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As the number of offshore wind-power installations increases, collision accidents with vessels occur more frequently. This study investigates the risk of collision damage with operating vessels that may occur during the operation of an offshore wind turbine. The floater used in the collision study is a 15 MW UMaine VolturnUS-S (semi-submersible type), and the colliding ships are selected as multi-purpose vessels, service operation vessels, or anchor-handling tug ships based on their operational purpose. Collision analysis is performed using ABAQUS and substantiation is performed via a drop impact test. The collision analyses are conducted by varying the ship velocity, displacement, collision angle, and ship shape. By applying this numerical model, the extent of damage and deformation of the collision area is confirmed. The analysis results show that a vessel with a bulbous bow can cause flooding, depending on the collision conditions. For damage caused by collision, various collision angles must be considered based on the internal stiffener arrangement. Additionally, the floater can be flooded with relatively small collision energy when the colliding vessel has a bulbous bow.

Abstract Purpose Composite models have become commonplace for the assessment of fixation and stability of total joint replacements; however, there are no comparable models for the cervical spine to evaluate fixation. The goal of this study was to create the framework for a tunable non‐homogeneous model of cervical vertebral body by identifying the relationships between strength, in‐fill density, and lattice structure and creating a final architectural framework for specific strengths to be applied to the model. Methods The range of material properties for cervical spine were identified from literature. Using additive manufacturing software, rectangular prints with three lattice structures, gyroid, triangle, zig‐zag, and a range of in‐fill densities were 3D‐printed. The compressive and shear strengths for all combinations were calculated in the axial and coronal planes. Eleven unique vertebral regions were selected to represent the distribution of density. Each bone density was converted to strength and subsequently correlated to the lattice structure and in‐fill density with the desired material properties. Finally, a complete cervical vertebra model was 3D‐printed to ensure sufficient print quality. Results Materials testing identified a relationship between in‐fill densities and strength for all lattice structures. The axial compressive strength of the gyroid specimens ranged from 1.5 MPa at 10% infill to 31.3 MPa at 100% infill and the triangle structure ranged from 2.7 MPa at 10% infill to 58.4 MPa at 100% infill. Based on these results, a cervical vertebra model was created utilizing cervical cancellous strength values and the corresponding in‐fill density and lattice structure combination. This model was then printed with 11 different in‐fill densities ranging from 33% gyroid to 84% triangle to ensure successful integration of the non‐homogeneous in‐fill densities and lattice structures. Conclusions The findings from this study introduced a framework for using additive manufacturing to create a tunable, customizable biomimetic model of a cervical vertebra.

The study of blowfly (Diptera: Calliphoridae) biodiversity and distribution is crucial for forensic investigations. Abiotic and biotic factors, such as season and habitat type, have a significant impact on blowfly populations. However, only a few forensic entomology studies have been conducted in South Korea, particularly in the Gyeongsangnam-do region. To address this, an extensive year-long survey was conducted to analyze the compositions, habitat preferences, distribution, and seasonal abundance of forensically relevant blowflies in urban and forested habitats of Gyeongsangnam-do, with sampling conducted twice a month using mouse carcass-baited traps set for 48 h each time. A total of 3470 adult blowflies were recorded, encompassing five genera and 13 species, with a noted absence of specimens during the winter months. The predominant species was Lucilia porphyrina, accounting for 37.2% of the total sample, followed by Chrysomya pinguis (27.6%), Lucilia sericata (7.6%), and Lucilia illustris (7.1%). The species composition was consistent across all surveyed regions; however, seasonal variation in species diversity was evident, with a peak in spring and a decline in summer. Notably, certain species exhibited clear preferences for either urban (Calliphora calliphoroides and L. sericata) or forested habitats (L. porphyrina and Ch. pinguis). This pioneering study elucidates the diverse blowfly communities in Gyeongsangnam-do, highlighting significant seasonal and habitat-dependent variations. These findings enrich our understanding of blowfly ecology in this region, offering valuable insights for forensic applications and underscoring the necessity for ongoing entomological surveillance and research.

Corrosion damage to submarine pressure hulls is a crucial consideration during the structural design phase because it diminishes the structural strength of a submarine, reducing its operational depth and posing a severe risk to the life of the crew. This necessitates using a validated analytical method to estimate the residual strength and assess the safety of corrosion-affected pressure hulls. This paper presents an experimental and numerical investigation of the residual strength of corroded ring-stiffened cylinders, which are typical components of submarine pressure hulls, the main legs of semi-submersibles, and Floating Offshore Wind Turbine (FOWT) foundations. Four steel ring-stiffened cylinder models were fabricated: two remained intact, whereas the other two were artificially corroded by machining. Hydrostatic collapse tests were conducted in a pressure chamber. To evaluate the effect of initial shape imperfections caused by welding fabrication on the strength of the structure, the initial shape imperfections were measured using a three-dimensional coordinate measuring machine. The experimental results illustrate a significant reduction in the residual strengths of the two damaged models compared with those of the intact models. The collapse processes simulated using the Abaqus software package are presented, demonstrating a close agreement between the experimental results and numerical predictions.

Outbreaks caused by foot-and-mouth disease (FMD) A/ASIA/G-VII lineage viruses have often occurred in Middle Eastern and Southeast Asian countries since 2015. Because A/ASIA/G-VII lineage viruses are reported to have distinct antigenic relatedness with available commercial FMD vaccine strains, it is necessary to investigate whether inoculation with vaccines used in Korea could confer cross-protection against A/ASIA/G-VII lineage viruses. In the present study, we conducted two vaccination challenge trials to evaluate the efficacy of three commercial FMD vaccines (O/Manisa + O/3039 + A/Iraq, O/Campos + A/Cruzeiro + A/2001, and O/Primorsky + A/Zabaikalsky) against heterologous challenge with ASIA/G-VII lineage viruses (A/TUR/13/2017 or A/BHU/3/2017 strains) in pigs. In each trial, clinical signs, viremia, and salivary shedding of virus were measured for 7 days after challenge. In summary, the O/Campos + A/Cruzeiro + A/2001 vaccine provided full protection against two A/ASIA/G-VII lineage viruses in vaccinated pigs, where significant protection was observed. Although unprotected animals were observed in groups vaccinated with O/Manisa + O/3039 + A/Iraq or O/Primorsky + A/Zabaikalsky vaccines, the clinical scores and viral RNA levels in the sera and oral swabs of vaccinated animals were significantly lower than those of unvaccinated controls.

Aims: Taper corrosion has been widely reported to be problematic for modular total hip arthroplasty implants. A simple and systematic method to evaluate taper damage with sufficient resolution is needed. We introduce a semiquantitative grading system for modular femoral tapers to characterize taper corrosion damage. Methods: After examining a unique collection of retrieved cobalt-chromium (CoCr) taper sleeves (n = 465) using the widely-used Goldberg system, we developed an expanded six-point visual grading system intended to characterize the severity, visible material loss, and absence of direct component contact due to corrosion. Female taper sleeve damage was evaluated by three blinded observers using the Goldberg scoring system and the expanded system. A subset (n = 85) was then re-evaluated following destructive cleaning, using both scoring systems. Material loss for this subset was quantified using metrology and correlated with both scoring systems. Results: There was substantial agreement in grading among all three observers with uncleaned (n = 465) and with the subset of cleaned (n = 85) implants. The expanded scoring criteria provided a wider distribution of scores which ultimately correlated well with corrosion material loss. Cleaning changed the average scores marginally using the Goldberg criteria (p = 0.290); however, using the VGS, approximately 40% of the scores for all observers changed, increasing the average score from 4.24 to 4.35 (p = 0.002). There was a strong correlation between measured material loss and new grading scores. Conclusion: The expanded scoring criteria provided a wider distribution of scores which ultimately correlated well with corrosion material loss. This system provides potential advantages for assessing taper damage without requiring specialized imaging devices. Cite this article: Bone Joint Res 2023;12(3):155–164.

Abstract. Objectives:. Implant prominence after ulnar fracture fixation may be mitigated by the use of lower profile plates. The biomechanical strength and stability of 2.7-mm and 3.5-mm locking compression plates for fixation were compared. Methods:. Two fracture conditions, transverse (N = 10) and oblique (N = 10), were evaluated in an in vitro study. Half of the specimens for each condition were fixed with 2.7-mm plates and the other half with 3.5-mm plates, all fixed with conventional dynamic compression mechanisms. Specimens were loaded under ±2 Nm of cyclic axial torsion, then under 10 Nm of cyclic cantilever bending, and bending to failure. Interfragmentary motion and strain were analyzed to determine construct stability as a function of fracture pattern and plate size. Results:. Interfragmentary motion was significantly larger in all constructs fixed with 2.7-mm plates, compared with 3.5-mm plates (P < 0.01). The 2.7-mm constructs with transverse fractures had the greatest motion, ranging between 5° and 10° under axial rotation and 5.0–6.0 mm under bending. Motions were the lowest for 3.5-mm constructs with oblique fractures, ranging between 3.2 and 4.2 mm under bending and 2°–3.5° for axial rotation. For oblique fractures, the bending moment at ultimate failure was 31.4 ± 3.6 Nm for the 2.7-mm constructs and 10.0 ± 1.9 Nm for 3.5-mm constructs (P < 0.01). Similarly, for transverse fractures, the bending moment was 17.9 ± 4.0 Nm for the 2.7-mm constructs and 9.7 ± 1.3 Nm for the 3.5-mm constructs (P < 0.01). Conclusions:. Although 3.5-mm plates were more effective at reducing fracture motion, they were consistently associated with refracture at the distal-most screw hole under load to failure. By contrast, 2.7-mm plates plastically deformed despite excessive loads, potentially avoiding a subsequent fracture. Level of Evidence:. Level V.

Ensuring safe high-quality food is an ongoing priority, yet consumers face heightened risk from foodborne pathogens due to extended supply chains and climate change in the food industry. Nanomaterial-based assays are popular and have recently been developed to ensure food safety and high quality. This review discusses strategies for utilizing gold nanoparticles in colorimetric biosensors. The visible-signal biosensor proves to be a potent sensing technique for directly measuring targets related to foodborne pathogens in the field of food analysis. Among visible-signal biosensors, the localized surface plasmon resonance (LSPR) biosensor has garnered increasing attention and experienced rapid development in recent years. This review succinctly introduces the origin of LSPR theory, providing detailed insights into its fundamental principles. Additionally, this review delves into the application of nanotechnology for the implementation of the LSPR biosensor, exploring methods for utilizing gold nanoparticles and elucidating the factors that influence the generation of visible signals. Several emerging technologies aimed at simple and rapid immunoassays for onsite applications have been introduced in the food industry. In the foreseeable future, field-friendly colorimetric biosensors could be adopted in food monitoring systems. The onsite and real-time detection of possible contaminants and biological substances in food and water is essential to ensure human health and safety.

To analyze the relationship between homologous and heterologous serological titers of immunized pigs and their protection statuses against FMD virus challenges, in the present study, the correlation between the virus neutralization titers at 21 and 28 dpv and the protection statuses at 28 dpv against challenge with FMD virus was analyzed using data sets comprising five different combinations of homologous or heterologous challenge experiments in pigs vaccinated with type O (n = 96), A (n = 69), and Asia 1 (n = 74). As a result, the experiments were divided into three groups (21D-1, 21D-2, and 21D-3) in the 21-dpv model and two groups (28D-1 and 28D-2) in the 28-dpv model. Each response curve of groups 21D-1 and 21D-2 in the 21-dpv model was very similar to each curve of groups 28D-1 and 28D-2 in the 28-dpv model, respectively, even though there was an exceptional extra group (21D-3) in the 21-dpv model. The average titers estimating 0.75 probability of protection ranged from 1.06 to 1.62 log10 in the 21-dpv model and from 1.26 to 1.64 log10 in the 28-dpv model. In summary, we demonstrated that the serological method is useful for predicting the homologous and heterologous protection statuses of vaccinated pigs.

Background To evaluate the association of dental diseases and oral hygiene care with incidence of heart failure (HF) among patients with type 2 diabetes. Methods and Results This study included 173 927 patients with type 2 diabetes aged ≥40 years, who underwent Korean National Health Insurance Service health examinations in 2008 and were followed up until the end of 2017. Hazard ratios (HRs) and 95% CIs for HF were estimated using multivariable Cox proportional hazards regression analysis. During a median follow‐up of 9.3 years, 1.94% of participants developed HF. An increased number of missing teeth was associated with a higher risk of HF (P

A biofilm is a three-dimensional microbial community, which is difficult to completely control with a typical sanitizer owing to its complex structure. The aim of this study was to establish a system for the combined treatment of biofilms with 10 ppmv gaseous chlorine dioxide (ClO2) and antimicrobial agents (2% citric acid, 2% hydrogen peroxide [H2O2], and 100 ppm peracetic acid [PAA]), and to investigate the synergistic microbicidal efficacy of the combination treatments to inactivate Listeria monocytogenes, Salmonella Typhimurium, and Escherichia coli O157:H7 in biofilms. The antimicrobial agents were aerosolized using a humidifier on top of a chamber to achieve a relative humidity of 90% (within a range of ±2%). While biofilm treatment with the aerosolized antimicrobial agents for 20 min inactivated approximately 1 log CFU/cm2 (0.72–1.26 log CFU/cm2) of the pathogens and the gaseous ClO2 gas treatment for 20 min inactivated

The present study aims to investigate the dynamic properties of a novel isolation system composed of separate rubber and wire isolators. The testing program comprised pure compressive, pure-shear, compressive-stress dependence, and shear-strain dependence tests that used full-scale test specimens according to ISO 22762-1. A total of 22 test specimens were fabricated and investigated. Among the tests, the pure compressive test was a destructive test that reached up to the failure stage, whereas the others were nondestructive tests before the failure stage. Similar to the pure-shear test, at each compressive-stress level in the compressive dependence test or at each shear-strain level in the shear-strain dependence test, the cyclic loading was conducted for three cycles. In the nondestructive tests, examination of the dynamic shear properties in the X-direction was independent of the Y-direction. The test results revealed that the increase in the shear strain increased the energy dissipation but decreased the damping ratio, whereas the increase in the compressive stress increased the damping ratio. In addition, a macro model was developed to simulate the load-displacement response of the isolation systems, and the prediction results were consistent with the experimental results.

BackgroundFurther studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians.ObjectivesTo determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients.MethodsUsing the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m2 at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population.ResultsWe identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA2DS2-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23–2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300–0.499, p

Most (90%) vitamin D synthesis occurs in the skin using sunlight (ultraviolet rays), and 10% is obtained through food. Vitamin D is an essential nutrient for skeletal growth and maintenance, cell proliferation and differentiation, and immune function. This study investigated whether maternal serum vitamin D concentrations induce maternofetal effects. Hematological analysis, serological changes, and precision fetal ultrasound findings were analyzed by maternal vitamin D concentration in gestational weeks 22–25 to ascertain direct effects on fetal growth. Bone density–vitamin D concentration correlation was analyzed. No hematologic or serological effect of maternal vitamin D concentration was detected; however, the sexually transmitted infection and cross-infection rates were inversely proportional to maternal vitamin D concentration. No significant correlation between vitamin D concentration and vertebral and femoral BMD was detected. For fetal growth, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length were analyzed. Humerus (p < 0.05) and femur (p < 0.001) lengths were higher in the vitamin D-sufficient group than in the vitamin D-deficient group. Vitamin D concentration did not positively affect hematologic changes and bone density; maternal vitamin D concentration essentially affected fetal bone growth. Vitamin D inhibits sexually transmitted infections in mothers and promotes fetal bone growth. Prevention of vitamin D deficiency, supplementation, or outdoor activities is recommended.

Background We estimated the effect of obesity on the incidence of cardiovascular disease (CVD) and mortality in women according to menopausal status. Methods Women aged 40 to 69 years under routine health check-ups provided by the National Health Insurance Service in 2009 were followed up till 2018 (n=2,208,559). Results In premenopausal women, a significant increment of mortality rate was found in underweight and obesity class II (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.67; and HR, 1.25; 95% CI, 1.12 to 1.39) compared to normal body mass index (BMI); overweight and obesity class I did not affect mortality rate. In postmenopausal women, obesity as well as overweight status reduced the risk of mortality compared to normal BMI (HR, 0.86; 95% CI, 0.83 to 0.88; and HR, 0.84; 95% CI, 0.82 to 0.86). By contrast, there was a linear association between CVD and BMI above the normal range irrespective of menopausal status, which was attenuated in diabetic women. Conclusion The current study replicated the J-shaped relationship between BMI and mortality, being more prominent in the postmenopausal group. The risk of CVD was linearly increased as BMI was increased above the normal range irrespective of menopausal status.

The genus Lactococcus is a gram-positive, catalase-negative, non-motile bacterium. It is a facultative anaerobe and can be cultured at 10∼40°C. The genus Lactococcus consists of 16 species, of which Lactococcus garvieae and Lactococcus lactis are known to cause disease in humans. This study reports the first case in which L. garvieae was identified in the urine culture of a 74-year-old woman. The patient confirmed the findings of acute urinary tract infection through blood tests, microbial identification tests, antibiotic susceptibility tests, and computed tomography performed at a hospital. The patient was admitted to the nephrology ward and was treated with IV fluids and erythromycin antibiotics and discharged 5 days later. This is the first case in Korea in which L. garvieae was isolated from the urine of a patient with a urinary tract infection and is expected to be useful in treating patients with L. garvieae infection in the future.

Abstract Background There have been concerns regarding the safety of renin-angiotensin-aldosterone-system (RAAS)-blocking agents including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) during the coronavirus disease 2019 (COVID-19) pandemic. This study sought to evaluate the impact of hypertension and the use of ACEI/ARB on clinical severity in patients with COVID-19. Methods A total of 3,788 patients aged 30 years or older who were confirmed with COVID-19 with real time reverse transcription polymerase chain reaction were identified from a claims-based cohort in Korea. The primary study outcome was severe clinical events, a composite of intensive care unit admission, need for ventilator care, and death. Results Patients with hypertension (n = 1,190, 31.4 %) were older and had higher prevalence of comorbidities than those without hypertension. The risk of the primary study outcome was significantly higher in the hypertension group, even after multivariable adjustment (adjusted odds ratio [aOR], 1.67; 95 % confidence interval [CI], 1.04 to 2.69). Among 1,044 patients with hypertensive medical treatment, 782 (74.9 %) were on ACEI or ARB. The ACEI/ARB subgroup had a lower risk of severe clinical outcomes compared to the no ACEI/ARB group, but this did not remain significant after multivariable adjustment (aOR, 0.68; 95 % CI, 0.41 to 1.15). Conclusions Patients with hypertension had worse COVID-19 outcomes than those without hypertension, while the use of RAAS-blocking agents was not associated with increased risk of any adverse study outcomes. The use of ACE inhibitors or ARBs did not increase the risk of adverse COVID-19 outcomes, supporting current guidance to continue these medications when indicated.

Abstract Increasing evidence suggests that obstructive sleep apnea (OSA) is a metabolic syndrome-related disease; however, the association between nonalcoholic fatty liver disease (NAFLD) and OSA is not firmly established. In this study, we investigated the relationship between NAFLD and OSA in a general population drawn from a nationwide population-based cohort. Data from the Korean National Health Insurance System between January 2009 and December 2009 were analyzed using Cox proportional hazards model. NAFLD was defined as a fatty liver index (FLI) ≥ 60 in patients without excessive alcohol consumption (who were excluded from the study). Newly diagnosed OSA during follow-up was identified using claims data. Among the 8,116,524 participants, 22.6% had an FLI score of 30–60 and 11.5% had an FLI ≥ 60. During median follow-up of 6.3 years, 45,143 cases of incident OSA occurred. In multivariable analysis, the risk of OSA was significantly higher in the higher FLI groups (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.12–1.18 for FLI 30–60 and aHR 1.21, 95% CI 1.17–1.26 for FLI ≥ 60). These findings were consistent regardless of body mass index and presence of abdominal obesity. In conclusion, a high FLI score may help identify individuals with a high risk of OSA. Understanding the association between NAFLD and OSA may have clinical implications for risk-stratification of individuals with NAFLD.

Classifying myocardial infarction by subtype is crucial for appropriate patient management. Although troponin is currently the most commonly used biomarker, it is not a specific marker for myocardial infarction and cannot distinguish subtypes. Furthermore, previous studies have confirmed that proteins known as myocardial infarction markers could function to distinguish the type of myocardial infarction. Therefore, we identify a marker that can distinguish type 1 myocardial infarction from other diseases with elevated troponin. We used mass spectrometry to compare type 1 myocardial infarction with other conditions characterized by troponin elevation and identified new candidate markers for disease classification. We then verified these markers, along with those already known to be associated with cardiovascular disease and plaque rupture. We identified α-1 acid glycoprotein 2, corticosteroid-binding globulin, and serotransferrin as potential distinguishing markers. The presence of these markers and other parameters, such as chest pain, electrocardiogram, and troponin levels from the complementary diagnostic processes, could provide valuable information to specifically diagnose type 1 myocardial infarction.

We examined whether recombinant human bone morphogenetic protein-2 (rhBMP-2) when applied to collagen membranes, would reinforce them during guided bone regeneration. Four critical cranial bone defects were created and treated in 30 New Zealand white rabbits, including a control group, critical defect only; group 1, collagen membrane only; group 2, biphasic calcium phosphate (BCP) only; group 3, collagen membrane + BCP; group 4, collagen membrane with rhBMP-2 (1.0 mg/mL); group 5, collagen membrane with rhBMP-2 (0.5 mg/mL); group 6, collagen membrane with rhBMP-2 (1.0 mg/mL) + BCP; and group 7, collagen membrane with rhBMP-2 (0.5 mg/mL) + BCP. After a 2-, 4-, or 8-week healing period, the animals were sacrificed. The combination of collagen membranes with rhBMP-2 and BCP yielded significantly higher bone formation rates compared to the other groups (control group and groups 1–5 < groups 6 and 7; p < 0.05). A 2-week healing period yielded significantly lower bone formation than that at 4 and 8 weeks (2 < 4 = 8 weeks; p < 0.05). This study proposes a novel GBR concept in which rhBMP-2 is applied to collagen membranes outside instead of inside the grafted area, thereby inducing quantitatively and qualitatively enhanced bone regeneration in critical bone defects.

The positive association between metabolic syndrome (MetS) and hepatocellular carcinoma (HCC) has been suggested. However, no studies have yet looked at how the risk of developing HCC varies with changes in MetS status. Therefore, we aimed to investigate the association between changes in MetS and subsequent HCC development. Data were obtained from the Korean National Health Insurance Service. In this study, 5,975,308 individuals who participated in health screenings both in 2009–2010 and 2011–2012 were included. Individuals with preexisting viral hepatitis, liver cirrhosis, or cancer diagnoses were excluded. Subjects were divided into four groups according to change in MetS status during the 2-year interval screening (from 2009 to 2011): sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. Cox regression analysis was used to examine the hazard ratios of HCC. The subjects were followed through December 31, 2018. During a median of 7.3 years of follow-up, 25,880 incident HCCs were identified. Compared to the sustained non-MetS group, age, sex, smoking, alcohol, regular exercise, and body mass index-adjusted hazard ratios (95% confidence interval) for HCC development were 1.01 (0.97–1.05) for the transition to MetS group, 1.05 (1.003–1.09) for the transition to non-MetS group, and 1.07 (1.03–1.10) for the sustained MetS group. Stratified analyses according to age, sex, smoking, alcohol intake, exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease showed similar results. A significantly increased HCC risk was observed in the sustained MetS and transition to non-MetS groups. The baseline status of MetS was associated with the risk of HCC development. Strategies to improve MetS, especially targeting insulin resistance, might prevent HCC development.

Abstract Background This study developed a diagnostic tool to automatically detect normal, unclear and tumor images from colonoscopy videos using artificial intelligence. Methods For the creation of training and validation sets, 47,555 images in the jpg format were extracted from colonoscopy videos for 24 patients in Korea University Anam Hospital. A gastroenterologist with the clinical experience of 15 years divided the 47,555 images into three classes of Normal (25,895), Unclear (2038) and Tumor (19,622). A single shot detector, a deep learning framework designed for object detection, was trained using the 47,255 images and validated with two sets of 300 images—each validation set included 150 images (50 normal, 50 unclear and 50 tumor cases). Half of the 47,255 images were used for building the model and the other half were used for testing the model. The learning rate of the model was 0.0001 during 250 epochs (training cycles). Results The average accuracy, precision, recall, and F1 score over the category were 0.9067, 0.9744, 0.9067 and 0.9393, respectively. These performance measures had no change with respect to the intersection-over-union threshold (0.45, 0.50, and 0.55). This finding suggests the stability of the model. Conclusion Automated detection of normal, unclear and tumor images from colonoscopy videos is possible by using a deep learning framework. This is expected to provide an invaluable decision supporting system for clinical experts.

The residual strength of denting- and fracture-damaged box girders were experimentally and numerically investigated. The experiments were conducted under a pure bending moment using the four-point bending test method. The load, deflection, and strain were measured. The strains of the extension structures were also measured, and the frictional forces between the model and the supported round bar were estimated. Test models consisting of two groups were fabricated. These groups were designed to estimate the residual strength of denting- and fracture-damaged models. The damage was induced by releasing a striker using a drop-testing machine to consider the dynamic effect. Additionally, numerical analyses were performed via a nonlinear finite element analysis, where the measured initial imperfection data and welding residual stresses were considered. The ultimate longitudinal moments that considered the frictional force of the round bars were reduced by 12% (on average) compared with those obtained by neglecting the frictional forces.

Abstract The objective of this research was to precisely simulate the temperature distribution and inactivation of Escherichia coli O157:H7 by batch ohmic heating pasteurization of orange juice based on a time‐dependent numerical model. A finite element method (FEM) embedded with pathogen inactivation codes using Java language simultaneously solved electric heating, k‐ε turbulent flow, and heat transfer equations and dealt with natural heat losses through the walls and air as the boundary conditions. The simulated temperature distribution and populations of E. coli O157:H7 did not differ from the experimental data for every treatment time within a relative error of 6.0%. A cold point problem was observed in the bottom corner, which was more severe for large orange juice samples, leading to an increased treatment time in order to ensure a 5‐log reduction of E. coli O157:H7.

Drought intensity modifies the assimilatory pathway of glutathione (GSH) synthesis. Abscisic acid (ABA) is a representative signaling hormone involved in regulating plant stress responses. This study aimed to investigate an interactive regulation of sulfate and/or ABA in GSH metabolism and redox. The drought-responsive alterations in sulfate assimilation and GSH-based redox reactions were assessed relative to ABA responses on the time-course of drought intensity. Drought-responsive H2O2 concentrations were divided into two distinct phases—an initial 4 days of no change (Ψw ≥ −0.49 MPa) and a phase of higher accumulation during the late phase of the drought (days 10–14; Ψw ≤ −1.34 MPa). During the early phase of the drought, GSH/GSSG redox state turned to the slightly reduced state with a transient increase in GSH, resulting from a strong activation of H2O2 scavenging enzymes, ascorbate peroxidase (APOX) and glutathione reductase (GR). The late phase of the drought was characterized by a decrease in GSH due to cysteine accumulation, shifting GSH- and NADPH-based redox states to higher oxidization, increasing sulfate and ABA in xylem, and causing ABA accumulation in leaves. Regression analysis revealed that sulfate in xylem sap was positively correlated with H2O2 concentrations and ABA was closely related to decreases in the GSH pool and the oxidation of GSH catalyzed by glutathione peroxidase (GPOX). These results indicate that drought-induced oxidation proceeds through the suppression of GSH synthesis and further GSH oxidation in a sulfate-activated ABA-dependent manner.

In plants, prolonged drought induces oxidative stress, leading to a loss of reducing potential in redox components. Abscisic acid (ABA) is a representative hormonal signal regulating stress responses. This study aimed to investigate the physiological significance of dimethylthiourea (DMTU, an H2O2 scavenger) in the hormonal regulation of the antioxidant system and redox control in rapeseed (Brassica napus L.) leaves under drought stress. Drought treatment for 10 days provoked oxidative stress, as evidenced by the increase in O2•− and H2O2 concentrations, and lipid peroxidation levels, and a decrease in leaf water potential. Drought-induced oxidative responses were significantly alleviated by DMTU treatment. The accumulation of O2•− and H2O2 in drought-treated plants coincided with the enhanced expression of the NADPH oxidase and Cu/Zn-SOD genes, leading to an up-regulation in oxidative signal-inducible 1 (OXI1) and mitogen-activated protein kinase 6 (MAPK6), with a concomitant increase in ABA levels and the up-regulation of ABA-related genes. DMTU treatment under drought largely suppressed the drought-responsive up-regulation of these genes by depressing ABA responses through an antagonistic interaction with salicylic acid (SA). DMTU treatment also alleviated the drought-induced loss of reducing potential in GSH- and NADPH-based redox by the enhanced expression of glutathione reductase 1 (GR1) and up-regulation of oxidoreductase genes (TRXh5 and GRXC9). These results indicate that DMTU effectively alleviates drought-induced oxidative responses by suppressing ABA-mediated oxidative burst signaling in an antagonistic regulation of SA.

We analyzed the relationship between chronic rhinosinusitis (CRS) and the incidence of head and neck cancers (HNCs) in a Korean adult population. This retrospective cohort study included data from the Korean National Health Insurance Service database. Adjustments were made to minimize risk variables for sex, age, diabetes, hypertension, dyslipidemia, and rhinitis between the two groups. The primary endpoint was newly diagnosed HNC between January 2009 and December 2018. Among 1,337,120 subjects in the Korean National Health Insurance Service database, data from 324,774 diagnosed with CRS (CRS group) and 649,548 control subjects (control group) were selected. Patients with CRS exhibited a statistically significant greater risk for nasal cavity/paranasal sinus cancer, hypopharynx/larynx cancer, and thyroid cancer compared with the control group. In the CRS group, the adjusted hazard ratios for nasal cavity/paranasal sinus cancer were 1.809 (95% confidence interval (CI) 1.085–3.016), 1.343 (95% CI 1.031–1.748) for hypopharynx and larynx cancer, and 1.116 (95% CI 1.063–1.173) for thyroid cancer. CRS was associated with a higher incidence of HNCs. Therefore, physicians should carefully consider the possibility of HNC progression and implement therapeutic strategies to minimize the impact of these diseases.

Human enterokinase light chain (hEKL) specifically cleaves the sequence (Asp)4-Lys↓X (D4K), making this a frequently used enzyme for site-specific cleavage of recombinant fusion proteins. However, hEKL production from Escherichia coli is limited due to intramolecular disulphide bonds. Here, we present strategies to obtain soluble and active hEKL from E. coli by expressing the hEKL variant C112S fused with maltose-binding protein (MBP) through D4K and molecular chaperons including GroEL/ES. The fusion protein self-cleaved in vivo, thereby removing the MBP in the E. coli cells. Thus, the self-cleaved hEKL variant was released into the culture medium. One-step purification using HisTrap™ chromatography purified the hEKL variant exhibiting an enzymatic activity of 3.1 × 103 U/mL (9.934 × 105 U/mg). The approaches presented here greatly simplify the purification of hEKL from E. coli without requiring refolding processes.

Summary: Hsp70 inhibitors have great potential as chemical probes and anticancer agents. Thus, it is important to elucidate their modes of action on cancer cell death. This protocol describes a step-by-step process for the synthesis of apoptozole as an inhibitor of Hsp70, analysis of internalization of apoptozole into lysosomes, and assessment of lysosomal membrane permeabilization induced by apoptozole. The current protocol can be used for detailed mechanistic studies of Hsp70 inhibitors and further substances targeting lysosomal proteins on cancer cell death.For complete information on the use and execution of this protocol, please refer to Park et al. (2018).

Drought alters the level of endogenous reactive oxygen species (ROS) and hormonal status, which are both involved in the regulation of stress responses. To investigate the interplay between ROS and hormones in proline metabolism, rapeseed (Brassica napus L.) plants were exposed to drought or exogenous H2O2 (Exo-H2O2) treatment for 10 days. During the first 5 days, the enhanced H2O2 concentrations in drought treatment were associated with the activation of superoxide dismutase (SOD) and NADPH oxidase, with enhanced ABA and SA levels, while that in Exo-H2O2 treatment was mainly associated with SA-responsive POX. During the latter 5 days, ABA-dependent ROS accumulation was predominant with an upregulated oxidative signal-inducible gene (OXI1) and MAPK6, leading to the activation of ABA synthesis and the signaling genes (NCED3 and MYC2). During the first 5 days, the enhanced levels of P5C and proline were concomitant with SA-dependent NDR1-mediated signaling in both drought and Exo-H2O2 treatments. In the latter 5 days of drought treatment, a distinct enhancement in P5CR and ProDH expression led to higher proline accumulation compared to Exo-H2O2 treatment. These results indicate that SA-mediated P5C synthesis is highly activated under lower endogenous H2O2 levels, and ABA-mediated OXI1-dependent proline accumulation mainly occurs with an increasing ROS level, leading to ProDH activation as a hypersensitive response to ROS and proline overproduction under severe stress.

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome (MetS). However, the temporal relationship between NAFLD and MetS has yet to be evaluated, especially in young adults. In this study, we investigated whether NAFLD could be a precursor for MetS in metabolically healthy young adults. Using the Korean nationwide health screening database, we analyzed subjects aged 20–39 years who were free from any component of MetS between 2009 and 2012. A total of 1,659,192 subjects without excessive alcohol consumption or concomitant liver disease were categorized into three groups according to the fatty liver index (FLI): (1) NAFLD (FLI ≥ 60); (2) borderline NAFLD (30 ≤ FLI < 60); and (3) control (FLI < 30). During the 6,699,462 person-years of follow-up, 109,239 subjects developed MetS (16.3 per 1000-person-years). The NAFLD group and the borderline NAFLD group were associated with a higher risk of MetS than the control group (incidence rate ratios, 2.9 (95% confidence interval (CI), 2.7–3.1) for the NAFLD group and 2.1 (95% CI, 2.1–2.2) for the borderline NAFLD group, respectively). In addition, all of the metabolic components were positively associated with FLI in a proportional manner. NAFLD is associated with the future onset of MetS in young adults. Therefore, active lifestyle intervention is required for young adults diagnosed with NAFLD to prevent MetS and other metabolic diseases.

Background: Nonalcoholic fatty liver disease is considered to be the hepatic component of metabolic syndrome (MetS). However, the association between changes in MetS status and the risk of liver cirrhosis (LC) has not been investigated to date. This study assessed the association between changes in MetS and subsequent nonviral LC development. Methods: Data were obtained from the Korean National Health Insurance Service. Individuals who participated in health screenings from both 2009 to 2010 and 2011 to 2012 were included. The primary outcome was LC development according to the static and dynamic MetS status. Subjects were stratified into four groups according to the change in MetS status observed from the two-year interval screening (2009–2011). Cox regression analysis was used to examine the hazard ratios of LC. Results: During a median of 7.3 years of follow-up, 24,923 incident LC cases developed among 5,975,308 individuals. After adjusting for age, sex, smoking, alcohol, regular exercise, and body mass index, the adjusted hazard ratios (95% confidence intervals) for LC development were 1.39 (1.33–1.44) for the MetS-Developed group, 1.32 (1.26–1.37) for the MetS-Recovered group, and 1.51 (1.45–1.56) for the MetS-Sustained group, relative to the MetS-Free group. Stratified analyses according to age, sex, smoking, alcohol intake, exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease showed similar results. Conclusions: Both static and dynamic MetS status are independent risk factors for LC development. The risk of LC was the highest in people with sustained MetS and was lower in the MetS-Recovered group than in the MetS-Sustained group. These results suggest that improving a person’s MetS status may be helpful in preventing LC.

During winter, foraging activity of ants is considered low in temperate regions. Winter activity of ground-dwelling ants was investigated using bait traps and quadrat sampling in an urban area of Fukuoka City, western Japan. Six study sites were grouped into two categories: 4 open land types and 2 forest types. A total of 18 ant species were recorded between the end of January and beginning of March. The foraging activity of ants was generally low, except during relatively warm periods when the surface ground temperature was above 6℃–7℃ or soil temperature was above 4℃–5℃. Tetramorium tsushimae, Messor aciculatus, and Pheidole noda were the most abundant in the open land type, whereas Nylanderia flavipes, P. noda, and Crematogaster osakensis were the most abundant in the forest type. Bait preference varied among the different species, e.g., P. noda preferred tuna over honey, whereas N. flavipes similarly responded to tuna and honey. This is the first detailed study on the relationship between temperature and ant activity in Japanese mainland fauna.

To investigate the regulatory role of ethylene in the source-sink relationship for nitrogen remobilization, short-term effects of treatment with different concentrations (0, 25, 50, and 75 ppm) of ethephon (2-chloroethylphosphonic acid, an ethylene inducing agent) for 10 days (EXP 1) and long-term effects at 20 days (Day 30) after treatment with 100 ppm for 10 days (EXP 2) on protein degradation and amino acid transport in foliar sprayed mature leaves of Brassica napus (cv. Mosa) were determined. In EXP 1, endogenous ethylene concentration gradually increased in response to the treated ethephon concentration, leading to the upregulation of senescence-associated gene 12 (SAG12) expression and downregulation of chlorophyll a/b-binding protein (CAB) expression. Further, the increase in ethylene concentration caused a reduction in protein, Rubisco, and amino acid contents in the mature leaves. However, the activity of protease and expression of amino acid transporter (AAP6), an amino acid transport gene, were not significantly affected or slightly suppressed between the treatments with 50 and 75 ppm. In EXP 2, the enhanced ethylene level reduced photosynthetic pigments, leading to an inhibition of flower development without any pod development. A significant increase in protease activity, confirmed using in-gel staining of protease, was also observed in the ethephon-treated mature leaves. Ethephon application enhanced the expression of four amino acid transporter genes (AAP1, AAP2, AAP4, and AAP6) and the phloem loading of amino acids. Significant correlations between ethylene level, induced by ethephon application, and the descriptive parameters of protein degradation and amino acid transport were revealed. These results indicated that an increase in ethylene upregulated nitrogen remobilization in the mature leaves (source), which was accompanied by an increase in proteolytic activity and amino acid transport, but had no benefit to pod (sink) development.

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.

Nuclear power is a major source of electricity in the international community. However, a significant problem with nuclear power is that, if a severe nuclear accident occurs, radiation may leak and cause great damage. As such, research on nuclear safety has become increasingly popular worldwide. In this paper, the structural integrity of a reactor cavity during a steam explosion—one kind of the aforementioned severe nuclear accidents—was evaluated. Steam explosions are primarily caused by fuel–coolant interactions (FCI), and result from issues in the cooling system that discharges the melt from the reactor core to the outside. A steam explosion can damage the nuclear power plant, and radiation leakage, the greatest concern, may occur. In the Chernobyl or Fukushima Daiichi accidents, significant radiation leakages resulted in damages extending beyond the country of origin. In this paper, a steam explosion was simulated using values given by the transient analysis code for explosive reactions (TRACER-II)—the only steam explosion code in Korea. The walls of the reactor cavity were modeled after the APR-1400 currently operating in Korea. The integrity of the concrete, rebars, and liner plate in the reactor cavity during a steam explosion was evaluated in terms of stress and ductile failure strain limits.

South Korea has experienced FMD outbreaks almost every year since 2014. Therefore, a novel local vaccine that can cover various topotypes of viruses is required. Two virus strains, O/Boeun/SKR/2017 and A/Yeoncheon/SKR/2017, were cultured up to the pilot scale based on the optimized conditions set up on the flask scale. FMDV particles (146S) of 2 µg/mL or more were obtained from the virus culture supernatant using a 100 L bioreactor. The viruses were fully inactivated using binary ethylenimine within 16 h through two inactivation cycles and mixed with an adjuvant into a bivalent vaccine (types O and A) consisting of 15 µg viruses per strain. The experimental bivalent vaccine showed a broad spectrum of high neutralizing antibody titers against heterologous viruses, including type O Cathay strain and type A Asia topotypes, except for GVII. The 50% protective dose was determined as 12.5 for O/Boeun/SKR/2017 and 15.6 for A/Yeoncheon/SKR/2017. Collectively, we expect that the bivalent vaccine could protect against FMDV types O and A circulating in South Korea and neighboring countries. To our knowledge, this is the first report demonstrating that the vaccine strains could be successfully scaled-up to a 100 L bioreactor, with the determination of its protective efficacy in pigs.

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

Background and Aims: Altered lipid metabolism has been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development. Methods: Data were obtained from the Korean National Health Insurance Service from 2009 to 2017. Cox regression analysis was used to examine the hazard ratios of HCC in 8,528,790 individuals who had undergone health check-ups in 2009. Results: During a median of 7.3 years follow-up, 26,891 incidents of HCCs were identified. The incidence of HCC (per 100,000 person-years) gradually decreased according to the increase in total-cholesterol and LDL-cholesterol; the incidence of HCC was 69.2, 44.0, 33.9, and 25.8 in quartile-1 (Q1), Q2, Q3, and Q4 population of total-cholesterol, and 63.6, 44.5, 37.2, and 28.3 in Q1, Q2, Q3, and Q4 population of LDL-cholesterol, respectively. Compared to Q1 of total-cholesterol, subjects in higher total-cholesterol levels were associated with a lower incidence of HCC (multiple covariates-adjusted hazard ratio (aHR): Q2 0.61; Q3 0.46; Q4 0.36). These associations were consistently observed in stratified subgroup analysis by the presence of liver cirrhosis or viral hepatitis. Conclusions: Low serum lipid levels were significantly associated with the increased risk of developing HCC. A low lipid profile might be an independent risk factor and preclinical marker for HCC.

The aim of this study was to characterize hormonal crosstalk with the sugar signaling and metabolic pathway based on a time course analysis of drought intensity. Drought intensity-responsive changes in the assimilation of newly fixed carbon (C) into soluble sugar, the content of sugar and starch, and expression of genes involved in carbohydrate metabolism were interpreted as being linked to endogenous abscisic acid (ABA) and salicylic acid (SA) levels and their signaling genes. The ABA and SA levels in the drought-stressed leaves increased together during the early drought period (days 0–6), and additional ABA accumulation occurred with depressed SA during the late period (days 6–14). Although drought treatment decreased the assimilation of newly fixed C into soluble sugar, representing a 59.9%, 33.1%, and 62.9% reduction in 13C-glucose, 13C-fructose, and 13C-sucrose on day 14, respectively, the drought-responsive accumulation of soluble sugars was significant. During the early period, the drought-responsive accumulation of hexose and sucrose was concurrent with the upregulated expression of hexokinase 1 (HXK1), which, in turn, occurred parallel to the upregulation of ABA synthesis gene 9-sis-epoxycarotenoid dioxygenase (NCED3) and SA-related genes (isochorismate synthase 1 (ICS1) and non-expressor of pathogenesis-related gene (NPR1)). During the late period, hexose accumulation, sucrose phloem loading, and starch degradation were dominant, with a highly enhanced expression of the starch degradation-related genes β-amylase 1 (BAM1) and α-amylase 3 (AMY3), which were concomitant with the parallel enhancement of sucrose non-fermenting−1 (Snf1)-related protein kinase 2 (SnRK2).2 and ABA-responsive element binding 2 (AREB2) expression in an ABA-dependent manner. These results indicate that the drought-responsive accumulation of sugars (especially SA-mediated sucrose accumulation) is part of the acclamatory process during the early period. Conversely, ABA-responsive hexose accumulation and sucrose phloem loading represent severe drought symptoms during the late drought period.

Abstract In this study we examined the anti-leukemia activity of a small molecule inhibitor of Hsp70 proteins, apoptozole (Az), and hybrids in which it is linked to an inhibitor of either Hsp90 (geldanamycin) or Abl kinase (imatinib). The results of NMR studies revealed that Az associates with an ATPase domain of Hsc70 and thus blocks ATP binding to the protein. Observations made in the cell study indicated that Az treatment promotes leukemia cell death by activating caspase-dependent apoptosis without affecting the caspase-independent apoptotic pathway. Importantly, the hybrids composed of Az and geldanamycin, which have high inhibitory activities towards both Hsp70 and Hsp90, exhibit enhanced anti-leukemia activity relative to the individual inhibitors. However, the Az and imatinib hybrids have weak inhibitory activities towards Hsp70 and Abl, and display lower cytotoxicity against leukemia cells compared to those of the individual constituents. The results of a mechanistic study showed that the active hybrid molecules promote leukemia cell death through a caspase-dependent apoptotic pathway. Taken together, the findings suggest that Hsp70 inhibitors as well as their hybrids can serve as potential anti-leukemia agents.

Background. Several factors influence the choice of antihypertensive drugs. To facilitate the rational use of drugs it is important to assess their prescription patterns over time. This study aims to evaluate doctors’ prescribing patterns of antihypertensive drugs for drug-naïve patients in South Korea. Methods. The claims data of the Korean National Health Insurance Research Database from 1 January 2011 to 31 December 2015 were analyzed. The data virtually cover the entire South Korean population. Antihypertensive drugs were further subdivided into angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEis), calcium channel blockers (CCBs), beta-blockers (BBs), and thiazide diuretics. The prescription pattern of antihypertensive drugs and associated factors were assessed according to the patients’ characteristics, including associated comorbidities. Results. A total of 2,919,162 subjects had started taking antihypertension medications during the study period. ARB was the most frequently prescribed drug (51.6%) followed by CCB (45.0%), BB (18.5%), diuretics (17.0%), and ACEi (11.7%). Most patients were prescribed with monotherapy (66.7%) rather than combination therapy (33.3%), and CCB was the most frequently prescribed monotherapy drug (25.7%). For combination therapy, ARB + CCB was the most frequently prescribed combination, and the prescription frequency was found to be increasing. In patients prescribed with combination therapy, most had been prescribed single-pill fixed-dose combination. Conclusion. We identified the physicians’ prescription patterns of antihypertensive drugs for treatment-naïve patients. The findings of this study can lead to a rational, evidence-based, and cost-effective improvement of prescription patterns in newly diagnosed hypertensive patients.

Proline metabolism influences the metabolic and/or signaling pathway in regulating plant stress responses. This study aimed to characterize the physiological significance of glutamate (Glu)-mediated proline metabolism in the drought stress responses, focusing on the hormonal regulatory pathway. The responses of cytosolic Ca2+ signaling, proline metabolism, and redox components to the exogenous application of Glu in well-watered or drought-stressed plants were interpreted in relation to endogenous hormone status and their signaling genes. Drought-enhanced level of abscisic acid (ABA) was concomitant with the accumulation of ROS and proline, as well as loss of reducing potential, which was assessed by measuring NAD(P)H/NAD(P)+ and GSH/GSSG ratios. Glu application to drought-stressed plants increased both salicylic acid (SA) and cytosolic Ca2+ levels, with the highest expression of calcium-dependent protein kinase (CPK5) and salicylic acid synthesis-related ICS1. The SA-enhanced CPK5 expression was closely associated with further enhancement of proline synthesis-related genes (P5CS1, P5CS2, and P5CR) expression and a reset of reducing potential with enhanced expression of redox regulating genes (TRXh5 and GRXC9) in a SA-mediated NPR1- and/or PR1-dependent manner. These results clearly indicate that Glu-activated interplay between SA- and CPK5-signaling as well as Glu-enhanced proline synthesis are crucial in the amelioration of drought stress in Brassica napus.

This study aimed to directly elucidate cultivar variation in disease susceptibility and disease responses in relation to hormonal status in the interaction of Brassica napus cultivars and Xanthomonas campestris pv. campestris (Xcc), the causal agent of black rot disease. Fully expanded leaves of six B. napus cultivars (cvs. Capitol, Youngsan, Saturnin, Colosse, Tamra, and Mosa) were inoculated with Xcc. At 14 days post-inoculation with Xcc, cultivar variation in susceptibility or resistance was interpreted with defense responses as estimated by redox status, defensive metabolites, and expression of phenylpropanoid synthesis-related genes in relation to endogenous hormonal status. Disease susceptibility of six cultivars was distinguished by necrotic lesions in the Xcc-inoculated leaves and characterized concurrently based on the higher increase in reactive oxygen species and lipid peroxidation. Among these cultivars, as the susceptibility was higher, the ratios of abscisic acid (ABA)/jasmonic acid (JA) and salicylic acid (SA)/JA tended to increase with enhanced expression of SA signaling regulatory gene NPR1 and transcriptional factor TGA1 and antagonistic suppression of JA-regulated gene PDF 1.2. In the resistant cultivar (cv. Capitol), accumulation of defensive metabolites with enhanced expression of genes involved in flavonoids (chalcone synthase), proanthocyanidins (anthocyanidin reductase), and hydroxycinnamic acids (ferulate-5-hydroxylase) biosynthesis and higher redox status were observed, whereas the opposite results were obtained for susceptible cultivars (cvs. Mosa and Tamra). These results clearly indicate that cultivar variation in susceptibility to infection by Xcc was determined by enhanced alteration of the SA/JA ratio, as a negative regulator of redox status and phenylpropanoid synthesis in the Brasica napus–Xcc pathosystem.

The effects of direct hemoperfusion with polymyxin B immobilized fiber (PMX) treatment for septic shock have been recently reported. However, little evidence of a true benefit on clinical outcomes, including mortality, is available. Herein, we report three cases of intra-abdominal infection associated with refractory septic shock Case 1 was Escherichia coli peritonitis after a colectomy. PMX treatment improved the hemodynamic parameters and lactic acid levels of the patient. In case 2, secondary peritonitis was associated with septic or cardiogenic shock. Septic cardiomyopathy was assumed to be the cause of shock. 24 hours after the use of PMX, cardiac contractility assessed by echocardiography returned to baseline. In case 3, a patient with Burkitt’s lymphoma and neutropenia was found to be gastroenteritis and Klebsiella pneumoniae bacteremia. Intravenous meropenem was administered for 3 days. Hemodynamic parameters improve after the twice use of PMXOverall, the change of serial sequential organ failure assessment score (SOFA) was more significant in surgical cases as compared to the medical case at 72 hours after PMX administration. All patients were discharged from the hospital. In addition to early resuscitation efforts and infection source control, PMX treatment may be beneficial to patients with refractory intra-abdominal infection associated with septic shock.

Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia.

In patients with cervical spine injuries, respiratory function requires careful attention. Voluntary respiratory control is usually possible with lesions below C4 level although paralysis of the abdominal musculature results in a decreased ability to cough and to clear secretions, which may later lead to respiratory insufficiency. Therefore, injuries above C5 usually necessitate long term mechanical ventilation. Even though weaning criteria are not definitive for the quadriplegic patient, M-mode ultrasonography of the diaphragm may be useful in identifying patients at high risk of difficulty weaning. Diaphragmatic dysfunction (vertical excursion < 10 mm or paradoxical movements) results in frequent early and delayed weaning failures. We present our clinical experience with successful weaning by using M-mode ultrasonography and a cough-assist device for secretion clearance after extubation in a quadriplegic patient undergoing C2-4 spine laminoplasty.

BackgroundThe purpose of this study was to evaluate the gender-related changes in the function and distribution of α1-adrenoceptors in the distal mesenteric artery of streptozotocin (STZ)-induced diabetic rats at the level of α1-adrenoceptor subtypes.MethodsDiabetes was induced by intravenous injection of STZ in a dose of 60 mg/kg through the tail vein in 8 week-old male or female Sprague-Dawley rats (n = 13/group). Age-matched normal rats (n = 15) were used as a control group. Four weeks after STZ injection, the change in mean arterial pressure caused by a 45° tilting was recorded. The α1-adrenoceptor subtypes mediating contractions of the distal mesenteric artery were investigated using the agonist, phenylephrine as well as subtype-selective antagonists including prazocin, 5-methylurapidil, and BMY 7378. The expression of α1-adrenoceptor subtypes of each artery was examined by immunofluorescence staining and western blotting using subtype selective antibodies.ResultsCompared with normal male rats, the contractile response to phenylephrine was decreased in the distal mesenteric artery in normal female rats. Moreover, a decrease in contractile force was observed in STZ-induced diabetic rats compared with age-matched controls. Western blotting revealed that there was the difference between normal male and female rats in manifestation of the α1D-adrenoceptor. In STZ-induced male and female diabetic rats, all α1-adrenoceptor subtypes were decreased in distal mesenteric arteries, compared with normal rats.ConclusionsThere was the gender-related functional difference of α1-adrenoceptors in normal rats. In both male and female rats, diabetes decreased the contractile response in mesenteric arteries, which might be caused by the overall change in α1-adrenoceptor.

BackgroundThis randomized single-blinded, cross-over study was done to evaluate the influence of the size of tracheal tubes on air leaks around the cuffs.MethodsIn a benchtop model, the number of longitudinal folds on the cuffs was evaluated for different sizes of tracheal tubes. In an anesthetized patient study, thirty patients scheduled for elective surgery under general anesthesia were included. After induction of anesthesia, the trachea was intubated with two sizes of tracheal tubes in a random sequence: in men, internal diameter of 7.5 mm and 8.0 mm; in women, internal diameter of 7.0 mm and 7.5 mm. After tracheal intubation with each tube, air leak pressures were evaluated at intracuff pressures of 20, 25 and 30 cmH2O by auscultation. To calculate the tracheal tube resistance (R), an inspiratory pause of 20% was applied and the resulting peak airway pressure (Ppeak), plateau pressure (Ppl) and mean expiratory tidal volume (Flow) were inserted in the formula R = (Ppeak - Ppl)/Flow.ResultsMore longitudinal folds of the tracheal tube cuffs occurred in larger sized tubes compared to the smaller ones in a benchtop model. Air leakage was significantly less for the smaller tracheal tubes than for the larger ones for each gender at intracuff pressures of 20, 25 and 30 cmH2O. Tracheal tube resistances were not significantly altered by the size of tracheal tube.ConclusionsThe use of a smaller tracheal tube within an acceptable size can reduce air leakage around the cuff without significantly changing the tracheal tube resistance.