bluuebunny/crossref_metadata_2025 huggingface dataset:
Facial Swelling as a Primary Manifestation of Multiple Myeloma
Authors: Thomas Anju E. , Kurup Seema , Jose Renju , Soman Cristalle
Published: July 2015

Facial swellings are commonly encountered in the dental office, the cause of which could range from a congenital etiology to an acquired one or it may even be a manifestation of an underlying systemic disease. The clinician must have a thorough knowledge of the various clinical and imaging manifestations and the sites of occurrence of the various conditions to arrive at the appropriate diagnosis. Facial swellings can be classified into different groups which include acute swellings with inflammation, nonprogressive swellings, and slowly or rapidly progressive swellings. The various imaging modalities like CT and MRI are useful for assessing the extent of the swelling as well as evaluating the soft tissue and osseous involvement of the swelling. Multiple myeloma represents clonal proliferation of plasma cells and is a condition in which a facial swelling might be present, though not common. This paper reports a case of a patient with a unilateral facial swelling, which on investigation led to a diagnosis of multiple myeloma.
Spectral Monitoring CH/C2 Ratio of Methane Plasma for Growing Single‐Layer Graphene on Cu
Authors: Chan Shih-Hao , Liao Shih-Fang , Chen Hung-Pin , Wei Hung-Sen , Chen Sheng-Hui , Lee Cheng-Chung , Kuo Chien-Cheng
Published: July 2015

Single‐layer graphene was grown on copper at a low temperature of 600°C by plasma‐assisted thermal chemical vapor deposition. Its growth mechanism was discussed with reference to the emission spectra of the plasma. The methane plasma produces the active species (Hx, CHx, and Cx) without the addition of flowing hydrogen, and the amounts of hydrogen‐containing species can be controlled by varying the plasma power. The effective distance was found between the plasma initial stage and the deposition stage for the single‐layer graphene synthesis. The results reveal that high‐quality graphene can be synthesized using methane plasma at a suitable plasma power.
Titanium Carbide Nanocrystals Synthesized from a Metatitanic Acid‐Sucrose Precursor via a Carbothermal Reduction
Authors: Shin Hyunho , Eun Jun-Ho
Published: July 2015

A TiC powder is synthesized from a micron‐sized mesoporous metatitanic acid‐sucrose precursor (precursor M) by a carbothermal reduction process. Control specimens are also prepared using a nanosized TiO2‐sucrose precursor (precursor T) with a higher cost. When synthesized at 1500°C for 2 h in flowing Ar, the characteristics of the synthesized TiC from precursor M are similar to those of the counterpart from precursor T in terms of the crystal size (58.5 versus 57.4 nm), oxygen content (0.22 wt% versus 0.25 wt%), and representative sizes of mesopores: approximately 2.5 and 19.7–25.0 nm in both specimens. The most salient differences of the two specimens are found in the TiC from precursor M demonstrating (i) a higher crystallinity based on the distinctive doublet peaks in the high‐two‐theta XRD regime and (ii) a lower specific surface area (79.4 versus 94.8 m2/g) with a smaller specific pore volume (0.1 versus 0.2 cm3/g) than the counterpart from precursor T.
Chronotropic Modulation of the Source-Sink Relationship of Sinoatrial-Atrial Impulse Conduction and Its Significance to Initiation of AF: A One-Dimensional Model Study
Authors: Cacciani Francesca , Zaniboni Massimiliano
Published: July 2015

Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulationGKr, which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase inICaL. Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies.
Intravascular Hemolysis and Septicemia due toClostridium perfringensEmphysematous Cholecystitis and Hepatic Abscesses
Authors: Cochrane Justin , Bland Lacie , Noble Mary
Published: July 2015

Context.Clostridium perfringenssepticemia is often associated with translocation from the gastrointestinal or gastrourinary tract and occurs in patients who have malignancy or are immunocompromised.Clostridium perfringenssepticemia is usually fatal without early identification, source control, and antibiotics.Case. We present a case of a 65-year-old female withClostridium perfringenssepticemia secondary to emphysematous cholecystitis, with progression to hepatic abscesses.Conclusion. Septicemia secondary toClostridium perfringensis generally fatal if not detected early. Source control with surgery or percutaneous drainage and early antibiotic therapy is imperative. Hyperbaric oxygen therapy may reduce mortality. Clinicians caring for patients with sepsis and intravascular hemolysis must haveClostridium perfringenssepticemia on their differential diagnosis with a low threshold for starting antibiotics and pursuing source of infection.
A Large Intra-Abdominal Hiatal Hernia as a Rare Cause of Dyspnea
Authors: Sahin Cem , Akın Fatih , Cullu Nesat , Özseker Burak , Kirli İsmail , Altun İbrahim
Published: July 2015

Giant hiatal hernias, generally seen at advanced ages, can rarely cause cardiac symptoms such as dyspnea and chest pain. Here, we aimed to present a case with a large hiatal hernia that largely protruded to intrathoracic cavity and caused dyspnea, particularly at postprandial period, by compressing the left atrium and right pulmonary vein. We considered presenting this case as large hiatal hernia is a rare, intra-abdominal cause of dyspnea.
Simulation-Based Optimization of Cure Cycle of Large Area Compression Molding for LED Silicone Lens
Authors: Song Min-Jae , Kim Kwon-Hee , Hong Seok-Kwan , Lee Jeong-Won , Park Jeong-Yeon , Yoon Gil-Sang , Kim Heung-Kyu
Published: July 2015

Three-dimensional heat transfer-curing simulation was performed for the curing process by introducing a large area compression molding for simultaneous forming and mass production for the lens and encapsulants in the LED molding process. A dynamic cure kinetics model for the silicone resin was adopted and cure model and analysis result were validated and compared through a temperature measurement experiment for cylinder geometry with cure model. The temperature deviation between each lens cavity could be reduced by implementing a simulation model on the large area compression mold and by optimizing the location of heat source. A two-step cure cycle was constructed to reduce excessive reaction peak at the initial stage and cycle time. An optimum cure cycle that could reduce cycle time by more than 29% compared to a one-step cure cycle by adjusting dwell temperature, heating rate, and dwell time was proposed. It was thus confirmed that an optimization of large area LED lens molding process was possible by using the present experiment and the finite element method.
Repeatability of Perimacular Ganglion Cell Complex Analysis with Spectral-Domain Optical Coherence Tomography
Authors: Ng Dorothy S. K. , Gupta Preeti , Tham Yih Chung , Peck Chye Fong , Wong Tien Yin , Ikram Mohammad Kamran , Cheung Carol Y.
Published: July 2015

Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms.Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-inner plexiform layer thickness measured by Cirrus HD-OCT Ganglion Cell Analysis algorithm. Intraclass correlation coefficient and Pearson’s correlation analyses were performed.Results. Subfields of both macular and perimacular ganglion cell complex thicknesses had high intraclass correlation coefficient values between 0.979 (95% confidence interval [CI]: 0.958–0.989) and 0.981 (95% CI: 0.963, 0.991) and between 0.70 (95% CI: 0.481–0.838) and 0.987 (95% CI: 0.956–0.989), respectively. The overall average ganglion cell complex and macular average ganglion cell-inner plexiform layer thicknesses were strongly correlated(r=0.83, P<0.001).  Conclusions. The assessment of macular and perimacular retinal ganglion cell parameters by OCT-HS100 Glaucoma 3D algorithm is highly repeatable, and strongly correlates to retinal ganglion cell parameters assessed by Ganglion Cell Analysis algorithm. A comprehensive evaluation of retinal ganglion cells may be possible with OCT-HS100.
Risk Factors for Premenopausal Breast Cancer in Bangladesh
Authors: Iqbal Javaid , Ferdousy Tahmina , Dipi Rahela , Salim Reza , Wu Wei , Narod Steven A. , Kotsopoulos Joanne , Mostafa Mohammad G. , Ginsburg Ophira
Published: July 2015

Background. The incidence of premenopausal breast cancer is rising throughout South Asia. Our objective was to determine the role of risk factors associated with Westernization for premenopausal breast cancer in Bangladesh.Methods. We conducted a matched case-control study between January 1, 2007, and December 31, 2010, at four hospitals in Bangladesh. Cases were premenopausal women diagnosed with invasive breast cancer. Controls were premenopausal women with no personal history of breast cancer. Logistic regression was used to calculate the odds ratios (OR) for breast cancer.Results. We identified 129 age-matched pairs. The mean age of breast cancer diagnosis was 37.5 years. Each year decrease in the age of menarche significantly increased the risk of breast cancer (OR = 1.67, 95% CI 1.09–2.56,P=0.02). The risk was also increased with a current body mass index of ≥25 kg/m2(OR = 5.24, 95% CI 1.10–24.9,P=0.04). Age at first childbirth, parity, and breastfeeding were not significantly associated with premenopausal breast cancer risk (P>0.05).Conclusions. Age at menarche and adult weight gain were associated with premenopausal breast cancer risk. Other factors associated with Westernization may not be relevant to premenopausal breast cancer risk in Bangladesh.
A Study on Effect of Electroacupuncture on Gene Expression in Hypothalamus of Rats with Stress-Induced Prehypertension Based on Gene Chip Technology
Authors: Xie Xiaojia , Guo Yan , Liu Qingguo , Wang Zhaoyang , Guo Changqing
Published: July 2015

Objective. To explore the effect of electroacupuncture (EA) on gene expression in the hypothalamus of rats with stress-induced prehypertension and try to reveal its biological mechanism with gene chip technology.Methods. The stress-induced hypertensive rat model was prepared by combining electric foot-shocks with generated noise. Molding cycle lasted for 14 days and EA intervention was applied on model + EA group during model preparation. Rat Gene 2.0 Array technology was used for the determination of gene expression profiles and the screened key genes were verified by real-time fluorescence quantitative PCR method.Results. Compared with the blank group, 234 genes were upregulated and 73 were downregulated in the model group. Compared with the model group, 110 genes were upregulated and 273 genes were downregulated in model + EA group. The PCR results of the key genes including HSPB1, P2RX4, PPP1R14A, and TH are consistent with that of gene chip test.Conclusion. EA could significantly lower blood pressure of stress-induced prehypertension rats and affect its gene expression profile in hypothalamus. Genes and their signal transduction pathway that related to the contraction of vascular smooth muscle, concentration of Ca2+, and excitability of sympathetic nerve may be involved in EA’s antihypertensive mechanism.
Research of Herb-Partitioned Moxibustion for Primary Dysmenorrhea Patients Based on the LC-MS Metabonomics
Authors: Ma Yu-xia , Yang Xing-yue , Guo Gang , Du Dong-qing , Yu Yan-pu , Gao Shu-zhong
Published: July 2015

Objective. To explore the efficacy and mechanism of primary dysmenorrhea patients were treated with herb-partitioned moxibustion through metabonomics.Methods. 20 patients with primary dysmenorrhea were randomized into two groups, separately treated with herb-partitioned moxibustion at CV8 (shenque) and acupuncture at SP6 (sanyinjiao). After three menstrual cycles’ treatment, the intensity of menstrual pain using VAS and the changes of metabolites of plasma using LC-MS were observed.Results. The VAS of two groups decreased with different descending range. Herb-partitioned moxibustion upregulated 20α-dihydroprogesterone, pregnenolone, prostaglandin E2andγ-aminobutyric acid and downregulated the content of estrone and prostaglandin H2, while acupuncture upregulated pregnenolone and 20α-dihydroprogesterone and downregulated 2-methoxyestradiol-3-methylether, 15-hydroxyeicosatrienoic acid and 6-keto-prostaglandin.Discussion. It was effective in relieving the abdominal pain by these two therapies. Herb-partitioned moxibustion is superior to acupuncture for primary dysmenorrhea, which could be related to regulating the endocrine hormone.
Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion
Authors: Hadj Ayed Tka Kaouther , Mahfoudh Boussaid Asma , Zaouali Mohamed Amine , Kammoun Rym , Bejaoui Mohamed , Ghoul Mazgar Sonia , Rosello Catafau Joan , Ben Abdennebi Hassen
Published: July 2015

Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3βand VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury.
Narrow-Band Imaging Magnifying Endoscopy versus Lugol Chromoendoscopy with Pink-Color Sign Assessment in the Diagnosis of Superficial Esophageal Squamous Neoplasms: A Randomised Noninferiority Trial
Authors: Goda Kenichi , Dobashi Akira , Yoshimura Noboru , Kato Masayuki , Aihara Hiroyuki , Sumiyama Kazuki , Toyoizumi Hirobumi , Kato Tomohiro , Ikegami Masahiro , Tajiri Hisao
Published: July 2015

Previous studies have shown the high diagnostic accuracy of narrow-band imaging magnifying endoscopy (NBI-ME) and Lugol chromoendoscopy with pink-color sign assessment (LCE-PS) for superficial esophageal squamous cell carcinoma (SESCC). However, there has been no controlled trial comparing these two diagnostic techniques. We conducted a randomized noninferiority trial to compare the diagnostic accuracy of NBI-ME and LCE-PS. We recruited patients with, or with a history of, squamous cell carcinoma in the head and neck region or in the esophagus. They were randomly assigned to either NBI-ME or LCE-PS. When lesions > 5 mm in diameter were found as brownish areas on NBI or as Lugol-voiding lesions (LVL), they were evaluated to determine whether they are SESCC on the basis of the findings of NBI-ME or PS in the LVL. NBI-ME and LCE-PS were completed in 147 patients each. There was no significant difference in all diagnostic values between the two techniques. Compared with LCE-PS, NBI-ME showed a significantly shorter examination time but a larger number of misdiagnosed lesions especially in patients with many irregularly shaped multiform LVLs. Compared with LCE-PS, NBI-ME might be similarly accurate and less invasive, but less reliable in patients with many LVLs, in the diagnosis of SESCC.
Boundary Criteria for the Stability of Delay Differential-Algebraic Equations
Authors: Sun Leping , Cong Yuhao
Published: July 2015

This paper is concerned with the asymptotic stability of delay differential-algebraic equations. Two stability criteria described by evaluating a corresponding harmonic analytical function on the boundary of a certain region are presented. Stability regions are also presented so as to show the method geometrically. Our results are not reported.
Cyclic Tensile Strain Induces Tenogenic Differentiation of Tendon-Derived Stem Cells in Bioreactor Culture
Authors: Xu Yuan , Wang Qiang , Li Yudong , Gan Yibo , Li Pei , Li Songtao , Zhou Yue , Zhou Qiang
Published: July 2015

Different loading regimens of cyclic tensile strain impose different effects on cell proliferation and tenogenic differentiation of TDSCs in three-dimensional (3D) culture in vitro, which has been little reported in previous literatures. In this study we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation in the custom-designed 3D tensile bioreactor, which revealed that cyclic tensile strain with different frequencies (0.3 Hz, 0.5 Hz, and 1.0 Hz) and amplitudes (2%, 4%, and 8%) had no influence on TDSC viability, while it had different effects on the proliferation and the expression of type I collagen, tenascin-C, tenomodulin, and scleraxis of TDSCs, which was most obvious at 0.5 Hz frequency with the same amplitude and at 4% amplitude with the same frequency. Moreover, signaling pathway from microarray analysis revealed that reduced extracellular matrix (ECM) receptor interaction signaling initiated the tendon genius switch. Cyclic tensile strain highly upregulated genes encoding regulators of NPM1 and COPS5 transcriptional activities as well as MYC related transcriptional factors, which contributed to cell proliferation and differentiation. In particular, the transcriptome analysis provided certain new insights on the molecular and signaling networks for TDSCs loaded in these conditions.
The Transcription Factor ZNF395 Is Required for the Maximal Hypoxic Induction of Proinflammatory Cytokines in U87‐MG Cells
Authors: Herwartz Christine , Castillo-Juárez Paola , Schröder Linda , Barron Blanca L. , Steger Gertrud
Published: July 2015

Hypoxia activates the expression of proangiogenic and survival promoting factors as well as proinflammatory cytokines that support tissue inflammation. Hypoxia and inflammation are associated with tumor progression. The identification of the factors participating in the hypoxia associated inflammation is essential to develop strategies to control tumor hypoxia. The transcription factor ZNF395 was found to be overexpressed in various tumors including glioblastomas particularly in the network of a hypoxic response pointing to a functional role of ZNF395. On the other hand, ZNF395 was suggested to have tumor suppressor activities which may rely on its repression of proinflammatory factors. To address these conflictive observations, we investigated the role of ZNF395 in the expression of proinflammatory cytokines in the astrocytoma cell line U87‐MG under hypoxia. We show that ZNF395 is a target gene of the hypoxia inducible factor HIF‐1α. By gene expression analysis, RT‐PCR and ELISA, we demonstrated that the siRNA‐mediated suppression of ZNF395 impairs the hypoxic induction of IL‐1β, IL‐6, IL‐8, and LIF in U87‐MG cells. At ambient oxygen concentrations, ZNF395 had no enhancing effect, indicating that this transcriptional activation by ZNF395 is restricted to hypoxic conditions. Our results suggest that ZNF395 contributes to hypoxia associated inflammation by superactivating proinflammatory cytokines.
Heartbeat Cycle Length Detection by a Ballistocardiographic Sensor in Atrial Fibrillation and Sinus Rhythm
Authors: Zink Matthias Daniel , Brüser Christoph , Winnersbach Patrick , Napp Andreas , Leonhardt Steffen , Marx Nikolaus , Schauerte Patrick , Mischke Karl
Published: July 2015

Background.Heart rate monitoring is especially interesting in patients with atrial fibrillation (AF) and is routinely performed by ECG. A ballistocardiography (BCG) foil is an unobtrusive sensor for mechanical vibrations. We tested the correlation of heartbeat cycle length detection by a novel algorithm for a BCG foil to an ECG in AF and sinus rhythm (SR).Methods.In 22 patients we obtained BCG and synchronized ECG recordings before and after cardioversion and examined the correlation between heartbeat characteristics.Results.We analyzed a total of 4317 heartbeats during AF and 2445 during SR with a correlation between ECG and BCG during AF ofr=0.70(95% CI 0.68–0.71,P<0.0001) andr=0.75(95% CI 0.73–0.77,P<0.0001) during SR. By adding a quality index, artifacts could be reduced and the correlation increased for AF to 0.76 (95% CI 0.74–0.77,P<0.0001,n=3468) and for SR to 0.85 (95% CI 0.83–0.86,P<0.0001,n=2176).Conclusion.Heartbeat cycle length measurement by our novel algorithm for BCG foil is feasible during SR and AF, offering new possibilities of unobtrusive heart rate monitoring. This trial is registered with IRB registration number EK205/11. This trial is registered with clinical trials registration numberNCT01779674.
In Vitro Differentiation Potential of Human Placenta Derived Cells into Skin Cells
Authors: Mahmood Ruhma , Choudhery Mahmood S. , Mehmood Azra , Khan Shaheen N. , Riazuddin Sheikh
Published: July 2015

Skin autografting is the most viable and aesthetic technique for treatment of extensive burns; however, this practice has potential limitations. Harvesting cells from neonatal sources (such as placental tissue) is a simple, inexpensive, and noninvasive procedure. In the current study authors sought to evaluate in vitro potential of human placenta derived stem cells to develop into skin-like cells. After extensive washing, amniotic membrane and umbilical cord tissue were separated to harvest amniotic epithelial cells (AECs) and umbilical cord mesenchymal stem cells (UC-MSCs), respectively. Both types of cells were characterized for the expression of embryonic lineage markers and their growth characteristics were determined. AECs and UC-MSCs were induced to differentiate into keratinocytes-like and dermal fibroblasts-like cells, respectively. After induction, morphological changes were detected by microscopy. The differentiation potential was further assessed using immunostaining and RT-PCR analyses. AECs were positive for cytokeratins and E-Cadherin while UC-MSCs were positive for fibroblast specific makers. AECs differentiated into keratinocytes-like cells showed positive expression of keratinocyte specific cytokeratins, involucrin, and loricrin. UC-MSCs differentiated into dermal fibroblast-like cells indicated expression of collagen type 3, desmin, FGF-7, fibroblast activation protein alpha, procollagen-1, and vimentin. In conclusion, placenta is a potential source of cells to develop into skin-like cells.
Synthesis of Three‐Dimensional Fe3O4/Graphene Aerogels for the Removal of Arsenic Ions from Water
Authors: Ye Yan , Yin Da , Wang Bin , Zhang Qingwen
Published: July 2015

We report the synthesis of three‐dimensional Fe3O4/graphene aerogels (GAs) and their application for the removal of arsenic (As) ions from water. The morphology and properties of Fe3O4/GAs have been characterized by scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, X‐ray photoelectron spectroscopy, and superconducting quantum inference device. The 3D nanostructure shows that iron oxide nanoparticles are decorated on graphene with an interconnected network structure. It is found that Fe3O4/GAs own a capacity of As(V) ions adsorption up to 40.048 mg/g due to their remarkable 3D structure and existence of magnetic Fe3O4 nanoparticles for separation. The adsorption isotherm matches well with the Langmuir model and kinetic analysis suggests that the adsorption process is pseudo‐second‐ordered. In addition to the excellent adsorption capability, Fe3O4/GAs can be easily and effectively separated from water, indicating potential applications in water treatment.
Severe Rhabdomyolysis without Systemic Involvement: A Rare Case of Idiopathic Eosinophilic Polymyositis
Authors: Farooq Ayesha , Choksi Vivek , Chu Andrew , Mankodi Dhruti , Shaharyar Sameer , O’Brien Keith , Shankar Uday
Published: July 2015

Introduction. Eosinophilic polymyositis (EPM) is a rare cause of rhabdomyolysis characterized by eosinophilic infiltrates in the muscle. We describe the case of a young patient with eosinophilic polymyositis causing isolated severe rhabdomyolysis without systemic involvement.Case Presentation. A 22-year-old Haitian female with no past medical history presented with progressive generalized muscle aches without precipitating factors. Examination of the extremities revealed diffuse muscle tenderness. Laboratory findings demonstrated peripheral eosinophilia and high creatinine phosphokinase (CPK) and transaminase levels. Workup for the common causes of rhabdomyolysis were negative. Her CPK continued to rise to greater than 100,000 units/L so a muscle biopsy was performed which showed widespread eosinophilic infiltrate consistent with eosinophilic polymyositis. She was started on high dose systemic corticosteroids with improvement of her symptoms, eosinophilia, and CPK level.Discussion. This case illustrates a systematic workup of rhabdomyolysis in the presence of peripheral eosinophilia. Many differential diagnoses must be considered before establishing a diagnosis of idiopathic eosinophilic polymyositis. To our knowledge, our case of eosinophilic polymyositis is unique as it presented with severe rhabdomyolysis without another organ involvement. Clinicians should maintain a high index of suspicion for this physically debilitating disease to aid in prompt diagnosis.
Diagnosing Paroxysmal Atrial Fibrillation: Are Biomarkers the Solution to This Elusive Arrhythmia?
Authors: Howlett P. J. , Hatch F. S. , Alexeenko V. , Jabr R. I. , Leatham E. W. , Fry C. H.
Published: July 2015

Atrial fibrillation (AF) is the commonest sustained arrhythmia globally and results in significantly increased morbidity and mortality including a fivefold risk of stroke. Paroxysmal atrial fibrillation (PAF) constitutes approximately half of all AF cases and is thought to represent an early stage of the disease. This intermittent form of atrial arrhythmia can be a challenge to identify and as a result many affected individuals are not prescribed appropriate antithrombotic therapy and hence are at risk of stroke and thromboembolism. Despite these adverse outcomes there have been relatively few diagnostic advances in the field since the introduction of the Holter monitor in 1949. This review aims to establish the available evidence for electrophysiological, molecular, and morphological biomarkers to improve the detection of PAF with reference to the underlying mechanisms for the condition.
Chronic Exertional Compartment Syndrome in a High School Soccer Player
Authors: Bresnahan James J. , Hennrikus William L.
Published: July 2015

Chronic exertional compartment syndrome (CECS) is a relatively rare condition that affects young adult athletes and often causes them to present to the emergency department. If left untreated, those who continue to compete at high levels may experience debilitating leg pain. Physicians may have difficulty differentiating CECS from other syndromes of the lower leg such as medial tibial stress syndrome, stress fractures, and popliteal artery entrapment. The gold standard for diagnosing CECS is intramuscular compartment pressure monitoring before and/or after 10 minutes of exercise. Some patients may choose to stop participation in sports in order to relieve their pain, which otherwise does not respond well to nonoperative treatments. In patients who wish to continue to participate in sports and live an active life, fasciotomy provides relief in 80% or more. The typical athlete can return to training in about 8 weeks. This is a case of a high school soccer player who stopped competing due to chronic exertional compartment syndrome. She had a fascial hernia, resting intramuscular pressure of 30 mmHg, and postexercise intramuscular pressure of 99 mmHg. Following fasciotomy she experienced considerable life improvement and is once again training and playing soccer without symptoms.
RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway–Dependent Tumors
Authors: Zhao Xuesong , Ponomaryov Tatyana , Ornell Kimberly J. , Zhou Pengcheng , Dabral Sukriti K. , Pak Ekaterina , Li Wei , Atwood Scott X. , Whitson Ramon J. , Chang Anne Lynn S. , Li Jiang , Oro Anthony E. , Chan Jennifer A. , Kelleher Joseph F. , Segal Rosalind A.
Published: July 2015

Aberrant Shh signaling promotes tumor growth in diverse cancers. The importance of Shh signaling is particularly evident in medulloblastoma and basal cell carcinoma (BCC), where inhibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise. However, the emergence of drug resistance limits long-term efficacy, and the mechanisms of resistance remain poorly understood. Using new medulloblastoma models, we identify two distinct paradigms of resistance to Smo inhibition. Sufu mutations lead to maintenance of the Shh pathway in the presence of Smo inhibitors. Alternatively activation of the RAS–MAPK pathway circumvents Shh pathway dependency, drives tumor growth, and enhances metastatic behavior. Strikingly, in BCC patients treated with Smo inhibitor, squamous cell cancers with RAS/MAPK activation emerged from the antecedent BCC tumors. Together, these findings reveal a critical role of the RAS–MAPK pathway in drug resistance and tumor evolution of Shh pathway–dependent tumors. Cancer Res; 75(17); 3623–35. ©2015 AACR.
Molecular Pathways: Overcoming Radiation Resistance by Targeting DNA Damage Response Pathways
Authors: Morgan Meredith A. , Lawrence Theodore S.
Published: July 2015

DNA double-strand breaks are the critical lesions responsible for the majority of ionizing radiation–induced cell killing. Thus, the ability of tumor cells to elicit a DNA damage response following radiation, via activation of DNA repair and cell-cycle checkpoints, promotes radiation resistance and tumor cell survival. Consequently, agents that target these DNA damage response pathways are being developed to overcome radiation resistance. Overall, these agents are effective radiosensitizers; however, their mechanisms of tumor cell selectivity are not fully elucidated. In this review, we focus on the crucial radiation-induced DNA damage responses as well as clinical and translational advances with agents designed to inhibit these responses. Importantly, we describe how synthetic lethality can provide tumor cell–selective radiosensitization by these agents and expand the therapeutic window for DNA damage response–targeted agents used in combination with radiotherapy. Clin Cancer Res; 21(13); 2898–904. ©2015 AACR.
mTORC2 Balances AKT Activation and eIF2α Serine 51 Phosphorylation to Promote Survival under Stress
Authors: Tenkerian Clara , Krishnamoorthy Jothilatha , Mounir Zineb , Kazimierczak Urszula , Khoutorsky Arkady , Staschke Kirk A. , Kristof Arnold S. , Wang Shuo , Hatzoglou Maria , Koromilas Antonis E.
Published: July 2015

The mTOR nucleates two complexes, namely mTOR complex 1 and 2 (mTORC1 and mTORC2), which are implicated in cell growth, survival, metabolism, and cancer. Phosphorylation of the α-subunit of translation initiation factor eIF2 at serine 51 (eIF2αS51P) is a key event of mRNA translation initiation and a master regulator of cell fate during cellular stress. Recent studies have implicated mTOR signaling in the stress response, but its connection to eIF2αS51P has remained unclear. Herein, we report that genetic as well as catalytic inhibition of mTORC2 induces eIF2αS51P. On the other hand, the allosteric inhibitor rapamycin induces eIF2αS51P through pathways that are independent of mTORC1 inactivation. Increased eIF2αS51P by impaired mTORC2 depends on the inactivation of AKT, which primes the activation of the endoplasmic reticulum (ER)-resident kinase PERK/PEK. The biologic function of eIF2αS51P was characterized in tuberous sclerosis complex (TSC)-mutant cells, which are defective in mTORC2 and AKT activity. TSC-mutant cells exhibit increased PERK activity, which is downregulated by the reconstitution of the cells with an activated form of AKT1. Also, TSC-mutant cells are increasingly susceptible to ER stress, which is reversed by AKT1 reconstitution. The susceptibility of TSC-mutant cells to ER stress is further enhanced by the pharmacologic inhibition of PERK or genetic inactivation of eIF2αS51P. Thus, the PERK/eIF2αS51P arm is an important compensatory prosurvival mechanism, which substitutes for the loss of AKT under ER stress.

Implications: A novel mechanistic link between mTOR function and protein synthesis is identified in TSC-null tumor cells under stress and reveals potential for the development of antitumor treatments with stress-inducing chemotherapeutics. Mol Cancer Res; 13(10); 1377–88. ©2015 AACR.
Assessment of Esophageal Adenocarcinoma Risk Using Somatic Chromosome Alterations in Longitudinal Samples in Barrett's Esophagus
Authors: Li Xiaohong , Paulson Thomas G. , Galipeau Patricia C. , Sanchez Carissa A. , Liu Karen , Kuhner Mary K. , Maley Carlo C. , Self Steven G. , Vaughan Thomas L. , Reid Brian J. , Blount Patricia L.
Published: July 2015

Cancers detected at a late stage are often refractory to treatments and ultimately lethal. Early detection can significantly increase survival probability, but attempts to reduce mortality by early detection have frequently increased overdiagnosis of indolent conditions that do not progress over a lifetime. Study designs that incorporate biomarker trajectories in time and space are needed to distinguish patients who progress to an early cancer from those who follow an indolent course. Esophageal adenocarcinoma is characterized by evolution of punctuated and catastrophic somatic chromosomal alterations and high levels of overall mutations but few recurrently mutated genes aside from TP53. Endoscopic surveillance of Barrett's esophagus for early cancer detection provides an opportunity for assessment of alterations for cancer risk in patients who progress to esophageal adenocarcinoma compared with nonprogressors. We investigated 1,272 longitudinally collected esophageal biopsies in a 248 Barrett's patient case–cohort study with 20,425 person-months of follow-up, including 79 who progressed to early-stage esophageal adenocarcinoma. Cancer progression risk was assessed for total chromosomal alterations, diversity, and chromosomal region-specific alterations measured with single-nucleotide polymorphism arrays in biopsies obtained over esophageal space and time. A model using 29 chromosomal features was developed for cancer risk prediction (area under receiver operator curve, 0.94). The model prediction performance was robust in two independent esophageal adenocarcinoma sets and outperformed TP53 mutation, flow cytometric DNA content, and histopathologic diagnosis of dysplasia. This study offers a strategy to reduce overdiagnosis in Barrett's esophagus and improve early detection of esophageal adenocarcinoma and potentially other cancers characterized by punctuated and catastrophic chromosomal evolution. Cancer Prev Res; 8(9); 845–56. ©2015 AACR.
EUS-Guided FNA for Diagnosis of Pancreatic Cystic Lesions: a Meta-Analysis
Authors: Wang Qi-Xian , Xiao Jun , Orange Matthew , Zhang Hu , Zhu You-Qing
Published: July 2015

Background: Preoperative diagnosis of pancreatic cystic lesions (PCLs) must be reliable as the current standard treatment, major or total pancreatectomy, dramatically affects quality of life. Additionally, early diagnosis of malignancy is essential to an improved prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been demonstrated in pancreatic solid lesions. The utility of this technique in the diagnosis of PCLs is still unknown. Methods: A comprehensive search was performed in multiple databases. Studies differentiating benign and malignant PCLs via EUS-FNA were included in this meta-analysis. The quality of diagnostic accuracy studies (QUADAS) was adopted to evaluate the selected studies. Pooled sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curve analyses were conducted. Two main classification types of malignancy were characterized and analyzed. We also generated a subgroup analysis of available clinical factors. Publication bias was evaluated by Begg's and Egger's tests. Results: Sixteen studies containing 1024 subjects have been published. The pooled sensitivity for malignant cytology according to classification 1 was 0.51 (95% CI, 0.45-0.58), and pooled specificity was 0.94 (95% CI, 0.92-0.96). When the detected PCLs were identified as classification 2, suspicious malignancy or potential malignancy, sensitivity and specificity were similar, 0.52 (95% CI, 0.46-0.57) and 0.97 (95% CI, 0.95-0.98) respectively. Conclusion: This meta-analysis demonstrates that EUS-FNA is a reliable clinical tool for the diagnosis of PCLs. However, a more accurate algorithm is needed to reduce various biases and to improve the sensitivity of EUS-FNA in the detection of malignant PCLs.
Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways
Authors: Zhang Aiqing , Han Ying , Wang Bin , Li Shanwen , Gan Weihua
Published: July 2015

Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC) proliferation from a new point of view considering Connexin 43 (Cx43). Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR). Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT), and the intracellular calcium concentrations ([Ca2+]i) were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P<0.05). SLDT studies revealed that there was no difference in the gap junction channel function between the normal and Aldosterone (Aldo)-stimulated groups (P>0.05). Our data also showed that the mineralcorticoid receptor (MR) antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (P<0.05), suggesting that the classical PKC pathway might be activated. Conclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.
Carbon Monoxide Inhibits Receptor Activator of NF-κB (RANKL)-Induced Osteoclastogenesis
Authors: Tseng Feng-Jen , Chia Wei-Tso , Wang Chih-Hung , Shyu Jia-Fwu , Gou Guo-Hau , Shui Hao-Ai , Sytwu Huey-Kang , Pan Ru-Yu , Weng Ching-Feng
Published: July 2015

Background: Low concentrations of carbon monoxide (CO) have anti-inflammatory effects and can reduce bone erosion in a murine collagen-induced arthritis model. The objective of this study was to assess the effects of CO on receptor activator of NF-γB ligand (RANKL), one of the key stimulators of osteoclastogenesis. Methods: The in vivo effects of CO on RANKL expression were assessed in a collagen antibody-induced arthritis model in mice. Cell proliferation and apoptosis were assessed in the RAW246.7 cell line stimulated with RANKL and exposed to either air or CO. The number of tartrate resistant acid phosphatase (TRAP)-positive RAW246.7 cells was also examined after treatment with RANKL and the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, Troglitazone. Results: CO reduced RANKL expression in the synovium of arthritic mice. Although CO slightly increased RAW246.7 cell proliferation, no differences in activated caspase 3 levels were detected. In addition, Troglitazone ameliorated the inhibitory effects of CO on RANKL-induced TRAP expression by RAW246.7 cells. Conclusions: CO suppresses osteoclast differentiation by inhibiting the RANKL-induced activation of PPAR-γ. Given the role of the PPAR-γ/cFos (AP-1) pathway in regulating the transcription factor, NFATc1, the master regulator of osteoclastogenesis, further studies are warranted to explore CO in treating inflammatory bone disorders.
IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis
Authors: Seiffart Virginia , Zoeller Julia , Klopfleisch Robert , Wadwa Munisch , Hansen Wiebke , Buer Jan , Riedel Christian , Westendorf Astrid M.
Published: July 2015

Background/Aims: IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopathology associated with the infection. Because IL10 plays an important role in both intestinal homeostasis and infection, we studied the function of IL10 in infection-associated intestinal inflammation. Methods: Wildtype mice and mice deficient in CD4+ T cell-derived or regulatory T cells-derived IL10 were infected with the enteric pathogen Citrobacter (C.) rodentium and analyzed for the specific immune response and pathogloy in the colon. Results: We found that IL10 expression is upregulated in colonic tissue after infection with C. rodentium, especially in CD4+ T cells, macrophages and dendritic cells. Whereas the deletion of IL10 in regulatory T cells had no effect on C. rodentium induced colitis, infection of mice deficient in CD4+ T cell-derived IL10 exhibited faster clearance of the bacterial burden but worse colitis, crypt hyperplasia, and pathology than did WT mice. In addition, the depletion of CD4+ T cell-derived IL10 in infected animals was accompanied by an accelerated IFNγ and IL17 response in the colon. Conclusion: Thus, we conclude that CD4+ T cell-derived IL10 is strongly involved in the control of C. rodentium-induced colitis. Interference with this network could have implications for the treatment of infection-associated intestinal inflammation.
Blockade of KCa3.1 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction
Authors: Ju Chen-Hui , Wang Xian-Pei , Gao Chuan-Yu , Zhang Shuang-Xia , Ma Xing-Hua , Liu Chang
Published: July 2015

Background/Aims: After myocardial infarction (MI), cardiac fibrosis greatly contributes to left ventricular remodeling and heart failure. The intermediate-conductance calcium-activated potassium Channel (KCa3.1) has been recently proposed as an attractive target of fibrosis. The present study aimed to detect the effects of KCa3.1 blockade on ventricular remodeling following MI and its potential mechanisms. Methods: Myocardial expression of KCa3.1 was initially measured in a mouse MI model by Western blot and real time-polymerase chain reaction. Then after treatment with TRAM-34, a highly selective KCa3.1 blocker, heart function and fibrosis were evaluated by echocardiography, histology and immunohistochemistry. Furthermore, the role of KCa3.1 in neonatal mouse cardiac fibroblasts (CFs) stimulated by angiotensin II (Ang II) was tested. Results: Myocardium expressed high level of KCa3.1 after MI. Pharmacological blockade of KCa3.1 channel improved heart function and reduced ventricular dilation and fibrosis. Besides, a lower prevalence of myofibroblasts was found in TRAM-34 treatment group. In vitro studies KCa3.1 was up regulated in CFs induced by Ang II and suppressed by its blocker.KCa3.1 pharmacological blockade attenuated CFs proliferation, differentiation and profibrogenic genes expression and may regulating through AKT and ERK1/2 pathways. Conclusion: Blockade of KCa3.1 is able to attenuate ventricular remodeling after MI through inhibiting the pro-fibrotic effects of CFs.
Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages
Authors: Liu Xin-Hua , Wang Xi-Ling , Xin Hong , Wu Dan , Xin Xiao-Ming , Miao Lei , Zhang Qiu-Yan , Zhou Yang , Liu Qian , Zhang Qian , Zhu Yi-Zhun
Published: July 2015

Background/Aim: Sodium 9-acetoxyltanshinone IIA sulfonate (ZY-1A4), a novel compound derived from sodium 9-hydroxyltanshinone IIA sulfonate, was synthesized with potential biological activities. This study aimed to explore the effects of ZY-1A4 on lipopolysaccharide (LPS)-triggered inflammatory response and the underlying mechanisms. Methods: Activation of RAW264.7 macrophages was induced by LPS. The effects of ZY-1A4 on inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, nuclear factor-κB (NF-κB) activation, heme oxygenase-1 (HO-1) expression, and nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway were evaluated to elucidate its underlying mechanisms on inflammatory responses. Results: ZY-1A4 concentration-dependently reduced iNOS expression and NO production, and inhibited c-Jun-N-terminal kinase 1/2 (JNK1/2) phosphorylation and NF-κB activation in LPS-stimulated macrophages. In addition, ZY-1A4 concentration- and time-dependently induced HO-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of Nrf2, while the effect of ZY-1A4 was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Intriguingly, pharmacological inactivation of HO-1 with zinc protoporphyrin IX reversed anti-inflammatory effect of ZY-1A4, but the anti-inflammatory effect of ZY-1A4 was largely mimicked by HO-1 by-products carbon monoxide and bilirubin. Furthermore, the inhibitory effect of ZY-1A4 on LPS-induced iNOS expression and NO release was abolished by HO-1 siRNA or LY294002. Conclusion: Our results demonstrated that ZY-1A4 suppressed LPS-induced iNOS expression and NO generation via modulation of NF-κB activation and HO-1 expression. This new finding might shed light to the prevention and therapy of cardiovascular diseases.