Possible Novel Therapy for Malignant Gliomas with Secretable Trimeric TRAIL

Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL) and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL) delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI). Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas

The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data

Background/AimsLiver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis.MethodsLSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG ≥10 and ≥12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves.ResultsA strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG ≥10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG ≥12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively.ConclusionsLSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis

Lactational coumestrol exposure increases ovarian apoptosis in adult rats

This study is the first to examine the increased apoptosis in the adult rat ovary after lactational exposure to coumestrol (COU), a potent phytoestrogen. Lactating dams were gavaged at doses of 0.01, 0.1, 1, and 10 mg/kg COU during the lactation period and the reproductive effects of female pups were investigated in young adults. Rats were sacrificed at postnatal days (PND) 81–84. Ovarian weights were reduced significantly at 0.1 and 1.0 mg/kg COU. The reduction in the ovarian weight occurred in parallel with an increase in the apoptosis at PND 135–140. A marked dose-dependent increase in the expressions of active caspase-3 and -7 was observed in ovarian granulosa cells. Immunostaining for active caspase-3 and the TUNEL staining of apoptotic cells were also increased in ovaries exposed to COU in a dose-dependent manner. These results suggest new sights into the effect of lactational exposure to COU on the female reproductive health

Manipulation of Structural Colors in Liquid-Crystal Helical Structures Deformed by Surface Controls

Structural colors from cholesteric liquid crystals (CLCs) are manipulated by changing the only surface anchoring energy of an alignment layer. This behavior comes from the fact that weak surface energy of the perfluoropolymer induces the tilting of the cholesteric helix. Such deformed CLC structures with durability are successfully demonstrated without any external field applications and additional solidification processes. In addition, electrical tunings of structural colors from the deformed CLCs occur at very low operating voltages, compared to those of conventional CLC structures. On the basis of easy and simple fabrication, high durability, electrical tunability at low operating voltages, and the unique optical characteristics, the new deformed CLC structure could lead to extension in applications of CLCs, including multifunctional sensors, displays, and lasers. © 2018 American Chemical Society.FALS

Effect of Deposition Temperature on the Formation of Defect Phases in BiFeO3 Thin Films

We report the effects of deposition temperature on the evolution of defect and second phases and on the ferroelectric properties of BiFeO3 thin films. We grew BiFeO3 thin films on (001) SrTiO3 substrates by using pulsed laser deposition at temperatures in the range of 570 − 600 ◦ C at intervals of 10 ◦ C. We found that defects and a resulting second phase appeared at temperatures greater than 590 ◦ C. The second phase led to significant changes in the optical absorption and to the appearance of impurity peaks in the X-ray diffraction data. An analysis of the X-ray diffraction data indicated that the second phase was Fe2O3. Atomic force microscopy measurements showed that the appearance of defects accompanied an abrupt increase in the surface roughness. Furthermore, the presence of the second phase significantly affected the ferroelectric hysteresis. Our results suggest that the evolution of defects and resulting second phase in BiFeO3 thin films depends strongly on the deposition temperature.101sciescopuskc

Progression of hip displacement during radiographic surveillance in patients with cerebral palsy

Progression of hip displacement is common in patients with cerebral palsy (CP). We aimed to investigate the rate of progression of hip displacement in patients with CP by assessing changes in radiographic indices according to Gross Motor Function Classification System (GMFCS) level during hip surveillance. We analyzed the medical records of patients with CP aged &lt; 20 years who underwent at least 6 months interval of serial hip radiographs before any surgical hip intervention, including reconstructive surgery. After panel consensus and reliability testing, radiographic measurements of migration percentage (MP), neck-shaft angle (NSA), acetabular index (AI), and pelvic obliquity (PO) were obtained during hip surveillance. For each GMFCS level, annual changes in radiographic indices were analyzed and adjusted for affecting factors, such as sex, laterality, and type of CP. A total of 197 patients were included in this study, and 1,097 radiographs were evaluated. GMFCS classifications were as follows: 100 patients were level I-III, 48 were level IV, and 49 were level V. MP increased significantly over the duration of hip surveillance in patients with GMFCS levels I-III, IV, and V by 0.3%/year (P&lt; 0.001), 1.9%/year (P&lt; 0.001), and 6.2%/year (P&lt; 0.001), respectively. In patients with GMFCS level IV, NSA increased significantly by 3.4 degrees/year (P&lt; 0.001). Our results suggest that periodic monitoring and radiographic hip surveillance is warranted for patients with CP, especially those with GMFCS level IV or V. Furthermore, physicians can predict and inform parents or caregivers regarding the progression of hip displacement in patients with CP.Y

Undercorrection of planovalgus deformity after calcaneal lengthening in patients with cerebral palsy

Calcaneal lengthening (CL) is one of the treatment options for planovalgus deformity in patients with cerebral palsy (CP). However, its indication still needs to be clarified according to the functional status of CP. The aim of this study was to investigate the radiographic outcome after CL in patients with CP and to evaluate the risk factors causing undercorrection of planovalgus deformities. We included consecutive patients with CP who underwent CL for planovalgus deformity, were followed for more than 2 years, and had preoperative and postoperative weight-bearing anteroposterior (AP) and lateral foot radiographs. Six radiographic indices were used to assess the radiographic outcome. The patient age, sex, and Gross Motor Function Classification System (GMFCS) level were evaluated as possible risk factors, and we controlled for the interaction of potentially confounding variables using multivariate analysis. A total of 44 (77 feet) patients were included in this study. The mean age of the patients at the time of surgery was 10.5 +/- 4.0 years and the mean follow-up was 5.1 +/- 2.2 years. Patients with GMFCS III/IV achieved less correction than those with GMFCS I/II in the AP talus-first metatarsal angle (P=0.001), lateral talocalcaneal angle (P=0.028), and the lateral talus-first metatarsal angle (P&lt;0.001). The rate of undercorrection in the GMFCS III/IV group was 1.6 times higher than that in the GMFCS I/II group in the AP talus-first metatarsal angle (odds ratios: 1.6; 95% confidence interval: 1.2-2.0; P&lt;0.001) and 1.6 times higher in the lateral talus-first metatarsal angle (odds ratios: 1.6; 95% confidence interval: 1.3-1.9; P&lt;0.001). In GMFCS I/II patients with CP, we found CL to be an effective procedure for the correction of planovalgus foot deformities. However, in GMFCS III/IV patients with planovalgus deformities, CL appears to be insufficient on the basis of the high rate of undercorrection in these patients. For patients with GMFCS level III/IV, additional or alternative procedures should be considered to correct the deformity and maintain the correction achieved. Level of evidence: Level III, therapeutic study.N

Association of gross motor function classification system level and school attendance with bone mineral density in patients with cerebral palsy

The present study aimed to evaluate bone mineral density (BMD) in children and adolescents with cerebral palsy (CP) and to critically analyze the effects of a variety of factors, particularly the Gross Motor Function Classification System (GMFCS) level, the Caregiver Priorities and Child Health Index of Life with Disabilities questionnaire, and the Pediatric Outcomes Data Collection Instrument (PODCI), on BMD. Fifty patients with CP who underwent dual-energy X-ray absorptiometry were included. Collected data included the extent of involvement, muscle tone, demographic data, factors determined through chart review, and laboratory results. Factors associated with BMD in this group were analyzed by performing multiple regression analysis. The mean Z-scores in male and female patients were -3.252 +/- 1.822 and -3.789 +/- 1.764, respectively, in the proximal part of the femur and -2.219 +/- 1.323 and -2.451 +/- 1.434, respectively, in the lumbar spine. In multiple regression analysis, the GMFCS level and the average frequency of missed school in the PODCI were significant factors associated with both femur and lumbar spine BMD. Both the GMFCS level and school attendance were independently associated with BMD and should be considered for the prevention and management of osteoporosis in patients with CP.N

Reliability and Validity of Lower Extremity Computed Tomography as a Screening Tool for Osteoporosis

Category: Ankle Introduction/Purpose: Although previous studies have demonstrated the potential of conventional computed tomography (CT) as a screening tool for osteoporosis, the assessment correlation of BMD in those studies was limited to the spine. This study aimed to evaluate the reliability and validity of CT as a screening tool for osteoporosis and to estimate the correlation between central BMD and peripheral bone attenuation using lower extremity CT. Methods: In total, 292 patients who underwent a lower extremity, lumbar spine, or abdomen and pelvic CT scan within a 3- month interval of a dual-energy X-ray absorptiometry (DEXA) examination were included (Fig 1). Following reliability testing, bone attenuation of the L1, L2, L3, L4, femoral head, femoral neck, greater trochanter, distal femur, proximal tibia, distal tibia, and talus was measured by placing a circular region of interest on the central part of each bony region on a coronal CT image (Fig 2 and 3). Partial correlation was used to assess the correlation between CT and DEXA, after adjusting for age and body mass index. Results: In terms of reliability, all bone attenuation measurements, except the femoral neck, showed good to excellent interobserver reliability (intraclass correlation coefficients, 0.691–0.941). In terms of validity, bone attenuation of the L1 to L4, femoral neck, and greater trochanter on CT showed significant correlations with BMD of each area on DEXA (correlation coefficients, 0.399–0.613). Bone attenuation of the distal tibia and talus on CT showed significant correlations with BMD of all parts on DEXA (correlation coefficients, 0.493–0.581 for distal tibia, 0.396–0.579 for talus). Conclusion: Lower extremity CT is a useful screening tool for osteoporosis, and peripheral bone attenuation on lower extremity CT adequately reflects central BMD on DEXA