Recognition and management of dermatologic complications from interventional radiology procedures.

A variety of dermatologic complications can occur after interventional radiology procedures, including fluoroscopy-induced radiation dermatitis, thermal skin injury from tumor ablation, non-target embolization to the skin, allergic reactions related to interventional radiology procedures, and dermatitis and infections at catheter sites. Yet, interventional radiologists typically lack training in dermatology. This review focuses on recognition of dermatologic complications and introduces basic principles for management of these complications. By taking a more active role in the diagnosis, management, and follow-up of dermatologic complications, interventional radiologists can improve the care for patients suffering iatrogenic skin inury.

Functional characterisation of two phytochelatin synthases in rice (Oryza sativa cv. Milyang 117) that respond to cadmium stress.

Cadmium (Cd) is one of the most toxic heavy metals and a non-essential element to all organisms, including plants; however, the genes involved in Cd resistance in plants remain poorly characterised. To identify Cd resistance genes in rice, we screened a rice cDNA expression library treated with CdCl2 using a yeast (Saccharomyces cerevisiae) mutant ycf1 strain (DTY167) and isolated two rice phytochelatin synthases (OsPCS5 and OsPCS15). The genes were strongly induced by Cd treatment and conferred increased resistance to Cd when expressed in the ycf1 mutant strain. In addition, the Cd concentration was twofold higher in yeast expressing OsPCS5 and OsPCS15 than in vector-transformed yeast, and OsPCS5 and OsPCS15 localised in the cytoplasm. Arabidopsis thaliana plants overexpressing OsPCS5/-15 paradoxically exhibited increased sensitivity to Cd, suggesting that overexpression of OsPCS5/-15 resulted in toxicity due to excess phytochelatin production in A. thaliana. These data indicate that OsPCS5 and OsPCS15 are involved in Cd tolerance, which may be related to the relative abundances of phytochelatins synthesised by these phytochelatin synthases.

Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial.

BACKGROUND: Tumor treating fields (TTFields) is a non-invasive, antimitotic therapy. In the EF-14 phase 3 trial in newly diagnosed glioblastoma, TTFields plus temozolomide (TTFields/TMZ) improved progression free (PFS) and overall survival (OS) versus TMZ alone. Previous data indicate a ≥ 75% daily compliance improves outcomes. We analyzed compliance data from TTFields/TMZ patients in the EF-14 study to correlate TTFields compliance with PFS and OS and identify potential lower boundary for compliance with improved clinical outcomes. METHODS: Compliance was assessed by usage data from the NovoTTF-100A device and calculated as percentage per month of TTFields delivery. TTFields/TMZ patients were segregated into subgroups by percent monthly compliance. A Cox proportional hazard model controlled for sex, extent of resection, MGMT methylation status, age, region, and performance status was used to investigate the effect of compliance on PFS and OS. RESULTS: A threshold value of 50% compliance with TTFields/TMZ improved PFS (HR 0.70, 95% CI 0.47-1.05) and OS (HR 0.67, 95% CI 0.45-0.99) versus TMZ alone with improved outcome as compliance increased. At compliance > 90%, median survival was 24.9 months (28.7 months from diagnosis) and 5-year survival rate was 29.3%. Compliance was independent of gender, extent of resection, MGMT methylation status, age, region and performance status (HR 0.78; p = 0.031; OS at compliance ≥ 75% vs. < 75%). CONCLUSION: A compliance threshold of 50% with TTFields/TMZ correlated with significantly improved OS and PFS versus TMZ alone. Patients with compliance > 90% showed extended median and 5-year survival rates. Increased compliance with TTFields therapy is independently prognostic for improved survival in glioblastoma.

Albumin-bilirubin grade versus MELD score for predicting survival after transjugular intrahepatic portosystemic shunt (TIPS) creation.

OBJECTIVES: The purpose of this study was to compare the albumin-bilirubin (ALBI) grade and model for end-stage liver disease (MELD) scores for predicting survival after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: A retrospective study of pre-procedure ALBI and MELD scores was performed in 197 patients who underwent TIPS from 2005 to 2012. There were 140 men and 57 women, with a mean age of 56±11 (SD) (range: 19-90years). The prognostic capability of ALBI and MELD scores were evaluated using competing risks survival analysis. Discriminatory ability was compared between models using the C-index derived from cause specific Cox proportional hazards models. RESULTS: TIPS were created for ascites or hydrothorax (128 patients), variceal hemorrhage (61 patients), or both (8 patients). Prior to TIPS, 5 patients were ALBI grade 1, 76 were grade 2, and 116 were grade 3. The average pre-TIPS MELD score was 14. Pre-TIPS ALBI score, ALBI grade, and MELD were each significant predictors of 30-day mortality from hepatic failure and overall survival (all P<0.05). Based on the C-index, the MELD score was a better predictor of both 30-day and overall survival (C-index=0.74 and 0.63) than either ALBI score (0.70 and 0.59) or ALBI grade (0.64 and 0.56). In multivariate models, after accounting for MELD score ALBI score provided no additional short- or long-term survival information. CONCLUSION: Although ALBI score and grade were statistically significantly associated with risk of death after TIPS, MELD remains the superior predictor.

Hemorrhage risk with transjugular intrahepatic portosystemic shunt (TIPS) insertion at the main portal vein bifurcation with stent grafts.

PURPOSE: The purpose of this study was to assess the incidence of major hemorrhage after transjugular intrahepatic portosystemic shunt (TIPS) insertion using a stent graft at the main portal vein bifurcation. PATIENTS AND METHODS: TIPS insertion using stent grafts was performed in 215 patients due to non-variceal hemorrhage indications. There were 137 men and 78 women, with a mean age of 57 years±10.6 (SD) (range: 19-90 years). Based on retrospective review of portal venograms, TIPS inserted within 5mm from the portal vein bifurcation were considered "bifurcation TIPS", while those inserted 2cm or greater from the bifurcation were considered intrahepatic. Suspicion for acute major periprocedural hemorrhage were categorized as low, moderate, and high, based on the number of signs of hemorrhage. RESULTS: Of 215 TIPS inserted for purposes other than hemorrhage, the TIPS was inserted at the portal bifurcation in 41 patients (29 men, 12 women; mean age, 55.9±11.7 (SD); range: 26-79 years) and intrahepatic in 62 patients (37 men, 25 women; mean age, 57.6±10.6 (SD), range: 34-82 years), whereas 112 were indeterminate in location. No active extravasations were identified on post-TIPS portal venograms. Suspicion for acute major hemorrhage was moderate or high in 3/41 (7%) of patients in the TIPS bifurcation group compared to 5/62 (8%) in the intrahepatic TIPS group (P>0.99). There were no significant differences in 30-day mortality rates (1/41 [2%] and 3/62 [5%] respectively; P> 0.99). No deaths or interventions were attributed to acute hemorrhage. CONCLUSION: TIPS insertion at the portal bifurcation with stent grafts did not incur an elevated risk of hemorrhagic complications.

Onion (Allium cepa L.) peel extract (OPE) regulates human sperm motility via protein kinase C-mediated activation of the human voltage-gated proton channel.

Onion (Allium cepa L.) and quercetin protect against oxidative damage and have positive effects on multiple functional parameters of spermatozoa, including viability and motility. However, the associated underlying mechanisms of action have not yet been identified. The aim of this study was to investigate the effect of onion peel extract (OPE) on voltage-gated proton (Hv1) channels, which play a critical role in rapid proton extrusion. This process underlies a wide range of physiological processes, particularly male fertility. The whole-cell patch-clamp technique was used to record the changes in Hv1 currents in HEK293 cells transiently transfected with human Hv1 (HVCN1). The effects of OPE on human sperm motility were also analyzed. OPE significantly activated the outward-rectifying proton currents in a concentration-dependent manner, with an EC50 value of 30 µg/mL. This effect was largely reversible upon washout. Moreover, OPE induced an increase in the proton current amplitude and decreased the time constant of activation at 0 mV from 4.9 ± 1.7 to 0.6 ± 0.1 sec (n = 6). In the presence of OPE, the half-activation voltage (V1/2 ) shifted in the negative direction, from 20.1 ± 5.8 to 5.2 ± 8.7 mV (n = 6), but the slope was not significantly altered. The OPE-induced current was profoundly inhibited by 10 µm Zn2+ , the most potent Hv1 channel inhibitor, and was also inhibited by treatment with GF109203X, a specific protein kinase C (PKC) inhibitor. Furthermore, sperm motility was significantly increased in the OPE-treated groups. OPE exhibits protective effects on sperm motility, at least partially via regulation of the proton channel. Moreover, similar effects were exerted by quercetin, the major flavonoid in OPE. These results suggest OPE, which is rich in the potent Hv1 channel activator quercetin, as a possible new candidate treatment for human infertility.

Effects of eupatilin on the contractility of corpus cavernosal smooth muscle through nitric oxide-independent pathways.

Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is one of the main compounds present in Artemisia species. Eupatilin has both antioxidative and anti-inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (CC) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (CCSM) cells. Isolated rabbit CC strips were mounted in an organ bath system. A conventional whole-cell patch clamp technique was used to measure activation of calcium-sensitive K+ -channel currents in human CCSM cells. The relaxation effect of eupatilin was evaluated by cumulative addition (10-5  m ~ 3 × 10-4  m) to CC strips precontracted with 10-5  m phenylephrine. Western blotting analysis was performed to measure myosin phosphatase targeting subunit 1 (MYPT1) and protein kinase C-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17-kDa (CPI-17) expression and to evaluate the effect of eupatilin on the RhoA/Rho-kinase pathway. Eupatilin effectively relaxed the phenylephrine-induced tone in the rabbit CC strips in a concentration-dependent manner with an estimated EC50 value of 1.2 ± 1.6 × 10-4  m (n = 8, p < 0.05). Iberiotoxin and tetraethylammonium significantly reduced the relaxation effect (n = 8, p < 0.001 and p = 0.003, respectively). Removal of the endothelium or the presence of L-NAME or indomethacin did not affect the relaxation effect of eupatilin. In CCSM cells, the extracellular application of eupatilin 10-4  m significantly increased the outward currents, and the eupatilin-stimulated currents were significantly attenuated by treatment with 10-7  m iberiotoxin (n = 13, p < 0.05). Eupatilin reduced the phosphorylation level of MYPT1 at Thr853 of MLCP and CPI-17 at Thr38. Eupatilin-induced relaxation of the CCSM cells via NO-independent pathways. The relaxation effects of eupatilin on CCSM cells were partially due to activation of BKCa channels and inhibition of RhoA/Rho-kinase.

Chronologic Trends in Studies on Fluoride Mechanisms of Action.

Fluoride has been widely used for the prevention of dental caries since the mid-20th century. The aim of this study was to investigate the chronologic trends in studies on fluoride mechanisms of action against dental caries during the years 1950 to 2015. To this aim, queries such as "fluoride," "fluoride and demineralization," "fluoride and remineralization," "fluoride and (plaque or biofilms)," and "fluoride and (bacteria or microbials)" were submitted to PubMed to collect research article information, including titles, abstracts, publication dates, author affiliations, and publication journals. The article information that PubMed produced was then collected by an automatic web crawler and examined through informetrics and linguistic analyses. We found that the number of articles concerned with fluoride mechanisms of action against dental caries was 6,903 and gradually increased over time during the years 1950 to 2015. They were published by 1,136 journals-most notably, Caries Research and Journal of Dental Research. Of the articles published, those related to bacteria/microbials had a higher percentage (44%) than those dealing with plaque/biofilms, demineralization, and remineralization. With regard to the geographic distribution of authors, Europe and North America accounted for 65% of the articles during the years 1987 to 2015, although the number of authors in Asia sharply increased in recent years. Among the fluoride compounds, NaF was mentioned more frequently than SnF2, Na2PO3F, amine fluoride, and acidulated phosphate fluoride during the years 1986 to 2015. Water fluoridation received the most attention among the various fluoride application methods (toothpastes, mouthwashes, fluoride varnishes, and fluoride gels) during the same period. These results, obtained from employing informetrics and linguistic analyses, suggest that in studies on fluoride mechanisms of action, 1) the unbalanced geographic distribution of articles and 2) the heavy concentration of articles on particular fluoride compounds and application methods should be overcome in future research.

Correlation between lymph node count and survival and a reappraisal of lymph node ratio as a predictor of survival in gastric cancer: A multi-institutional cohort study.

PURPOSE: The purpose of this study is to evaluate the correlation between lymph node count (LNC) and survival and to evaluate whether lymph node ratio (LNR) which is related to LNC is a better predictor of survival for gastric cancer than the N category of UICC/AJCC through a multi-institutional cohort study. METHODS: The study cohort included 3284 patients from eight institutions. Lower and upper quartiles of LNC were used for comparisons. The cut-off values (0, 0.06, 0.27, and 0.49) for the LNR categories were based on Classification and Regression Trees techniques. Akaike information criteria (AIC) for Cox regression models was used to evaluate goodness of fit between competing predictor variables (LNR vs. N category). RESULTS: The 5-year disease-specific survival (DSS) rates of lower and upper quartiles of LNC were 82.2% and 84.8%. In the subgroup analysis of pN category, the upper quartile of LNC showed better survival than the lower quartile in pN2, pN3a, and pN3b subgroups. Regarding LNR, 5-year DSS of LNR 0, 0-0.06, 0.06-0.27, 0.27-0.49, and >0.49 was 95.3%, 88.7%, 70.6%, 42.7%, and 17.2% respectively. Multivariate analysis showed that pT, pN, LNR, residual tumor status, distant metastasis, and tumor differentiation significantly affected survival. The analysis also confirmed superiority of LNR compared with N category in the AIC analysis. CONCLUSION: Higher LNC correlated with better survival in patients with pN2, pN3a, and pN3b gastric cancer. Our data indicate that LNR is a better predictor of survival than N category of UICC/AJCC.

Additive effects of Artemisia capillaris extract and scopoletin on the relaxation of penile corpus cavernosum smooth muscle.

The objective was to investigate the cellular effect and action mechanism of Artemisia capillaris extract (ACE) and its component, scopoletin, on penile corpus cavernosum smooth muscle (PCCSM). In vitro study with PCCSM, the precontracted PCCSM with phenylephrine was treated with ACE or scopoletin. Cyclic nucleotides in the perfusate were measured by radioimmunoassay and expression of protein and mRNA of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase in the perfused PCCSM were measured by western blot and real-time PCR, respectively. The interaction of ACE or scopoletin with udenafil was also evaluated. ACE and scopoletin exerted a significant and concentration-dependent relaxation in PCCSM. The perfusion with ACE or scopoletin significantly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) and the perfusion with ACE or scopoletin increased the expression of eNOS mRNA and protein. Furthermore, ACE or scopoletin enhanced udenafil-inducing relaxation in PCCSM. ACE and scopoletin relaxed the PCCSM mainly by activating nitric oxide-cGMP system and cAMP pathway and they may be additive therapeutic candidates for ED patients who do not completely respond to udenafil.

Purification and functional characterization of the first stilbene glucoside-specific ß-glucosidase isolated from Lactobacillus kimchi.

This study aimed to develop viable enzymes for bioconversion of resveratrol-glucoside into resveratrol. Out of 13 bacterial strains tested, Lactobacillus kimchi JB301 could completely convert polydatin into resveratrol. The purified enzyme had an optimum temperature of 30-40°C and optimum pH of pH 5.0 against polydatin. This enzyme showed high substrate specificities towards different substrates in the following order: isorhaponticin>>polydatin>>mulberroside A>oxyresveratrol-3-O-glucoside. Additionally, it rarely hydrolyzed astringin and desoxyrhaponticin. Based on these catalytic specificities, we suggest this enzyme be named stilbene glucoside-specific ß-glucosidase. Furthermore, polydatin extracts from Polygonum cuspidatum were successfully converted to resveratrol with a high yield (of over 99%). Stilbene glucoside-specific ß-glucosidase is the first enzyme isolated from lactic acid bacteria capable of bio-converting various stilbene glucosides into stilbene.

The effectiveness of gadolinium MRI to improve target delineation for radiotherapy in hepatocellular carcinoma: a comparative study of rigid image registration techniques.

To achieve consistent target delineation in radiotherapy for hepatocellular carcinoma (HCC), image registration between simulation CT and diagnostic MRI was explored. Twenty patients with advanced HCC were included. The median interval between MRI and CT was 11 days. CT was obtained with shallow free breathing and MRI at exhale phase. On each CT and MRI, the liver and the gross target volume (GTV) were drawn. A rigid image registration was taken according to point information of vascular bifurcation (Method[A]) and pixel information of volume of interest only including the periphery of the liver (Method[B]) and manually drawn liver (Method[C]). In nine cases with an indefinite GTV on CT, a virtual sphere was generated at the epicenter of the GTV. The GTV from CT (VGTV[CT]) and MRI (VGTV[MR]) and the expanded GTV from MRI (V+GTV[MR]) considering geometrical registration error were defined. The underestimation (uncovered V[CT] by V[MR]) and the overestimation (excessive V[MR] by V[CT]) were calculated. Through a paired T-test, the difference between image registration techniques was analyzed. For method[A], the underestimation rates of VGTV[MR] and V+GTV[MR] were 16.4 ± 8.9% and 3.2 ± 3.7%, and the overestimation rates were 16.6 ± 8.7% and 28.4 ± 10.3%, respectively. For VGTV[MR] and V+GTV[MR], the underestimation rates and overestimation rates of method[A] were better than method[C]. The underestimation rates and overestimation rates of the VGTV[MR] were better in method[B] than method[C]. By image registration and additional margin, about 97% of HCC could be covered. Method[A] or method[B] could be recommended according to physician preference.

Relationship between polymorphisms near the IL28B gene and spontaneous HBsAg seroclearance: a systematic review and meta-analysis.

Polymorphisms near the interleukin (IL) 28B gene have been proposed to be associated with spontaneous clearance of the hepatitis C virus. The purpose of this study was to assess the relationship between IL28B polymorphisms and the rate of spontaneous hepatitis B surface antigen (HBsAg) seroclearance by means of meta-analysis. MEDLINE/PubMed and EMBASE were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analyses were mainly performed according to ethnicity. A total of 4028 cases with persistent chronic hepatitis B and 2327 spontaneously recovered controls were included from 11 studies. The single nucleotide polymorphism (SNP), rs12979860, had no significant association with HBsAg seroclearance (OR = 0.98, 95% CI: 0.84-1.14 in the dominant model; OR = 1.00, 95% CI: 0.68-1.46 in the recessive model; and OR = 0.95, 95% CI: 0.82-1.09 in the allelic model). The SNP, rs12980275, had no significant association either (OR = 1.03, 95% CI: 0.84-1.26 in the dominant model; OR = 1.17, 95% CI: 0.46-2.96 in the recessive model; and OR = 1.04, 95% CI: 0.86-1.26 in the allelic model), nor did the SNP, rs8099917 (OR = 0.94, 95% CI: 0.77-1.15 in the dominant model; OR = 0.74, 95% CI: 0.34-1.62 in the recessive model; and OR = 0.93, 95% CI: 0.77-1.13 in the allelic model). Similarly, the results of subgroup analyses by ethnicity also showed no association in either the Asian group or non-Asian group. We concluded that there was no significant association between common IL28B polymorphisms and the rate of spontaneous HBsAg seroclearance.

Interfractional variability in intensity-modulated radiotherapy of prostate cancer with or without thermoplastic pelvic immobilization.

PURPOSE: To determine the variability of patient positioning errors associated with intensity-modulated radiotherapy (IMRT) for prostate cancer and to assess the impact of thermoplastic pelvic immobilization on these errors using kilovoltage (kV) cone-beam computed tomography (CBCT). MATERIALS AND METHODS: From February 2012 to June 2012, the records of 314 IMRT sessions in 19 patients with prostate cancer, performed with or without immobilization at two different facilities in the Korea University Hospital were analyzed. The kV CBCT images were matched to simulation computed tomography (CT) images to determine the simulation-to-treatment variability. The shifts along the x (lateral)-, y (longitudinal)- and z (vertical)-axes were measured, as was the shift in the three dimensional (3D) vector. RESULTS: The measured systematic errors in the immobilized group during treatment were 0.46 ± 1.75 mm along the x-axis, - 0.35 ± 3.83 mm along the y-axis, 0.20 ± 2.75 mm along the z-axis and 4.05 ± 3.02 mm in the 3D vector. Those of nonimmobilized group were - 1.45 ± 7.50 mm along the x-axis, 1.89 ± 5.07 mm along the y-axis, 0.28 ± 3.81 mm along the z-axis and 8.90 ± 4.79 mm in the 3D vector. The group immobilized with pelvic thermoplastics showed reduced interfractional variability along the x- and y-axes and in the 3D vector compared to the nonimmobilized group (p < 0.05). CONCLUSION: IMRT with thermoplastic pelvic immobilization in patients with prostate cancer appears to be useful in stabilizing interfractional variability during the planned treatment course.

Lung niches for the generation and maintenance of tissue-resident memory T cells.

The extent to which tissue-specific viral infections generate memory T cells specifically adapted to and maintained within the target infection site is unknown. Here, we show that respiratory virus-specific memory T cells in mice and humans are generated and maintained in compartmentalized niches in lungs, distinct from populations in lymphoid tissue or circulation. Using a polyclonal mouse model of influenza infection combined with an in vivo antibody labeling approach and confocal imaging, we identify a spatially distinct niche in the lung where influenza-specific T-cell responses are expanded and maintained long term as tissue-resident memory (T(RM)) CD4 and CD8 T cells. Lung T(RM) are further distinguished from circulating memory subsets in lung and spleen based on CD69 expression and persistence independent of lymphoid stores. In humans, influenza-specific T cells are enriched within the lung T(RM) subset, whereas memory CD8 T cells specific for the systemic virus cytomegalovirus are distributed in both lung and spleen, suggesting that the site of infection affects T(RM) generation. Our findings reveal a precise spatial organization to virus-specific T-cell memory, determined by the site of the initial infection, with important implications for the development of targeted strategies to boost immunity at appropriate tissue sites.

Scleral fixation of Ahmed glaucoma valve tube tip for adjustment of cornea-touching malposition.

PURPOSE: Tube-corneal touch occurring after Ahmed glaucoma valve (AGV) implantation is conventionally treated by tube cutting or tube transposition from the original pathway. However, in some cases, tube cutting is insufficient, and rearranging the pathway of the tube through a new sclera tunnel, ciliary sulcus, or pars plana is not feasible, as the conjunctiva and sclera covering the tube are difficult to be redissected. So, we propose a novel technique that repositions malpositioned AGV tube using scleral fixation and its successful applications in two patients with tube-corneal touch. METHODS: (A) A scleral flap is made at the point for scleral fixation. (B) The anterior chamber is maintained using an anterior chamber maintainer. The incision is made immediately above the tube entering the anterior chamber and the tube end is flipped out using a Sinskey. (C) A double-armed 10/0 prolene straight needle is penetrated through the tube end. The leading needle enters the anterior chamber through the previously made incision and is pulled through the scleral flap. (D) The tube tip and the second needle of the double-armed 10/0 prolene straight needle also enter the anterior chamber through the previously made incision and the second needle is pulled through the scleral flap. The tube end is extended to be parallel to the cornea surface. RESULTS: Patients maintained good tube positioning without any serious complications during average of 15 months of follow-up after operation. CONCLUSION: We believe that our method is a simple and minimally invasive surgical method for treating AGV tube touching of the corneal endothelium. However, considering the limited number of cases studied and the short follow-up period, a larger group with a longer follow-up period is necessary.