A Study on the Application of Machine and Deep Learning Using the Impact Response Test to Detect Defects on the Piston Rod and Steering Rack of Automobiles.

The main parts of automobiles are the piston rod of the shock absorber and the steering rack of the steering gear, and their quality control is critical in the product process. In the process line, these products are normally inspected through visual inspection, sampling, and simple tensile tests; however, if there is a problem or abnormality, it is difficult to identify the type and location of the defect. Usually, these defects are likely to cause surface cracks during processing, which in turn accelerate the deterioration of the shock absorber and steering, causing serious problems in automobiles. As a result, the purpose of this study was to present, among non-destructive methods, a shock response test method and an analysis method that can efficiently and accurately determine the defects of the piston rod and steering rack. A test method and excitation frequency range that can measure major changes according to the location and degree of defects were proposed. A defect discrimination model was constructed using machine and deep learning through feature derivation in the time and frequency domains for the collected data. The analysis revealed that it was possible to effectively distinguish the characteristics according to the location as well as the presence or absence of defects in the frequency domain rather than the time domain. The results indicate that it will be possible to quickly and accurately check the presence or absence of defects in the shock absorber and steering in the automobile manufacturing process line in the future. It is expected that this will play an important role as a key factor in building a smart factory.

Application of a Wireless and Contactless Ultrasonic System to Evaluate Optimal Sawcut Time for Concrete Pavements.

A recently developed contactless ultrasonic testing scheme is applied to define the optimal saw-cutting time for concrete pavement. The ultrasonic system is improved using wireless data transfer for field applications, and the signal processing and data analysis are proposed to evaluate the modulus of elasticity of early-age concrete. Numerical simulation of leaky Rayleigh wave in joint-half space including air and concrete is performed to demonstrate the proposed data analysis procedure. The hardware and algorithms developed for the ultrasonic system are experimentally validated with a comparison of saw-cutting procedures. In addition, conventional methods for the characterization of early-age concrete, including pin penetration and maturity methods, are applied. The results demonstrated that the developed wireless system presents identical results to the wired system, and the initiation time of leaky Rayleigh wave possibly represents 5% of raveling damage compared to the optimal saw cutting. Further data analysis implies that saw-cutting would be optimally performed at approximately 11.5 GPa elastic modulus of concrete obtained by the wireless and contactless ultrasonic system.

A Study on the Applicability of the Impact-Echo Test Using Semi-Supervised Learning Based on Dynamic Preconditions.

The Impact-Echo (IE) test is an effective method for determining the presence, depth, and area of cracks in concrete as well as the dimensions of the sound concrete without defects. In addition, shallow delamination can be measured by confirming a flexural mode in the low-frequency region. Owing to the advancement of non-contact sensors and automated measurement equipment, the IE test can be measured at multiple points in a short period. To analyze and distinguish a large volume of data, applying supervised learning (SL) associated with various contemporary algorithms is necessary. However, SL has limitations due to the difficulty in accurate labeling for increased volumes of test data, and reflection of new specimen characteristics, and it is necessary to apply semi-supervised learning (SSL) to overcome them. This study analyzes the accuracy and evaluates the applicability of a model trained with SSL rather than SL using the data from the air-coupled IE test based on dynamic preconditions. For the detection of delamination defects, the dynamic behavior-based flexural mode was identified, and 21 features were extracted in the time and frequency domains. Three principal components (PCs) such as the real moment, real RMS, and imaginary moment were derived through principal component analysis (PCA). PCs were identical in slab, pavement, and deck. In the case of SSL considering a dynamic behavior, the accuracy increased by 7-8% compared with SL, and it could categorize good, fair, and poor status to a higher level for actual structures. The applicability of SSL to the IE test was confirmed, and because the crack progress varies under field conditions, other parameters must be considered in the future to reflect this.

Effectiveness Analysis for Smart Construction Safety Technology (SCST) by Test Bed Operation on Small- and Medium-Sized Construction Sites.

In the global construction industry, government policies have recently focused on smart construction technologies, such as those concerning the "smartization" of construction, improvements of productivity, and automation technologies. In addition, smart construction safety technologies (SCSTs) have been developed to ensure workers' safety, under the initiative of the private sector. In regards to overseas occupational safety, wearable technologies have been developed for various types of industries, and the integrated platform developments needed to link them have become mainstream. In South Korea, individual companies are focusing on developing basic SCSTs and platforms for integrated control, aiming to prevent accidents in the construction field. The goal of this study was to identify the pros and cons of SCSTs through test bed operation and to derive improvement directions. Therefore, a test bed embedded with SCSTs was built and operated to provide effective safety management for small- and medium-sized sites exposed to fatal accidents. From analyzing the data from the test bed, it was found that it is difficult to change the tendencies of workers' behaviors based solely on the introduction of SCSTs. This indicates that the effects of SCSTs are insignificant without the cooperation of workers. In addition, technical problems in field application were identified for each sensor and equipment, and the necessity, problems, and effectiveness of SCSTs were analyzed. As a result, both the installation and attachment types were found to be effective; however, workers avoided wearing certain attachment types. Based on the results derived through analysis of the pros and cons of SCSTs, the directions and guidelines were suggested for future use. This result can be used for future technology development directions, and policy establishment. Additionally, for the activation of SCSTs in the field, the cooperation of workers and the interest of managers remain essential factors, and improvements to the equipment are required.

RANTES 59029A/G Polymorphisms Associated with Diabetic Compilations in Korean Patients with Type 2 Diabetes for over 15 Years.

BACKGROUND: Polymorphisms in the RANTES gene are known to be associated with several diseases related to insulin resistance. In this study, we investigated the association between RANTES 59029A/G polymorphisms and the prevalence of diabetic complications relative to obesity in Korean patients who had type 2 diabetes (T2D) for over 15 years. METHODS: A single-center, retrospective case-control study was performed. We included 271 patients with a duration of diabetes greater than 15 years. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze RANTES polymorphisms, identifying genotypes as GG, AG, or AA. Obesity was defined using the body mass index with a cutoff value of 25 kg/m2. Both microvascular (retinopathy and nephropathy) and macrovascular (coronary artery disease and cerebrovascular disease) complications were evaluated. RESULTS: The duration of T2D and hemoglobin A1c values at enrollment were 24.4 ± 5.0 years and 7.8 ± 1.6%, respectively, in the non-obese group, and 25.4 ± 6.1 years and 7.7 ± 1.7%, respectively, in the obese group. The prevalence of microvascular complications was significantly higher in the obese group compared with that in the non-obese group (83.5% vs. 72.0%, p = 0.039). Compared to the non-obese group, the obese group showed a higher proportion of the patients with AA or AG genotypes (64.3% vs. 84.5%, p = 0.001). CONCLUSIONS: The A allele of the RANTES gene is associated with obesity and may affect diabetic microvascular complications in patients with T2D for over 15 years.

A Study on the Detection of Internal Defect Types for Duct Depth of Prestressed Concrete Structures Using Electromagnetic and Elastic Waves.

Prestressed concrete (PSC) is widely used for the construction of bridges. The collapse of several bridges with PSC has been reported, and insufficient grout and tendon corrosion were found inside the ducts of these bridges. Therefore, non-destructive testing (NDT) technology is important for identifying defects inside ducts in PSC structures. Electromagnetic (EM) waves have limited detection of internal defects in ducts due to strong reflections from the surface of the steel ducts. Spectral analysis of the existing impact echo (IE) method is limited to specific conditions. Moreover, the flexural mode in upper defects of ducts located at a shallow depth and delamination defects inside ducts are not considered. In this study, the applicability of the elastic wave of IE was analyzed, and multichannel analysis of surface, EM, and shear waves was employed to evaluate six types of PSC structures. A procedure using EM waves, IE, and principal component analysis (PCA) was proposed for a more accurate classification of defect types inside ducts. The proposed procedure was effective in classifying upper, internal, and delamination defects of ducts under 100 mm in thickness, and it could be utilized up to 200 mm in the case of duct defect limitations.

LiDAR-Based Bridge Displacement Estimation Using 3D Spatial Optimization.

As civil engineering structures become larger, non-contact inspection technology is required to measure the overall shape and size of structures and evaluate safety. Structures are easily exposed to the external environment and may not be able to perform their original functions depending on the continuous load for a long time. Therefore, in this study, we propose a method for estimating the vertical displacement of structures using light detection and ranging, which enables non-contact measurement. The point cloud acquired through laser scanning was rearranged into a three-dimensional space, and internal nodes were created by continuously dividing the space. The generated node has its own location information, and the vertical displacement value was calculated by searching for the node where the deformation occurred. The performance of the proposed displacement estimation technique was verified through static loading experiments, and the octree space partitioning method is expected to be applied and utilized in structural health monitoring.

Metabolomics profiles associated with diabetic retinopathy in type 2 diabetes patients.

Diabetic retinopathy (DR) is a common complication of diabetes, and it is the consequence of microvascular retinal changes due to high glucose levels over a long time. Metabolomics profiling is a rapidly evolving method used to identify the metabolites in biological fluids and investigate disease progression. In this study, we used a targeted metabolomics approach to quantify the serum metabolites in type 2 diabetes (T2D) patients. Diabetes patients were divided into three groups based on the status of their complications: non-DR (NDR, n = 143), non-proliferative DR (NPDR, n = 123), and proliferative DR (PDR, n = 51) groups. Multiple logistic regression analysis and multiple testing corrections were performed to identify the significant differences in the metabolomics profiles of the different analysis groups. The concentrations of 62 metabolites of the NDR versus DR group, 53 metabolites of the NDR versus NPDR group, and 30 metabolites of the NDR versus PDR group were found to be significantly different. Finally, sixteen metabolites were selected as specific metabolites common to NPDR and PDR. Among them, three metabolites including total DMA, tryptophan, and kynurenine were potential makers of DR progression in T2D patients. Additionally, several metabolites such as carnitines, several amino acids, and phosphatidylcholines also showed a marker potential. The metabolite signatures identified in this study will provide insight into the mechanisms underlying DR development and progression in T2D patients in future studies.

Clinical efficacy and plausibility of a smartphone-based integrated online real-time diabetes care system via glucose and diet data management: a pilot study.

BACKGROUND: Smartphones have become novel healthcare tools for patients with diabetes. However, it is uncertain whether the smartphone application support system helps in glycaemic control in patients with type 2 diabetes. AIMS: To evaluate the efficacy and plausibility of smartphone-based integrated online real-time diabetes care. METHODS: Forty patients with type 2 diabetes were randomly assigned to the smartphone-based care (SC) (n = 20) and conventional care (CC) (n = 20) groups for 12 weeks. The SC group was instructed to use smartphone application (Noom Coach) and a glucose meter, and was provided medical supervision based on blood glucose level and food intake information sent to the central database server. The efficacy was evaluated by glycated haemoglobin (A1C ≤ 6.5%). The Summary of Diabetes Self-Care Activities (SDSCA) questionnaire was collected at baseline and at week 12. RESULTS: Seventeen and 18 patients of the SC and CC groups completed the study respectively. In the SC group, more patients achieved target A1C compared with the CC group (47.1% vs 11.1%, P = 0.019). In both group, SDSCA scores excluding the exercise item showed overall improvement (general diet, 1.4 ± 2.0 → 2.6 ± 2.3 vs 0.4 ± 1.1 → 1.8 ± 2.2; specific diet, 4.2 ± 1.7 → 5.4 ± 1.2 vs 3.8 ± 1.6 → 5.1 ± 1.1; blood glucose test, 3.3 ± 2.8 → 4.9 ± 2.3 vs 1.0 ± 2.2 → 4.7 ± 2.3; foot care, 1.5 ± 1.6 → 3.6 ± 2.8 vs 1.4 ± 1.9 → 6.1 ± 1.4; all P < 0.05). There was no difference between both groups other than the aspect of foot care (P = 0.008). CONCLUSIONS: The smartphone-based integrated online real-time diabetes care system through glucose and diet data management showed clinical plausibility in glucose control in real clinical practice.

Efficacy and safety of gemigliptin as add-on therapy to insulin, with or without metformin, in patients with type 2 diabetes mellitus (ZEUS II study).

The objective of this study was to evaluate the efficacy and safety of gemigliptin added to a stable dose of insulin alone or of insulin in combination with metformin in patients with type 2 diabetes mellitus. After a two-week run-in period, patients were randomized 2:1 to receive gemigliptin 50 mg or placebo once daily as add-on to background therapy with insulin or insulin plus metformin for 24 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) from baseline at Week 24. Baseline characteristics were similar between the gemigliptin (n = 188) and placebo (n = 95) groups in terms of HbA1c (8.1%). At Week 24, the gemigliptin group showed a statistically significant reduction in mean HbA1c from baseline as compared with placebo (between-group mean difference, -0.7% [95% CI, -0.9% to -0.4%]; P-value < 0.0001). The incidence of overall adverse events and the number of hypoglycaemic adverse events were similar between the study groups. Gemigliptin added to insulin alone or to insulin in combination with metformin resulted in superior glycaemic control compared to that in the placebo group and was well tolerated for 24 weeks in patients with type 2 diabetes mellitus, without causing weight gain or increasing the incidence of hypoglycaemia.

Metabolomics profiles associated with HbA1c levels in patients with type 2 diabetes.

Glycated hemoglobin (HbA1c) is an indicator of the average blood glucose concentration. Failing to control HbA1c levels can accelerate the development of complications in patients with diabetes. Although metabolite profiles associated with HbA1c level in diabetes patients have been characterized using different platforms, more studies using high-throughput technology will be helpful to identify additional metabolites related to diabetes. Type 2 diabetes (T2D) patients were divided into two groups based on the HbA1c level: normal (HbA1c ≤6%) and high (HbA1c ≥9%) in both discovery and replication sets. A targeted metabolomics approach was used to quantify serum metabolites and multivariate logistic regression was used to identify significant differences between groups. The concentrations of 22 metabolites differed significantly between the two groups in the discovery set. In the replication set, the levels of 21 metabolites, including 16 metabolites identified in the discovery set, differed between groups. Among these, concentrations of eleven amino acids and one phosphatidylcholine (PC), lysoPC a C16:1, were higher and four metabolites, including three PCs (PC ae C36:1, PC aa C26:0, PC aa C34:2) and hexose, were lower in the group with normal HbA1c group than in the group with high HbA1c. Metabolites with high concentrations in the normal HbA1c group, such as glycine, valine, and PCs, may contribute to reducing HbA1c levels in patients with T2D. The metabolite signatures identified in this study provide insight into the mechanisms underlying changes in HbA1c levels in T2D.

Teneligliptin versus sitagliptin in Korean patients with type 2 diabetes inadequately controlled with metformin and glimepiride: A randomized, double-blind, non-inferiority trial.

AIM: To assess the efficacy and safety of add-on therapy with the dipeptidyl peptidase-4 inhibitor teneligliptin compared with sitagliptin in patients with type 2 diabetes (T2DM) inadequately controlled with metformin and glimepiride. MATERIALS AND METHODS: This was a phase 3, randomized, double-blind, non-inferiority study of adult Korean subjects with T2DM (n = 201), with HbA1c ranging from 7.0% to 11.0%, on stable doses of metformin plus glimepiride. Subjects were randomized in a 1:1 fashion to receive either oral teneligliptin 20 mg or sitagliptin 100 mg for 24 weeks. The primary endpoint was change from baseline in HbA1c. RESULTS: At baseline, mean age was 60.56 ± 9.41 years, body mass index was 25.23 ± 2.85 kg/m2 and HbA1c was 8.11% ± 0.79%. At 24 weeks, both groups achieved significant reductions from baseline in HbA1c (teneligliptin, -1.03% ± 0.10% [P < 0.0001]; sitagliptin, -1.02% ± 0.10% [P < 0.0001]). The inter-group difference was -0.01% (95% confidence interval [CI]: -0.28, 0.26; P = 0.9497); the upper limit of the 95% CI was within the preset limit for non-inferiority (0.4%). There were no significant differences between groups in the proportion of patients achieving HbA1c targets, or changes from baseline in fasting plasma glucose, body weight or lipid levels at 24 weeks. Rates of adverse events (teneligliptin, n = 63 [61.76%]; sitagliptin, n = 61 [62.24%]; P = 0.9442) and hypoglycaemia (teneligliptin, n = 32 [31.37%]; sitagliptin, n = 28 [28.57%]; P = 0.6656) were similar. CONCLUSION: Teneligliptin was non-inferior to sitagliptin in the context of triple therapy for T2DM and is an important option in this setting.

A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients.

PURPOSE: Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. MATERIALS AND METHODS: Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. RESULTS: Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). CONCLUSION: We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.

The Simple Lamb Wave Analysis to Characterize Concrete Wide Beams by the Practical MASW Test.

In recent years, the Lamb wave analysis by the multi-channel analysis of surface waves (MASW) for concrete structures has been an effective nondestructive evaluation, such as the condition assessment and dimension identification by the elastic wave velocities and their reflections from boundaries. This study proposes an effective Lamb wave analysis by the practical application of MASW to concrete wide beams in an easy and simple manner in order to identify the dimension and elastic wave velocity (R-wave) for the condition assessment (e.g., the estimation of elastic properties). This is done by identifying the zero-order antisymmetric (A0) and first-order symmetric (S1) modes among multimodal Lamb waves. The MASW data were collected on eight concrete wide beams and compared to the actual depth and to the pressure (P-) wave velocities collected for the same specimen. Information is extracted from multimodal Lamb wave dispersion curves to obtain the elastic stiffness parameters and the thickness of the concrete structures. Due to the simple and cost-effective procedure associated with the MASW processing technique, the characteristics of several fundamental modes in the experimental Lamb wave dispersion curves could be measured. Available reference data are in good agreement with the parameters that were determined by our analysis scheme.

Association between Bsm1 Polymorphism in Vitamin D Receptor Gene and Diabetic Retinopathy of Type 2 Diabetes in Korean Population.

BACKGROUND: Type 2 diabetes is one of the most common diseases with devastating complications. However, genetic susceptibility of diabetic complications has not been clarified. The vitamin D endocrine system is related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes and cardiovascular disease. Recent studies reported that single nucleotide polymorphisms of vitamin D receptor (VDR) gene were associated with diabetic complications. METHODS: In present study, we evaluated the association of BsmI polymorphism of VDR with diabetic complications in Korean diabetes patients. Total of 537 type 2 diabetic subjects from the Endocrinology Clinic of Chungbuk National University Hospital were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI (rs1544410; BB, Bb, bb) polymorphisms. RESULTS: Mean age was 62.44±10.64 years and mean disease duration was 13.65±7.39 years. Patients with B allele (BB or Bb) was significantly associated with lower risk of diabetic retinopathy (severe non-proliferative diabetic retinopathy or proliferative retinopathy; 7.4%, 5/68) compared with patients without B allele (bb; 17.3%, 81/469; P=0.035). This association was also significant after adjusting for hemoglobin A1c level, body mass index, age, sex, and diabetes mellitus duration, concurrent dyslipidemia and hypertension (odds ratio, 2.99; 95% confidence interval, 1.08 to 8.29; P=0.035) in logistic regression analysis. CONCLUSION: Our findings suggest that B allele of Bsm1 polymorphism in VDR gene is associated with lower risk of diabetic retinopathy in type 2 diabetic patients. Bsm1 genotype could be used as a susceptibility marker to predict the risk of diabetes complication.

Impact of hyperglycemia on survival and infection-related adverse events in patients with metastatic colorectal cancer who were receiving palliative chemotherapy.

PURPOSE: Non-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC. MATERIALS AND METHODS: We reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results. RESULTS: The mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 (< 106.7 mg/dL), group 2 (106.7-117.2 mg/dL), group 3 (117.3-142.6 mg/dL), and group 4 (> 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). CONCLUSION: Hyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy.

Transcription factor 7-like 2 (TCF7L2) gene polymorphism rs7903146 is associated with stroke in type 2 diabetes patients with long disease duration.

Associations between TCF7L2 SNP and diabetic complications and diabetes-related factors were investigated. Subjects with rs7903146 variant had significantly higher prevalence of stroke (24.1% vs. 11.1%; P=0.039) among subjects exhibiting a long disease duration (≥10 years). In conclusion, the TCF7L2 SNP variant may confer a higher risk of stroke in diabetic patients.

Association of monocyte chemoattractant protein-1 (MCP-1) 2518A/G polymorphism with proliferative diabetic retinopathy in Korean type 2 diabetes.

PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that can increase adhesion molecule expression on monocytes and produce superoxide anions. Hyperglycemia induces MCP-1 production in vascular endothelial cells and retinal pigmented epithelial cells, and has been implicated as a causal factor in the facilitation of vascular complications in diabetes. In the present study, we evaluated the association of a single nucleotide polymorphism (SNP) in the MCP-1 gene with proliferative diabetic retinopathy (PDR) in a Korean population with type 2 diabetes. MATERIALS AND METHODS: We conducted a case-control study, which enrolled 590 subjects with type 2 diabetes, and SNP genotyping of c.2518A/G in the MCP-1 gene was performed using polymerase chain reaction followed by digestion with PvuII restriction enzyme. RESULTS: The prevalence of c.2518A/G polymorphism in diabetic patients was 13.2% (A/A), 47.1% (A/G) and 39.7% (G/G). In patients with diabetic retinopathy, the prevalence of PDR was significantly higher (p=0.009) in diabetic subjects with the c.2518A/A genotype (35.9%; n=78) compared to those with either the A/G or G/G genotype (22.3%, n=512). The prevalence of any other micro and macro-complications, including nephropathy and cerebrovascular events, were not different according to the c.2518A/G genotype. CONCLUSION: Our new genetic findings suggest that the c.2518A/A genotype in MCP-1 could be used as a susceptibility gene to predispose Koreans exhibiting type 2 diabetes for the development of PDR.

A pilot study of adrenal suppression after dexamethasone therapy as an antiemetic in cancer patients.

PURPOSE: Dexamethasone has a high therapeutic index when used to prevent chemotherapy-induced nausea and vomiting. However, the chronic use of glucocorticoids has been associated with suppression of the hypothalamic-pituitary-adrenal axis. Therefore, the authors designed this pilot study to assess the incidence of adrenal insufficiency after dexamethasone therapy as an antiemetic in cancer patients receiving chemotherapy. METHODS: The rapid adrenocorticotropic hormone (ACTH) stimulation test was performed in 103 cancer patients, who had been treated with high-dose dexamethasone as an antiemetic for more than 3 months. When response to the rapid ACTH stimulation test was abnormal, the patient received corticosteroid replacement by prednisolone 7.5 mg daily for 1-2 weeks and after prednisolone replacement, changes in symptoms associated with adrenal insufficiency were investigated using a visual analog scale. RESULTS: Forty-five of the 103 patients (43.7%) showed a suppressed adrenal response to the rapid ACTH stimulation test, and the incidence of adrenal suppression was found to be significantly affected by megestrol acetate use (P = 0.035). Thirty-three patients with a suppressed adrenal function achieved an improvement in quality of life after prednisolone replacement, as determined using a self-report questionnaire (22.9 ± 14.7 to 14.8 ± 11.0, P < 0.001). CONCLUSIONS: We suggest that suppression of adrenal response is common after antiemetic dexamethasone therapy in cancer patients receiving chemotherapy.

Lentiviral vector design using alternative RNA export elements.

BACKGROUND: Lentiviral vectors have been designed with complex RNA export sequences in both the integrating and packaging plasmids in order to co-ordinate efficient vector production. Recent studies have attempted to replace the existing complex rev/RRE system with a more simplistic RNA export system from simple retroviruses to make these vectors in a rev-independent manner. RESULTS: Towards this end, lentiviral transfer plasmids were modified with various cis-acting DNA elements that co-ordinate RNA export during viral production to determine their ability to affect the efficiency of vector titer and transduction in different immortalized cell lines in vitro. It was found that multiple copies of the constitutive transport element (CTE) originating from different simian retroviruses, including simian retrovirus type 1 (SRV-1) and type-2 (SRV-2) and Mason-Pfizer (MPV) could be used to eliminate the requirement for the rev responsive element (RRE) in the transfer and packaging plasmids with titers >106 T.U./mL (n = 4-8 preparations). The addition of multiple copies of the murine intracisternal type A particle, the woodchuck post-regulatory element (WPRE), or single and dual copies of the simian CTE had minimal effect on viral titer. Immortalized cell lines from different species were found to be readily transduced by VSV-G pseudotyped lentiviral vectors containing the multiple copies of the CTE similar to the findings in HeLa cells, although the simian-derived CTE were found to have a lower infectivity into murine cell lines compared to the other species. CONCLUSION: These studies demonstrated that the rev-responsive element (RRE) could be replaced with other constitutive transport elements to produce equivalent titers using lentivectors containing the RRE sequence in vitro, but that concatemerization of the CTE or the close proximity of RNA export sequences was needed to enhance vector production.