bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis Induced by Tanshinone IIA and Cryptotanshinone Is Mediated by Distinct JAK/STAT3/5 and SHP1/2 Signaling in Chronic Myeloid Leukemia K562 Cells
Authors: Jung Ji Hoon , Kwon Tae-Rin , Jeong Soo-Jin , Kim Eun-Ok , Sohn Eun Jung , Yun Miyong , Kim Sung-Hoon
Published: June 2013

Though tanshinone IIA and cryptotanshinone possess a variety of biological effects such as anti-inflammatory, antioxidative, antimetabolic, and anticancer effects, the precise molecular targets or pathways responsible for anticancer activities of tanshinone IIA and cryptotanshinone in chronic myeloid leukemia (CML) still remain unclear. In the present study, we investigated the effect of tanshinone IIA and cryptotanshinone on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. We found that both tanshinone IIA and cryptotanshinone induced apoptosis by activation of caspase-9/3 and Sub-G1 accumulation in K562 cells. However, they have the distinct JAK/STAT pathway, in which tanshinone IIA inhibits JAK2/STAT5 signaling, whereas cryptotanshinone targets the JAK2/STAT3. In addition, tanshinone IIA enhanced the expression of both SHP-1 and -2, while cryptotanshinone regulated the expression of only SHP-1. Both tanshinone IIA and cryptotanshinone attenuated the expression of bcl-xL, survivin, and cyclin D1. Furthermore, tanshinone IIA augmented synergy with imatinib, a CML chemotherapeutic drug, better than cryptotanshinone in K562 cells. Overall, our findings suggest that the anticancer activity of tanshinone IIA and cryptotanshinone is mediated by the distinct the JAK/STAT3/5 and SHP1/2 signaling, and tanshinone IIA has the potential for combination therapy with imatinib in K562 CML cells.
Primary Small Cell Carcinoma of the Vagina
Authors: Oliveira Rafael , Bócoli Mayra Coelho , Saldanha João Carlos , Murta Eddie Fernando Candido , Nomelini Rosekeila Simões
Published: June 2013

The primary small cell carcinoma of the vagina is rare, and it is a highly aggressive malignancy with no consensus regarding the treatment of this tumor. The survival rate for patients treated in the early stages is around two years. We related the case report of a patient of 41 years with a vegetative and necrotic lesion in left vaginal wall, in middle and upper third, and involvement of parametrium in its proximal third and medium third. A biopsy showed a small cell undifferentiated carcinoma composed of epithelial cells with round nuclei, oval or elongated, hyperchromatic nuclei, with little distinct nucleoli, and scarce cytoplasm. Immunohistochemistry showed positivity for AE1/AE3, CD57, and chromogranin A. The patient received 6 cycles of chemotherapy with cisplatin and etoposide and radiotherapy, achieving complete response, with complete regression of the lesion. The patient had no sign of tumor recurrence and locoregional or distant metastases after 5 months of followup.
Clinical Outcomes of Peripheral Iridotomy in Patients with the Spectrum of Chronic Primary Angle Closure
Authors: Cumba Ricardo J. , Nagi Kundandeep S. , Bell Nicholas P. , Blieden Lauren S. , Chuang Alice Z. , Mankiewicz Kimberly A. , Feldman Robert M.
Published: June 2013

Purpose. To evaluate outcomes of peripheral iridotomy (PI) for initial management of primary angle closure suspects (PACS), chronic primary angle closure (CPAC), and chronic primary angle closure glaucoma (CPACG). Patients and Methods. Seventy-nine eyes with PACS, CPAC, or CPACG and better than 20/50 visual acuity that underwent PI as initial management were included. Eyes with previous acute angle closure attacks, laser trabeculoplasties, surgeries, or intraocular injections were excluded. Additional treatments, glaucomatous progression, intraocular pressure, visual acuity, and the number of medications were evaluated. Results. The mean followup was months (range 13.8–150.6 months). Sixty-eight eyes (86.1%) underwent additional medical, laser, or surgical treatment. Forty eyes (50.6%) underwent lens extraction due to reduced visual acuity. The mean 10× logMAR visual acuity score for all patients significantly declined from at baseline to (, ) at the last followup. Conclusions. Most patients who undergo PI for CPAC spectrum will require additional intervention for either IOP lowering or improvement of visual acuity. This suggests that a procedure that not only deepens the angle but also lowers IOP and improves visual acuity would be desirable as further intervention could be avoided. Evaluation of techniques that achieve all 3 goals is warranted.
Modeling Computer Virus and Its Dynamics
Authors: Peng Mei , He Xing , Huang Junjian , Dong Tao
Published: June 2013

Based on that the computer will be infected by infected computer and exposed computer, and some of the computers which are in suscepitible status and exposed status can get immunity by antivirus ability, a novel coumputer virus model is established. The dynamic behaviors of this model are investigated. First, the basic reproduction numberR0, which is a threshold of the computer virus spreading in internet, is determined. Second, this model has a virus-free equilibriumP0, which means that the infected part of the computer disappears, and the virus dies out, andP0is a globally asymptotically stable equilibrium ifR0<1. Third, ifR0>1then this model has only one viral equilibriumP*, which means that the computer persists at a constant endemic level, andP*is also globally asymptotically stable. Finally, some numerical examples are given to demonstrate the analytical results.
The Epidermal Growth Factor Receptor Increases Cytokine Production and Cutaneous Inflammation in Response to Ultraviolet Irradiation
Authors: El-Abaseri Taghrid Bahig , Hammiller Brianna , Repertinger Susan K. , Hansen Laura A.
Published: June 2013

The epidermal growth factor receptor (EGFR) is activated in cutaneous keratinocytes upon ultraviolet (UV) exposure and has been implicated in ultraviolet-(UV-)induced inflammation and skin tumorigenesis.Egfrmutant mice and EGFR inhibitors were used to investigate the hypothesis that EGFR activation augments inflammation following UV irradiation. Topical treatment of mouse skin with the EGFR inhibitor AG1478 before UV exposure suppressed UV-induced erythema, edema, mast cell infiltration, and neutrophil infiltration. Genetic ablation ofEgfrand EGFR inhibition by AG1478 also suppressed the increase in the proinflammatory cytokines tumor necrosis factorα(TNF-α), interleukin-1α, KC (murine IL-8), and cyclooxygenase-2 (COX-2) after UV exposure of cultured keratinocytes. Finally, genetic ablation of inhibition of EGFR in cultured keratinocytes decreased p38 activation after UV, while inhibition of p38 kinase reduced COX-2 expression after UV. These data demonstrate that EGFR regulates multiple aspects of UV-induced inflammation and suggest activation of p38 kinase leading to increased COX-2 and cytokine expression as one mechanism through which it acts.
Antibacterial Effect of Juglans Regia Bark against Oral Pathologic Bacteria
Authors: Zakavi Faramarz , Golpasand Hagh Leila , Daraeighadikolaei Arash , Farajzadeh Sheikh Ahmad , Daraeighadikolaei Arsham , Leilavi Shooshtari Zahra
Published: June 2013

Background. In this study antimicrobial effect of ethanolic and aqueous extracts of Juglans regia bark in Iran was evaluated on four different oral bacteria,Streptococcus mutans,Streptococcus salivarius,Streptococcus sanguis, andStaphylococcus aureus.Methods. Aqueous and ethanol extracts of Juglans regia bark were prepared by using disk diffusion technique and Minimal Inhibitory Concentration (MIC) methods. Tetracycline 30 μg and Erythromycin 15 μg were used as positive control and water as negative control in disk diffusion and MIC methods. Data were analyzed by ANOVA test.Results. The results showed thatS. sanguisandS. mutanswere the most sensitive and the most resistant bacteria against ethanolic and aqueous extracts, respectively. Ethanolic extract had significant antibacterial effect against all tested bacteria. Aqueous extract did not show antibacterial effect onS. mutans, in contrast to ethanolic extract. Aqueous extract had significantly antibacterial effect againstStaphylococcus aureus,S. salivarius, andS. sanguiscompared to control (P<0.0001), but it did not show effect onS. mutanswhen compared with Erythromycin. According to the obtained MIC values, ethanol extract of Juglans regia bark had the lowest rate.Conclusion. The results may provide the basis for using natural antimicrobial substance for oral hygiene prophylaxis purposes.
Quantifying Gait Impairment Using an Instrumented Treadmill in People with Multiple Sclerosis
Authors: Kalron Alon , Dvir Zeevi , Frid Lior , Achiron Anat
Published: June 2013

Background and Objective. Treadmill gait analysis has been proposed as an attractive alternative for overground walking measuring systems. The purpose of this study was twofold: first to determine spatiotemporal parameters of treadmill gait in patients with multiple sclerosis (MS) and second to examine whether these parameters are associated with specific functional impairments in this cohort. Method. Eighty-seven relapsing-remitting patients diagnosed with MS, 50 women and 37 men, aged 40.9 ± 11.9 with an expanded disability status scale (EDSS) score of 2.7 ± 1.6, participated in this study. Twenty-five apparently healthy subjects, 14 women and 11 men, aged 38.5 ± 9.4, served as controls. Spatiotemporal gait parameters were obtained using the Zebris FDM-T Treadmill (Zebris Medical GmbH, Germany). People with MS demonstrated significantly shorter steps, extended stride time, wider base of support, longer step time, reduced single support phase, and a prolonged double support phase compared to the healthy controls. The EDSS score was significantly correlated with all spatiotemporal gait parameters. Conclusion. The instrumented treadmill may be an effective tool in assessing ambulation capabilities of people with MS.
A New Approach to Numerical Solution of Nonlinear Klein-Gordon Equation
Authors: Bülbül Berna , Sezer Mehmet
Published: June 2013

A numerical method based on collocation points is developed to solve the nonlinear Klein-Gordon equations by using the Taylor matrix method. The method is applied to some test examples and the numerical results are compared with the exact solutions. The results reveal that the method is very effective, simple, and convenient. In addition, an error estimation of proposed method is presented.
Inhibitory Effects of PC-SPESII Herbal Extract on Human Breast Cancer Metastasis
Authors: Wang Xiu-Feng , Du Jia , Zhang Tian-Ling , Zhou Qian-Mei , Lu Yi-Yu , Zhang Hui , Su Shi-Bing
Published: June 2013

Cancer metastasis is refractory to most forms of chemotherapy. Conventional and alternative drugs, such as Chinese herbal remedies, have been developed to target metastatic cancer cells. In this study, we investigated the effects of PC-SPESII, an herbal formulation, on the migration, invasion, and metastasis of an experimental human breast cancer cell linein vivoandin vitro. PC-SPESII suppressed pulmonary metastasis and tumor growth of MDA-MB-231 human breast cancer xenografts without affecting body weight, liver function, and kidney function. PC-SPESII also inhibited MDA-MB-231 cell migration and invasionin vitroin a dose-dependent manner. Based on ELISA analysis, secretion of MMP-2 and MMP-9, proteins associated with extracellular matrix degradation, was reduced in response to PC-SPESII treatment. Western blot analysis of whole-cell extracts revealed that the levels of proteolytic proteins associated with matrix and base membrane degradation (MMP-2, MMP-9, and uPA) were decreased and the levels of their endogenous inhibitors (TIMP1 and TIMP2) were increased. Moreover, the p38MAPK and SAPK/JNK signaling pathway, which stimulates proteolytic enzymes and matrix degradation, was inhibited by PC-PSESII. Remarkably, cotreatment with PC-PSESII and p38MAPK or SAPK/JNK inhibitors magnified the antimetastatic phenotype. Our results indicate that PC-PSESII impairs human breast cancer metastasis by regulating proteolytic enzymes and matrix dynamics through the p38MAPK and SAPK/JNK pathway.
Effects of Community-Based Cardiac Rehabilitation on Body Composition and Physical Function in Individuals with Stable Coronary Artery Disease: 1.6-Year Followup
Authors: Mandic Sandra , Hodge Claire , Stevens Emily , Walker Robert , Nye Edwin R. , Body Dianne , Barclay Leanne , Williams Michael J. A.
Published: June 2013

Objective. To examine long-term changes in physical function and body composition in coronary artery disease (CAD) patients participating in ongoing community-based cardiac rehabilitation (CR).Design. Thirty-four individuals (69.7±8.2years; 79% men) participated in this longitudinal observational study. Baseline and follow-up assessments included incremental shuttle walk, short physical performance battery, handgrip strength, chair stands, body composition, last year physical activity, and CR attendance.Results. Participants attended38.5±30.3%sessions during1.6±0.2year followup. A significant increase in 30-second chair stands (17.0±4.7to19.6±6.4,P<0.001), body weight (75.8±11.1to77.2±12.1 kg,P=0.001), and body fat (27.0±9.5to29.1±9.6%,P<0.001) and a decline in handgrip strength (36.4±9.4to33.0±10.6kg·f,P<0.001) and muscle mass (40.8±5.6to39.3±5.8%,P<0.001) were observed during followup. There was no significant change in shuttle walk duration. CR attendance was not correlated to observed changes.Conclusions. Elderly CAD patients participating in a maintenance CR program improve lower-body muscle strength but experience a decline in handgrip strength and unfavourable changes in body composition, irrespective of CR attendance.
Phase Stability and Site Preference of Tb‐Fe‐Co‐V Compounds
Authors: Sun Jing , Shen Jiang , Qian Ping
Published: June 2013

The effect of cobalt on the structural properties of intermetallic Tb3Fe27.4−xCoxV1.6 with Nd3(Fe,Ti)29 structure has been studied by using interatomic pair potentials obtained through the lattice inversion method. Calculated results show that the preferential occupation site of the V atom is found to be the 4i(Fe3) site, and Fe atoms are substituted for Co atoms with a strong preference for the 8j(Fe8) site. The calculated lattice constants coincide quite well with experimental values. The calculated crystal structure can recover after either an overall wide‐range macrodeformation or atomic random motion, demonstrating that this system has the stable structure of Nd3(Fe,Ti)29. All these prove the effectiveness of interatomic pair potentials obtained through the lattice inversion method in the description of rare‐earth materials.
A Multilevel Gamma-Clustering Layout Algorithm for Visualization of Biological Networks
Authors: Hruz Tomas , Wyss Markus , Lucas Christoph , Laule Oliver , von Rohr Peter , Zimmermann Philip , Bleuler Stefan
Published: June 2013

Visualization of large complex networks has become an indispensable part of systems biology, where organisms need to be considered as one complex system. The visualization of the corresponding network is challenging due to the size and density of edges. In many cases, the use of standard visualization algorithms can lead to high running times and poorly readable visualizations due to many edge crossings. We suggest an approach that analyzes the structure of the graph first and then generates a new graph which contains specific semantic symbols for regular substructures like dense clusters. We propose a multilevel gamma-clustering layout visualization algorithm (MLGA) which proceeds in three subsequent steps: (i) a multilevel γ-clustering is used to identify the structure of the underlying network, (ii) the network is transformed to a tree, and (iii) finally, the resulting tree which shows the network structure is drawn using a variation of a force-directed algorithm. The algorithm has a potential to visualize very large networks because it uses modern clustering heuristics which are optimized for large graphs. Moreover, most of the edges are removed from the visual representation which allows keeping the overview over complex graphs with dense subgraphs.
Pathological Changes in Internal Organs after Blocking Low Hydraulic Resistance Channels along the Stomach Meridian in Pigs
Authors: Zhou Wen-Ting , Jia Shu-Yong , Zhang Yu-Qing , Tian Yu-Ying , Wang Guang-Jun , Huang Tao , Pang Li , Zhou Yong-Sheng , Sun Xue-Yan , Zhang Wei-Bo
Published: June 2013

Objective.The correlation between meridians and organs (Zang-fu) is an important aspect of meridian theory. The objective of this paper is to investigate the pathological changes in the organs resulting from blocking low hydraulic resistance channel (LHRC) along the stomach meridian by injecting gel in pigs so as to offer some insight into the correlation between meridians and internal organs.Methods.Four white piglets and twelve black minipigs were divided into four batches and were observed in different periods. Each batch included two pairs of pigs and each pair matched two pigs with similar conditions among which gel was injected into 6~8 low hydraulic resistance points along the the stomach meridian in the experimental pig and the same amount of saline was injected into the same points in the control pig. The state of stomach and intestine was observed 6~10 weeks after the blocking model was developed.Results.The results showed that there were bloated stomach or/and intestine in all the experimental pigs while there were normal states in seven control pigs except one dead during the experiment.Conclusion.The findings confirmed that the blockage of LHRC along the stomach meridian can influence the state of stomach and intestine, leading to a distension on stomach or/and intestine.
A Digital Interface for the Part Designers and the Fixture Designers for a Reconfigurable Assembly System
Authors: Kumar Vishwa V. , Yadav Salik R. , Liou F. W. , Balakrishnan S. N.
Published: June 2013

This paper presents a web-based framework for interfacing product designers and fixture designers to fetch the benefits of early supplier involvement (ESI) to a reconfigurable assembly system (RAS). The interfacing of the two members requires four steps, namely, collaboration chain, fixture supplier selection, knowledge share, and accommodation of service facilities so as to produce multiple products on a single assembly line. The interfacing not only provokes concurrency in the activities of product and fixture designer but also enables the assembly systems to tackle the spatial and generational variety. Among the four stages of interfacing, two steps are characterized by optimization issues, one from the product customer side and the other from the fixture designer side. To impart promptness in the optimization and hence the interaction, computationally economic tools are also presented in the paper for both of the supplier selection and fixture design optimization.
Total Hip Arthroplasty after Treatment of Pseudojoint Infection in a Patient with a Highly Dislocated Hip
Authors: Park Kyung-Soon , Seon Jong-Keun , Nah Seon-Yoon , Yoon Taek-Rim
Published: June 2013

Infection at the pseudoacetabulum in a patient with a high hip dislocation has not been reported previously in the English literature. We report a case of total hip arthroplasty in a 28-year-old female who presented to us with hip pain following debridement of the infected pseudojoint in a case of neglected developmental dysplasia of the hip. The infection was treated with thorough debridement and drainage. However, even after achieving complete infection control, this patient complained of disabling right hip joint pain. Total hip arthroplasty with subtrochanteric osteotomy was performed to relieve the pain and improve gait. After surgery, the patient's symptoms were relieved. We consider that in this case of acute pseudojoint infection simple arthrotomy and debridement combined with irrigation and drainage provide effective treatment. But muscle weakness and more increased joint laxity can cause hip pain even after infection control. So total hip arthroplasty is likely to be necessary after the infection has been controlled in a patient with a highly dislocated hip.
Seismic Response Analysis of Masonry Minaret and Possible Strengthening by Fiber Reinforced Cementitious Matrix (FRCM) Materials
Authors: Turk Ahmet Murat
Published: June 2013

This paper presents the analytical study on the dynamic response of a natural stone block masonry minaret of a historical mosque located in Istanbul, Turkey. A three-dimensional finite element model of the whole minaret, adjusted with former in situ ambient vibration test results, was used in order to get probable lateral displacements, stresses, and understanding of failure modes under seismic loading. Particularly, FEM has been used to evaluate the seismic safety of the minaret in present-day condition and after the application of a proposed strengthening method. In this method, by utilizing the fiber reinforced cementitious matrix (FRCM) material, the critical cross-sections were jacketed. The appearing damage for the bare minaret obtained from FEM analyses was located at the boot and transition part of the minaret. After FRCM material was wrapped around these critical cross-sections, the analytical results indicated that such method appears effective in terms of the seismic response. It also appears less invasive in terms of the conservation of historical heritage like minarets without causing aesthetic conflict on the existing structure when compared to other available techniques.
JC Polyomavirus (JCV) and Monoclonal Antibodies: Friends or Potential Foes?
Authors: Diotti Roberta Antonia , Nakanishi Akira , Clementi Nicola , Mancini Nicasio , Criscuolo Elena , Solforosi Laura , Clementi Massimo
Published: June 2013

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS), observed in immunodeficient patients and caused by JC virus ((JCV), also called JC polyomavirus (JCPyV)). After the HIV pandemic and the introduction of immunomodulatory therapy, the PML incidence significantly increased. The correlation between the use of natalizumab, a drug used in multiple sclerosis (MS), and the PML development of particular relevance. The high incidence of PML in natalizumab-treated patients has highlighted the importance of two factors: the need of PML risk stratification among natalizumab-treated patients and the need of effective therapeutic options. In this review, we discuss these two needs under the light of the major viral models of PML etiopathogenesis.
A General Framework of Mechatronic Modular Architecture
Authors: Zou Ying , Zhao Gang , Wang Tianmiao
Published: June 2013

The independent designs guided by domain technologies of mechatronic system lead to the problem of hard compatibility and the difficulty to reuse resources between the systems. This paper presents an approach based on the reuse for modular mechatronic system, and a general framework for modular mechatronic system is designed. After the analysis of related characteristics of the mechatronic system, the modular principle of mechatronic system is proposed. Secondly, a general framework (F-Model) based on reusability of software and hardware in mechatronic system is developed. Following is to elaborate in details on the parts of software, hardware, and infrastructure of mechatronic system. Finally, 6-DOF industrial robot arm and medical accompany robot are taken as our experiment platform to design system based on F-Model. Results in practical application confirm the value of F-Model for reusing modules in designing mechatronic systems.
Impact Toughness and Ductility Enhancement of Biodegradable Poly(lactic acid)/Poly(ε-caprolactone) Blends via Addition of Glycidyl Methacrylate
Authors: Chee Wei Kit , Ibrahim Nor Azowa , Zainuddin Norhazlin , Abd Rahman Mohd Faizal , Chieng Buong Woei
Published: June 2013

Poly(lactic acid) (PLA)/poly(ε-caprolactone) (PCL) blends were prepared via melt blending technique. Glycidyl methacrylate (GMA) was added as reactive compatibilizer to improve the interfacial adhesion between immiscible phases of PLA and PCL matrices. Tensile test revealed that optimum in elongation at break of approximately 327% achieved when GMA loading was up to 3wt%. Slight drop in tensile strength and tensile modulus at optimum ratio suggested that the blends were tuned to be deformable. Flexural studies showed slight drop in flexural strength and modulus when GMA wt% increases as a result of improved flexibility by finer dispersion of PCL in PLA matrix. Besides, incorporation of GMA in the blends remarkably improved the impact strength. Highest impact strength was achieved (160% compared to pure PLA/PCL blend) when GMA loading was up to 3 wt%. SEM analysis revealed improved interfacial adhesion between PLA/PCL blends in the presence of GMA. Finer dispersion and smooth surface of the specimens were noted as GMA loading increases, indicating that addition of GMA eventually improved the interfacial compatibility of the nonmiscible blend.
Current Pharmacological Management of Gastroesophageal Reflux Disease
Authors: Wang Yao-Kuang , Hsu Wen-Hung , Wang Sophie S. W. , Lu Chien-Yu , Kuo Fu-Chen , Su Yu-Chung , Yang Sheau-Fang , Chen Chiao-Yun , Wu Deng-Chyang , Kuo Chao-Hung
Published: June 2013

Gastroesophageal reflux disease (GERD), a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment.
Inflammatory Chemokine Expression via Toll-Like Receptor 3 Signaling in Normal Human Mesangial Cells
Authors: Tanaka Hiroshi , Imaizumi Tadaatsu
Published: June 2013

The innate and adaptive immune systems have been reported to play an important role in the pathogenesis of glomerular diseases. Since viral infections may trigger the development of inflammatory renal disease or the worsening of preexisting renal disease, recent studies have focused on the involvement of toll-like receptors (TLRs) and their signaling pathways in the inflammatory processes of glomerular cells. Viral double-stranded RNA (dsRNA) can activate not only TLR3 located within intracellular endosomes but also retinoic-acid-inducible-gene-I- (RIG-I-) like helicase receptors located within the cytosol. RIG-I and melanoma differentiation-associated gene 5 (MDA5) are members of the RNA helicase family in the cytosol, and both act as pathogen recognition receptors. The activation of TLRs and their downstream immune responses can be induced by both infectious pathogens and noninfectious stimuli such as endogenous ligands, and this mechanism may be involved in the pathogenesis of autoimmune renal diseases. However, there are few data on the interaction between TLR3, MDA5, and RIG-I in autoimmune glomerular diseases. Based on our recent experimental studies using cultured normal human mesangial cells (MCs), we found that novel TLR3-mediated signaling pathways in MCs may be involved in the pathogenesis of glomerular diseases. In the present paper, we summarize our recent findings.
Auricular Acupuncture with Laser
Authors: Round Regina , Litscher Gerhard , Bahr Frank
Published: June 2013

Auricular acupuncture is a method which has been successfully used in various fields of medicine especially in the treatment of pain relief. The introduction of lasers especially low-level lasers into medicine brought besides the already existing stimulation with needles and electricity an additional technique to auricular acupuncture. This literature research looks at the historical background, the development and the anatomical and neurological aspects of auricular acupuncture in general and auricular laser acupuncture in detail. Preliminary scientific findings on auricular acupuncture with laser have been described in detail and discussed critically in this review article. The results of the studies have shown evidence of the effect of auricular laser acupuncture. However, a comparison of these studies was impossible due to their different study designs. The most important technical as well as study parameters were described in detail in order to give more sufficient evidence and to improve the quality of future studies.
Regulation of the Transcriptional Coactivator FHL2 Licenses Activation of the Androgen Receptor in Castrate-Resistant Prostate Cancer
Authors: McGrath Meagan J. , Binge Lauren C. , Sriratana Absorn , Wang Hong , Robinson Paul A. , Pook David , Fedele Clare G. , Brown Susan , Dyson Jennifer M. , Cottle Denny L. , Cowling Belinda S. , Niranjan Birunthi , Risbridger Gail P. , Mitchell Christina A.
Published: June 2013

It is now clear that progression from localized prostate cancer to incurable castrate-resistant prostate cancer (CRPC) is driven by continued androgen receptor (AR), signaling independently of androgen. Thus, there remains a strong rationale to suppress AR activity as the single most important therapeutic goal in CRPC treatment. Although the expression of ligand-independent AR splice variants confers resistance to AR-targeted therapy and progression to lethal castrate-resistant cancer, the molecular regulators of AR activity in CRPC remain unclear, in particular those pathways that potentiate the function of mutant AR in CRPC. Here, we identify FHL2 as a novel coactivator of ligand-independent AR variants that are important in CRPC. We show that the nuclear localization of FHL2 and coactivation of the AR is driven by calpain cleavage of the cytoskeletal protein filamin, a pathway that shows differential activation in prostate epithelial versus prostate cancer cell lines. We further identify a novel FHL2-AR–filamin transcription complex, revealing how deregulation of this axis promotes the constitutive, ligand-independent activation of AR variants, which are present in CRPC. Critically, the calpain-cleaved filamin fragment and FHL2 are present in the nucleus only in CRPC and not benign prostate tissue or localized prostate cancer. Thus, our work provides mechanistic insight into the enhanced AR activation, most notably of the recently identified AR variants, including AR-V7 that drives CRPC progression. Furthermore, our results identify the first disease-specific mechanism for deregulation of FHL2 nuclear localization during cancer progression. These results offer general import beyond prostate cancer, given that nuclear FHL2 is characteristic of other human cancers where oncogenic transcription factors that drive disease are activated like the AR in prostate cancer. Cancer Res; 73(16); 5066–79. ©2013 AACR.
FOXL1, a Novel Candidate Tumor Suppressor, Inhibits Tumor Aggressiveness and Predicts Outcome in Human Pancreatic Cancer
Authors: Zhang Geng , He Peijun , Gaedcke Jochen , Ghadimi B. Michael , Ried Thomas , Yfantis Harris G. , Lee Dong H. , Hanna Nader , Alexander H. Richard , Hussain S. Perwez
Published: June 2013

The forkhead box L1 (FOXL1) transcription factor regulates epithelial proliferation and development of gastrointestinal tract and has been implicated in gastrointestinal tumorigenesis in mouse models. However, the role of FOXL1 in pancreatic cancer development and progression remains to be elucidated. Here, we report that higher expression of FOXL1 is significantly associated with better clinical outcome in human pancreatic ductal adenocarcinoma (PDAC). A lower FOXL1 expression is correlated with metastasis and advanced pathologic stage of pancreatic cancer. Mechanistic analyses showed that overexpression of FOXL1 induces apoptosis and inhibits proliferation and invasion in pancreatic cancer cells, whereas silencing of FOXL1 by siRNA inhibits apoptosis and enhances tumor cell growth and invasion. Furthermore, FOXL1 overexpression significantly suppressed the growth of tumor xenografts in nude mice. FOXL1 promoted apoptosis partly through the induction of TNF-related apoptosis-inducing ligand (TRAIL) in pancreatic cancer cells. In addition, FOXL1 suppressed the transcription of zinc finger E-box–binding homeobox 1 (ZEB1), an activator of epithelial–mesenchymal transition, and the negative regulation of ZEB1 contributed to the inhibitory effect of FOXL1 on tumor cell invasion. Taken together, our findings suggest that FOXL1 expression is a candidate predictor of clinical outcome in patients with resected PDAC and it plays an inhibitory role in pancreatic tumor progression. Cancer Res; 73(17); 5416–25. ©2013 AACR.
Urine Erythropoietin Level Is Associated with Kidney and Brain Injury in Critically Ill Neonates
Authors: Li Yanhong , Xiao Zhihui , Yan Jie , Li Xiaozhong , Wang Qing , Zhu Hong , Pan Jian , Zhu Xueming , Wang Jian , Feng Xing
Published: June 2013

Background: Erythropoietin (EPO) is a glycoprotein hormone produced predominantly in the kidneys. The protective effect of exogenous EPO in hypoxic-ischemic brain injury has been thoroughly examined in neonates. However, the metabolism of endogenous EPO in neonates remains unclear. Objectives: We aimed to evaluate the concentration of urinary EPO (uEPO) in critically ill neonates and to identify possible clinical and laboratory variables that may be associated with uEPO levels. Methods: The concentrations of EPO, cystatin-C, microalbumin, and α1-microglobulin in the first available urine sample during the initial 72 h of life were measured in 103 critically ill neonates. Clinical and laboratory data were collected for each neonate. Results: There was a positive correlation between uEPO levels and urinary levels of cystatin-C (r = 0.265, p = 0.008), microalbumin (r = 0.422, p < 0.001), and α1-microglobulin (r = 0.421, p < 0.001). The concentration of uEPO was elevated in neonates who developed acute kidney injury (AKI) during the first week of life compared with those without AKI (p = 0.002) and was also elevated in neonates with brain injury, as demonstrated by ultrasound or magnetic resonance imaging, compared to neonates without brain injury (p = 0.008). An increased log10 uEPO level was associated with the occurrence of AKI (OR 2.70, p = 0.007) and brain injury (OR 2.33, p = 0.016). Conclusions: An increased urinary EPO level in the early postnatal period is significantly associated with kidney and brain injury in critically ill neonates.
Randomized Double-Blind Study of Prophylactic Treatment with an Antihistamine for Seasonal Allergic Rhinitis
Authors: Yonekura Syuji , Okamoto Yoshitaka , Yamamoto Heizaburo , Sakurai Toshioki , Iinuma Tomohisa , Sakurai Daiju , Hanazawa Toyoyuki
Published: June 2013

Background: The efficacy of prophylactic treatment before the start of pollen dispersal for prevention of aggravation of symptoms is unclear. The aim of the present study was to examine the efficacy of prophylactic treatment with an antihistamine for seasonal allergic rhinitis (SAR) using an environmental challenge chamber (ECC). Methods: The study was performed in a randomized double-blind manner with a 3-way crossover design. The subjects were 50 patients with SAR caused by Japanese cedar pollen who were randomized for treatment with levocetirizine hydrochloride 5 mg (Xyzal®) or placebo as follows: administration of placebo for 8 days (treatment A), single administration of levocetirizine on day 8 after placebo for 7 days (treatment B) or administration of levocetirizine for 8 days (treatment C). Efficacy in each treatment arm was evaluated based on cedar pollen exposure for 3 h on day 9 in an ECC, following 1-hour exposure on day 8. The primary endpoint was the total nasal symptom score for 12 h on day 9. Other nasal and ocular symptoms were secondary endpoints. Results: The evaluation was performed in 45 subjects. The total nasal symptom score on day 9 was significantly lower with treatment B compared with treatment A. Treatment C did not show superior efficacy compared with treatment B. Conclusions: Our results suggest that early intervention with levocetirizine soon after onset of symptoms may attenuate these symptoms as effectively as prophylactic treatment before pollen dispersal. These results are important from the perspective of patient convenience and reduction of medical costs.
Docosahexaenoic Acid Augments Hypothermic Neuroprotection in a Neonatal Rat Asphyxia Model
Authors: Berman Deborah R. , Mozurkewich Ellen , Liu Yiqing , Shangguan Yu , Barks John D. , Silverstein Faye S.
Published: June 2013

Background: In neonatal rats, early post-hypoxia-ischemia (HI) administration of the omega-3 fatty acid docosahexaenoic acid (DHA) improves sensorimotor function, but does not attenuate brain damage. Objective: To determine if DHA administration in addition to hypothermia, now standard care for neonatal asphyxial brain injury, attenuates post-HI damage and sensorimotor deficits. Methods: Seven-day-old (P7) rats underwent right carotid ligation followed by 90 min of 8% O2 exposure. Fifteen minutes later, pups received injections of DHA 2.5 mg/kg (complexed to 25% albumin) or equal volumes of albumin. After a 1-hour recovery, pups were cooled (3 h, 30°C). Sensorimotor and pathology outcomes were initially evaluated on P14. In subsequent experiments, sensorimotor function was evaluated on P14, P21, and P28; histopathology was assessed on P28. Results: At P14, left forepaw function scores (normal: 20/20) were near normal in DHA + hypothermia-treated animals (mean ± SD 19.7 ± 0.7 DHA + hypothermia vs. 12.7 ± 3.5 albumin + hypothermia, p < 0.0001) and brain damage was reduced (mean ± SD right hemisphere damage 38 ± 17% with DHA + hypothermia vs. 56 ± 15% with albumin + hypothermia, p = 0.003). Substantial improvements on three sensorimotor function measures and reduced brain damage were evident up to P28. Conclusion: Unlike post-HI treatment with DHA alone, treatment with DHA + hypothermia produced both sustained functional improvement and reduced brain damage after neonatal HI.
Acute Promyelocytic Leukemia with Flt3-TKD and WT1 Mutations Relapsing in a Testicle and Followed by Systemic Relapse
Authors: Zou Xing-li , Zeng Ke , Xie Li-ping , Wang Lin , Chen Min , Liu Ting , Niu Ting
Published: June 2013

Extramedullary relapse is a rare phenomenon in patients with acute promyelocytic leukemia (APL), especially that derived from urogenital systems like the testicles. In this report, we describe an APL patient who had received standard induction/maintenance therapy resulting in durable remission for 4.5 years, when he presented with a unilateral testicular mass confirmed as myeloid sarcoma; this was followed by systemic relapse of APL. Retrospective analysis of the involved blood and bone marrow samples at the time of the initial diagnosis revealed a rare point mutation of FLT3-TKD and a novel mutation of WT1. These mutations were detected recurrently throughout the course of the disease. After reinduction therapy with arsenic trioxide and all-trans retinoic acid combined with daunorubicin, complete hematological remission was achieved for the ensuing salvage allogeneic hematopoietic stem cell transplant.
Pharmacokinetics of Macitentan in Caucasian and Japanese Subjects: The Influence of Ethnicity and Sex
Authors: Bruderer Shirin , Marjason Joanne , Sidharta Patricia N. , Dingemanse Jasper
Published: June 2013

Background/Aims: Macitentan is a novel dual endothelin receptor antagonist with sustained receptor binding in clinical development for pulmonary arterial hypertension. The present study compared the pharmacokinetics and safety of macitentan in healthy Caucasian and Japanese subjects and explored the potential sex differences. Methods: In this single-center, open-label, phase I study 10 healthy subjects of each ethnic origin with a male/female ratio of 1:1 in each group were administered a single oral 10-mg dose of macitentan. Blood samples were taken to determine plasma levels of macitentan and its pharmacologically active metabolite, ACT-132577, and safety and tolerability were monitored using standard assessments. Results: For both macitentan and its metabolite, values for Cmax were similar but a shorter half-life was determined in Japanese subjects resulting in an exposure to both compounds being approximately 15% lower in Japanese when compared to Caucasian subjects. The exposure to macitentan was similar in Japanese males and females whereas Caucasian females had an approximately 25% higher exposure than Caucasian males. In both ethnic groups, females had an approximately 15% higher exposure to ACT-132577 than male subjects. Macitentan was well tolerated in both ethnic groups. There were no clinically significant differences in adverse event profile, clinical laboratory, electrocardiographic parameters, and vital signs between both groups. Conclusion: The data suggest that the minor differences in pharmacokinetics between the two groups are not clinically relevant and no dose adjustment of macitentan based on Japanese ethnic origin or sex is necessary.
The Outcome of Isolated Primary Fetal Hydrothorax: A 10-Year Review from a Tertiary Center
Authors: Petersen Scott , Kaur Ravinderjit , Thomas Joseph T. , Cincotta Robert , Gardener Glenn
Published: June 2013

Introduction: The management of primary fetal pleural effusion remains a challenge for clinicians given the paucity of clinical information to guide practice. Materials and Methods: A retrospective descriptive study of cases referred for management to our fetal therapy center over a 10-year period. Survival to hospital discharge was evaluated against case characteristics and prenatal intervention. For this study, we categorized the severity of the pleural effusion at diagnosis as mild, moderate or severe, and the clinical course as regression, stable or progression. Results: Forty-five of the 103 pregnancies complicated by fetal pleural effusions during the study period were managed for primary effusions. Termination of pregnancy was requested in 6 cases. Thirty-nine pregnancies continued management, with 14 undergoing prenatal intervention. The overall survival rate to hospital discharge was 51%, including 7 survivors after prenatal intervention. The rate of survival was low if the effusion was categorized as severe at diagnosis or if there was progression of the clinical course. Conclusions: Case characteristics at the time of diagnosis and clinical course can be used to guide patient counseling and decision-making regarding fetal therapy. Prenatal intervention may improve the chance of survival in cases with characteristics associated with a poor prognosis.
Visual and Refractive Outcomes after Cataract Surgery with Implantation of a New Toric Intraocular Lens
Authors: Mazzini Cinzia
Published: June 2013

Purpose: The aim of this study was to evaluate and report the visual, refractive and aberrometric outcomes of cataract surgery with implantation of the new aspheric Tecnis ZCT toric intraocular lens (IOL) in eyes with low to moderate corneal astigmatism. Methods: We conducted a prospective study of 19 consecutive eyes of 17 patients (mean age: 78 years) with a visually significant cataract and moderate corneal astigmatism [higher than 1 diopter (D)] undergoing cataract surgery with implantation of the aspheric Tecnis ZCT toric IOL (Abbott Medical Optics). Visual, refractive and aberrometric changes were evaluated during a 6-month follow-up. Ocular aberrations as well as IOL rotation were evaluated by means of the OPD-Station II (Nidek). Results: The six-month postoperative spherical equivalent and power vector components of the refractive cylinder were within ±0.50 D in all eyes (100%). Postoperative logMAR uncorrected and corrected distance visual acuities (UDVA/CDVA) were 0.1 (about 20/25) or better in almost all eyes (94.74%). The mean logMAR CDVA improved significantly from 0.41 ± 0.23 to 0.02 ± 0.05 (p < 0.01). No significant changes were found in corneal astigmatism (p = 0.73). The mean IOL rotation was 3.33 ± 1.94°. This parameter did not correlate with higher-order aberrations (r = -0.09, p = 0.73). A significant improvement in the Strehl ratio was also observed (p < 0.01), which was consistent with the significant reduction in higher-order aberrations (p = 0.02). Conclusion: Cataract surgery with implantation of the aspheric Tecnis ZCT IOL is a predictable and effective procedure for visual rehabilitation in eyes with cataract and low to moderate corneal astigmatism, providing an excellent postoperative ocular optical quality.
Cardiopulmonary Resuscitation Quality: Improving Cardiac Resuscitation Outcomes Both Inside and Outside the Hospital
Authors: Meaney Peter A. , Bobrow Bentley J. , Mancini Mary E. , Christenson Jim , de Caen Allan R. , Bhanji Farhan , Abella Benjamin S. , Kleinman Monica E. , Edelson Dana P. , Berg Robert A. , Aufderheide Tom P. , Menon Venu , Leary Marion
Published: June 2013

The "2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" increased the focus on methods to ensure that high-quality cardiopulmonary resuscitation (CPR) is performed in all resuscitation attempts. There are 5 critical components of high-quality CPR: minimize interruptions in chest compressions, provide compressions of adequate rate and depth, avoid leaning between compressions, and avoid excessive ventilation. Although it is clear that high-quality CPR is the primary component in influencing survival from cardiac arrest, there is considerable variation in monitoring, implementation, and quality improvement. As such, CPR quality varies widely between systems and locations. Victims often do not receive high-quality CPR because of provider ambiguity in prioritization of resuscitative efforts during an arrest. This ambiguity also impedes the development of optimal systems of care to increase survival from cardiac arrest. This consensus statement addresses the following key areas of CPR quality for the trained rescuer: metrics of CPR performance; monitoring, feedback, and integration of the patient’s response to CPR; team-level logistics to ensure performance of high-quality CPR; and continuous quality improvement on provider, team, and systems levels. Clear definitions of metrics and methods to consistently deliver and improve the quality of CPR will narrow the gap between resuscitation science and the victims, both in and out of the hospital, and lay the foundation for further improvements in the future.