Reversible Wrinkling Surfaces for Enhanced Grip on Wet/Dry Conditions.

Friction is important in material design for robotic systems that need to perform tasks regardless of environmental changes. Generally, robotic systems lose their friction in wet environments and fail to accomplish their tasks. Despite the significance of maintaining friction in dry and wet environments, it is still challenging. Here, we report a smart switching surface, which helps to complete missions in both wet and dry environments. Inspired by the reversible wrinkling mechanism of a human finger, the surface reversibly generates and removes wrinkles to adapt to both environments using volume-changing characteristics of the Nafion film. The switchable surfaces with manipulated wrinkle morphologies via patterns of diverse densities, sizes, and shapes induce a relationship between the wrinkle morphologies and friction: wrinkles on denser and smaller hexagonal patterns generate six times more friction than non-switching flat surfaces in wet environments and a similar amount of friction to the flat surfaces in dry environments. In addition, the wrinkle morphologies according to the patterns are predicted through numerical simulation, which is in good agreement with experimental results. This work presents potential applications in robotic systems that are required to perform in and out of water and paves the way for further understanding of wrinkling dynamics, manipulation, and evolutionary function in skin.

Neuroimaging in Randomized, Multi-Center Clinical Trials of Endovascular Treatment for Acute Ischemic Stroke: A Systematic Review.

Appropriate use and analysis of neuroimaging techniques is an inevitable aspect of clinical trials for patients with acute ischemic stroke. Neuroimaging examinations were recently used to define the core eligibility criteria and outcomes in acute ischemic stroke research. Recent clinical trials for endovascular treatment in acute ischemic stroke have also demonstrated the efficacy or safety of endovascular treatment using various imaging modalities as well as clinical indices. Furthermore, independent imaging reviews and imaging core laboratory assessments are essential to manage and analyze imaging data in order to enhance the reliability of the outcomes. Therefore, we systematically reviewed the use of neuroimaging in recent randomized clinical trials for endovascular treatment of acute ischemic stroke in order to provide a thorough summary, which would serve as a resource guiding the use of appropriate imaging protocols and analyses in future clinical trials for acute ischemic stroke. This review will help researchers select appropriate imaging biomarkers among the various imaging protocols available and apply the selected type of imaging examination for each study in accordance with the academic purpose.

MRI for prediction of hemorrhagic transformation in acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Hemorrhagic transformation increases mortality and morbidity in patients with acute ischemic stroke. PURPOSE: The purpose of this study is to evaluate the diagnostic performance of magnetic resonance imaging (MRI) for prediction of hemorrhagic transformation in acute ischemic stroke. MATERIAL AND METHODS: A systematic literature search of MEDLINE and EMBASE was performed up to 27 July 2018, including the search terms "acute ischemic stroke," "hemorrhagic transformation," and "MRI." Studies evaluating the diagnostic performance of MRI for prediction of hemorrhagic transformation in acute ischemic stroke were included. Diagnostic meta-analysis was conducted with a bivariate random-effects model to calculate the pooled sensitivity and specificity. Subgroup analysis was performed including studies using advanced MRI techniques including perfusion-weighted imaging, diffusion-weighted imaging, and susceptibility-weighted imaging. RESULTS: Nine original articles with 665 patients were included. Hemorrhagic transformation is associated with high permeability, hypoperfusion, low apparent diffusion coefficient (ADC), and FLAIR hyperintensity. The pooled sensitivity was 82% (95% confidence interval [CI] 61-93) and the pooled specificity was 79% (95% CI 71-85). The area under the hierarchical summary receiver operating characteristic curve was 0.85 (95% CI 0.82-0.88). Although study heterogeneity was present in both sensitivity (I2=67.96%) and specificity (I2=78.93%), a threshold effect was confirmed. Studies using advanced MRI showed sensitivity of 92% (95% CI 70-98) and specificity of 78% (95% CI 65-87) to conventional MRI. CONCLUSION: MRI may show moderate diagnostic performance for predicting hemorrhage in acute ischemic stroke although the clinical significance of this hemorrhage is somewhat uncertain.

Finite element analysis of long-term changes of the breast after augmentation mammoplasty: Implications for implant design.

The development of breast implant technology continues to evolve over time, but changes in breast shape after implantation have not been fully elucidated. Thus, we performed computerized finite element analysis in order to better understand the trajectory of changes and stress variation after breast implantation. The finite element analysis of changes in breast shape involved two components: a static analysis of the position where the implant is inserted, and a dynamic analysis of the downward pressure applied in the direction of gravity during physical activity. Through this finite element analysis, in terms of extrinsic changes, it was found that the dimensions of the breast implant and the position of the top-point did not directly correspond to the trajectory of changes in the breast after implantation. In addition, in terms of internal changes, static and dynamic analysis showed that implants with a lower top-point led to an increased amount of stress applied to the lower thorax. The maximum stress values were 1.6 to 2 times larger in the dynamic analysis than in the static analysis. This finding has important implications for plastic surgeons who are concerned with long-term changes or side effects, such as bottoming-out, after anatomic implant placement.

Perfusion CT for prediction of hemorrhagic transformation in acute ischemic stroke: a systematic review and meta-analysis.

OBJECTIVE: To investigate the diagnostic performance of perfusion CT for prediction of hemorrhagic transformation in acute ischemic stroke. METHODS: A computerized literature search of Ovid MEDLINE and EMBASE was conducted up to October 29, 2018. Search terms included acute ischemic stroke, hemorrhagic transformation, and perfusion CT. Studies assessing the diagnostic performance of perfusion CT for prediction of hemorrhagic transformation in acute ischemic stroke were included. Two reviewers independently evaluated the eligibility of the studies. A bivariate random effects model was used to calculate the pooled sensitivity and pooled specificity. Multiple subgroup analyses were performed. RESULTS: Fifteen original articles with a total of 1134 patients were included. High blood-brain barrier permeability and hypoperfusion status derived from perfusion CT are associated with hemorrhagic transformation. The pooled sensitivity and specificity were 84% (95% CI, 71-91%) and 74% (95% CI, 67-81%), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.84 (95% CI, 0.81-0.87). The Higgins I2 statistic demonstrated that heterogeneity was present in the sensitivity (I2 = 80.21%) and specificity (I2 = 85.94%). CONCLUSION: Although various perfusion CT parameters have been used across studies, the current evidence supports the use of perfusion CT to predict hemorrhagic transformation in acute ischemic stroke. KEY POINTS: • High blood-brain barrier permeability and hypoperfusion status derived from perfusion CT were associated with hemorrhagic transformation. • Perfusion CT has moderate diagnostic performance for the prediction of hemorrhagic transformation in acute ischemic stroke. • The pooled sensitivity was 84%, and the pooled specificity was 74%.

Influence of CYP2D6 Polymorphism on the Pharmacokinetic/Pharmacodynamic Characteristics of Carvedilol in Healthy Korean Volunteers.

BACKGROUND: Carvedilol is commonly used to treat hypertension as a ß- and α1-adrenoreceptor blocker, but it is metabolized by CYP2D6, and CYP2D6*10 allele is dominant in Asian population. The objective of this study was to assess the influence of CYP2D6 polymorphisms on the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of carvedilol in healthy Korean volunteers. METHODS: A PK/PD study for a single and multiple dosing of carvedilol were conducted. All volunteers in 3 genotypic groups received single oral dose of carvedilol 12.5 mg for 3 days, then 25 mg QD for 5 days, and 12.5 mg QD for another 3 days. PK parameters for carvedilol and its three metabolites were determined using non-compartmental analysis. For PD properties, blood pressure, heart rate, and the chronotropic dose 25 (CD25) value were obtained. RESULTS: The IM_2 group with two *10 alleles (intermediate metabolizers) exhibited lower clearance of carvedilol as well as higher area under the curve (AUC) for O-desmethyl carvedilol. The ratio of CD25 to baseline at multiple dosing was significantly higher in the combined IM group (IM_1 and IM_2) than in the EM group, however, the ratio of CD25 after single and multiple dosing and the other PD markers were not significantly different between the 3 genotypic groups compared with the baseline. CONCLUSION: These findings showed that CYP2D6 genotype influenced the PK characteristics of carvedilol and no differences in PD response were observed in Korean healthy volunteers. Registered at the ClinicalTrials.gov, NCT02286934.

Shear Wave Elastography as a Quantitative Biomarker of Clinically Significant Portal Hypertension: A Systematic Review and Meta-Analysis.

OBJECTIVE: To qualify shear wave elastography (SWE) as a biomarker for clinically significant portal hypertension (CSPH) beyond proof of concept, we aimed to accumulate and summarize the current evidence through systematic review and meta-analysis. MATERIALS AND METHODS: A computerized literature search was performed to identify studies from MEDLINE and EMBASE up to February 9, 2017. Studies on the diagnostic performance of liver stiffness measurements using SWE for CSPH with hepatic venous pressure gradient (HVPG) as the reference standard were included. Various aspects of SWE were comprehensively assessed. The summary diagnostic performance of SWE for the diagnosis of CSPH and the summary correlation coefficient between liver stiffness measured using SWE and HVPG were evaluated through a meta-analysis. RESULTS: Nine articles (including 746 patients) were retrieved. The diagnostic performance of SWE for the diagnosis of CSPH was fairly good, with a summary sensitivity of 85% (95% CI, 75-91%; I2 = 78.56%) and summary specificity of 85% (95% CI, 77-90%; I2 = 0%); the area under the ROC curve was 0.88 (95% CI, 0.85-0.91). The summary correlation coefficient between liver stiffness and HVPG measurements was 0.741 (95% CI, 0.658-0.825; I2 = 0%). These results support the value of SWE as a diagnostic biomarker for CSPH. However, there was significant heterogeneity in the imaging devices, protocols, liver stiffness measurement methods, and cutoff values used, which suggests that standardization is required. CONCLUSION: The consistent evidence favoring SWE as a biomarker for CSPH should be considered in the biomarker qualification process and management of patients with CSPH.

Correlations between renal function and the total kidney volume measured on imaging for autosomal dominant polycystic kidney disease: A systematic review and meta-analysis.

PURPOSE: To provide a systematic summary of total kidney volume (TKV) as an imaging biomarker in clinical trials for autosomal dominant polycystic kidney disease (ADPKD), focusing on the correlation between TKV and renal function. METHODS: A computerized literature search was performed using MEDLINE and EMBASE databases for studies that evaluated the correlation between TKV and the glomerular filtration rate (GFR) and between the TKV growth rate and GFR decline rate. A meta-analysis was performed to generate the summary correlation coefficient (r). A qualitative review was performed to evaluate the characteristics of TKV as an imaging biomarker. RESULTS: Eighteen articles including a total sample size of 2835 patients were retrieved. Meta-analysis revealed substantial correlations between TKV and GFR [r, -0.520; 95% confidence interval (CI), -0.60 to -0.43] and between the TKV growth rate and GFR decline rate [r, -0.320; 95% CI, -0.54 to -0.10]. The quantitative review revealed that baseline TKV can affect the TKV growth rate and GFR decline rate, such that patients with a higher baseline TKV showed faster TKV growth and GFR decline. There was significant variability in image acquisition and analysis methods. CONCLUSION: There were significant negative correlations between TKV and GFR as well as between TKV growth and GFR decline rates, suggesting that TKV imaging is a useful biomarker in clinical trials. However, standardization-or at least trial-specific standardization-of image acquisition and analysis techniques is required to use TKV as a reliable biomarker.

Current globalization of drug interventional clinical trials: characteristics and associated factors, 2011-2013.

BACKGROUND: Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013. METHODS: The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis. RESULTS: The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p < 0.001) while phase 3 trials were much more prevalent in all nine representative countries than in the USA. A larger number of "child" age group trials was performed in Poland (OR 1.852, p < 0.001), Israel (OR 1.546, p = 0.005), and South Africa (OR 1.963, p < 0.001) than in the USA. Multivariate analysis showed that health care expenditure per capita, Economic Freedom Index, Human Capital Index, and Intellectual Property Rights Index could explain the variance of regional distribution of clinical trials by 63.6%. CONCLUSIONS: The globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers.

The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers.

The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition.

AIM: To investigate the combined effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition. METHODS: We conducted a single-dose pharmacokinetic study of simvastatin in 26 healthy volunteers screened for their SLCO1B1 c.521T>C and ABCB1 c.1236C>T-2677G>T-3435C>T genotypes, with and without amlodipine pretreatment. The genetic effects and drug-interaction effect on simvastatin pharmacokinetic parameters were analyzed using a linear-mixed model. RESULTS: The SLCO1B1 c.521T>C variant significantly increased exposure to simvastatin acid by around 40% (p < 0.05), similar to that caused by the amlodipine pretreatment. The ABCB1 gene showed no influence on exposure to simvastatin or simvastatin acid. CONCLUSION: Only SLCO1B1, not ABCB1 genotype, is likely to be associated with simvastatin-induced myopathy. SLCO1B1 genotyping may be particularly beneficial in simvastatin users who are co-administered CYP3A4 inhibitors.

Sequential Folding using Light-activated Polystyrene Sheet.

A pre-strained polystyrene (PS) polymer sheet is deformed when it approaches the glass transition state as a result of light absorption. By controlling the light absorption of the polymer sheet, non-contact sequential folding can be accomplished. Line patterns of different transparencies and shapes are used to control the light absorption. The line pattern shape is closely related to the folding angle and folding start time. The relation between the line pattern design and folding performance was evaluated experimentally to develop a technique for folding PS sheets. The results show that sequential folding of PS sheets can be accomplished by changing the degree of transparency of the line pattern. Using the technique developed in this study, self-folding origami structures with complicated shapes can be designed and manufactured.

Flytrap-inspired robot using structurally integrated actuation based on bistability and a developable surface.

The Venus flytrap uses bistability, the structural characteristic of its leaf, to actuate the leaf's rapid closing motion for catching its prey. This paper presents a flytrap-inspired robot and novel actuation mechanism that exploits the structural characteristics of this structure and a developable surface. We focus on the concept of exploiting structural characteristics for actuation. Using shape memory alloy (SMA), the robot actuates artificial leaves made from asymmetrically laminated carbon fiber reinforced prepregs. We exploit two distinct structural characteristics of the leaves. First, the bistability acts as an implicit actuator enabling rapid morphing motion. Second, the developable surface has a kinematic constraint that constrains the curvature of the artificial leaf. Due to this constraint, the curved artificial leaf can be unbent by bending the straight edge orthogonal to the curve. The bending propagates from one edge to the entire surface and eventually generates an overall shape change. The curvature change of the artificial leaf is 18 m(-1) within 100 ms when closing. Experiments show that these actuation mechanisms facilitate the generation of a rapid and large morphing motion of the flytrap robot by one-way actuation of the SMA actuators at a local position.

Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia.

The activation of microglia plays an important role in a variety of brain disorders by the excessive production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)) and proinflammatory cytokines. We investigated here whether pinoresinol isolated from the fruits of Forsythia koreana Nakai inhibits the inflammatory responses in LPS-activated microglia. Pinoresinol inhibited the production of NO, PGE(2), TNF-alpha, IL-1beta and IL-6 in LPS-activated primary microglia. Also, pinoresinol attenuated mRNA and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and proinflammatory cytokines in LPS-activation. However, most of these inhibitory effects of pinoresinol have been mediated by extracellular-signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) phosphorylation and the NF-kappaB dependent. The results suggest that pinoresinol attenuates inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in brain disorders.

Anti-inflammatory activity of phylligenin, a lignan from the fruits of Forsythia koreana, and its cellular mechanism of action.

AIM OF THE STUDY: The fruits of Forsythia koreana have long been used in Chinese medicine to treat inflammatory disorders. However, the pharmacological data is not sufficient to clearly establish a scientific rationale for the anti-inflammatory medicinal use of this plant material, and the search for its active principles has been limited so far. MATERIALS AND METHODS: Phylligenin (lignan) was isolated from the fruits of Forsythia koreana and its anti-inflammatory activity was examined. RESULTS AND CONCLUSION: Phylligenin (1-100 microM) and the methanol extract of Forsythia koreana fruits inhibited cyclooxygenase-2 (COX-2)-mediated prostaglandin E(2) and inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) synthesis from lipopolysaccharide-treated RAW 264.7 cells. In the mechanism study, phylligenin inhibited iNOS expression and nuclear factor-kappaB (NF-kappaB) activation but had no effect on COX-2 expression. Moreover, phylligenin significantly inhibited mouse carrageenan-induced paw edema by intraperitoneal administration (22.1-34.7% inhibition at 12.5-100 mg/kg). These pharmacological properties indicate that phylligenin possesses significant anti-inflammatory activity in vitro and in vivo, and may provide the scientific rationale for anti-inflammatory use of the fruits of Forsythia koreana.

Melanogenesis inhibitory compounds from Saussureae Radix.

Ten compounds were isolated from the EtOAc soluble part of the MeOH extract of Saussureae Radix, with their effects on melanin production also evaluated in B-16 mouse melanoma cell lines stimulated with 3-isobutyl-1-methylxanthine (IBMX), an elevator of cellular cAMP. The compounds were identified as aplotaxene (1), 1 beta-hydroxy arbusculin A (2), costunolide (3), dehydrocostuslactone (4), 11 beta,13-dihydrocostunolide (5), reynosin (6), heptadec-(9Z)-enoic acid (7), beta-sitosterol (8), linoleic acid methyl ester (9) and betulinic acid methyl ester (10). Compounds 2, 9 and 10 were identified from Saussureae Radix for the first time. Furthermore, compounds 2, 3 and 6 showed potent inhibitory effects on the IBMX-induced melanogenesis, in dose-dependent manners, with IC50 values of 11, 3 and 2.5 microg/mL, respectively. As a positive control, arbutin exhibited an IC50 value of 29 microg/mL.

Growth inhibition and G1 cell cycle arrest mediated by 25-methoxyhispidol A, a novel triterpenoid, isolated from the fruit of Poncirus trifoliata in human hepatocellular carcinoma cells.

Poncirus trifoliata (Rutaceae) extracts have been known to possess anti-allergic, anti-inflammatory and antiviral activities. However, other biological activities, especially, the anticancer potential of extracts of P. trifoliata or its constituents, have not been fully investigated yet. In this study, we have evaluated the antiproliferative effects of a novel triterpenoid, 25-methoxyhispidol A, isolated from the fruit of P. trifoliata against SK-HEP-1 human hepatocellular carcinoma cells. Flow cytometric analysis indicated that 25-methoxyhispidol A arrests the cell cycle in the G1 phase at the earlier time and subsequently induces apoptosis of the cancer cells. Further study revealed that the cell cycle arrest in the G1 phase by 25-methoxyhispidol A correlated well with the inhibition of phosphorylation of the retinoblastoma (Rb) protein, and with the down-regulation of cyclin D1 and cyclin-dependent kinase cdk4 and the induction of cdk inhibitor p21 (WAF1/Cip1) protein. These findings suggest the potential of 25-methoxyhispidol A isolated from the fructus of P. trifoliata as an antitumor agent against human hepatocarcinoma cells by arresting the cell cycle and inducing apoptosis.

Evaluation of field epidemiology specialist training program based on the satisfaction and the changes of educational needs.

OBJECTIVE: To evaluate the learning achievement and satisfaction levels for the Field Epidemiology Specialist Training Program (FESTP), on infectious disease control between March 19 and October 31, 2002. METHODS: The FESTP was designed as a set of 84 hours curricula including lectures, discussions, self-studies, and field practicals, and organized both centrally and locally by the Division of Communicable Disease Control of the National Institute of Health and 11 universities. Before and after the program, a questionnaire survey on the educational need (49 items) and satisfaction (15 items) was conducted on 484 trainees, who were responsible for communicable disease control and immunization at 242 regional health centers. The data were analyzed with paired t-tests for comparison of the educational needs between the pre and post scores. RESULTS: The average score for satisfaction was 3.06 out of 5.0; with relatively higher scores for sincerity (4.10) and professionalism (4.01) of the tutors, adequacy (3.54) and clearness (3.51) of the evaluation criteria, usefulness (3.54) and fitness (3.52) of the contents, but with relatively lower satisfaction for schedule (2.96) and self-studies (2.91). The average for requirement for education improved, as shown by the decrease from 2.72 to 2.22 (p< .0001) with the biggest decrease in the outbreak investigation from 2.60 to 2.08. CONCLUSIONS: The FESTP was evaluated as being effective, the trainees showed moderate satisfaction and decrease educational needs. However, the actual schedules and self-studies should be rearranged to improve the satisfaction level.