bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-induced hepatitis following use of octreotide for long-term treatment of congenital hyperinsulinism: Figure 1
Authors: Avatapalle Bindu , Padidela Raja , Randell Tabitha , Banerjee Indraneel
Published: July 2012

Congenital hyperinsulinism (CHI) is a rare disorder of hypoglycaemia in children due to excessive and dysregulated insulin secretion. Octreotide, a somatostatin analogue, is used in the treatment of hypoglycaemia in Diazoxide unresponsive CHI, but is associated with side effects such as gastrointestinal dysmotility and rarely, necrotising enterocolitis. It would be important to recognise rare but serious side effects from Octreotide therapy, particularly with long-term use. In this report, we have described drug-induced hepatitis with moderately high doses of Octreotide in a child with diffuse CHI. While serum alanine transaminase levels rose significantly with Octreotide therapy (maximum dose 30 μg/kg/day), hepatitis resolved following discontinuation of medical treatment. Liver enzymes should be monitored routinely in children with CHI using long-term Octreotide treatment, particularly with high doses. The presence of drug-induced hepatitis should prompt discontinuation of Octreotide treatment with likely subsequent resolution.
Oxidative photobleaching of phthalocyanines in solution
Authors: Kuznetsova Nina A. , Kaliya Oleg L.
Published: July 2012

Metallophthalocyanines form a very important class of commercial dyes and have achieved significant success in a variety of applications, in which their photostability is of fundamental importance. On this ground, considerable data on phthalocyanine photobleaching were published over recent years. We do not intend to give exhaustive compilation of the photobleaching quantum yields, which are known for wide circle of phthalocyanines in different solvents. This review begins by discussing pertinent background information about processes following phthalocyanine excitation. Then using selected examples of the recent literature, including authors' works, we survey a variety of photobleaching effects from the fundamental origins to specific for phthalocyanine chromophore. Finally, the mechanisms of phthalocyanine oxidative photobleaching are discussed.
Metallophthalocyanines and metalloporphyrins as electrocatalysts: a case of hydrogen peroxide and glucose detection
Authors: Mashazi Philani N. , Nombona Nolwazi , Muchindu Munkombwe , Vilakazi Sibulelo
Published: July 2012

This review summarizes the applications of metallophthalocyanine (MPc) and metallo-porphyrin (MP) complexes as electrocatalysts immobilized onto various electrodes for the detection of hydrogen peroxide and glucose. The uses of MPc and MP complexes as electron mediators for the detection of glucose at glucose oxidase modified surfaces are discussed.
Coordination and electrochemistry of new substituted manganese phthalocyanines
Authors: Dolotova Olga , Konarev Alexandr , Volkov Konstantin , Negrimovsky Vladimir , Kaliya Oleg L.
Published: July 2012

A number of substituted manganese phthalocyanines PcMn have been synthesized from the corresponding phthalonitriles with rather good yields (up to 67%) and high purity. All complexes were characterized by elemental analysis, electronic absorption spectra, and some of them by redox potentials. Three coordination forms — PcMn(II), PcMn(III)X and [LPcMn(III)]2O were fixed for all complexes. The equilibrium of three electronic isomers — Pc+· Mn(I) × L, PcMn(II) × Ln and Pc-· Mn(III) × 2L — has been observed in solutions of all PcMn(II) in the presence of organic base L.
Structure and morphology in thin films of perfluorinated copper phthalocyanine grown on alkali halide surfaces (001)
Authors: Lorenz Enno , Keil Christopher , Schlettwein Derck
Published: July 2012

Thin films from the monolayer range to the thickness of 40 nm of the perfluorinated copper phthalocyanine (F16PcCu) were prepared by physical vapor deposition on freshly cleaved (001) faces of the alkali halides NaCl , KCl and KBr . The different lattice constants of the substrates provided sufficient difference to trigger the growth of differently ordered phases of F16PcCu . Electron diffraction, Atomic Force Microscopy and UV-vis spectroscopy were used to characterize the structure for F16PcCu monolayers and for films of increasing average film thickness towards bulk films. A square lattice of flat-lying F16PcCu is proposed for the first monolayers. In the bulk films, phases already described for F16PcCu on other substrates were formed, but also a new phase was discovered.
Semantics for UML model transformation and generation of regular grammar
Authors: Arora Deepak , Hazela Bramah , Saxena Vipin
Published: July 2012

Graphs are one of the most popular non linear data structures used to represent various data objects. These graphical structures can further be classified into directed and undirected graph representations. For modeling purpose, UML has adopted the phenomenon of directed graphical structures as statechart diagrams, to exhibit dynamic specification of any software or non software system. These diagrams are important as they are used to represent all possible values that an object can retain throughout its life cycle. Three key components are required to change the state of any object namely transition function, action and possible inputs. Statechart diagrams are also useful to determine all possible paths that an object will undergo during its entire life span, while changing its state. Further these paths can be represented with the help of various established graphical modeling techniques like Finite State Automata. The mapping and further analysis of these path structures can be very helpful in determining the correctness of the diagram as well as to highlight the possible deficiencies in the diagram. In the present work, authors have proposed semantics for automatic transformation of UML statechart diagram into its equivalent finite state automata, by taking the advantage of both of the models. Authors have also presented an approach to generate regular grammar for the generated finite state automata. This equivalent grammar can further be useful to generate various test cases, to test UML statechart diagram, against various test conditions. To better illustrate, authors have also presented a case study of an ATM machine and demonstrated that how this approach is helpful to verify the correctness of design
Method configuration from situational method engineering
Authors: Gupta Daya , Dwivedi Rinky
Published: July 2012

This paper presents a brief on evolution and subsequent developments in the field of Situation Method Engineering (SME) through exhaustive literature review. The efforts of the various method engineers are gathered, summarized and presented to show the overall growth of this vital discipline. This research paper starts with the assembly-based approaches and moves towards method generation. The paper further analyzes the proposals presented on the architecture of SME processes followed by the OPEN Process Framework (OPF). OPF depend on the four major components-Object-oriented Process, Environment and Notation (OPEN). We evaluate these proposals for various issues leading to method configuration. The survey concludes with the proposals on configurability of methods and current unresolved issues that need to be addressed in one single approach to configure a situation-specific coherent method
Supporting semantic conflict prevention in real-time collaborative programming environments
Authors: Fan Hongfei , Sun Chengzheng
Published: July 2012

Real-time collaborative programming environments support multiple programmers to concurrently edit shared source code documents at the same time over communication networks. One of the key challenges in supporting real-time collaborative programming is semantic conflicts, which may occur when multiple programmers are performing concurrent and incompatible programming work in the same source code region or in different source code regions with dependency relationships. Semantic conflicts may result in programming errors that are difficult to detect and costly to resolve. This paper presents in-depth analyses of representative collaborative programming scenarios for understanding the nature and general conditions of semantic conflicts, and proposes a novelDependency-based Automatic Locking(DAL) approach for supporting semantic conflict prevention in real-time collaborative programming environments. The novelty of the DAL approach lies in its capabilities of supporting automatic and fine-grained locking on selected source code regions with dependency relationships to balance conflict prevention, concurrent work, and programmer convenience in real-time collaborative programming. The DAL approach and technical solutions have been implemented in theCoEclipseprototype system as a proof-of-concept for this emerging technique, which is being continuously extended for further exploration and evaluation.
Passive Smoking as a Risk Factor of Dry Eye in Children
Authors: El-Shazly Amany Abdel-Fattah , El-Zawahry Walid Mohamed Abd El Raouf , Hamdy Ahmad Mohamed , Ahmed Manal Basyouni
Published: July 2012

Purpose. Adult active smoking is a risk factor for dry eye. We hypothesize that passive smoking in children can also produce the same effects.Methods. We included 112 school children presenting with eye discomfort. Assessment of eye dryness and its severity levels depending on symptoms of dry eye, visual symptoms, tear breakup time (TBUT), Schirmer-1 test, and corneal fluorescein staining were done for all of them. Exposure to cigarette smoking was assessed by history-taking and urinary cotinine levels.Results. Dry eye was found in 80/112 children. Passive smoking was documented in 76/112 children. Number of cigarettes to which the child was exposed per day and the duration of exposure to passive smoking were significantly higher in children with dry eye compared to those without. Urinary cotinine, and cotinine/creatinine ratio (CCR) was significantly higher in children with dry eye compared to those without dry eye. Multiregression analysis showed that the most important determinants of dry eye were CCR and number of cigarettes/day.Conclusion. Passive smoking represents a significant risk factor of dry eye in children comparable to that shown with active adult smoking. Male children are more prone to this effect.
Effects of Long Distance Transportation on Honey Bee Physiology
Authors: Ahn Kiheung , Xie Xianbing , Riddle Joseph , Pettis Jeff , Huang Zachary Y.
Published: July 2012

Despite the requirement of long distance transportation of honey bees used for pollination, we understand little how transportation affects honey bees. Three trials in three different states (CA, GA, and MI) were conducted to study the effects of long distance transportation on honey bee physiology. Newly emerged bees from one colony were split into two groups and introduced into a transported (T) colony or a stationary (S) colony in each trial. Volumes of hypopharyngeal gland acini in T colonies were significantly smaller than S colonies in all three trials. There were no significant differences between S and T colonies in juvenile hormone titers. Protein content in head showed no significant differences between S and T either in 7-day-old or 17-day-old bees of MI trial, but GA trial showed a significant reduction in bees experiencing transportation. Protein content in thorax was only measured in GA trial and was not significantly different between the two groups. Lipid content in abdomen was not significantly different between the S and T colonies in all three trials. This study suggests that bees experiencing transportation have trouble fully developing their food glands and this might affect their ability to nurse the next generation of workers.
Probiotics, Symptoms, and Gut Microbiota: What Are the Relations? A Randomized Controlled Trial in Subjects with Irritable Bowel Syndrome
Authors: Farup Per G. , Jacobsen Morten , Ligaarden Solveig C. , Rudi Knut
Published: July 2012

Introduction. Knowledge of the mechanism of action of probiotics in subjects with irritable bowel syndrome (IBS) is imperfect. Objective. This trial aimed at discriminating between a direct effect on the gut wall and an indirect effect caused by modulation of the fecal microbiota. Design. Randomized, double-blind, crossover trial. Material and Methods. Patients with IBS were given one capsule of 1010 CFU L. plantarum MF 1298 or placebo once daily. Symptoms were registered (score 0–15) and feces collected at the end of each period. The gut microbiota was analyzed with 16S rRNA gene analyses and results reported as proportions of Bacteroides, Faecalibacterium, and Lachnospiraceae and Simpson’s D diversity score. Results. Sixteen participants (11 women) with a mean age of 50 years (SD 11) were available for the analyses. Intake of L. plantarum MF 1298 was associated with a significant aggravation of symptoms, but neither intake of L. plantarum MF 1298 nor symptoms were associated with the composition of the fecal microbiota (P values >0.10). Conclusions. The trial indicates that the symptomatic aggravation related to intake of L. plantarum MF 1298 was a direct effect of the microbe on the gut wall and not caused by changes in the fecal microbiota.
The Microendoscopic Decompression of Lumbar Stenosis: A Review of the Current Literature and Clinical Results
Authors: Wong Albert P. , Smith Zachary A. , Lall Rohan R. , Bresnahan Lacey E. , Fessler Richard G.
Published: July 2012

Lumbar stenosis is a well-defined pathologic condition with excellent surgical outcomes. Empiric evidence as well as randomized, prospective trials has demonstrated the superior efficacy of surgery compared to medical management for lumbar stenosis. Traditionally, lumbar stenosis is decompressed with open laminectomies. This involves removal of the spinous process, lamina, and the posterior musculoligamentous complex (posterior tension band). This approach provides excellent improvement in symptoms, but is also associated with potential postoperative spinal instability. This may result in subsequent need for spinal fusion. Advances in technology have enabled the application of minimally invasive spine surgery (MISS) as an acceptable alternative to open lumbar decompression. Recent studies have shown similar to improved perioperative outcomes when comparing MISS to open decompression for lumbar stenosis. A literature review of MISS for decompression of lumbar stenosis with tubular retractors was performed to evaluate the outcomes of this modern surgical technique. In addition, a discussion of the advantages and limitations of this technique is provided.
Adjuvant Growth Hormone for Ovulation Induction with Gonadotropins in the Treatment of a Woman with Hypopituitarism
Authors: Daniel Ariadne , Ezzat Shereen , Greenblatt Ellen
Published: July 2012

Objective. To report the prestimulation use of adjuvant GH for gonadotropin ovulation induction in a woman with hypopituitarism and GH deficiency who previously failed to respond.Design, Patients, and Measurements. A 31-year-old nulliparous woman presented with hypopituitarism and GH deficiency after failing ovulation induction with high dose gonadotropins. A trial of GH was undertaken for 5 months prior to ovulation induction resulting in normalization of IGF-I levels.Results. Women with hypopituitarism are known to have lower pregnancy rates after ovulation induction with need for higher doses of gonadotropins. A small subset of these patients do not ovulate. This patient had successful ovulation induction and pregnancy with prestimulation GH.Conclusions. This case suggests that the use of adjuvant GH in a GH-deficient patient several months before the use of human menopausal gonadotropin results in ovulation and pregnancy.
Deriving Weights of Criteria from Inconsistent Fuzzy Comparison Matrices by Using the Nearest Weighted Interval Approximation
Authors: Izadikhah Mohammad
Published: July 2012

Deriving the weights of criteria from the pairwise comparison matrix with fuzzy elements is investigated. In the proposed method we first convert each element of the fuzzy comparison matrix into the nearest weighted interval approximation one. Then by using the goal programming method we derive the weights of criteria. The presented method is able to find weights of fuzzy pairwise comparison matrices in any form. We compare the results of the presented method with some of the existing methods. The approach is illustrated by some numerical examples.
Immunohistochemical Characteristics of IgG4-Related Tubulointerstitial Nephritis: Detailed Analysis of 20 Japanese Cases
Authors: Kawano Mitsuhiro , Mizushima Ichiro , Yamaguchi Yutaka , Imai Naofumi , Nakashima Hitoshi , Nishi Shinichi , Hisano Satoshi , Yamanaka Nobuaki , Yamamoto Motohisa , Takahashi Hiroki , Umehara Hisanori , Saito Takao , Saeki Takako
Published: July 2012

Although tubulointerstitial nephritis with IgG4+ plasma cell (PC) infiltration is a hallmark of IgG4-related kidney disease (IgG4-RKD), only a few studies are available about the minimum number of IgG4+ PC needed for diagnosis along with IgG4+/IgG+ PC ratio in the kidney. In addition, the significance of the deposition of IgG or complement as a reflection of humoral immunity involvement is still uncertain. In this study, we analyzed 20 Japanese patients with IgG4-RKD to evaluate the number of IgG4+ PCs along with IgG4+/IgG+ PC ratio and involvement of humoral immunity. The average number of IgG4+ PCs was 43.8/hpf and the average IgG4+/IgG+ or IgG4+/CD138+ ratio was 53%. IgG and C3 granular deposits on the tubular basement membrane (TBM) were detected by immunofluorescence microscopy in 13% and 47% of patients, respectively. Nine patients had a variety of glomerular lesions, and 7 of them had immunoglobulin or complement deposition in the glomerulus. In conclusion, we confirmed that infiltrating IgG4+ PCs > 10/hpf and/or IgG4/IgG (CD138)+ PCs > 40% was appropriate as an item of the diagnostic criteria for IgG4-RKD. A relatively high frequency of diverse glomerular lesions with immunoglobulin or complement deposits and deposits in TBM may be evidence of immune complex involvement in IgG4-related disease.
Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties
Authors: Schwarz Adam J. , Gozzi Alessandro , Chessa Alessandro , Bifone Angelo
Published: July 2012

Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine) to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited.
Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism
Authors: Yates D. T. , Macko A. R. , Nearing M. , Chen X. , Rhoads R. P. , Limesand S. W.
Published: July 2012

Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship ofβ-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, thisβ-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.
Baseline Factors Predictive of SLT Response: A Prospective Study
Authors: Bruen Robin , Lesk Mark R. , Harasymowycz Paul
Published: July 2012

Purpose. To study the response to Selective Laser Trabeculoplasty (SLT) according to baseline medical treatment, angle pigmentation, age, diagnosis (open-angle glaucoma or ocular hypertension), and baseline intraocular pressure (IOP).Methods. 74 eyes of 74 patients were enrolled in this study. Baseline characteristics were recorded for each patient. IOP in the treated and fellow eyes was measured at baseline, and 1 month, 6 months, and 12 months following SLT. IOP changes in the different groups were compared using two-way ANOVA and Pearson's correlation.Results. The mean age of our cohort was71±10years. The mean baseline IOP was21.5±5 mmHg, and the mean change in IOP from baseline in the treated eye at one year was−4.67±3.40 mmHg. Higher baseline IOP was highly correlated with greater absolute IOP decrease. Prostaglandin analogue use at baseline was shown to be associated with a statistically decreased IOP-lowering response following SLT when corrected for baseline IOP. No significant differences in IOP response were found when comparing groups stratified for age, angle pigmentation, phakic status, gender, or diagnosis.Discussion. The results of this study confirm the finding that higher baseline IOP is a predictor of greater IOP response following SLT, and that pretreatment with prostaglandin analogue therapy is associated with a decreased IOP-lowering response following SLT. The study is limited by the small number of eyes with data available for complete case analysis.
Positive Modulation Effect of 8-Week Consumption ofKaempferia parvifloraon Health-Related Physical Fitness and Oxidative Status in Healthy Elderly Volunteers
Authors: Wattanathorn Jintanaporn , Muchimapura Supaporn , Tong-Un Terdthai , Saenghong Narisara , Thukhum-Mee Wipawee , Sripanidkulchai Bungorn
Published: July 2012

Health-related physical fitness declines as the age advances. Oxidative stress is reported to contribute the crucial role on this phenomenon. This condition is also enhanced by antioxidant. Therefore, we aimed to determine the effect ofKaempferia parviflora, a plant reputed for antifatigue, longevity promotion, and antioxidant effects, on health-related quality physical fitness and oxidative status of the healthy elderly volunteers. Total 45 subjects had been randomized to receive placebo orK. parvifloraextract at doses of 25 or 90 mg once daily for 8 weeks. They were determined baseline data of physical performance using 30 sec chair stand test, hand grip test, 6 min walk test, and tandem test. Serum oxidative stress markers including malondialdehde (MDA) level and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were also assayed. All assessments were performed every 4 weeks throughout the 8-week study period. The results showed thatK. parvifloraincreased performance in 30-second chair stand test and 6 min walk test together with the increased all scavenger enzymes activities and the decreased MDA level. Therefore,K. parvifloracan enhance physical fitness partly via the decreased oxidative stress. In conclusion,K. parviflorais the potential health supplement for elderly. However, further study is required.
Influence of Material Properties on Rate of Resorption of Two Bone Graft Materials after Sinus Lift Using Radiographic Assessment
Authors: Riachi Fawzi , Naaman Nada , Tabarani Carine , Aboelsaad Nayer , Aboushelib Moustafa N. , Berberi Antoine , Salameh Ziad
Published: July 2012

Purpose. The aim of this study was to investigate the influence of chemical and physical properties of two graft materials on the rate of resorption.Materials and Methods. Direct sinus graft procedure was performed on 22 patients intended for implant placement. Two types of graft materials were used (Bio-Oss and Cerabone) and after 8 months healing time the implants were inserted. Radiographic assessment was performed over the period of four years. Particle size, rate of calcium release, and size and type of crystal structure of each graft were evaluated.Results.The average particle size of Bio-Oss (1 mm) was much smaller compared to Cerabone (2.7 mm). The amount of calcium release due to dissolution of material in water was much higher for Bio-oss compared to Cerabone. X-ray image analysis revealed that Bio-Oss demonstrated significantly higher volumetric loss (33.4 ± 3.1%) of initial graft size compared to Cerabone (23.4 ± 3.6%). The greatest amount of vertical loss of graft material volume was observed after one year of surgery.Conclusion. The chemical and physical properties of bone graft material significantly influence resorption rate of bone graft materials used for sinus augmentation.
An Elite Decision Making Harmony Search Algorithm for Optimization Problem
Authors: Zhang Lipu , Xu Yinghong , Liu Yousong
Published: July 2012

This paper describes a new variant of harmony search algorithm which is inspired by a well‐known item “elite decision making.” In the new algorithm, the good information captured in the current global best and the second best solutions can be well utilized to generate new solutions, following some probability rule. The generated new solution vector replaces the worst solution in the solution set, only if its fitness is better than that of the worst solution. The generating
and updating steps and repeated until the near‐optimal solution vector is obtained. Extensive computational comparisons are carried out by employing various standard benchmark optimization problems, including continuous design variables and integer variables minimization problems from the literature. The computational results show that the proposed new algorithm is competitive in finding solutions with the state‐of‐the‐art harmony search variants.
RKI-1447 Is a Potent Inhibitor of the Rho-Associated ROCK Kinases with Anti-Invasive and Antitumor Activities in Breast Cancer
Authors: Patel Ronil A. , Forinash Kara D. , Pireddu Roberta , Sun Ying , Sun Nan , Martin Mathew P. , Schönbrunn Ernst , Lawrence Nicholas J. , Sebti Saïd M.
Published: July 2012

The Rho-associated kinases ROCK1 and ROCK2 are critical for cancer cell migration and invasion, suggesting they may be useful therapeutic targets. In this study, we describe the discovery and development of RKI-1447, a potent small molecule inhibitor of ROCK1 and ROCK2. Crystal structures of the RKI-1447/ROCK1 complex revealed that RKI-1447 is a Type I kinase inhibitor that binds the ATP binding site through interactions with the hinge region and the DFG motif. RKI-1447 suppressed phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells, but had no effect on the phosphorylation levels of the AKT, MEK, and S6 kinase at concentrations as high as 10 μmol/L. RKI-1447 was also highly selective at inhibiting ROCK-mediated cytoskeleton re-organization (actin stress fiber formation) following LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation following PDGF and Bradykinin stimulation, respectively. RKI-1447 inhibited migration, invasion and anchorage-independent tumor growth of breast cancer cells. In contrast, RKI-1313, a much weaker analog in vitro, had little effect on the phosphorylation levels of ROCK substrates, migration, invasion or anchorage-independent growth. Finally, RKI-1447 was highly effective at inhibiting the outgrowth of mammary tumors in a transgenic mouse model. In summary, our findings establish RKI-1447 as a potent and selective ROCK inhibitor with significant anti-invasive and antitumor activities and offer a preclinical proof-of-concept that justify further examination of RKI-1447 suitability as a potential clinical candidate. Cancer Res; 72(19); 5025–34. ©2012 AACR.
Let-7 Expression Is a Significant Determinant of Response to Chemotherapy through the Regulation of IL-6/STAT3 Pathway in Esophageal Squamous Cell Carcinoma
Authors: Sugimura Keijiro , Miyata Hiroshi , Tanaka Koji , Hamano Rie , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Nakajima Kiyokazu , Takiguchi Shuji , Mori Masaki , Doki Yuichiro
Published: July 2012

Purpose: Cisplatin-based chemotherapy is widely used for esophageal cancer, sometimes in combination with surgery/radiotherapy, but poor response to chemotherapy is not uncommon. The aim of this study was to examine whether miRNA expression is useful to predict the response to chemotherapy in patients with esophageal cancer.

Experimental Design: Using pretreatment biopsy samples from 98 patients with esophageal cancer who received preoperative chemotherapy, we measured the expression level of several miRNAs whose expression was altered in cisplatin-resistant esophageal cancer cell lines compared with those parent cell lines and examined the relationship between the miRNA expression and response to chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA-induced changes in chemosensitivity.

Results: The expression levels of 15 miRNAs were altered in cisplatin-resistant cells. Of these, low expression of let-7b and let-7c in before-treatment biopsies from 74 patients of the training set correlated significantly with poor response to chemotherapy, both clinically and histopathologically. Low expression of let-7c also correlated with poor prognosis (P = 0.032). The relationship between let-7b and let-7c expression and response to chemotherapy was confirmed in the other 24 patients of the validation set. In in vitro assay, transfection of let-7c restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin. Let-7c directly repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway.

Conclusions: Let-7 expression in esophageal cancer can be potentially used to predict the response to cisplatin-based chemotherapy. Let-7 modulates the chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in esophageal cancer. Clin Cancer Res; 18(18); 5144–53. ©2012 AACR.
Phase I Clinical Trial of Mixed Bacterial Vaccine (Coley's Toxins) in Patients with NY-ESO-1 Expressing Cancers: Immunological Effects and Clinical Activity
Authors: Karbach Julia , Neumann Antje , Brand Kathrin , Wahle Claudia , Siegel Ekkehard , Maeurer Markus , Ritter Erika , Tsuji Takamasa , Gnjatic Sacha , Old Lloyd J. , Ritter Gerd , Jäger Elke
Published: July 2012

Purpose: Mixed bacterial vaccine (MBV, Coley's toxins) is a historical, vaguely defined preparation of heat-inactivated Streptococcus pyogenes and Serratia marcescens used as nonspecific immunotherapy in the treatment of cancer. The mechanism of action is suspected to have an immunologic basis, yet it is poorly defined up to now. We developed a new, biochemically well defined and current good manufacturing practice–compliant MBV preparation, which has been investigated in patients with NY-ESO-1 expressing cancers.

Experimental Design: Patients received MBV subcutaneously at a starting dose of 250 EU (endotoxin units) twice a week. The MBV dose was escalated in each patient until a body temperature of 38°C to 39.5°C was induced or up to the maximum dose of 547.000 EU. Changes in serum cytokine levels were determined and immune responses to NY-ESO-1 were evaluated. Tumor response was assessed according to RECIST.

Results: Twelve patients were enrolled and 11 of them developed fever after the administration of MBV. Ten of 12 patients showed a consistent increase in serum IL-6 levels with the highest levels coinciding with the highest body temperature. A subgroup of patients showed increasing levels of TNF-α, IFN-γ, and IL1-β. A patient with metastatic bladder cancer showed a partial tumor response strongly correlated with MBV-induced fever and highly elevated levels of several cytokines.

Conclusions: MBV at fever-inducing dose levels can lead to a massive induction of immunoregulatory cytokines that may be involved in inducing tumor regressions. We propose to further explore the role of MBV as a potent immune modulator at higher dose levels and in conjunction with antigen-specific cancer vaccines. Clin Cancer Res; 18(19); 5449–59. ©2012 AACR.
Targeting Subcellular Localization through the Polo-Box Domain: Non-ATP Competitive Inhibitors Recapitulate a PLK1 Phenotype
Authors: McInnes Campbell , Estes Kara , Baxter Merissa , Yang Zhengguan , Farag Doaa Boshra , Johnston Paul , Lazo John S. , Wang Jianjun , Wyatt Michael D.
Published: July 2012

The polo-box domain (PBD) has critical roles in the mitotic functions of polo-like kinase 1 (PLK1). The replacement with partial ligand alternative through computational enrichment (REPLACE) strategy to develop inhibitors of protein–protein interactions has identified alternatives for the N-terminal tripeptide of a Cdc25C substrate. In addition, a peptide structure–activity relationship described key determinants and novel information useful for drug design. Fragment-ligated inhibitory peptides (FLIP) were generated with comparable affinity to peptide PBD inhibitors and possessed antiproliferative phenotypes in cells consistent with the observed decrease in PLK1 centrosomal localization. These FLIPs showed evidence of enhanced PLK1 inhibition in cells relative to peptides and induced monopolar and multipolar spindles, which stands in contrast to previously reported small-molecule PBD inhibitors that display phenotypes only partially representative of PLK1 knockdown. Progress obtained applying REPLACE validates this approach for identifying fragment alternatives for determinants of the Cdc25C-binding motif and extends its applicability of the strategy for discovering protein–protein interaction inhibitors. In addition, the described PBD inhibitors retain high specificity for PLK1 over PLK3 and therefore show promise as isotype selective, non-ATP competitive kinase inhibitors that provide new impetus for the development of PLK1-selective antitumor therapeutics. Mol Cancer Ther; 11(8); 1683–92. ©2012 AACR.
Better Prognosis of Multiple Sclerosis in Patients Who Experienced a Full-Term Pregnancy
Authors: Keyhanian Kiandokht , Davoudi Vahid , Etemadifar Masoud , Amin Mohammad
Published: July 2012

Objective: We conducted a longitudinal prospective study to evaluate the long-term effect of pregnancy on the progression of multiple sclerosis (MS). Method: Parous female MS patients were extracted from the database of Isfahan Multiple Sclerosis Society (IMSS). Through comparing the annual relapsing rate during a mean of 4 years before pregnancy versus a mean of 6 years after delivery, MS progression influenced by the pregnancy was analyzed. Result: 102 female patients were included in our study. The mean annual relapsing rate 4 years prior to pregnancy was significantly higher than at the subsequent 6 years after delivery (1.06 vs. 0.45, p < 0.001). In addition, the annual relapsing rate in years prior to pregnancy was significantly higher than each trimester of gestation (p < 0.001). Furthermore, there was a 2.2-fold increased risk of having a relapse in individuals who had experienced more relapses prior to pregnancy, and a 0.8-fold decreased in the risk of having more relapses with older age at the onset of MS. Conclusion: Although the course of MS was deteriorated 3 months after delivery, it was not statistically significant comparing annual relapsing rates during the years prior to pregnancy. Moreover, the rate of disease progression slowed down in the 6-year period monitored after delivery.
Process and Domain Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation
Authors: Collins Heather R. , Zhu Xun , Bhatt Ramesh S. , Clark Jonathan D. , Joseph Jane E.
Published: July 2012

The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.
Moving Beyond Deterrence
Authors: Dugan Laura , Chenoweth Erica
Published: July 2012

Rational choice approaches to reducing terrorist violence would suggest raising the costs of terrorism through punishment, thereby reducing the overall expected utility of terrorism. In this article, we argue that states should also consider raising the expected utility of abstaining from terrorism through rewards. We test effects of repressive (or punishing) and conciliatory (or rewarding) actions on terrorist behavior using the newly developed GATE-Israel dataset, which identifies events by Israeli state actors toward Palestinian targets on a full range of counterterrorism tactics and policies from 1987 to 2004. Results show that repressive actions are either unrelated to terror or related to subsequent increases in terror, and conciliatory actions are generally related to decreases in terror, depending on the tactical period. Findings also reveal the importance of understanding the role of terrorists’ constituencies for reducing violence.
Can a six-week exercise intervention improve gross motor function for non-ambulant children with cerebral palsy? A pilot randomized controlled trial
Authors: Bryant Elizabeth , Pountney Terry , Williams Heather , Edelman Natalie
Published: July 2012

Objective:

To determine the effect of a six-week exercise intervention on gross motor function for non-ambulant children with cerebral palsy.

Design:

A parallel arm randomized controlled trial.

Setting:

Four special schools.

Participants:

Thirty-five children aged 8–17 with bilateral cerebral palsy; Gross Motor Function Classification System levels IV–V.

Method:

Participants were randomly allocated to a static bike group, a treadmill group or control group. Participants in the bike and treadmill groups received exercise training sessions, three times weekly for six weeks. The control group received their usual care. Blinded assessments were performed at baseline and six weeks and followed up at 12 and 18 weeks.

Outcome measures:

Gross Motor Function Measures GMFM-66, GMFM-88D and GMFM-88E.

Results:

At six weeks significant differences were found in GMFM-88D scores between the bike group and the control group, and the treadmill group and the control group ( P < 0.05). The mean change (SD) in GMFM-88D score was 5.9 (6.8) for the bike group; 3.7 (4.4) for the treadmill group and 0.5 (1.9) for the control group. No significant differences were found for GMFM-66 or GMFM-88E scores between the bike group and control group, or the treadmill group and control group, although trends of improvement were observed for both exercise groups. The improvements observed declined during the follow-up period.

Conclusion:

This study provides preliminary evidence that exercising on a bike or treadmill may provide short-term improvements in gross motor function for non-ambulant children with cerebral palsy. This needs to be tested in a large-scale randomized trial.
Behavior of urban residents toward the discarding of waste electrical and electronic equipment: a case study in Baoding, China
Authors: Li Jinhui , Liu Lili , Ren Junshu , Duan Huabo , Zheng Lixia
Published: July 2012

The volume of waste electrical and electronic equipment (WEEE) is growing rapidly worldwide, making its management difficult; therefore, this should be improved as a matter of urgency. WEEE includes both essential household appliances [including televisions, refrigerators, and washing machines; but not air conditioners, where the consumption mode is more like information, communication and technology (ICT)] ICT equipment (also called high-tech household appliances). In the present study, Baoding, a medium-sized, prefecture-level city in north central China with a population of 11 million, including 1.1 million urban residents, was selected as a representative city for an investigation of recycling behaviors. A valid sample size of 346 households in Baoding was investigated, and categorized into various income and educational levels. The results showed that the major reason for discarding WEEE was malfunction of the appliance, accounting for 52% of disposals. Surveyed households with either high income or good education were more likely to consume high-tech household appliances, attracted by advanced technology, versatile functions or flexibility of use. Personal computer ownership rates were highest in households with a high income and good education—1.2 and 0.9 per home respectively. WEEE was most often sold to peddlers or hawkers from where the WEEE flowed into the second-hand market to be refurbished or repaired, and then re-sold. However, 56.3% of residents in the college community were in support of charging consumers for disposal and 61.7% were in support of including a disposal surcharge in the purchase price of new products—a percentage approximately three times that for high-income residents. Thus, high educational level appears to be currently the most important factor in raising the potential of a household’s willingness to pay for WEEE treatment cost. The findings of this study can be used to develop sound recycling systems for WEEE in mainland China.
Assessment of total aflatoxin level in red pepper obtained from Istanbul
Authors: Alpsoy Lokman , Kiren Artin , Can Sevde Nur , Koprubasi Ayşenur
Published: July 2012

Aflatoxins ( Aspergillus flavus toxins (AFT)) are biologically active secondary metabolites mostly produced by some Aspergillus species that causes hepatotoxicity, teratogenicity, immunotoxicity, and cancers in human. The aim of this study is to determine the level of total AFT in powdered red pepper in the retail markets in 40 district of Istanbul using enzyme-linked immunosorbent assay. Of the 36 unpacked powdered red pepper samples, 32 samples (88%) contained AFT in the range of 0.2–106.4 µg/kg; 16 samples (44.4%) were above the regulatory limit which is at 10 µg/kg for total AFT in Turkey. More precautions on the production, transport, harvest, and storage of red pepper should be taken on hygiene to prevent toxic and carcinogenic effects of AFT.
The Post-School Outcomes Transition Survey
Authors: Eaves Ronald C. , Rabren Karen , Hall George
Published: July 2012

This study investigated the validity of the Post-School Outcomes Transition Survey (PSOTS). The PSOTS was designed to ascertain whether individuals who received special education services in secondary school have obtained postschool employment or have enrolled in postsecondary education or training within 1 to 2 years of exiting high school. The PSOTS also attempts to obtain continuous scores for transition program services provided to students while they were enrolled in secondary school. Two representative data sets of PSOTS respondents (Year 2004, n = 539, and Year 2005, n = 415) were employed to validate the PSOTS via exploratory factor analysis. A total of 16 salient factors were supported, 8 of which were regarded as postschool outcome dimensions with 8 construed as in-school program dimensions. Because the factors represent robust, continuous measures of transition constructs, they can be used to link transition practices to postschool outcomes through experimental research as suggested by Test, Fowler, et al.
Rehabilitation of the Overhead Athlete’s Elbow
Authors: Wilk Kevin E. , Macrina Leonard C. , Cain E. Lyle , Dugas Jeffrey R. , Andrews James R.
Published: July 2012

The activities required during overhead sports, particularly during baseball pitching, produce large forces at the elbow joint. Injuries to the elbow joint frequently occur in the overhead athlete because of the large amount of forces observed during the act of throwing, playing tennis, or playing golf. Injuries may result because of repetitive overuse, leading to tissue failure. Rehabilitation following injury or surgery to the throwing elbow is vital to fully restore normal function and return the athlete to competition as quickly and safely as possible. Rehabilitation of the elbow, whether following injury or postsurgical, must follow a progressive and sequential order, building on the previous phase, to ensure that healing tissues are not compromised. Emphasis is placed on restoring full motion, muscular strength, and neuromuscular control while gradually applying loads to healing tissue. In addition, when one is creating a rehabilitation plan for athletes, it is imperative to treat the entire upper extremity, core, and legs to create and dissipate the forces generated at each joint.
The Ulnar Collateral Ligament Procedure Revisited
Authors: Andrews James R. , Jost Patrick W. , Cain E. Lyle
Published: July 2012

Context:

The ulnar collateral ligament of the elbow (UCL) is frequently injured in throwing athletes, most commonly baseball pitchers. The ligament is reconstructed through bone tunnels using palmaris longus or gracilis autograft.

Results:

This study highlights the following technique for UCL reconstruction in over 2000 athletes. 2

Conclusion:

When conservative management fails, ligament reconstruction can allow the athlete to return to their sport. 1