bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific targeting of the IL-23 receptor, using a novel small peptide noncompetitive antagonist, decreases the inflammatory response
Authors: Quiniou Christiane , Domínguez-Punaro Maria , Cloutier Frank , Erfani Atefeh , Ennaciri Jamila , Sivanesan Durgajini , Sanchez Mélanie , Chognard Gaëlle , Hou Xin , Rivera José Carlos , Beauchamp Claudine , Charron Guy , Vilquin Marie , Kuchroo Vijay , Michnick Stephen , Rioux John D. , Lesage Sylvie , Chemtob Sylvain
Published: August 2014

IL-23 is part of the IL-12 family of cytokines and is composed of the p19 subunit specific to IL-23 and the p40 subunit shared with IL-12. IL-23 specifically contributes to the inflammatory process of multiple chronic inflammatory autoimmune disorders, including psoriasis, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. So far, one antibody targeting the shared p40 subunit of IL-12 and IL-23, Ustekinumab, is approved clinically to treat psoriasis. However, there are no treatments inhibiting specifically the IL-23 proinflammatory response. We have developed small IL-23R-specific antagonists by designing all D-peptides arising from flexible regions of IL-23R. Of these peptides, we selected 2305 (teeeqqly), since in addition to its soluble properties, it inhibited IL-23-induced STAT3 phosphorylation in spleen cells. Peptide 2305 specifically binds to IL-23R/IL-12Rβ1-expressing HEK-293 cells and not to cells devoid of the receptor. Peptide 2305 showed functional selectivity by modulating IL-23-induced gene expression in IL-23R/IL-12Rβ1-expressing cells and in Jurkat cells; 2305 does not inhibit IL-12-induced cytokine expression in IL-12Rβ-IL-12Rβ2-HEK-293 cells. Finally, compared with anti-p40 treatment, 2305 effectively and selectively inhibits IL-23-induced inflammation in three in vivo mouse models: IL-23-induced ear inflammation, anti-CD40-induced systemic inflammatory response, and collagen-induced arthritis. We, hereby, describe the discovery and characterization of a potent IL-23R small-peptide modulator, 2305 (teeeqqly), that is effective in vivo. 2305 may be more convenient, less cumbersome, less costly, and most importantly, more specific than current biologics for the treatment of inflammatory conditions, and conceivably complement the actual therapies for these chronic and debilitating inflammatory diseases.
Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney
Authors: Chang EunSun , Park Eun Young , Woo Yu mi , Kang Duk-Hee , Hwang Young-Hwan , Ahn Curie , Park Jong Hoon
Published: August 2014

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal proliferation of renal tubular epithelial cells, resulting in the loss of renal function. Despite identification of the genes responsible for ADPKD, few effective drugs are currently available for the disease. Thus finding additional effective drug targets is necessary. The functions of multidrug- resistance-associated protein 3 (MRP3) have been reported only in the field of drug resistance, and the renal functions of MRP3 are mostly unknown. In this study, we found that MRP3 was significantly downregulated in kidneys of human patients with ADPKD and polycystic kidney disease (PKD) mouse models. Our results suggest that downregulated MRP3 stimulated renal epithelial cell proliferation through the B-Raf/MEK/ERK signaling pathway. In contrast, we found that restoring MRP3 reduced cell proliferation and cystogenesis in vitro. These results suggest that the renal function of MRP3 is related to renal cell proliferation and cyst formation and that restoring MRP3 may be an effective therapeutic approach for PKD.
Renal medullary cyclooxygenase-2 and (pro)renin receptor expression during angiotensin II-dependent hypertension
Authors: Gonzalez Alexis A. , Green Torrance , Luffman Christina , Bourgeois Camille R. T. , Gabriel Navar L. , Prieto Minolfa C.
Published: August 2014

The (pro)renin receptor [(P)RR] upregulates cyclooxygenase-2 (COX-2) in inner medullary collecting duct (IMCD) cells through ERK1/2. Intrarenal COX-2 and (P)RR are upregulated during chronic ANG II infusion. However, the duration of COX-2 and (P)RR upregulation has not been determined. We hypothesized that during the early phase of ANG II-dependent hypertension, membrane-bound (P)RR and COX-2 are augmented in the renal medulla, serving to buffer the hypertensinogenic and vasoconstricting effects of ANG II. In Sprague-Dawley rats infused with ANG II (0.4 μg·min−1·kg−1), systolic blood pressure (BP) increased by day 7 (162 ± 5 vs. 114 ± 10 mmHg) and continued to increase by day 14 (198 ± 15 vs. 115 ± 13 mmHg). Membrane-bound (P)RR was augmented at day 3 coincident with phospho-ERK1/2 levels, COX-2 expression, and PGE2in the renal medulla. In contrast, membrane-bound (P)RR was reduced and COX-2 protein levels were not different from controls by day 14. In cultured IMCD cells, ANG II increased secretion of the soluble (P)RR. In anesthetized rats, COX-2 inhibition decreased the glomerular filtration rate (GFR) and renal blood flow (RBF) during the early phase of ANG II infusion without altering BP. However, at 14 days of ANG II infusions, COX-2 inhibition decreased mean arterial BP (MABP), RBF, and GFR. Thus, during the early phase of ANG II-dependent hypertension, the increased (P)RR and COX-2 expression in the renal medulla may contribute to attenuate the vasoconstrictor effects of ANG II on renal hemodynamics. In contrast, at 14 days the reductions in RBF and GFR caused by COX-2 inhibition paralleled the reduced MABP, suggesting that vasoconstrictor COX-2 metabolites contribute to ANG II hypertension.
Effect of preemptive treatment with human umbilical cord blood-derived mesenchymal stem cells on the development of renal ischemia-reperfusion injury in mice
Authors: Jang Hye Ryoun , Park Ji Hyeon , Kwon Ghee Young , Lee Jung Eun , Huh Wooseong , Jin Hye Jin , Choi Soo Jin , Oh Wonil , Oh Ha Young , Kim Yoon-Goo
Published: August 2014

Human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) have been studied in several models of immune-mediated disease because of their unique immunomodulatory properties. We hypothesized that HUCB-MSCs could suppress the inflammatory response in postischemic kidneys and attenuate early renal injury. In 8- to 10-wk-old male C57BL/6 mice, bilateral ischemia-reperfusion injury (IRI) surgery was performed, and 1 × 106 HUCB-MSCs were injected intraperitoneally 24 h before surgery and during reperfusion. Renal functional and histological changes, HUCB-MSC trafficking, leukocyte infiltration, and cytokine expression were analyzed. Renal functional decline and tubular injury after IRI were attenuated by HUCB-MSC treatment. PKH-26-labeled HUCB-MSCs trafficked into the postischemic kidney. Although numbers of CD45-positive leukocytes in the postischemic kidney were comparable between groups, the expression of interferon-γ in the postischemic kidney was suppressed by HUCB-MSC treatment. The rapid decrease in intrarenal VEGF after IRI was markedly mitigated by HUCB-MSC treatment. In inflammatory conditions simulated in a cell culture experiment, VEGF secretion from HUCB-MSCs was substantially enhanced. VEGF inhibitor abolished the renoprotective effect of HUCB-MSCs after IRI. Flow cytometry analysis revealed the decreased infiltration of natural killer T cells and increased number of regulatory T cells in postischemic kidneys. In addition, these effects of HUCB-MSCs on kidney infiltrating mononuclear cells after IRI were attenuated by VEGF inhibitor. HUCB-MSCs attenuated renal injury in mice in the early injury phase after IRI, mainly by humoral effects and secretion of VEGF. Our results suggest a promising role for HUCB-MSCs in the treatment of renal IRI.
Differential contribution of Kv4-containing channels to A-type, voltage-gated potassium currents in somatic and visceral dorsal root ganglion neurons
Authors: Yunoki Takakazu , Takimoto Koichi , Kita Kaori , Funahashi Yasuhito , Takahashi Ryosuke , Matsuyoshi Hiroko , Naito Seiji , Yoshimura Naoki
Published: August 2014

Little is known about electrophysiological differences of A-type transient K+ (KA) currents in nociceptive afferent neurons that innervate somatic and visceral tissues. Staining with isolectin B4 (IB4)-FITC classifies L6-S1 dorsal root ganglion (DRG) neurons into three populations with distinct staining intensities: negative to weak, moderate, and intense fluorescence signals. All IB4 intensely stained cells are negative for a fluorescent dye, Fast Blue (FB), injected into the bladder wall, whereas a fraction of somatic neurons labeled by FB, injected to the external urethral dermis, is intensely stained with IB4. In whole-cell, patch-clamp recordings, phrixotoxin 2 (PaTx2), a voltage-gated K+ (Kv)4 channel blocker, exhibits voltage-independent inhibition of the KA current in IB4 intensely stained cells but not the one in bladder-innervating cells. The toxin also shows voltage-independent inhibition of heterologously expressed Kv4.1 current, whereas its inhibition of Kv4.2 and Kv4.3 currents is voltage dependent. The swapping of four amino acids at the carboxyl portion of the S3 region between Kv4.1 and Kv4.2 transfers this characteristic. RT-PCRs detected Kv4.1 and the long isoform of Kv4.3 mRNAs without significant Kv4.2 mRNA in L6-S1 DRGs. Kv4.1 and Kv4.3 mRNA levels were higher in laser-captured, IB4-stained neurons than in bladder afferent neurons. These results indicate that PaTx2 acts differently on channels in the Kv4 family and that Kv4.1 and possibly Kv4.3 subunits functionally participate in the formation of KA channels in a subpopulation of somatic C-fiber neurons but not in visceral C-fiber neurons innervating the bladder.
Differential modulation of descending signals from the reticulospinal system during reaching and locomotion
Authors: Dyson Kenneth S. , Miron Jean-Philippe , Drew Trevor
Published: August 2014

We tested the hypothesis that the same spinal interneuronal pathways are activated by the reticulospinal system during locomotion and reaching. If such were the case, we expected that microstimulation within the pontomedullary reticular formation (PMRF) would evoke qualitatively similar responses in muscles active during both behaviors. To test this, we stimulated in 47 sites within the PMRF during both tasks. Stimulation during locomotion always produced a strongly phase-dependent, bilateral pattern of activity in which activity in muscles was generally facilitated or suppressed during one phase of activity (swing or stance) and was unaffected in the other. During reaching, stimulation generally activated the same muscles as during locomotion, although the modulation of the magnitude of the evoked responses was less limb dependent than during locomotion. An exception was found for some forelimb flexor muscles that were strongly facilitated by stimulation during the swing phase of locomotion but were not influenced by stimulation during the transport phase of the reach. We suggest that during locomotion the activity in interneuronal pathways mediating signals from the reticulospinal system is subject to strong modulation by the central pattern generator for locomotion. During reach, we suggest that, for most muscles, the same spinal interneuronal pathways are used to modify muscle activity but are not as strongly gated according to limb use as during locomotion. Finally, we propose that the command for movement during discrete voluntary movements suppresses the influence of the reticulospinal system on selected forelimb flexor muscles, possibly to enhance fractionated control of movement.
The organization and dynamics of corticostriatal pathways link the medial orbitofrontal cortex to future behavioral responses
Authors: Verstynen Timothy D.
Published: August 2014

Accurately making a decision in the face of incongruent options increases the efficiency of making similar congruency decisions in the future. Contextual factors like reward can modulate this adaptive process, suggesting that networks associated with monitoring previous success and failure outcomes might contribute to this form of behavioral updating. To evaluate this possibility, a group of healthy adults ( n = 30) were tested with functional MRI (fMRI) while they performed a color-word Stroop task. In a conflict-related region of the medial orbitofrontal cortex (mOFC), stronger BOLD responses predicted faster response times (RTs) on the next trial. More importantly, the degree of behavioral adaptation of RTs was correlated with the magnitude of mOFC-RT associations on the previous trial, but only after accounting for network-level interactions with prefrontal and striatal regions. This suggests that congruency sequencing effects may rely on interactions between distributed corticostriatal circuits. This possibility was evaluated by measuring the convergence of white matter projections from frontal areas into the striatum with diffusion-weighted imaging. In these pathways, greater convergence of corticostriatal projections correlated with stronger functional mOFC-RT associations that, in turn, provided an indirect pathway linking anatomical structure to behavior. Thus distributed corticostriatal processing may mediate the orbitofrontal cortex's influence on behavioral updating, even in the absence of explicit rewards.
Breast Surgery Using Thoracic Paravertebral Blockade and Sedation Alone
Authors: Simpson James , Ariyarathenam Arun , Dunn Julie , Ford Pete
Published: August 2014

Introduction. Thoracic paravertebral block (TPVB) provides superior analgesia for breast surgery when used in conjunction with general anesthesia (GA). Although TPVB and GA are often combined, for some patients GA is either contraindicated or undesirable. We present a series of 28 patients who received a TPVB with sedation alone for breast cancer surgery.Methods. A target controlled infusion of propofol or remifentanil was used for conscious sedation. Ultrasound guided TPVB was performed at one, two, or three thoracic levels, using up to 30 mL of local anesthetic. If required, top-up local infiltration analgesia with prilocaine 0.5% was performed by the surgeon.Results. Most patients were elderly with significant comorbidities and had TPVB injections at just one level (54%). Patient choice and anxiety about GA were indications for TVPB in 9 patients (32%). Prilocaine top-up was required in four (14%) cases and rescue opiate analgesia in six (21%).Conclusions. Based on our technique and the outcome of the 28 patients studied, TPVB with sedation and ultrasound guidance appears to be an effective and reliable form of anesthesia for breast surgery. TPVB with sedation is a useful anesthetic technique for patients in which GA is undesirable or poses an unacceptable risk.
A Case of Chronic Ethylene Glycol Intoxication Presenting without Classic Metabolic Derangements
Authors: Toth-Manikowski Stephanie M. , Menn-Josephy Hanni , Bhatia Jasvinder
Published: August 2014

Acute ethylene glycol ingestion classically presents with high anion gap acidosis, elevated osmolar gap, altered mental status, and acute renal failure. However, chronic ingestion of ethylene glycol is a challenging diagnosis that can present as acute kidney injury with subtle physical findings and without the classic metabolic derangements. We present a case of chronic ethylene glycol ingestion in a patient who presented with acute kidney injury and repeated denials of an exposure history. Kidney biopsy was critical to the elucidation of the cause of his worsening renal function.
The Smarandache Curves onS12and Its Duality onH02
Authors: Yakut Atakan Tuğkan , Savaş Murat , Tamirci Tuğba
Published: August 2014

We introduce special Smarandache curves based on Sabban frame onS12and we investigate geodesic curvatures of Smarandache curves on de Sitter and hyperbolic spaces. The existence of duality between Smarandache curves on de Sitter space and Smarandache curves on hyperbolic space is shown. Furthermore, we give examples of our main results.
Molecular Determinants for the Self-Assembly of Elastin Peptides
Authors: Bochicchio Brigida , Armenante Maria Rosaria , Crudele Maria Antonietta , Pepe Antonietta
Published: August 2014

Elastin and elastin-related peptides have great potential in the biomaterial field, because of their peculiar mechanical properties and spontaneous self-assembling behavior. Depending on their sequences and under appropriate experimental conditions, they are able to self-assemble in different fiber morphologies, including amyloid-like fibers. In this work, we will review recent data on elastin peptides derived from exon 30-coded domain of human tropoelastin. This domain has been shown to be fundamental for the correct assembly of elastin. However, the N-terminal region forms amyloid-like fibers, while the C-terminal fragment forms elastin-like fibers. A rationale for the varied aggregation pattern has been sought in the molecular structure of the peptides. Minimal differences in the sequences, adopting alternative conformations, are shown to be responsible for the observed data.
Narrow-Band Ultraviolet B versus Oral Minocycline in Treatment of Unstable Vitiligo: A Prospective Comparative Trial
Authors: Siadat Amir Hossein , Zeinali Naser , Iraji Fariba , Abtahi-Naeini Bahareh , Nilforoushzadeh Mohammad Ali , Jamshidi Kioumars , Khosravani Parastoo
Published: August 2014

Background. We have compared NB-UVB and oral minocycline in stabilizing vitiligo for the first time.Subjects and Methods. 42 patients were divided equally into two groups: the NB-UVB and minocycline groups. Phototherapy was administered twice a week on nonconsecutive days. In the minocycline group, patients were advised to take minocycline 100 mg once daily. The treatment period was 3 months. Vitiligo disease activity (VIDA) score was noted every 4 weeks for 12 months. Digital photographs were taken at baseline and monthly intervals.Results. Before the therapy, disease activity was present in 100% of the patients, which was reduced to 23.8% and 66.1% by the end of therapy in the NB-UVB and minocycline groups retrospectively (P<0.05). 16 of the 21 (76/1%) patients with unstable disease in the NB-UVB group achieved stability, whereas this was the case for only 7 of the 21 (33.3%) in the minocycline group (P<0.001). The diameter changes were statistically significant at the end of treatment in the NB-UVB group compared to the minocycline group (P=0.031). Side effects in both groups were mild.Conclusion. NB-UVB was statistically more advantageous than oral minocycline in unstable vitiligo in terms of efficacy and the resulting stability.
Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina) Hospital Wastewater
Authors: Magdaleno Anahí , Juárez Ángela Beatriz , Dragani Valeria , Saenz Magalí Elizabeth , Paz Marta , Moretton Juan
Published: August 2014

Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was performed using the green algaePseudokirchneriella subcapitataand theAllium cepatest, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8). TheA. cepatest showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA) and micronucleus (MN) showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic toA. cepabut toxic to the algae (%I = 41%), showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system.
Composite Differential Search Algorithm
Authors: Liu Bo
Published: August 2014

Differential search algorithm (DS) is a relatively new evolutionary algorithm inspired by the Brownian-like random-walk movement which is used by an organism to migrate. It has been verified to be more effective than ABC, JDE, JADE, SADE, EPSDE, GSA, PSO2011, and CMA-ES. In this paper, we propose four improved solution search algorithms, namely “DS/rand/1,” “DS/rand/2,” “DS/current to rand/1,” and “DS/current to rand/2” to search the new space and enhance the convergence rate for the global optimization problem. In order to verify the performance of different solution search methods, 23 benchmark functions are employed. Experimental results indicate that the proposed algorithm performs better than, or at least comparable to, the original algorithm when considering the quality of the solution obtained. However, these schemes cannot still achieve the best solution for all functions. In order to further enhance the convergence rate and the diversity of the algorithm, a composite differential search algorithm (CDS) is proposed in this paper. This new algorithm combines three new proposed search schemes including “DS/rand/1,” “DS/rand/2,” and “DS/current to rand/1” with three control parameters using a random method to generate the offspring. Experiment results show that CDS has a faster convergence rate and better search ability based on the 23 benchmark functions.
The Study of Mechanisms of Protective Effect of Rg1 against Arthritis by Inhibiting Osteoclast Differentiation and Maturation in CIA Mice
Authors: Gu Yanqing , Fan Weimin , Yin Guoyong
Published: August 2014

Ginsenoside Rg1 is a natural product extracted fromPanax ginsengC.A. Although Rg1 protects tissue structure and functions by inhibiting local inflammatory reaction, the mechanism remains poorly understood.In vitro, Rg1 dose-dependently inhibited TRAP activity in receptor activator of nuclear factor-κB ligand- (RANKL-) induced osteoclasts and decreased the number of osteoclasts and osteoclast resorption area. Rg1 also significantly inhibited the RANK signaling pathway, including suppressing the expression of Trap, cathepsin K, matrix metalloproteinase 9 (MMP9), and calcitonin receptor (CTR).In vivo, Rg1 dramatically decreased arthritis scores in CIA mice and effectively controlled symptoms of inflammatory arthritis. Pathologic analysis demonstrated that Rg1 significantly attenuated pathological changes in CIA mice. Pronounced reduction in synovial hyperplasia and inflammatory cell invasion were observed in CIA mice after Rg1 therapy. Alcian blue staining results illustrated that mice treated with Rg1 had significantly reduced destruction in the articular cartilage. TRAP and cathepsin K staining results demonstrated a significant reduction of numbers of OCs in the articular cartilage in proximal interphalangeal joints and ankle joints in Rg1-treated mice. In summary, this study revealed that Rg1 reduced the inflammatory destruction of periarticular bone by inhibiting differentiation and maturation of osteoclasts in CIA mice.
Synthesis and Application of One-Dimensional La(OH)3Nanostructures: An Overview
Authors: Xiao Xiang , Huang Yu , Dong Fan
Published: August 2014

One-dimensional (1D) semiconductor nanomaterials are of particular importance owing to their unique properties and potential applications. This review attempts to provide a comprehensive introduction of 1D La(OH)3nanostructures including nanowires, nanoneedles, nanobelts, and nanorods. Firstly, various strategies developed to fabricate the 1D La(OH)3nanostructures are discussed, such as precipitation and composite-hydroxide-mediated, hydrothermal, and solvothermal methods, accompanying the description of the corresponding growth mechanisms. Then, the unique properties such as novel physical properties of 1D La(OH)3nanostructures resulting from their unique electronic structures and numerous transition modes involving the 4f shells of these ions are represented in detail. Also, the wide applications in photocatalyst, capacitors, and photoluminescence based on the unique properties are discussed. Finally, the paper ends with a summary and some perspectives on the challenges and new directions in this emerging area.
A Case of Airway Obstruction Secondary to Acute Haemorrhage into a Benign Thyroid Cyst
Authors: Vijapurapu Ravi , Kaur Kamal , Crooks Neil H.
Published: August 2014

A 70-year-old female, with a history of progressive dyspnoea, was admitted to the critical care unit after successful resuscitation following a witnessed, out of hospital cardiorespiratory arrest. A presumptive diagnosis of cardiorespiratory arrest secondary to an exacerbation of chronic obstructive pulmonary disease was made. However, on more detailed examination a large anterior, midline neck mass was noted. Following tracheal intubation, a computerised tomography scan of the patient’s neck and thorax revealed a seven-centimetre, well-defined, nonenhancing, rounded homogeneous opacity at the thoracic inlet, consistent with a large midline thyroid cyst. Needle aspiration of the cyst was performed and yielded approximately 50 mL of frank blood. After an uncomplicated tracheal extubation and recovery, an elective subtotal thyroidectomy was performed prior to hospital discharge. Histology of the specimen revealed a benign thyroid cyst within a multinodular goitre. Euthyroid multinodular goitres are more likely to be managed conservatively due to an asymptomatic clinical course in most patients. However, the risk of respiratory distress and acute airway obstruction from tracheal compression or acute haemorrhage should be kept in mind. Patients at risk of this life threatening complication should be managed with elective thyroidectomy to reduce morbidity and mortality.
Clinical Characteristics Related to Central Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma: A Retrospective Study of 916 Patients
Authors: Jiang Lie-Hao , Chen Chao , Tan Zhuo , Lu Xiao-Xiao , Hu Si-Si , Wang Qing-Liang , Hou Xiu-Xiu , Cao Jun , Ge Ming-Hua
Published: August 2014

Background.Papillary thyroid carcinoma (PTC) is a form of thyroid cancer with high risk of cervical lymph node metastasis.Aim.The aim of this study was to investigate the incidence and the predictive factors for occult ipsilateral central lymph node (CLN) metastasis in the patients with papillary thyroid carcinoma.Methods.A total of 916 PTC patients (1017 lesions) undergoing central lymph node dissection in our hospital from 2005 to 2011 were enrolled. The relationship between CLN metastasis and clinical factors such as gender, age, tumor size, tumor number, capsule invasion, and tumor location was analyzed.Results.Occult CLN metastasis was observed in 52.41% (533/1017) of PTC lesions, respectively. Multivariate analysis showed that age ≤ 35 years, tumor size > 1.5 cm, present capsule invasion/extracapsular invasion, and tumor located in upper/middle pole/whole lobe were risk factors of CLN metastasis.Conclusions.Tumor located in upper/middle pole/whole lobe, less than 35 years old, tumor size > 1.5 cm, and present capsule invasion/extracapsular invasion were risk factors of CLN metastasis. We recommend performing ipsilateral prophylactic CLN dissection in cN0 PTC patients.
On an Iterative Method for Finding a Zero to the Sum of Two Maximal Monotone Operators
Authors: Jiao Hongwei , Wang Fenghui
Published: August 2014

In this paper we consider a problem that consists of finding a zero to the sum of two monotone operators. One method for solving such a problem is the forward-backward splitting method. We present some new conditions that guarantee the weak convergence of the forward-backward method. Applications of these results, including variational inequalities and gradient projection algorithms, are also considered.
Highly Enhanced Vapor Sensing of Multiwalled Carbon Nanotube Network Sensors by n‐Butylamine Functionalization
Authors: Slobodian P. , Riha P. , Cavallo P. , Barbero C. A. , Benlikaya R. , Cvelbar U. , Petras D. , Saha P.
Published: August 2014

The sensing of volatile organic compounds by multiwall carbon nanotube networks of randomly entangled pristine nanotubes or the nanotubes functionalized by n‐butylamine, which were deposited on polyurethane supporting electrospinned nonwoven membrane, has been investigated. The results show that the sensing of volatile organic compounds by functionalized nanotubes considerably increases with respect to pristine nanotubes. The increase is highly dependent on used vapor polarity. For the case of highly polar methanol, the functionalized MWCNT network exhibits even more than eightfold higher sensitivity in comparison to the network prepared from pristine nanotubes.
Is Lipid Profile Associated with Bone Mineral Density and Bone Formation in Subjects with Spinal Cord Injury?
Authors: Sabour Hadis , Norouzi Javidan Abbas , Latifi Sahar , Hadian Mohammad Reza , Emami Razavi Seyed-Hassan , Shidfar Farzad , Vafa Mohammad Reza , Aghaei Meybodi Hamidreza
Published: August 2014

Purpose. The association between serum lipids and bone mineral density (BMD) has been investigated previously but, up to now, these relationships have not yet been described in spinal cord injury (SCI). We tried to assess the correlation between serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) and BMD in male subjects with SCI.Methods. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD in femoral neck, trochanter, intertrochanteric zone, and lumbar vertebras. Blood samples were taken to measure serums lipids and bone biomarkers including osteocalcin, cross-linked type I collagen (CTX), and bone alkaline phosphatase (BALP). Partial correlation analysis was used to evaluate the relationships between mentioned measurements after adjustment for weight and age.Results. We found a positive correlation between HDL and femoral neck BMD (P: 0.004,r=0.33). HDL was negatively correlated with osteocalcin (P: 0.017,r=-0.31) which was not in consistency with its relationship with BMD. TC and LDL were not related to CTX, BALP and BMD.Conclusion. This study does not support a strong association between serum lipids and BMD in subjects with SCI. Moreover it seems that positive association between HDL and BMD is not mediated through increased bone formation.
Clinical Biomarkers and Pathogenic-Related Cytokines in Rheumatoid Arthritis
Authors: Niu Xiaoyin , Chen Guangjie
Published: August 2014

Rheumatoid arthritis (RA) is a common autoimmune disease with unknown etiology and pathogenesis. Although major therapeutic advances have been made in recent years, there is no cure for the disease. Current medications mainly reduce inflammation in order to relieve pain and slow joint damage, but many have potentially serious side effects. Therefore, to find specific biomarkers will benefit both RA patients to find relief from the disease and physicians to monitor the disease development. A number of biomarkers have been discovered and used clinically, and others are still under investigation. The autoantibodies, which are widely used in diagnosis and prognosis, novel biomarkers, which reflect clinical disease activity, and newly found biomarkers and pathogenic-related cytokines are discussed in this review.
Bilateral Jugular Vein and Sigmoid Sinus Thrombosis Related to an Inherited Coagulopathy: An Unusual Presentation
Authors: Altıntaş Özge , Gürsoy Azize Esra , Baran Gözde , Mehdi Elnur , Asil Talip
Published: August 2014

Internal jugular vein thrombosis (IJVT) is a rare condition associated with malignancy, coagulopathy, and trauma. The optimal management of any IJVT must be individualized and depends on the condition of the patient.Case Presentation.We report the case of a 42-year-old woman with a history of a first trimester spontaneous abortion. Apart from a tension-type headache, she had no neurological symptoms. She reported an incidental diagnosis of right-sided IJVT when she was evaluated for hyperthyroidism ultrasonographically. On ultrasonography, we observed bilateral jugular vein thrombosis. The patient was started on oral warfarin. Seven months later, when she was adequately anticoagulated, she developed a second thrombosis. According to the etiological workup, she had a mutation in the homozygous methylene tetrahydrofolate reductase (MTHFR) gene and reduced protein C levels and activity.Conclusion.This report illustrates an unusual presentation of a rare condition. In this case, the etiology was associated with the coagulopathy, which occurred despite adequate anticoagulation.
LRS Bianchi Type-I Inflationary String Cosmological Model in Brans-Dicke Theory of Gravitation
Authors: Venkateswarlu R. , Satish J.
Published: August 2014

We investigate locally rotational symmetric (LRS) Bianchi type I space time coupled with scalar field. String cosmological models generated by a cloud of strings with particles attached to them are studied in the Brans-Dicke theory. We assume that the expansion scalar is proportional to the shear scalar and also power law ansatz for scalar field. The physical behavior of the resulting model is discussed through different parameters.
Valuation of Credit Derivatives with Multiple Time Scales in the Intensity Model
Authors: Kim Beom Jin , Park Chan Yeol , Ma Yong-Ki
Published: August 2014

We propose approximate solutions for pricing zero-coupon defaultable bonds, credit default swap rates, and bond options based on the averaging principle of stochastic differential equations. We consider the intensity-based defaultable bond, where the volatility of the default intensity is driven by multiple time scales. Small corrections are computed using regular and singular perturbations to the intensity of default. The effectiveness of these corrections is tested on the bond price and yield curve by investigating the behavior of the time scales with respect to the relevant parameters.
Is End-Stage Ankle Arthrosis Best Managed with Total Ankle Replacement or Arthrodesis? A Systematic Review
Authors: Jordan Robert W. , Chahal Gurdip S. , Chapman Anna
Published: August 2014

Introduction. End-stage ankle osteoarthritis is a debilitating condition. Traditionally, ankle arthrodesis (AA) has been the surgical intervention of choice but the emergence of total ankle replacement (TAR) has challenged this concept. This systematic review aims to address whether TAR or AA is optimal in terms of functional outcomes.Methods. We conducted a systematic review according to PRISMA checklist using the online databases Medline and EMBASE after January 1, 2005. Participants must be skeletally mature and suffering from ankle arthrosis of any cause. The intervention had to be an uncemented TAR comprising two or three modular components. The comparative group could include any type of ankle arthrodesis, either open or arthroscopic, using any implant for fixation. The study must have reported at least one functional outcome measure.Results. Of the four studies included, two reported some significant improvement in functional outcome in favour of TAR. The complication rate was higher in the TAR group. However, the quality of studies reviewed was poor and the methodological weaknesses limited any definitive conclusions being drawn.Conclusion. The available literature is insufficient to conclude which treatment is superior. Further research is indicated and should be in the form of an adequately powered randomised controlled trial.
Longitudinal Time-Dependent Effects of Irradiation on Multidrug Resistance in a Non–Small Lung Cancer Cell Line
Authors: Kono Yumiko , Utsunomiya Keita , Kanno Shohei , Tanigawa Noboru
Published: August 2014

Multidrug resistance (MDR) in cancer is known to decrease the therapeutic efficacy of chemotherapy. The effects of irradiation on MDR in cancer cells remain unclear. Tc-99m methoxyisobutylisonitrile (MIBI) exhibits the same ATP-binding cassette (ABC) transporter kinetics as the chemotherapeutic compound doxorubicin. In this study, we investigated the synergistic effects of chemotherapeutics and irradiation [0 Gy: C (control) group; 3, 6, 9, 12 Gy: I (irradiation) group] in the human non–small lung cancer cell line H1299 exhibiting MDR, on MIBI and doxorubicin ABC transporter kinetics, in vitro and in vivo, respectively. In vitro, inhibition of H1299 cell proliferation by irradiation was found to be irradiation dose dependent. The degree and duration of MDR inhibition in vitro in H1299 were also dose dependent. In the cells of both the C group and 3-Gy I group, no significant difference of MIBI accumulation was observed. In the 6-Gy I group, a higher MIBI accumulation was observed at only 7 days after irradiation relative to the C group. A higher MIBI accumulation in the 9- and 12-Gy I groups with a significant difference from the C group was observed at 4 to 14 days after irradiation. A significant negative correlation between intracellular MIBI accumulation and cell replication was found. In vivo, high accumulation and retention of doxorubicin were observed in irradiated tumors in the H1299 xenograft mice group at 4 to 14 days after 9-Gy irradiation compared with the control mice group. These results provide evidence for a synergistic effect of concurrent chemotherapy and radiotherapy. Mol Cancer Ther; 13(11); 2706–12. ©2014 AACR.
Constitutively Active ErbB2 Regulates Cisplatin-Induced Cell Death in Breast Cancer Cells via Pro- and Antiapoptotic Mechanisms
Authors: Sigurðsson Haraldur H. , Olesen Christina W. , Dybboe Rie , Lauritzen Gitte , Pedersen Stine F.
Published: August 2014

Despite the frequent expression of N-terminally truncated ErbB2 (ΔNErbB2/p95HER2) in breast cancer and its association with Herceptin resistance and poor prognosis, it remains poorly understood how ΔNErbB2 affects chemotherapy-induced cell death. Previously it was shown that ΔNErbB2 upregulates acid extrusion from MCF-7 breast cancer cells and that inhibition of the Na+/H+ exchanger (SLC9A1/NHE1) strongly sensitizes ΔNErbB2-expressing MCF-7 cells to cisplatin chemotherapy. The aim of this study was to identify the mechanism through which ΔNErbB2 regulates cisplatin-induced breast cancer cell death, and determine how NHE1 regulates this process. Cisplatin treatment elicited apoptosis, ATM phosphorylation, upregulation of p53, Noxa (PMAIP1), and PUMA (BBC3), and cleavage of caspase-9, -7, fodrin, and PARP-1 in MCF-7 cells. Inducible ΔNErbB2 expression strongly reduced cisplatin-induced ATM- and p53-phosphorylation, augmented Noxa upregulation and caspase-9 and -7 cleavage, doubled p21WAF1/Cip1 (CDKN1A) expression, and nearly abolished Bcl-2 expression. LC3-GFP analysis demonstrated that autophagic flux was reduced by cisplatin in a manner augmented by ΔNErbB2, yet did not contribute to cisplatin-induced death. Using knockdown approaches, it was shown that cisplatin-induced caspase-7 cleavage in ΔNErbB2-MCF-7 cells was Noxa- and caspase-9 dependent. This pathway was augmented by NHE1 inhibition, while the Na+/HCO3− cotransporter (SLC4A7/NBCn1) was internalized following cisplatin exposure.

Implications: This work reveals that ΔNErbB2 strongly affects several major pro- and antiapoptotic pathways and provides mechanistic insight into the role of NHE1 in chemotherapy resistance. These findings have relevance for defining therapy regimens in breast cancers with ΔNErbB2 and/or NHE1 overexpression. Mol Cancer Res; 13(1); 63–77. ©2014 AACR.
SIRT1 Inactivation Evokes Antitumor Activities in NSCLC through the Tumor Suppressor p27
Authors: Zhu Lijia , Chiao Christine Y. , Enzer Katelyn G. , Stankiewicz Alexander J. , Faller Douglas V. , Dai Yan
Published: August 2014

P27Kip1 (CDKN1B) regulates cellular proliferation and senescence, and p27Kip1 deficiency in cancer is strongly correlated with poor prognosis of multiple cancer types. Understanding the mechanism of p27Kip1 loss in cancer and the consequences of restoring p27Kip1 levels is therefore critical for effective management during therapy. Here, SIRT1, a class III histone deacetylase (HDAC), is identified as an important regulator of p27Kip1 expression. Mechanistically, SIRT1 reduces p27Kip1 expression by decreasing p27Kip1 protein stability through the ubiquitin–proteasome pathway. In addition, SIRT1 silencing suppresses non–small cell lung cancer (NSCLC) proliferation and induces senescence in a p27Kip1-dependent manner. Furthermore, SIRT1 silencing dramatically suppresses tumor formation and proliferation in two distinct NSCLC xenograft mouse models. Collectively, these data demonstrate that not only SIRT1 is an important regulator of p27Kip1 but also SIRT inhibition induces senescence and antigrowth potential in lung cancer in vivo.

Implications: SIRT1 is a key regulator of p27 protein levels and SIRT1 inhibition is a viable strategy for NSCLC therapy by means of p27 reactivation. Mol Cancer Res; 13(1); 41–49. ©2014 AACR.
BIRO1, a Cell-Permeable BH3 Peptide, Promotes Mitochondrial Fragmentation and Death of Retinoblastoma Cells
Authors: Allaman-Pillet Nathalie , Oberson Anne , Schorderet Daniel F.
Published: August 2014

Retinoblastoma is the most common pediatric intraocular neoplasm. While retinoblastoma development requires the inactivation of both alleles of the retinoblastoma tumor suppressor gene (RB1) in the developing retina, additional genomic changes are involved in tumor progression, which progressively lead to resistance of tumor cells to death. Therapeutics acting at very downstream levels of death signaling pathways should therefore be interesting in killing retinoblastoma cells. The BH3-only proteins promote apoptosis by modulating the interaction between the pro- and antiapoptotic members of the BCL2 protein family, and this effect can be recapitulated by the BH3 domains. This report analyzes the effect of various BH3 peptides, corresponding to different BH3-only proteins, on two retinoblastoma cell lines, Y79 and WERI-Rb, as well as on the photoreceptor cell line 661W. The BH3 peptide BIRO1, derived from the BCL2L11 death domain, was very effective in promoting Y79 and WERI-Rb cell death without affecting the 661W photoreceptor cells. This cell death was efficient even in absence of BAX and was shown to be caspase independent. While ROS production or AIF release was not detected from mitochondria of treated cells, BIRO1 initiated mitochondria fragmentation in a short period of time following treatment.

Implications: The BIRO1 peptide is highly effective at killing retinoblastoma cells and has potential as a peptidomimetic. Mol Cancer Res; 13(1); 86–97. ©2014 AACR.
Visualization of Epicardial Cryoablation Lesions Using Endogenous Tissue Fluorescence
Authors: Swift Luther , Gil Daniel A.B. , Jaimes Rafael , Kay Matthew , Mercader Marco , Sarvazyan Narine
Published: August 2014

Background—

Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures.

Methods and Results—

Cryoablation of either blood-perfused or saline-perfused hearts was associated with a marked decrease in nicotinamide adenine dinucleotide (NADH) fluorescence, leading to a 60% to 70% loss of signal intensity at the lesion site. The total lesion area observed on the NADH channel exhibited a strong correlation with the area identified by triphenyl tetrazolium staining (
r
=0.89,
P
<0.001). At physiological temperatures, loss of NADH became visually apparent within 26±8 s after detachment of the cryoprobe from the epicardial surface and plateaued within minutes after which the boundaries of the lesions remained stable for several hours. The loss of electrical activity within the cryoablation site exhibited a close spatial correlation with the loss of NADH (
r
=0.84±0.06,
P
<0.001). Cryoablation led to a decrease in diffuse reflectance across the entire visible spectrum, which was in stark contrast to radiofrequency ablation that markedly increased the intensity of reflected light at the lesion sites.

Conclusions—

We confirmed the feasibility of using endogenous NADH fluorescence for the real-time visualization of cryoablation lesions in blood-perfused cardiac muscle preparations and revealed similarities and differences between imaging cryo- and radiofrequency ablation lesions when using ultraviolet and visible light illumination.
D. H. Lawrence’s Theology of the Body: Intersections with John Paul II’s Man and Woman He Created Them
Authors: Boone N. S.
Published: August 2014

This article examines the philosophical foundations of both D. H. Lawrence’s sexual ethics and the “theology of the body” developed by Pope John Paul II. Although Lawrence is often viewed, rightly in most cases, as a critic of Christianity, and even though his work has been scorned or outright banned by Christian groups over the years, Lawrence’s overarching view of life in his later years was remarkably amenable to Catholic Christianity. Linking Lawrence with Christian and even Catholic thought is not unique, as two books from the 1950s make claims very similar to mine. But these critical works are almost six decades past, and this article primarily contributes to this earlier criticism by aligning Lawrence with the theology of sexuality developed by Pope John Paul II. Though the Pope and Lawrence do differ on some points, they do not differ substantially in their philosophical stances regarding the mind/body relationship or the absolute necessity of full reciprocity in sexual intercourse. This essay does not claim that Lawrence was a Catholic, or even a Christian, or that if he had lived longer he would have converted to Catholicism. In his own mind, he had made a clean break with Christianity. But as some of his late essays extol the virtues of the Catholic Church’s development of the sacrament of marriage, Lawrence may not have been surprised to see how thoroughly his thoughts on sex and marriage align with those of the late Pope.
A Hobbesian Defense of International Criminal Law
Authors: May Larry
Published: August 2014

I argue that when a Hobbesian State sovereign is not protecting, or is actively oppressing, his subjects, this opens the door for the possibility that another State or international institution could intervene to protect these people who are not having their security protected. Pursuing peace often means forming alliances and agreements that will lead to the establishment of a society that creates laws that are obeyed. Hobbes is quite explicit in allowing for just this possibility, and given that this is true, as I show, one wonders why Hobbes has been misunderstood for so long. The uncharitable explanation is that some theorists have seized on one quotation, which I examine in detail, and largely taken it out of context.
Justice and Recognizing the Rights of States
Authors: Viner Steve
Published: August 2014

In this article, I reject Allen Buchanan's justice-based account of recognizing states as legitimate states in an international community of states. I argue that his account can fail to implement justice and that it does not properly consider the nature or importance of international law. After rejecting Buchanan's approach, I offer my account. My account calls for the unbundling of state rights, and it allows each state right to be subject to moral and legal scrutiny. My unbundling account subjects the rights of states to morally justified international laws, and it supports the conclusion that sovereignty and legitimacy should be seen in degrees. It also provides a framework for thinking about how, why and when, morally speaking, international institutions should have the power to grant or withhold legal rights from states.