Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population.

BACKGRUOUND: There is debate about ultrasonography screening for thyroid cancer and its cost-effectiveness. This study aimed to evaluate the cost-effectiveness of early screening (ES) versus symptomatic detection (SD) for differentiated thyroid cancer (DTC) in Korea. METHODS: A Markov decision analysis model was constructed to compare the cost-effectiveness of ES and SD. The model considered direct medical costs, health outcomes, and different diagnostic and treatment pathways. Input data were derived from literature and Korean population studies. Incremental cost-effectiveness ratio (ICER) was calculated. Willingness-to-pay (WTP) threshold was set at USD 100,000 or 20,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address uncertainties of the model's variables. RESULTS: In a base case scenario with 50 years of follow-up, ES was found to be cost-effective compared to SD, with an ICER of $2,852 per QALY. With WTP set at $100,000, in the case with follow-up less than 10 years, the SD was cost-effective. Sensitivity analysis showed that variables such as lobectomy probability, age, mortality, and utility scores significantly influenced the ICER. Despite variations in costs and other factors, all ICER values remained below the WTP threshold. CONCLUSION: Findings of this study indicate that ES is a cost-effective strategy for DTC screening in the Korean medical system. Early detection and subsequent lobectomy contribute to the cost-effectiveness of ES, while SD at an advanced stage makes ES more cost-effective. Expected follow-up duration should be considered to determine an optimal strategy for DTC screening.

Identification of Terpene Compositions in the Leaves and Inflorescences of Hybrid Cannabis Species Using Headspace-Gas Chromatography/Mass Spectrometry.

Although cannabidiol and tetrahydrocannabinol in Cannabis species exert their pharmacological effects via the endocannabinoid system, it is believed that other phytochemicals, particularly terpenes, can modulate therapeutic outcomes through the entourage effect. Therefore, to gain a better understanding of the pharmacological effects of Cannabis, obtaining information on phytochemical compositions, including mono-, di-, and sesqui-terpenes in Cannabis species is essential. Applying a sophisticated analytical method is indispensable. In this study, headspace-gas chromatography/mass spectrometry (HS-GC/MS) was employed to identify major terpenes in the leaves and inflorescences of hybrid Cannabis species. The incubation time and temperature conditions for HS-GC/MS were optimized. This method was successfully applied to the leaves (n = 9) and inflorescences (n = 7) of hybrid Cannabis species. A total of 26 terpenes in Cannabis species were detected, and six major components, such as α-pinene (9.8-2270 µg/g), ß-pinene (2.6-930 µg/g), myrcene (0.7-17,400 µg/g), limonene (1.3-300 µg/g), ß-caryophyllene (60-3300 µg/g), and α-humulene (40-870 µg/g), were quantified. Each sample showed different terpene compositions, but six major terpenes among all the terpenes detected were consistently found in both the leaves and inflorescences of hybrid Cannabis species. In this study, the six major terpenes' potential in hybrid Cannabis species was evaluated as biomarkers to distinguish hybrid Cannabis species samples. This study contributes to a better understanding of the entourage effect of Cannabis-based botanical drugs.

Engineering homoeologs provide a fine scale for quantitative traits in polyploid.

Numerous staple crops exhibit polyploidy and are difficult to genetically modify. However, recent advances in genome sequencing and editing have enabled polyploid genome engineering. The hexaploid black nightshade species Solanum nigrum has immense potential as a beneficial food supplement. We assembled its genome at the scaffold level. After functional annotations, we identified homoeologous gene sets, with similar sequence and expression profiles, based on comparative analyses of orthologous genes with close diploid relatives Solanum americanum and S. lycopersicum. Using CRISPR-Cas9-mediated mutagenesis, we generated various mutation combinations in homoeologous genes. Multiple mutants showed quantitative phenotypic changes based on the genotype, resulting in a broad-spectrum effect on the quantitative traits of hexaploid S. nigrum. Furthermore, we successfully improved the fruit productivity of Boranong, an orphan cultivar of S. nigrum suggesting that engineering homoeologous genes could be useful for agricultural improvement of polyploid crops.

Broadband soft X-ray source from a clustered gas target dedicated to high-resolution XCT and X-ray absorption spectroscopy.

The development of the broad-bandwidth photon sources emitting in the soft X-ray range has attracted great attention for a long time due to the possible applications in high-resolution spectroscopy, nano-metrology, and material sciences. A high photon flux accompanied by a broad, smooth spectrum is favored for the applications such as near-edge X-ray absorption fine structure (NEXAFS), extended X-ray absorption fine structure (EXAFS), or XUV/X-ray coherence tomography (XCT). So far, either large-scale facilities or technologically challenging systems providing only limited photon flux in a single shot dominate the suitable sources. Here, we present a soft, broad-band (1.5 nm - 10.7 nm) soft X-ray source. The source is based on the interaction of very intense laser pulses with a target formed by a cluster mixture. A photon yield of 2.4 × 1014 photons/pulse into 4π (full space) was achieved with a medium containing Xe clusters of moderate-size mixed with a substantial amount of extremely large ones. It is shown that such a cluster mixture enhances the photon yield in the soft X-ray range by roughly one order of magnitude. The size of the resulting source is not beneficial (≤500 µm but this deficit is compensated by a specific spectral structure of its emission fulfilling the specific needs of the spectroscopic (broad spectrum and high signal dynamics) and metrological applications (broad and smoothed spectrum enabling a sub-nanometer resolution limit for XCT).

Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review.

Papillary thyroid microcarcinoma (PTMC) has indolent features and low mortality. Recently, active surveillance (AS) instead of early surgery (ES) has been introduced as one treatment option but economical preference has not been established. The study objective was to systemically review the literature relating to cost-effectiveness of AS compared to ES for PTMC. Keywords were selected through PICO (Population, Intervention, Comparison, and Outcomes) tools. The search was conducted using PubMed, Cochrane, EMBASE, and Elsevier databases. Papers that had irrelevant titles were written in foreign languages, or had no original results were excluded. Out of the 62 papers extracted, five relevant to the subject matter of this study were identified. Three papers made their own decision models and proceeded with cost-effectiveness analysis (CEA), but the remaining two simply compared costs rather than cost-effectiveness. In terms of cost-effectiveness, three papers preferred AS, one preferred ES, and one preferred neither. The major differences in the CEA might arise from variations in each country's medical insurance system, the utility score systems, and decision models used. In subgroup analysis, two papers preferred AS to ES for patients at a younger age at diagnosis in terms of cost-effectiveness as well as tumor biological characteristics. Although AS has been generally more cost-effective than ES in previous publications, younger age at diagnosis could be one factor contributing to preference for ES. The CEA of prospective cohorts based on the decision model and utility score for thyroid cancer should be undertaken to confirm the cost-effectiveness of AS.

3D-Printed Collagen Scaffolds Promote Maintenance of Cryopreserved Patients-Derived Melanoma Explants.

The development of an in vitro three-dimensional (3D) culture system with cryopreserved biospecimens could accelerate experimental research screening anticancer drugs, potentially reducing costs and time bench-to-beside. However, minimal research has explored the application of 3D bioprinting-based in vitro cancer models to cryopreserved biospecimens derived from patients with advanced melanoma. We investigated whether 3D-printed collagen scaffolds enable the propagation and maintenance of patient-derived melanoma explants (PDMEs). 3D-printed collagen scaffolds were fabricated with a 3DX bioprinter. After thawing, fragments from cryopreserved PDMEs (approximately 1-2 mm) were seeded onto the 3D-printed collagen scaffolds, and incubated for 7 to 21 days. The survival rate was determined with MTT and live and dead assays. Western blot analysis and immunohistochemistry staining was used to express the function of cryopreserved PDMEs. The results show that 3D-printed collagen scaffolds could improve the maintenance and survival rate of cryopreserved PDME more than 2D culture. MITF, Mel A, and S100 are well-known melanoma biomarkers. In agreement with these observations, 3D-printed collagen scaffolds retained the expression of melanoma biomarkers in cryopreserved PDME for 21 days. Our findings provide insight into the application of 3D-printed collagen scaffolds for closely mimicking the 3D architecture of melanoma and its microenvironment using cryopreserved biospecimens.

Obesity, abdominal obesity and subsequent risk of kidney cancer: a cohort study of 23.3 million East Asians.

BACKGROUND: Limited evidence exists regarding associations between obesity and kidney cancer among Asians. We examined the associations between obesity measures and risk of kidney cancer. METHODS: We included 23,313,046 adults who underwent health examinations provided by the Korean National Health Insurance Service 2009-2012 and performed multivariable Cox proportional hazards regression analyses. RESULTS: During 5.4 years of follow-up, 18,036 cases of kidney cancer were recorded, and cumulative incidence was 0.12%. General and abdominal obesity were associated with 1.32-fold increased risk of kidney cancer compared with groups without either obesity status. Underweight individuals showed decreased adjusted hazard ratio (HR) for kidney cancer (0.76, 95% confidence interval: 0.68-0.85) compared to those with normal body mass index (BMI), while the HRs increased among individuals with BMI 23-24.9 kg/m2 (1.23, 1.18-1.28), 25-29.9 kg/m2 (1.41, 1.36-1.46) and ≥30 kg/m2 (1.77, 1.65-1.90) (P for trend < 0.001). HRs of kidney cancer increased with increasing waist circumference (WC) (P for trend < 0.001). Compared to non-obese condition, the coexistence of general and abdominal obesity increased the HR (1.45, 1.40-1.50). CONCLUSIONS: This study demonstrated positive associations of BMI and WC with kidney cancer risk. General and abdominal obesity may be risk factors of kidney cancer.

Enhanced Strain Measurement Range of an FBG Sensor Embedded in Seven-Wire Steel Strands.

FBG sensors offer many advantages, such as a lack of sensitivity to electromagnetic waves, small size, high durability, and high sensitivity. However, their maximum strain measurement range is lower than the yield strain range (about 1.0%) of steel strands when embedded in steel strands. This study proposes a new FBG sensing technique in which an FBG sensor is recoated with polyimide and protected by a polyimide tube in an effort to enhance the maximum strain measurement range of FBG sensors embedded in strands. The validation test results showed that the proposed FBG sensing technique has a maximum strain measurement range of 1.73% on average, which is 1.73 times higher than the yield strain of the strands. It was confirmed that recoating the FBG sensor with polyimide and protecting the FBG sensor using a polyimide tube could effectively enhance the maximum strain measurement range of FBG sensors embedded in strands.

Oral health behaviors and bone mineral density in South Korea: the 2008-2010 Korean National Health and Nutrition Examination Survey.

The purpose of this study was to examine the association between oral health behaviors and bone mineral density (BMD) by using data from the Korean National Health and Nutrition Examination Survey conducted in 2008-2010. We included 6,620 subjects (3,140 men aged more than 50 years and 3,480 postmenopausal women). BMD was measured at three sites-namely, the lumbar spine, total femur, and femur neck. Oral health behaviors were assessed by use of a self-administered questionnaire in the Korean National Health and Nutrition Examination Survey. After adjustment for all covariates, BMD of the lumbar spine and femur neck tended to increase as the frequency of tooth brushing increased in men (p trend = 0.020 and p trend = 0.028, respectively). Women using secondary oral products had increased lumbar spine BMD compared with women who did not use secondary oral products. However, after adjustment for all covariates, no significant relationship was observed between BMD and the use of secondary oral products. As the frequency of tooth brushing and the number of secondary oral products used increased, the prevalence of osteoporosis decreased. The frequency of tooth brushing is associated with increased lumbar spine and femur neck BMD in South Korean men.

Serum and urine concentrations of morphine and morphine metabolites in patients with advanced cancer receiving continuous intravenous morphine: an observational study.

BACKGROUND: The feasibility and clinical implication of drug monitoring of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) need further investigation. This study aimed to determine what predicts serum concentrations of morphine in cancer patients receiving continuously intravenous morphine, the relationships between serum concentration of morphine/its metabolites and urinary concentrations, and the relation between morphine concentrations and with clinical outcomes. METHODS: We collected serum and urine samples from 24 patients with advanced cancer undergoing continuously intravenous morphine therapy. Serum samples were obtained at day one. Spot urine samples were collected once daily on three consecutive days. Pain and adverse drug events were assessed using the Korean version of MD Anderson Symptom Inventory. RESULTS: A total of 96 samples (72 urine and 24 serum samples) were collected. Median dose of morphine was 82.0 mg/24 h. In a multivariate analysis, total daily morphine dose was the most significant predictors of both serum and urine concentration of morphine. Morphine, M6G, and M3G in serum and urine were statistical significantly correlated (correlation coefficient = 0.81, 0.44, 0.56; p values < 0.01, 0.03, 0.01, respectively). CONCLUSION: Spot urine concentrations of morphine and its metabolites were highly correlated to those of serum. Total dose of daily morphine was related to both serum and urine concentration of morphine and its metabolites.

Is carotid artery evaluation necessary for primary prevention in asymptomatic high-risk patients without atherosclerotic cardiovascular disease?

OBJECTIVE: Routine measurement of the carotid intima-media thickness is not recommended in recent clinical practice guidelines for risk assessment of the first atherosclerotic cardiovascular disease (ASCVD) event (the definition of which includes acute coronary syndromes, a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin). The aim of the present study was to elucidate the role of carotid artery evaluation for primary prevention of ASCVD in asymptomatic high-risk patients visiting a teaching hospital. METHODS: Eight hundred seventy-three patients (487 male [55.8%], mean age 59.4±11.5 years) who were statin-naive and without ASCVD, which was proven by coronary angiography or coronary CT angiography, were enrolled in this study. The patients underwent carotid scanning in the Medical Department of St Mary's Hospital from September 2003 to March 2009. ASCVD outcomes were evaluated for median follow-up of 1,402 days. RESULTS: A total of 119 participants experienced ASCVD events. In multivariate Cox regression analysis, age (hazard ratio [HR] =1.026, 95% confidence interval [CI] =1.002-1.050, P=0.033), history of smoking (HR =1.751, 95% CI =1.089-2.815, P=0.021), statin therapy (HR =0.388, 95% CI =0.205-0.734, P=0.004), and carotid plaques (HR =1.556, 95% CI =1.009-2.400, P=0.045) were associated with ASCVD events. In middle-aged group (45≤ age <65, n=473), history of smoking (HR =1.995, 95% CI =1.142-3.485, P=0.015), statin therapy (HR =0.320, 95% CI =0.131-0.780, P=0.012), and carotid plaques (HR =1.993, 95% CI =1.116-3.560, P=0.020) were associated with ASCVD events. CONCLUSION: The presence of carotid plaques, history of smoking, and statin therapy might be important factors for primary prevention of ASCVD in asymptomatic high-risk patients, especially in middle-aged patients. Therefore, the results suggest that carotid artery parameters may have an additional predictive value for primary prevention of ASCVD in the middle-aged high-risk patients.

Hyponatremia as an independent prognostic factor in patients with terminal cancer.

PURPOSE: Hyponatremia is a common and associated with poor clinical outcome in cancer patients. But little is known regarding hyponatremia in terminal cancer patients. The purpose of this study is to investigate the prognostic role of the hyponatremia in terminal cancer patients. METHODS: A retrospective observational study was conducted between January 2010 and December 2012 in a tertiary hospital palliative care unit. Medical records were collected from hospitalized patients who were eligible for obtaining serum sodium level. Hyponatremia was defined as serum sodium <136 mEq/L. And we classified patients into three groups; eunatremia (sodium 136-145 mEq/L), mild to moderate hyponatremia (sodium 126-135 mEq/L), and severe hyponatremia (sodium ≤125 mEq/L). Univariate and multivariate Cox regression analyses were performed to determine factors affecting survival time. RESULTS: Of the 576 patients, hyponatremia was present in 367 individuals (63.7 %). In the univariate analysis, serum CRP, PPS, and sodium ≤125 mEq/L were associated with survival time (HR = 1.22; p < 0.001, HR = 0.69; p < 0.001, HR = 1.91; p < 0.001). In the multivariate analysis, serum CRP, PPS, sodium 126-135 mEq/L, and sodium ≤125 mEq/L were associated with survival time (HR = 1.16; p < 0.001, HR = 0.70; p < 0.001, HR = 1.19; p = 0.048, HR = 1.75; p < 0.001). CONCLUSIONS: Hyponatremia is an independent prognostic factor in terminal cancer patients and careful clinical concern is needed. In the future, large prospective study is warranted in terminal cancer patients.

Tauroursodeoxycholic acid, a bile acid, promotes blood vessel repair by recruiting vasculogenic progenitor cells.

Although serum bile acid concentrations are approximately 10 µM in healthy subjects, the crosstalk between the biliary system and vascular repair has never been investigated. In this study, tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34(+) hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34(+) /Sca1(+) progenitors in mice peripheral blood (PB), and CD34(+) , CD31(+) , and c-kit(+) progenitors in human PB. In addition, TUDCA increased differentiation of CD34(+) HSCs into EPC lineage cells via Akt activation. EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein via Akt activation. Interestingly, TUDCA induced integration of EPCs into human aortic endothelial cells (HAECs) by increasing adhesion molecule expression. In the mouse hind limb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1(+) /CD34(+) and Sca-1(+) /c-kit(+) progenitors into damaged tissue. In GFP(+) bone marrow-transplanted hind limb ischemia, TUDCA induced recruitment of GFP(+) /c-kit(+) progenitors to the ischemic area, resulting in an increased blood perfusion ratio. Histological analysis suggested that GFP(+) progenitors mobilized from bone marrow, integrated into blood vessels, and differentiated into VEGFR(+) cells. In addition, TUDCA decreased cellular senescence by reducing levels of p53, p21, and reactive oxygen species and increased nitric oxide. Transplantation of TUDCA-primed senescent EPCs in hind limb ischemia significantly improved blood vessel regeneration, as compared with senescent EPCs. Our results suggested that TUDCA promoted neovascularization by enhancing the mobilization of stem/progenitor cells from bone marrow, their differentiation into EPCs, and their integration with preexisting endothelial cells.

Association between the duration of palliative care service and survival in terminal cancer patients.

PURPOSE: Preliminary studies of early palliative care showed improved quality of life, less medical cost, and better survival time. But, most terminal cancer patients tend to be referred to palliative care late. For the proper care of terminal cancer patients, it is necessary to refer to hospice and palliative care timely. The aim of this study is to analyze the effect of the duration of palliative care services on the survival in terminal cancer patients. METHODS: We reviewed 609 patients who had died from terminal cancer between January 2010 and December 2012. We analyzed correlations of age, first Palliative Performance Scale (PPS) level, duration of palliative care service, and survival time. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. RESULTS: Duration of palliative care services was significantly correlated with survival time. In univariate Cox regression analysis, age, and each group of duration of palliative care service showed significant associations with survival. Final multivariate Cox regression model retained four parameters as independent prognostic factors for survival (age HR = 0.99 (p = 0.002), 1∼10 days HR = 2.64 (p < 0.001), 11∼30 days HR = 2.43 (p < 0.001), 31∼90 days HR = 1.87 (p < 0.001)). CONCLUSIONS: Shorter duration of palliative care services showed poor prognostic factor. Timely referral system from the end of chemotherapy is warranted.

The Association between Phase Angle of Bioelectrical Impedance Analysis and Survival Time in Advanced Cancer Patients: Preliminary Study.

BACKGROUND: A frequent manifestation of advanced cancer patients is malnutrition, which is correlated with poor prognosis and high mortality. Bioelectrical impedance analysis (BIA) is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated BIA-derived phase angle as a prognostic indicator for survival in advanced cancer patients. METHODS: Twenty-eight patients treated at the hospice center of Seoul St. Mary's Hospital underwent BIA measurements from January, 2013 to May, 2013. We also evaluated palliative prognostic index (PPI) and palliative performance scale to compare with the prognostic value of phase angle. Cox's proportional hazard models were constructed to evaluate the prognostic effect of phase angle. The Kaplan Meier method was used to calculate survival. RESULTS: Using univariate Cox analysis, phase angle (hazard ratio [HR], 0.61/per degree increase; 95% confidence interval [CI], 0.42 to 0.89; P = 0.010), PPI (HR, 1.21; 95% CI, 1.00 to 1.47; P = 0.048) were found to be significantly associated with survival. Adjusting age, PPI, body mass index, phase angle significantly showed association with survival in multivariate analysis (HR, 0.64/per degree increase; 95% CI, 0.42 to 0.95; P = 0.028). Survival time of patients with phase angle ≥ 4.4° was longer than patients with phase angle < 4.4° (log rank, 6.208; P-value = 0.013). CONCLUSION: Our data suggest BIA-derived phase angle may serve as an independent prognostic indicator in advanced cancer patients.

Herpesvirus-associated ubiquitin-specific protease (HAUSP) modulates peroxisome proliferator-activated receptor γ (PPARγ) stability through its deubiquitinating activity.

The peroxisome proliferator-activated receptor γ (PPARγ) is a central regulator of adipogenesis and modulates glucose and lipid metabolism. In this study, herpesvirus-associated ubiquitin-specific protease (HAUSP) was isolated as a binding partner of PPARγ. Both endogenous and exogenous PPARγ associated with HAUSP in co-immunoprecipitation analysis. HAUSP, but not the catalytically inactive HAUSP C223S mutant, increased the stability of both endogenous and exogenous PPARγ through its deubiquitinating activity. Site-directed mutagenesis experiments showed that the Lys(462) residue of PPARγ is critical for ubiquitination. HBX 41,108, a specific inhibitor of HAUSP, abolished the increase in PPARγ stability induced by HAUSP. In addition, knockdown of endogenous HAUSP using siRNA decreased PPARγ protein levels. HAUSP enhanced the transcriptional activity of both exogenous and endogenous PPARγ in luciferase activity assays. Quantitative RT-PCR analysis showed that HAUSP increased the transcript levels of PPARγ target genes in HepG2 cells, resulting in the enhanced uptake of glucose and fatty acids, and vice versa, upon siRNA knockdown of HAUSP. In vivo analysis using adenoviruses confirmed that HAUSP, but not the HAUSP C223S mutant, decreased blood glucose and triglyceride levels, which are associated with the increased expression of endogenous PPARγ and lipid accumulation in the liver. Our results demonstrate that the stability and activity of PPARγ are modulated by the deubiquitinating activity of HAUSP, which may be a target for the development of anti-diabetic drugs.

A spontaneous epithelial-myoepithelial carcinoma of the submandibular gland in a sprague-dawley rat.

The present report describes a rare case of spontaneous tumor of the salivary gland in a male Sprague-Dawley rat. The clinically confirmed mass rapidly developed in the cervical region between 19 and 21 weeks of age, and the animal was subsequently euthanized. At necropsy, a well-circumscribed nodule approximately 7 × 6 cm in diameter was found at the site of the salivary gland. The cut surface of the nodule was lobulated and soft and had a pinkish tan fish-flesh appearance. One large cyst (approximately 3 × 2 cm in size) containing reddish fluid was also present in the nodule. Histopathologically, the tumor, with a partially lobulated structure, was surrounded by a thin fibrous capsule. The majority of tumor cells formed a diffuse solid sheet structure that mainly consisted of small ovoid or spindle-shaped cells. In the tumor periphery, some cells were arranged in nest-like structures. Small duct-like structures lined with a monolayer of cuboidal epithelial cells resembling an intercalated duct or large polygonal clear cells with a myoepithelial component were also observed. Mitotic figures and necrotic foci were frequently observed in solid areas. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, p63, α-smooth muscle actin and calponin. The cells were negative for calcitonin, synaptophysin and chromogranin A. On the basis of these findings, the tumor was diagnosed as an epithelial-myoepithelial carcinoma originating from the luminal epithelial cells and myoepithelial cells in the submandibular gland.

ARS-interacting multi-functional protein 1 induces proliferation of human bone marrow-derived mesenchymal stem cells by accumulation of ß-catenin via fibroblast growth factor receptor 2-mediated activation of Akt.

ARS-Interacting Multi-functional Protein 1 (AIMP1) is a cytokine that is involved in the regulation of angiogenesis, immune activation, and fibroblast proliferation. In this study, fibroblast growth factor receptor 2 (FGFR2) was isolated as a binding partner of AIMP peptide (amino acids 6-46) in affinity purification using human bone marrow-derived mesenchymal stem cells (BMMSCs). AIMP1 peptide induced the proliferation of adult BMMSCs by activating Akt, inhibiting glycogen synthase kinase-3ß, and thereby increasing the level of ß-catenin. In addition, AIMP1 peptide induced the translocation of ß-catenin to the nucleus and increased the transcription of c-myc and cyclin D1 by activating the ß-catenin/T-cell factor (TCF) complex. By contrast, transfection of dominant negative TCF abolished the effect of AIMP1. The inhibition of Akt, using LY294002, abolished the accumulation and nuclear translocation of ß-catenin induced by AIMP1, leading to a decrease in c-myc and cyclin D1 expression, which decreased the proliferation of BMMSCs. An intraperitoneal injection of AIMP1 peptide into C57/BL6 mice increased the colony formation of fibroblast-like cells. Fluorescence activated cell sorting analysis showed that the colony-forming cells were CD29(+)/CD44(+)/CD90(+)/CD105(+)/CD34(-)/CD45(-), which is characteristic of MSCs. In addition, the fibroblast-like cells differentiated into adipocytes, chondrocytes, and osteocytes. Taken together, these data suggest that AIMP1 peptide promotes the proliferation of BMMSCs by activating the ß-catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in MSCs in peripheral blood.

Achieving recommended low density lipoprotein cholesterol goals and the factors associated with target achievement of hypercholesterolemia patients with rosuvastatin in primary care.

OBJECTIVE: Hypercholesterolemia is a major risk factor for cardiovascular disease and requires continuous management. The role of primary physicians in this regard is important, yet the factors associated with successful lipid lowering treatments in primary clinics have not been clearly identified. We aimed to evaluate the rate of successful hypercholesterolemia treatment in Korean primary care, and to identify the factors associated with achieving low density lipoprotein cholesterol (LDL-C) targets. METHODS: We prospectively recruited and retrospectively assessed 1851 Korean patients with hypercholesterolemia who visited family physicians and were prescribed rosuvastatin for the first time. LDL-C lowering targets, defined according to NCEP ATP III guidelines, were evaluated at 6 months after the first prescription. The factors associated with achieving these targets were also assessed. RESULTS: Overall, 87.6% of our participants attained their LDL-C goals. In multiple logistic regression analysis, good adherence to medication was strongly associated with the achievement of target LDL-C levels, whereas higher cardiovascular risk factors including diabetes (in both sexes), low high density lipoprotein, and current smoking status (in males), and hypertension (in females) were related to LDL-C target level failures. CONCLUSION: Our observations of the short period for hypercholesterolemia in Korean primary care has revealed that the rate of achieving target LDL-C levels was high in these patients, whereas patients at higher risk for cardiovascular disease tended to have lower LDL-C achievement outcomes. Primary care physicians should pay more attention to patients showing higher cardiovascular risk and stress the need for good adherence and management regimens in these individuals.