Immediate effects of transcutaneous electrical nerve stimulation on gait patterns in chronic stroke survivors: A single group, pretest-posttest clinical trial.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) has been used to reduce muscle spasticity and improve locomotion in stroke survivors. We speculate that acute changes in gait performance after TENS mediate functional improvement in the long-term. However, no previous study has investigated the effect of TENS on ankle kinetics and kinematics during walking in stroke survivors. PURPOSE: We aimed to investigate whether TENS applied over the paretic leg could rapidly improve the plantar flexion moment and ankle kinematics in chronic stroke survivors with lower limb paresis. METHODS: Twenty chronic stroke survivors were recruited. They underwent 30 min of TENS over the area innervated by the common peroneal nerve on the paretic leg. Three-dimensional (3D) motion capture was performed and ankle plantar flexor spasticity was assessed before and immediately after stimulation. Ankle kinematics and kinetic and spatiotemporal data were collected using 3D motion capture. Ankle plantar flexor spasticity was assessed using the Modified Tardieu Scale. PRINCIPAL RESULTS: A significant increase in the ankle plantar flexion moment of the paretic side during the pre-swing phase was observed immediately after stimulation (p = 0.009, maximal mean difference = 0.035, 95%CI = 0.0125 to 0.0575). The step length of the paretic limb also increased significantly after stimulation (p = 0.023, mean difference = -0.02, 95%CI = -0.04 to -0.004). TENS had no immediate effect on paretic ankle spasticity, as measured by the Modified Tardieu Scale, or on other temporo-spatial parameters. CONCLUSION: The findings support the use of TENS to improve the motor function and gait pattern in chronic stroke survivors. The study indicated that the application of TENS to the paretic leg before gait training might improve rehabilitation outcomes. Future studies investigating the effects of TENS on functional outcomes, the optimal stimulation duration, and assessing spasticity using more sensitive measures are warranted.

Muscle insulin-like growth factor-I modulates murine craniofacial bone growth.

Insulin-like growth factor I (IGF-I) is essential for muscle and bone development and a primary mediator of growth hormone (GH) actions. While studies have elucidated the importance of IGF-I specifically in muscle or bone development, few studies to date have evaluated the relationship between muscle and bone modulated by IGF-I in vivo, during post-natal growth. Mice with muscle-specific IGF-I overexpression (mIgf1+/+) were utilised to determine IGF-I- and muscle-mass-dependent effects on craniofacial skeleton development during post-natal growth. mIgf1+/+ mice displayed accelerated craniofacial bone growth when compared to wild-type animals. Virus-mediated expression of IGF-I targeting the masseter was performed to determine if post-natal modulation of IGF-I altered mandibular structures. Increased IGF-I in the masseter affected the mandibular base plane angle in a lateral manner, increasing the width of the mandible. At the cellular level, increased muscle IGF-I also accelerated cartilage thickness in the mandibular condyle. Importantly, mandibular length changes associated with increased IGF-I were not present in mice with genetic inhibition of muscle IGF-I receptor activity. These results demonstrated that muscle IGF-I could indirectly affect craniofacial growth through IGF-I-dependent increases in muscle hypertrophy. These findings have clinical implications when considering IGF-I as a therapeutic strategy for craniofacial disorders.

Association between body mass index and stroke severity in acute ischaemic stroke with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log-linear regression with a Poisson distribution and binary logistic regression analysis. RESULTS: A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores [median 5, interquartile range (IQR) 2-14] of normal-weight patients, the NIHSS scores (median 9, IQR 4-19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1-12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09-2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal-weight patients. CONCLUSION: An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short-term outcomes in patients with NVAF.

Vertebral fracture is associated with myocardial infarction in incident hemodialysis patients: a Korean nationwide population-based study.

Chronic kidney disease (CKD)-mineral and bone disorder suggests that fragile bone and vascular disorder might be connected closely in CKD patients. In this study, fracture event was significantly associated with myocardial infarction (MI) in end-stage renal disease patients on hemodialysis (HD), especially for vertebral fractures. INTRODUCTION: CKD-mineral and bone disorder is characterized by biochemical abnormalities, bone disorders, and vascular calcification. We aimed to verify the association between fracture and MI in CKD patients. METHODS: Records for incident CKD stage 3 to 5 patients and patients who initiated HD between July 2014 and June 2018 were retrieved from the Korean Health Insurance Review & Assessment Service Database. Fractures were defined using diagnostic codes and were classified into vertebral, femoral, and other site fractures. MI was defined using a combination of MI diagnostic codes and related procedure codes. Multiple logistic regressions and 1:1 propensity score matching analysis were conducted. RESULTS: A total of 38,935 patients (HD, 11,379; pre-dialysis CKD, 27,556) were included in this study. A total of 5,057 (13.0%) patients experienced fracture, and 1,431 (3.7%) patients had MI. Multiple logistic regression analysis showed that fracture was significantly associated with MI in the HD group (odds ratio (OR) 1.34, P = 0.024), but not in the pre-dialysis CKD group (OR 1.04, P = 0.701). After propensity score matching for age, gender, and diabetes mellitus between patients with and without fracture, fracture still significantly correlated with MI in HD patients (OR 1.47, P = 0.034) but not in patients with pre-dialysis CKD (OR 1.04, P = 0.751). Subgroup analysis by fracture site found that vertebral fracture was associated with MI in HD patients (OR 2.11, P = 0.024), but femoral or other site fractures were not. CONCLUSION: In HD patients, fracture was significantly associated with MI, especially for vertebral fractures patients.

Risk of diabetes in viral hepatitis B or C patients compared to that in noninfected individuals in Korea, 2002-2013: A population-based cohort study.

While the association between hepatitis C virus (HCV) infection and diabetes has been established, the relationship between hepatitis B virus (HBV) infection and diabetes remains unclear. Therefore, we compared the association between diabetes development in HBV, HCV and co-infected (HBV/HCV) patients to that in noninfected participants using population-based cohort data. We used the National Health Insurance Service-National Sample Cohort, which consists of 514 791 randomly selected persons among those who underwent health check-ups from 2002 to 2003 aged 40-79 years. Adults found to have HBV or HCV infection from 2002 to 2003, without a prior history of diabetes, were selected as subjects. Competing risk regression models were used to estimate cumulative incidence and hazards ratios (HRs) of diabetes development. The cumulative incidences, incidence densities and HRs of diabetes were highest in the co-infected group, followed by those in the HCV-, HBV- and noninfected groups. The 12-year cumulative incidences were as follows: 42.0% in HBV/HCV-, 32.9% in HCV-, 23.9% in HBV- and 18.3% in the noninfected groups. The incidence density per 1000 person-years was 55.0, 51.5, 38.2 and 28.2 for the HBV/HCV-, HCV-, HBV- and noninfected groups, respectively. The adjusted HRs for diabetes were 1.90, 1.68 and 1.41 for the HBV/HCV-, HCV- and HBV-infected groups, respectively. Our findings suggest that both HCV and HBV infections are associated with the development of diabetes; therefore, prevention of, screening for, and treatment of both may reduce the risk of diabetes in these patients.

Comparison of 3D and 2D shear-wave elastography for differentiating benign and malignant breast masses: focus on the diagnostic performance.

AIM: To evaluate the diagnostic performance of three-dimensional (3D) image shear-wave elastography (SWE) for differentiating benign from malignant breast masses compared to two-dimensional (2D) SWE and B-mode ultrasound (US). MATERIALS AND METHODS: This study consisted of 205 breast lesions from 199 patients who underwent B-mode US and SWE before biopsy from January 2014 to March 2016. Quantitative elasticity values (maximum and mean elasticity, Emax and Emean) obtained from 2D and 3D SWE (axial, sagittal, and coronal images) were reviewed retrospectively, in addition to the histopathological findings including immunohistochemistry profiles (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer) in cases of malignancy. Histopathological findings were regarded as the reference standard. The diagnostic performance of each data set was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) analysis to compare sensitivity and specificity. RESULTS: Among 205 lesions, 105 (51.22%) were malignant and 100 (48.78%) were benign. Compared to benign masses, malignant masses had higher values of Emax and Emean on both 2D and 3D SWE, the differences of which were statistically significant (p<0.001). The AUCs of 2D, 3D axial, and sagittal SWE were significantly higher than that of 3D coronal SWE (p<0.05). In addition, the sensitivities of axial, sagittal, and coronal 3D SWE were all higher than that of 2D SWE for Emean (81.9%, 87.6%, and 89.5% versus 70.5%, respectively, p<0.05). Conversely, the specificity of 2D and 3D axial SWE was higher than that of 3D sagittal and coronal SWE (Emax, 84%, 83% versus 76%, 73%; Emean, 85%, 81% versus 68%, 50%, respectively, p<0.05). We also assessed changes in Breast Imaging-Reporting and Data System (BI-RADS) category 3 and category 4a lesions by adding each of the parameters for 2D and 3D SWE in B-mode US. The specificity, PPV, and accuracy of combined 2D or combined 3D SWE with B-mode US was statistically higher than that of B-mode US alone for differentiating benign and malignant lesions (p<0.05). CONCLUSIONS: Among SWE images, 2D SWE, and 3D SWE axial and sagittal images exhibited superior diagnostic performance compared to 3D coronal images. Addition of 3D SWE images to B-mode US improved the diagnostic performance for distinguishing benign from malignant masses.

A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans.

We performed a double-blinded, genotype-based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. Twenty-four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N-demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19. The extent of hydroxylation of amitriptyline or nortriptyline was significantly reduced in subjects carrying two CYP2D6 decreased functional alleles compared with those with no or one decreased functional allele. The overall metabolic pathway of amitriptyline was more likely to be dominated by CYP2C19 than CYP2D6. The gene variations of CYP2C19 and CYP2D6 did not change the pharmacodynamic effect. The findings of this study will provide useful information on individualized drug treatment with amitriptyline considering both CYP2D6 and CYP2C19 gene variations.

Compensatory structural and functional adaptation after radical nephrectomy for renal cell carcinoma according to preoperative stage of chronic kidney disease. Choi DK, Jung SB, Park BH, Jeong BC, Seo SI, Jeon SS, Lee HM, Choi HY, Jeon HG.J Urol. 2015 Oct;194(4):910-5. [Epub 2015 Apr 28]. doi: 10.1016/j.juro.2015.04.093.

PURPOSE: We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. MATERIALS AND METHODS: We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease-glomerular filtration rate 90ml/min/1.73m2 or greater (230, 42.4%), chronic kidney disease stage II-glomerular filtration rate 60 to less than 90ml/min/1.73m2 (227, 41.8%), and chronic kidney disease stage III-glomerular filtration rate 30 to less than 60ml/min/1.73m2 (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. RESULTS: Among all patients (mean age = 56.0y) mean preoperative glomerular filtration rate, functional renal volume, and glomerular filtration rate/functional renal volume were 83.2ml/min/1.73m2, 340.6cm3, and 0.25ml/min/1.73m2/cm3, respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs. stage II 26.5% vs. stage III 12.8%, P<0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs. stage II 17.3% vs. stage III 16.5%, P = 0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs. stage II 20.1% vs. stage III 45.9%, P<0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (P = 0.012), diabetes mellitus (P = 0.023), hypertension (P = 0.015), and chronic kidney disease stage (P<0.001). CONCLUSIONS: Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration.

KRT19 directly interacts with ß-catenin/RAC1 complex to regulate NUMB-dependent NOTCH signaling pathway and breast cancer properties.

Studies have reported that interactions between keratins (KRTs) and other proteins initiate signaling cascades that regulate cell migration, invasion, and metastasis. In the current study, we found that expression of KRT19 was specifically high in breast cancers and significantly correlated with their invasiveness. Moreover, knockdown of KRT19 led to increased proliferation, migration, invasion, drug resistance, and sphere formation in breast cancer cells via an upregulated NOTCH signaling pathway. This was owing to reduced expression of NUMB, an inhibitory protein of the NOTCH signaling pathway. In addition, we found that KRT19 interacts with ß-catenin/RAC1 complex and enhances the nuclear translocation of ß-catenin. Concordantly, knockdown of KRT19 suppressed the nuclear translocation of ß-catenin as well as ß-catenin-mediated NUMB expression. Furthermore, modulation of KRT19-mediated regulation of NUMB and NOTCH1 expression led to the repression of the cancer stem cell properties of breast cancer patient-derived CD133high/CXCR4high/ALDH1high cancer stem-like cells (CSLCs), which showed very low KRT19 and high NOTCH1 expression. Taken together, our study suggests a novel function for KRT19 in the regulation of nuclear import of the ß-catenin/RAC1 complex, thus modulating the NUMB-dependent NOTCH signaling pathway in breast cancers and CSLCs, which might bear potential clinical implications for cancer or CSLC treatment.

On-scene factors that predict severe injury of patients involved in frontal crashes of passenger cars.

PURPOSE: We sought to determine on-scene factors that predict severe injury to the occupants of passenger cars involved in frontal crashes. METHODS: From January 2011 to December 2014, we collected data from patients who were taken to two emergency centres following a frontal motor vehicle crash. Binomial logistic regression was used to model the effects of occupant characteristics (sex, age, body mass index), vehicle damage (according to the collision deformation classification code), and safety devices on severe injuries (injury severity score >15). RESULTS: Of 344 subjects, 75 (21.8 %) had severe injuries. Sex, seat belt status, extent of vertical crash, intrusion, and deformation extent (DE) were significantly different between severe and non-severe injuries. After adjusting for confounders, non-use of seat belt tripled the odds of severe injury [odds ratio (OR) 2.7, 95 % confidence interval (CI) 1.461-5.105]. DE ≥4 and intrusion increased the risk of severe injury (OR 2.4, 95 % CI 1.120-5.204 and OR 5.2, 95 % CI 2.525-10.780, respectively). A combination model to predict severe injury using intrusion, seat belt use, and DE ≥4 demonstrated 56.0 % sensitivity, 88.9 % specificity, and 58.4 % positive predictive value (AUC = 0.781, 95 % CI 0.734-0.824). CONCLUSIONS: For passenger cars involved in a frontal crash, intrusion, unbelted status, and DE ≥4 are good predictors of severe injury. Sequential criteria using vehicle DE, seat belt use, and intrusion can be used by first responders to triage patients involved in a frontal collision.

Quality analysis of randomized controlled trials in the International Journal of Impotence Research: quality assessment and relevant clinical impact.

The quality of randomized controlled trials (RCTs) reported in the International Journal of Impotence Research (IJIR) was analyzed. The original articles that reported RCTs and were published in the IJIR in 1997-2014 were identified by PubMed. Their methodological quality was assessed using the Jadad scale, van Tulder scale and Cochrane Collaboration Risk of Bias Tool. The review period was divided into three periods: early (1997-2002), mid (2003-2008) and late (2009-2014). The effect of study subject and presence of Institutional Review Board approval, intervention, funding and adequate allocation concealment on RCT quality was assessed. The frequency of RCT publication in the IJIR did not change over the 19-year study period. Numbers of low risk of bias articles were 1 (3.0%), 2 (4.4%) and 4 (12.1%) in the early, mid and late periods in Cochrane Collaboration Risk of Bias Tool (P=0.04). High-quality low risk of bias RCT publication frequency increased over time. Intervention and funding significantly influenced RCT quality. Thus, the number of RCTs published in the IJIR over time has remained constant while their quality has improved. Ongoing efforts to expand the numbers of RCTs and further improve the quality of research published by the IJIR will improve clinical practice.

Population Pharmacokinetic and Pharmacodynamic Modeling Analysis of GCC-4401C, a Novel Direct Factor Xa Inhibitor, in Healthy Volunteers.

GCC-4401C, an orally active direct factor Xa inhibitor that is similar to rivaroxaban, is currently under development for venous thromboembolic disease (VTE). The purpose of this study was to characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of GCC-4401C by population modeling analysis and to predict proper dosage regimens compared to rivaroxaban using data from two phase I clinical studies. Plasma GCC-4401C concentrations over time were best described by a two-compartment linear model and body weight was associated with central volume of distribution. Relevant PD markers generally changed in a dose-dependent manner and were described well with sigmoid, simple maximum effect, or linear models. GCC-4401C was absorbed more rapidly than rivaroxaban. Comparisons based on simulations of PD marker changes over time suggest that 20 mg and 40 mg of GCC-4401C administered under fasted status are comparable to 10 mg and 20 mg of rivaroxaban under fed status.

Metal allergy in eyelid dermatitis and the evaluation of metal contents in eye shadows.

BACKGROUND: Allergic contact dermatitis is a common diagnosis in eyelid dermatitis. Sensitization to metals is prevalent in eyelid dermatitis and colour cosmetic products are frequently suspected as the source of metal exposure. OBJECTIVE: To investigate the contact allergens for eyelid dermatitis and to assess metal contents in eye shadow products. METHODS: Data were collected in the department of dermatology of Ewha Womans University hospital from December 1998 to February 2014. A total of 983 patients were patch tested during the period and 67 patients had eyelid dermatitis among them. To examine metal elements in colour cosmetic products for eyes, randomly selected 10 eye shadows were analysed. RESULTS: Frequent allergens were metals, thiomersal and phenylenediamine in patients with eyelid dermatitis. The sensitization rates of individual allergens were not significantly different between patients with eyelid dermatitis and without eyelid dermatitis. All 10 eye shadow products contained more than 5 ppm of at least one element, nickel, cobalt or chromium. CONCLUSION: Metals were top-rank allergens in patients with eyelid dermatitis as in the remaining patients patch tested. The eye shadow products contained significant amount of nickel, cobalt or chromium to elicit allergic reactions.

Population-based epidemiology of primary biliary cirrhosis in South Korea.

BACKGROUND: As a rare disease, only a few population-based epidemiology studies of primary biliary cirrhosis (PBC) have been reported. AIMS: To elucidate the nationwide prevalence, incidence, complications, fatality and direct medical costs of PBC in South Korea. METHODS: The nationwide Health Insurance Review and Assessment Service claims data and Rare Intractable Disease registration data on PBC, identified with the International Classification of Diseases (ICD) 10 code of K74.3, were obtained from 2009 to 2013. Age- and gender-specific prevalence and incidence rates of PBC were calculated, and data on complications, comorbidities, prescribed drugs, therapeutic procedures and direct medical costs were analysed. RESULTS: A total of 2824 patients over 20 years old with PBC were identified in 2009-2013 (female-to-male ratio 6.2, median age 57 years old). The average age- and sex-adjusted incidence from 2011 to 2013 was 8.57 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 47.50 per million population. About 10% of patients presented with complications such as ascites (10.3%), variceal bleeding (5.8%) and/or hepatocellular carcinoma (HCC) (1.3%). Liver transplantation was undertaken in 71 patients (2.5%) for 5 years. Case fatality was 2.2% and the transplantation-free survival was 95.4% for 5 years. CONCLUSIONS: This is the first report on the nationwide epidemiology of primary biliary cirrhosis in South Korea, demonstrating lower incidence and prevalence rates than those of Western countries, but a considerable disease burden, representing at least 10% were complicated with decompensated cirrhosis or hepatocellular carcinoma requiring liver transplantation.

Investigation of the magnetic properties in double perovskite R2CoMnO6 single crystals (R = rare earth: La to Lu).

We have successfully synthesized the series of the double-perovskite R2CoMnO6 (R = rare earth: La to Lu) single crystals and have investigated their magnetic properties. The ferromagnetic order of Co(2+)/Mn(4+) spins emerges mainly along the c axis. Upon decreasing the size of rare earth ion, the magnetic transition temperature decreases linearly from 204 K for La2CoMnO6 to 48 K for Lu2CoMnO6, along with the enhancement of monoclinic distortion. The temperature and magnetic-field dependences of magnetization reveal the various magnetic characteristics such as the metamagnetic transition in R = Eu, the isotropic nature of rare earth moment in R = Gd, and the reversal of magnetic anisotropy in R = Tb and Dy. Our results offer comprehensive information for understanding the roles of mixed-valent magnetic ions and rare earth magnetic moments on the magnetic properties.

Effect of thermal treatment on the bio-corrosion and mechanical properties of ultrafine-grained ZK60 magnesium alloy.

The combination of solid solution heat treatments and severe plastic deformation by high-ratio differential speed rolling (HRDSR) resulted in the formation of an ultrafine-grained microstructure with high thermal stability in a Mg-5Zn-0.5Zr (ZK60) alloy. When the precipitate particle distribution was uniform in the matrix, the internal stresses and dislocation density could be effectively removed without significant grain growth during the annealing treatment (after HRDSR), leading to enhancement of corrosion resistance. When the particle distribution was non-uniform, rapid grain growth occurred in local areas where the particle density was low during annealing, leading to development of a bimodal grain size distribution. The bimodal grain size distribution accelerated corrosion by forming a galvanic corrosion couple between the fine-grained and coarse-grained regions. The HRDSR-processed ZK60 alloy with high thermal stability exhibited high corrosion resistance, high strength and high ductility, and excellent superplasticity, which allow the fabrication of biodegradable magnesium devices with complicated designs that have a high mechanical integrity throughout the service life in the human body.

Nodular Fasciitis of the Breast: A Case and Literature Review.

Nodular fasciitis is a benign fibroblastic proliferation in soft tissue that is most commonly found in the upper extremities, trunk, head, and neck region. Its occurrence in the breast has been rarely reported. The most characteristic features are the sudden appearance and rapid growth of a palpable lesion. Nodular fasciitis can clinically, radiologically, and histopathologically mimic a breast carcinoma. We present a case of nodular fasciitis of the breast and a review of the relevant literature.

Association of glypican-4 with body fat distribution, insulin resistance, and nonalcoholic fatty liver disease.

CONTEXT AND OBJECTIVE: Glypican-4 was identified as a novel adipokine capable of enhancing insulin signaling and modulating adipocyte differentiation. We investigated associations between glypican-4 and body composition, insulin resistance, arterial stiffness, and nonalcoholic fatty liver disease (NAFLD) in nondiabetic Asian subjects. DESIGN AND PARTICIPANTS: We analyzed baseline cross-sectional data from the Korean Sarcopenic Obesity Study, an ongoing prospective cohort study. NAFLD was diagnosed by unenhanced computed tomography using the liver attenuation index. We also examined the effects of a 3-month combined aerobic and resistance exercise program on glypican-4 levels and cardiometabolic risk factors. RESULTS: Circulating glypican-4 levels were higher in men than in women (1.83 [1.19, 2.78] ng/mL vs 1.17 [0.66, 2.00] ng/mL, P < .001) and had a significant positive relationship with the waist-to-hip ratio (WHR) (r = 0.20, P = .014) and the ratio of visceral to sc fat area (r = 0.30, P < .001). Furthermore, glypican-4 levels in women were correlated with cardiometabolic risk factors, including insulin resistance and arterial stiffness, and were independently associated with NAFLD by multiple logistic regression analysis (P = .017, R² = 0.33). The 3-month combined exercise training program significantly improved several cardiometabolic parameters and reduced retinol binding protein-4 levels. Changes in glypican-4 levels after the exercise program were significantly different between subjects with an increased WHR compared with those with a decreased WHR (P = .034). CONCLUSION: A gender-based difference in circulating glypican-4 levels was apparent as these were increased in women with NAFLD and related to body fat distribution, insulin resistance, and arterial stiffness.

Change in cytokines in patients with warts after contact immunotherapy with squaric acid dibutylester.

BACKGROUND: A wart is a skin lesion caused by infection with human papillomavirus (HPV). Contact immunotherapy is one of the many therapeutic options that have been used to treat warts; however, the effectiveness of contact immunotherapy differs from patient to patient, and the cause of this variation in clinical response is unclear. AIM: To assess cytokine changes in patients after contact immunotherapy with squaric acid dibutylester (SADBE). METHODS: In total, 21 patients with warts and 9 healthy control subjects were enrolled in the study. The frequencies of CD3+ T cells expressing interleukin (IL)-4, IL-10, IL-12, tumour necrosis factor-α and interferon-γ were measured by flow cytometry analysis of peripheral blood at baseline in both patients and controls, and after SADBE treatment in patients. RESULTS: Lower expression of IL-4 and higher expression of IL-12 in CD3+ T cells were found in patients compared with controls. The percentage of CD3+/IL-4+ T cells significantly increased after contact immunotherapy in all responders, but was significantly higher in those with an excellent response, who also had a significantly higher percentage of CD3+/IL-10+ T cells. The patients with an excellent response also had a significant decrease in the percentage of CD3+/IL-12+ T cells, and the percentage of CD3+/IL-4+ T cells normalized. CONCLUSIONS: Response to contact immunotherapy can vary depending on the types of cytokine changes produced by treatment. An excessive shift to a Th2 pattern and increased IL-10 production after contact immunotherapy may hinder clearance of HPV.