by its own immune system is less well-understood. Here, we established an autoimmune model of melanotic mass formation in Drosophila by genetically disrupting the basement membrane. We found that the basement membrane endows otherwise susceptible target tissues with self-tolerance that prevents autoimmunity, and further demonstrated that laminin is a key component for both structural maintenance and the self-tolerance checkpoint function of the basement membrane. Moreover, we found that cell integrity, as determined by cell-cell interaction and apicobasal polarity, functions as a second discrete checkpoint. Target tissues became vulnerable to blood cell encapsulation and subsequent melanization only after loss of both the basement membrane and cell integrity.

Polymorphisms of interleukin-1ß and MUC7 genes in burning mouth syndrome.

OBJECTIVE: The objectives of the present study are to compare polymorphisms of the IL-1ß and MUC7 genes between patients with burning mouth syndrome (BMS) and controls and to investigate relationships between these polymorphisms and clinical characteristics in BMS patients. MATERIALS AND METHODS: Forty female BMS patients and 40 gender- and age-matched controls were included. Genomic DNA was extracted from saliva samples. Single-nucleotide polymorphisms of IL-1ß -511 and +3954 and variation in number of tandem repeat (VNTR) polymorphism of MUC7 were analyzed. Relationships between genotypic polymorphism data and clinical characteristics in BMS patients were also analyzed. RESULTS: There were no significant differences in the genotypes of IL-1ß -511 and +3954 and of MUC7 between the groups. There were no significant differences in symptom duration and intensity of BMS patients according to their IL-1ß and MUC7 genotypes. The T allele of IL-1ß -511 showed associations with psychometry results in BMS patients: paranoid ideation (P = 0.014), Global Severity Index (P = 0.025), and Positive Symptom Total (P = 0.008). CONCLUSIONS: The genotypic polymorphisms of IL-1ß -511 and +3954, and of MUC7 VNTR, had no direct associations with the development of BMS. However, the T allele of IL-1ß -511 may increase the risk of BMS by increasing psychological asthenia. CLINICAL RELEVANCE: The genotypic polymorphisms of IL-1ß -511 may increase the risk for the development of BMS by increasing psychological asthenia.

Effects of carbon source and light intensity on the growth and total lipid production of three microalgae under different culture conditions.

We attempted to enhance the growth and total lipid production of three microalgal species, Isochrysis galbana LB987, Nannochloropsis oculata CCAP849/1, and Dunaliella salina, which are capable of accumulating high content of lipid in cells. Low nitrogen concentration under photoautotrophic conditions stimulated total lipid production, but a decreasing total lipid content and an increasing biomass were observed with increasing nitrogen concentration. Among the different carbon sources tested for heterotrophic cultivation, glucose improved the growth of all three strains. The optimal glucose concentration for growth of I. galbana LB987 and N. oculata CCAP849/1 was 0.02 M, and that of D. salina was 0.05 M. Enhanced growth occurred when they were cultivated under heterotrophic or mixotrophic conditions compared with photoautotrophic conditions. Meanwhile, high total lipid accumulation in cells occurred when they were cultivated under photoautotrophic or mixotrophic conditions. During mixotrophic cultivation, biomass production was not affected significantly by light intensity; however, both chlorophyll concentration and total lipid content increased dramatically with increasing light intensity up to 150 µmol/m(2)/s. The amount and composition ratio of saturated and unsaturated fatty acids in cells were different from each other depending on both species and light intensity. The highest accumulation of total fatty acid (C16-C18) among the three strains was found from cells of N. oculata CCAP849/1, which indicates that this species can be used as a source for production of biodiesel.

Oral manifestations in vitamin B12 deficiency patients with or without history of gastrectomy.

BACKGROUND: The purpose of this study was to compare clinical features of vitamin B12 deficiency patients with a history of gastrectomy to those without a history of gastrectomy. METHODS: Twenty-two patients with vitamin B12 deficiency were included. Patients' chief complaints, oral manifestations, blood examination results, and past medical histories were reviewed. RESULTS: Eleven patients had a history of gastrectomy and 11 did not. The chief complaint was glossodynia in all patients. No significant differences were observed between the two groups regarding age, sex, symptom duration, or plasma vitamin B12 level. Erythema and depapillation of the tongue were the most common findings, however less common among patients without a history of gastrectomy. Two patients with a history of gastrectomy and 5 patients without a history of gastrectomy had normal oral mucosa. Patients with a history of gastrectomy were more anemic. Oral symptoms of the majority of patients responded to antifungals and vitamin B12 replacement. The suggested etiologies for vitamin B12 deficiency in the patients without a history of gastrectomy were gastritis, medications, diet, autoimmunity, and early gastric cancer. CONCLUSIONS: Vitamin B12 deficiency and its associated etiological factors should be considered in patients with glossodynia, even those whose oral mucosa appears normal and who lack a history of gastrectomy.

Decreased muscle mass is not an independent risk factor for metabolic syndrome in Korean population aged 70 or older.

CONTEXT: The association of low muscle mass with cardiometabolic risks is still controversial. OBJECTIVE: The aim of this study was to investigate the relationship between low muscle mass and metabolic syndrome (MetS) according to the various muscle mass indices and to evaluate the influence of muscle mass on MetS independent of fat mass. DESIGN: Cross-sectional study SUBJECTS: About 841 men and 1106 women aged 70 or older from Korea National Health and Nutrition Examination Survey 2008-2010 MEASUREMENTS: We used various muscle mass indices: appendicular skeletal muscle mass (ASM) divided by height squared (ASM/Ht(2) ), ASM divided by body weight (ASM/Wt) and ASM adjusted for height and fat mass (residual). Low muscle mass is defined as ASM/Ht(2) and ASM/Wt below 2 SD of the sex-specific mean for healthy young adults. The sex-specific lowest quintile of the distribution of the residual was regarded as low muscle mass. RESULTS: The prevalence of MetS was higher in the population with low muscle mass defined by ASM/Wt, but lower in those defined by ASM/Ht(2) . However, after stratification according to the central obesity, low muscle mass was barely related with MetS. Meanwhile, when both ASM and fat mass were included in a logistic regression model, the odds ratios of 1 SD change of ASM for MetS were 1·07 (0·85-1·34) for men and 1·24 (1·04-1·47) for women, respectively. CONCLUSIONS: The relationship between low muscle mass and MetS was different according to the various muscle mass indices. After controlling the influence of fat mass, decreased muscle mass was not an independent risk factor for MetS.

Coronary artery calcification is associated with high serum concentration of undercarboxylated osteocalcin in asymptomatic Korean men.

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.

Prediction of prevalent but not incident non-alcoholic fatty liver disease by levels of serum testosterone.

BACKGROUND AND AIMS: The association between testosterone level and development of non-alcoholic fatty liver disease (NAFLD) is not well known. We examined the relationship of total testosterone level with development and regression of NAFLD. METHODS: Among the men who had undergone repeated liver ultrasonography in 2 years or more at a health promotion center, subjects with available serum testosterone level at baseline were included in the study. Alcohol consumers (> 20 g/day) were excluded from the study. RESULTS: Among the 1944 men, 44.3% of subjects were diagnosed with NAFLD. Higher level of testosterone significantly lowered the prevalence of fatty liver (odds ratios per SD increase, 0.686 and 0.795 at baseline and follow-up, respectively). During the median 4.2 years follow-up, 22.4% of subjects in the normal group developed fatty liver, and 21.0% of subjects in the NAFLD group recovered at the follow-up. In longitudinal analyses, higher level of testosterone was significantly associated with the development or regression of fatty liver, before adjustment for obesity and metabolic parameters. However, in the full-adjusted model, testosterone level did not influence the development or regression of fatty liver. CONCLUSIONS: Although testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses, baseline testosterone level did not independently influence the development or regression of fatty liver at the median 4.2 years follow-up. Obesity and metabolic parameters may play key roles in the link between testosterone level and NAFLD.